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Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location and implants used, there are also a wide range of animal models described modelling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to 1) animal model considerations, 2) outcome measurements, and 3) imaging. This article is protected by copyright. All rights reserved.

This paper presents a new voice conversion (VC) framework capable of dealing with both additive noise and reverberation, and its performance evaluation. There have been studied some VC researches focusing on real-world circumstances where speech data are interfered with background noise and reverberation. To deal with more practical conditions where no clean target dataset is available, one possible approach is zero-shot VC, but its performance tends to degrade compared with VC using sufficient amount of target speech data. To leverage large amount of noisy-reverberant target speech data, we propose a three-stage VC framework based on denoising process using a pretrained denoising model, dereverberation process using a dereverberation model, and VC process using a nonparallel VC model based on a variational autoencoder. The experimental results show that 1) noise and reverberation additively cause significant VC performance degradation, 2) the proposed method alleviates the adverse effects caused by both noise and reverberation, and significantly outperforms the baseline directly trained on the noisy-reverberant speech data, and 3) the potential degradation introduced by the denoising and dereverberation still causes noticeable adverse effects on VC performance., Comment: Accepted to INTERSPEECH 2022

Stretchable strain sensors have drawn tremendous attention due to their wide applications in various emerging scenarios. Various application scenarios have different performance requirements for the sensors, mainly including sensitivity and sensing range. It is necessary but challenging to customize the design to achieve the various required performance. Here, we propose a method to easily modulate stretchable strain sensors by patterning the hybrid film, which infiltrates Ecoflex into the patterned vertical aligned carbon nanotube (VACNT) arrays and combining the pre-stretching transfer. The pre-stretching level of the Ecoflex substrate, the pattern design, and the height of the VACNT arrays are the main factors to modulate the sensitivity and sensing range of the sensors. The typical sensors show tunable sensitivity (from 0.6 to 417.7) and sensing range (from 0-40% to 0–150%), high mechanical repeatability, as well as durability (>10000 operation cycles). The sensors are applied to detect human body motion and recognize speech and emotional signals. These show the application potentials of the sensors in movement monitoring, human-machine interfaces, and electronic skins. © 2022 Elsevier Ltd

A design of peel-speed sensitive flexible fastener was proposed based on a novel modified polyurethane. Taking the microtrichia of the head-arrester system of lestes barbarous as the bionic prototype, the structure of the micro protuberance was designed as self-mating type with hemispherical caps. Considering the nonlinearities of contact behavior and of the material property, a micromechanical model of typical interlocking element is established. Adopting the explicit dynamics finite element method, the mechanical responses of fastener in peeling are analyzed. The detachment of interlocking element is predicated by taking the total strain energy as an indicator. The influences of peel speed and friction coefficient on the mechanical performances are parametrically studied. The results show that the maximum peel force and the strength increased with respect to the enhancing peel speed because of the intrinsic nonlinearity in the constitutive relation of novel modified polyurethane the investigation adopted. With larger friction coefficient, the maximum peel force, the total strain energy and the corresponding de-adhesion displacements are respectively enhanced.

Metal-semiconductor-Metal (M-S-M) structure is widely used in electronic devices, which plays a key role in device performance. Here, we propose a simple and effective way to modulate the contact characteristics of aluminum (AI)-amorphous indium gallium zinc oxide (a-IGZO)-molybdenum (Mo) structure by applying local strain at the interface between Al layer and a-IGZO layer. Four types of I-V curves including forward rectifying, backward rectifying, linear and approximately symmetric are achieved under different pressures. Due to the nanoscale strain gradient induced by inhomogeneous local strain, flexoelectric potential is generated at the interface of the Al and the a-IGZO, which leads to the energy band bending. Therefore, the barrier height modulation can be realized. Meanwhile, the charges induced by flexoelectric effect in the a-IGZO layer can also modulate the barrier height at the a-IGZO/Mo interface. This work shows great potential to enhance the performance of electronic devices and it is promising for novel electromechanical applications. © 2021 IEEE.

