bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen Uptake and Distribution in Different Chinese Cabbage Genotypes under Low Nitrogen Stress
Authors: Zhang Yihui , Li Jingjuan , Zhou Dandan , Song Jie , Gao Jianwei
Published: January 2022

In order to understand the effects of low nitrogen (LN) stress on the growth and development in different genotypes of Chinese cabbage, the L40 genotype with high nitrogen utilization and the L14 genotype with LN utilization were selected as experimental materials. Field experiments and indoor hydroponic methods were used to study the different responses of two Chinese cabbage genotypes to low nitrogen levels. In this study, we also analyzed the genome-wide gene expression profiles of L40 and L14 in response to LN stress by high-throughput RNA sequencing technology. The results reveal that the L40 root system responds better to LN compared with L14. After LN stress, L40 can effectively absorb and transport NO3− and store it in the ground. It is precisely because of this characteristic of the L40 genotype that LN treatment did not have a significant effect on the chlorophyll (Chl) content and net photosynthetic rate (Pn) of the L40 Chinese cabbage compared with the L14 Chinese cabbage. These two different Chinese cabbage genotypes were shown to have differently expressed genes related to nitrate transport, auxin synthesis, and glutamate dehydrogenase synthesis. These genes function in the nitrogen pathway, which are important candidates for understanding the molecular host-response mechanisms to LN stress.
The Role of Nutrients in Maintaining Hematopoietic Stem Cells and Healthy Hematopoiesis for Life
Authors: Tadokoro Yuko , Hirao Atsushi
Published: January 2022

Nutrients are converted by the body to smaller molecules, which are utilized for both anabolic and catabolic metabolic reactions. Cooperative regulation of these processes is critical for life-sustaining activities. In this review, we focus on how the regulation of nutrient-driven metabolism maintains healthy hematopoietic stem cells (HSCs). For this purpose, we have examined the metabolic regulation of HSCs from two perspectives: (1) the control of intracellular metabolism by the balance of anabolic and catabolic reactions; and (2) the control of organismal metabolic status and hematopoiesis by dietary intake of nutrients. Critical roles of catabolic regulators in stem cell homeostasis are conserved in several types of tissues, including hematopoiesis. These catabolic signals are also major regulators of organismal lifespan in multiple species. In parallel, changes to nutrients via alterations to dietary intake affect not only an organism’s metabolic state but also the behavior of its stem cells. While the molecular mechanisms involved in these two aspects of nutrient function may not necessarily overlap, a deeper understanding of these phenomena will point to new avenues of medical research and may furnish new agents for improving human health care.
A Review of the Advantages, Disadvantages and Limitations of Chemotaxis Assays for Campylobacter spp.
Authors: Elgamoudi Bassam A. , Korolik Victoria
Published: January 2022

Reproducible qualitative and quantitative assessment of bacterial chemotactic motility, particularly in response to chemorepellent effectors, is experimentally challenging. Here we compare several established chemotaxis assays currently used to investigate Campylobacter jejuni chemotaxis, with the aim of improving the correlation between different studies and establishing the best practices. We compare the methodologies of capillary, agar, and chamber-based assays, and discuss critical technical points, in terms of reproducibility, accuracy, and the advantages and limitations of each.
The Cellular and Subcellular Organization of the Glucosinolate–Myrosinase System against Herbivores and Pathogens
Authors: Lv Qiaoqiao , Li Xifeng , Fan Baofang , Zhu Cheng , Chen Zhixiang
Published: January 2022

Glucosinolates are an important class of secondary metabolites in Brassicales plants with a critical role in chemical defense. Glucosinolates are chemically inactive but can be hydrolyzed by myrosinases to produce a range of chemically active compounds toxic to herbivores and pathogens, thereby constituting the glucosinolate–myrosinase defense system or the mustard oil bomb. During the evolution, Brassicales plants have developed not only complex biosynthetic pathways for production of a large number of glucosinolate structures but also different classes of myrosinases that differ in catalytic mechanisms and substrate specificity. Studies over the past several decades have made important progress in the understanding of the cellular and subcellular organization of the glucosinolate–myrosinase system for rapid and timely detonation of the mustard oil bomb upon tissue damage after herbivore feeding and pathogen infection. Progress has also been made in understanding the mechanisms that herbivores and pathogens have evolved to counter the mustard oil bomb. In this review, we summarize our current understanding of the function and organization of the glucosinolate–myrosinase system in Brassicales plants and discuss both the progresses and future challenges in addressing this complex defense system as an excellent model for analyzing plant chemical defense.
Structural Basis of Redox-Sensing Transcriptional Repressor Rex with Cofactor NAD+ and Operator DNA
Authors: Jeong Kang Hwa , Lee Hyun Jin , Park Young Woo , Lee Jae Young
Published: January 2022

