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Habitat loss and human threats are putting the marbled polecat (Vormela peregusna) on the brink of extinction. Numerous recent studies have found that climate change will further deteriorate the living environment of endangered species, leading to their eventual extinction. In this study, we used the results of infrared camera surveys in China and worldwide distribution data to construct an ensemble model consisting of 10 commonly used ecological niche models to specify potential suitable habitat areas for V. peregusna under current conditions with similar environments to the sighting record sites. Changes in the suitable habitat for V. peregusna under future climate change scenarios were simulated using mid-century (2050s) and the end of the century (2090s) climate scenarios provided by the Coupled Model Intercomparison Project Phase 6 (CMIP6). We evaluated the accuracy of the model to obtain the environmental probability values (cutoff) of the V. peregusna distribution, the current distribution of suitable habitats, and future changes in moderately and highly suitable habitat areas. The results showed that the general linear model (GLM) was the best single model for predicting suitable habitats for V. peregusna, and the kappa coefficient, area under the curve (AUC), and true skill statistic (TSS) of the ensemble model all exceeded 0.9, reflecting greater accuracy and stability than single models. Under the current conditions, the area of suitable habitat for V. peregusna reached 3935.92 × 104 km2, suggesting a wide distribution range. In the future, climate change is predicted to severely affect the distribution of V. peregusna and substantially reduce the area of suitable habitats for the species, with 11.91 to 33.55% of moderately and highly suitable habitat areas no longer suitable for the survival of V. peregusna. This shift poses an extremely serious challenge to the conservation of this species. We suggest that attention be given to this problem in Europe, especially the countries surrounding the Black Sea, Asia, China, and Mongolia, and that measures be taken, such as regular monitoring and designating protected areas for the conservation of vulnerable animals.

Abstract Background Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. Syndrome differentiation is the premise of individualized treatment of traditional Chinese medicine (TCM), but TCM syndrome lacks objective identification in CRC. This study is to investigate the correlation and significance of tumor heterogeneity and TCM syndromes classification in CRC. Methods In this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC. Results The results showed that 662 cells isolated from 11 primary CRC tumors are divided into 14 different cell clusters, and each cell subtype and its genes have different functions and signal transduction pathways, indicating significant heterogeneity. CRC tumor cell clusters have different proportions in Excess, Deficiency and Deficiency-Excess syndromes, and have their own characteristic genes, gene co-expression networks, gene functional interpretations as well as monocle functional evolution. Moreover, there were significant differences between the high expressions of MUC2, REG4, COL1A2, POSTN, SDPR, GPX1, ELF3, KRT8, KRT18, KRT19, FN1, SERPINE1, TCF4 and ZEB1 genes in Excess and Deficiency syndrome classification in CRC (P

Abstract Introduction Total hip arthroplasty (THA) is generally considered to be one of the most successful orthopedic surgical procedures. However, no research has been conducted on the postoperative mental health of patients who underwent different approaches of THA. This paper seeks to compare the differences among three THA approaches: the normal lateral approach (NLA), the direct anterior approach (DAA) and the orthopädische chirurgie münchen (OCM) regarding their influence on patients’ postoperative anxiety and depression. Method A total of 95 THA patients were recruited for this study. All patients’ preoperative information including results of Harris, SF-36 and Visual Analogue Scale (VAS) was carefully evaluated. Surgery-related data as well as five-day postoperative data were also collected. Three months after the surgery, a telephone follow-up was conducted to further evaluate patients’ HADS and SF-36 results. Result In the three-month postoperative evaluation of anxiety and depression, the NLA group scored significantly higher than both the DAA group and the OCM group, which was found relevant to the patient’s incision length and five-day postoperative VAS results. A correlation between anxiety scores and the days of postoperative hospitalization was also noticed. Further analysis of patients’ psychological state based on the SF-36 results revealed considerable differences in viability (VT) and social function (SF) between the NLA group and the OCM group. Other surgery-related data and postoperative data all demonstrated better results of the DAA group and the OCM group compared to the NLA group. Conclusion Among the three different surgical approaches of THA, DAA and OCM compared with NLA are found to ease patients’ postoperative anxiety and depression. Level of evidence III

Abstract Background Fat deposition is an important economic consideration in pig production. The amount of fat deposition in pigs seriously affects production efficiency, quality, and reproductive performance, while also affecting consumers’ choice of pork. Weighted gene co-expression network analysis (WGCNA) is effective in pig genetic studies. Therefore, this study aimed to identify modules that co-express genes associated with fat deposition in pigs (Songliao black and Landrace breeds) with extreme levels of backfat (high and low) and to identify the core genes in each of these modules. Results We used RNA sequences generated in different pig tissues to construct a gene expression matrix consisting of 12,862 genes from 36 samples. Eleven co-expression modules were identified using WGCNA and the number of genes in these modules ranged from 39 to 3,363. Four co-expression modules were significantly correlated with backfat thickness. A total of 16 genes (RAD9A, IGF2R, SCAP, TCAP, SMYD1, PFKM, DGAT1, GPS2, IGF1, MAPK8, FABP, FABP5, LEPR, UCP3, APOF, and FASN) were associated with fat deposition. Conclusions RAD9A, TCAP, SMYD1, PFKM, GPS2, and APOF were the key genes in the four modules based on the degree of gene connectivity. Combining these results with those from differential gene analysis, SMYD1 and PFKM were proposed as strong candidate genes for body size traits. This study explored the key genes that regulate porcine fat deposition and lays the foundation for further research into the molecular regulatory mechanisms underlying porcine fat deposition.

Ocean fronts are widespread on the eastern China shelf, especially in winter and early spring. Previous studies have shown that sediments on the northern coast of the Shandong Peninsula could penetrate the coastal fronts and deposit on the southern coast of the Liaodong Peninsula, and this cross-front transport process is closely related to winter storms. However, the detailed mechanisms of cross-front transport remain unclear. In this study, through realistic numerical modeling and physical mechanism analysis, a dynamic mechanism involving cross-front transport triggered by winter storms was proposed, and two locations with the highest probability of frontal instability around the Shandong Peninsula were identified. In detail, forced by winter storms, the Lubei Coastal Current significantly intensifies first and causes frontal inertial instability in the early stage of the winter storm, favoring cross-front exchange between both sides of the front. Then, serving as a compensation current, the Yellow Sea Warm Current intensifies in the late stage of the winter storm, leading to the northward transport of the materials out of the front. Furthermore, the intensity, distance, and path of the cross-front transport under varying winter storms are also investigated. The winter storm, with longer duration, greater wind speed, and westward wind direction, tends to trigger stronger cross-front transport and longer transport distance. Transport paths also differ under different winter storms. This study provides a theoretical explanation for cross-front transport and analyzes the role of winter storms in it, providing some new ideas for nearshore materials dispersal to the sea, which is of great significance for future studies on pollutant diffusion, nutrient distribution, and sediment transport in coastal areas.

