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In this study, we successfully synthesized silicon nanotubes (Si-NTs) and silicon nanowires (Si-NWs) in a controllable manner using a catalyst- and template-free method through the direct electrolysis of SiO2 in a molten CaCl2-CaO system, while also proposing a novel formation mechanism for Si-NTs. Si-NWs are formed through electro-deoxidation when the cell voltage is within the range of CaO decomposition voltage and SiO2 decomposition voltage. By subsequently adjusting the voltage to a value between the decomposition potentials of CaCl2 and CaO, in-situ electro-deoxidation of CaO takes place on the surface of the synthesized Si-NWs, leading to the formation of a Ca layer. The formation of Ca-Si diffusion couple leads to the creation of vacancies within the Si-NWs, as the outward diffusion rate of Si exceeds the inward diffusion rate of Ca. These differential diffusion rates between Si and Ca in a diffusion couple exhibit an analogy to the Kirkendall effect. These vacancies gradually accumulate and merge, forming large voids, which ultimately result in the formation of hollow SiCa-NTs. Through a subsequent dealloying process, the removal of the embedded calcium leads to the formation of Si-NTs. Following the application of a carbon coating, the Si-NTs@C composite showcases a high initial discharge capacity of 3211 mAh·g−1 at 1.5 A·g−1 and exhibits exceptional long-term cycling stability, maintaining a capacity of 977 mAh·g−1 after 2000 cycles at 3.0 A·g−1. [ABSTRACT FROM AUTHOR]

Herein, a novel fluorescence probe Fla-DNP based on flavonol has been designed and synthesized for rapid, specific detection of H2S. With the addition of H2S, Fla-DNP triggered thiolysis and released Fla displaying the "turn-on" fluorescence response at 566 nm, which is consistent with the reaction site predicted by calculating Electrostatic potential and ADCH charges. As an easily available H2S probe, Fla-DNP has the advantages of high selectivity, anti-interference, low detection limit (0.834 μM), short response time (6 min), and large Stokes shift (124 nm). The sensing mechanism of H2S was determined by HRMS analysis and DFT calculation. Moreover, Fla-DNP processes a wide range of multiple applications, including the detection of H2S in environmental water samples with good recovery rates ranging from 89.6% to 102.0%, as well as tracking the production of H2S during food spoilage. Meanwhile, the probe exhibits superior biocompatibility and can not only be available used for H2S detection in living cells but be further designed as an H2S-activated CO photoreleaser, based on which it can be developed as a targeted anti-cancer drug. A novel fluorescence probe Fla-DNP was synthesized utilizing 4-dimethylaminobenzoxanthone fluorescent dye (Fla) as the fluorophore, 2, 4-dinitrobenzenether group (DNP) as the recognition group, which can rapidly respond to H2S with high selectivity, anti-interference, low detection limit (0.834 μM), short response time (6 min), and large Stokes shift (124 nm) characteristics. The practical applications of Fla-DNP were further explored in water, foodstuffs samples and living cells. It is reflected that Fla-DNP can not only track H2S in complex environment water, but also can detect H2S produced during foodstuffs spoilage to monitor food freshness. More importantly, Fla-DNP can be available used for H2S detection in living cells and utilize the properties of the photoinduced release of CO from flavonols to be designed as a bifunctional platform for H2S detection and CO release. It is demonstrated that H2S-activated CO photoreleaser Fla-DNP has promise for development as an anti-cancer drug. [ABSTRACT FROM AUTHOR]

Classifying network time series (NTS) is crucial for automating network administration and ensuring cyberspace security. It enables the detection of anomalies, the identification of network attacks, and the monitoring of performance issues, thereby providing valuable support for network protection and optimization. However, modern communication networks pose challenges for NTS classification methods. These include handling large-scale and complex NTS data, extracting features from intricate datasets, and addressing explainability requirements. These challenges are particularly pronounced for complex 5G networks. Notably, explainability has become crucial for the widespread deployment of network automation for 5G networks and beyond. To tackle these challenges, we propose a path-signature-based NTS classification model called recurrent signature (RecurSig). This innovative model is designed to overcome the time-consuming feature selection problem by utilizing deep-learning (DL) techniques. Additionally, it provides a solution for addressing the black-box issue associated with DL models in network automation systems (NAS) by incorporating an explainable classification approach. Extensive experimentation on various public datasets demonstrates that RecurSig outperforms existing models in accuracy and explainability. The results indicate its potential for application in cyberspace security and automated network management, offering an explainable solution for network protection and optimization. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to investigate the incidence of deep venous thrombosis (DVT), outcomes and its characteristics in patients with chronic heart failure (CHF) in a retrospective setting. Outcomes: Patients died of cardiac shock or acute exacerbation of heart failure (HF), admitted to intensive care unit (ICU) due to acute exacerbation of HF, patients decided to withdraw treatment and return home due to acute exacerbation of HF. Methods: From January 2015 to June 2022, we admitted 359 patients diagnosed with CHF, and lower limb ultrasonography was performed for the examination of DVT after admission. The incidence of DVT was recorded and patients with known risk factors of VTE were identified and excluded after incidence of DVT was calculated. Patients' clinical data were then collected. Results: The occurrence of DVT was 10.0% (36/359), as calf intramuscular vein thrombosis was the main constitution (n = 28, 75%). DVT patients with other factors (carcinoma, surgery, stroke, previous history of DVT) constituted a considerable part (33.3%, 12/36). Age, history of Diabetes Mellitus (DM), levels of DDi (D-Dimer), levels of alanine transferase (ALT) and left ventricular end-diastolic diameter (LVEDd) were independent predictors or risk factors of DVT in CHF patients, while chronic kidney disease (CKD) stage 1–4, white blood cell (WBC) and direct oral anticoagulant (DOAC) were protective factors. Incidence of DVT was correlated with a poor outcome of CHF patients (Pearson Chi-Square test, Value 19.612, P < 0.001). Conclusions: In this retrospective study, incidence of DVT was found to be relatively high among hospitalized CHF patients, while patients with DVT was associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