The transcriptional repressor Rex plays important roles in regulating the expression of respiratory genes by sensing the reduction–oxidation (redox) state according to the intracellular NAD+/NADH balance. Previously, we reported on crystal structures of apo, NAD+-bound, and NADH-bound forms of Rex from Thermotoga maritima to analyze the structural basis of transcriptional regulation depending on either NAD+ or NADH binding. In this study, the crystal structure of Rex in ternary complex with NAD+ and operator DNA revealed that the N-terminal domain of Rex, including the helix-turn-helix motif, forms extensive contacts with DNA in addition to DNA sequence specificity. Structural comparison of the Rex in apo, NAD+-bound, NADH-bound, and ternary complex forms provides a comprehensive picture of transcriptional regulation in the Rex. These data demonstrate that the conformational change in Rex when binding with the reduced NADH or oxidized NAD+ determines operator DNA binding. The movement of the N-terminal domains toward the operator DNA was blocked upon binding of NADH ligand molecules. The structural results provide insights into the molecular mechanism of Rex binding with operator DNA and cofactor NAD+/NADH, which is conserved among Rex family repressors. Structural analysis of Rex from T. maritima also supports the previous hypothesis about the NAD+/NADH-specific transcriptional regulation mechanism of Rex homologues.
Deciphering Genetic Alterations of Taiwanese Patients with Pancreatic Adenocarcinoma through Targeted Sequencing
Authors: Huang Chi-Cheng , Liu Chih-Yi , Huang Chi-Jung , Hsu Yao-Chun , Lien Heng-Hui , Wong Jia-Uei , Tai Feng-Chuan , Ku Wen-Hui , Hung Chi-Feng , Lin Jaw-Town , Huang Ching-Shui , Chiang Han-Sun
Published: January 2022

Pancreatic adenocarcinoma (PAC) is the 8th leading cause of cancer-related deaths in Taiwan, and its incidence is increasing. The development of PAC involves successive accumulation of multiple genetic alterations. Understanding the molecular pathogenesis and heterogeneity of PAC may facilitate personalized treatment for PAC and identify therapeutic agents. We performed tumor-only next-generation sequencing (NGS) with targeted panels to explore the molecular changes underlying PAC patients in Taiwan. The Ion Torrent Oncomine Comprehensive Panel (OCP) was used for PAC metastatic lesions, and more PAC samples were sequenced with the Ion AmpliSeq Cancer Hot Spot (CHP) v2 panel. Five formalin-fixed paraffin-embedded (FFPE) metastatic PAC specimens were successfully assayed with OCP, and KRAS was the most prevalent alteration, which might contraindicate the use of anti-EGFR therapy. One PAC patient harbored a FGFR2 p. C382R mutation, which might benefit from FGFR tyrosine kinase inhibitors. An additional 38 samples assayed with CHP v2 showed 100 hotspot variants, collapsing to 54 COSMID IDs. The most frequently mutated genes were TP53, KRAS, and PDGFRA (29, 23, 10 hotspot variants), impacting 11, 23, and 10 PAC patients. Highly pathogenic variants, including COSM22413 (PDGFRA, FATHMM predicted score: 0.88), COSM520, COSM521, and COSM518 (KRAS, FATHMM predicted score: 0.98), were reported. By using NGS with targeted panels, somatic mutations with therapeutic potential were identified. The combination of clinical and genetic information is useful for decision making and precise selection of targeted medicine.
Polymodal Control of TMEM16x Channels and Scramblases
Authors: Agostinelli Emilio , Tammaro Paolo
Published: January 2022

The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion transport. The channel is a founding member of a family of 10 proteins (TMEM16x) with varied functions; some members (i.e., TMEM16A and TMEM16B) serve as CaCCs, while others are lipid scramblases, combine channel and scramblase function, or perform additional cellular roles. TMEM16x proteins are typically activated by agonist-induced Ca2+ release evoked by Gq-protein-coupled receptor (GqPCR) activation; thus, TMEM16x proteins link Ca2+-signalling with cell electrical activity and/or lipid transport. Recent studies demonstrate that a range of other cellular factors—including plasmalemmal lipids, pH, hypoxia, ATP and auxiliary proteins—also control the activity of the TMEM16A channel and its paralogues, suggesting that the TMEM16x proteins are effectively polymodal sensors of cellular homeostasis. Here, we review the molecular pathophysiology, structural biology, and mechanisms of regulation of TMEM16x proteins by multiple cellular factors.
Endocrine-Disrupting Chemicals and Their Adverse Effects on the Endoplasmic Reticulum
Authors: Kim Kangmin , Kwon Jin-Sook , Ahn Changhwan , Jeung Eui-Bae
Published: January 2022