An eight-week trial was conducted to investigate the effects of sanguinarine supplementation (600 μg and 1200 μg/kg) in high-fat (crude fat: 10%) diets (HF) on the intestinal physiological function of Ctenopharyngodon idellus (initial weight 50.21 ± 0.68 g), based on a basic diet (5% crude fat, CON), which were named HFLS and HFHS, respectively. The results showed that the HF diet significantly impaired the intestinal immune and physical barrier function, and disrupted the balance of the intestinal microbiota in grass carp. Compared to the HF diet, sanguinarine supplementation significantly improved the levels of serum C4, C3, AKP, IgA, and IgM, and enhanced the intestinal antioxidant capacity (gr, CuZnsod, gpx4, cat, gsto, and nrf2 expression were significantly up-regulated). Sanguinarine significantly down-regulated the expression of claudin-15 and up-regulated the expression of claudin-b, claudin-c, occludin, and zo-1 by inhibiting MLCK signaling molecules. Additionally, sanguinarine significantly down-regulated the expression of il-6, il-1β, and tnf-α and up-regulated the expression of il-10, tgf-β2, and tgf-β1 by inhibiting NF-κB signaling molecules, thereby alleviating intestinal inflammation caused by HF diets. Furthermore, compared to the HF diet, the abundance of Fusobacterium and Cetobacterium in the HFHS diet increased significantly, while the abundance of Firmicutes and Streptococcus showed the opposite trend. In conclusion, the HF diet had a negative impact on grass carp, while sanguinarine supplementation enhanced intestinal antioxidant ability, alleviated intestinal barrier damage, and ameliorated the homeostasis of the intestinal microbiota.

Brucella suis, the causative agent of brucellosis, poses a significant public health and animal husbandry threat. However, the role of the alanine racemase (alr) gene, which encodes alanine racemase in Brucella, remains unclear. Here, we analyzed an alr deletion mutant and a complemented strain of Brucella suis S2. The knockout strain displayed an unaltered, smooth phenotype in acriflavine agglutination tests but lacked the core polysaccharide portion of lipopolysaccharide (LPS). Genes involved in the LPS synthesis were significantly upregulated in the deletion mutant. The alr deletion strain exhibited reduced intracellular viability in the macrophages, increased macrophage-mediated killing, and upregulation of the apoptosis markers. Bcl2, an anti-apoptotic protein, was downregulated, while the pro-apoptotic proteins, Bax, Caspase-9, and Caspase-3, were upregulated in the macrophages infected with the deletion strain. The infected macrophages showed increased mitochondrial membrane permeability, Cytochrome C release, and reactive oxygen species, activating the mitochondrial apoptosis pathway. These findings revealed that alanine racemase was dispensable in B. suis S2 but influenced the strain’s rough features and triggered the mitochondrial apoptosis pathway during macrophage invasion. The deletion of the alr gene reduced the intracellular survival and virulence. This study enhances our understanding of the molecular mechanism underlying Brucella’s survival and virulence and, specifically, how alr gene affects host immune evasion by regulating bacterial LPS biosynthesis.

Solar sailing enables efficient propellant-free attitude adjustment and orbital maneuvers of solar sail spacecraft with high area-to-mass ratios. However, the heavy supporting mass for large solar sails inevitably leads to low area-to-mass ratios. Inspired by chip-scale satellites, a chip-scale solar sail system named ChipSail, consisting of microrobotic solar sails and a chip-scale satellite, was proposed in this work. The structural design and reconfigurable mechanisms of an electrothermally driven microrobotic solar sail made of Al\Ni50Ti50 bilayer beams were introduced, and the theoretical model of its electro-thermo-mechanical behaviors was established. The analytical solutions to the out-of-plane deformation of the solar sail structure appeared to be in good agreement with the finite element analysis (FEA) results. A representative prototype of such solar sail structures was fabricated on silicon wafers using surface and bulk microfabrication, followed by an in-situ experiment of its reconfigurable property under controlled electrothermal actuation. The experimental results demonstrated significant electro-thermo-mechanical deformation of such microrobotic bilayer solar sails, showing great potential in the development of the ChipSail system. Analytical solutions to the electro-thermo-mechanical model, as well as the fabrication process and characterization techniques, provided a rapid performance evaluation and optimization of such microrobotic bilayer solar sails for the ChipSail.

Abstract Purpose Growing evidence demonstrates that long non-coding RNAs (lncRNAs) play a crucial role as competing endogenous RNAs (ceRNAs) in tumor occurrence. The lncRNAs’ functions and clinical significance in laryngeal squamous cell carcinoma (LSCC) remain unclear. The study aims to reveal the lncRNA-associated ceRNA regulatory network of LSCC and clarify its clinical relevance. Methods Here, we obtained LSCC transcriptome data from The Cancer Genome Atlas (TCGA) database and identified the differential expression profile of lncRNAs, miRNAs, and mRNAs by the EdgeR R package. The function enrichment analysis of mRNAs was performed using clusterProfiler R package and GSEA3.0. Then, we constructed a ceRNA network and prognosis model based on lncRNAs through bioinformatic methods. Moreover, we explored the functions of prognosis-related lncRNA in LSCC by CCK-8 and transwell assay. Results 1961 lncRNAs, 69 miRNAs, and 2224 mRNAs were identified as differentially expressed genes in LSCC tissues. According to the transcriptome differential expression profile, a ceRNA network containing 61 lncRNAs, 21 miRNAs, and 77 mRNAs was established. Then, four lncRNAs (AC011933.2, FAM30A, LINC02086, LINC02575) were identified from the ceRNA network to build a prognosis model for LSCC patients. And we found that LINC02086 and LINC02575 promoted the proliferation, migration, and invasion of LSCC cells while AC011933.2 and FAM30A inhibited these biological functions in vitro. Furthermore, we validated that LINc02086/miR-770-5p/SLC26A2 axis promoted migration in LSCC. Conclusion Four lncRNAs of the ceRNA network were abnormally expressed and related to patient prognosis in LSCC. They played a significant role in the progress of LSCC via affecting the proliferation and metastasis of tumor cells.

Natural processes and anthropogenic activities are vital in dictating the amount and character of organic carbon (OC) input into large river deltas and adjacent shelves. Previous studies have indicated that sediment from the Huanghe River (HR) has significantly affected the formation of the northern Yangtze River subaqueous delta (YRD) over the past several hundred years. However, whether this process has changed sedimentary OC burial in the YRD remains unclear. A sediment core was collected from the YRD in 2018 CE for optically stimulated luminescence and 210Pb dating as well as grain size, total OC, total nitrogen, and stable-isotope analyses to investigate temporal changes in sedimentary OC over the past 2000 years. The results indicate that changes in terrestrial OC inputs to the YRD have been controlled mainly by the East Asian summer monsoon and anthropogenic influences in the past 2000 years. However, the decreased terrestrial OC inputs after 1385 CE, have been significantly affected by increased contribution of HR sediment to the YRD when the HR lower courses shifted to enter the southern Yellow Sea. This study demonstrates that sediment source changes should not be neglected in analyses of mechanisms and variations in OC burial in estuarine and coastal areas.