Nowadays, more and more brands use interesting anime characters to promote and increase brand awareness. However, real-time and interesting promotional materials are also one of the key factors to attract people, so real-time processing of anime characters has also become an effective way to enhance brand awareness. In recent years, with the rapid development of deep learning, image style conversion based on AI technology has become a much-attended artificial intelligence application, but it also suffers from the disadvantages of complex model structure, slow conversion speed, and inconspicuous identity features, which need to be improved. In view of this, this study proposes an anime portrait realization (ARF-GAN) algorithm based on generative adversarial network. This algorithm is based on the Pix2Pix architecture and also uses the U-net network structure with jump connections to connect the encoder’s feature maps directly to the decoder, which in turn enables the network to reconstruct the output data in a better way and the network architecture is more lightweight.This algorithm is based on the Pix2Pix architecture and also uses the U-net network structure with jump connections to connect the encoder’s feature maps directly to the decoder, which in turn enables the network to reconstruct the output data in a better way and the network architecture is more lightweight. It also introduces the CBAM module, which can enhance the model’s expressive and generative capabilities without increasing the model’s complexity, and improve the model’s real-time image processing capability. In addition, this paper also compensates for the problem of image blurring brought by the original architecture by introducing the deblurring module. The experimental results on CartoonFaceAB, DanBooru show that the proposed ARF-GAN has a better generative effect for the task of realizing anime portraits. And comparing with different types of image generating models, it shows better accuracy and lower complexity by using several evaluation indexes such as PSNR and SSIM. This makes it more suitable for brand advertisement promotion, so it has good application value for improving brand awareness. [ABSTRACT FROM AUTHOR]

This paper presents a novel classification method based on spatial–spectral low-rank representation in the hidden field under a Bayesian framework for hyperspectral imagery. The key idea of the method is to simultaneously explore the low-rank property in the spectral domain and nonlocal self-similarity in the spatial domain of the hidden field, which is estimated by sparse multinomial logistic regression in a supervised manner. First, the low rank property in the spectral domain is exploited in local cubic patches. Following this, similar cubic patches are clustered into several groups in a nonlocal sense and patches in each group are assumed to lie in a low-rank subspace. The final model could be efficiently solved by the augmented Lagrangian method. Experimental results on two real hyperspectral datasets validate that the proposed classifier produces a superior performance compared to other state-of-the-art classifiers in terms of overall accuracy, average accuracy and the kappa statistic (k). [ABSTRACT FROM AUTHOR]

Ageing is a critical factor in spinal-cord-associated disorders1, yet the ageing-specific mechanisms underlying this relationship remain poorly understood. Here, to address this knowledge gap, we combined single-nucleus RNA-sequencing analysis with behavioural and neurophysiological analysis in non-human primates (NHPs). We identified motor neuron senescence and neuroinflammation with microglial hyperactivation as intertwined hallmarks of spinal cord ageing. As an underlying mechanism, we identified a neurotoxic microglial state demarcated by elevated expression of CHIT1 (a secreted mammalian chitinase) specific to the aged spinal cords in NHP and human biopsies. In the aged spinal cord, CHIT1-positive microglia preferentially localize around motor neurons, and they have the ability to trigger senescence, partly by activating SMAD signalling. We further validated the driving role of secreted CHIT1 on MN senescence using multimodal experiments both in vivo, using the NHP spinal cord as a model, and in vitro, using a sophisticated system modelling the human motor-neuron–microenvironment interplay. Moreover, we demonstrated that ascorbic acid, a geroprotective compound, counteracted the pro-senescent effect of CHIT1 and mitigated motor neuron senescence in aged monkeys. Our findings provide the single-cell resolution cellular and molecular landscape of the aged primate spinal cord and identify a new biomarker and intervention target for spinal cord degeneration.Motor neuron senescence and neuroinflammation with microglial hyperactivation are intertwined hallmarks of spinal cord ageing. [ABSTRACT FROM AUTHOR]

Time series reconstruction of astronomical catalogues is an important part of data archiving and a basis for time-domain astronomical analysis in the era of time-domain astronomy. As the field of view and sampling frequency of various time-domain telescopes increase, the amount of data to be processed becomes larger and larger. How to optimize the spatial and temporal efficiency of this process with the aid of computer technology becomes a hot issue. To address the problem of spatial efficiency, in this paper, we propose a time series data compression algorithm based on the negative database and dynamic programming, and on this basis, we design a multi-level storage and access query architecture for hot data and non-hot data, which greatly compresses the storage space of data while ensuring the query efficiency. To address the issue of time efficiency, this paper proposes a spatio-temporal data partitioning and layout algorithm suitable for distributed architecture, whose nested round-robin strategy has a wide range of load balancing effects on different spatial locations, temporal locations, and different ranges of temporal data queries, which can effectively ensure the execution efficiency of the distributed system. Experimental results show that the proposed optimization algorithm can keep the system at a low load skewness level of about 4% and save about 83% of storage space. [ABSTRACT FROM AUTHOR]

