bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Prenatal Whole-Exome Sequencing to Identify a Novel Heterozygous Synonymous Variant in NIPBL in a Fetus With Cornelia de Lange Syndrome
Authors: Qiao Fengchang , Zhang Cuiping , Wang Yan , Liu Gang , Shao Binbin , Hu Ping , Xu Zhengfeng
Published: February 2021

Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder characterized by a wide spectrum of abnormalities, including craniofacial dysmorphism, upper limb anomalies, pre- and post-natal growth restrictions, hirsutism and intellectual disability. Approximately 60% of cases are caused by NIPBL variants. Herein we report on a prenatal case presented with bilateral upper-extremity malformations and cardiac defects. Whole-exome sequencing (WES) was performed on the fetus–parental trio and a de novo heterozygous synonymous variant in NIPBL [chr5:37020979; NM_133433.4: c.5328G>A, p. (Gln1776=)] was identified. Reverse transcriptase–polymerase chain reaction (RT–PCR) was conducted to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (103 bp) by disrupting the splice-donor site and changed the reading frame with the insertion of at least three stop codons. Our finding not only expands the mutation spectrum of NIPBL gene but also establishes the crucial role of WES in searching for underlying genetic variants. In addition, our research raises the important issue that synonymous mutations may be potential pathogenic variants and should not be neglected in clinical diagnoses.
The Impact of Vessels on Humpback Whale Behavior: The Benefit of Added Whale Watching Guidelines
Authors: Currie Jens J. , McCordic Jessica A. , Olson Grace L. , Machernis Abigail F. , Stack Stephanie H.
Published: February 2021

The concurrent increase in marine tourism and vessel traffic around the world highlights the need for developing responsible whale watching guidelines. To determine the impact of vessel presence on humpback whale behaviors in Maui Nui, a land-based study was conducted from 2015 to 2018 in Maui, Hawai'i. Theodolite tracks were used to summarize humpback whale swim speed, respiration rate, dive time, and path directness to determine the potential impacts of various types of vessel presence on whale behavior. Vessel presence, proximity, and approach type in conjunction with biological parameters were used in a generalized additive modeling framework to explain changes in whale behaviors. The results presented here show increases in swim speed, respiration rate, and path directness in conjunction with decreasing dive times, which has been shown to be an energetically demanding avoidance strategy. These observations, in conjunction with increasing awareness on the implication of non-lethal effects of human disturbance and changing oceanic environments on humpback whales, highlights the need for a pre-cautionary approach to management. Stricter guidelines on whale watching will limit the level of disturbance to individual humpback whales in Hawai'i and ensure they maintain the fitness required to compensate for varying ecological and anthropogenic conditions.
Fish Specialize Their Metabolic Performance to Maximize Bioenergetic Efficiency in Their Local Environment: Conspecific Comparison Between Two Stocks of Pacific Chub Mackerel (Scomber japonicus)
Authors: Guo Chenying , Ito Shin-ichi , Yoneda Michio , Kitano Hajime , Kaneko Hitoshi , Enomoto Megumi , Aono Tomoya , Nakamura Masahiro , Kitagawa Takashi , Wegner Nicholas C. , Dorval Emmanis
Published: February 2021

Species-specific ecological traits in fishes are likely to vary between populations or stocks due to differences in regional oceanic conditions, such as latitudinal temperature. We examined potential intraspecific differences in the swimming performance and metabolism of Pacific chub mackerel (Scomber japonicus) from the Northwest and Northeast Pacific stocks, which are distributed on opposite sides of the North Pacific at similar latitudes, but where the temperature contrast is large. Swimming bioenergetics and metabolic data of Northwest stock mackerel were measured at 14, 18, and 24°C using variable-speed swim-tunnel respirometers, and then the resulting bioenergetic parameters were compared with previous findings from the Northeast stock. At a given size, the maximum sustainable swimming speed (Umax) of the Northwest stock showed no significant difference compared to the Northeast stock at 18 and 24°C, but was lower at 14°C. In addition, the oxygen consumption rate (MO2) of the Northwest stock showed lower mass dependence and different temperature dependence at a given swimming speed than in the Northeast stock. Combined with stock-specific data on growth and experienced temperatures in the wild, these bioenergetic differences indicate that the swimming performance and metabolism of the two stocks are specific to their local environment to maximize bioenergetic efficiency.
Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models
Authors: Zhang Song , Zhang Yingmiao , Gan Lu , Wei Fen , Chai Bao , A Aljaafreh Amaneh Abdel Hafez , Liu Xinxin , Duan Xiaoru , Jiang Jian , Wang Xin , He Mengwen , Huang Xian , Cai Huahua , Chen Tie , Chen Hongxiang
Published: February 2021

Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal infections correlate with higher serum progesterone (P4) levels and lower IL-1β levels in cervical secretions. We used murine infection model and THP-1 cells to determine whether P4 exerts anti-inflammatory effects on gonococcal infections. In the murine infection model, P4 (1 mg/day) inhibited the inflammatory effects induced by gonococcal infections which led to decreased neutrophil infiltration, reduced polymorphonuclear neutrophils (PMNs) numbers, IL-1β, TNF-α, and IL-6 levels in vaginal secretions. In addition, P4 down-regulated the mRNA and protein levels of NLRP3, associated with lower mRNA levels of pro-IL-1β, repressed caspase-1 activity in genital tissues and THP-1 cells. Moreover, P4 suppressed the phosphorylation levels of NF-κB and attenuated Neisseria gonorrhoeae (N. gonorrhoeae, gonococci or GC)-induced ROS generation. This is consistent with the two signals required for activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. In conclusion, our result shows that P4 suppresses the gonococci induced-inflammation, especially through the NLRP3 inflammasome pathway, and partially explains the pathogenesis of asymptomatic GC infection in women.
In vitro Selection of Probiotics for Microbiota Modulation in Normal-Weight and Severely Obese Individuals: Focus on Gas Production and Interaction With Intestinal Epithelial Cells
Authors: Nogacka Alicja Maria , de los Reyes-Gavilán Clara G. , Arboleya Silvia , Ruas-Madiedo Patricia , Martínez-Faedo Ceferino , Suarez Adolfo , He Fang , Harata Gaku , Endo Akihito , Salazar Nuria , Gueimonde Miguel
Published: February 2021

The intestinal microbiota plays important roles in the maintenance of health. Strategies aiming at its modulation, such as probiotics, have received a deal of attention. Several strains have been studied in different in vitro models; however, the correlation of results obtained with the in vivo data has been limited. This questions the usefulness of such in vitro selection models, traditionally relying on over-simplified tests, not considering the influence of the accompanying microbiota or focusing on microbiota composition without considering functional traits. Here we assess the potential of six Bifidobacterium, Lactobacillus and Lacticaseibacillus strains in an in vitro model to determine their impact on the microbiota not just in terms of composition but also of functionality. Moreover, we compared the responses obtained in two different population groups: normal-weight and severely obese subjects. Fecal cultures were conducted to evaluate the impact of the strains on specific intestinal microbial groups, on the production of short-chain fatty acids, and on two functional responses: the production of gas and the interaction with human intestinal epithelial cells. The response to the different probiotics differed between both human groups. The addition of the probiotic strains did not induce major changes on the microbiota composition, with significant increases detected almost exclusively for the species added. Higher levels of gas production were observed in cultures from normal-weight subjects than in the obese population, with some strains being able to significantly reduce gas production in the latter group. Moreover, in obese subjects all the Bifidobacterium strains tested and Lacticaseibacillus rhamnosus GG were able to modify the response of the intestinal cells, restoring values similar to those obtained with the microbiotas of normal-weight subjects. Our results underline the need for the screening and selection of probiotics in a target-population specific manner by using appropriate in vitro models before enrolling in clinical intervention trials.
Genetic Plurality of OXA/NDM-Encoding Features Characterized From Enterobacterales Recovered From Czech Hospitals
Authors: Chudejova Katerina , Kraftova Lucie , Mattioni Marchetti Vittoria , Hrabak Jaroslav , Papagiannitsis Costas C. , Bitar Ibrahim
Published: February 2021

The aim of this study was to characterize fourEnterobacteralesco-producing NDM- and OXA-48-like carbapenemases from Czech patients with travel history or/and previous hospitalization abroad.Klebsiella pneumoniaeisolates belonged to “high risk” clones ST147, ST11, and ST15, while theEscherichia coliisolate was assigned to ST167. All isolates expressed resistance against most β-lactams, including carbapenems, while retaining susceptibility to colistin. Furthermore, analysis of WGS data showed that all four isolates co-produced OXA-48- and NDM-type carbapenemases, in different combinations (Kpn47733:blaNDM–5+blaOXA–181; Kpn50595:blaNDM–1+blaOXA–181; Kpn51015:blaNDM–1+blaOXA–244; Eco52418:blaNDM–5+blaOXA–244). In Kpn51015, theblaOXA–244was found on plasmid p51015_OXA-244, while the respective gene was localized in the chromosomal contig ofE. coliEco52418. On the other hand,blaOXA–181was identified on a ColKP3 plasmid in isolate Kpn47733, while ablaOXA–181-carrying plasmid being an IncX3-ColKP3 fusion was identified in Kpn50595. TheblaNDM–1gene was found on two different plasmids, p51015_NDM-1 belonging to a novel IncH plasmid group and p51015_NDM-1 being an IncFK1-FIB replicon. Furthermore, theblaNDM–5was found in two IncFII plasmids exhibiting limited nucleotide similarity to each other. In both plasmids, the genetic environment ofblaNDM–5was identical. Finally, in all four carbapenemase-producing isolates, a diverse number of additional replicons, some of these associated with important resistance determinants, likeblaCTX–M–15,arr-2andermB, were identified. In conclusion, this study reports the first description of OXA-244-producingEnterobacteralesisolated from Czech hospitals. Additionally, our findings indicated the genetic plurality involved in the acquisition and dissemination of determinants encoding OXA/NDM carbapenemases.
Specific Oscillatory Power Changes and Their Efficacy for Determining Laterality in Mesial Temporal Lobe Epilepsy: A Magnetoencephalographic Study
Authors: Tanoue Yuta , Uda Takehiro , Hoshi Hideyuki , Shigihara Yoshihito , Kawashima Toshiyuki , Nakajo Kosuke , Tsuyuguchi Naohiro , Goto Takeo
Published: February 2021