Deng et al. assess the effects of CRISPR/Cas9-mediated genome editing in two transgenic mouse models of amyotrophic lateral sclerosis (ALS) for up to 2 years. They find that the genomic editing prevented the development of ALS-like pathology without any notable side-effects, which provides preclinical evidence of the effectiveness and long-term safety of the CRISPR/Cas9 therapeutic approach.

Abstract Background Osmanthus fragrans is an important economical plant containing multiple secondary metabolites including flavonoids and anthocyanins. During the past years, the roles of miRNAs in regulating the biosynthesis of secondary metabolites in plants have been widely investigated. However, few studies on miRNA expression profiles and the potential roles in regulating flavonoid biosynthesis have been reported in O. fragrans. Results In this study, we used high-throughput sequencing technology to analyze the expression profiles of miRNAs in leaf and flower tissues of O. fragrans. As a result, 106 conserved miRNAs distributed in 47 families and 88 novel miRNAs were identified. Further analysis showed there were 133 miRNAs differentially expressed in leaves and flowers. Additionally, the potential target genes of miRNAs as well as the related metabolic pathways were predicted. In the end, flavonoid content was measured in flower and leaf tissues and potential role of miR858 in regulating flavonoid synthesis was illustrated in O. fragrans. Conclusions This study not only provided the genome-wide miRNA profiles in the flower and leaf tissue of O. fragrans, but also investigated the potential regulatory role of miR858a in flavonoid synthesis in O. fragrans. The results specifically indicated the connection of miRNAs to the regulation of secondary metabolite biosynthesis in non-model economical plant.

Imbalanced data classification is a major challenge in the field of data mining and machine learning, and oversampling algorithms are a widespread technique for re-sampling imbalanced data. To address the problems that existing oversampling methods tend to introduce noise points and generate overlapping instances, in this paper, we propose a novel oversampling method based on density peaks clustering. Firstly, density peaks clustering algorithm is used to cluster minority instances while screening outlier points. Secondly, sampling weights are assigned according to the size of clustered sub-clusters, and new instances are synthesized by interpolating between cluster cores and other instances of the same sub-cluster. Finally, comparative experiments are conducted on both the artificial data and KEEL datasets. The experiments validate the feasibility and effectiveness of the algorithm and improve the classification accuracy of the imbalanced data.

High-performance DC interfaces play a pivotal role in microgrids with distributed energy resources (DERs), which would significantly improve the utilization of DERs and the flexibility of the prosumers. For a candidate DC interface converter, how to maintain the performance over a wide operation range becomes the biggest challenge. This paper proposes a flexible structure soft-switching three-level (TL) dc-dc converter, which adds four high-speed MOSFETs and one low-speed electronic relay to achieve overall optimum performance over a wide range. Under high output or low input voltage conditions, the relay and the extra MOSFETs on the primary side are ON permanently. The proposed converter is a zero-voltage switching (ZVS) converter, which guarantees ZVS for all primary switches even under 0 load currents. Under low output or high input voltage conditions, the relay and the extra MOSFETs in the secondary side are OFF permanently. The proposed converter is a zero-voltage and zero-current switching (ZVZCS) converter, and two added MOSFETs provide ZVZCS operation not only for the main primary switches but also themselves over a wide range. Other advantages of the presented converter include reduced filter size, no primary side circulating currents, and reduced current stress of the clamping capacitor. Besides, the switching loss caused by the added power devices is low because of the full range of soft-switching operation and low on-state resistance of these devices. This paper discusses the circuit configuration, operation principle, soft switching characteristics, technical comparison, and experimental results from a 1-kW prototype prove the rightness of the presented converter.

Although the transcriptional alterations inside the facial nucleus after facial nerve injury have been well studied, the gene expression changes in the facial nerve trunk after injury are still unknown. In this study, we established an adult rat model of facial nerve crush injury by compressing the right lateral extracranial nerve trunk. Transcriptome sequencing, differential gene expression analysis, and cluster analysis of the injured facial nerve trunk were performed, and 39 intersecting genes with significant variance in expression were identified. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the 39 intersecting genes revealed that these genes are mostly involved in leukocyte cell-cell adhesion and phagocytosis and have essential roles in regulating nerve repair. Quantitative real-time polymerase chain reaction assays were used to validate the expression of pivotal genes. Finally, nine pivotal genes that contribute to facial nerve recovery were identified, including Arhgap30, Akr1b8, C5ar1, Csf2ra, Dock2, Hcls1, Inpp5d, Sla, and Spi1. Primary Schwann cells were isolated from the sciatic nerve of neonatal rats. After knocking down Akr1b8 in Schwann cells with an Akr1b8-specific small interfering RNA plasmid, expression levels of monocyte chemoattractant protein-1 and interleukin-6 were decreased, while cell proliferation and migration were not obviously altered. These findings suggest that Akr1b8 likely regulates the interaction between Schwann cells and macrophages through regulation of cytokine expression to promote facial nerve regeneration. This study is the first to reveal a transcriptome change in the facial nerve trunk after facial nerve injury, thereby revealing the potential mechanism underlying repair of facial nerve injury. This study was approved by the Animal Ethics Committee of Nantong University, China in 2018 (approval No. S20180923-007).

Under the dual effects of aerodynamic heating and high-power electronic equipment heating, the heat sink and power demand of advanced high-speed aircraft have been exponentially rising, which seriously restricts the aircraft performance. To improve system cooling and power supply performance and reduce engine performance loss, a power and thermal management system (PTMS) with high performance, low energy consumption, and light weight urgently needs to be developed. In this paper, three modes of a potential PTMS with different heat sinks and bleed air sources are further discussed to analyze and compare the optimal matching with the flight mission at Mach 1–4.4. The equivalent mass method is used to uniformly assess the costs of the fixed weight, bleed, resistance, etc. as a function of the fuel weight penalty, which is chosen as the optimization objective. The optimization variables consist of the compressor outlet temperature, cooling air flow rate, and fan duct heat exchanger structure size. The results show that the intermediate-stage bleed air and fan duct heat sink are more suitable when the Mach number is less than 2, but the ram air bleed is highly suitable for flight missions at a high Mach number. Especially at Mach 3.4–4.4, the ram air bleed mode can respond to the cooling and power demands with a simple architecture.