The non-receptor protein tyrosine phosphatases gene family (PTPNs) is involved in the tumorigenesis and development of many cancers, but the role of PTPNs in acute myeloid leukemia (AML) remains unclear. After a comprehensive evaluation on the expression patterns and immunological effects of PTPNs using a pan-cancer analysis based on RNA sequencing data obtained from The Cancer Genome Atlas, the most valuable gene PTPN2 was discovered. Further investigation of the expression patterns of PTPN2 in different tissues and cells showed a robust correlation with AML. PTPN2 was then systematically correlated with immunological signatures in the AML tumor microenvironment and its differential expression was verified using clinical samples. In addition, a prediction model, being validated and compared with other models, was developed in our research. The systematic analysis of PTPN family reveals that the effect of PTPNs on cancer may be correlated to mediating cell cycle-related pathways. It was then found that PTPN2 was highly expressed in hematologic diseases and bone marrow tissues, and its differential expression in AML patients and normal humans was verified by clinical samples. Based on its correlation with immune infiltrates, immunomodulators, and immune checkpoint, PTPN2 was found to be a reliable biomarker in the immunotherapy cohort and a prognostic predictor of AML. And PTPN2'riskscore can accurately predict the prognosis and response of cancer immunotherapy. These findings revealed the correlation between PTPNs and immunophenotype, which may be related to cell cycle. PTPN2 was differentially expressed between clinical AML patients and normal people. It is a diagnostic biomarker and potentially therapeutic target, providing targeted guidance for clinical treatment. [ABSTRACT FROM AUTHOR]

Iron is important for life, and iron deficiency impairs development, but whether the iron level regulates neural differentiation remains elusive. In this study, with iron-regulatory proteins (IRPs) knockout embryonic stem cells (ESCs) that showed severe iron deficiency, we found that the Pax6- and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1−/−IRP2−/− ESCs were significantly decreased after inducing neural differentiation. Consistently, in vivo study showed that the knockdown of IRP1 in IRP2−/− fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons. These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation. When supplementing IRP1−/−IRP2−/− ESCs with iron, these ESCs could differentiate normally. Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species (ROS) production caused by the substantially low level of iron and the down-regulation of iron-sulfur cluster protein ISCU, which, in turn, affected the proliferation and differentiation of stem cells. Thus, the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation. [ABSTRACT FROM AUTHOR]

The development of medical sensors and the Internet of Things (IoT) offers many opportunities for research on disease diagnosis and prognosis in the electronic healthcare (eHealth) industry. IoT medical applications use wearable medical sensor devices that can be connected to the Internet for remote monitoring. However, cloud computing technology cannot meet the real-time and low-latency requirements of IoT applications in eHealth. As an intermediate layer between things and clouds, fog computing has features such as enhanced low latency, mobility, network bandwidth, security and privacy. Therefore, fog computing is very useful for the diagnosis and prognosis of diseases in the eHealth industry. In this paper, we undertake a comprehensive survey on fog computing used in eHealth. We summarize the main challenges in the eHealth industry and analyze the corresponding solutions proposed by the existing works. [ABSTRACT FROM AUTHOR]

The chemically-crosslinked composite hydrogel based on acylated xylan and silanized graphene oxide was prepared via free radical polymerization as a novel adsorbent for the removal of Cu2+ ions from aqueous solution. The chemical structures and morphologies of the silanized graphene oxide and acylated xylan as well as the prepared hydrogels were characterized by FT-IR, XPS, SEM and TEM. The swelling ratios of the prepared hydrogels were determined, and the results showed that the chemically-crosslinked hydrogel was pH-sensitive, and the swelling kinetics of the hydrogels followed Schott second-order kinetic. The optimum pH for the adsorption of Cu2+ ions onto the chemically-crosslinked composite hydrogel was found at the value of 5 and the maximum adsorption amount of Cu2+ ions was evaluated to be 228 mg/g. The adsorption isotherm accorded with the Freundlich model, and the pseudo-second order kinetic model was suitable to describe the adsorption process. The study of adsorption thermodynamics indicated that the adsorption of Cu2+ ions onto the chemically-crosslinked composite hydrogel was endothermal and spontaneous, and the adsorption amount rose with an increase in temperature. In addition, higher desorption percentages of Cu2+ ions from the used hydrogel were also achieved (77.3% after recycling for 6 times). All obtained results indicated that the prepared chemically-crosslinked hydrogel is promising for water treatment and collection of metal ions. [ABSTRACT FROM AUTHOR]