Appropriate determination of the epileptic focus and its laterality are important for the diagnosis of mesial temporal lobe epilepsy (MTLE). The aims of this study are to establish a specific oscillatory distribution and laterality of the oscillatory power in unilateral MTLE with frequency analysis of magnetoencephalography (MEG), and to confirm their potential to carry significant information for determining lateralization of the epileptic focus. Thirty-five patients with MTLE [left (LtMTLE), 16; right (RtMTLE), 19] and 102 healthy control volunteers (CTR) were enrolled. Cortical oscillatory powers were compared among the groups by contrasting the source images using a one-way ANOVA model for each frequency band. Further, to compare the lateralization of regional oscillatory powers between LtMTLEs and RtMTLEs, the laterality index (LI) was calculated for four brain regions (frontal, temporal, parietal, and occipital) in each frequency band, which were compared between patient groups (LtMTLE, RtMTLE, and CTR), and used for machine learning prediction of the groups with support vector machine (SVM) with linear kernel function. Significant oscillatory power differences between MTLE and CTR were found in certain areas. In the theta to high-frequency oscillation bands, there were marked increases in the parietal lobe, especially on the left side, in LtMTLE. In the theta, alpha, and high-gamma bands, there were marked increases in the parietal lobe, especially on the right side in RtMTLE. Compared with CTR, LIs were significantly higher in 24/28 regions in LtMTLE, but lower in 4/28 regions and higher in 10/28 regions in RtMTLE. LI at the temporal lobe in the theta band was significantly higher in LtMTLE and significantly lower in RtMTLE. Comparing LtMTLE and RtMTLE, there were significant LI differences in most regions and frequencies (21/28 regions). In all frequency bands, there were significant differences between LtMTLE and RtMTLE in the temporal and parietal lobes. The leave-one-out cross-validation of the linear-SVM showed the classification accuracy to be over 91%, where the model had high specificity over 96% and mild sensitivity ~68–75%. Using MEG frequency analysis, the characteristics of the oscillatory power distribution in the MTLE were demonstrated. Compared with CTR, LIs shifted to the side of the epileptic focus in the temporal lobe in the theta band. The machine learning approach also confirmed that LIs have significant predictive ability in the lateralization of the epileptic focus. These results provide useful additional information for determining the laterality of the focus.
Brain-Machine Interfaces to Assist the Blind
Authors: Ptito Maurice , Bleau Maxime , Djerourou Ismaël , Paré Samuel , Schneider Fabien C. , Chebat Daniel-Robert
Published: February 2021

The loss or absence of vision is probably one of the most incapacitating events that can befall a human being. The importance of vision for humans is also reflected in brain anatomy as approximately one third of the human brain is devoted to vision. It is therefore unsurprising that throughout history many attempts have been undertaken to develop devices aiming at substituting for a missing visual capacity. In this review, we present two concepts that have been prevalent over the last two decades. The first concept is sensory substitution, which refers to the use of another sensory modality to perform a task that is normally primarily sub-served by the lost sense. The second concept is cross-modal plasticity, which occurs when loss of input in one sensory modality leads to reorganization in brain representation of other sensory modalities. Both phenomena are training-dependent. We also briefly describe the history of blindness from ancient times to modernity, and then proceed to address themeansthat have been used to help blind individuals, with an emphasis on modern technologies, invasive (various type of surgical implants) and non-invasive devices. With the advent of brain imaging, it has become possible to peer into the neural substrates of sensory substitution and highlight the magnitude of the plastic processes that lead to a rewired brain. Finally, we will address the important question of the value and practicality of the available technologies and future directions.
Pain Relief Dependent on IL-17–CD4+ T Cell–β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy
Authors: Xu Zihang , Zhu Yangzhuangzhuang , Shen Jun , Su Lin , Hou Yifei , Liu Mingxi , Jiao Xiaoning , Chen Xiao , Zhu Shiguo , Lu Yechen , Yao Chao , Wang Lixin , Gong Chenyuan , Ma Zhenzhen , Zou Chunpu , Xu Jianguang
Published: February 2021

Background and purpose

Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17–CD4+ T lymphocyte–β-endorphin axis.

Methods

After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4+ T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and β-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested.

Results

The pain of BPRA was significantly relieved, and the amount of CD4+ T lymphocytes was increased after EA treatment. The release of β-endorphin was up-regulated with the up-regulation of IL-17A in CD4+ T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of β-endorphin and the analgesic effect were almost completely abolished when CD4+ T lymphocytes were depleted.