Gas explosions and outbursts were the leading types of gas accidents in mining in China with gas concentration exceeding the threshold limit value (TLV) as the leading cause. Current research is focused mainly on using machine learning approaches for avoiding exceeding the TLV of the gas concentration. no published reports were found in the literature of attempts to uncover the correlation between gas data and other data to predict gas concentration. This research aimed to fill this gap and develop an innovative gas warning system for increasing coal mining safety. A mixed qualitative and quantitative research methodology was adopted, including a case study and correlational research. This research found that strong correlations exist between gas, temperature, and wind. It suggests that integrating correlation analysis of data on temperature and wind into gas would improve warning systems' sensitivity and reduce the incidence of explosions and other adverse events. A Unified Modeling Language (UML) model was developed by integrating the Correlation Analysis Theoretical Framework to the existing gas monitoring system for demonstrating an innovative gas warning system. Feasibility verification studies were conducted to verify the proposed method. This informed the development of an Innovative Integrated Gas Warning System which was deployed for user acceptance testing in 2020.

A coreless hybrid magnetic coupling mechanism has been studied and designed in the dynamic wireless charging system, through the mathematical model building, the parameter analysis and the model simulation comparison. The mechanism can improve the endurance of the electric vehicles, reduce the times of the power supply of the electric vehicles, and increase the offset ability. First of all, the dynamic model of the magnetic coupling mechanism is established based on the Kirchhoff’s law of the voltage and current, and the output power and the system efficiency are deduced considering the driving speed of the electric vehicle. Then, the influence of the mutual inductance between coils on the output power and the system efficiency is deeply analyzed, and the mutual inductance between coils is increased by adding the magnetic potential at a proper position, to propose and analyze a coreless hybrid magnetic coupling coil structure. Finally, the co-simulations are implemented through the finite element analysis simulations to compare and analyze the coil structure performance before and after the optimization. The results show that the designed coil structure can effectively improve the coupling between magnetic fields, and increase the offset ability. The mechanism has the characteristics of the small dynamic output power fluctuation range and high efficiency, and then can realize the stable power supply for the mobile power load.

The present experiment was conducted to evaluate the effect of enzymatically treated Artemisia annua L. (EA) on intestinal digestive function and immune capacity in weaned pigs. Firstly, a total of 300 21-day-old piglets were randomly allotted to five groups, including CON, EA1, EA2, EA3, and EA4 groups (basal diet supplemented with 0, 0.5, 1, 2, 4 g/kg EA, respectively). At 50 days of age, the results showed that pigs in the EA3 group presented significant improvements (p

To investigate the effect of lactic acid bacteria fermentation on jujube bioactivity, Streptococcus thermophilus was used to ferment jujube puree. The number of viable bacteria cells, physicochemical properties, phenolics profile and antioxidant capacity were analyzed, and their correlation were investigated. Streptococcus thermophilus exhibited a high growth capacity in jujube puree, and significantly (p

Nano-piezoelectric materials have drawn tremendous research interest. However, characterization of their piezoelectric properties, especially measuring the piezoelectric strain coefficients, remains a challenge. Normally, researchers use an AFM-based method to directly measure nano-materials’ piezoelectric strain coefficients. But, the extremely small piezoelectric deformation, the influence from the parasitic electrostatic force, and the environmental noise make the measurement results questionable. In this paper, a resonant piezo-force microscopy method was used to accurately measure the piezoelectric deformation from 1D piezoelectric nanofibers. During the experiment, the AFM tip was brought into contact with the piezoelectric sample and set to work at close to its first resonant frequency. A lock-in amplifier was used to pick up the sample’s deformation signal at the testing frequency. By using this technique, the piezoelectric strain constant d33 of the Lead Zirconate Titanate (PZT) nanofiber with a diameter of 76 nm was measured. The result showed that d33 of this PZT nanofiber was around 387 pm/V. Meanwhile, by tracking the piezoelectric deformation phase image, domain structures inside PZT nanofibers were identified.

Abstract Background pUL21 is a conserved protein of Alphaherpesvirinae that performs multiple important functions. The C-terminus of pUL21 in other members of this subfamily has RNA-binding ability; this domain contributes to pseudorabies virus (PRV) retrograde axonal transport in vitro and in vivo and participates in newly replicated viral DNA packaging and intracellular virus transport. However, knowledge regarding duck enteritis virus (DEV) pUL21 is limited. Results We verified that DEV UL21 is a γ2 gene that encodes a structural protein. Moreover, we observed that pUL21 localized to the nucleus and cytoplasm. DEV pUL21 interacted with pUL16 and formed a complex in transfected human embryonic kidney (HEK) 293 T cells and DEV-infected duck embryo fibroblasts (DEFs). These results were further confirmed by CO-IP assays. Conclusions The DEV UL21 gene is a late gene, and pUL21 localizes to the nucleus and cytoplasm. DEV UL21 is a virion component. In addition, pUL21 can interact with pUL16. These findings provide insight into the characteristics of UL21 and the interaction between pUL21 and its binding partner pUL16. Our study enhances the understanding of DEV pUL21.

Data-driven models are widely used in the field of water level prediction due to their generalizability and predictive abilities. In long-series prediction, however, data-driven models degrade rapidly due to the uncertainty and constraints of model data and parameters. To address the problem of inaccurate continuous water level prediction, this study introduced a data assimilation technique, the unscented Kalman filter (UKF), and embedded support vector regression (SVR) into the framework and applied it to Dongting Lake, the second largest freshwater lake in China. The results demonstrated that the assimilation model is significantly better than the non-assimilation model in predicting water levels and is not affected by the characteristics of lake level changes, with the R2 increasing from 0.975–0.982 to 0.998–0.999 and the RMSE decreasing from 0.436–0.159 m to 0.105–0.042 m. The prediction lead time also increased with the increase of continuous assimilation data. Further analysis of the assimilation model showed that when there was an assimilation cycle, the prediction remained stable for successive sets of two or more assimilated data, and the prediction lead time increased with successive assimilated data, from 4–8 days (one successive assimilation data) to 9–12 days (five successive assimilation data). Overall, this study found that the data assimilation framework can improve the prediction ability of data-driven models, with assimilated models having a smaller fluctuation range and higher degree of concentration than non-assimilated models. The increase in assimilated data will improve model accuracy as well as the number of days of prediction lead time when an assimilation cycle exists.