In this paper, two efficient quantum image steganography protocols based on double-layer matrix coding are proposed. The first protocol is based on the high embedding efficiency of the classic Zhang Weiming, Zhang Xinpeng and Wang Shuozhong's steganography framework and matrix coding, combined with quantum image carrier, so that the new protocol not only has very high embedding efficiency but also has high security. The second protocol further proposes a more efficient quantum image steganography protocol, which not only achieves a higher embedding efficiency than the first protocol but also doubles the capacity of the first protocol. To reflect the practicality of these two protocols, we also designed dedicated quantum circuits to embed and extract secret information. Based on the IBMQ quantum experiment platform, we successfully ran the core circuits of the protocol and gave the corresponding results. The simulation results based on MATLAB and the mathematical analysis also show that the two new protocols not only have good imperceptibility but also have high embedding efficiency. [ABSTRACT FROM AUTHOR]

The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been implicated with many diseases. Here, we determine structures of the human T-type CaV3.3 channel, in the absence and presence of antihypertensive drug mibefradil, antispasmodic drug otilonium bromide and antipsychotic drug pimozide. CaV3.3 contains a long bended S6 helix from domain III, with a positive charged region protruding into the cytosol, which is critical for T-type CaV channel activation at low voltage. The drug-bound structures clearly illustrate how these structurally different compounds bind to the same central cavity inside the CaV3.3 channel, but are mediated by significantly distinct interactions between drugs and their surrounding residues. Phospholipid molecules penetrate into the central cavity in various extent to shape the binding pocket and play important roles in stabilizing the inhibitor. These structures elucidate mechanisms of channel gating, drug recognition, and actions, thus pointing the way to developing potent and subtype-specific drug for therapeutic treatments of related disorders. T-type calcium channels are implicated in many diseases. Here, multiple structures of CaV3.3 channel elucidate molecular mechanisms of T-type CaV channels activation at low voltage and interaction with different clinically used channel blockers. [ABSTRACT FROM AUTHOR]

STAT3 plays a particularly important role in several cancer-related signal transduction pathways. Silencing STAT3 via RNA interference or small molecule inhibitors induces the apoptosis of tumor cells, thereby inhibiting the growth of the tumors. In this study, short-hairpin RNA sequences targeting the STAT3 genes were designed, synthesized, and then connected to pGPU6/GFP/Neo plasmids as the shRNA-expression vectors. The expression of STAT3-shRNA was analyzed by real-time PCR, western blotting, and cell apoptosis assay to study the growth and apoptosis of the cells. Then, the effect of STAT3 knockdown on the NCI-H1650 cells was studied in a tumor mouse model. The results revealed that, after an in vitro transfection, the proliferation of NCI-H1650 cells was inhibited, and the cells were induced to apoptosis. The mRNA and protein expression levels of STAT3 were downregulated in the STAT3-shRNA group. In vivo, the tumor mass and volume in the STAT3-shRNA group were significantly lower than in the other two groups. Both the in vivo and in vitro results demonstrated a long-period inhibiting effect on NSCLC, especially in vivo, when the tumor inhibition rate could reach 50% in the STAT3-shRNA group, which is an exciting outcome. Moreover, the study of the conjugation of STAT3-shRNA and chitosan-based vectors revealed that they could be combined steadily with good cytocompatibility and transfection efficiency. These results together provide convincing evidence for the application of STAT3-shRNA used in the treatment of non-small lung cancer, which could be a promoting prospect for the development of gene therapy. [ABSTRACT FROM AUTHOR]

FDA-approved anti-PD-L1 antibody drug Atezolizumab is a human IgG1 without glycosylation by an N297A mutation. Aglycosylation of IgG1 has been used to completely remove the unwanted Fc-mediated functions such as antibody-dependent cytotoxicity (ADCC). However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy. Here, we report the development of the anti-PD-L1 antibody drug Maxatezo, a glycosylated version of Atezolizumab, with no ADCC activity, better thermo-stability, and significantly improved anti-tumor activity in vivo. Using Atezolizumab as the starting template, we back-mutated A297N to re-install the glycosylation, and inserted a short, flexible amino acid sequence (GGGS) between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shows that insertion of GGGS, does not alter the anti-PD-L1′s affinity and inhibitory activity, while completely abolishing ADCC activity. Maxatezo has a similar glycosylation profile and expression level (up to 5.4 g/L) as any normal human IgG1. Most importantly, Maxatezo's thermal stability is much better than Atezolizumab, as evidenced by dramatic increases of Tm1 from 63.55 °C to 71.01 °C and Tagg from 60.7 °C to 71.2 °C. Furthermore, the levels of ADA in mice treated with Maxatezo were significantly lower compared with animals treated with Atezolizumab. Most importantly, at the same dose (10 mg/kg), the tumor growth inhibition rate of Maxatezo was 98%, compared to 68% for Atezolizumab. [ABSTRACT FROM AUTHOR]

Cenpj is a centrosomal protein located at the centrosomes and the base of cilia, it plays essential roles in regulating neurogenesis and cerebral cortex development. Although centrosomal and cilium dysfunction are one of the causes of obesity, insulin resistance, and type 2 diabetes, the role that Cenpj plays in the regulation of body weight remains unclear. Here, we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice. Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size. We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages, resulting in a dramatic decrease in the number of Proopiomelanocortin (POMC) neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus (ARC) in adults. Furthermore, depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus (PVN), with decreased melanocortin-4 receptors (MC4R) expression in PVN neurons. The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight, providing a foundation for further understanding of the pathological mechanisms of related diseases. [ABSTRACT FROM AUTHOR]