Conclusion

We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17–CD4+ T lymphocyte–β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.
The Complexity of the cGAS-STING Pathway in CNS Pathologies
Authors: Fryer Amelia L. , Abdullah Amar , Taylor Juliet M. , Crack Peter J.
Published: February 2021

Neuroinflammation driven by type-I interferons in the CNS is well established to exacerbate the progression of many CNS pathologies both acute and chronic. The role of adaptor protein Stimulator of Interferon Genes (STING) is increasingly appreciated to instigate type-I IFN-mediated neuroinflammation. As an upstream regulator of type-I IFNs, STING modulation presents a novel therapeutic opportunity to mediate inflammation in the CNS. This review will detail the current knowledge of protective and detrimental STING activity in acute and chronic CNS pathologies and the current therapeutic avenues being explored.
Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS
Authors: Natale Gianfranco , Limanaqi Fiona , Busceti Carla L. , Mastroiacovo Federica , Nicoletti Ferdinando , Puglisi-Allegra Stefano , Fornai Francesco
Published: February 2021

The classic concept of the absence of lymphatic vessels in the central nervous system (CNS), suggesting the immune privilege of the brain in spite of its high metabolic rate, was predominant until recent times. On the other hand, this idea left questioned how cerebral interstitial fluid is cleared of waste products. It was generally thought that clearance depends on cerebrospinal fluid (CSF). Not long ago, an anatomically and functionally discrete paravascular space was revised to provide a pathway for the clearance of molecules drained within the interstitial space. According to this model, CSF enters the brain parenchyma along arterial paravascular spaces. Once mixed with interstitial fluid and solutes in a process mediated by aquaporin-4, CSF exits through the extracellular space along venous paravascular spaces, thus being removed from the brain. This process includes the participation of perivascular glial cells due to a sieving effect of their end-feet. Such draining space resembles the peripheral lymphatic system, therefore, the term “glymphatic” (glial-lymphatic) pathway has been coined. Specific studies focused on the potential role of the glymphatic pathway in healthy and pathological conditions, including neurodegenerative diseases. This mainly concerns Alzheimer’s disease (AD), as well as hemorrhagic and ischemic neurovascular disorders; other acute degenerative processes, such as normal pressure hydrocephalus or traumatic brain injury are involved as well. Novel morphological and functional investigations also suggested alternative models to drain molecules through perivascular pathways, which enriched our insight of homeostatic processes within neural microenvironment. Under the light of these considerations, the present article aims to discuss recent findings and concepts on nervous lymphatic drainage and blood–brain barrier (BBB) in an attempt to understand how peripheral pathological conditions may be detrimental to the CNS, paving the way to neurodegeneration.
Brain More Resistant to Energy Restriction Than Body: A Systematic Review
Authors: Sprengell Marie , Kubera Britta , Peters Achim
Published: February 2021

The gluco-lipostatic theory and its modern variants assume that blood glucose and energy stores are controlled in closed-loop feedback processes. The Selfish Brain theory is based on the same assumptions, but additionally postulates that the brain, as an independent energy compartment, self-regulates its energy concentration with the highest priority. In some clinical situations these two theories make opposite predictions. To investigate one of these situations, namely caloric restriction, we formulated a hypothesis which, if confirmed, would match the predictions of the Selfish Brain theory—but not those of the gluco-lipostatic theory. Hypothesis: Calorie restriction causes minor mass (energy) changes in the brain as opposed to major changes in the body. We conducted a systematic review of caloric-restriction studies to test whether or not the evaluated studies confirmed this hypothesis. We identified 3,157 records, screened 2,804 works by title or abstract, and analyzed 232 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines, and the pre-defined hypothesis-decision algorithm), 8 papers provided enough information to decide on the hypothesis: In animals, high-energy phosphates were measured by 31P-nuclear magnetic resonance, and organ and total body weights were measured by scales, while in humans organ sizes were determined by magnetic resonance imaging. All 8 decidable papers confirmed the hypothesis, none spoke against it. The evidence presented here clearly shows that the most accurate predictions are possible with a theory that regards the brain as independently self-regulating and as occupying a primary position in a hierarchically organized energy metabolism.
Up and Down States During Slow Oscillations in Slow-Wave Sleep and Different Levels of Anesthesia
Authors: Torao-Angosto Melody , Manasanch Arnau , Mattia Maurizio , Sanchez-Vives Maria V.
Published: February 2021

Slow oscillations are a pattern of synchronized network activity generated by the cerebral cortex. They consist of Up and Down states, which are periods of activity interspersed with periods of silence, respectively. However, even when this is a unique dynamic regime of transitions between Up and Down states, this pattern is not constant: there is a range of oscillatory frequencies (0.1–4 Hz), and the duration of Up vs. Down states during the cycles is variable. This opens many questions. Is there a constant relationship between the duration of Up and Down states? How much do they vary across conditions and oscillatory frequencies? Are there different sub regimes within the slow oscillations? To answer these questions, we aimed to explore a concrete aspect of slow oscillations, Up and Down state durations, across three conditions: deep anesthesia, light anesthesia, and slow-wave sleep (SWS), in the same chronically implanted rats. We found that light anesthesia and SWS have rather similar properties, occupying a small area of the Up and Down state duration space. Deeper levels of anesthesia occupy a larger region of this space, revealing that a large variety of Up and Down state durations can emerge within the slow oscillatory regime. In a network model, we investigated the network parameters that can explain the different points within our bifurcation diagram in which slow oscillations are expressed.
Plant-Derived Food Grade Substances (PDFGS) Active Against Respiratory Viruses: A Systematic Review of Non-clinical Studies
Authors: Umeoguaju Francis U. , Ephraim-Emmanuel Benson C. , Patrick-Iwuanyanwu Kingsley C. , Zelikoff Judith T. , Orisakwe Orish Ebere
Published: February 2021

