bluuebunny/crossref_metadata_2025 huggingface dataset:
Drinking Non-nutritive Sweetness Solution of Sodium Saccharin or Rebaudioside a for Guinea Pigs: Influence on Histologic Change and Expression of Sweet Taste Receptors in Testis and Epididymis
Authors: Shen Ting , Li Junrong
Published: August 2021

Saccharin sodium and rebaudioside A are extensively used as non-nutritive sweeteners (NNSs) in daily life. NNSs elicit a multitude of endocrine influences on animals, differing across species and chemically distinct sweeteners, whose exposure induce activation of sweet taste receptors in oral and extra-oral tissues with consequences of metabolic changes. To evaluate the influence of NNSs on histologic change and expression of sweet taste receptors in testis and epididymis of young male guinea pigs, thirty 4-week-old male guinea pigs with body weight 245.73 ± 6.02 g were randomly divided into five groups (n = 6) and received normal water (control group) and equivalent sweetness low dose or high dose of sodium saccharin (L-SS, 1.5 mM or H-SS, 7.5 mM) or rebaudioside A (L-RA, 0.5 mM or H-RA, 2.5 mM) solution for 28 consecutive days. The results showed that the relative testis weight in male guinea pig with age of 56 days represented no significant difference among all groups; in spite of heavier body weight in L-SS and H-RA, NNS contributes no significant influence on serum testosterone and estradiol level. Low-dose 0.5 mM rebaudioside A enhanced testicular and epididymal functions by elevating the expressions of taste receptor 1 subunit 2 (T1R2) and gustducin α-subunit (GNAT3), and high-dose 7.5 mM sodium saccharin exerted adverse morphologic influences on testis and epididymis with no effect on the expression of T1R2, taste receptor 1 subunit 2 (T1R3), and GNAT3. In conclusion, these findings suggest that a high dose of sodium saccharin has potential adverse biologic effects on the testes and epididymis, while rebaudioside A is a potential steroidogenic sweetener for enhancing reproductive functions.
Global Analysis of Microbiota Signatures in Four Major Types of Gastrointestinal Cancer
Authors: Wang Jihan , Wang Yangyang , Li Zhenzhen , Gao Xiaoguang , Huang Dageng
Published: August 2021

The gut microbiota has been previously linked with tumorigenesis and gastrointestinal cancer progression; however, intra-tumor microbiota analysis has just emerged and deserves increasing attention. Based on the public databases of The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA), this study identified the tissue/organ microbial signatures generated from 443 biosamples of four major gastrointestinal cancer types, including esophageal carcinoma (ESCA), which further includes esophageal adenocarcinoma (EAD) and esophageal squamous cell carcinoma (ESCC), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). According to partial least squares discrimination analysis (PLS-DA), the profile differences in microbial communities between the tumor and normal samples were not particularly noticeable across the four cancer cohorts, whereas paired comparison analyses revealed several specific differences in bacteria between tumor and normal samples in the EAD, STAD, and COAD samples. The taxa classified from the phylum to genus level revealed a trend of distinguishable microbial profiles between upper and lower gastrointestinal tumors. The Bacteroidetes/Firmicutes ratio in lower gastrointestinal tract tumors was nearly three times that in upper gastrointestinal tract tumors. We also determined the relative tissue/organ-prevalent microbes for each of the four cohorts at the order and genus levels. Microbe Alistipes, Blautia, Pasteurellales, and Porphyromonas compositions were correlated with the clinical characteristics of patients with gastrointestinal cancer, particularly colorectal cancer. Taken together, our findings indicate that microbial profiles shift across different gastrointestinal cancer types and that microbial colonization is highly site-specific. Composition of specific microbes can be indicative of cancer stage or disease progression. Overall, this study indicates that the microbial community and abundance in human tissues can be determined using publicly available data, and provides a new perspective for intra-tissue/organ microbiota research.
The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress and In Vivo Tumor Growth
Authors: Roque Dario R. , Zhang Lu , Wysham Weiya Z. , Han Jianjun , Sun Wenchuan , Yin Yajie , Livingston James N. , Batchelor Ken W. , Zhou Chunxiao , Bae-Jump Victoria L.
Published: August 2021

Objectives

Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors. Metformin requires organic cation transporters (OCTs) for entry into cells, and NT-1044 is an AMPK activator designed to have greater affinity for two of these transporters, OCT1 and OCT3. We sought to compare the effects of NT-1044 on cell proliferation in human endometrial cancer (EC) cell lines and on tumor growth in an endometrioid EC mouse model.

Methods

Cell proliferation was assessed in two EC cell lines, ECC-1 and Ishikawa, by MTT assay after exposure to NT-1044 for 72 hours of treatment. Apoptosis was analyzed by Annexin V-FITC and cleaved caspase 3 assays. Cell cycle progression was evaluated by Cellometer. Reactive oxygen species (ROS) were measured using DCFH-DA and JC-1 assays. For the in vivo studies, we utilized the LKB1fl/flp53fl/fl mouse model of endometrioid endometrial cancer. The mice were treated with placebo or NT-1044 or metformin following tumor onset for 4 weeks.

