bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Magnesium on Reperfusion Arrhythmias in STEMI Patients, Treated With PPCI. A Systematic Review With a Meta-Analysis and Trial Sequential Analysis
Authors: Szapary Laszlo B. , Szakacs Zsolt , Farkas Nelli , Schonfeld Kristof , Babocsay Dora , Gajer Mate , Kittka Balint , Magyari Balazs , Hegyi Peter , Szokodi Istvan , Horvath Ivan G.
Published: January 2021

Aims: The restoration of coronary circulation plays a crucial role in treating ST-segment elevation myocardial infarction (STEMI), however successful reperfusion with primary percutaneous coronary intervention (PPCI) may induce life-threatening arrhythmias. The relation between myocardial electrical instability, as a background factor in reperfusion arrhythmia, and magnesium administered periprocedurally is still questionable. Several randomized clinical trials have been conducted predominantly in the thrombolysis era. Due to the contradictory results of these studies, there is little evidence of the potential preventive effect of magnesium on reperfusion arrhythmias. The aim of our study is to review and meta-analytically analyze data from all studies published so far in the PPCI era, comparing STEMI patients who have undergone primary PCI and received either magnesium or a placebo before the reperfusion procedure.

Methods and Results: Our meta-analysis follows the points in the PRISMA protocol and, meets all of their criteria. We conducted a search in five scientific databases using the following keyword combination: (myocardial infarction OR myocardial injury OR acute coronary syndrome OR acs OR stemi) AND magnesium. The 7,295 collected publications were filtered with the Endnote program by title, abstract and full-text based on predefined criteria. A statistical analysis was performed on three randomized-controlled trials using three common parameters, involving 336 patients Trial sequential analysis (TSA) was applied to assess the risk of random error associated with sparse data and multiple testing which can affect cumulative meta-analysis. The incidence of ventricular tachycardias (VTs) was not significantly increased in the non-magnesium control group. (OR: 1.36; CI: 0.619; −2.986, P = 0.263). For the ejection fraction (EF), a non-significant decrease was observed in the magnesium group by weighted mean difference calculation. (WMD: 7.262, 95% CI: −0.238; 0.053; P = 0.057). There was significant decrease in the infarct zone wall motion index (IZWMSI) in the magnesium treatment group. (WMD: 0.384, 95% CI: −0.042; 0.811, P = 0.015). Based on the TSA assessments, the results of all parameters are not significant, objectively demonstrating the lack of reasonable data pertaining to our question.

Conclusions: The preventive effect of magnesium on reperfusion arrhythmia associated with primary PCI can still be considered contradictory based on previous studies. In our study, we found, that magnesium is ineffective with a very weak evidence, due to the small number of patients and the biases of the included studies, and a well-designed clinical trial is needed in this area, based on the TSA.
Function and Regulation of Nuclear DNA Sensors During Viral Infection and Tumorigenesis
Authors: Zhang Fan , Yuan Yi , Ma Feng
Published: January 2021

IFI16, hnRNPA2B1, and nuclear cGAS are nuclear-located DNA sensors that play important roles in initiating host antiviral immunity and modulating tumorigenesis. IFI16 triggers innate antiviral immunity, inflammasome, and suppresses tumorigenesis by recognizing double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), damaged nuclear DNA, or cooperatively interacting with multiple tumor suppressors such as p53 and BRCA1. hnRNPA2B1 initiates interferon (IFN)-α/β production and enhances STING-dependent cytosolic antiviral signaling by directly binding viral dsDNA from invaded viruses and facilitating N6-methyladenosine (m6A) modification of cGAS, IFI16, and STING mRNAs. Nuclear cGAS is recruited to double-stranded breaks (DSBs), suppresses DNA repair, and promotes tumorigenesis. This review briefly describes the nuclear functions of IFI16, hnRNPA2B1, and cGAS, and summarizes the transcriptional, post-transcriptional, and post-translational regulation of these nuclear DNA sensors.
Age-Specific Imbalance of Circulating Tfh Cell Subsets and Its Association With Gout-Targeted Kidney Impairment
Authors: Huang Yefei , Wu Xinyu , Gui Lian , Jiang Yutong , Tu Liudan , Li Xiaomin , Jiang Boxiong , Wang Yina , Zheng Xuqi , Wei Qiujing , Li Qiuxia , Ou Jiayong , Chen Zena , Xie Ya , Lin Zhiming , Liao Zetao , Fang Linkai , Qiu Minli , Cao Shuangyan , Gu Jieruo
Published: January 2021

Objective

Gout is a chronic disease characterized by the deposition of monosodium urate (MSU) crystals in tissue. Study with a focus on adaptive immune response remains to be understood although innate immune response has been reported extensively in gout etiology. Our study attempted to investigate the association of gout-related immune cell imbalance with clinical features and comorbidity with renal impairment and the implicated pathogenesis via the assessment of T and B cell subsets in different activity phases or with immune effects combined with the analyses of clinical parameters.