Human diet comprises several classes of phytochemicals some of which are potentially active against human pathogenic viruses. This study examined available evidence that identifies existing food plants or constituents of edible foods that have been reported to inhibit viral pathogenesis of the human respiratory tract. SCOPUS and PUBMED databases were searched with keywords designed to retrieve articles that investigated the effect of plant-derived food grade substances (PDFGS) on the activities of human pathogenic viruses. Eligible studies for this review were those done on viruses that infect the human respiratory tract. Forty six (46) studies met the specified inclusion criteria from the initial 5,734 hits. The selected studies investigated the effects of different PDFGS on the infectivity, proliferation and cytotoxicity of different respiratory viruses including influenza A virus (IAV), influenza B virus (IBV), Respiratory syncytial virus (RSV), human parainfluenza virus (hPIV), Human coronavirus NL63 (HCoV-NL63), and rhinovirus (RV) in cell lines and mouse models. This review reveals that PDFGS inhibits different stages of the pathological pathways of respiratory viruses including cell entry, replication, viral release and viral-induced dysregulation of cellular homeostasis and functions. These alterations eventually lead to the reduction of virus titer, viral-induced cellular damages and improved survival of host cells. Major food constituents active against respiratory viruses include flavonoids, phenolic acids, tannins, lectins, vitamin D, curcumin, and plant glycosides such as glycyrrhizin, acteoside, geniposide, and iridoid glycosides. Herbal teas such as guava tea, green and black tea, adlay tea, cistanche tea, kuding tea, licorice extracts, and edible bird nest extracts were also effective against respiratory viruses in vitro. The authors of this review recommend an increased consumption of foods rich in these PDFGS including legumes, fruits (e.g berries, citrus), tea, fatty fish and curcumin amongst human populations with high prevalence of respiratory viral infections in order to prevent, manage and/or reduce the severity of respiratory virus infections.
Diffusion Mechanism Modeling of Metformin in Human Organic Cationic Amino Acid Transporter one and Functional Impact of S189L, R206C, and G401S Mutation
Authors: Cano Leydy , Soto-Ospina Alejandro , Araque Pedronel , Caro-Gomez Maria Antonieta , Parra-Marin Maria Victoria , Bedoya Gabriel , Duque Constanza
Published: February 2021

Metformin used as a first-line drug to treat Type 2 Diabetes Mellitus is transported via organic cation channels to soft tissues. Mutations in the SLC22A1 gene, such as Gly401Ser, Ser189Leu, and Arg206Cys, may affect the drug’s therapeutic effect on these patients. This study aims at proposing a potential structural model for drug interactions with the hOCT1 transporter, as well as the impact of these mutations at both topological and electronic structure levels on the channel’s surface, from a chemical point of view with, in addition to exploring the frequency distribution. To chemically understand metformin diffusion, we used an open model from the protein model database, with ID PM0080367, viewed through UCSF Chimera. The effect of the mutations was assessed using computational hybrid Quantum Mechanics/Molecular Mechanics, based on the Austin Model 1 semi-empirical method using Spartan 18’ software. The results demonstrate coupling energy for metformin with amino acids F, W, H and Y, because of the interaction between the metformin dication and the electron cloud of π orbitals. The mutations analyzed showed changes in the chemical polarity and topology of the structure. The proposed diffusion model is a possible approach to the interaction mechanism between metformin and its transporter, as well as the impacts of variants, suggesting structural changes in the action of the drug. Metformin efficacy considerably varies from one patient to another; this may be largely attributed to the presence of mutations on the SLC22A1 gene. This study aims at proposing a potential structural model for metformin-hOCT1 (SLC22A1) transporter interaction, as well as the identification of the effect of mutations G401S (rs34130495), S189L (rs34104736), and R206C (616C > T) of the SLC22A1 gene at the topological and electronic structure levels on the channel surfaces, from a chemical viewpoint. Our results demonstrated that the coupling energies for metformin with aromatic amino acids F, W, H and Y, because of the interaction between the metformin dication and the electron cloud of π orbitals. Changes in the chemical environment’s polarity and the structure’s topology were reported in the mutations assessed. The diffusion model proposed is a potential approach for the mechanism of interaction of metformin with its transporter and the effects of variants on the efficacy of the drug in the treatment of type 2 diabetes. The assessment of the frequency of these mutations in a sample of Colombian type 2 diabetes patients suggests that different SLC22A1 gene variants might be involved in reduced OCT1 activity in the Colombian population since none of these mutations were detected.
Systematic Transcriptome Analysis Reveals the Inhibitory Function of Cinnamaldehyde in Non-Small Cell Lung Cancer
Authors: Chen Ru , Wu Juan , Lu Chang , Yan Ting , Qian Yu , Shen Huiqing , Zhao Yujing , Wang Jianzhen , Kong Pengzhou , Zhang Xinri
Published: February 2021