Results

NT-1044 and metformin significantly inhibited cell proliferation in a dose-dependent manner in both EC cell lines after 72 hours of exposure (IC50 218 μM for Ishikawa; 87 μM for ECC-1 cells). Treatment with NT-1044 resulted in G1 cell cycle arrest, induced apoptosis and increased ROS production in both cell lines. NT-1044 increased phosphorylation of AMPK and decreased phosphorylation of S6, a key downstream target of the mTOR pathway. Expression of the cell cycle proteins CDK4, CDK6 and cyclin D1 decreased in a dose-dependent fashion while cellular stress protein expression was induced in both cell lines. As compared to placebo, NT-1044 and metformin inhibited endometrial tumor growth in obese and lean LKB1fl/flp53fl/fl mice.

Conclusions

NT-1044 suppressed EC cell growth through G1 cell cycle arrest, induction of apoptosis and cellular stress, activation of AMPK and inhibition of the mTOR pathway. In addition, NT-1044 inhibited EC tumor growth in vivo under obese and lean conditions. More work is needed to determine if this novel biguanide will be beneficial in the treatment of women with EC, a disease strongly impacted by obesity and diabetes.
A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells
Authors: Xue Yaqi , Wang Ping , Jiang Fei , Yu Jing , Ding Hongmei , Zhang Zengli , Pei Hailong , Li Bingyan
Published: August 2021

Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3.
The Prognostic Value of Early Detection of Minimal Residual Disease as Defined by Flow Cytometry and Gene Mutation Clearance for Myelodysplastic Syndrome Patients After Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Hou Chang , Zhou Lili , Yang Menglu , Jiang Shuhui , Shen Hongjie , Zhu Mingqing , Chen Jia , Miao Miao , Xu Yang , Wu Depei
Published: August 2021

High relapse incidence remains a major problem for myelodysplastic syndrome (MDS) patients who have received an allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We retrospectively analyzed the correlations between clinical outcomes and minimal residual disease (MRD) by using mutations (MUT) and flow cytometry (FCM) analysis of 115 MDS patients with allo-HSCT. We divided 115 MDS patients into four groups based on molecular genetics and FCM MRD results at day 30 post-HSCT. There were significant differences in the 2-year progression-free survival (PFS) between the FCMhigh MUTpos and FCMlow MUTneg groups (20% vs 79%, P < 0.001). In addition, by univariate analysis, we found that an IPSS-R score ≥4 pre-HSCT (HR, 5.061; P=0.007), DNMT3A mutations (HR, 2.291; P=0.052), TP53 mutations (HR, 3.946; P=0.011), and poor and very poor revised International Prognostic Scoring System (IPSS-R) cytogenetic risk (HR, 4.906; P < 0.001) were poor risk factors for PFS. In multivariate analysis, we found that an IPSS-R score ≥ 4 pre-HSCT (HR, 4.488; P=0.015), DNMT3A mutations (HR, 2.385; P=0.049), positive FCM MRD combined with persistence gene mutations at day 30 (HR, 5.198; P=0.013) were independent risk factors for disease progression. In conclusion, our data indicated that monitoring MRD by FCM combined with gene mutation clearance at day 30 could help in the prediction of disease progression for MDS patients after transplantation.
The Characteristics and Distribution of Nerve Plexuses in the Dartos Fascia From Concealed Penis Children
Authors: Huang WenFang , Tang DaXing , Gu WeiZhong
Published: August 2021

The purpose of this study is to analyze the nerve plexus distribution in dartos fascia of concealed penis (CP). A total of 28 CP patients met ASA categories I and II were included, with median age of 3.5 years (8 months−5 years). During the surgery, tissue samples of dartos fascia at points 3, 6, 9, and 12 o'clock of the penile shaft were collected. Standard hematoxylin and eosin (H&E) staining and S-100 immunohistochemical staining were used to analyze the nerve plexus distribution among different positions. The number of nerve plexuses in superficial fascia collected at the 6 o'clock position of the penile shaft was the most abundant among four positions (median 7.25, range 1–24). The abundant nerve plexuses in the dartos fascia of CP patients, especially at the 6 o'clock position, indicate that the surgery on the preputial frenulum should avoid damage to the dartos fascia, as it might be related to maintain the erection and sexual function in adolescence.
Pain Treatment in the Companion Canine Model to Validate Rodent Results and Incentivize the Transition to Human Clinical Trials
Authors: Iadarola Michael J. , Brown Dorothy Cimino , Nahama Alexis , Sapio Matthew R. , Mannes Andrew J.
Published: August 2021