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has serious adverse health effects through both hormone-direct and hormone-indirect ways. Accordingly, some EDCs can be a pathogen and an inducer to the susceptibility of disease, even if they have a very low affinity on the estrogen receptor, or no estrogenic effect. Endoplasmic reticulum (ER) stress recently attracted attention in this research area. Because ER and ER stress could be key regulators of the EDC’s adverse effects, such as the malfunction of the organ, as well as the death, apoptosis, and proliferation of a cell. In this review, we focused on finding evidence which shows that EDCs could be a trigger for ER stress and provide specific examples of EDCs, which are known to cause ER stress currently.
Eupatilin Suppresses OVA-Induced Asthma by Inhibiting NF-κB and MAPK and Activating Nrf2 Signaling Pathways in Mice
Authors: Bai Donghui , Sun Tianxiao , Lu Fang , Shen Yancheng , Zhang Yan , Zhang Bo , Yu Guangli , Li Haihua , Hao Jiejie
Published: January 2022

To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.
Time-Dependent Molecular Motifs of Pulmonary Fibrogenesis in COVID-19
Authors: Kamp Jan C. , Neubert Lavinia , Ackermann Maximilian , Stark Helge , Werlein Christopher , Fuge Jan , Haverich Axel , Tzankov Alexandar , Steinestel Konrad , Friemann Johannes , Boor Peter , Junker Klaus , Hoeper Marius M. , Welte Tobias , Laenger Florian , Kuehnel Mark P. , Jonigk Danny D.
Published: January 2022

(1) Background: In COVID-19 survivors there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood; (2) Methods: In this multicentric study, n = 12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within ≤7 and >7 days of hospitalization, respectively) and compared to n = 11 healthy controls; mRNA and protein expression as well as biological pathway analysis were performed to gain insights into the evolution of pulmonary fibrogenesis in COVID-19; (3) Results: Median duration of hospitalization until death was 3 (IQR25-75, 3–3.75) and 14 (12.5–14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of BST2 and IL1R1, independent of hospitalization time. In the early group there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB) and pathways dominated in the late group; (4) Conclusions: After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.
Synthetic Collagen-like Polymer That Undergoes a Sol–Gel Transition Triggered by O–N Acyl Migration at Physiological pH
Authors: Ichise Shinichiro F. , Koide Takaki
Published: January 2022

We previously reported an artificial collagen gel that can be used as a cell-culture substrate by end-to-end cross-linking of collagen-like triple-helical peptides via disulfide bonds. However, the gel had to be formed a priori by polymerizing the peptide in an acidic solution containing dimethyl sulfoxide for several days, which prevented its use as an injectable gel or three-dimensional (3D) scaffold for cell culture. In this study, we developed a collagen-like peptide polymer by incorporating an O–N acyl migration-triggered triple helix formation mechanism into a collagen-like peptide, which formed a gel within 10 min. We demonstrated that the collagen-like peptide polymer can be used as a 3D cell scaffold and that the 3D structure formation of cells can be controlled by collagen-derived bioactive sequences introduced into the peptide sequence.
Update on Novel Targeted Therapy for Pleural Organization and Fibrosis
Authors: Tucker Torry A. , Idell Steven
Published: January 2022

Pleural injury and subsequent loculation is characterized by acute injury, sustained inflammation and, when severe, pathologic tissue reorganization. While fibrin deposition is a normal part of the injury response, disordered fibrin turnover can promote pleural loculation and, when unresolved, fibrosis of the affected area. Within this review, we present a brief discussion of the current IPFT therapies, including scuPA, for the treatment of pathologic fibrin deposition and empyema. We also discuss endogenously expressed PAI-1 and how it may affect the efficacy of IPFT therapies. We further delineate the role of pleural mesothelial cells in the progression of pleural injury and subsequent pleural remodeling resulting from matrix deposition. We also describe how pleural mesothelial cells promote pleural fibrosis as myofibroblasts via mesomesenchymal transition. Finally, we discuss novel therapeutic targets which focus on blocking and/or reversing the myofibroblast differentiation of pleural mesothelial cells for the treatment of pleural fibrosis.
An Efficient Marker Gene Excision Strategy Based on CRISPR/Cas9-Mediated Homology-Directed Repair in Rice
Authors: Tan Jiantao , Wang Yaxi , Chen Shuifu , Lin Zhansheng , Zhao Yanchang , Xue Yang , Luo Yuyu , Liu Yao-Guang , Zhu Qinlong
Published: January 2022

In order to separate transformed cells from non-transformed cells, antibiotic selectable marker genes are usually utilized in genetic transformation. After obtaining transgenic plants, it is often necessary to remove the marker gene from the plant genome in order to avoid regulatory issues. However, many marker-free systems are time-consuming and labor-intensive. Homology-directed repair (HDR) is a process of homologous recombination using homologous arms for efficient and precise repair of DNA double-strand breaks (DSBs). The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) system is a powerful genome editing tool that can efficiently cause DSBs. Here, we isolated a rice promoter (Pssi) of a gene that highly expressed in stem, shoot tip and inflorescence, and established a high-efficiency sequence-excision strategy by using this Pssi to drive CRISPR/Cas9-mediated HDR for marker free (PssiCHMF). In our study, PssiCHMF-induced marker gene deletion was detected in 73.3% of T0 plants and 83.2% of T1 plants. A high proportion (55.6%) of homozygous marker-excised plants were obtained in T1 progeny. The recombinant GUS reporter-aided analysis and its sequencing of the recombinant products showed precise deletion and repair mediated by the PssiCHMF method. In conclusion, our CRISPR/Cas9-mediated HDR auto-excision method provides a time-saving and efficient strategy for removing the marker genes from transgenic plants.
The Inherent Coupling of Intrinsically Disordered Regions in the Multidomain Receptor Tyrosine Kinase KIT
Authors: Ledoux Julie , Trouvé Alain , Tchertanov Luba
Published: January 2022