Cinnamaldehyde (CA) is the main component extracted from the traditional Chinese medicine cinnamon. Recent studies revealed that CA has antiviral and anti-tumor effects. However, the effect and mechanism of CA on non-small cell lung cancer (NSCLC) through whole transcriptome sequencing integrated analysis have not been systematically investigated. In this study, whole transcriptome sequencing was used to identify differentially expressed messenger RNAs (mRNAs), micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were influenced by CA and screen regulatory pathways. The results showed that CA significantly inhibited proliferation, invasion, and migration, whereas it induced the apoptosis of NSCLC cells. CA inhibited tumor growth in vivo. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that these differentially expressed mRNAs were potentially implicated in the CA-suppressing malignant phenotypes of NSCLC. According to the competing endogenous RNA (ceRNA) hypothesis, a ceRNA network was constructed, including 13 mRNAs, 6 miRNAs, and 11 lncRNAs. Kyoto Encyclopedia of Genes and Genomes analysis of the 13 mRNAs in the ceRNA network showed that suppressors of cytokine signaling 1 (SOCS1), BTG anti-proliferation factor 2 (BTG2), and Bruton tyrosine kinase (BTK) were significantly enriched in the JAK/STAT signaling pathway, RNA degradation, and nuclear factor-κB (NF-κB) signaling pathway related to cancer. These findings indicated that SOCS1, BTG2, and BTK play an essential role in CA against NSCLC. Meanwhile, based on the ceRNA network, three lncRNAs (long intergenic non-protein coding RNA 1504 [LINC01504], LINC01783, and THUMPD3 antisense RNA 1 [THUMPD3-AS1]) and three miRNAs (has-miR-155-5p, has-miR-7-5p, and has-miR-425-5p) associated with SOCS1, BTG2, and BTK may be important in CA against NSCLC. Taken together, the present study demonstrated the activity of CA against lung cancer and its potential use as a therapeutic agent.
Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells
Authors: Herold Jacqueline , Kalucka Joanna
Published: February 2021

Obesity is a worldwide health problem, and as its prevalence increases, so does the burden of obesity-associated co-morbidities like type 2 diabetes or cardiovascular diseases (CVDs). Adipose tissue (AT) is an endocrine organ embedded in a dense vascular network. AT regulates the production of hormones, angiogenic factors, and cytokines. During the development of obesity, AT expands through the increase in fat cell size (hypertrophy) and/or fat cell number (hyperplasia). The plasticity and expansion of AT is related to its angiogenic capacities. Angiogenesis is a tightly orchestrated process, which involves endothelial cell (EC) proliferation, migration, invasion, and new tube formation. The expansion of AT is accelerated by hypoxia, inflammation, and structural remodeling of blood vessels. The paracrine signaling regulates the functional link between ECs and adipocytes. Adipocytes can secrete both pro-angiogenic molecules, e.g., tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or vascular endothelial growth factor (VEGF), and anti-angiogenic factors, e.g., serpins. If the pro-angiogenic molecules dominate, the angiogenesis is dysregulated and the endothelium becomes dysfunctional. However, if anti-angiogenic molecules are overexpressed relative to the angiogenic regulators, the angiogenesis is repressed, and AT becomes hypoxic. Furthermore, in the presence of chronic nutritional excess, endothelium loses its primary function and contributes to the inflammation and fibrosis of AT, which increases the risk for CVDs. This review discusses the current understanding of ECs function in AT, the cross-talk between adipose and ECs, and how obesity can lead to its dysfunction. Understanding the interplay of angiogenesis with AT can be an approach to therapy obesity and obesity-related diseases such as CVDs.
Gly Betaine Surpasses Melatonin to Improve Salt Tolerance in Dalbergia odorifera
Authors: Cisse El Hadji Malick , Miao Ling-Feng , Yang Fan , Huang Jin-Fu , Li Da-Dong , Zhang Juan
Published: February 2021

Salinity is one of the most serious factors limiting plant growth which can provoke significant losses in agricultural crop production, particularly in arid and semi-arid areas. This study aimed to investigate whether melatonin (MT; 0.05 and 0.1 mM), which has pleiotropic roles, has a better effect than glycine betaine (GB; 10 and 50 mM) on providing salt tolerance in a woody plant Dalbergia odorifera T. Chen. Also, the alternative oxidase activity (AOX) in plant subjected to MT or GB under salinity (150 and 250 mM) was evaluated given that the effect of exogenous MT or GB on AOX has not been reported yet. The results showed that the exogenous application of GB on the seedlings of D. odorifera increased the plant growth parameters, relative water content, total of chlorophyll content, and carotenoid content compared with well-watered and MT treatments. Under severe salinity, the seedlings subjected to GB showed, a significant enhancement in water use efficiency, transpiration, and net photosynthetic rate regardless to MT-treated seedlings. The levels of proline and soluble sugar in the seedlings treated with MT or GB decreased significantly under mild and severe salinity correlated with those in salt-stressed seedlings. Furthermore, GB-treated plants exhibited a significant inhibition of malondialdehyde content compared with MT-treated plants. The concentration of thiols and phenolic compounds were significantly enhanced in the leaves of seedlings treated with MT compared with those treated with GB. Under salt stress condition, GB scavenged significantly higher levels of hydrogen peroxide than MT; while under severe salinity, plants subjected to MT showed better scavenging ability for hydroxyl radicals compared with GB-treated seedlings. The results demonstrated also an enhancement of the levels of superoxide dismutase (SOD), guaiacol peroxidase, and AOX activities in seedlings treated with GB or MT compared with salt-stressed plants. The catalase activity (CAT) was increased by 0.05 mM MT and 0.1 mM GB under mild salinity. Meanwhile, the AOX activity under severe salinity was enhanced only by GB 50 mM. The findings of this study suggested that GB-treated seedlings possessed a better salt tolerance in comparison with MT-treated seedlings.
Identification of Vicia Species Native to South Korea Using Molecular and Morphological Characteristics
Authors: Han Seahee , Sebastin Raveendar , Wang XiaoHan , Lee Kyung Jun , Cho Gyu-Taek , Hyun Do Yoon , Chung Jong-Wook
Published: February 2021

