Search

Abstract As human‐machine interaction (HMI) in healthcare continues to evolve, the issue of trust in HMI in healthcare has been raised and explored. It is critical for the development and safety of healthcare that humans have proper trust in medical machines. Intelligent machines that have applied machine learning (ML) technologies continue to penetrate deeper into the medical environment, which also places higher demands on intelligent healthcare. In order to make machines play a role in HMI in healthcare more effectively and make human‐machine cooperation more harmonious, the authors need to build good human‐machine trust (HMT) in healthcare. This article provides a systematic overview of the prominent research on ML and HMT in healthcare. In addition, this study explores and analyses ML and three important factors that influence HMT in healthcare, and then proposes a HMT model in healthcare. Finally, general trends are summarised and issues to consider addressing in future research on HMT in healthcare are identified.

Abstract Kluyveromyces marxianus is a food‐safe yeast with great potential for producing heterologous proteins. Improving the yield in K. marxianus remains a challenge and incorporating large‐scale functional modules poses a technical obstacle in engineering. To address these issues, linear and circular yeast artificial chromosomes of K. marxianus (KmYACs) were constructed and loaded with disulfide bond formation modules from Pichia pastoris or K. marxianus. These modules contained up to seven genes with a maximum size of 15 kb. KmYACs carried telomeres either from K. marxianus or Tetrahymena. KmYACs were transferred successfully into K. marxianus and stably propagated without affecting the normal growth of the host, regardless of the type of telomeres and configurations of KmYACs. KmYACs increased the overall expression levels of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins. In high‐density fermentation, the use of KmYACs resulted in a glucoamylase yield of 16.8 g/l, the highest reported level to date in K. marxianus. Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased flavin adenine dinucleotide biosynthesis, enhanced flux entering the tricarboxylic acid cycle, and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins. Consistently, supplementing lysine or arginine further improved the yield. Therefore, KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research. Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins, and this strategy may be applied to optimize other microbial cell factories.

On September 16, 2021, a MS6.0 earthquake struck Luxian County, one of the shale gas blocks in the Southeastern Sichuan Basin, China. To understand the seismogenic environment and its mechanism, we inverted a fine three-dimensional S-wave velocity model from ambient noise tomography using data from a newly deployed dense seismic array around the epicenter, by extracting and jointly inverting the Rayleigh phase and group velocities in the period of 1.6–7.2 s. The results showed that the velocity model varied significantly beneath different geological units. The Yujiasi syncline is characterized by low velocity at depths of ∼ 3.0–4.0 km, corresponding to the stable sedimentary layer in the Sichuan Basin. The eastern and western branches of the Huayingshan fault belt generally exhibit high velocities in the NE-SW direction, with a few local low-velocity zones. The Luxian MS6.0 earthquake epicenter is located at the boundary between the high- and low-velocity zones, and the earthquake sequences expand eastward from the epicenter at depths of 3.0–5.0 km. Integrated with the velocity variations around the epicenter, distribution of aftershock sequences, and focal mechanism solution, it is speculated that the seismogenic mechanism of the main shock might be interpreted as the reactivation of pre-existing faults by hydraulic fracturing.

Soy leghemoglobin, when bound to heme, imparts a meat-like color and flavor and can serve as a substitute for animal-derived proteins. Enhancing cellular heme synthesis improves the recombinant expression of leghemoglobin in yeast. To achieve high-level expression of leghemoglobin A (LBA) in Kluyveromyces marxianus, a food-safe yeast, large-scale heme synthesis modules were transferred into K. marxianus using yeast artificial chromosomes (KmYACs). These modules contained up to 8 native and heterologous genes to promote the supply of heme precursors and downstream synthesis. Next, eight genes inhibiting heme or LBA synthesis were individually or combinatorially deleted, with the lsc1Δssn3Δ mutant yielding the best results. Subsequently, heme synthesis modules were combined with the lsc1Δssn3Δ mutant. In the resulting strains, the module genes were all actively expressed. Among these module genes, heterologous S. cerevisiae genes in the downstream heme synthesis pathway significantly enhanced the expression of their counterparts in K. marxianus, resulting in high heme content and LBA yield. After optimizing the medium recipe by adjusting the concentrations of glucose, glycine, and FeSO4·7H2O, a heme content of 66.32 mg/L and an intracellular LBA titer of 7.27 g/L were achieved in the engineered strain in a 5 L fermentor. This represents the highest intracellular expression of leghemoglobin in microorganisms to date. The leghemoglobin produced by K. marxianus can be utilized as a safe ingredient for plant-based protein products.

Abstract Depression has become one of the most common mental illnesses in the world. For better prediction and diagnosis, methods of automatic depression recognition based on speech signal are constantly proposed and updated, with a transition from the early traditional methods based on hand‐crafted features to the application of architectures of deep learning. This paper systematically and precisely outlines the most prominent and up‐to‐date research of automatic depression recognition by intelligent speech signal processing so far. Furthermore, methods for acoustic feature extraction, algorithms for classification and regression, as well as end to end deep models are investigated and analysed. Finally, general trends are summarised and key unresolved issues are identified to be considered in future studies of automatic speech depression recognition.