RTK KIT regulates a variety of crucial cellular processes via its cytoplasmic domain (CD), which is composed of the tyrosine kinase domain, crowned by the highly flexible domains—the juxtamembrane region, kinase insertion domain, and C-tail, which are key recruitment regions for downstream signalling proteins. To prepare a structural basis for the characterization of the interactions of KIT with its signalling proteins (KIT INTERACTOME), we generated the 3D model of the full-length CD attached to the transmembrane helix. This generic model of KIT in inactive state was studied by molecular dynamics simulation under conditions mimicking the natural environment of KIT. With the accurate atomistic description of the multidomain KIT dynamics, we explained its intrinsic (intra-domain) and extrinsic (inter-domain) disorder and represented the conformational assemble of KIT through free energy landscapes. Strongly coupled movements within each domain and between distant domains of KIT prove the functional interdependence of these regions, described as allosteric regulation, a phenomenon widely observed in many proteins. We suggested that KIT, in its inactive state, encodes all properties of the active protein and its post-transduction events.
Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations
Authors: Hsueh Shu-Shun , Wang S.-S. (Steven) , Chen Shu-Han , Wang Chia-Lin , Wu W. (Josephine) , Lin Ta-Hsien
Published: January 2022

Human γD-crystallin (HGDC) is an abundant lens protein residing in the nucleus of the human lens. Aggregation of this and other structural proteins within the lens leads to the development of cataract. Much has been explored on the stability and aggregation of HGDC and where detailed investigation at the atomic resolution was needed, the X-ray structure was used as an initial starting conformer for molecular modeling. In this study, we implemented NMR-solution HGDC structures as starting conformers for molecular dynamics simulations to provide the missing pieces of the puzzle on the very early stages of HGDC unfolding leading up to the domain swap theories proposed by past studies. The high-resolution details of the conformational dynamics also revealed additional insights to possible early intervention for cataractogenesis.
Implantable Immunosuppressant Delivery to Prevent Rejection in Transplantation
Authors: Anggelia Madonna Rica , Huang Ren-Wen , Cheng Hui-Yun , Lin Chih-Hung , Lin Cheng-Hung
Published: January 2022

An innovative immunosuppressant with a minimally invasive delivery system has emerged in the biomedical field. The application of biodegradable and biocompatible polymer forms, such as hydrogels, scaffolds, microspheres, and nanoparticles, in transplant recipients to control the release of immunosuppressants can minimize the risk of developing unfavorable conditions. In this review, we summarized several studies that have used implantable immunosuppressant delivery to release therapeutic agents to prolong allograft survival. We also compared their applications, efficacy, efficiency, and safety/side effects with conventional therapeutic-agent administration. Finally, challenges and the future prospective were discussed. Collectively, this review will help relevant readers understand the different approaches to prevent transplant rejection in a new era of therapeutic agent delivery.
Genome-Wide Identification and Expression Analysis of the 14-3-3 Gene Family in Mango (Mangifera indica L.)
Authors: Xia Liming , He Xinhua , Huang Xing , Yu Haixia , Lu Tingting , Xie Xiaojie , Zeng Xuemei , Zhu Jiawei , Luo Cong
Published: January 2022

Members of the Mi14-3-3 gene family interact with target proteins that are widely involved in plant hormone signal transduction and physiology-related metabolism and play important roles in plant growth, development and stress responses. In this study, 14-3-3s family members are identified by the bioinformatic analysis of the mango (Mangifera indica L.) genome. The gene structures, chromosomal distributions, genetic evolution, and expression patterns of these genes and the physical and chemical properties and conserved motifs of their proteins are analysed systematically. The results identified 16 members of the 14-3-3 genes family in the mango genome. The members were not evenly distributed across the chromosomes, and the gene structure analysis showed that the gene sequence length and intron number varied greatly among the different members. Protein sequence analysis showed that the Mi14-3-3 proteins had similar physical and chemical properties and secondary and tertiary structures, and protein subcellular localization showed that the Mi14-3-3 family proteins were localized to the nucleus. The sequence analysis of the Mi14-3-3s showed that all Mi14-3-3 proteins contain a typical conserved PFAM00244 domain, and promoter sequence analysis showed that the Mi14-3-3 promoters contain multiple hormone-, stress-, and light-responsive cis-regulatory elements. Expression analysis showed that the 14-3-3 genes were expressed in all tissues of mango, but that their expression patterns were different. Drought, salt and low temperature stresses affected the expression levels of 14-3-3 genes, and different 14-3-3 genes had different responses to these stresses. This study provides a reference for further studies on the function and regulation of Mi14-3-3 family members.
Removal of Antimony in Wastewater by Antimony Tolerant Sulfate-Reducing Bacteria Isolated from Municipal Sludge
Authors: Li He , Fei Yue , Xue Shuwen , Zhang Gege , Bian Ziqi , Guo Fanfan , Wang Li , Chai Ruiqing , Zhang Shuqi , Cui Zhenyu , Wang Shiwei , Zhang Jun
Published: January 2022

