bluuebunny/crossref_metadata_2025 huggingface dataset:
Heavy Metal Distribution and Bioaccumulation Combined With Ecological and Human Health Risk Evaluation in a Typical Urban Plateau Lake, Southwest China
Authors: Liu Xi , Zhang Junqian , Huang Xiaolong , Zhang Lu , Yang Chao , Li Enhua , Wang Zhi
Published: February 2022

Heavy metal contamination in lakes caused by the rapid industrialization and urbanization is a serious problem. In this study, 12 heavy metals were systematically surveyed in aquatic environment and organisms of Dianchi Lake. Results showed that heavy metals pollutions in surface water exhibited a decreasing order of Ba > Fe > Zn > Mn > As > Ni > Cr > Cu > Pb > Cd > Co, equipped a consistency in spatial distribution, seriously contaminating the northern and southern parts. The average concentration of sedimentary heavy metals appeared in an order of Fe > Mn > Zn > Ba > Cu > Pb > Cr > As > Ni > Co > Cd > Ag. The main existing fraction (51.9–75.0%) of Cu, Pb, Cr, As, Fe, Co, Ni, Ag, and Ba in sediments was residual fraction, whereas the exchangeable fraction (40.9–62.0%) was the dominant component for Cd, Zn, and Mn. Among the selected aquatic organisms, Cu, Pb, Zn, and Ag possessed a strong bioaccumulation effect, followed by Mn, Fe, Co, and Ni. Ecological risk assessment indicated that Cu, Cr, and Zn were the dominant heavy metal contaminants in surface water; Cd presented the disastrous risk and accounted for the considerable proportion of ecological risk in sediments. Human health risk evaluation showed that the selected aquatic products of Dianchi Lake were not absolutely safe, and As was the major contributor. This study systematically revealed heavy metal distributions in aquatic environments, which was conductive to environmental safety and human health.
Spatiotemporal Differentiation of Land Ecological Security and Its Influencing Factors: A Case Study in Jinan, Shandong Province, China
Authors: Liu Jinhua , Cao Xiangyang , Zhao Lesong , Dong Guanglong , Jia Kun
Published: February 2022

Land ecological security plays an important role in the sustainable land resources utilization and social economic development. In this study, the Pressure-State-Response (PSR) model was constructed to measure the land ecological security pattern based on grids scale of Jinan from 2006 to 2016. Then, Moran’s index was used to explore the spatial autocorrelation of the land ecological security score. Finally, the driving factors of land ecological security pattern differentiation in Jinan were revealed by using geographical detector method. The results showed that the level of land ecological security in Jinan, generally, decreased at the beginning and then gradually increased during the research periods. More specifically, land ecological security was represented as a downward trend in the central region and an upward trend in the southern mountainous area. The apparent regional heterogeneity of land ecological security level in Jinan showed the overall distribution pattern “low in the middle and high around” and the direction of urban expansion consistent with the low-level land ecological security. Land ecological security presented a significant spatial autocorrelation. The differentiation of land ecological security pattern was mainly driven by social and economic development factors, among which urban expansion was most important, so urban development should try to avoid occupying those areas with high level of land ecological security. From the study, the valuable information could be provided in the improvement of land ecosystem environment and in the facilitation of sustainable development.
Biased Learning as a Simple Adaptive Foraging Mechanism
Authors: Avgar Tal , Berger-Tal Oded
Published: February 2022

Adaptive cognitive biases, such as “optimism,” may have evolved as heuristic rules for computationally efficient decision-making, or as error-management tools when error payoff is asymmetrical. Ecologists typically use the term “optimism” to describe unrealistically positive expectations from the future that are driven by positively biased initial belief. Cognitive psychologists on the other hand, focus on valence-dependent optimism bias, an asymmetric learning process where information about undesirable outcomes is discounted (sometimes also termed “positivity biased learning”). These two perspectives are not mutually exclusive, and both may lead to similar emerging space-use patterns, such as increased exploration. The distinction between these two biases may becomes important, however, when considering the adaptive value of balancing the exploitation of known resources with the exploration of an ever-changing environment. Deepening our theoretical understanding of the adaptive value of valence-dependent learning, as well as its emerging space-use and foraging patterns, may be crucial for understanding whether, when and where might species withstand rapid environmental change. We present the results of an optimal-foraging model implemented as an individual-based simulation in continuous time and discrete space. Our forager, equipped with partial knowledge of average patch quality and inter-patch travel time, iteratively decides whether to stay in the current patch, return to previously exploited patches, or explore new ones. Every time the forager explores a new patch, it updates its prior belief using a simple single-parameter model of valence-dependent learning. We find that valence-dependent optimism results in the maintenance of positively biased expectations (prior-based optimism), which, depending on the spatiotemporal variability of the environment, often leads to greater fitness gains. These results provide insights into the potential ecological and evolutionary significance of valence-dependent optimism and its interplay with prior-based optimism.
Genome-Wide Identification of Aldehyde Oxidase Genes in Moths and Butterflies Suggests New Insights Into Their Function as Odorant-Degrading Enzymes
Authors: Godoy Ricardo , Mutis Ana , Carabajal Paladino Leonela , Venthur Herbert
Published: February 2022