The body shape of a pig is the most direct production index, which can fully reflect the pig’s growth status and is closely related to important economic traits. In this study, a genome-wide association study on seven body size traits, the body length (BL), height (BH), chest circumference (CC), abdominal circumference (AC), cannon bone circumference (CBC), rump width (RW), and chest width (CW), were conducted in Yorkshire pigs. Illumina Porcine 80K SNP chips were used to genotype 589 of 5,572 Yorkshire pigs with body size records, and then the chip data was imputed to sequencing data. After quality control of imputed sequencing data, 784,267 SNPs were obtained, and the averaged linkage disequilibrium (r2) was 0.191. We used the single-trait model and the two-trait model to conduct single-step genome wide association study (ssGWAS) on seven body size traits; a total of 198 significant SNPS were finally identified according to the P-value and the contribution to the genetic variance of individual SNP. 11 candidate genes (CDH13, SIL1, CDC14A, TMRPSS15, TRAPPC9, CTNND2, KDM6B, CHD3, MUC13, MAPK4, and HMGA1) were found to be associated with body size traits in pigs; KDM6B and CHD3 jointly affect AC and CC, and MUC13 jointly affect RW and CW. These genes are involved in the regulation of bone growth and development as well as the absorption of nutrients and are associated with obesity. HMGA1 is proposed as a strong candidate gene for body size traits because of its important function and high consistency with other studies regarding the regulation of body size traits. Our results could provide valuable information for pig breeding based on molecular breeding.

In China, environmental pollution responsibilities are divided according to administrative regions. However, because of the strong externality of environmental pollution, the movement of environmental pollution undoubtedly increases the complexity of pollution governance. To divide the responsibility of environmental pollution governance in each province, we effectively quantify the unequal relationship between environmental pollution costs and economic benefits in each province to understand the mechanism and characteristics of inter-provincial environmental pollution movement. Based on the regional input–output model and an inventory we compiled of sulfur dioxide(SO2) emissions of air pollutants in 2012, we calculate the implied inter-provincial environmental pollution emissions and economic benefits from trade, based on production and consumption (supply-side and demand-side). In addition, the movement relationship is explored, and the cost and economic value-added indexes of air pollution control are further constructed to provide effective evidence for a reasonable division of responsibility for environmental pollution control. The results show that there are obvious environmental inequities in the regional trade process in each province, indicating that environmental pollution has been moved. Developed provinces have more economic benefits but pay less in the process of trading goods with less-developed provinces due to the advantages of their industrial structure, while the opposite is true for less-developed provinces. Finally, we propose corresponding policy recommendations to change this condition.

In stock trading markets, trade duration (i. e., inter-arrival times of trades) usually exhibits high uncertainty and excessive zero values. To forecast conditional distribution of trade duration, this study proposes a hybrid model called “DL-ZIACD” for short, which addresses the problem of excessive zero values by a zero-inflated distribution. Meanwhile, dynamics of the distribution time-varying parameters are captured by a specially designed deep learning (DL) architecture in which the behavioral patterns of large traders and small individual traders are represented separately by different blocks. The proposed hybrid model takes advantage of the strong fitting ability of deep learning methods while allowing for providing a probabilistic output. This paper empirically applied the established model to a large-scale dataset, containing 9,900,000 transactions of the Chinese Shenzhen Stock Exchange 100 Index (SZSE 100) constituents. To the best of our knowledge, no previous studies have applied conditional duration models to a dataset of such a large scale. For both the central location forecasting and the extreme quantile forecasting, our proposed model exhibited significant superiority over the benchmark models, which indicates that our DL-ZIACD model can provide accurate forecasts in conditional duration distribution.

BackgroundPrevious studies suggest that the vaginal microbiome is associated with polycystic ovary syndrome (PCOS). However, the clinical manifestations of PCOS are heterogeneous. Whether the vaginal microbiome is related with different clinical symptoms was unknown.Materials and MethodsIn this cross-sectional study, 89 female patients with PCOS admitted to Zhongda Hospital (Nanjing, China) were included. Basic demographic information, health-related behaviors, clinical manifestations and sex hormone levels were comprehensively recorded for all patients. Vaginal swabs were acquired for microbiota sequencing of the V3–V4 region of the 16S rRNA gene.ResultsThe prevalence of bacterial vaginitis and vulvovaginal candidiasis was 15.7% and 13.5%, respectively, within the PCOS patients, which were the most important factors affecting the vaginal microbiome (permutational multivariate analysis of variance test, R2 = 0.108, P = 0.001). The vaginal microbiome was associated with specific clinical manifestations of PCOS, including acanthosis nigricans, intermenstrual bleeding, pregnancy history, testosterone level and anti-müllerian hormone level, with P values < 0.05. The abundance of Lactobacillus crispatus was higher (P = 0.010) while that of Lactobacillus iners was lower (P = 0.036) among PCOS patients with elevated testosterone levels. Other potential bacterial biomarkers were not statistically significant after adjusting for confounding factors. No evidence of associations of other common manifestations of PCOS, such as obesity and acne, with the vaginal microbiome was obtained.ConclusionVaginal bacterial species among PCOS patients with variable clinical manifestations, especially differences in testosterone levels, are distinct. Further studies are essential to investigate the microbiota and molecular mechanisms underpinning this disease.

Unsupervised feature learning via auto-encoders results in low-dimensional representations in latent space that capture the patterns of input data. The auto-encoders with robust regularization learn qualified features that are less sensitive to small perturbations of inputs. However, the previous robust auto-encoders highly depend on pre-defined structure settings and often learn full-connected networks that are easily prone to over-fitting. To solve the above limitations, we propose in this paper an explicitly regularized framework which improves the sparsity and flexibility of robust auto-encoders. First, our model encourages the activation functions to automatically adjust themselves between linear and non-linear ones. Second, the mapping functions of the encoder are constrained by group sparsity and exclusive sparsity to reduce the redundancy of parameters. The proximal gradient method is used to optimize our model since the objective function contains non-smooth components. We conduct experiments in single-layer and multiple-layer auto-encoders in the classification task. The numerical results show that our model achieves better accuracy than baseline models. Our method also shows better performance in denoising task.

An 8-week feeding trial with high-carbohydrate- and 100, 200 and 300 mg/kg mulberry leaf flavonoids (MLF)-supplemented diets (HCF1, HCF2 and HCF3, respectively) was conducted to evaluate the protective effect of MLF on oxidized high-carbohydrate-induced glucose metabolism disorder, liver oxidative damage and intestinal microbiota disturbance in Monopterus albus. The results showed that HC diets had significant negative effects on growth, glucose metabolism, liver antioxidant and immunity, as well as intestinal microbiota, in comparison to CON diets. However, WGR and SR in the HCF3 group dramatically increased compared to the HC group. With the increase of MLF in the HC diet, the activities of glycolysis and antioxidant enzymes in the liver tended to increase, while the changes of gluconeogenesis-related enzyme activities showed the opposite trend and significantly changed in the HCF3 group. Additionally, MLF supplementation dramatically increased the mRNA expression involved in glycolysis, antioxidative enzymes and anti-inflammatory cytokines in comparison with the HC group. Furthermore, gluconeogenesis and pro-inflammatory cytokine genes’ expression dramatically decreased. Furthermore, the proportion of Clostridium and Rhodobacter in the HC group dramatically declined, and the proportion of Lactococcus dramatically increased, compared to the HC group. In addition, 300 mg/kg MLF supplementation significantly improved the species composition and homeostasis of intestinal microbiota. These results indicate that MLF can alleviate the negative effects of low growth performance, glucose metabolism disorder, liver oxidative damage and intestinal microbiota disturbance caused by HC diets, and the relief of MLF is dose-related.