Metal-semiconductor-Metal (M-S-M) structure is widely used in electronic devices, which plays a key role in device performance. Here, we propose a simple and effective way to modulate the contact characteristics of aluminum (AI)-amorphous indium gallium zinc oxide (a-IGZO)-molybdenum (Mo) structure by applying local strain at the interface between Al layer and a-IGZO layer. Four types of I-V curves including forward rectifying, backward rectifying, linear and approximately symmetric are achieved under different pressures. Due to the nanoscale strain gradient induced by inhomogeneous local strain, flexoelectric potential is generated at the interface of the Al and the a-IGZO, which leads to the energy band bending. Therefore, the barrier height modulation can be realized. Meanwhile, the charges induced by flexoelectric effect in the a-IGZO layer can also modulate the barrier height at the a-IGZO/Mo interface. This work shows great potential to enhance the performance of electronic devices and it is promising for novel electromechanical applications. © 2021 IEEE.

Beyond the conventional voice conversion (VC) where the speaker information is converted without altering the linguistic content, the background sounds are informative and need to be retained in some real-world scenarios, such as VC in movie/video and VC in music where the voice is entangled with background sounds. As a new VC framework, we have developed a noisy-to-noisy (N2N) VC framework to convert the speaker's identity while preserving the background sounds. Although our framework consisting of a denoising module and a VC module well handles the background sounds, the VC module is sensitive to the distortion caused by the denoising module. To address this distortion issue, in this paper we propose the improved VC module to directly model the noisy speech waveform while controlling the background sounds. The experimental results have demonstrated that our improved framework significantly outperforms the previous one and achieves an acceptable score in terms of naturalness, while reaching comparable similarity performance to the upper bound of our framework.

Metal-semiconductor-Metal (M-S-M) structure is widely used in electronic devices, which plays a key role in device performance. Here, we propose a simple and effective way to modulate the contact characteristics of aluminum (AI)-amorphous indium gallium zinc oxide (a-IGZO)-molybdenum (Mo) structure by applying local strain at the interface between Al layer and a-IGZO layer. Four types of I-V curves including forward rectifying, backward rectifying, linear and approximately symmetric are achieved under different pressures. Due to the nanoscale strain gradient induced by inhomogeneous local strain, flexoelectric potential is generated at the interface of the Al and the a-IGZO, which leads to the energy band bending. Therefore, the barrier height modulation can be realized. Meanwhile, the charges induced by flexoelectric effect in the a-IGZO layer can also modulate the barrier height at the a-IGZO/Mo interface. This work shows great potential to enhance the performance of electronic devices and it is promising for novel electromechanical applications. © 2021 IEEE.

In a conventional voice conversion (VC) framework, a VC model is often trained with a clean dataset consisting of speech data carefully recorded and selected by minimizing background interference. However, collecting such a high-quality dataset is expensive and time-consuming. Leveraging crowd-sourced speech data in training is more economical. Moreover, for some real-world VC scenarios such as VC in video and VC-based data augmentation for speech recognition systems, the background sounds themselves are also informative and need to be maintained. In this paper, to explore VC with the flexibility of handling background sounds, we propose a noisy-to-noisy (N2N) VC framework composed of a denoising module and a VC module. With the proposed framework, we can convert the speaker's identity while preserving the background sounds. Both objective and subjective evaluations are conducted, and the results reveal the effectiveness of the proposed framework.

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The use of nitrogen fertilizers has been estimated to have supported 27% of the world’s population over the past century. Urea (CO(NH2)2) is conventionally synthesized through two consecutive industrial processes, N2 + H2 → NH3 followed by NH3 + CO2 → urea. Both reactions operate under harsh conditions and consume more than 2% of the world’s energy. Urea synthesis consumes approximately 80% of the NH3 produced globally. Here we directly coupled N2 and CO2 in H2O to produce urea under ambient conditions. The process was carried out using an electrocatalyst consisting of PdCu alloy nanoparticles on TiO2 nanosheets. This coupling reaction occurs through the formation of C–N bonds via the thermodynamically spontaneous reaction between *N=N* and CO. Products were identified and quantified using isotope labelling and the mechanism investigated using isotope-labelled operando synchrotron-radiation Fourier transform infrared spectroscopy. A high rate of urea formation of 3.36 mmol g–1 h–1 and corresponding Faradic efficiency of 8.92% were measured at –0.4 V versus reversible hydrogen electrode. [Figure not available: see fulltext.]