Antimony (Sb), a global and priority controlled pollutant, causes severe environmental issues. Bioremediation by microbial communities containing sulfate-reducing bacteria (SRB) is considered to be among the safest, economical, and environmentally friendly methods to remove Sb from wastewater. However, the roles of SRB species in these communities remain uncertain, and pure cultures of bacteria that may be highly efficient have not yet been developed for Sb removal. In this study, an Sb tolerant community was enriched from municipal sludge, and molecular ecological analysis showed that Escherichia (40%) and Desulfovibrio (15%) were the dominant bacteria. Further isolation and identification showed that the enriched SRB strains were closely related to Cupidesulfovibrio oxamicus, based on the molecular analyses of 16S rRNA and dsrB genes. Among them, a strain named SRB49 exhibited the highest activity in removal of Sb(V). SRB49 was able to remove 95% of Sb(V) at a concentration of 100 mg/L within 48 h under optimum conditions: a temperature of 37–40 °C, an initial pH value of 8, 4 mM of sulfate, and an initial redox potential of 145–229 mV. SEM-EDX analysis showed that SRB49 did not adsorb Sb(V) but reduced and precipitated Sb(V) via the formation of Sb2S3. The results demonstrated the potential roles that pure cultures of SRB species may play in Sb removal and the use of Sb-tolerant SRB strains for Sb remediation.
Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments
Authors: Liu Dan , Luo Ling , Wang Zhengxing , Ma Xiaoyun , Gan Xiuhai
Published: January 2022

Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC50 value of that was 2.9 μg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC50 = 12.5 μg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 μg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.
Identification of Growth Factors, Cytokines and Mediators Regulated by Artemisia annua L. Polyphenols (pKAL) in HCT116 Colorectal Cancer Cells: TGF-β1 and NGF-β Attenuate pKAL-Induced Anticancer Effects via NF-κB p65 Upregulation
Authors: Jung Eun Joo , Paramanantham Anjugam , Kim Hye Jung , Shin Sung Chul , Kim Gon Sup , Jung Jin-Myung , Hong Soon Chan , Chung Ky Hyun , Kim Choong Won , Lee Won Sup
Published: January 2022

The anticancer effects of natural phytochemicals are relevant to the modulation of cytokine signaling pathways in various cancer cells with stem-like properties as well as immune cells. The aim of this study was to elucidate a novel anticancer mechanism of Artemisia annua L. polyphenols (pKAL) involved in the regulation of growth factors, cytokines and mediators in stem-like HCT116 colorectal cancer cells. Through RayBiotech human L-1000 antibody array and bioinformatics analysis, we show here that pKAL-induced anticancer effects are associated with downregulation of growth factor and cytokine signaling proteins including TGFA, FGF16, PDGFC, CCL28, CXCR3, IRF6 and SMAD1. Notably, we found that TGF-β signaling proteins such as GDF10, ENG and TGFBR2 and well-known survival proteins such as NGF-β, VEGFD and insulin were significantly upregulated by pKAL. Moreover, the results of hematoxylin staining, cell viability assay and Western blot analysis demonstrated that TGF-β1 and NGF-β attenuated pKAL-induced anticancer effects by inhibiting pKAL-induced downregulation of caspase-8, NF-κB p65 and cyclin D1. These results suggest that certain survival mediators may be activated by pKAL through the TGF-β1 and NGF-β signaling pathways during pKAL-induced cell death and thus, strategies to inhibit the survival signaling are inevitably required for more effective anticancer effects of pKAL.
The Enhanced Cytotoxic Effects in B-Cell Leukemia and Lymphoma Following Activation of Prostaglandin EP4 Receptor and Targeting of CD20 Antigen by Monoclonal Antibodies
Authors: Markovič Tijana , Podgornik Helena , Avsec Damjan , Nabergoj Sanja , Mlinarič-Raščan Irena
Published: January 2022