Aldehyde oxidases (AOXs) are common detoxifying enzymes in several organisms. In insects, AOXs act in xenobiotic metabolism and as odorant-degrading enzymes (ODEs). These last appear as crucial enzymes in the life cycle of insects, helping to reset their olfactory system, particularly in lepidopterans, which fulfill important ecological roles (e.g., pollination or destructive life cycles). A comprehensive understanding of their olfactory system has provided opportunities to study key chemosensory proteins. However, no significant advance has been made around lepidopteran AOXs research, and even less around butterflies, a recently evolved lineage. In this study we have identified novel AOX gene families in moths and butterflies in order to understand their role as ODEs. Eighteen genomes from both moths and butterflies were used for phylogenetics, molecular evolution and sequence analyses. We identified 164 AOXs, from which 91 are new. Their phylogeny showed two main clades that are potentially related to odorant-degrading function, where both moths and butterflies have AOXs. A first ODE-related clade seems to have a non-ditrysian origin, likely related to plant volatiles. A second ODE-related clade could be more pheromone-biased. Molecular evolution analysis suggests a slight purifying selection process, though a number of sites appeared under positive selection. ODE-related AOXs have changed a phenylalanine residue by proline in the active site. Finally, this study could serve as a reference for further evolutionary and functional studies around Lepidopteran AOXs.
Mycorrhizal Fungi Associated With Juniper and Oak Seedlings Along a Disturbance Gradient in Central Mexico
Authors: Bermúdez-Contreras Ana I. , Monroy-Guzmán Camila , Pérez-Lucas Lizbeth , Escutia-Sánchez Jorge Alberto , Del Olmo-Ruiz Mariana , Truong Camille
Published: February 2022

Competition for resources between arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) plants can alter belowground mycorrhizal communities, but few studies have investigated host effects on both AM and ECM communities. In Central Mexico, the AM plant Juniperus deppeana is frequently used for reforesting areas affected by soil erosion, while the surrounding native forests are dominated by ECM oak trees. Oaks are capable of associating with both AM and ECM fungi during part of their life cycle (a feature known as dual mycorrhization) but it is unclear whether junipers possess such ability. To assess how juniper planting may affect belowground fungal interactions with oaks, we investigated mycorrhizal associations in J. deppeana and Quercus rugosa seedlings along a disturbance gradient: a native oak forest, a mixed Juniperus-Quercus population in secondary vegetation and a juniper site severely degraded by mining extraction. We measured root colonization and identified fungal communities using soil and root meta-barcoding of the ITS2 rDNA region. ECM fungal community composition was strongly affected by disturbance (regardless of host), while the community composition of AM fungi was mostly host-dependent, with a higher AM fungal richness in J. deppeana. Importantly, the fungal communities associated with Q. rugosa seedlings significantly changed in the vicinity of juniper trees, while those of J. deppeana seedlings were not affected by the presence of oak trees. Even though ECM fungal richness was higher in Q. rugosa and in the native forest, we detected a variety of ECM fungi associated exclusively with J. deppeana seedlings, suggesting that this plant species may be colonized by ECM fungi. Our results indicate that J. deppeana can alter ECM native fungal communities, with implications for its use in reforestation of mixed oak forests.
Integrated Analysis of circRNA-miRNA-mRNA ceRNA Network in Cardiac Hypertrophy
Authors: Chen Yang-Hao , Zhong Ling-Feng , Hong Xia , Zhu Qian-Li , Wang Song-Jie , Han Ji-Bo , Huang Wei-Jian , Ye Bo-Zhi
Published: February 2022

Cardiac hypertrophy is an adaptive cardiac response that accommodates the variable hemodynamic demands of the human body during extended periods of preload or afterload increase. In recent years, an increasing number of studies have pointed to a potential connection between myocardial hypertrophy and abnormal expression of non-coding RNAs. Circular RNA (circRNA), as one of the non-coding RNAs, plays an essential role in cardiac hypertrophy. However, few studies have systematically analyzed circRNA-related competing endogenous RNA (ceRNA) regulatory networks associated with cardiac hypertrophy. Therefore, we used public databases from online prediction websites to predict and screen differentially expressed mRNAs and miRNAs and ultimately obtained circRNAs related to cardiac hypertrophy. Based on this result, we went on to establish a circRNAs-related ceRNA regulatory network. This study is the first to establish a circRNA-mediated ceRNA regulatory network associated with myocardial hypertrophy. To verify the results of our analysis, we used PCR to verify the differentially expressed mRNAs and miRNAs in animal myocardial hypertrophy model samples. Our findings suggest that three mRNAs (Col12a1, Thbs1, and Tgfbr3), four miRNAs (miR-20a-5p, miR-27b-3p, miR-342-3p, and miR-378a-3p), and four related circRNAs (circ_0002702, circ_0110609, circ_0013751, and circ_0047959) may play a key role in cardiac hypertrophy.
Innate Immune Activation and Circulating Inflammatory Markers in Preschool Children
Authors: Collier Fiona , Chau Cerys , Mansell Toby , Faye-Chauhan Keshav , Vuillermin Peter , Ponsonby Anne-Louise , Saffery Richard , Tang Mimi L. K. , O’Hely Martin , Carlin John , Gray Lawrence E. K. , Bekkering Siroon , Burgner David ,   the Barwon Infant Study Investigator Group
Published: February 2022