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The use of nitrogen fertilizers has been estimated to have supported 27% of the world’s population over the past century. Urea (CO(NH2)2) is conventionally synthesized through two consecutive industrial processes, N2 + H2 → NH3 followed by NH3 + CO2 → urea. Both reactions operate under harsh conditions and consume more than 2% of the world’s energy. Urea synthesis consumes approximately 80% of the NH3 produced globally. Here we directly coupled N2 and CO2 in H2O to produce urea under ambient conditions. The process was carried out using an electrocatalyst consisting of PdCu alloy nanoparticles on TiO2 nanosheets. This coupling reaction occurs through the formation of C–N bonds via the thermodynamically spontaneous reaction between *N=N* and CO. Products were identified and quantified using isotope labelling and the mechanism investigated using isotope-labelled operando synchrotron-radiation Fourier transform infrared spectroscopy. A high rate of urea formation of 3.36 mmol g–1 h–1 and corresponding Faradic efficiency of 8.92% were measured at –0.4 V versus reversible hydrogen electrode. [Figure not available: see fulltext.]

© 2020 Elsevier Ltd Pt/WO3 catalysts have been reported to possess excellent HER activity closing to commercial Pt/C, however, the promoting mechanism of WO3 in enhancing HER activity has not been clarified. Herein, we have successfully prepared a series of Pt-WO3 catalysts with outstanding HER performance and low Pt contents by a simple method. Via in-situ Raman spectroscopy and electrochemical impedance spectroscopy characterization, the electrochemically driven in-situ phase transition from WO3 to HxWO3 was identified and the significant role of HxWO3 in promoting electron transfer during HER process and accelerating HER kinetics by providing the hydrogen transfer pathway from HxWO3 onto Pt have been revealed. This work emphasized the importance of tracking the catalyst structure dynamic evolution and provided a deep insight into the electron/hydrogen transfer process for electrocatalytic HER.

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The use of nitrogen fertilizers has been estimated to have supported 27% of the world’s population over the past century. Urea (CO(NH2)2) is conventionally synthesized through two consecutive industrial processes, N2 + H2 → NH3 followed by NH3 + CO2 → urea. Both reactions operate under harsh conditions and consume more than 2% of the world’s energy. Urea synthesis consumes approximately 80% of the NH3 produced globally. Here we directly coupled N2 and CO2 in H2O to produce urea under ambient conditions. The process was carried out using an electrocatalyst consisting of PdCu alloy nanoparticles on TiO2 nanosheets. This coupling reaction occurs through the formation of C–N bonds via the thermodynamically spontaneous reaction between *N=N* and CO. Products were identified and quantified using isotope labelling and the mechanism investigated using isotope-labelled operando synchrotron-radiation Fourier transform infrared spectroscopy. A high rate of urea formation of 3.36 mmol g–1 h–1 and corresponding Faradic efficiency of 8.92% were measured at –0.4 V versus reversible hydrogen electrode. [Figure not available: see fulltext.]

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The use of nitrogen fertilizers has been estimated to have supported 27% of the world’s population over the past century. Urea (CO(NH2)2) is conventionally synthesized through two consecutive industrial processes, N2 + H2 → NH3 followed by NH3 + CO2 → urea. Both reactions operate under harsh conditions and consume more than 2% of the world’s energy. Urea synthesis consumes approximately 80% of the NH3 produced globally. Here we directly coupled N2 and CO2 in H2O to produce urea under ambient conditions. The process was carried out using an electrocatalyst consisting of PdCu alloy nanoparticles on TiO2 nanosheets. This coupling reaction occurs through the formation of C–N bonds via the thermodynamically spontaneous reaction between *N=N* and CO. Products were identified and quantified using isotope labelling and the mechanism investigated using isotope-labelled operando synchrotron-radiation Fourier transform infrared spectroscopy. A high rate of urea formation of 3.36 mmol g–1 h–1 and corresponding Faradic efficiency of 8.92% were measured at –0.4 V versus reversible hydrogen electrode. [Figure not available: see fulltext.]