One of the biggest challenges for analgesic drug development is how to decide if a potential analgesic candidate will work in humans. What preclinical data are the most convincing, incentivizing and most predictive of success? Such a predicament is not unique to analgesics, and the pain field has certain advantages over drug development efforts in areas like neuropsychiatry where the etiological origins are either unknown or difficult to ascertain. For pain, the origin of the problem frequently is known, and the causative peripheral tissue insult might be observable. The main conundrum centers around evaluation of translational cell- and rodent-based results. While cell and rodent models are undeniably important first steps for screening, probing mechanism of action, and understanding factors of adsorption, distribution metabolism and excretion, two questions arise from such studies. First, are they reliable indicators of analgesic performance of a candidate drug in human acute and chronic pain? Second, what additional model systems might be capable of increasing translational confidence? We address this second question by assessing, primarily, the companion canine model, which can provide particularly strong predictive information for candidate analgesic agents in humans. This statement is mainly derived from our studies with resiniferatoxin (RTX) a potent TRPV1 agonist but also from protein therapeutics using a conjugate of Substance P and saporin. Our experience, to date, is that rodent models might be very well suited for acute pain translation, but companion canine models, and other large animal studies, can augment initial discovery research using rodent models for neuropathic or chronic pain. The larger animal models also provide strong translational predictive capacity for analgesic performance in humans, better predict dosing parameters for human trials and provide insight into behavior changes (bladder, bowel, mood, etc.) that are not readily assessed in laboratory animals. They are, however, not without problems that can be encountered with any experimental drug treatment or clinical trial. It also is important to recognize that pain treatment is a major veterinary concern and is an intrinsically worthwhile endeavor for animals as well as humans.
Recent Developments About the Pathogenesis of Dry Eye Disease: Based on Immune Inflammatory Mechanisms
Authors: Yu Lifei , Yu Chunjing , Dong He , Mu Yanan , Zhang Rui , Zhang Qiaosi , Liang Wei , Li Wenjia , Wang Xun , Zhang Lijun
Published: August 2021

Dry eye disease is a common and frequently occurring ophthalmology with complex and diverse causes, and its incidence is on the upward trend. The pathogenesis of DED is still completely clear. However, the immune response based on inflammation has been recognized as the core basis of this disease. In this review, we will systematically review the previous research on the treatment of DED in immune inflammation, analyze the latest views and research hotspots, and provide reference for the prevention and treatment of DED.
Efficacy and Mechanism of Electroacupuncture Treatment of Rabbits With Different Degrees of Knee Osteoarthritis: A Study Based on Synovial Innate Immune Response
Authors: Ruan Anmin , Wang Qingfu , Ma Yufeng , Zhang Dong , Yang Lili , Wang Zhongpeng , Xie Qi , Yin Yueshan
Published: August 2021

Knee osteoarthritis (KOA) is a chronic degenerative bone and joint disease, which is often clinically manifested as pain, joint swelling, and deformity. Its pathological manifestations are mainly synovial inflammation and cartilage degeneration. This study aims to investigate the efficacy of electro-acupuncture (EA) on model rabbits with varying degrees of KOA and to study the mechanism of EA on KOA based on the innate immune response. Mild and moderate rabbit KOA models were established using a modified Hluth method, and EA was given to both the mild and moderate model groups. The Lequesne-MG index was used to evaluate the behavioral changes in the rabbits before and after EA treatment. Morphological changes in the synovial membrane and cartilage of each group were observed by H&E staining. The Mankin scoring standard and the Krenn scoring standard were used to score the pathology of the cartilage tissue and synovial tissue, respectively. The inflammatory factors and metalloproteinases were detected in the serum of each group by ELISA. The protein and messenger RNA (mRNA) expressions of important elements related to Toll-like receptors (TLRs)-mediated innate immune response in the synovial tissue were detected by Western blot and quantitative PCR (qPCR). The Lequesne-MG index score of the rabbits gradually increased with the modeling prolonged but decreased significantly after EA treatment, indicating that EA has a better effect on alleviating the pain and improving the dysfunction. The morphological analysis showed that the inflammation of and the damage to the synovial membrane and the cartilage tissue gradually deteriorated with the modeling prolonged. However, the synovial membrane inflammation was significantly relieved after EA treatment, and the cartilage injury showed signs of repair. The ELISA analysis showed that, with the modeling prolonged, the serum-related inflammatory factors and mechanism of metalloproteinases gradually increased but decreased after EA treatment. The tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and matrix metalloproteinase3 (MMP3) of EA1 group were significantly lower than those of EA2 group. Both Western blot and qPCR results showed that the protein and mRNA expressions of the elements related to the innate immune response in the synovial membrane increased gradually with the modeling prolonged, but decreased significantly after EA treatment. Additionally, the expression of some components in EA1 group was significantly lower than that in EA2 group. These results confirm that synovial inflammation gradually aggravated with time from the early to mid-stage of KOA. EA alleviated the inflammation and histological changes in KOA rabbits by inhibiting the TLRs-mediated innate synovial immune response. This suggests that using EA in the early stage of KOA may achieve a desirable efficacy.
Metabolomic Alterations in the Digestive System of the Mantis Shrimp Oratosquilla oratoria Following Short-Term Exposure to Cadmium
Authors: Xu Yingjiang , Liu Huan , Han Dianfeng , Ren Lihua , Gong Xianghong , Jiang Fang , Cui Yanmei , Liu Xiaojing , Ren Chuanbo , Xue Jinglin , Tian Xiuhui
Published: August 2021