Early childhood is characterised by repeated infectious exposures that result in inflammatory responses by the innate immune system. In addition, this inflammatory response to infection is thought to contribute to the epidemiological evidence linking childhood infection and adult non-communicable diseases. Consequently, the relationship between innate immune responses and inflammation during early life may inform prevention of NCDs later in life. In adults, non-genetic host factors such as age, sex, and obesity, strongly impact cytokine production and circulating mediators, but data in children are lacking. Here, we assessed cytokine responses and inflammatory markers in a population of healthy preschool children (mean age 4.2 years). We studied associations between cytokines, plasma inflammatory markers and non-genetic host factors, such as sex, age, adiposity, season, and immune cell composition. Similar to adults, boys had a higher inflammatory response than girls, with IL-12p70 and IL-10 upregulated following TLR stimulation. Adiposity and winter season were associated with increased circulating inflammatory markers but not cytokine production. The inflammatory markers GlycA and hsCRP were positively associated with production of a number of cytokines and may therefore reflect innate immune function and inflammatory potential. This dataset will be informative for future prospective studies relating immune parameters to preclinical childhood NCD phenotypes.
Phytogenics From Sage and Lemon Verbena Promote Growth, Systemic Immunity and Disease Resistance in Atlantic Salmon (Salmo salar)
Authors: Salomón Ricardo , Furones M. Dolors , Reyes-López Felipe E. , Tort Lluis , Firmino Joana P. , Quintela José C. , Pinilla-Rosas José M. , Vallejos-Vidal Eva , Gisbert Enric
Published: February 2022

The transcriptomic response of the head kidney, the main lymphohematopoietic tissue of the body, was evaluated in Atlantic salmon (Salmo salar) smolts fed a functional feed containing a phytogenic rich in verbascoside and triterpenic compounds like ursolic acid. Fish (initial body weight = 55.0 ± 0.1 g) were fed two experimental diets (40% crude protein, 22% crude fat; 21.6 MJ/kg gross energy) that only differed in the phytogenic content (0.1% inclusion). Each diet has six replicates and was tested over a period of 133 days. The tested zootechnical feed additive a medicinal plant leaf extract (MPLE) obtained from sage (Salvia officinalis) and lemon verbena (Lippia citriodora). At the end of the trial, smolts fed the MPLE diet were heavier than their congeners from the control group (271.5 ± 7.9 g vs. 240.2 ± 19.3 g, respectively; P < 0.05). Feed conversion ratio (FCR) values in fish fed the control diet were higher than those in fish fed the MPLE diet (FCRcontrol diet = 1.27 ± 0.08 vs. FCR0.1% MPLE diet = 1.08 ± 0.05; P < 0.05). The immunomodulatory properties of the functional diet were evaluated by means of an in vivo challenge with Aeromonas salmonicida subsp. salmonicida (1 × 107 CFU mL–1). The microarray analysis of head kidney samples from both dietary groups revealed 1,178 differentially expressed genes (802 upregulated and 376 downregulated). Among them, several biological processes related to immunity were identified in fish fed the MPLE diet (i.e., interferon-gamma-mediated signaling pathway, antigen processing and presentation of peptide antigen via MHC class II, autophagy, regulation of i-kappaB kinase/NF-kappaB signaling, and leukocyte activation). Results from the bacterial challenge showed that survival rates were higher in smolts from the MPLE group (90.6 ± 6.4%) in comparison to the control group (60.7 ± 13.5%), confirming the functional benefits of the phytogenic in terms of host’s immunity and disease resistance. Biological processes such as cytoskeleton organization and regulation of cellular protein metabolic process detected in fish fed the MPLE diet supported the metabolic changes related to increased somatic growth promoted. The present findings showed that the inclusion at 0.1% of the tested MPLE obtained from sage and lemon verbena in diets for Atlantic salmon smolts promoted somatic growth, and enhanced their systemic immune response and reduced mortality when fish were challenged with A. salmonicida cumulative, the causative agent of furunculosis in salmonids.
Investigation on the Effects of RAP Proportions on the Pavement Performance of Recycled Asphalt Mixtures
Authors: Ma Xiang , Wang Jiaqing , Xu Yinyin
Published: February 2022