Methods

Fifty-eight gout patients and 56 age- and sex-matched healthy individuals were enrolled. To learn the roles of circulating T cells, a lymphocyte profile incorporating 32 T cell subsets was tested from isolated freshly peripheral blood monocyte cells (PBMCs) with multiple-color flow cytometry. Furthermore, the collected clinical features of participants were used to analyze the characteristics of these differential cell subsets. Stratified on the basis of the level of creatinine (Cr, enzymatic method), all patients were categorized into Crlow (Cr ≤ 116 μmol/L) and Crhi (Cr > 116 μmol/L) groups to exploit whether these gout-associated T cell subsets were functional in gout-targeted kidney dysfunction. The differentiation of B cells was investigated in gout patients.

Results

Our results show that CD 4+ T cells, Th2 cells, and Tc2 cells were upregulated, whereas Tc17 cells were downregulated. Tfh cells skewed toward the polarization of Tfh2 cells. Specifically, Tfh2 cells increased, but Tfh1 cells decreased, accompanied with aging for gout patients, suggesting that age might trigger the skewing of Tfh1/Tfh2 cell subsets to influence gout development. Moreover, Tfh2 cells were connected to renal dysfunction as well. No alterations of B cell subsets were observed in patients when compared to controls.

Conclusions

Our data demonstrate age-specific dysfunctions of Tfh1/2 cells in gout occurrence, and Tfh2 cell upregulation is associated with gout-targeted renal dysfunction. However, Tfh2 cells may function in auto-inflammatory gout independent of helping B differentiation, and an in-depth study remains to be conducted.
Evaluation of Wearable Technology in Dementia: A Systematic Review and Meta-Analysis
Authors: Cote Alanna C. , Phelps Riley J. , Kabiri Nina Shaafi , Bhangu Jaspreet S. , Thomas Kevin “Kip”
Published: January 2021

Background: The objective of this analysis was to systematically review studies employing wearable technology in patients with dementia by quantifying differences in digitally captured physiological endpoints.

Methods: This systematic review and meta-analysis was based on web searches of Cochrane Database, PsycInfo, Pubmed, Embase, and IEEE between October 25–31st, 2017. Observational studies providing physiological data measured by wearable technology on participants with dementia with a mean age ≥50. Data were extracted according to PRISMA guidelines and methodological quality assessed independently using Downs and Black criteria. Standardized mean differences between cases and controls were estimated using random-effects models.

Results: Forty-eight studies from 18,456 screened abstracts (Dementia: n = 2,516, Control: n = 1,224) met inclusion criteria for the systematic review. Nineteen of these studies were included in one or multiple meta-analyses (Dementia: n = 617, Control: n = 406). Participants with dementia demonstrated lower levels of daily activity (standardized mean difference (SMD), −1.60; 95% CI, −2.66 to −0.55), decreased sleep efficiency (SMD, −0.52; 95% CI, −0.89 to −0.16), and greater intradaily circadian variability (SMD, 0.46; 95% CI, 0.27 to 0.65) than controls, among other measures. Statistical between-study heterogeneity was observed, possibly due to variation in testing duration, device type or patient setting.

Conclusions and Relevance: Digitally captured data using wearable devices revealed that adults with dementia were less active, demonstrated increased fragmentation of their sleep-wake cycle and a loss of typical diurnal variation in circadian rhythm as compared to controls.
Automatic Recognition of Auditory Brainstem Response Characteristic Waveform Based on Bidirectional Long Short-Term Memory
Authors: Chen Cheng , Zhan Li , Pan Xiaoxin , Wang Zhiliang , Guo Xiaoyu , Qin Handai , Xiong Fen , Shi Wei , Shi Min , Ji Fei , Wang Qiuju , Yu Ning , Xiao Ruoxiu
Published: January 2021

Background: Auditory brainstem response (ABR) testing is an invasive electrophysiological auditory function test. Its waveforms and threshold can reflect auditory functional changes in the auditory centers in the brainstem and are widely used in the clinic to diagnose dysfunction in hearing. However, identifying its waveforms and threshold is mainly dependent on manual recognition by experimental persons, which could be primarily influenced by individual experiences. This is also a heavy job in clinical practice.