Magnetic-geared dual-rotor motor (MGDRM) has been considered as a promising candidate of the power split device in the hybrid electric vehicles. Essentially, the MGDRM is a pure electrical component without the brush, slip ring and mechanical gears, so its reliability and lifetime can perform well. However, the design principle of the MGDRM has not been fully transferred to a practical technology. The asymmetrical back-EMF of this motor is an issue, which is a sake of the torque ripple produced by the MGDRM. The complementary structure has been proposed to improve the back-EMF, but some detailed problems of this solution have not been addressed. This paper gives the analysis and discussion on the segment design of the complementary MGDRM. Two prototype machines are also fabricated for the experimental validation of the research results. [ABSTRACT FROM AUTHOR]

A novel Gram-stain-positive, aerobic, cocci-shaped actinobacterium, designated YIM 75000T, was isolated from a soil sample collected from a dry-hot river valley in Yunnan Province, P.R. China. Growth was observed at 10–45 °C (optimal 37 °C), 0–8% (w/v) NaCl (optimal at 0–3% NaCl) and pH 6.0–8.0 (optimal at pH 7.3). The peptidoglycan contained LL-diaminopimelic acid, glycine, glutamic acid as well as alanine and its type was A3γ with an LL-Dpm-Gly interpeptide bridge. The major cellular fatty acids (> 10%) were C16:0, Summed In Feature 3 (C16:1ω6c/C16:1ω7c) and C17:1ω8c. The predominant menaquinone was MK-9(H4). The major whole-cell sugars contained rhamnose, ribose, arabinose and mannose. The DNA G+C content was 77.0 mol%. The 16S rRNA gene sequence similarities of strain YIM 75000T with other species were less than 94%. Phylogenetic analyses based on 16S rRNA gene sequences and genome data, revealed that strain YIM 75000T together with the genus Motilibacter formed a distinct phylogenetic lineage within the phylum Actinobacteria, separating them from members of all orders. Strain YIM 75000T showed 73.4–73.7% average nucleotide identity and 19.5–19.7% digital DNA–DNA hybridization identity with the closely related genus Motilibacter. Based on the phenotypic, phylogenetic and chemotaxonomic data, it is proposed that the new isolate represents the nomenclature type of the novel species Vallicoccus soli gen. nov., sp. nov. (YIM 75000T = DSM 45377T = KCTC 49228T = CGMCC 1.13844T) which is the nomenclature type of the novel genus Vallicoccus gen. nov. within Vallicoccaceae fam. nov and Motilibacterales ord. nov in the phylum Actinobacteria. The family Vallicoccaceae fam. nov. and the order Motilibacterales (contains Vallicoccaceae fam. nov. and Motilibacteraceae Lee 2013) ord. nov. are formally proposed. [ABSTRACT FROM AUTHOR]

Cardiac arrhythmia has been identified as a type of cardiovascular diseases (CVDs) that causes approximately 12% of all deaths globally. The development of Internet-of-Things has spawned novel ways for heart monitoring but also presented new challenges for manual arrhythmia detection. An automated method is highly demanded to provide support for physicians. Current attempts for automatic arrhythmia detection can roughly be divided as feature-engineering based and deep-learning based methods. Most of the feature-engineering based methods are suffering from adopting single classifier and use fixed features for classifying all five types of heartbeats. This introduces difficulties in identification of the problematic heartbeats and limits the overall classification performance. The deep-learning based methods are usually not evaluated in a realistic manner and report overoptimistic results which may hide potential limitations of the models. Moreover, the lack of consideration of frequency patterns and the heart rhythms can also limit the model performance. To fill in the gaps, we propose a framework for arrhythmia detection from IoT-based ECGs. The framework consists of two modules: a data cleaning module and a heartbeat classification module. Specifically, we propose two solutions for the heartbeat classification task, namely Dynamic Heartbeat Classification with Adjusted Features (DHCAF) and Multi-channel Heartbeat Convolution Neural Network (MCHCNN). DHCAF is a feature-engineering based approach, in which we introduce dynamic ensemble selection (DES) technique and develop a result regulator to improve classification performance. MCHCNN is deep-learning based solution that performs multi-channel convolutions to capture both temporal and frequency patterns from heartbeat to assist the classification. We evaluate the proposed framework with DHCAF and with MCHCNN on the well-known MIT-BIH-AR database, respectively. The results reported in this paper have proven the effectiveness of our framework. [ABSTRACT FROM AUTHOR]

The neuroendocrine hypothalamus is the central regulator of vital physiological homeostasis and behavior. However, the cellular and molecular properties of hypothalamic neural progenitors remain unexplored. Here, hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells are found to be neural progenitors in the developing mammalian hypothalamus. The hmRG cells originate from hRG cells and produce neurons. During the early development of hypothalamus, neurogenesis occurs in radial columns and is initiated from hRG cells. The radial glial fibers are oriented toward the locations of hypothalamic subregions which act as a scaffold for neuronal migration. Furthermore, we use single-cell RNA sequencing to reveal progenitor subtypes in human developing hypothalamus and characterize specific progenitor genes, such as TTYH1, HMGA2, and FAM107A. We also demonstrate that HMGA2 is involved in E2F1 pathway, regulating the proliferation of progenitor cells by targeting on the downstream MYBL2. Different neuronal subtypes start to differentiate and express specific genes of hypothalamic nucleus at gestational week 10. Finally, we reveal the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. Our identification of cellular and molecular properties of neural progenitors provides a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus. The hypothalamus performs a wide range of vital physiological functions, including growth and reproductive behaviors, and circadian rhythms. The authors identify and characterize hypothalamic radial glial and hypothalamic mantle zone radial glial cells as the neural progenitors in the hypothalamus. [ABSTRACT FROM AUTHOR]