Abstract Background The Coronavirus Disease 2019 (COVID-19) pandemic was a huge shock to society, and the ensuing information problems had a huge impact on society at the same time. The urgent need to understand the Infodemic, i.e., the importance of the spread of false information related to the epidemic, has been highlighted. However, while there is a growing interest in this phenomenon, studies on the topic discovery, data collection, and data preparation phases of the information analysis process have been lacking. Objective Since the epidemic is unprecedented and has not ended to this day, we aimed to examine the existing Infodemic-related literature from January 2019 to December 2022. Methods We have systematically searched ScienceDirect and IEEE Xplore databases with some search limitations. From the searched literature we selected titles, abstracts and keywords, and limitations sections. We conducted an extensive structured literature search and analysis by filtering the literature and sorting out the available information. Results A total of 47 papers ended up meeting the requirements of this review. Researchers in all of these literatures encountered different challenges, most of which were focused on the data collection step, with few challenges encountered in the data preparation phase and almost none in the topic discovery section. The challenges were mainly divided into the points of how to collect data quickly, how to get the required data samples, how to filter the data, what to do if the data set is too small, how to pick the right classifier and how to deal with topic drift and diversity. In addition, researchers have proposed partial solutions to the challenges, and we have also proposed possible solutions. Conclusions This review found that Infodemic is a rapidly growing research area that attracts the interest of researchers from different disciplines. The number of studies in this field has increased significantly in recent years, with researchers from different countries, including the United States, India, and China. Infodemic topic discovery, data collection, and data preparation are not easy, and each step faces different challenges. While there is some research in this emerging field, there are still many challenges that need to be addressed. These findings highlight the need for more articles to address these issues and fill these gaps.

Depression has become a widespread health concern today. Understanding the influencing factors can promote human mental health as well as provide a basis for exploring preventive measures. Combining LassoNet with recurrent neural network (RNN), this study constructed a screening model ,LassoNet-RNN, for identifying influencing factors of individual depression. Based on multi-wave surveys of China Health and Retirement Longitudinal Study (CHARLS) dataset (11,661 observations), we analyzed the multivariate time series data and recognized 27 characteristic variables selected from four perspectives: demographics, health-related risk factors, household economic status, and living environment. Additionally, the importance rankings of the characteristic variables were obtained. These results offered insightful recommendations for theoretical developments and practical decision making in public health.

The interest of advertising designers and operators in crafting appealing images is steadily increasing. With a primary focus on image attractiveness, this study endeavors to uncover the correlation between image features and attractiveness. The ultimate objective is to enhance the accuracy of predicting image attractiveness to achieve visually captivating effects. The experimental subjects encompass images sourced from the Shutterstock website, and the correlation between image features and attractiveness is analyzed through image attractiveness scores. In our experiments, we extracted traditional features such as color, shape, and texture from the images. Through a detailed analysis and comparison of the accuracy in predicting image attractiveness before and after feature selection using Lasso and LassoNet,, we confirmed that feature selection is an effective method for improving prediction accuracy. Subsequently, the Lasso and LassoNet feature selection methods were applied to a dataset containing image content features. The results verified an enhancement in the model’s accuracy for predicting image attractiveness with the inclusion of image content features. Finally, through an analysis of the four-dimensional features of color, texture, shape, and content, we identified specific features influencing image attractiveness, providing a robust reference for image design.

Abstract Hand pose recognition has been one of the most fundamental tasks in computer vision and pattern recognition, and substantial effort has been devoted to this field. However, owing to lack of public large‐scale benchmark dataset, there is little literature to specially study pen‐holding hand pose (PHHP) recognition. As an attempt to fill this gap, in this paper, a PHHP image dataset, consisting of 18,000 PHHP samples is established. To the best of the authors’ knowledge, this is the largest vision‐based PHHP dataset ever collected. Furthermore, the authors design a coarse‐to‐fine PHHP recognition network consisting of a coarse multi‐feature learning network and a fine pen‐grasping‐specific feature learning network, where the coarse learning network aims to extensively exploit the multiple discriminative features by sharing a hand‐shape‐based spatial attention information, and the fine learning network further learns the pen‐grasping‐specific features by embedding a couple of convolutional block attention modules into three convolution blocks models. Experimental results show that the authors’ proposed method can achieve a very competitive PHHP recognition performance when compared with the baseline recognition models.

The domain wall structure of ferroelectric/ paraelectric superlattices can be much more complex due to the influence of the superlattice stacking structure, the in-plane strain induced by the substrate and environmental temperature. In this study, we employed a phase field model to investigate the domain wall state of the SrTi[Formula: see text]/BaTi[Formula: see text] superlattice structure. The domain wall thickness for the SrTi[Formula: see text]/BaTi[Formula: see text] layer was measured using a hyperbolic function. Based on the simulation results, here, we show a domain wall state diagram to distinguish the hard and soft domain states. The polarization profiles across hard/ soft domain walls were illustrated and analyzed. Our simulation results offer a useful concept for the control of the domain wall state in the ferroelectric superlattice.

Abstract Shear‐wave velocity (Vs) structures can reveal the shallow sediment thickness and deep tectonic features of buried faults and geological units. They are important for reducing seismic and geological disasters in urban areas. Based on ambient noise data from the Tongzhou dense array (919 seismographic stations), we obtain a fine shallow‐deep (0–5 km) 3D Vs model, by jointly inverting the phase‐velocity dispersions of Rayleigh waves, including short‐period (0.3–2 s) multimode dispersions using the frequency‐Bessel transform method and the long‐period (2–6 s) fundamental‐mode dispersions using the fast marching method. Our results show that the Vs inhomogeneities agree well with the distribution of geological units. We use the 1 km/s isodepth of Vs as the reference thickness of quaternary sediments. Fengbo sag (FBS) and Dachang sag (DCS), which mainly show low velocity and density, have thick sediment thicknesses (approximately 550–600 and 320–420 m, respectively). The NE high‐velocity belt in Daxing high (DXH) has a thinner sediment thickness (∼230 m). Thus, FBS and DCS have a greater risk of earthquake hazards owing to the strong amplification effects of ground motion. Additionally, Vs distribution in the FBS, DCS, DXH, and Yanshan Fold Belt are spatially related to the medium density and buried faults (Nanyuan‐Tongxian, Daxing, and Xiadian faults). We infer that the Vs structures are associated with the controlling effects of these large normal faults and inhomogeneous strata density. The discontinuity of the NE high‐velocity belt in DXH probably results from the intense tectonic activity of Nankou‐Sunhe fault.

Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of mixed skin tumor. Methods We retrospectively analyzed the data of 18 patients with mixed skin tumors from our department from March 2017 to September 2021. Results The male to female ratio of the 18 cases was 1 ∶1, with the onset age of 24 to 64 years. All patients had facial involvement (most common on the nose), and exhibited asymptomatic singular nodule in light red or skin color. The histological findings revealed mixed skin tumor, including differentiation toward eccrine glands in 3 cases and apocrine glands in 15 cases. None of the 18 patients was clinically diagnosed as mixed skin tumor. All 18 patients underwent surgical resection and were followed up for 2 months to 1 year without recurrence. Conclusions Mixed skin tumor is a rare benign tumor. The diagnosis of the disease is mainly dependent on histopathological examination.

Abstract Flexible multichannel electrode arrays (fMEAs) with multiple filaments can be flexibly implanted in various patterns. It is necessary to develop a method for implanting the fMEA in different locations and at various depths based on the recording demands. This study proposed a strategy for reducing the microelectrode volume with integrated packaging. An implantation system was developed specifically for semiautomatic distributed implantation. The feasibility and convenience of the fMEA and implantation platform were verified in rodents. The acute and chronic recording results provied the effectiveness of the packaging and implantation methods. These methods could provide a novel strategy for developing fMEAs with more filaments and recording sites to measure functional interactions across multiple brain regions.

Addressing critical ecological issues is one of the core objectives of the Chinese National New-type Urbanization Plan (NTU). However, there is not enough research to clearly demonstrate NTU's impact on environmental pollution. There is a need to provide solid empirical evidence from evaluation of the effects of NTU on environmental pollution. This study implements a series of propensity score matching and difference-in-difference analyses based on a comprehensive panel dataset spanning the period 2006–2017. The quantitative results show that NTU is largely conducive to curbing environmental pollution, with PM2.5 concentrations as a proxy, and its robustness is demonstrated by the parallel trend test and placebo test. Further, the ecological effect of NTU is heterogeneous in terms of city level, location, and former pollution level. Small and medium cities benefit more than larger or central cities from NTU, and eastern cities exhibit better air quality improvement than cities in western regions. In addition, through quantile regression, we find that the positive outcomes of NTU are restricted by level of pollution, i.e., heavier pollution adds greatly to the difficulty of abatement.

The magnetic domain structures and martensite microstructures of porous Ni2MnGa Heusler alloys with various circle-shaped and ellipse-shaped pores were systematically studied by the phase field method. The magnetization curves and magnetic field-induced strains (MFIS) at the external field were determined. A mesoscopic mechanism was proposed for simulation to reveal the influence of the pores on the microstructures and the MFIS of porous magnetic shape memory alloy. The stress concentration effect and the recovery strain of the porous alloy are studied. The results indicate the MFIS value increases when ellipse-shaped pores elongate along the twin boundary. The effects of porosity and pore size on MFIS for porous Ni-Mn-Ga alloys with randomly distributed pores were also explored. The present study is of guiding significance for understanding the role played by pores on the MFIS and may provide a possible way to adjust the functional properties of ferromagnetic shape memory alloys.

Azobenzene mesogens have garnered considerable research attention in the realm of photo-responsive materials due to their reversible trans–cis isomerization. In this paper, we demonstrate an azobenzene inverse opal film synthesized via photo-polymerization from a SiO2 opal template. The proposed design exhibits intriguing optical properties, including dynamic fluorescent features, distinct fluorescent enhancement, and an anti-fake micropattern with a switchable structure color. This work holds significant importance for advancing the development of novel optical devices.

Abstract Background Hemicellulose acts as one factor contributing to the recalcitrance of lignocellulose that prevents cellulases to degrade the cellulose efficiently even in low quantities. Supplement of hemicellulases can enhance the performance of commercial cellulases in the enzymatic hydrolyses of lignocellulose. Kluyveromyce marxianus is an attractive yeast for cellulosic ethanol fermentation, as well as a promising host for heterologous protein production, since it has remarkable thermotolerance, high growth rate, and broad substrate spectrum etc. In this study, we attempted to coordinately express multiple hemicellulases in K. marxianus through a 2A-mediated ribosome skipping to self-cleave polyproteins, and investigated their capabilities for saccharification and ethanol production from corncobs. Results Two polycistronic genes IMPX and IMPαX were constructed to test the self-cleavage of P2A sequence from the Foot-and-Mouth Disease virus (FMDV) in K. marxianus. The IMPX gene consisted of a β-mannanase gene M330 (without the stop codon), a P2A sequence and a β-xylanase gene Xyn-CDBFV in turn. In the IMPαX gene, there was an additional α-factor signal sequence in frame with the N-terminus of Xyn-CDBFV. The extracellular β-mannanase activities of the IMPX and IMPαX strains were 21.34 and 15.50 U/mL, respectively, but the extracellular β-xylanase activity of IMPαX strain was much higher than that of the IMPX strain, which was 136.17 and 42.07 U/mL, respectively. Subsequently, two recombinant strains, the IXPαR and IMPαXPαR, were constructed to coordinately and secretorily express two xylantic enzymes, Xyn-CDBFV and β-D-xylosidase RuXyn1, or three hemicellulolytic enzymes including M330, Xyn-CDBFV and RuXyn1. In fed-batch fermentation, extracellular activities of β-xylanase and β-xylosidase in the IXPαR strain were 1664.2 and 0.90 U/mL. Similarly, the IMPαXPαR strain secreted the three enzymes, β-mannanase, β-xylanase, and β-xylosidase, with the activities of 159.8, 2210.5, and 1.25 U/mL, respectively. Hemicellulolases of both strains enhanced the yields of glucose and xylose from diluted acid pretreated (DAP) corncobs when acted synergistically with commercial cellulases. In hybrid saccharification and fermentation (HSF) of DAP corncobs, hemicellulases of the IMPαXPαR strain increased the ethanol yield by 8.7% at 144 h compared with the control. However, both ethanol and xylose yields were increased by 12.7 and 18.2%, respectively, at 120 h in HSF of aqueous ammonia pretreated (AAP) corncobs with this strain. Our results indicated that coordinate expression of hemicellulolytic enzymes in K. marxianus promoted the saccharification and ethanol production from corncobs. Conclusions The FMDV P2A sequence showed high efficiency in self-cleavage of polyproteins in K. marxianus and could be used for secretory expression of multiple enzymes in the presence of their signal sequences. The IMPαXPαR strain coexpressed three hemicellulolytic enzymes improved the saccharification and ethanol production from corncobs, and could be used as a promising strain for ethanol production from lignocelluloses.