Methods: In this work, human ABR was recorded. First, binarization is created to mark 1,024 sampling points accordingly. The selected characteristic area of ABR data is 0–8 ms. The marking area is enlarged to expand feature information and reduce marking error. Second, a bidirectional long short-term memory (BiLSTM) network structure is established to improve relevance of sampling points, and an ABR sampling point classifier is obtained by training. Finally, mark points are obtained through thresholding.

Results: The specific structure, related parameters, recognition effect, and noise resistance of the network were explored in 614 sets of ABR clinical data. The results show that the average detection time for each data was 0.05 s, and recognition accuracy reached 92.91%.

Discussion: The study proposed an automatic recognition of ABR waveforms by using the BiLSTM-based machine learning technique. The results demonstrated that the proposed methods could reduce recording time and help doctors in making diagnosis, suggesting that the proposed method has the potential to be used in the clinic in the future.
Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury
Authors: Huntemer-Silveira Anne , Patil Nandadevi , Brickner Megan A. , Parr Ann M.
Published: January 2021

A major consequence of traumatic brain and spinal cord injury is the loss of the myelin sheath, a cholesterol-rich layer of insulation that wraps around axons of the nervous system. In the central nervous system (CNS), myelin is produced and maintained by oligodendrocytes. Damage to the CNS may result in oligodendrocyte cell death and subsequent loss of myelin, which can have serious consequences for functional recovery. Demyelination impairs neuronal function by decelerating signal transmission along the axon and has been implicated in many neurodegenerative diseases. After a traumatic injury, mechanisms of endogenous remyelination in the CNS are limited and often fail, for reasons that remain poorly understood. One area of research focuses on enhancing this endogenous response. Existing techniques include the use of small molecules, RNA interference (RNAi), and monoclonal antibodies that target specific signaling components of myelination for recovery. Cell-based replacement strategies geared towards replenishing oligodendrocytes and their progenitors have been utilized by several groups in the last decade as well. In this review article, we discuss the effects of traumatic injury on oligodendrocytes in the CNS, the lack of endogenous remyelination, translational studies in rodent models promoting remyelination, and finally human clinical studies on remyelination in the CNS after injury.
Long Noncoding RNA LINC-PINT Suppresses Cell Proliferation, Invasion, and EMT by Blocking Wnt/β-Catenin Signaling in Glioblastoma
Authors: Zhu Hanshuo , Chen Zheng , Shen Lin , Tang Tianchi , Yang Min , Zheng Xuesheng
Published: January 2021

Background:Glioblastoma (GBM) represents the most aggressive glioma with high invasive potential. Recent studies proved the involvement of epithelial-mesenchymal transition (EMT) process in increasing the malignancy and invasiveness of GBM. LncRNAs have been verified to play pivotal roles in human disease including GBM. However, the molecular mechanisms of lncRNA-mediated EMT in GBM remain largely unknown. LINC-PINT, a LncRNA which has never been studied in GBM before, was predicted to be negatively associated with EMT in GBM. This study aimed to explore the biological function and the EMT relevance of LINC-PINT in GBM and further explore the molecular mechanism.

Methods:The bioinformatic prediction data of LINC-PINT in GBM was derived from The Cancer Genome Atlas (TCGA) database by R software and GEPIA website. qRT-PCR assay was performed to detect the expression level of LINC-PINT in GBM cell lines. Cell counting kit-8 (CCK8), clone formation, transwell, and wound healing assays were performed to determine the biological function of LINC-PINTin vivo. Tumor xenograft experiment and tumor peritoneal metastasis experiments were performed to verify thein vivofunction. Western blot and immunofluorescence staining assays were carried out to detect the relevance of LINC-PINT with EMT and Wnt/β-catenin signaling. Rescue assays were performed to check the regulation mechanism of LINC-PINT/Wnt signaling/EMT axis in GBM.

Results:LINC-PINT was downregulated in GBM cell lines. LINC-PINT suppressed cell progression, invasion, and EMT in GBM. LINC-PINT blocked Wnt/β-catenin signaling in GBM.