Cloud service selection is one of the key issues for service users. An important concern for this issue is to make an optimal policy that adapt to a dynamic cloud marketplace that different types of changes may happen during a service consumption process, for example, the change of the cloud service providers and the provisioned cloud services in this marketplace, the change of the requirements of service users on service performance, e.g. Quality of services (QoSs) and service functions, and the change of the termination time points of a consumed service. These changes require a dynamic modelling method for cloud service selection, while existing service selection approaches rarely consider such dynamicity. Therefore, we propose a novel Cloud service selection framework based on Markov decision processes (MDPs), which can help Cloud service users to select a set of services meeting the QoS requirements and the economic constraints of service users. The MDP, as one of the primary decision theoretic planning tools, is capable of formalizing the uncertainties in the dynamic marketplace, and making service selection policies to achieve the best trade-off between costs and benefits. We use the causal-mapping approach to construct the structure of influence diagrams, and a Gauss kernel estimation method to estimate the marginal distributions of QoSs. Our experiments are based on simulated scenarios and real datasets. The experimental results show that the proposed framework is capable of accurately capturing the features of QoS values, predicting the QoS performance, and efficiently adapting to the changes in a long-term service consumption to facilitate policy determinations in a dynamic marketplace. [ABSTRACT FROM AUTHOR]

Hyperspectral unmixing is essential for efficient hyperspectral image processing. Nonnegative matrix factorization based on minimum volume constraint (MVC-NMF) is one of the most widely used methods for unsupervised unmixing for hyperspectral image without the pure-pixel assumption. But the model of MVC-NMF is unstable, and the traditional solution based on projected gradient algorithm (PG-MVC-NMF) converges slowly with low accuracy. In this paper, a novel parallel method is proposed for minimum volume constrained hyperspectral image unmixing on CPU-GPU Heterogeneous Platform. First, a optimized unmixing model of minimum logarithmic volume regularized NMF is introduced and solved based on the second-order approximation of function and alternating direction method of multipliers (SO-MVC-NMF). Then, the parallel algorithm for optimized MVC-NMF (PO-MVC-NMF) is proposed based on the CPU-GPU heterogeneous platform, taking advantage of the parallel processing capabilities of GPUs and logic control abilities of CPUs. Experimental results based on both simulated and real hyperspectral images indicate that the proposed algorithm is more accurate and robust than the traditional PG-MVC-NMF, and the total speedup of PO-MVC-NMF compared to PG-MVC-NMF is over 50 times. [ABSTRACT FROM AUTHOR]

Background: Chemical peeling is an efficient method for the treatment of pigment disorders. For freckles, medium-depth to deep peeling using a phenol solution is one of the most effective chemical peels, and modifications of facial skin can be observed up to 20 years after peeling. However, applying phenol to the skin may cause serious side effects. Phenol peeling has been rarely used in Asia due to its tendency to cause permanent pigmentary changes and hypertrophic scars.Methods: In total, 896 Chinese inpatients with facial freckles were enrolled in this study. The phenol formula was modified with crystalline phenol, dyclonine, camphor, anhydrous alcohol and glycerin and adjusted to a concentration of 73.6-90.0%. The entire peeling treatment was divided into two procedures performed separately on 2 days.Results: All patients exhibited 26% or greater improvement, and 99.66% of patients exhibited 51% or greater improvement (good and excellent). Scarring and systemic complications were not observed in any patient.Conclusions: The modified phenol formula is very effective and safe for the treatment of facial freckles in Asian patients.Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of p70S6K in the transdifferentiation of fibroblasts to myofibroblasts in pterygium tissue growth on the cornea.Results: Quantitative real-time PCR and immunohistochemistry showed that p70S6K expression was higher in pterygium tissues than in normal conjunctival tissues. Higher p70S6K RNA expression levels were correlated with higher pterygium grades. Additionally, western blot analysis revealed that phosphorylated (activated) p70S6K (p-p70S6K) expression was significantly correlated with α-smooth muscle actin (α-SMA, a hallmark of transdifferentiation) expression in cultured human pterygium fibroblasts (HPFs). Furthermore, p70S6K knockdown and the specific mTOR inhibitor rapamycin decreased the expression levels of p-p70S6K and α-SMA in cultured fibroblasts from grade T3 pterygium.Conclusions: p70S6K activation promotes the transdifferentiation of pterygium fibroblasts to myofibroblasts. Thus, targeting p70S6K may be a useful strategy in the management of pterygium. [ABSTRACT FROM AUTHOR]