Recently, within the Fabaceae family, the Vicia genus has been recognized for its vital role in sustainable agriculture. Vicia species are economically important grain and forage crops. However, the presence of complex morphological characteristics makes identification and recognition of native species difficult. In this study, the possibility of using DNA barcoding regions (ITS2, matK, and rbcL) to distinguish among 19 Vicia taxa (59 accessions) found in South Korea was evaluated. The sequence alignment analysis revealed considerable nucleotide diversity (π) between the loci, in which ITS2 showed the highest mean interspecific distance, whereas there was no intraspecific variability among the barcode regions in 12 of the 19 taxa. Phylogenetic analysis of combined barcoding regions revealed well-resolved phylogeny with the highest species level discrimination. Combinations of barcode loci were also used in classification at the subgenera and section levels. The results revealed that the combined barcoding regions can be used effectively to differentiate the following species: Vicia angustifolia var. segetilis, Vicia bungei, Vicia villosa, Vicia cracca, Vicia dasycarpa, Vicia hirsuta, Vicia tetrasperma, Vicia amurensis, Vicia hirticalycina, and Vicia chosenensis. However, it is difficult to differentiate the species of Vicia unijuga, Vicia unijuga var. kaussanensis, Vicia linearifolia, Vicia unijuga f. angustifolia, Vicia nipponica, Vicia amoena, Vicia venosa var. cuspidata, Vicia pseudo-orobus, and Vicia japonica with the tested barcode regions. These species come under sect. Vicilla and are found to be closely related or species that have recently undergone speciation; thus, it has limitation to distinguish with recommended barcodes. Hence, to differentiate the unclassified species, 39 morphological characteristics were investigated, in which 16 useful characteristics were selected for efficient classification. Finally, the 16 selected morphological useful traits efficiently differentiated all the Vicia species. In conclusion, a combination of barcoding loci together with morphological characteristics of this study efficiently discriminated all the Korean Vicia species.
The Impact of Chair–Team Sociodemographic Dissimilarity on the Relation Between Chair Power and Entrepreneurial Ventures’ R&D Intensity: Evidence From China
Authors: Zheng Yaoyi , Dai Shufen , Li Yueting , Su Yi
Published: February 2021

Contemplating the actual leaders of entrepreneurial firms and socio demographic dissimilarity between leaders and their teams, this study adopts panel data on the entrepreneurial firms of the China’s Growth Enterprise Market and empirically examines the influence of chair power on research and development (R&D) intensity of entrepreneurial firms from the perspective of social identity. The results indicate that chair power positively affects entrepreneurial firms’ R&D intensity. The chair–team sociodemographic dissimilarity moderates the relationship in such a way that chair power is negatively related to entrepreneurial firms’ R&D intensity only when chair–team sociodemographic dissimilarity is high. The execution of robustness checks authenticates the veracity of the empirical results.
Family Resource Dilution in Expanded Families and the Empowerment of Married Only Daughters: Evidence From the Educational Investment in Children in Urban China
Authors: Wang Xiaotao , Feng Xiaotian
Published: February 2021

The One-Child Policy dramatically changed the Chinese family structure, and the literature indicates that only children may have an advantage in terms of family resource dilution. Moreover, as Chinese families traditionally prioritize investing in sons, only daughters are found to have been empowered by the policy because they did not need to compete with their brothers for parental investment. However, the literature is limited to only teenage children when they were still living in their parents' homes. It is unclear whether—when the generation of only children grew up and married—their family structure differed from that of children with siblings and whether married only daughters retained more family resources from their parents. Based on the data analysis of a 2016 survey, “Study of Youths in 12 Cities of Mainland China,” including a sample of 1,007 fathers and 2,168 mothers born between 1975 and 1985, this study explores the empowerment of married only daughters, employing the theory of family resource dilution in expanded Chinese families. Using educational investment in children as an example, and with random intercept models, this study presents empirical evidence that the dilution of family resources in Chinese expanded families still benefits males and patrilineal practices. Thus, this study demonstrates that Chinese families still tend to sacrifice the interests of married daughters to ensure support for their adult sons. However, it also illustrates that married only daughters could still connect to their parents' resources, giving them a relatively dominant position for decision-making regarding the family's educational expenditure on her own children. Thus, this study extends our understanding of the family resource dilution theory to Chinese expanded families, underscoring the need for further research on Chinese only children after they marry and form families of their own.
The Reliability and Agreement of the Fibromyalgia Survey Questionnaire in an Italian Sample of Obese Patients
Authors: Varallo Giorgia , Ghiggia Ada , Arreghini Marco , Capodaglio Paolo , Manzoni Gian Mauro , Giusti Emanuele Maria , Castelli Lorys , Castelnuovo Gianluca
Published: February 2021