Mantis shrimp Oratosquilla oratoria is an economically critical aquatic species along the coast of China but strongly accumulates marine pollutant cadmium (Cd) in its digestive system. It is necessary to characterize the toxicity of Cd in the digestive system of mantis shrimp. The metabolic process is an essential target of Cd toxicity response. In this work, we used ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-TOF-MS) for untargeted metabolomics to characterize the metabolic changes in the digestive system of O. oratoria, exposed to 0.05 mg/L for 96 h. The aim of this study was to further investigate the effect of O. oratoria on Cd response to toxicity and develop biomarkers. Metabolomics analysis showed the alteration of metabolism in the digestive system of mantis shrimp under Cd stress. A total of 91 metabolites were differentially expressed and their main functions were classified into amino acids, phospholipids, and fatty acid esters. The enrichment results of differential metabolite functional pathways showed that biological processes such as amino acid metabolism, transmembrane transport, energy metabolism, and signal transduction are significantly affected. Based on the above results, the Cd-induced oxidative stress and energy metabolism disorders were characterized by the differential expression of amino acids and ADP in mantis shrimp, while the interference of transmembrane transport and signal transduction was due to the differential expression of phospholipids. Overall, this work initially discussed the toxicological response of Cd stress to O. oratoria from the metabolic level and provided new insights into the mechanism.
Skeletal Muscle Quality: A Biomarker for Assessing Physical Performance Capabilities in Young Populations
Authors: Naimo Marshall A. , Varanoske Alyssa N. , Hughes Julie M. , Pasiakos Stefan M.
Published: August 2021

Muscle quality (MQ), defined as the amount of strength and/or power per unit of muscle mass, is a novel index of functional capacity that is increasingly relied upon as a critical biomarker of muscle health in low functioning aging and pathophysiological adult populations. Understanding the phenotypical attributes of MQ and how to use it as an assessment tool to explore the efficacy of resistance exercise training interventions that prioritize functional enhancement over increases in muscle size may have implications for populations beyond compromised adults, including healthy young adults who routinely perform physically demanding tasks for competitive or occupational purposes. However, MQ has received far less attention in healthy young populations than it has in compromised adults. Researchers and practitioners continue to rely upon static measures of lean mass or isolated measures of strength and power, rather than using MQ, to assess integrated functional responses to resistance exercise training and physical stress. Therefore, this review will critically examine MQ and the evidence base to establish this metric as a practical and important biomarker for functional capacity and performance in healthy, young populations. Interventions that enhance MQ, such as high-intensity stretch shortening contraction resistance exercise training, will be highlighted. Finally, we will explore the potential to leverage MQ as a practical assessment tool to evaluate function and enhance performance in young populations in non-traditional research settings.
VDAC Genes Expression and Regulation in Mammals
Authors: Zinghirino Federica , Pappalardo Xena Giada , Messina Angela , Nicosia Giuseppe , De Pinto Vito , Guarino Francesca
Published: August 2021

VDACs are pore-forming proteins, coating the mitochondrial outer membrane, and playing the role of main regulators for metabolites exchange between cytosol and mitochondria. In mammals, three isoforms have evolutionary originated, VDAC1, VDAC2, and VDAC3. Despite similarity in sequence and structure, evidence suggests different biological roles in normal and pathological conditions for each isoform. We compared Homo sapiens and Mus musculus VDAC genes and their regulatory elements. RNA-seq transcriptome analysis shows that VDAC isoforms are expressed in human and mouse tissues at different levels with a predominance of VDAC1 and VDAC2 over VDAC3, with the exception of reproductive system. Numerous transcript variants for each isoform suggest specific context-dependent regulatory mechanisms. Analysis of VDAC core promoters has highlighted that, both in a human and a mouse, VDAC genes show features of TATA-less ones. The level of CG methylation of the human VDAC genes revealed that VDAC1 promoter is less methylated than other two isoforms. We found that expression of VDAC genes is mainly regulated by transcription factors involved in controlling cell growth, proliferation and differentiation, apoptosis, and bioenergetic metabolism. A non-canonical initiation site termed “the TCT/TOP motif,” the target for translation regulation by the mTOR pathway, was identified in human VDAC2 and VDAC3 and in every murine VDACs promoter. In addition, specific TFBSs have been identified in each VDAC promoter, supporting the hypothesis that there is a partial functional divergence. These data corroborate our experimental results and reinforce the idea that gene regulation could be the key to understanding the evolutionary specialization of VDAC isoforms.
Methyl Jasmonate and Sodium Nitroprusside Jointly Alleviate Cadmium Toxicity in Wheat (Triticum aestivum L.) Plants by Modifying Nitrogen Metabolism, Cadmium Detoxification, and AsA–GSH Cycle
Authors: Kaya Cengiz , Ugurlar Ferhat , Ashraf Muhammad , Noureldeen Ahmed , Darwish Hadeer , Ahmad Parvaiz
Published: August 2021