Si-si Wang, Dao-xiong Ye, Bo Wang, Chao Xie Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, The People’s Republic of ChinaCorrespondence: Dao-xiong YeDepartment of General Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian Province 350001, The People’s Republic of ChinaTel/Fax +86-591-86218015Email daoxiongy@163.comPurpose: Primary squamous cell carcinoma is a rare malignancy in the thyroid gland (SCCTh). The overall prognosis of this carcinoma is poor. This study aimed to explore the application of Raman spectroscopy in investigating the expression of CK5/6 and P63 in SCCTh.Patients and Methods: Tissues of the SCCTh and adjacent normal thyroid, as well as blood serum, were collected from a patient with pathology-confirmed SCCTh. Whole genome sequencing analysis was performed with the tissue of the SCCTh. The expressions of keratins and TP53 family gene were investigated by the Raman spectroscopy in tissues of the SCCTh and adjacent normal thyroid. The serum was also investigated by the Raman spectroscopy for the expression of keratins and TP53 family gene.Results: The whole genome sequencing analysis identified the mutation of the TP53 gene (42%) in the tissues of SCCTh. Accordingly, the Raman spectra analyses showed higher expression of keratins and TP53 family gene in the tissues of SCCTh compared with that in the adjacent normal thyroid. Raman spectra analyses of the serum of the patient also showed the expressions of the keratins and TP53 family gene.Conclusion: The expressions of the keratins and TP53 are different in the tissues of SCCTh and adjacent normal thyroid, and the difference could be identified with high sensitivity by the Raman spectra analyses.Keywords: SCCTh, thyroid neoplasms, CK5/6, P53, Raman spectrum analysis

© 2020 Elsevier Ltd Pt/WO3 catalysts have been reported to possess excellent HER activity closing to commercial Pt/C, however, the promoting mechanism of WO3 in enhancing HER activity has not been clarified. Herein, we have successfully prepared a series of Pt-WO3 catalysts with outstanding HER performance and low Pt contents by a simple method. Via in-situ Raman spectroscopy and electrochemical impedance spectroscopy characterization, the electrochemically driven in-situ phase transition from WO3 to HxWO3 was identified and the significant role of HxWO3 in promoting electron transfer during HER process and accelerating HER kinetics by providing the hydrogen transfer pathway from HxWO3 onto Pt have been revealed. This work emphasized the importance of tracking the catalyst structure dynamic evolution and provided a deep insight into the electron/hydrogen transfer process for electrocatalytic HER.

The HLA gene complex on human chromosome 6 is one of the most polymorphic regions in the human genome and contributes in large part to the diversity of the immune system. Accurate typing of HLA genes with short-read sequencing data has historically been difficult due to the sequence similarity between the polymorphic alleles. Here, we introduce an algorithm, xHLA, that iteratively refines the mapping results at the amino acid level to achieve 99-100% four-digit typing accuracy for both class I and II HLA genes, taking only [Formula: see text]3 min to process a 30× whole-genome BAM file on a desktop computer.

In his article “Narrating Animal Suffering in Ye Guangqin’s Animal Stories,” Chao Xie analyzes animal suffering depicted in the contemporary Chinese writer Ye Guangqin’s animal story collection The Tiger Dafu (2004). Through reading the interconnected suffering of animals and humans represented in Ye’s works, Xie argues that Ye expresses an attitude of posthumanism which is needed to examine animal suffering. The shared victimhood between animals and humans in Ye’s works, which is largely due to the process of Chinese modernization, provides a new insight into the idea of the Anthropocene.