In-plant hot mix recycling technology has been widely used in maintenance and reconstruction due to its good recycling performance. However, the utilization rate of recycled asphalt pavement (RAP) is still only 10–25%, resulting in excessive accumulation and landfilling of RAP materials, which fails to promote the sustainable value of RAP in recycling. Therefore, this paper comprehensively explores the pavement performance of AC-20 ordinary asphalt recycled mixture and AC-13 modified asphalt recycled mixture with different proportions of RAP. The pavement performance test includes the dynamic modulus, rutting, dynamic creep, semicircular bending, and freeze-thaw splitting tests. The results show that, with the increase of RAP content, the mechanical properties and high-temperature properties of the two types of recycled asphalt mixtures are improved, the low temperature properties and moisture susceptibility properties are enhanced first and then weakened, and the best performance is reached when RAP content is 20 and 40%, respectively. According to the entire pavement performance test results, the influence of RAP content on AC-13 recycled modified asphalt mixtures is relatively smaller than that of AC-20 normal recycled asphalt mixtures. The addition of rejuvenator can improve the low-temperature performance and moisture susceptibility of recycled asphalt mixtures to a certain extent, especially for AC-20 ordinary recycled asphalt mixture. Consequently, it is suggested to use AC-13 recycled modified asphalt mixture in the upper layer of road; the RAP content can reach 20%, and rejuvenator can be used to improve its moisture susceptibility and low-temperature performance. AC-20 ordinary recycled asphalt mixture can be used in the middle surface layer, and the RAP content can reach 40%, or using AC-13 recycled modified asphalt mixture, the RAP content can reach 50%.
Solea senegalensis Bacterial Intestinal Microbiota Is Affected by Low Dietary Inclusion of Ulva ohnoi
Authors: Cerezo Isabel M. , Fumanal Milena , Tapia-Paniagua Silvana T. , Bautista Rocio , Anguís Victoria , Fernández-Díaz Catalina , Alarcón Francisco Javier , Moriñigo Miguel A. , Balebona M. Carmen
Published: February 2022

The inclusion of macroalgae in the diets of farmed fish offers the opportunity for an added-value dietary ingredient to the nutraceutical feed. The composition of algae varies greatly among species. Several Ulva species have been considered in aquafeed formulations for different farmed fish, and Ulva ohnoi is being applied recently. However, the effects of seaweed dietary inclusion on the host must be evaluated. Considering the important role of the host intestinal microbiota, the potential effects of U. ohnoi dietary inclusion need to be studied. In this study, the characterization of the intestinal microbiome of Solea senegalensis, a flatfish with high potential for aquaculture in South Europe, receiving U. ohnoi (5%)-supplemented diet for 90 days has been carried out. In addition, the functional profiles of bacterial communities have been determined by using PICRUSt, a computational approach to predict the functional composition of a metagenome by using marker gene data and a database of reference genomes. The results show that long-term dietary administration of U. ohnoi (5%)-supplemented feed modulates S. senegalensis intestinal microbiota, especially in the posterior intestinal section. Increased relative abundance of Vibrio jointly with decreased Stenotrophomonas genus has been detected in fish receiving Ulva diet compared to control-fed fish. The influence of the diet on the intestinal functionality of S. senegalensis has been studied for the first time. Changes in bacterial composition were accompanied by differences in predicted microbiota functionality. Increased abundance of predicted genes involved in xenobiotic biodegradation and metabolism were observed in the microbiota when U. ohnoi diet was used. On the contrary, predicted percentages of genes associated to penicillin and cephalosporin biosynthesis as well as beta-lactam resistance were reduced after feeding with Ulva diet.
In Silico Infection Analysis (iSFA) Identified Coronavirus Infection and Potential Transmission Risk in Mammals
Authors: Zou Yanyan , Cao Xiaojian , Yang Bing , Deng Lulu , Xu Yangyang , Dong Shuang , Li Wentao , Wu Chengchao , Cao Gang
Published: February 2022

Coronaviruses are a great source of threat to public health which could infect various species and cause diverse diseases. However, the epidemic’s spreading among different species remains elusive. This study proposed an in silico infection analysis (iSFA) system that includes pathogen genome or transcript mining in transcriptome data of the potential host and performed a comprehensive analysis about the infection of 38 coronaviruses in wild animals, based on 2,257 transcriptome datasets from 89 mammals’ lung and intestine, and revealed multiple potential coronavirus infections including porcine epidemic diarrhea virus (PEDV) infection in Equus burchellii. Then, through our transmission network analysis, potential intermediate hosts of five coronaviruses were identified. Notably, iSFA results suggested that the expression of coronavirus receptor genes tended to be downregulated after infection by another virus. Finally, binding affinity and interactive interface analysis of S1 protein and ACE2 from different species demonstrated the potential inter-species transmission barrier and cross-species transmission of SARS-CoV-2. Meanwhile, the iSFA system developed in this study could be further applied to conduct the source tracing and host prediction of other pathogen-induced diseases, thus contributing to the epidemic prevention and control.
Development and External Validation of a Dynamic Nomogram With Potential for Risk Assessment of Ruptured Multiple Intracranial Aneurysms
Authors: Chen TingTing , Xiong WeiGen , Zhao ZhiHong , Shan YaJie , Li XueMei , Guo LeHeng , Xiang Lan , Chu Dong , Fan HongWei , Li YingBin , Zou JianJun
Published: February 2022

Background and Purpose

About 20.1% of intracranial aneurysms (IAs) carriers are multiple intracranial aneurysms (MIAs) patients with higher rupture risk and worse prognosis. A prediction model may bring some potential benefits. This study attempted to develop and externally validate a dynamic nomogram to assess the rupture risk of each IA among patients with MIA.