The principal intent of the investigation was to examine the influence of joint application of methyl jasmonate (MeJA, 10 μM) and a nitric oxide–donor sodium nitroprusside (SNP, 100 μM) to wheat plants grown under cadmium (Cd as CdCl2, 100 μM) stress. Cd stress suppressed plant growth, chlorophylls (Chl), and PSII maximum efficiency (Fv/Fm), but it elevated leaf and root Cd, and contents of leaf proline, phytochelatins, malondialdehyde, and hydrogen peroxide, as well as the activity of lipoxygenase. MeJA and SNP applied jointly or singly improved the concentrations of key antioxidant biomolecules, e.g., reduced glutathione and ascorbic acid and the activities of the key oxidative defense system enzymes such as catalase, superoxide dismutase, dehydroascorbate reductase, glutathione S-transferase, and glutathione reductase. Exogenously applied MeJA and SNP jointly or singly also improved nitrogen metabolism by activating the activities of glutamine synthetase, glutamate synthase, and nitrate and nitrite reductases. Compared with individual application of MeJA or SNP, the combined application of both showed better effect in terms of improving plant growth and key metabolic processes and reducing tissue Cd content, suggesting a putative interactive role of both compounds in alleviating Cd toxicity in wheat plants.

Main findings

The main findings are that exogenous application of methyl jasmonate and nitric oxide–donor sodium nitroprusside alleviated the cadmium (Cd)–induced adverse effects on growth of wheat plants grown under Cd by modulating key physiological processes and up-regulating enzymatic antioxidants and the ascorbic acid–glutathione cycle–related enzymes.
A Large Root Phenome Dataset Wide-Opened the Potential for Underground Breeding in Soybean
Authors: Kim Ki-Seung , Kim Se-Hun , Kim Jaeyoung , Tripathi Pooja , Lee Jeong-Dong , Chung Yong Suk , Kim Yoonha
Published: August 2021

The root is the most critical plant organ for water and nutrient acquisition. Although the root is vital for water and nutrient uptake, the diverse root characters of soybean still need to be identified owing to the difficulty of root sampling. In this study, we used 150 wild and 50 cultivated soybean varieties to collect root image samples. We analyzed root morphological traits using acquired-image. Except for the main total length (MTL), the root morphological traits for most cultivated and wild plants were significantly different. According to correlation analysis, the wild and cultivated plants showed a significant correlation among total root length (TRL), projected area (PA), forks, total lateral length (TLL), link average diameter, and MTL. In particular, TRL was highly correlated with PA in both cultivated (0.92) and wild (0.82) plants compared with between MTL (0.43 for cultivated and 0.27 for wild) and TLL (0.82 for cultivated and 0.52 for wild). According to principal component analysis results, both plants could be separated; however, there was some overlap of the traits among the wild and cultivated individuals from some regions. Nevertheless, variation among the cultivated plants was higher than that found in the wild plants. Furthermore, three groups, including MTL, TLL, and the remaining traits, could explain all the variances.
Multiplex Genome Editing in Yeast by CRISPR/Cas9 – A Potent and Agile Tool to Reconstruct Complex Metabolic Pathways
Authors: Utomo Joseph Christian , Hodgins Connor Lorne , Ro Dae-Kyun
Published: August 2021

Numerous important pharmaceuticals and nutraceuticals originate from plant specialized metabolites, most of which are synthesized via complex biosynthetic pathways. The elucidation of these pathways is critical for the applicable uses of these compounds. Although the rapid progress of the omics technology has revolutionized the identification of candidate genes involved in these pathways, the functional characterization of these genes remains a major bottleneck. Baker’s yeast (Saccharomyces cerevisiae) has been used as a microbial platform for characterizing newly discovered metabolic genes in plant specialized metabolism. Using yeast for the investigation of numerous plant enzymes is a streamlined process because of yeast’s efficient transformation, limited endogenous specialized metabolism, partially sharing its primary metabolism with plants, and its capability of post-translational modification. Despite these advantages, reconstructing complex plant biosynthetic pathways in yeast can be time intensive. Since its discovery, CRISPR/Cas9 has greatly stimulated metabolic engineering in yeast. Yeast is a popular system for genome editing due to its efficient homology-directed repair mechanism, which allows precise integration of heterologous genes into its genome. One practical use of CRISPR/Cas9 in yeast is multiplex genome editing aimed at reconstructing complex metabolic pathways. This system has the capability of integrating multiple genes of interest in a single transformation, simplifying the reconstruction of complex pathways. As plant specialized metabolites usually have complex multigene biosynthetic pathways, the multiplex CRISPR/Cas9 system in yeast is suited well for functional genomics research in plant specialized metabolism. Here, we review the most advanced methods to achieve efficient multiplex CRISPR/Cas9 editing in yeast. We will also discuss how this powerful tool has been applied to benefit the study of plant specialized metabolism.
Pollination and Plant Reproductive Success of Two Ploidy Levels in Red Clover (Trifolium pratense L.)
Authors: Jing Shuxuan , Kryger Per , Markussen Bo , Boelt Birte
Published: August 2021