Direct Z-scheme photocatalysts have attracted extensive attention due to their strong redox ability and efficient separation of photogenerated electron-hole pairs. In this study, we constructed two types of ZnS/SnS2 heterojunctions with different stacking models of ZnS and SnS2 layers, and investigated their structures, stabilities, and electronic and optical properties. Both types of heterojunctions are stable and are direct Z-scheme photocatalysts with band gaps of 1.87 eV and 1.79 eV, respectively. Furthermore, their oxidation and reduction potentials straddle the redox potentials of water, which makes them suitable as photocatalysts for water splitting. The built-in electric field at the heterojunction interface improves the separation of photogenerated electron-hole pairs, thus enhancing their photocatalytic efficiency. In addition, ZnS/SnS2 heterojunctions have higher carrier mobilities and light absorption intensities than ZnS and SnS2 monolayers. Therefore, the ZnS/SnS2 heterojunction has a broad application prospect as a direct Z-scheme visible-light-driven photocatalyst for overall water splitting.

Some recent studies associated insulin therapy with negative cardiovascular events and shorter lifespan. SUR2A, a KATP channel subunit, regulate cardioprotection and cardiac ageing. Here, we have tested whether glucose and insulin regulate expression of SUR2A/KATP channel subunits and resistance to metabolic stress in heart H9c2 cells. Absence of glucose in culture media decreased SUR2A mRNA, while mRNAs of Kir6.2, Kir6.1, SUR1 and IES SUR2B were increased. 2-deoxyglucose (50 mM) decreased mRNAs of SUR2A, SUR2B and SUR1, did not affect IES SUR2A and IES SUR2B mRNAs and increased Kir6.2 mRNA. No glucose and 2-deoxyglucose (50 mM) decreased resistance to an inhibitor of oxidative phosphorylation, DNP (10 mM). 50 mM glucose did not alter KATP channel subunits nor cellular resistance to DNP (10 mM). Insulin (20 ng/ml) in both physiological and high glucose (50 mM) down-regulated SUR2A while upregulating Kir6.1 and Kir6.2 (in high glucose only). Insulin (20 ng/ml) in physiological and high glucose decreased cell survival in DNP (10 mM). As opposed to Kir6.2, infection with SUR2A resulted in titre-dependent cytoprotection. We conclude that insulin decreases resistance to metabolic stress in H9c2 cells by decreasing SUR2A expression. Lower cardiac SUR2A levels underlie increased myocardial susceptibility to metabolic stress and shorter lifespan. Keywords: Insulin, Glucose, SUR2A, Heart

One of the most notoriously altered genes in human cancer is the tumor-suppressor TP53, which is mutated with high frequency in more cancers than any other tumor suppressor gene. Beyond the loss of wild-type p53 functions, mutations in the TP53 gene often lead to the expression of full-length proteins with new malignant properties. Among the defined oncogenic functions of mutant p53 is its effect on cell metabolism and autophagy. Due to the importance of autophagy as a stress adaptive response, it is frequently dysfunctional in human cancers. However, the role of p53 is enigmatic in autophagy regulation. While the complex action of the wild-type p53 on autophagy has extensively been described in literature, in this review, we focus on the conceivable role of distinct mutant p53 proteins in regulating different autophagic pathways and further discuss the available evidence suggesting a possible autophagy stimulatory role of mutant p53. Moreover, we describe the involvement of different autophagic pathways in targeting and degrading mutant p53 proteins, exploring the potential strategies of targeting mutant p53 in cancer by autophagy.

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a leading cancer with high morbidity and mortality worldwide. The aim is to identify genes with clinical significance by integrated bioinformatics analysis and investigate their function in HNSCC.MethodsWe downloaded and analyzed two gene expression datasets of GSE6631 and GSE107591 to screen differentially expressed genes (DEGs) in HNSCC. Common DEGs were functionally analyzed by Gene ontology and KEGG pathway enrichment analysis. Protein-protein interaction (PPI) network was constructed with STRING database and Cytoscape. ENDOU was overexpressed in FaDu and Cal-27 cell lines, and cell proliferation and migration capability were evaluated with MTT, scratch and transwell assay. The prognostic performance of ENDOU and expression correlation with tumor infiltrates in HNSCC were validated with TCGA HNSCC datasets.ResultsNinety-eight genes shared common differential expression in both datasets, with core functions like extracellular matrix organization significantly enriched. 15 genes showed prognostic significance, and COBL and ENDOU serve as independent survival markers in HNSCC. In-vitro ENDOU overexpression inhibited FaDu and Cal-27 cells proliferation and migration, indicating its tumor-suppressing role in HNSCC progression. GSEA analysis indicated ENDOU down-stream pathways like DNA replication, mismatch repair, cell cycle and IL-17 signaling pathway. ENDOU showed relative lower expression in HNSCC, especially HPV-positive HNSCC samples. At last, ENDOU showed negative correlation with tumor purity and tumor infiltrating macrophages, especially M2 macrophages.ConclusionThis study identified ENDOU as a biomarker with prognostic significance in HNSCC progression.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with dysregulation of liver metabolism and inflammation. G-protein coupled bile acid receptor 1 (TGR5) is a cell surface receptor that is involved in multiple metabolic pathways. However, the functions of TGR5 in regulating macrophage innate immune activation in NASH remain unclear. Here, we found that TGR5 expression was decreased in liver tissues from humans and mice with NASH. Compared to wild type (WT) mice, TGR5-knockout (TGR5−/−) mice exhibited exacerbated liver damage, increased levels of proinflammatory factors, and enhanced M1 macrophage polarization. Moreover, TGR5 deficiency facilitated M1 macrophage polarization by promoting NLRP3 inflammasome activation and caspase-1 cleavage. Taken together, our findings revealed that TGR5 signaling attenuated liver steatosis and inflammation and inhibited NLRP3-mediated M1 macrophage polarization in NASH.

Catalases (CATs) are present in almost all living organisms and play important roles in plant development and response to various stresses. However, there is relatively little information on CAT genes in wheat and related Triticeae species. A few studies on CAT family genes in wheat have been reported. In this study, ten CAT proteins (TaCATs) were identified in wheat and classified into three groups based on their phylogenetic features and sequence analysis. The analysis of the structure and motif composition of the TaCAT proteins suggested that a segmental duplication event occurred in the TaCAT gene family. Collinearity relationship analysis among different species showed that there were three orthologous CAT genes in rice and in maize. By analyzing the cis-elements in the promoter regions, we speculated that TaCAT genes expression might be regulated by light, oxygen deficit, methyl jasmonate and abscisic acid, and by transcription factors such as MYB. A Gene Ontology (GO)-based analysis showed that TaCAT proteins may be related to the response to various stresses, are cytoplasm localized, and may function as antioxidant enzymes. RT-qPCR and transcriptome data analyses exhibited distinct expression patterns of TaCAT genes in different tissues and in response to various treatments. In this study, a comprehensive analysis of wheat CAT genes was performed, enriching our knowledge of CAT genes and providing a foundation for further functional analyses of this gene family in wheat.