Background: Colon cancer is one of the most common malignant tumors in the world. FOLFIRI (leucovorin, fluorouracil, and irinotecan) is a common combination in chemotherapy regimens. However, insensitivity to FOLFIRI is an important factor in the effectiveness of the treatment for advanced colon cancer. Our study aimed to explore precise molecular targets associated with chemotherapy responses in colon cancer.Methods: Gene expression profiles of 21 patients with advanced colorectal cancer who received chemotherapy based on FOLFIRI were obtained from the Gene Expression Omnibus (GEO) database. The gene co-expression network was constructed by the weighted gene co-expression network analysis (WGCNA) and functional gene modules were screened out. Clinical phenotypic correlation analysis was used to identify key gene modules. Gene Ontology and pathway enrichment analysis were used to screen enriched genes in key modules. Protein–protein interaction (PPI) analysis was used to screen out key node genes. Based on the Gene Expression Profiling Interactive Analysis (GEPIA) database, the correlation between the expression levels of these genes and the overall survival (OS) and disease-free survival (DFS) of colon cancer patients was investigated, and the hub genes were screened out. Immunohistochemistry of candidate hub genes was identified using the Human Protein Atlas database. Finally, clinical information and RNA sequencing data of colon cancer were obtained from The Cancer Genome Atlas project database (TCGA), the GEPIA, and the Human Atlas databases for validation.Results: The WGCNA revealed that three hub genes were closely related to chemotherapy insensitivity of colon cancer: AEBP1, BGN, and TAGLN. The protein expression levels of AEBP1, BGN, and TAGLN in tumor tissues were higher than those in normal tissues. In addition, the gene expression levels of AEBP1, BGN, and TAGLN were negatively correlated with OS and DFS in colon cancer patients. Therefore, AEBP1, BGN, and TAGLN have been identified as potential biomarkers related to the response to FOLFIRI treatment of colon cancer.Conclusion: We found that AEBP1, BGN, and TAGLN, as potential predictive biomarkers, may play an important role in the response to FOLFIRI treatment of colon cancer and as a precise molecular target associated with chemotherapy response in colon cancer.

On August 8, 2017, a magnitude 7.0 earthquake occurred in Jiuzhaigou County, Sichuan Province, China. The deep seismogenic environment and potential seismic risk in the eastern margin of Tibetan Plateau have once again attracted the close attention of seismologists and scholars at home and abroad. The post-earthquake scientific investigation could not identify noticeable surface rupture zones in the affected area; the complex tectonic background and the reason(s) for the frequent seismicity in the Jiuzhaigou earthquake region are unclear. In order to reveal the characteristics of the deep medium and the seismogenic environment of the M7.0 Jiuzhaigou earthquake region, and to interpret the tectonic background and genesis of the seismicity comprehensively, in this paper, we have reviewed all available observation data recorded by the regional digital seismic networks and large-scale, dense mobile seismic array (China Array) for the northern section of the North–South Seismic Belt around Jiuzhaigou earthquake region. Using double-difference seismic tomography method to invert the three-dimensional P-wave velocity structure characteristics of the upper crust around the Jiuzhaigou earthquake region, we have analyzed and discussed such scientific questions as the relationship between the velocity structure characteristics and seismicity in the Jiuzhaigou earthquake region, its deep tectonic environment, and the ongoing seismic risk in this region. We report that: the P-wave velocity structure of the upper crust around the Jiuzhaigoug earthquake region exhibits obvious lateral inhomogeneity; the distribution characteristics of the shallow P-wave velocity structure are closely related to surface geological structure and formation lithology; the M7.0 Jiuzhaigou earthquake sequence is closely related to the velocity structure of the upper crust; the mainshock of the M7.0 earthquake occurred in the upper crust; the inhomogeneous variation of the velocity structure of the Jiuzhaigou earthquake area and its surrounding medium appears to be the deep structural factor controlling the spatial distribution of the mainshock and its sequence. The 3D P-wave velocity structure also suggests that the crustal low-velocity layer of northeastern SGB (Songpan–Garzê Block) stretches into MSM (Minshan Mountain), and migrates to the northeast, but the tendency to emerge as a shallow layer is impeded by the high-velocity zone of Nanping Nappe tectonics and the Bikou Block. Our results reveal an uneven distribution of high- and low-velocity structures around the Tazang segment of the East Kunlun fault zone. Given that the rupture caused by the Jiuzhaigou earthquake has enhanced the stress fields at both ends of the seismogenic fault, it is very important to stay vigilant to possible seismic hazards in the large seismic gap at the Maqu–Maqên segment of the East Kunlun fault zone.