Plant reproduction in red clover requires cross-fertilization via insect pollination. However, the influences of visitation rate and timing on maximizing ovule utilization are yet to be determined. We aimed to study the influences of visitation rate, flowering stage, and self-incompatibility on reproductive success. We applied hand and honey bee pollination in the study of eight red clover cultivars with two ploidy levels released between 1964 and 2001. In hand pollination, increasing the visitation rates (from 10 to 80 pollinated florets per flower head) increased the seed number per flower head but reduced the seed number per pollinated floret. Different flowering stages (early, middle, and full flowering) did not influence the seed number per pollinated floret significantly. There was a marked difference in reproductive success depending on the ploidy level, with 0.52 seeds per pollinated floret in diploid and 0.16 in tetraploid cultivars. During the cultivar release history, seed number per pollinated floret seemed to decrease in diploid cultivars, whereas it increased in tetraploids. In honey bee pollination, diploid cultivars had more two-seeded florets than tetraploids. Different visitation rates and the stochastic nature of pollen transfer resulted in difficulties when the plant reproductive success between hand and bee pollination was compared. A maximum of 0.27 seeds per pollinated floret were produced in hand pollination compared to the 0.34 in honey bee pollination. In spite of this, hand pollination provided a valuable method for studying the pollination biology and reproduction of red clover. Future studies may employ hand pollination to unravel further aspects of the low reproductive success with the future perspective of improving seed number per pollinated floret in tetraploid red clover.
Procedural Control Versus Resources as Potential Origins of Human Hyper Selectivity
Authors: Ansorge Ulrich , Büsel Christian , Forstinger Marlene , Gugerell Daniel , Grüner Markus , Pomper Ulrich , Stolte Moritz , Schmid Rebecca Rosa , Valuch Christian
Published: August 2021

In the current review, we argue that experimental results usually interpreted as evidence for cognitive resource limitations could also reflect functional necessities of human information processing. First, we point out that selective processing of only specific features, objects, or locations at each moment in time allows humans to monitor the success and failure of their own overt actions and covert cognitive procedures. We then proceed to show how certain instances of selectivity are at odds with commonly assumed resource limitations. Next, we discuss examples of seemingly automatic, resource-free processing that challenge the resource view but can be easily understood from the functional perspective of monitoring cognitive procedures. Finally, we suggest that neurophysiological data supporting resource limitations might actually reflect mechanisms of how procedural control is implemented in the brain.
Causes and Characteristics of Children Unintentional Injuries in Emergency Department and Its Implications for Prevention
Authors: Gong Hairong , Lu Guoping , Ma Jian , Zheng Jicui , Hu Fei , Liu Jing , Song Jun , Hu Shenjie , Sun Libo , Chen Yang , Xie Li , Zhang Xiaobo , Duan Leilei , Xu Hong
Published: August 2021

Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China.

Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged <18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t-test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital.

Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93–4.63, P < 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93–433.14, P < 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07–1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48–4.49, P < 0.001) had a significantly higher risk of admission.

Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission.
Formerly Incarcerated Community Health Workers Engaging Individuals Returning From Incarceration Into Primary Care: Results From the Transition Clinic Network
Authors: Aminawung Jenerius A. , Harvey Tyler D. , Smart Jerry , Calderon Joseph , Steiner Anna , Kroboth Elizabeth , Wang Emily A. , Shavit Shira
Published: August 2021