The outbreak of COVID-19 seriously challenges every government with regard to capacity and management of public health systems facing the catastrophic emergency. Culture and anti-epidemic policy do not necessarily conflict with each other. All countries and governments should be more tolerant to each other in seeking cultural and political consensus to overcome this historically tragic pandemic together.

There is a colourful palette of metaheuristics for solving continuous optimisation problems in the literature. Unfortunately, it is not easy to pick a suitable one for a specific practical scenario. Moreover, oftentimes the selected metaheuristic must be tuned until finding adequate parameter settings. Therefore, this work presents a framework based on a hyper-heuristic powered by Simulated Annealing for tailoring population-based metaheuristics. To do so, we recognise search operators from well-known techniques as building blocks for new ones. The presented framework comprises six main modules coded in Python, which can be used independently, and which help explore new metaheuristics.

Liver fibrosis is a major endpoint of patients with chronic liver diseases. The molecular mechanisms behind liver fibrosis remain largely unknown. Many studies have indicated the role of microRNA (miRNA) in hepatic tumorigenesis. But the role of miRNA in liver fibrosis is little known. Activated hepatic stellate cells (HSCs) can secret extracellular matrix proteins (ECM) and are the major contributors to liver fibrosis/cirrhosis. Here, a microarray assay of quiescent and transforming growth factor β1 (TGF-β1) activated HSCs indicated that miR-98 might play a crucial role in liver fibrosis. We found that miR-98 was significantly downregulated in activated HSCs. miR-98 overexpression inhibited HSCs activation. Furthermore, we hypothesized that miR-98 regulated hepatic leukemia factor (HLF) expression by binding to the 3′ UTR of its mRNA directly, as evidenced by luciferase reporter assay. HLF overexpression increased HSCs activation by inducing hypoxia inducible factor-1 alpha (HIF-1α) expression, resulting in the activation of TGF-β/Smad2/3 signaling pathway. Besides, low expression of miR-98 was also found in liver tissues from various fibrotic murine models, including carbon tetrachloride (CCl4), bile duct ligation (BDL), and high-fat diet (HFD)-induced liver fibrosis. miR-98 overexpression in vivo by ago-miR-98 injection could attenuate CCl4-, BDL-, and HFD-induced murine hepatic fibrosis. Meanwhile, miR-98 overexpression suppressed HLF expression and reduced fibrosis marker expression. Collectively, our study demonstrates that miR-98 suppress HSCs activation by targeting HLF directly and interacting with HIF-1α/TGF-β/Smad2/3 signaling pathway, which may be an effective therapeutic target for liver fibrosis.

Background: COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods: In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0–6 years old (children); 7–14 (primary and junior high school students); 15–17 (high school students); 18–22 (university students); 23–44 (young/middle-aged people); 45–64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups in each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings: We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19 in China, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4–14). Moreover, the surge in the number of new cases reported on Feb. 12 and 13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient policies, such as Beijing, and those with strict policies, such as Shenzhen. Interpretation: With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding: General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Natural Science Foundation of China.

Maize (Zea mays) is a major cereal crop that originated at low latitudes, and thus photoperiod sensitivity is an important barrier to the use of tropical/subtropical germplasm in temperate regions. However, studies of the mechanisms underlying circadian regulation in maize are at an early stage. In this study we cloned ZmCCA1a on chromosome 10 of maize by map-based cloning. The gene is homologous to the Myb transcription factor genes AtCCA1/AtLHY in Arabidopsis thaliana; the deduced Myb domain of ZmCCA1a showed high similarity with that of AtCCA1/AtLHY and ZmCCA1b. Transiently or constitutively expressed ZmCCA1a-YFPs were localized to nuclei of Arabidopsis mesophyll protoplasts, agroinfiltrated tobacco leaves, and leaf and root cells of transgenic seedlings of Arabidopsis thaliana. Unlike AtCCA1/AtLHY, ZmCCA1a did not form homodimers nor interact with ZmCCA1b. Transcripts of ZmCCA1a showed circadian rhythm with peak expression around sunrise in maize inbred lines CML288 (photoperiod sensitive) and Huangzao 4 (HZ4; photoperiod insensitive). Under short days, transcription of ZmCCA1a in CML288 and HZ4 was repressed compared with that under long days, whereas the effect of photoperiod on ZmCCA1a expression was moderate in HZ4. In ZmCCA1a-overexpressing A. thaliana (ZmCCA1a-ox) lines, the circadian rhythm was disrupted under constant light and flowering was delayed under long days, but the hypocotyl length was not affected. In addition, expression of endogenous AtCCA1/AtLHY and the downstream genes AtGI, AtCO, and AtFt was repressed in ZmCCA1a-ox seedlings. The present results suggest that the function of ZmCCA1a is similar, at least in part, to that of AtCCA1/AtLHY and ZmCCA1b, implying that ZmCCA1a is likely to be an important component of the circadian clock pathway in maize.

In many disciplines, the evaluation of algorithms for processing massive data is a challenging research issue. However, different algorithms can produce different or even conflicting evaluation performance, and this phenomenon has not been fully investigated. The motivation of this paper aims to propose a solution scheme for the evaluation of clustering algorithms to reconcile different or even conflicting evaluation performance. The goal of this research is to propose and develop a model, called decision-making support for evaluation of clustering algorithms (DMSECA), to evaluate clustering algorithms by merging expert wisdom in order to reconcile differences in their evaluation performance for information fusion during a complex decision-making process. The proposed model is tested and verified by an experimental study using six clustering algorithms, nine external measures, and four MCDM methods on 20 UCI data sets, including a total of 18,310 instances and 313 attributes. The proposed model can generate a list of algorithm priorities to produce an optimal ranking scheme, which can satisfy the decision preferences of all the participants. The results indicate our developed model is an effective tool for selecting the most appropriate clustering algorithms for given data sets. Furthermore, our proposed model can reconcile different or even conflicting evaluation performance to reach a group agreement in a complex decision-making environment.