Anti-CD20 monoclonal antibodies (MAbs) have revolutionized the treatment of B-cell leukemia and lymphoma. However, many patients do not respond to such treatment due to either deficiency of the complementary immune response or resistance to apoptosis. Other currently available treatments are often inadequate or induce major side effects. Therefore, there is a constant need for improved therapies. The prostaglandin E2 receptor 4 (EP4) receptor has been identified as a promising therapeutic target for hematologic B-cell malignancies. Herein, we report that EP4 receptor agonists PgE1-OH and L-902688 have exhibited enhanced cytotoxicity when applied together with anti-CD20 MAbs rituximab, ofatumumab and obinutuzumab in vitro in Burkitt lymphoma cells Ramos, as well as in p53-deficient chronic lymphocytic leukemia (CLL) cells MEC-1. Moreover, the enhanced cytotoxic effects of EP4 receptor agonists and MAbs targeting CD20 have been identified ex vivo on primary lymphocytes B obtained from patients diagnosed with CLL. Incubation of cells with PgE1-OH and L-902688 preserved the expression of CD20 molecules, further confirming the anti-leukemic potential of EP4 receptor agonists in combination with anti-CD20 MAbs. Additionally, we demonstrated that the EP4 receptor agonist PgE-1-OH induced apoptosis and inhibited proliferation via the EP4 receptor triggering in CLL. This work has revealed very important findings leading towards the elucidation of the anticancer potential of PgE1-OH and L-902688, either alone or in combination with MAbs. This may contribute to the development of potential therapeutic alternatives for patients with B-cell malignancies.
The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases
Authors: Nonogaki Katsunori
Published: January 2022

Central and peripheral serotonin (5-hydroxytryptamine, 5-HT) regulate feeding signals for energy metabolism. Disruption of central 5-HT signaling via 5-HT2C receptors (5-HT2CRs) induces leptin-independent hyperphagia in mice, leading to late-onset obesity, insulin resistance, and impaired glucose tolerance. 5-HT2CR mutant mice are more responsive than wild-type mice to a high-fat diet, exhibiting earlier-onset obesity and type 2 diabetes. High-fat and high-carbohydrate diets increase plasma 5-HT and fibroblast growth factor-21 (FGF21) levels. Plasma 5-HT and FGF21 levels are increased in rodents and humans with obesity, type 2 diabetes, and non-alcohol fatty liver diseases (NAFLD). The increases in plasma FGF21 and hepatic FGF21 expression precede hyperinsulinemia, insulin resistance, hyperglycemia, and weight gain in mice fed a high-fat diet. Nutritional, pharmacologic, or genetic inhibition of peripheral 5-HT synthesis via tryptophan hydroxylase 1 (Tph1) decreases hepatic FGF21 expression and plasma FGF21 levels in mice. Thus, perturbing central 5-HT signaling via 5-HT2CRs alters feeding behavior. Increased energy intake via a high-fat diet and/or high-carbohydrate diet can upregulate gut-derived 5-HT synthesis via Tph1. Peripheral 5-HT upregulates hepatic FGF21 expression and plasma FGF21 levels, leading to metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and NAFLD. The 5-HT network in the brain–gut–liver axis regulates feeding signals and may be involved in the development and/or prevention of metabolic diseases.
The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options
Authors: Jankovic Milena , Petrovic Bojana , Novakovic Ivana , Brankovic Slavko , Radosavljevic Natasa , Nikolic Dejan
Published: January 2022

Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.
Alzheimer’s Disease-Associated SNP rs708727 in SLC41A1 May Increase Risk for Parkinson’s Disease: Report from Enlarged Slovak Study
Authors: Cibulka Michal , Brodnanova Maria , Grendar Marian , Necpal Jan , Benetin Jan , Han Vladimir , Kurca Egon , Nosal Vladimir , Skorvanek Matej , Vesely Branislav , Stanclova Andrea , Lasabova Zora , Pös Zuzana , Szemes Tomas , Stuchlik Stanislav , Grofik Milan , Kolisek Martin
Published: January 2022

SLC41A1 (A1) SNPs rs11240569 and rs823156 are associated with altered risk for Parkinson’s disease (PD), predominantly in Asian populations, and rs708727 has been linked to Alzheimer’s disease (AD). In this study, we have examined a potential association of the three aforementioned SNPs and of rs9438393, rs56152218, and rs61822602 (all three lying in the A1 promoter region) with PD in the Slovak population. Out of the six tested SNPs, we have identified only rs708727 as being associated with an increased risk for PD onset in Slovaks. The minor allele (A) in rs708727 is associated with PD in dominant and completely over-dominant genetic models (ORD = 1.36 (1.05–1.77), p = 0.02, and ORCOD = 1.34 (1.04–1.72), p = 0.02). Furthermore, the genotypic triplet GG(rs708727) + AG(rs823156) + CC(rs61822602) might be clinically relevant despite showing a medium (h ≥ 0.5) size difference (h = 0.522) between the PD and the control populations. RandomForest modeling has identified the power of the tested SNPs for discriminating between PD-patients and the controls to be essentially zero. The identified association of rs708727 with PD in the Slovak population leads us to hypothesize that this A1 polymorphism, which is involved in the epigenetic regulation of the expression of the AD-linked gene PM20D1, is also involved in the pathoetiology of PD (or universally in neurodegeneration) through the same or similar mechanism as in AD.
Acknowledgment to Reviewers of Information in 2021
Authors:   Information Editorial Office
Published: January 2022