Method

We retrospectively analyzed the data of 262 patients with 611 IAs admitted to the Hunan Provincial People's Hospital between November 2015 and November 2021. Multivariable logistic regression (MLR) was applied to select the risk factors and derive a nomogram model for the assessment of IA rupture risk in MIA patients. To externally validate the nomogram, data of 35 patients with 78 IAs were collected from another independent center between December 2009 and May 2021. The performance of the nomogram was assessed in terms of discrimination, calibration, and clinical utility.

Result

Size, location, irregular shape, diabetes history, and neck width were independently associated with IA rupture. The nomogram showed a good discriminative ability for ruptured and unruptured IAs in the derivation cohort (AUC = 0.81; 95% CI, 0.774–0.847) and was successfully generalized in the external validation cohort (AUC = 0.744; 95% CI, 0.627–0.862). The nomogram was calibrated well, and the decision curve analysis showed that it would generate more net benefit in identifying IA rupture than the “treat all” or “treat none” strategies at the threshold probabilities ranging from 10 to 60% both in the derivation and external validation set. The web-based dynamic nomogram calculator was accessible on https://wfs666.shinyapps.io/onlinecalculator/.

Conclusion

External validation has shown that the model was the potential to assist clinical identification of dangerous aneurysms after longitudinal data evaluation. Size, neck width, and location are the primary risk factors for ruptured IAs.
Sleep Quality and Insomnia Are Associated With Quality of Life in Functional Dyspepsia
Authors: Wuestenberghs Fabien , Melchior Chloé , Desprez Charlotte , Leroi Anne-Marie , Netchitailo Marie , Gourcerol Guillaume
Published: February 2022

Background

Sleep disturbances are common in patients with functional dyspepsia. Our aim was to assess the relationship between subjective sleep and quality of life and to identify factors associated with impaired sleep in functional dyspepsia.

Methods

One thousand two hundred and twenty patients referred for functional gastrointestinal disorders at a single tertiary care center between end 2017 and June 2019 were studied using a self-administered questionnaire. 355 patients with Rome IV-based functional dyspepsia were identified. Sleep was assessed using both the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). The severity of dyspeptic symptoms was assessed using the Total Symptom Score (TSS). Quality of life was assessed by the GastroIntestinal Quality of Life Index (GIQLI). Anxiety and depression levels were evaluated using the Hospital Anxiety and Depression (HAD) scale.

Key Results

Among the 355 patients with functional dyspepsia, 66 (18.6%) patients displayed normal sleep quality whereas 289 (81.4%) patients had altered sleep quality. Functional dyspepsia patients with sleep disturbances were older (48.1 ± 15.4 vs. 41.4 ± 16.0, p = 0.0009), had decreased quality of life (GIQLI: 75.3 ± 18.5 vs. 92.1 ± 15.4, p < 0.0001), greater severity of their symptoms (TSS: 18.9 ± 3.6 vs. 17.2 ± 3.9, p = 0.0007), and higher anxiety and depression scores (HADS: 17.7 ± 7.2 vs. 11.9 ± 5.1, p < 0.0001). A correlation was found between sleep quality and quality of life [r = −0.43 (95% CI: −0.51 to −0.34), p < 0.0001]. Independent factors predicting poor sleep quality were age [OR 1.03 (95% CI = 1.01–1.05), p = 0.006], depression level [OR 1.27 (95% CI = 1.16–1.39); p < 0.0001], and the severity of dyspeptic symptoms [OR 1.13 (95% CI = 1.04–1.22); p = 0.004].

Conclusion and Inferences

A high prevalence of sleep disturbances was found in patients suffering from functional dyspepsia, with 81% of them having altered sleep quality and 61% having insomnia based on subjective assessment. Altered sleep quality and insomnia were associated with altered quality of life, higher severity of symptoms, and higher anxiety and depression scores in this disorder.
Let Complexity Bring Clarity: A Multidimensional Assessment of Cognitive Load Using Physiological Measures
Authors: Nilsson Emma J. , Bärgman Jonas , Ljung Aust Mikael , Matthews Gerald , Svanberg Bo
Published: February 2022