With the ultrahigh-speed, large-scale development of tourism and the increasing frequency, intensity, and scope of extreme natural hazards in the context of climate warming, tourism has entered a high-risk era. Based on the central urban area within the outer ring of Shanghai as the research area and the tourism attraction as the research object, this paper takes the flood scenario simulation combined with GIS network analysis to evaluate the spatial accessibility of the emergency response of urban key public service departments (120) under current and future river flood scenarios in different return periods. The results of the study show that, (1) under the current and future flood scenarios, the submergence range is mainly distributed within 2 ∼ 3 km along the banks of the Huangpu River, and it tends to increase from north to south; (2) there are 6, 9, and 21 tourism attractions in the emergency blind area under the once-in-a-century floods in 2010, 2030, and 2050 and 98, 105, and 112 tourism attractions in the emergency blind area under the once-in-a-millennium floods in 2010, 2030, and 2050, respectively; (3) in the flood scene, local road traffic in the inundation area is interrupted by water, and 120 first aid cannot get or be delayed to some tourist attraction (blind area); and (4) in 2030, under the normal and flooding scenarios, 120 first aid in the downtown area of Shanghai has the fastest route to tourism attractions according to the speed of S1, S2, S3, and S4. The flooding intensity (range and water depth), road traffic conditions (vehicle flow speed), and the number and location of key public service departments jointly determine the service scope and response time of medical emergency in urban floods. Since the flood control area of the central city in Shanghai is mainly distributed in the 2 ∼ 3 km area on both banks of the Huangpu River, the impact of flood on the emergency medical service in the entire central city is limited, mainly in some hospitals in the riverside area, where 120 emergency vehicles are unable or delayed to reach some tourism attractions. The research indicates that the quantitative assessment method of spatial accessibility of the emergency response under flood scenario simulation has important scientific value and practical significance, which can provide decision-making basis for emergency management of tourism in China’s urban flood disaster.

An eight-week feeding experiment was conducted to evaluate the effects of replacing fish meal with stickwater hydrolysate (SWH) on the growth, serum biochemical, immune indexes, intestinal health of Monopterus albus. The control diet was produced using fish meal (FM), and the other three diets replaced the fish meal with 5.0% (SWH5.0), 10.0% (SWH10.0), and 15.0% (SWH15.0) SWH. The results showed that the weight gain rate (WGR) of the SWH10.0 and SWH15.0 groups was significantly higher than that of the FM group, while the opposite result was found for feed conversion ratio (FCR). The activities of trypsin and amylase were significantly higher in the SWH10.0 groups than in the FM group. There were no significant differences in serum triglyceride (TG), complement 3 (C3) and malondialdehyde (MDA) contents and lysozyme (LZM), alkaline phosphatase (AKP) and superoxide dismutase (SOD) activities among all treatment groups. With increasing SWH replacement, the glucose (GLU) and alanine aminotransferase (ALT) contents were increased, and the SWH10.0 and SWH15.0 groups had a significant increase compared with the FM group. The serum aspartate aminotransferase (AST), immunoglobulin M (IgM) and C4 contents were significantly higher in the SWH10.0 group than that in the FM group. The villi length, goblet cell quantity and muscle thickness were significantly higher in the SWH10.0 groups than in the FM group. Furthermore, we observed that SWH replacement can decrease the richness and diversity of the intestinal microbiota. The dominant phylum and genus in the intestine of M. albus were Firmicutes and Clostridium, respectively. The partial replacement of fish meal with SWH increased the richness of Firmicutes and decreased the richness of Edwardsiella, which promoted the growth and immune performance of M. albus. Therefore, it could be inferred that the partial replacement of fish meal with SWH can improve the growth performance, immune function and intestinal health of M. albus. The optimal replacement ratio is 10%. Keywords: Monopterus albus, Stickwater hydrolysate, Growth, Immunity, Intestinal microbiota

Background/Aims: CD133+CD44+ cancer stem cells previously isolated from laryngeal squamous cell carcinoma (LSCC) cell lines showed strong malignancy and tumorigenicity. However, the molecular mechanism underlying the enhanced malignancy remained unclear. Methods: Cell proliferation assay, spheroid-formation experiment, RNA sequencing (RNA-seq), miRNA-seq, bioinformatic analysis, quantitative real-time PCR, migration assay, invasion assay, and luciferase reporter assay were used to identify differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs, construct transcription regulatory network, and investigate functional roles and mechanism of circRNA in CD133+CD44+ laryngeal cancer stem cells. Results: Differentially expressed genes in TDP cells were mainly enriched in the biological processes of cell differentiation, regulation of autophagy, negative regulation of cell death, regulation of cell growth, response to hypoxia, telomere maintenance, cellular response to gamma radiation, and regulation of apoptotic signaling, which are closely related to the malignant features of tumor cells. We constructed the regulatory network of differentially expressed circRNAs, miRNAs and mRNAs. qPCR findings for the expression of key genes in the network were consistent with the sequencing data. Moreover, our data revealed that circRNA hg19_circ_0005033 promotes proliferation, migration, invasion, and chemotherapy resistance of laryngeal cancer stem cells. Conclusions: This study provides potential biomarkers and targets for LSCC diagnosis and therapy, and provide important evidences for the heterogeneity of LSCC cells at the transcription level.

A combination process of completely non-thermal processing methods involving high hydrostatic pressure (HHP) and vacuum-freeze drying (VFD) for producing a new snack from fruit and vegetable blends was developed, and the effect of the process on flavor quality was investigated. The HHP–VFD treatment did not significantly reduce volatile compound contents compared to single HHP or VFD. Gas chromatography–olfactometry showed that HHP–VFD raised the contents of floral-like volatile compounds (e.g., β-ionone) compared to the untreated sample. Sensory evaluation analysis confirmed that the overall liking was unchanged after the HHP–VFD treatment. The HHP–VFD combined treatment is effective in maintaining the flavor and extending shelf life, and is convenient for the portability and transportation of ready-to-drink juice.

The arsenic acid-resistant (ArsR) family transcriptional regulators are widely distributed in microorganisms, including in the facultative intracellular pathogen Brucella spp. ArsR proteins are implicated in numerous biological processes. However, the specific roles of ArsR family members in Brucella remain obscure. Here, we show that ArsR6 (BSS2_RS07325) is required for Brucella survival both under heat, oxidative, and osmotic stress and in a murine infection model in vivo. RNA-seq and ChIP-seq reveal that 34 potential target genes for ArsR6 protein were identified, among which eight genes were up-regulated and 26 genes were down-regulated, including outer membrane protein 25D (Omp25D). ArsR6 autoregulates its own expression to maintain bacterial intracellular Cu/Ni homeostasis to benefit bacterial survival in hostile environments. Moreover, ArsR6 also regulates the production of virulence factor Omp25D, which is important for the survival of Brucella under stress conditions. Significantly, Omp25D deletion strain attenuated in a murine infection model in vivo. Altogether, our findings reveal a unique mechanism in which the ArsR family member ArsR6 autoregulates its expression and also modulates Omp25D expression to maintain metal ion homeostasis and virulence in Brucella.