Project citizenship behavior (PCB) has an important positive impact on project success. Researching how to promote PCB is an important issue in project management. Based on social learning theory and social cognitive theory, this paper adopted the method of questionnaire survey and hierarchical linear model (HLM) to analyze the collected data derived from the sample of Chinese construction enterprises and verified this hypothesis. The results show that responsible leadership has a significant positive effect on PCB, moral identity mediates this relationship, and collective moral sensitivity positively moderates this mediating effect. The findings of the study systematically and deeply reveal the intrinsic mechanism of the cross-level influence of responsible leadership on PCB, and provide new enlightenment for the practice of project management.

Tetrodotoxin (TTX) inhibits neurotransmission in animals, and there is no specific antidote. In clinical practice in China, Althaea rosea (A. rosea flower) extract has been used to treat TTX poisoning. In this work, the efficacy of the ethyl acetate fraction extract of A. rosea flower in treating TTX poisoning in rats was investigated. A high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed to determine nine neurotransmitters in rat brain tissue, including γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), noradrenaline (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), epinephrine (E), and tyramine (Tyn). The detoxifying effect of A. rosea flower was verified by comparing the changes in neurotransmitters’ content in brain tissue before and after poisoning in rats. The assay was performed in multiple reaction monitoring mode. The quantification method was performed by plotting an internal-standard working curve with good linearity (R2 > 0.9941) and sensitivity. Analyte recoveries were 94.04–107.53% (RSD < 4.21%). Results indicated that the levels of 5-HT, DA, E, and NE in the brains of TTX-intoxicated rats decreased, whereas the levels of GABA, Tyn, and 5-HIAA showed an opposite trend, and HVA and DOPAC were not detected. The levels of all seven neurotransmitters returned to normal after the gavage administration of ethyl acetate extract of A. rosea flower to prove that the ethyl acetate extract of A. rosea flower had a therapeutic effect on TTX poisoning. The work provided new ideas for studies on TTX detoxification.

Abstract In this paper, we propose a novel feature compensation algorithm based on independent noise estimation, which employs a Gaussian mixture model (GMM) with fewer Gaussian components to rapidly estimate the noise parameters from the noisy speech and monitor the noise variation. The estimated noise model is combined with a GMM with sufficient Gaussian mixtures to produce the noisy GMM for the clean speech estimation so that parameters are updated if and only if the noise variation occurs. Experimental results show that the proposed algorithm can achieve the recognition accuracy similar to that of the traditional GMM-based feature compensation, but significantly reduces the computational cost, and thereby is more useful for resource-limited mobile devices.

A Monte-Carlo-assisted phase field model for the simulation of grain growth in metals and alloys is presented. The simulation time in this model is connected to real time through an experimental data-based kinetic model. Site selection probability is introduced to simulate grain structure evolution under non-isothermal conditions. The grain evolutions with temporal and spatial distributions of temperature during the welding process are comprehensively reproduced. The average size and topological texture of the generated grains in the fusion zone and heat-affected zone are examined. The computed results are compared to experimental data for laser-welding two alloys: Fe–6.5 wt.%Si and low-carbon steel. The applications of real-time–temperature based phase field simulation to material processing indicate significant promise for understanding grain structures during the welding process or additive manufacturing processes.

Kluyveromyces marxianus is the fastest-growing eukaryote and a promising host for producing bioethanol and heterologous proteins. To perform a laboratory evolution of thermal tolerance in K. marxianus, diploid, triploid and tetraploid strains were constructed, respectively. Considering the genetic diversity caused by genetic recombination in meiosis, we established an iterative cycle of “diploid/polyploid - meiosis - selection of spores at high temperature” to screen thermotolerant strains. Results showed that the evolution of thermal tolerance in diploid strain was more efficient than that in triploid and tetraploid strains. The thermal tolerance of the progenies of diploid and triploid strains after a two-round screen was significantly improved than that after a one-round screen, while the thermal tolerance of the progenies after the one-round screen was better than that of the initial strain. After a two-round screen, the maximum tolerable temperature of Dip2-8, a progeny of diploid strain, was 3°C higher than that of the original strain. Whole-genome sequencing revealed nonsense mutations of PSR1 and PDE2 in the thermotolerant progenies. Deletion of either PSR1 or PDE2 in the original strain improved thermotolerance and two deletions displayed additive effects, suggesting PSR1 and PDE2 negatively regulated the thermotolerance of K. marxianus in parallel pathways. Therefore, the iterative cycle of “meiosis - spore screening” developed in this study provides an efficient way to perform the laboratory evolution of heat resistance in yeast.

Abstract Background Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer. Methods We developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of EGF-PLGA@5Fu/PFC NPs in vivo. Results The findings showed that EGF-PLGA@5Fu /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, EGF-PLGA@5Fu/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, EGF-PLGA@5Fu/PFC NPs suppressed tumor growth more effectively than 5Fu, PLGA@5Fu or PLGA@5Fu/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors. Conclusion We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.

Segmentation based methods have become the mainstream for detecting scene text with arbitrary orientations and shapes. In order to address challenging problems such as separating the text instances that are very close to each other, however, these methods often require time-consuming post-processing. In this paper, we propose an instance segmentation network (ISNet), which simultaneously generates prototype masks and per-instance mask coefficients. After linearly combining the two components, ISNet can implement fast text location. Furthermore, we apply self-distillation to train the ISNet and refine its detection accuracy. We have evaluated the proposed method on four popular benchmarks, i.e., ICDAR2015, ICDAR2017 MLT, CTW1500 and Total-Text, and the experimental results show that it can achieve better tradeoff between accuracy and efficiency for scene text detection.