In his article “Narrating Animal Suffering in Ye Guangqin’s Animal Stories,” Chao Xie analyzes animal suffering depicted in the contemporary Chinese writer Ye Guangqin’s animal story collection The Tiger Dafu (2004). Through reading the interconnected suffering of animals and humans represented in Ye’s works, Xie argues that Ye expresses an attitude of posthumanism which is needed to examine animal suffering. The shared victimhood between animals and humans in Ye’s works, which is largely due to the process of Chinese modernization, provides a new insight into the idea of the Anthropocene.

Visibility affects all forms of traffic: roads, sailing, and aviation. Visibility prediction is meaningful in guiding production and life. Different from weather prediction, which relies solely on atmosphere factors, the factors that affect meteorological visibility are more complicated, such as the air pollution caused by factory exhaust emission. However, the current prediction of visibility is mostly based on the numerical prediction method similar to the weather prediction. We proposed a method using multimodal fusion to build a weather visibility prediction system in this paper. An advanced numerical prediction model and a method for emission detection were used to build a multimodal fusion visibility prediction system. We used the most advanced regression algorithm, XGBoost, and LightGBM, to train the fusion model for numerical prediction. Through the estimation of factory emission by the traditional detector in the satellite image, we propose to add the result of estimation based on Landsat-8 satellite images to assist the prediction. By testing our numerical model in atmosphere data of various meteorological observation stations in Beijing-Tianjin-Hebei region from 2002 to 2018, our numerical prediction model turns out to be more accurate than other existing methods, and after fusing with emission detection method, the accuracy of our visibility prediction system has been further improved., QC 20190805

In his article “Narrating Animal Suffering in Ye Guangqin’s Animal Stories,” Chao Xie analyzes animal suffering depicted in the contemporary Chinese writer Ye Guangqin’s animal story collection The Tiger Dafu (2004). Through reading the interconnected suffering of animals and humans represented in Ye’s works, Xie argues that Ye expresses an attitude of posthumanism which is needed to examine animal suffering. The shared victimhood between animals and humans in Ye’s works, which is largely due to the process of Chinese modernization, provides a new insight into the idea of the Anthropocene.

In his article “Narrating Animal Suffering in Ye Guangqin’s Animal Stories,” Chao Xie analyzes animal suffering depicted in the contemporary Chinese writer Ye Guangqin’s animal story collection The Tiger Dafu (2004). Through reading the interconnected suffering of animals and humans represented in Ye’s works, Xie argues that Ye expresses an attitude of posthumanism which is needed to examine animal suffering. The shared victimhood between animals and humans in Ye’s works, which is largely due to the process of Chinese modernization, provides a new insight into the idea of the Anthropocene.

Deep learning (DL) defines a new data-driven programming paradigm where the internal system logic is largely shaped by the training data. The standard way of evaluating DL models is to examine their performance on a test dataset. The quality of the test dataset is of great importance to gain confidence of the trained models. Using an inadequate test dataset, DL models that have achieved high test accuracy may still lack generality and robustness. In traditional software testing, mutation testing is a well-established technique for quality evaluation of test suites, which analyzes to what extent a test suite detects the injected faults. However, due to the fundamental difference between traditional software and deep learning-based software, traditional mutation testing techniques cannot be directly applied to DL systems. In this paper, we propose a mutation testing framework specialized for DL systems to measure the quality of test data. To do this, by sharing the same spirit of mutation testing in traditional software, we first define a set of source-level mutation operators to inject faults to the source of DL (i.e., training data and training programs). Then we design a set of model-level mutation operators that directly inject faults into DL models without a training process. Eventually, the quality of test data could be evaluated from the analysis on to what extent the injected faults could be detected. The usefulness of the proposed mutation testing techniques is demonstrated on two public datasets, namely MNIST and CIFAR-10, with three DL models., Comment: he 29th IEEE International Symposium on Software Reliability Engineering (ISSRE 2018)