Over half a million individuals return from United States prisons and millions more from jails every year, many of whom with complex health and social needs. Community health workers (CHWs) perform diverse roles to improve health outcomes in disadvantaged communities, but no studies have assessed their role as integrated members of a primary care team serving individuals returning from incarceration. Using data from participants who received primary care through the Transitions Clinic Network, a model of care that integrates CHWs with a lived experienced of incarceration into primary care teams, we characterized how CHWs address participant health and social needs during interactions outside of clinic visits for 6 months after participants established primary care. Among the 751 participants, 79% had one or more CHW interactions outside of the clinic documented. Participants with more comorbid conditions, longer stays during their most recent incarceration, and released with a prescription had more interactions with CHWs compared to those with fewer comorbidities, shorter stays, and no prescription at release. Median number of interactions was 4 (interquartile range, IQR 2–8) and 56% were in person. The most common issues addressed (34%) were social determinants of health, with the most common being housing (35%). CHWs working in interdisciplinary primary care teams caring for people with histories of incarceration perform a variety of functions for clients outside of scheduled primary care visits. To improve health outcomes among disadvantaged populations, CHWs should be able to work across multiple systems, with supervision and support for CHW activities both in the primary care clinic and within the community.
On the Social-Relational Moral Standing of AI: An Empirical Study Using AI-Generated Art
Authors: Lima Gabriel , Zhunis Assem , Manovich Lev , Cha Meeyoung
Published: August 2021

The moral standing of robots and artificial intelligence (AI) systems has become a widely debated topic by normative research. This discussion, however, has primarily focused on those systems developed for social functions, e.g., social robots. Given the increasing interdependence of society with nonsocial machines, examining how existing normative claims could be extended to specific disrupted sectors, such as the art industry, has become imperative. Inspired by the proposals to ground machines’ moral status on social relations advanced by Gunkel and Coeckelbergh, this research presents online experiments (∑N = 448) that test whether and how interacting with AI-generated art affects the perceived moral standing of its creator, i.e., the AI-generative system. Our results indicate that assessing an AI system’s lack of mind could influence how people subsequently evaluate AI-generated art. We also find that the overvaluation of AI-generated images could negatively affect their creator’s perceived agency. Our experiments, however, did not suggest that interacting with AI-generated art has any significant effect on the perceived moral standing of the machine. These findings reveal that social-relational approaches to AI rights could be intertwined with property-based theses of moral standing. We shed light on how empirical studies can contribute to the AI and robot rights debate by revealing the public perception of this issue.
Relationship Between Cancer Related Fatigue, Physical Activity Related Health Competence, and Leisure Time Physical Activity in Cancer Patients and Survivors
Authors: Koeppel Maximilian , Körbi Carlotta , Winkels Renate M. , Schmitz Kathryn H. , Wiskemann Joachim
Published: August 2021

Background: A large body of evidence supports the positive effects of leisure time physical activity (LTPA) and exercise on cancer survivors. However, only a fraction of survivors manages to attain international PA recommendations. This can be attributed to several external and internal barriers toward PA those patients seem to encounter, with cancer related fatigue (CRF) being the most reported internal barrier. Nevertheless, self-efficacy and knowledge about the utilization of LTPA can serve as facilitators of PA, which also correspond to certain constituents of physical activity related health competence (PAHCO). Since PAHCO is not investigated in cancer survivors we investigated if PAHCO can mediate the negative relationship between CRF and LTPA.

Methods: We surveyed 398 cancer survivors with different cancer types and therapy status. The patients completed the EORTC QLQ-FA12 (EORTC FA12) to assess CRF, the PAHCO questionnaire to assess PAHCO and the SQUASH to assess LTPA. We followed a two-step structural equation modeling approach. The first step established the measurement model, in the second step we fitted the mediation model. Since 163 patients chose not to answer the SQUASH, the mediation model was only fitted to the data of the remaining 235 participants.

Results: The proposed measurement model of the PAHCO offered an excellent fit. We found small to moderate positive associations between the PAHCO dimensions and the LTPA, and negative moderate relationships between the PAHCO and the EORTC FA12 dimensions. We did not observe a relationship between the EORTC FA12 dimensions and the LTPA (p > 0.05). The hypothesized mediation models did not display an appropriate fit.

Conclusion: The PAHCO confirmed its factorial validity; furthermore, it appears to have a positive relationship to LTPA. Therefore, integrating psycho-educational aspects can be beneficial in order to increase the PAHCO in exercise interventions. Because of the cross-sectional character of this study, causal conclusions are not suitable, therefore the longitudinal relationships of LTPA, CRF, and PAHCO require further investigation.
Using Qualitative System Dynamics Analysis to Promote Inclusive Livestock Value Chains: A Case Study of the South African Broiler Value Chain
Authors: Cuevas Garcia-Dorado Soledad , Queenan Kevin , Shankar Bhavani , Häsler Barbara , Mabhaudhi Tafadzwanashe , Cooper Gregory , Slotow Rob
Published: August 2021