Various genetically modified bioreactor systems have been developed to meet the increasing demands of recombinant proteins. Silk gland of Bombyx mori holds great potential to be a cost-effective bioreactor for commercial-scale production of recombinant proteins. However, the actual yields of proteins obtained from the current silk gland expression systems are too low for the proteins to be dissolved and purified in a large scale. Here, we proposed a strategy that reducing endogenous sericin proteins would increase the expression yield of foreign proteins. Using transgenic RNA interference, we successfully reduced the expression of BmSer1 to 50%. A total 26 transgenic lines expressing Discosoma sp. red fluorescent protein (DsRed) in the middle silk gland (MSG) under the control of BmSer1 promoter were established to analyze the expression of recombinant. qRT-PCR and western blotting showed that in BmSer1 knock-down lines, the expression of DsRed had significantly increased both at mRNA and protein levels. We did an additional analysis of DsRed/BmSer1 distribution in cocoon and effect of DsRed protein accumulation on the silk fiber formation process. This study describes not only a novel method to enhance recombinant protein expression in MSG bioreactor, but also a strategy to optimize other bioreactor systems. [ABSTRACT FROM AUTHOR]

Background and Objectives: The US Food and Drug Administration, World Health Organization and European Medicines Agency have allowed biowaiver for some BCS class III drugs, but shortened the requisite dissolution time of BCS class III drugs from 30 to 15 min, considering their site-specific absorption and others risk. The objective of this study was to assess the effects of site-specific absorption, low absorbed fraction ( F ) and gastric emptying rate on the biowaiver extension of BCS class III drugs. Methods: The oral absorption of BCS class III drugs nadolol, acebutolol and atenolol which were P-gp substrates, was simulated using GastroPlus software with physiological parameters reflecting site-specific and site-independent absorption. Then, the simulation results were compared with the experimental data in literature. Simulation with different dissolution rates (>85 % solubility, T = 15-180 min) was performed to predict absorption (maximum concentration, C and area under the concentration-time curve from time 0 to infinity, AUC) of the above model/virtual drugs ( F 3.81-80.14 %). Results: The results of this study indicated that the site-specific absorption and low F magnified the effect of dissolution rate on C and AUC. However, the oral absorption of model drugs was not sensitive to the change of gastric emptying rate from 0.1, 0.25, 0.5 to 1 h. Conclusions: Based on the results of this study, we suggest that for BCS class III drug with high F (about >80 %), the biowaiver should extend to rapid dissolution ( T = 30 min), and 30 % of F as the boundary of intermediate permeability class (30 % < F < 85 %). [ABSTRACT FROM AUTHOR]

R-phycoerythrin prepared from red algae ( Bangia fusco- purpurea) was hydrolyzed by pepsin followed by trypsin to produce angiotensin I-converting enzyme (ACE) inhibitory peptides. The IC of the hydrolysate of R-phycoerythrin (HRPE) was 191.1 ± 4.1 μg/mL, and the molecular weight of most products (89.9 %) was below 2 kDa. After sequential gel permeation and reversed-phase chromatography steps to purify the hydrolysate, two peptides with the sequences of ALLAGDPSVLEDR and VVGGTGPVDEWGIAGAR were obtained and their IC values were 57.2 ± 5.0 and 66.2 ± 4.2 μg/mL, respectively. The ALLAGDPSVLEDR and VVGGTGPVDEWGIAGAR peptides were derived from the β- and α-subunit of R-phycoerythrin from Polysiphonia urceolata, with a 92.3 % (12/13) and 94.1 % (16/17) match, respectively. Both peptides were resistant to digestion by proteinases common in the gastrointestinal tract. Therefore, the identified novel peptides derived from R-phycoerythrin may be used as potential nutraceuticals for development of functional foods. [ABSTRACT FROM AUTHOR]

5, Atezolizumab induced high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). In the Abstract section, "However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy" now reads: "However, aglycosylated Atezolizumab is unstable and easy to form aggregates." 5, Atezolizumab induced extremely high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). [Extracted from the article]

Many sources of stress cause accumulation of unfolded or misfolded proteins in endoplasmic reticulum (ER), which elicits the unfolded protein response (UPR) to either promote cell survival or programmed cell death depending on different developmental context or stress severity. The Arabidopsis membrane-associated transcription factor, bZIP28, is the functional equivalent of mammalian ATF6, which relocates from the ER to the Golgi where it is proteolytically processed and released from the membrane to the nucleus to mediate the UPR. Although the canonical site-1 protease (S1P) cleavage site on the ER lumen-facing domain is well conserved between bZIP28 and ATF6, the importance of S1P cleavage on bZIP28 has not been experimentally demonstrated. Here we provide genetic evidence that the RRIL site, but not the RVLM site, on the lumen-facing domain of bZIP28 is critical for the biological function of bZIP28 under ER stress condition. Further biochemistry and cell biology studies demonstrated that the RRIL site, but not the RVLM site, is required for proteolytic processing and nuclear relocation of bZIP28 in response to ER stress. Our results reveal that S1P cleavage site plays a pivotal role in activation and function of bZIP28 during UPR in plants. [ABSTRACT FROM AUTHOR]