The effects of cognitive load on driver behavior and traffic safety are unclear and in need of further investigation. Reliable measures of cognitive load for use in research and, subsequently, in the development and implementation of driver monitoring systems are therefore sought. Physiological measures are of interest since they can provide continuous recordings of driver state. Currently, however, a few issues related to their use in this context are not usually taken into consideration, despite being well-known. First, cognitive load is a multidimensional construct consisting of many mental responses (cognitive load components) to added task demand. Yet, researchers treat it as unidimensional. Second, cognitive load does not occur in isolation; rather, it is part of a complex response to task demands in a specific operational setting. Third, physiological measures typically correlate with more than one mental state, limiting the inferences that can be made from them individually. We suggest that acknowledging these issues and studying multiple mental responses using multiple physiological measures and independent variables will lead to greatly improved measurability of cognitive load. To demonstrate the potential of this approach, we used data from a driving simulator study in which a number of physiological measures (heart rate, heart rate variability, breathing rate, skin conductance, pupil diameter, eye blink rate, eye blink duration, EEG alpha power, and EEG theta power) were analyzed. Participants performed a cognitively loading n-back task at two levels of difficulty while driving through three different traffic scenarios, each repeated four times. Cognitive load components and other coinciding mental responses were assessed by considering response patterns of multiple physiological measures in relation to multiple independent variables. With this approach, the construct validity of cognitive load is improved, which is important for interpreting results accurately. Also, the use of multiple measures and independent variables makes the measurements (when analyzed jointly) more diagnostic—that is, better able to distinguish between different cognitive load components. This in turn improves the overall external validity. With more detailed, diagnostic, and valid measures of cognitive load, the effects of cognitive load on traffic safety can be better understood, and hence possibly mitigated.
Clinical Applications of Liquid Biopsy in Hepatocellular Carcinoma
Authors: Yang Jin-Cui , Hu Jun-Jie , Li Yi-Xin , Luo Wei , Liu Jin-Zhou , Ye Da-Wei
Published: February 2022

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognosis in the world. The low rate of early diagnosis, as well as the high risk of postoperative metastasis and recurrence, led to the poor clinical prognosis of HCC patients. Currently, it mainly depends on serum markers, imaging examination, and tissue biopsy to diagnose and determine the recurrence and metastasis of HCC after treatments. Nevertheless, the accuracy and sensitivity of serum markers and imaging for early HCC diagnosis are suboptimal. Tissue biopsy, containing limited tissue samples, is insufficient to reveal comprehensive tumor biology information and is inappropriate to monitor dynamic tumor progression due to its invasiveness. Thus, low invasive diagnostic methods and novel biomarkers with high sensitivity and reliability must be found to improve HCC detection and prediction. As a non-invasive, dynamic, and repeatable detection method, “liquid biopsy”, has attracted much attention to early diagnosis and monitoring of treatment response, which promotes the progress of precision medicine. This review summarizes the clinical applications of liquid biopsy in HCC, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosome in early diagnosis, prognostic evaluation, disease monitoring, and guiding personalized treatment.
Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment
Authors: Li Zheng , Wang Jun , Ge Shuai-Shuai , Qiu Qiao-Cheng , Du Jia-Hui , Shan Shuang-Shuang , Shen Xiang-Dong , Wan Chao-Ling , Wang Bin-Ru , Wu De-Pei , Qiu Hui-Ying , Xue Sheng-Li
Published: February 2022

Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations.
The MicroRNA-Based Strategies to Combat Cancer Chemoresistance via Regulating Autophagy
Authors: Lei Yuhe , Chen Lei , Liu Junshan , Zhong Yinqin , Deng Lijuan
Published: February 2022

Chemoresistance frequently occurs in cancer treatment, which results in chemotherapy failure and is one of the most leading causes of cancer-related death worldwide. Understanding the mechanism of chemoresistance and exploring strategies to overcome chemoresistance have become an urgent need. Autophagy is a highly conserved self-degraded process in cells. The dual roles of autophagy (pro-death or pro-survival) have been implicated in cancers and chemotherapy. MicroRNA (miRNA) is a class of small non-coding molecules that regulate autophagy at the post-transcriptional level in cancer cells. The association between miRNAs and autophagy in cancer chemoresistance has been emphasized. In this review, we focus on the dual roles of miRNA-mediated autophagy in facilitating or combating chemoresistance, aiming to shed lights on the potential role of miRNAs as targets to overcome chemoresistance.
Stachytine Hydrochloride Improves Cardiac Function in Mice with ISO-Induced Heart Failure by Inhibiting the α-1,6-Fucosylation on N-Glycosylation of β1AR
Authors: Hu Panwei , Guo Shuting , Yang Songru , Wang Sining , Wang Sai , Shan Xiaoli , Zhao Pei , Guo Wei , Xu Ming , Zhang Chen , Lu Rong , Chen Huihua
Published: February 2022

Background: Cardiovascular diseases have become a major public health problem that seriously threatens human health. The cumulative effects of various cardiovascular events will eventually develop into chronic heart insufficiency and even heart failure, and the β1 adrenergic receptor signal pathway plays an important role in this process. Stachytine hydrochloride is the main active ingredient of Yimucao, which is a traditional Chinese medicine used to treat gynecological diseases. Modern studies have found that stachytine hydrochloride has a good cardioprotective effect, but it is still unclear whether stachytine hydrochloride has an effect on the β1 adrenergic receptor signal pathway. The purpose of this study is to explore the effect of stachytine hydrochloride on the β1 adrenergic receptor signal pathway.

Method: In this study, a continuous infusion of isoproterenol (40 mg/kg/day) was administered to mice and ventricular myocytes explored the potential mechanism of stachytine hydrochloride (12 mg/kg/day) on the β1 adrenergic receptor signal pathway in the heart. Evaluate changes in cardiac morphology and function by echocardiography, cardiac hemodynamics, and histological methods, and detect molecular changes by Western blot and immunofluorescence. Treat primary cultured adult mouse or neonatal rat ventricular myocytes with or without isoproterenol (0.1 μMol), PNGase F (10–2 units/ml), and stachytine hydrochloride (10 μMol) at different time points. Detect α-1,6-fucosylation on N-glycosylation, calcium transient, contraction, and relaxation function and related signals.