Microorganisms act both as drivers and indicators of perturbations in the marine environment. In an effort to establish baselines to predict the response of marine habitats to environmental change, here we report a broad survey of microbial diversity across the Indian Ocean, including the first microbial samples collected in the pristine lagoon of Salomon Islands, Chagos Archipelago. This was the first large-scale ecogenomic survey aboard a private yacht employing a 'citizen oceanography' approach and tools and protocols easily adapted to ocean going sailboats. Our data highlighted biogeographic patterns in microbial community composition across the Indian Ocean. Samples from within the Salomon Islands lagoon contained a community which was different even from adjacent samples despite constant water exchange, driven by the dominance of the photosynthetic cyanobacterium Synechococcus. In the lagoon, Synechococcus was also responsible for driving shifts in the metatranscriptional profiles. Enrichment of transcripts related to photosynthesis and nutrient cycling indicated bottom-up controls of community structure. However a five-fold increase in viral transcripts within the lagoon during the day, suggested a concomitant top-down control by bacteriophages. Indeed, genome recruitment against Synechococcus reference genomes suggested a role of viruses in providing the ecological filter for determining the β-diversity patterns in this system.

This study developed an adhesive and transferable free-standing (FS) film with dual function of osteoinductivity and antibacterial activity, which was obtained by sequentially assembling vancomycin immobilized oxidized sodium alginate and dexamethasone encapsulated chitosan coated BSA nanoparticles on a poly-dopamine layer. The FS films enabled the dual release of vancomycin and dexamethasone. The FS films had excellent osteoinductivity and antibacterial activity by cell culture and antibacterial assay. The FS film was detached from substrates and transferred to non-fouling surfaces by a wet transfer method, which demonstrated that the adhesive FS film is potential to modify biopolymers with non-fouling surfaces in mild and biocompatible conditions for biomedical applications. (C) 2015 Elsevier B.V. All rights reserved.

This study developed an adhesive and transferable free-standing (FS) film with dual function of osteoinductivity and antibacterial activity, which was obtained by sequentially assembling vancomycin immobilized oxidized sodium alginate and dexamethasone encapsulated chitosan coated BSA nanoparticles on a poly-dopamine layer. The FS films enabled the dual release of vancomycin and dexamethasone. The FS films had excellent osteoinductivity and antibacterial activity by cell culture and antibacterial assay. The FS film was detached from substrates and transferred to non-fouling surfaces by a wet transfer method, which demonstrated that the adhesive FS film is potential to modify biopolymers with non-fouling surfaces in mild and biocompatible conditions for biomedical applications. (C) 2015 Elsevier B.V. All rights reserved.

Xinzhe Yu,1,* Yang Di,2,* Chao Xie,3 Yunlong Song,4 Hang He,2 Hengchao Li,1 Xinming Pu,5 Weiyue Lu,3 Deliang Fu,2 Chen Jin1 1Pancreatic Surgery Department, Huashan Hospital, 2Pancreatic Disease Institute, Fudan University, 3School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, 4School of Pharmacy, The Second Military Medical University, 5The State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background and objectives: Gemcitabine (Gem) is far from satisfactory as the first-line regimen for pancreatic cancer, and the emergence of albumin nanoparticles offers new hope for the delivery of Gem. In this study, Gem-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully synthesized, characterized, and tested on a BxPC-3 cell line both in vitro and in vivo.Materials and methods: 4-N-myristoyl-gemcitabine (Gem-C14) was obtained first by coupling myristoyl with the 4-amino group of Gem. The Gem-HSA-NPs were then prepared by nanoparticle albumin-bound technology and characterized for particle size, zeta potential, morphology, encapsulation efficiency, drug-loading efficiency, and release characteristics. Using both in vitro and in vivo studies, Gem-C14 and Gem-HSA-NPs were tested on the human pancreatic cancer cell line BxPC-3.Results: Gem-HSA-NPs showed an average particle size of 150±27 nm, and with an encapsulation rate of 82.99%±3.5% and a drug-loading rate of 10.42%±3.5%, they exhibited a favorable controlled- and sustained-release nature. In in vitro, Gem-C14 was equivalent in cytotoxicity to Gem. In in vivo, the Gem-HSA-NPs exhibited the strongest inhibitory effect on tumor growth but the lowest toxicity among the four groups.Conclusion: The enhanced in vivo efficacy of Gem-HSA-NPs toward the pancreatic ca