BackgroundAlveolar rhabdomyosarcoma (ARMS) is a subtype of rhabdomyosarcoma characterized by its aggressive behavior and poor prognosis, highlighting the need for novel treatment options. Arsenic trioxide (ATO) has been shown to specifically inhibit tumor growth and the metastasis of ARMS in vitro by acting on the hedgehog pathway. Here we report on a pilot clinical study to evaluate the activity of an ATO-combined chemotherapy approach for the treatment of ARMS patients.MethodsWe designed a therapeutic schedule of an ATO-combined chemotherapy, incorporating comprehensive management according to the Intergroup Rhabdomyosarcoma Study Group protocol. ATO was administered at 0.16 mg/kg per day over 8 h via an IV for 10 days combined with a chemotherapeutic regimen of vincristine, actinomycin, and cyclophosphamide (VAC regimen) on the third day, which was repeated every 21 days. A total of eight cycles of ATO-combined chemotherapy were applied throughout the entire scheme.ResultsA total of three refractory/recurrent and one untreated ARMS patient, three male and one female, with a median age of 5.8 years (range, 5.1 to 12.5 years), were enrolled in the present study. All patients were sensitive to combined chemotherapy with ATO and achieved partial or complete remission during treatment. Except for reversible gastrointestinal reaction and myelosuppression, no other adverse events were observed during the process of treatment.ConclusionsThe combined chemotherapy of ATO and the VAC regimen exhibited beneficial activities against ARMS in pediatrics and was well tolerated, but prospective large-scale clinical trials are warranted to determine the long-term efficacy, optimal courses, and late toxicity in this population.

Abstract The reactive adsorption desulfurization is an important and efficient technology for the ultra‐deep desulfurization of gasoline. The performance of an adsorbent is vital for the efficiency of the reactive adsorption desulfurization process. The formation of inert spinels is commonly recognized for the deactivation of adsorbents. In this work, TiO2 was incorporated in the Ni/ZnO‐Al2O3 adsorbent to inhibit the formation of the spinel phase. The TiO2 formed a stable protection layer on the surface of Al2O3, which prevented the interaction between Al2O3 and ZnO, inhibiting the formation of the ZnAl2O4 spinel phase. The introduction of TiO2 significantly improved the stability of the adsorbents during cyclic hydrothermal treatments, while the sulfur capacity slightly dropped. Characterization results revealed that TiO2 was homogeneously dispersed on the surface of Al2O3 support and the incorporation of TiO2 could maintain a certain amount of Lewis acid sites in the adsorbents, which are favorable for the adsorption of organo‐sulfur compounds.

A co-location pattern is a set of spatial features whose instances are frequently correlated to each other in space. Its mining models always consist of two essential steps. One step is to generate neighbor relationships between spatial instances, and another step is to check the prevalence of candidate patterns on the clique, star or Delaunay triangulation relationships. At least three major issues are addressed in this paper. First, since different spatial regions, different distribution densities, it is difficult to set appropriate parameters to generate ideal neighbor relationships. Second, the clique relationship and the others are so strongly rigid that the users’ personal interests are suppressed; some interesting patterns are neglected without increasing redundancy. Third, the different strength of correlations among instances are neglected in prevalence calculation. It causes correlations among features to be undifferentiated. Accordingly, the main work of this paper includes: (1) The neighbor relationship generation can be improved on the idea that the distances between an instance and any of its neighbors are not remarkably different. (2) The type-β co-location pattern is defined and checked based on a co-occurrence where the closeness centrality of each instance is not less than a given threshold β. (3) Since the closeness centrality carries strength of correlations among instances, the strength of the correlations between a feature and the other ones in a type-β co-location pattern can be evaluated with prevalence calculation. Finally, experiments on synthetic and real-world spatial data sets are used to assess the effectiveness and efficiency of our works. The results show that fewer spatial neighbor relationships are generated, and more interesting patterns can be discovered by flexibly adjusting β according to the user’s preferences.

Colorectal cancer (CRC) is one of the most common malignancies, and multidrug resistance (MDR) severely restricts the effectiveness of various anticancer drugs. Therefore, the development of novel anticancer drugs for the treatment of CRC patients with MDR is necessary. Quaternized thiourea main-chain polymer (QTMP) is a self-assembled nanoparticle with good water solubility. Notably, QTMP is not a P-glycoprotein (P-gp) substrate, and it exhibits potent cytotoxic activity against CRC cells, including HCT116/DDP and P-gp-mediated multidrug-resistant Caco2 cells. QTMP also exhibits a strong anticancer activity against SW480 cells in vivo. Interestingly, reactive oxygen species (ROS) and reactive nitrogen species (RNS) production were increased in a concentration-dependent manner in QTMP-treated HCT116, SW480 and Caco2 cells. Importantly, QTMP causes DNA damage in these CRC cells via direct insertion into the DNA or regulation of ROS and/or RNS production. QTMP also induces caspase-dependent apoptosis via overproduction of ROS and RNS. Therefore, QTMP is a promising anticancer therapeutic agent for patients with CRC, including those cancer cells with P-gp-mediated MDR. The present study also indicates that the design and synthesis of anticancer drugs based on thiourea polymers is promising and valuable, thereby offering a new strategy to address MDR, and provides reference resources for further investigations of thiourea polymers.

The Cre-loxP system produces structural variations, such as deletion, duplication, inversion and translocation, at specific loci and induces chromosomal rearrangements in the genome. To achieve chromosomal rearrangements in Kluyveromyces marxianus, the positions and sequences of centromeres were identified in this species for the first time. Next, a Cre-loxP system was established in K. marxianus. In this system, the Cre recombinase was expressed from a leaky LAC4 promoter in a plasmid to alleviate the cytotoxicity of Cre, and the unstable plasmid contained a panARS element to facilitate the clearance of the plasmid from the cells. By using LAC4 as a reporter gene, the recombination frequencies between loxP sites or loxPsym sites were 99% and 73%, respectively. A K. marxianus strain containing 16 loxPsym sites in the genome was constructed. The recombination frequency of large-scale chromosomal rearrangements between 16 loxPsym sites was up to 38.9%. Our study provides valuable information and tools for studying chromosomal structures and functions in K. marxianus.