The Fibromyalgia Survey Questionnaire (FSQ) was self-administered by a sample of 207 Italian individuals with obesity to screen for fibromyalgia (FM). We aimed to investigate the inter-rater reliability and the agreement in the detection of FM symptomatology between the self-administered FSQ and the clinical interview conducted by a rheumatologist. All the patients were divided randomly into two groups (group A and group B): a rheumatologist first interviewed patients of group A and after 48 h, the patients completed the self-report FSQ. Patients of group B first completed the FSQ and 48 h later were interviewed by a rheumatologist. The agreement between the measurements was good with the Bland-Altman analysis showing low bias scores for the two subscales of the FSQ. Results showed that 33% of the sample satisfied the criteria for a diagnosis of fibromyalgia. The FSQ is a self-reporting measure that showed substantial reliability providing fast screening for FM symptomatology.
China Multi-Center Preschool Autism Project (CMPAP): Design and Methodologies to Identify Clinical Symptom Features and Biomarkers of Autism Spectrum Disorders
Authors: Yang Ting , Zhu Jiang , Li Qiu , Chen Li , Wu Li-Jie , Jia Fei-Yong , Hao Yan , Ke Xiao-Yan , Yi Ming-Ji , Jin Chun-Hua , Chen Jie , Li Ting Yu
Published: February 2021

Background: The etiology of autism spectrum disorder (ASD) has not yet been fully identified, but it seems to be triggered by complex genetic and environmental risk factors. Moreover, the tremendous etiological and clinical differences among individuals with ASD has had a major negative impact on early diagnosis and individualized treatment. Earlier diagnosis of precise clinical subtypes of ASD could lead to individualized treatment and a better prognosis. However, few large-scale epidemiological studies have explored precise clinical subtypes and clinically meaningful biomarkers, especially in China.

Methods and Design: The China Multi-center Preschool Autism Project (CMPAP) includes nearly 3,000 children−1,469 individuals with ASD and 1,499 typically-developing (TD) controls—from 13 cities in China. Using a case-control design, each participant was comprehensively characterized in terms of feeding and disease history, maternal history, family history, clinical core symptoms, comorbidities, biochemical markers, genomics, urine/fecal metabonomics, and intestinal flora. In addition, data on environmental risk factors were obtained using interviews and electronic medical records.

Conclusion: The study was designed to: (1) investigate age at diagnosis and treatment and family and social support for preschool children with ASD in China, (2) develop a more accurate clinical subtype and intervention system for the ICD-11, and (3) find the specific genes and environmental markers of different subtypes, which will help in the development of early diagnosis and individual intervention programs for preschool children with ASD. This study will provide the basis for improving national health policies for ASD in China.
Satisfaction With Life, Mental Health Problems and Potential Alcohol-Related Problems Among Norwegian University Students
Authors: Jensen Pia , Haug Ellen , Sivertsen Børge , Skogen Jens Christoffer
Published: February 2021

Objective: Recent studies have shown that today's college students more than ever are struggling with mental health and alcohol problems. While poor satisfaction with life and mental health problems have been linked to higher alcohol consumption, there is still a lack of studies examining in detail the shape and nature of the relationship between mental health and alcohol consumption.

Aim: To investigate the associations between satisfaction with life, mental health problems and potential alcohol-related problems among Norwegian university students. The shape of the associations was also examined.

Methods: Data were drawn from a 2018 national survey of students in higher education in Norway (the SHoT-study). Associations between satisfaction with life, mental health problems and potential alcohol-related problems (AUDIT; risky and harmful alcohol use) were investigated using logistic regression. Both crude models and models adjusted for age, gender and marital status were conducted. To investigate the shape of the associations, logistic regression with quadric and cubic terms was tested.

Results: Decreased satisfaction with life and increased mental health problems were associated with potential alcohol-related problems. For satisfaction with life, a curvilinear association with risky alcohol use and a linear association with harmful alcohol use was identified. For mental health problems, curvilinear associations were found for both risky and harmful alcohol use.

Conclusion: Many students report potential alcohol-related problems. Students with harmful alcohol use seem to be more at risk of reduced satisfaction with life and increased mental health problems than students with risky alcohol use. Educational institutions may be an ideal setting for raising awareness of mental health issues and responsible alcohol consumption among students. The present study contributes with important information about the shape of the associations between satisfaction with life, mental health problems and potential alcohol-related problems in the student population.