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Modelling Service Quality of Internet Service Providers during COVID-19: The Customer Perspective Based on Twitter Dataset
Authors: Rintyarna Bagus Setya , Kuswanto Heri , Sarno Riyanarto , Rachmaningsih Emy Kholifah , Rachman Fika Hastarita , Suharso Wiwik , Cahyanto Triawan Adi
Published: January 2022

Internet service providers (ISPs) conduct their business by providing Internet access features to their customers. The COVID-19 pandemic has shifted most activity being performed remotely using an Internet connection. As a result, the demand for Internet services increased by 50%. This significant rise in the appeal of Internet services needs to be overtaken by a notable increase in the service quality provided by ISPs. Service quality plays a great role for enterprises, including ISPs, in retaining consumer loyalty. Thus, modelling ISPs’ service quality is of great importance. Since a common technique to reveal service quality is a timely and costly pencil survey-based method, this work proposes a framework based on the Sentiment Analysis (SA) of the Twitter dataset to model service quality. The SA involves the majority voting of three machine learning algorithms namely Naïve Bayes, Multinomial Naïve Bayes and Bernoulli Naïve Bayes. Making use of Thaicon’s service quality metrics, this work proposes a formula to generate a rating of service quality accordingly. For the case studies, we examined two ISPs in Indonesia, i.e., By.U and MPWR. The framework successfully extracted the service quality rate of both ISPs, revealing that By.U is better in terms of service quality, as indicated by a service quality rate of 0.71. Meanwhile, MPWR outperforms By.U in terms of customer service.
Identification and Functional Characterization of Toxoneuron nigriceps Ovarian Proteins Involved in the Early Suppression of Host Immune Response
Authors: Salvia Rosanna , Cozzolino Flora , Scieuzo Carmen , Grimaldi Annalisa , Franco Antonio , Vinson S. Bradleigh , Monti Maria , Falabella Patrizia
Published: January 2022

The endophagous parasitoid Toxoneuron nigriceps (Viereck) (Hymenoptera, Braconidae) of the larval stages of the tobacco budworm Heliothis virescens (Fabricius) (Lepidoptera, Noctuidae) injects the egg, the venom, the calyx fluid, which includes a Polydnavirus (T. nigriceps BracoVirus: TnBV) and the Ovarian Proteins (OPs) into the host body during oviposition. The host metabolism and immune system are disrupted prematurely shortly after parasitization by the combined action of the TnBV, venom, and OPs. OPs are involved in the early suppression of host immune response, before TnBV infects and expresses its genes in the host tissues. In this work, we evaluated the effect of HPLC fractions deriving from in toto OPs. Two fractions caused a reduction in hemocyte viability and were subsequently tested to detect changes in hemocyte morphology and functionality. The two fractions provoked severe oxidative stress and actin cytoskeleton disruption, which might explain the high rate of hemocyte mortality, loss of hemocyte functioning, and hence the host’s reduced hemocyte encapsulation ability. Moreover, through a transcriptome and proteomic approach we identify the proteins of the two fractions: eight proteins were identified that might be involved in the observed host hemocyte changes. Our findings will contribute to a better understanding of the secreted ovarian components and their role in parasitoid wasp strategy for evading host immune responses.
A Phylogeographical Analysis of the Beetle Pest Species Callosobruchus chinensis (Linnaeus, 1758) in China
Authors: Wang Fang , Li Min , Zheng Haixia , Dong Tian , Zhang Xianhong
Published: January 2022

Callosobruchus chinensis (Coleoptera Bruchidae), is a pest of different varieties of legumes. In this paper, a phylogeographical analysis of C. chinensis was conducted to provide knowledge for the prevention and control of C. chinensis. A total of 224 concatenated mitochondrial sequences were obtained from 273 individuals. Suitable habitat shifts were predicted by the distribution modelling (SDM). Phylogeny, genetic structure and population demographic history were analyzed using multiple software. Finally, the least-cost path (LCP) method was used to identify possible dispersal corridors and genetic connectivity. The SDM results suggested that the distribution of C. chinensis experienced expansion and contraction with changing climate. Spatial distribution of mtDNA haplotypes showed there was partial continuity among different geographical populations of C. chinensis, except for the Hohhot (Inner Mongolia) population. Bayesian skyline plots showed that the population had a recent expansion during 0.0125 Ma and 0.025 Ma. The expansion and divergent events were traced back to Quaternary glaciations. The LCP method confirmed that there were no clear dispersal routes. Our findings indicated that climatic cycles of the Pleistocene glaciations, unsuitable climate and geographic isolation played important roles in the genetic differentiation of C. chinensis. Human activities weaken the genetic differentiation between populations. With the change in climate, the suitable areas of C. chinensis will disperse greatly in the future.
Could Sterile Aedes albopictus Male Releases Interfere with Aedes aegypti Population in Reunion Island?
Authors: Andrianjakarivony Harilanto Felana , Damiens David , Marquereau Lucie , Gaudillat Benjamin , Habchi-Hanriot Nausicaa , Gouagna Louis-Clément
Published: January 2022