Results: Stachytine hydrochloride reduces cardiac remodeling and modulates hemodynamic parameters during chronic β1 adrenergic receptor activation in vivo. The N-glycosylation of β1 adrenergic receptors decreased after continuous isoproterenol stimulation, while stachytine hydrochloride can increase the N-glycosylation of β1AR in the heart of mice with isoproterenol-induced heart failure. Decreased N-glycosylation of β1 adrenergic receptors will downregulate the cAMP/PKA signal pathway and inhibit myocardial excitation and contraction coupling. Stachytine hydrochloride significantly reduced isoproterenol-induced cardiac N-linked glycoproteins with α-1,6-fucosylation.

Conclusion: Our results show that stachytine hydrochloride inhibits the synthesis of α-1,6-fucosylation on the N-terminal sugar chain by reducing α-1,6-fucosyltransferase (FUT8) and α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase A (MGAT4a), upregulating the N-glycosylation level on β1 adrenergic receptors, and maintaining cAMP/PKA signal pathway activation.
Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis
Authors: Shou Xintian , Wang Yumeng , Zhang Xuesong , Zhang Yanju , Yang Yan , Duan Chenglin , Yang Yihan , Jia Qiulei , Yuan Guozhen , Shi Jingjing , Shi Shuqing , Cui Hanming , Hu Yuanhui
Published: February 2022

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein–protein interaction networks and herb–ingredient–target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)–Akt signaling pathway, advanced glycosylation end product (AGE)–RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.
Anti-Inflammatory and Anti-asthmatic Effects of TMDCT Decoction in Eosinophilic Asthma Through Treg/Th17 Balance
Authors: Zhou Yumei , Zhao Haihong , Wang Tieshan , Zhao Xiaoshan , Wang Ji , Wang Qi
Published: February 2022

Tuo-Min-Ding-Chuan decoction (TMDCT) is a Traditional Chinese Medicine (TCM) formula consisting of twelve herbs that can relieve the symptoms and treat allergic asthma. Yet, the underlying mechanism of action is still unclear. In this study, we investigated the effect of TMDCT in regulating Treg/Th17 cells immune balance and explored potential metabolic and gut biomarkers associated with Treg and Th17 cells in eosinophilic asthma mice treated by TMDCT. We found that TMDCT increases Treg cells percentage and decreases Th17 cells percentage in the ovalbumin (OVA) -induced eosinophilic asthma mice model. Furthermore, Imidazoleacetic acid, dL-glutamine, L-pyroglutamic acid, 2-deoxy-d-glucose were preliminary identified as biomarkers in plasma metabolites treated by TMDCT, meanwhile genus Desulfovibrio, genus Butyricimonas and genus Prevotella 9 were preliminary identified as gut microbiota biomarkers after TMDCT treatment. These results provide an experimental foundation for the treatment of allergic asthma with Chinese herbal compounds.
How Soluble Fms-Like Tyrosine Kinase 1 Could Contribute to Blood-Brain Barrier Dysfunction in Preeclampsia?
Authors: Torres-Vergara Pablo , Rivera Robin , Escudero Carlos
Published: February 2022

Preeclampsia is a pregnancy-related syndrome that courses with severe cerebrovascular complications if not properly managed. Findings from pre-clinical and clinical studies have proposed that the imbalance between pro- and anti-angiogenic factors exhibited in preeclampsia is a major component of its pathophysiology. In this regard, measurement of circulating levels of soluble tyrosine kinase-1 similar to fms (sFlt-1), a decoy receptor for vascular endothelial growth factor (VEGF), is a moderately reliable biomarker for the diagnosis of preeclampsia. However, few studies have established a mechanistic approach to determine how the high levels of sFlt-1 are responsible for the endothelial dysfunction, and even less is known about its effects at the blood-brain barrier (BBB). Since the expression pattern of VEGF receptors type 1 and 2 in brain endothelial cells differs from the observed in peripheral endothelial cells, and components of the neurovascular unit of the BBB provide paracrine secretion of VEGF, this compartmentalization of VEGF signaling could help to see in a different viewpoint the role of sFlt-1 in the development of endothelial dysfunction. In this article, we provide a hypothesis of how sFlt-1 could eventually be a protective factor for brain endothelial cells of the BBB under preeclampsia.
Clinical Parameters and Metabolomic Biomarkers That Predict Inhospital Outcomes in Patients With ST-Segment Elevated Myocardial Infarctions
Authors: Liu Jie , Huang Lei , Shi Xinrong , Gu Chungang , Xu Hongmin , Liu Shuye
Published: February 2022

Background

Postoperative risk stratification is challenging in patients with ST-segment elevation myocardial infarction (STEMI) who undergo percutaneous coronary intervention. This study aimed to characterize the metabolic fingerprints of patients with STEMI with different inhospital outcomes in the early stage of morbidity and to integrate the clinical baseline characteristics to develop a prognostic prediction model.