In the current work, a core-shell type exchange coupled composite structure was constructed by micromagnetic simulation with a phase FePt core and an iron shell. Four types of switching loops with magnetic domain structure evolution were demonstrated. Based on the simulation results, a switching type diagram was constructed, which displays various hysteresis loops as a function of core radius and shell thickness. Furthermore, the effects of switching type and composite structure on the coercivity and remanent magnetization were predicted and discussed. This finding indicates that core-shell type FePt/Fe composite structure film has a large advantage in designing exchange-coupled bit patterned media to realize high-density storage devices at the nanoscale.

Altruism can be spontaneously aroused by environmental factors. However, the mechanism behind these factors is subject to debate. We carried out a study of laboratory experiment using computer-based Mouselab method to determine the mechanism. We found that different colors altered the altruistic behaviors of people. Specifically, blue enhanced altruism, whereas red discouraged altruism. We used a process-tracing technique to monitor the selection of an adaptive strategy and demonstrate that different colors can simulate changes in information acquisition and then lead to the corresponding behaviors. The results suggested that the decision heuristic plays a mediating role in the link between colors and individual altruistic behaviors.

A phase-field model was developed to simulate the ferromagnetic domain structure and martensite variant microstructure of Ni-Mn-Ga shape-memory alloy. The evolution of reversible magnetic-field-induced strain (MFIS) and associated magnetic domain/martensite variant structure were modeled under an external magnetic field. It was found that MFIS increased significantly from 0.2% to 0.28% as the temperature increased from 265 K to 285 K. In addition, compressive pre-stress efficiently enhanced the MFIS of the alloy, while tensile stress reduced MFIS. Furthermore, it was proved that there was possibility of achieving similar enhancement of MFIS by replacing compressive stress with perpendicular biaxial tensile stress. The results revealed that the residual variant induced by stress plays an important role in the reversible MFIS effect.

The lattice phase field model is developed to simulate microstructures of nanoscale materials. The grid spacing in simulation is rescaled and restricted to the lattice parameter of real materials. Two possible approaches are used to solve the phase field equations at the length scale of lattice parameter. Examples for lattice phase field modeling of complex nanostructures are presented to demonstrate the potential and capability of this model, including ferroelectric superlattice structure, ferromagnetic composites, and the grain growth process under stress. Advantages, disadvantages, and future directions with this phase field model are discussed briefly.

Star fruit (Averrhoa carambola) is an important fruit tree in tropical and subtropical Asia. The tree blooms several times and fruits accordingly within one year. Controlling the flowering time and understanding the physiological mechanism of the induction of floral buds in A. carambola are indispensable to the industry. In this study, A. carambola potted trees were subjected to drought stress in a growth chamber. To avoid excessive drought stress and leaf abscission, trees were watered every 7 d and were sprayed with water every 2 d. The flowering rate was recorded, and the carbohydrate contents of the leaves, phloem, and xylem tissues were determined during the treatment and after re-watering. The results showed that drought stress increased the flowering rate in both drooping and water shoots, increased the relative conductivity, decreased the relative water content (RWC) of leaves. The total soluble sugar, sucrose, fructose, and glucose in leaves of the drooping shoots were increased. The starch contents in the xylem of both drooping and water shoots were also increased by the treatment. The results indicated that drought stress enhances carbohydrate accumulation in A. carambola. This study provides a potential way by water control to induce flowering without chemical in A. carambola.

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Accurate solar radiation estimation is very important for solar energy systems and is a precondition of solar energy utilization. Due to the rapid development of new energy sources, the demand for surface solar radiation estimation and observation has grown. Due to the scarcity of surface radiation observations, high-precision remote sensing data are trying to fill this gap. In this paper, a global solar irradiance estimation method (in different months, seasons, and weather conditions), using data from the advanced geosynchronous radiation imager (AGRI) sensor onboard the FengYun-4A satellite with cloud index methodology (CSD-SI), was tested. It was found that the FengYun-4A satellite data could be used to calculate the clear sky index through the Heliosat-2 method. Combined with McClear, the global horizontal irradiance (GHI) and the direct normal irradiance (DNI) in northeast China could be accurately obtained. The estimated GHI accuracy under clear sky was slightly affected by the seasons and the normalized root mean square error (nRMSE) values (in four sites) were higher in summer and autumn (including all weather conditions). Compared to the estimated GHI, the estimated DNI was less accurate. It was found that the estimated DNI in October had the best performance. In the meantime, the nRMSE, the normalized mean absolute error (nMAE), and the normalized mean bias error (nMBE) of Zhangbei were 35.152%, 27.145%, and −8.283%, while for Chengde, they were 43.150%, 28.822%, and −13.017%, respectively. In addition, the estimated DNI at ground level was significantly higher than the actual observed value in autumn and winter. Considering that the error mainly came from the overestimation of McClear, a new DNI radiation algorithm during autumn and winter is proposed for northern China. After applying the new algorithm, the nRMSE decreased from 49.324% to 48.226% for Chengde and from 48.342% to 41.631% for Zhangbei. Similarly, the nMBE decreased from −32.351% to −18.823% for Zhangbei and from −26.211% to −9.107% for Chengde.