In Reunion Island, the feasibility of an Aedes albopictus control program using the Sterile Insect Technique (SIT) is studied. Because, in some regions, Ae. albopictus is living in sympatry with Aedes aegypti, the impact of releasing millions of sterile male Ae. albopictus on female Ae. aegypti reproduction needs to be assessed. Thus, to study the potential heterospecific matings, a marking technique using rhodamine B has been used. Rhodamine is given in solution to male mosquitoes to be incorporated into the male body and seminal fluid and transferred during mating into the bursa inseminalis and spermathecae of females. The presence of rhodamine in females occurred in 15% of cases when Ae. aegypti females were offered non-irradiated Ae. albopictus males, 5% when offered irradiated Ae. albopictus males and 18% of cases in the inverse heterospecific matings. Moreover, our results also showed that these matings gave few eggs but were not viable. Finally, the results showed that whatever the type of mating crosses, females in cages previously crossed with males of another species can re-mate with males of their species and produce an equivalent amount of egg compared to females only mated with conspecific males. Despite the promiscuity of the males and females in small cages for three days, heterospecific mating between sterile male Ae. albopictus and female Ae aegypti, 95% of the females have not been inseminated suggesting that in the field the frequency satyrization would be very low.
Current State of DNA Barcoding of Sciaroidea (Diptera)—Highlighting the Need to Build the Reference Library
Authors: Kjærandsen Jostein
Published: January 2022

DNA barcoding has tremendous potential for advancing species knowledge for many diverse groups of insects, potentially paving way for machine identification and semi-automated monitoring of whole insect faunas. Here, I review the current state of DNA barcoding of the superfamily Sciaroidea (Diptera), a diverse group consisting of eight understudied fly families where the described species in the world makes up some 10% (≈16,000 species) of all Diptera. World data of Sciaroidea were extracted from the Barcode of Life online database BoldSystems (BOLD) and contrasted with results and experiences from a Nordic project to build the reference library. Well over 1.2 million (1,224,877) Sciaroidea specimens have been submitted for barcoding, giving barcode-compliant sequences resulting in 56,648 so-called barcode index numbers (BINs, machine-generated proxies for species). Although the BINs on BOLD already represent 3.5 times the number of described species, merely some 2850 named species (described or interim names, 5% of the BINs) currently have been assigned a BIN. The other 95% remain as dark taxa figuring in many frontier publications as statistics representing proxies for species diversity within a family. In the Nordic region, however, substantial progress has been made towards building a complete reference library, currently making up 55% of all named Sciaroidea BINs on BOLD. Another major source (31%) of named Sciaroidea BINs on BOLD comes from COI sequences mined from GenBank, generated through phylogenetic and integrative studies outside of BOLD. Building a quality reference library for understudied insects such as Sciaroidea requires heavy investment, both pre sequence and post sequence, by trained taxonomists to build and curate voucher collections, to continually improve the quality of the data and describe new species. Only when the BINs are properly calibrated by a rigorously quality-checked reference library can the great potential of both classical taxonomic barcoding, metabarcoding, and eDNA ecology be realized.
Quick Spreading of Populations of an Exotic Firefly throughout Spain and Their Recent Arrival in the French Pyrenees
Authors: Koken Marcel , Guzmán-Álvarez José Ramón , Gil-Tapetado Diego , Romo Bedate Miguel Angel , Laurent Geneviève , Rubio Lucas Ezequiel , Rovira Comas Segimon , Wolffler Nicole , Verfaillie Fabien , De Cock Raphaël
Published: January 2022

In August 2018, a firefly (Coleoptera: Lampyridae) of American origin was observed in several localities in Girona (Catalonia, Spain) and was described as Photinus immigrans by Zaragoza-Caballero and Vinolas, 2018. Here, we show that this species dispersed very quickly throughout northeastern Spain and was, in 2020, observed in the French Pyrenees. The animal’s quick progress is documented, and part of its biology is described (dispersion speed, land use, phenology, identification of all life stages). An additional population was localized in Extremadura, and its special status is discussed. We were able to determine its Argentinian–Uruguayan origin and propose, therefore, to consider Photinus immigrans as a synonym of Photinus signaticollis (Blanchard, 1846) (=Photinus immigrans Zaragoza-Caballero and Viñolas, 2018, syn. nov.). Our data clearly show that at least the Catalan and French populations are spreading very quickly and are able to settle permanently if adequate ecosystems are found. The species is highly expansive and may well be invasive; our citizen science platforms are ideally suited to monitor their progress throughout Spain and France. This is important for avoiding future ecological problems with diverse native faunas, such as glow-worms, fireflies and earthworms. If no ways are found to stop the species’ progression, the animals will quite probably invade substantial areas of France, Spain and the rest of Europe in the years to come.