The effect of high frequency oscillatory ventilation (HFOV) at early stage on hemodynamic parameters, extravascular lung water (EVLW), lung capillary permeability, CC16 and sICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome (ARDS) was explored. Central vein pressure (CVP) and pulse indicator continuous cardiac output (PiCCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index (EVLWI), EVLW/intratroracic blood volume (ITBV) and pulmonary vascular permeability index (PVPI) were measured before and after modeling (T0 and T1), and T2 (1 h), T3 (2 h), T4 (3 h) and T5 (4 h) after HFOV. CC16 and sICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group ( P<0.05). The EVLWI in ARDSp group was increased at T1 ( P=0.008), and sustained continuously within 2 h ( P=0.679, P=0.216), but decreased at T4 ( P=0.007) and T5 ( P=0.037). The EVLWI in ARDSexp group was also increased at T1 ( P=0.003), but significantly decreased at T3 ( P=0.002) and T4 ( P=0.019). PVPI was increased after modeling in both two groups ( P=0.004, P=0.012), but there was no significant change within 4 h (T5) under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI ( P=0.13), ΔPVPI ( P=0.28) and ΔEVLW/ITBV between the two groups ( P=0.63). The significant decreases in both CC16 and sICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV. [ABSTRACT FROM AUTHOR]

Abalone gonads were hydrolyzed using alcalase followed by papain to produce angiotensin I-converting enzyme (ACE) inhibitory peptides. Gel filtration column chromatography analysis showed that the molecular weight of the fraction with high ACE inhibitory activity was below 1 kDa, which occupied 93.1 % of total hydrolysate. The ACE inhibitory peptide was purified by a series of column chromatographies, and the sequence of purified peptide was further identified as Ala-Met-Asn (AMN) by automated Edman degradation method. The triple peptide was then synthesized and had an ACE inhibitory activity with IC value of 106.24 μg/mL. After gastrointestinal digestion, the peptide still remained bioactivity. Lineweaver-Burk plots indicated that AMN acts as a non-competitive inhibitor against ACE. Our present study suggested that AMN derived from abalone gonad by-products may be used as an ideal nutrient for development of functional foods. [ABSTRACT FROM AUTHOR]

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology, for which a genetic influence is suspected. But whether single nucleotide polymorphism (SNP) of caspase-3 rs72689236 is associated with Kawasaki disease is controversial. The aim of our study is to assess the association between the SNP of caspase-3 and risk for Kawasaki disease. We searched PubMed, MEDLINE, EMBASE, Springer, Elsevier Science Direct, Cochrane Library Google scholar, CNKI (China National Knowledge Infrastructure, in Chinese) and Wanfang database (in Chinese) to identify studies investigating the association between rs72689236 polymorphism and Kawasaki disease occurrence. There were five eligible studies, which included 4,241 (case group 1,560; control group 2,681) participants in this meta-analysis. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated in a fixed-effects model (the Mantel-Haenszel method) or a random-effects model (the DerSimonian and Laird method) when appropriate. Significant associations were found under the overall ORs for A-allele comparison (A vs. G, pooled OR 1.33, 95 % CI 1.21-1.46), AA versus GG comparison (pooled OR 1.64, 95 % CI 1.35-2.00), GA versus GG comparison (pooled OR 1.42, 95 % CI 1.24-1.63), recessive model (AA vs. GG + GA, pooled OR 1.37, 95 % CI 1.15-1.64) and dominant model (AA + GA vs. GG, pooled OR 1.47, 95 % CI 1.29-1.67). This meta-analysis suggested that SNP rs72689236 of caspase-3 might be associated with susceptibility of Kawasaki disease and the allele A might increase the risk of Kawasaki disease in Asian samples such as Japanese and Chinese. In addition, individual studies with large sample size are needed to further evaluate the associations in various ethnic populations. [ABSTRACT FROM AUTHOR]

Autolysis of North Pacific krill protein in acidic and alkaline solubilization during protein recovery via isoelectric solubilization/precipitation was investigated. Pronounced auto-degradation of myosin heavy chain and actin from krill protein was observed at alkaline pH values (pH 9.0-12.0), with maximum autolytic activity at about pH 12.0. Meanwhile, proteolytic activity in krill protein at pH 12.0 was observed at low temperatures, suggesting a possible cause for the autolysis of krill protein during the protein recovery process. Three major proteinases were detected by zymographic analysis of myofibrillar protein, with approximate molecular weights of 26 kDa (KP-1), 18 kDa (KP-2) and 17 kDa (KP-3). KP-3 was active over a pH range from pH 5.0-12.0, suggesting that it may be responsible for the autolysis of krill protein during alkaline-induced protein recovery. Further study on substrate specificity and inhibitory specificity of KP-3 showed that KP-3 is serine type proteinase. [ABSTRACT FROM AUTHOR]

Since 2008, enterovirus 71 (EV71) has been responsible for high-mortality seasonal epidemics of hand, foot and mouth disease in China. Currently many groups in the world are in the process of developing EV71 vaccines to combat this deadly disease. We have developed three EV71-specific monoclonal antibodies, and in this study we report the establishment of a fast and cost-effective sandwich ELISA kit for measurement of virus concentration in EV71 vaccines using a pair of mouse anti-EV71 monoclonal antibodies. The system is specific for EV71 virus, with no cross-reactivity to coxsackievirus A16, H1N1, rabies, and hepatitis A. Using a reference EV71 vaccine standard, the sensitivity of the assay kit was determined to be 0.82 U/ml, with a linear range between 3.75 and 120 U/ml. [ABSTRACT FROM AUTHOR]