Livestock value chains globally are increasingly dualistic, with integrated market-leaders co-existing with comparatively disadvantaged small producers who, nevertheless, support rural livelihoods and food access, and can also contribute to more resilient supply chains. The South African broiler value chain provides a highly illustrative case study. The purpose of this study is to identify potential leverage points for policy intervention to support small and emerging producers in the South African broiler value chain, and to discuss the strengths and limitations of system dynamics approaches to promote inclusive food value chains. This study develops a causal loop diagram (CLD) based on semi-structured stakeholder interviews and policy documents. The main challenges, key variables and causal relationships between them are systematically identified. Variables are coded, generalised and graphically represented, and entry points for intervention and their links to existing policies are mapped. The challenges faced by smallholders in the context of our study can be characterised, using a CLD, as a set of interlinked and reinforcing dynamics which perpetuate existing disadvantages and reinforce duality in the value chain. Key policy entry points have been identified that could be targeted by a coordinated policy package, including: Direct support for infrastructure investment and input access through grants, subsidies or other policies; credit and liquidity provision for day-to-day expenses; creation of aggregation mechanisms for both inputs and outputs; regulations or initiatives that directly target the relationship of farmers with the commercial segment to improve access to day-old-chicks and, finally, training in business and technical skills. Although most of these interventions have been addressed at some point, implementation has been fragmented, failing to fully consider their complementary nature, thus undermining effectiveness. Existing approaches to consensus building and stakeholder participation in system dynamics research can present challenges when it comes to engaging with complex policy processes and issues of conflict of interest that are relevant in the context of smallholder promotion and equitable food systems, but there are promising avenues for addressing. Despite some methodological challenges, we find that there is considerable scope for system dynamics approaches to inform policy for smallholder promotion, even in contexts characterised by complex policy processes.
Improved Duplication-Transfer-Loss Reconciliation with Extinct and Unsampled Lineages
Authors: Weiner Samson , Bansal Mukul S.
Published: August 2021

Duplication-Transfer-Loss (DTL) reconciliation is a widely used computational technique for understanding gene family evolution and inferring horizontal gene transfer (transfer for short) in microbes. However, most existing models and implementations of DTL reconciliation cannot account for the effect of unsampled or extinct species lineages on the evolution of gene families, likely affecting their accuracy. Accounting for the presence and possible impact of any unsampled species lineages, including those that are extinct, is especially important for inferring and studying horizontal transfer since many genes in the species lineages represented in the reconciliation analysis are likely to have been acquired through horizontal transfer from unsampled lineages. While models of DTL reconciliation that account for transfer from unsampled lineages have already been proposed, they use a relatively simple framework for transfer from unsampled lineages and cannot explicitly infer the location on the species tree of each unsampled or extinct lineage associated with an identified transfer event. Furthermore, there does not yet exist any systematic studies to assess the impact of accounting for unsampled lineages on the accuracy of DTL reconciliation. In this work, we address these deficiencies by (i) introducing an extended DTL reconciliation model, called the DTLx reconciliation model, that accounts for unsampled and extinct species lineages in a new, more functional manner compared to existing models, (ii) showing that optimal reconciliations under the new DTLx reconciliation model can be computed just as efficiently as under the fastest DTL reconciliation model, (iii) providing an efficient algorithm for sampling optimal DTLx reconciliations uniformly at random, (iv) performing the first systematic simulation study to assess the impact of accounting for unsampled lineages on the accuracy of DTL reconciliation, and (v) comparing the accuracies of inferring transfers from unsampled lineages under our new model and the only other previously proposed parsimony-based model for this problem.
Towards Autonomous Driving: Review and Perspectives on Configuration and Control of Four-Wheel Independent Drive/Steering Electric Vehicles
Authors: Hang Peng , Chen Xinbo
Published: August 2021

In this paper, the related studies of chassis configurations and control systems for four-wheel independent drive/steering electric vehicles (4WID-4WIS EV) are reviewed and discussed. Firstly, some prototypes and integrated X-by-wire modules of 4WID-4WIS EV are introduced, and the chassis configuration of 4WID-4WIS EV is analyzed. Then, common control models of 4WID-4WIS EV, i.e., the dynamic model, kinematic model, and path tracking model, are summarized. Furthermore, the control frameworks, strategies, and algorithms of 4WID-4WIS EV are introduced and discussed, including the handling of stability control, rollover prevention control, path tracking control and active fault-tolerate control. Finally, with a view towards autonomous driving, some challenges, and perspectives for 4WID-4WIS EV are discussed.
Control of a Round Jet Intermittency and Transition to Turbulence by Means of an Annular Synthetic Jet
Authors: Antošová Zuzana , Trávníček Zdeněk
Published: August 2021

This paper deals with active control of a continuous jet issuing from a long pipe nozzle by means of a concentrically placed annular synthetic jet. The experiments in air cover regimes of laminar, transitional, and turbulent main jet flows (Reynolds number ranges 1082–5181). The velocity profiles (time-mean and fluctuation components) of unforced and forced jets were measured using hot-wire anemometry. Six flow regimes are distinguished, and their parameter map is proposed. The possibility of turbulence reduction by forcing in transitional jets is demonstrated, and the maximal effect is revealed at Re = 2555, where the ratio of the turbulence intensities of the forced and unforced jets is decreased up to 0.45.