Methods

Plasma samples were collected retrospectively from two propensity score-matched STEMI cohorts from May 6, 2020 to April 20, 2021. Cohort 1 consisted of 48 survivors and 48 non-survivors. Cohort 2 included 48 patients with unstable angina pectoris, 48 patients with STEMI, and 48 age- and sex-matched healthy controls. Metabolic profiling was generated based on ultra-performance liquid chromatography and a mass spectrometry platform. The comprehensive metabolomic data analysis was performed using MetaboAnalyst version 5.0. The hub metabolite biomarkers integrated into the model were tested using multivariate linear support vector machine (SVM) algorithms and a generalized estimating equation (GEE) model. Their predictive capabilities were evaluated using areas under the curve (AUCs) of receiver operating characteristic curves.

Results

Metabonomic analysis from the two cohorts showed that patients with STEMI with different outcomes had significantly different clusters. Seven differentially expressed metabolites were identified as potential candidates for predicting inhospital outcomes based on the two cohorts, and their joint discriminative capabilities were robust using SVM (AUC = 0.998, 95% CI 0.983–1) and the univariate GEE model (AUC = 0.981, 95% CI 0.969–0.994). After integrating another six clinical variants, the predictive performance of the updated model improved further (AUC = 0.99, 95% CI 0.981–0.998).

Conclusion

A survival prediction model integrating seven metabolites from non-targeted metabonomics and six clinical indicators may generate a powerful early survival prediction model for patients with STEMI. The validation of internal and external cohorts is required.
Estimating Light Acclimation Parameters of Cucumber Leaves Using Time-Weighted Averages of Daily Photosynthetic Photon Flux Density
Authors: Yu Liyao , Fujiwara Kazuhiro , Matsuda Ryo
Published: February 2022

Leaves acclimate to day-to-day fluctuating levels of photosynthetic photon flux density (PPFD) by adjusting their morphological and physiological parameters. Accurate estimation of these parameters under day-to-day fluctuating PPFD conditions benefits crop growth modeling and light environment management in greenhouses, although it remains challenging. We quantified the relationships between day-to-day PPFD changes over 6 days and light acclimation parameters for cucumber seedling leaves, including leaf mass per area (LMA), chlorophyll (Chl) a/b ratio, maximum net photosynthetic rate (Pnmax), maximum rate of ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Vcmax), and maximum rate of electron transport (Jmax). The last two parameters reflect the capacity of the photosynthetic partial reactions. We built linear regression models of these parameters based on average or time-weighted averages of daily PPFDs. For time-weighted averages of daily PPFDs, the influence of daily PPFD was given a specific weight. We employed three types of functions to calculate this weight, including linear, quadratic, and sigmoid derivative types. We then determined the trend of weights that estimated each parameter most accurately. Moreover, we introduced saturating functions to calibrate the average or time-weighted averages of daily PPFDs, considering that light acclimation parameters are usually saturated under high PPFDs. We found that time-weighted average PPFDs, in which recent PPFD levels had larger weights than earlier levels, better estimated LMA than average PPFDs. This suggests that recent PPFDs contribute more to LMA than earlier PPFDs. Except for the Chl a/b ratio, the average PPFDs estimated Pnmax, Vcmax, and Jmax with acceptable accuracy. In contrast, time-weighted averages of daily PPFDs did not improve the estimation accuracy of these four parameters, possibly due to their low response rates and plasticity. Calibrating functions generally improved estimation of Chl a/b ratio, Vcmax, and Jmax because of their saturating tendencies under high PPFDs. Our findings provide a reasonable approach to quantifying the extent to which the leaves acclimate to day-to-day fluctuating PPFDs, especially the extent of LMA.
Virtual Reality-Integrated Immersion-Based Teaching to English Language Learning Outcome
Authors: Xie Yu , Liu Yang , Zhang Fengrui , Zhou Ping
Published: February 2022

Globalization and informatization are reshaping human life and social behaviors. The purpose is to explore the worldwide strategies to cultivate international talents with a global vision. As a global language with the largest population, English, and especially its learning effect, have always been the major concerns of scholars and educators. This work innovatively studies the combination of immersion-based English teaching with virtual reality (VR) technology. Then, based on the experimental design mode, 106 students from a Chinese school were selected for a quasi-experimental study for 16 weeks (3 h a week, and 48 h in total). The collected data were analyzed by computer statistical software, and hypotheses are verified. The results showed that there is a significantly positive correlation between VR and immersion-based language teaching (0.851, p < 0.01). There is a significantly positive correlation between immersion-based language teaching and academic achievement (0.824, p < 0.01), and VR is positively correlated with learning outcome (LO) (0.836, p < 0.01). Compared with other state-of-art research methods, this work modifies the students’ oral test through the analysis and comparison with the system database, and the students’ learning effect is greatly improved. Finally, some suggestions are put forward according to the research results to provide an experimental reference for English teachers and future linguistics teaching.