An algorithm to forecast very short-term (30–180 min) surface solar irradiance using visible and near infrared channels (AGRI) onboard the FengYun-4A (FY-4A) geostationary satellite was constructed and evaluated in this study. The forecasting products include global horizontal irradiance (GHI) and direct normal irradiance (DNI). The forecast results were validated using data from Chengde Meteorological Observatory for four typical months (October 2018, and January, April, and July 2019), representing the four seasons. Particle Image Velocimetry (PIV) was employed to calculate the cloud motion vector (CMV) field from the satellite images. The forecast results were compared with the smart persistence (SP) model. A seasonal study showed that July and April forecasting is more difficult than during October and January. For GHI forecasting, the algorithm outperformed the SP model for all forecasting horizons and all seasons, with the best result being produced in October; the skill score was greater than 20%. For DNI, the algorithm outperformed the SP model in July and October, with skill scores of about 12% and 11%, respectively. Annual performances were evaluated; the results show that the normalized root mean square error (nRMSE) value of GHI for 30–180 min horizon ranged from 26.78% to 36.84%, the skill score reached a maximum of 20.44% at the 30-min horizon, and the skill scores were all above 0 for all time horizons. For DNI, the maximum skill score was 6.62% at the 180-min horizon. Overall, compared with the SP model, the proposed algorithm is more accurate and reliable for GHI forecasting and slightly better for DNI forecasting.

Within an isogenic population, even in the same extracellular environment, individual cells can exhibit various phenotypic states. The exact role of stochastic gene-state switching regulating the transition among these phenotypic states in a single cell is not fully understood, especially in the presence of positive feedback. Recent high-precision single-cell measurements showed that, at least in bacteria, switching in gene states is slow relative to the typical rates of active transcription and translation. Hence using the lac operon as an archetype, in such a region of operon-state switching, we present a fluctuating-rate model for this classical gene regulation module, incorporating the more realistic operon-state switching mechanism that was recently elucidated. We found that the positive feedback mechanism induces bistability (referred to as deterministic bistability), and that the parameter range for its occurrence is significantly broadened by stochastic operon-state switching. We further show that in the absence of positive feedback, operon-state switching must be extremely slow to trigger bistability by itself. However, in the presence of positive feedback, which stabilizes the induced state, the relatively slow operon-state switching kinetics within the physiological region are sufficient to stabilize the uninduced state, together generating a broadened parameter region of bistability (referred to as stochastic bistability). We illustrate the opposite phenotype-transition rate dependence upon the operon-state switching rates in the two types of bistability, with the aid of a recently proposed rate formula for fluctuating-rate models. The rate formula also predicts a maximal transition rate in the intermediate region of operon-state switching, which is validated by numerical simulations in our model. Overall, our findings suggest a biological function of transcriptional "variations" among genetically identical cells, for the emergence of bistability and transition between phenotypic states.

Both membrane-bound and soluble forms of costimulatory molecules play important roles in immune-regulatory networks. B7-H3, a member of the B7 family, has been found with aberrant expression in tumors and infectious disease. However, the significance of sB7-H3 expression in systemic lupus erythematosus (SLE) has not been investigated. Using the peripheral blood of 78 SLE patients, we established a comprehensive database containing clinical data and relevant laboratory tests. We found that sB7-H3 expression in SLE patients was significantly lower compared with the healthy individuals. In addition, sB7-H3 levels in the patients were positively correlated with the disease activity as indicated by SLE disease activity index score, rashes, fever, and inflammatory cytokines. Moreover, sB7-H3 was associated with the counts of red blood cells and hemoglobin. Our findings suggest that sB7-H3 might counteract the aberrant immune response and potentially serve as a monitoring indicator of disease progression and therapeutic target in SLE treatment.

Battery production is one of the main sources of heavy metals that present great harm to human health even in low concentrations. Chromium (Cr), Cadmium (Cd) and Lead (Pb) were measured in edible portions of vegetables and soils around a battery production area in China, and the potential health risk of heavy metal contamination to the local population via vegetable consumption was evaluated. Their concentrations in edible portions of vegetables were 2.354 (0.078-14.878), 0.035 (0.003-0.230) and 0.039 (0.003-0.178) mg kg-1, respectively. Approximately 3 % of the Cd in the vegetable samples exceeded the maximum concentration allowable by national food safety criteria, although Pb content in all samples were within the criteria. Transfer factors (TF) from soils to vegetables were dependent on vegetable species. Leguminous vegetables were more likely to accumulate Cr, while leaf vegetables tended to show higher levels of concentration of Cd and Pb. Melon vegetables demonstrated a relatively low capacity for accumulating the heavy metals studied. TF were positively correlated with soil organic matter and negatively correlated with soil pH. The mean estimated daily intake of Cr, Cd and Pb via dietary consumption of vegetables was 0.011, 1.65 × 10-4 and 1.84 × 10-4 mg kg-1 of body weight per day, respectively, levels that were much lower than the reference doses recommended by USEPA (U.S. Environmental Protection Agency) and JECFA (Joint FAO/WHO Expert Committee on Food Additives), indicating that the potential health risk of Cr, Cd and Pb exposure via vegetable consumption to the local population around this battery production area could be negligible.

The optimal condition of spray drying purified flavonoids extract from R. tomentosa berries was studied by response surface methodology. The optimized condition for microencapsulation was of maltodextrin to gum Arabic ratio 1 : 1.3, total solid content 27.4%, glycerol monostearate content 0.25%, and core to coating material ratio 3 : 7, resulting in EE 91.75%. Prepared at the optimized condition, the flavonoids extract microcapsules (FEMs) were irregularly spherical particles with low moisture content (3.27%), high solubility (92.35%), and high bulk density (0.346 g/cm3). DPPH radical scavenging activity of FEMs was not decreased after spray drying (P>0.05) and higher than those in citric acid and rutin at the same concentration. Moreover, FEMs effectively retarded the oxidation of fresh lard during the 10-day storage period compared with vitamin C, nonencapsulated flavonoids extract, and rutin. Therefore, FEMs produced at the optimized condition could be used as powder ingredients with antioxidant capacities.