Xinzhe Yu,1,* Yang Di,2,* Chao Xie,3 Yunlong Song,4 Hang He,2 Hengchao Li,1 Xinming Pu,5 Weiyue Lu,3 Deliang Fu,2 Chen Jin1 1Pancreatic Surgery Department, Huashan Hospital, 2Pancreatic Disease Institute, Fudan University, 3School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, 4School of Pharmacy, The Second Military Medical University, 5The State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background and objectives: Gemcitabine (Gem) is far from satisfactory as the first-line regimen for pancreatic cancer, and the emergence of albumin nanoparticles offers new hope for the delivery of Gem. In this study, Gem-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully synthesized, characterized, and tested on a BxPC-3 cell line both in vitro and in vivo.Materials and methods: 4-N-myristoyl-gemcitabine (Gem-C14) was obtained first by coupling myristoyl with the 4-amino group of Gem. The Gem-HSA-NPs were then prepared by nanoparticle albumin-bound technology and characterized for particle size, zeta potential, morphology, encapsulation efficiency, drug-loading efficiency, and release characteristics. Using both in vitro and in vivo studies, Gem-C14 and Gem-HSA-NPs were tested on the human pancreatic cancer cell line BxPC-3.Results: Gem-HSA-NPs showed an average particle size of 150±27 nm, and with an encapsulation rate of 82.99%±3.5% and a drug-loading rate of 10.42%±3.5%, they exhibited a favorable controlled- and sustained-release nature. In in vitro, Gem-C14 was equivalent in cytotoxicity to Gem. In in vivo, the Gem-HSA-NPs exhibited the strongest inhibitory effect on tumor growth but the lowest toxicity among the four groups.Conclusion: The enhanced in vivo efficacy of Gem-HSA-NPs toward the pancreatic ca

This study developed an adhesive and transferable free-standing (FS) film with dual function of osteoinductivity and antibacterial activity, which was obtained by sequentially assembling vancomycin immobilized oxidized sodium alginate and dexamethasone encapsulated chitosan coated BSA nanoparticles on a poly-dopamine layer. The FS films enabled the dual release of vancomycin and dexamethasone. The FS films had excellent osteoinductivity and antibacterial activity by cell culture and antibacterial assay. The FS film was detached from substrates and transferred to non-fouling surfaces by a wet transfer method, which demonstrated that the adhesive FS film is potential to modify biopolymers with non-fouling surfaces in mild and biocompatible conditions for biomedical applications.

We present a high-quality, bias-free quantum random number generator (QRNG) using photon arrival time selectively in accordance with the number of photon detection events within a sampling time interval in attenuated light. It is well showed in both theoretical analysis and experiments verification that this random number production method eliminates both bias and correlation perfectly without more post processing and the random number can clearly pass the standard randomness tests. We fulfill theoretical analysis and experimental verification of the method whose rate can reach up to 45Mbps.

Minmin Li,1 Zhehai Wang,2 Jun Guo,2 Jie Liu,2 Changzheng Li,2 Lin Liu,2 Huan Shi,2 Liyan Liu,2 Huihui Li,2 Chao Xie,2 Xia Zhang,2 Wenwen Sun,1 Shu Fang,1 Xiang Bi11School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 2Department of Oncology, Shandong Cancer Hospital, Shandong, People's Republic of ChinaPurpose: The primary aim of this research was to investigate the association between uridine diphosphate glucuronosyltransferase (UGT)1A1 gene polymorphisms and the toxicities of irinotecan-based regimens in Chinese patients with metastatic colorectal cancer.Methods: The study analyzed the distribution of UGT1A1*28/*6 gene polymorphisms by polymerase chain reaction amplification and pyrosequencing. The adverse reactions and tumor response were evaluated according to National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0, and Response Evaluation Criteria In Solid Tumors, Version 1.0, criteria, respectively. The correlation between UGT1A1 gene polymorphisms and severe delayed diarrhea or neutropenia was analyzed. The influences of UGT1A1*6/*28 polymorphisms on response rate and progression-free survival were also analyzed. Survival analysis was performed by the Kaplan–Meier method, and we used the log-rank test to analyze the effect of genotypes on progression-free survival, the logistic regression model for multivariate analysis, and the Cox regression model for multivariate survival analysis.Results: A total of 167 patients with metastatic colorectal cancer who were treated with irinotecan-based regimens and with detected UGT1A1 gene polymorphisms were enrolled in this research. The rate of UGT1A1*28 homozygous wild-type TA6/6, heterozygous mutant-type TA6/7, and homozygous mutant-type TA7/7 was 65.3% (109/167), 32.3% (54/167), and 2.4% (4/167), respectively; the incidence of UGT1A1*6 wild-type G/G was 67.1% (112/167), heterozygous mutant-type G/A accounted for 28.7% (48/167), and

Previous studies have mainly focused on investigating one source of local item dependence (LID). However, in some cases, such as scenario-based science assessments, LID might be caused by two possible sources simultaneously. In this study, such kind of LID that is caused by two factors simultaneously is named as dual local item dependence (DLID). This study proposed a cross-classified model to account for DLID. Two simulation studies were conducted with the primary purpose of evaluating the performance of the proposed cross-classified model. Data sets with DLID were simulated with both testlet effects and content clustering effects. The second purpose of this study was to investigate the potential factors affecting the need to use the more complex cross-classified modeling of DLID over the simplified multilevel modeling of LID by ignoring cross-classification structure. For both simulation studies, five factors were manipulated, including sample size, number of testlets, testlet length, magnitude of the testlet effects represented by standard deviations (SDs), and magnitude of the content clustering effects represented by SDs. The difference between the two simulation studies was that, simulation study 1 constrained the SDs of the testlet effects and content clustering effects as the same across testlets and content areas, respectively; simulation study 2 released this constraint by having mixed SDs of the testlet effects and mixed SDs of the content clustering effects. Results of both simulation studies indicated that the proposed cross-classified model yielded more accurate parameter recovery, including item difficulty, persons' ability, and random effects' SD parameters with smaller estimation errors than the two multilevel models and the Rasch model which ignored one or both item clustering effects. The two manipulated variables, the magnitude of the testlet effects and the magnitude of the content clustering effects, determined the necessity of using the more c

Shu Fang,1 Zhehai Wang,2 Jun Guo,2 Jie Liu,2 Changzheng Li,2 Lin Liu,2 Huan Shi,2 Liyan Liu,2 Huihui Li,2 Chao Xie,2 Xia Zhang,2 Wenwen Sun,1 Minmin Li1 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 2Department of Oncology, Shandong Cancer Hospital, Jinan, Shandong Province, People's Republic of China Background: The purpose of this research was to investigate the relationship between epidermal growth factor receptor (EGFR) mutations and the response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 266 patients with stage IIIB or IV NSCLC who received platinum-based doublet therapies as first-line chemotherapy were investigated retrospectively, and their clinical data were assessed according to EGFR mutation. Results: EGFR mutations were identified in 45.5% of patients. There was no significant difference in response rate between EGFR mutation carriers and EGFR wild-type carriers (P=0.484). Among the patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type, however, those with EGFR mutations responded better to treatment than EGFR wild-type patients (46.2% versus 20.8%, P=0.043). The disease control rate associated with pemetrexed-based treatments was higher than for vinorelbine-based therapies in EGFR mutation patients (P=0.001). EGFR mutation was found in patients with longer progression-free survival and median survival time, and improved 1-year and 2-year overall survival when compared with EGFR wild-type patients (6.1 versus 5.0 months, P=0.004; 18.9 versus 13.8 months, P=0.001; 81.0% versus 63.4%, P=0.002; and 33.9% versus 22.8% P=0.044, respectively). Patients with the EGFR exon 19 mutation had longer progression-free survival than those with EGFR exon 21 mutation (P=0.007). Multivariate analysis showed that the response to first-line chemotherapy and the presence of EGFR mutations were independent prognostic factors in patie