Conclusion:LINC-PINT suppressed cell proliferation, invasion, and EMT by blocking Wnt/β-catenin signaling in GBM.
A Review on Plant Bioactive Compounds and Their Modes of Action Against Coronavirus Infection
Authors: Remali Juwairiah , Aizat Wan Mohd
Published: January 2021

The rapid outbreak of coronavirus disease 2019 (COVID-19) has demonstrated the need for development of new vaccine candidates and therapeutic drugs to fight against the underlying virus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Currently, no antiviral treatment is available to treat COVID-19 as treatment is mostly directed to only relieving the symptoms. Retrospectively, herbal medicinal plants have been used for thousands of years as a medicinal alternative including for the treatment of various viral illnesses. However, a comprehensive description using various medicinal plants in treating coronavirus infection has not to date been described adequately, especially their modes of action. Most other reports and reviews have also only focused on selected ethnobotanical herbs such as Traditional Chinese Medicine, yet more plants can be considered to enrich the source of the anti-viral compounds. In this review, we have screened and identified potential herbal medicinal plants as anti-coronavirus medication across major literature databases without being limited to any regions or ethnobotanic criteria. As such we have successfully gathered experimentally validated in vivo, in vitro, or in silico findings of more than 30 plants in which these plant extracts or their related compounds, such as those of Artemisia annua L., Houttuynia cordata Thunb., and Sambucus formosana Nakai, are described through their respective modes of action against specific mechanisms or pathways during the viral infection. This includes inhibition of viral attachment and penetration, inhibition of viral RNA and protein synthesis, inhibition of viral key proteins such as 3-chymotrypsin-like cysteine protease (3CLpro) and papain-like protease 2 (PLpro), as well as other mechanisms including inhibition of the viral release and enhanced host immunity. We hope this compilation will help researchers and clinicians to identify the source of appropriate anti-viral drugs from plants in combating COVID-19 and, ultimately, save millions of affected human lives.
Initial Characterization of Stressed Transgenic Mice With Cardiomyocyte-Specific Overexpression of Protein Phosphatase 2C
Authors: Bollmann Paula , Werner Franziska , Jaron Marko , Bruns Tom A. , Wache Hartmut , Runte Jochen , Boknik Peter , Kirchhefer Uwe , Müller Frank U. , Buchwalow Igor B. , Rothemund Sven , Neumann Joachim , Gergs Ulrich
Published: January 2021

As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated mice with cardiac-specific overexpression of PP2Cβ (PP2C-TG) and compared them with littermate wild type mice (WT) serving as a control. Cardiac fibrosis was noted histologically in PP2C-TG. Collagen 1a, interleukin-6 and the natriuretic peptides ANP and BNP were augmented in PP2C-TG vs. WT (p< 0.05). Left atrial preparations from PP2C-TG were less resistant to hypoxia than atria from WT. PP2C-TG maintained cardiac function after the injection of lipopolysaccharide (LPS, a model of sepsis) and chronic isoproterenol treatment (a model of heart failure) better than WT. Crossbreeding of PP2C-TG mice with PP2A-TG mice (a genetic model of heart failure) resulted in double transgenic (DT) mice that exhibited a pronounced increase of heart weight in contrast to the mild hypertrophy noted in the mono-transgenic mice. The ejection fraction was reduced in PP2C-TG and in PP2A-TG mice compared with WT, but the reduction was the highest in DT compared with WT. PP2A enzyme activity was enhanced in PP2A-TG and DT mice compared with WT and PP2C-TG mice. In summary, cardiac overexpression of PP2Cβ and co-overexpression of both the catalytic subunit of PP2A and PP2Cβ were detrimental to cardiac function. PP2Cβ overexpression made cardiac preparations less resistant to hypoxia than WT, leading to fibrosis, but PP2Cβ overexpression led to better adaptation to some stressors, such as LPS or chronic β-adrenergic stimulation. Hence, the effect of PP2Cβ is context sensitive.
Cryptotanshinone Is a Intervention for ER-Positive Breast Cancer: An Integrated Approach to the Study of Natural Product Intervention Mechanisms
Authors: Li Huayao , Gao Chundi , Liang Qing , Liu Cun , Liu Lijuan , Zhuang Jing , Yang Jing , Zhou Chao , Feng Fubin , Sun Changgang
Published: January 2021

Background: Resistance to endocrine therapy has hampered clinical treatment in patients with ER-positive breast cancer (BRCA). Studies have confirmed that cryptotanshinone (CPT) has cytotoxic effects on BRCA cells and can significantly inhibit the proliferation and metastasis of ER-positive cancer cells.

Methods: We analyzed the gene high-throughput data of ER-positive and negative BRCA to screen out key gene targets for ER-positive BRCA. Finally, the effects of CPT on BRCA cells (MCF-7 and MDA-MB-231) were examined, and quantitative RT-PCR was used to evaluate the expression of the key targets during CPT intervention.

Results: A total of 169 differentially expressed genes were identified, and revealed that CPT affects the ER-positive BRCA cells by regulating CDK1, CCNA2, and ESR1. The overall experimental results initially show that MCF-7 cells were more sensitive to CPT than MDA-MB-231 cells, and the expression of ESR1 was not affected in the BRCA cells during CPT intervention, while the expression of CDK1 and CCNA2 were significantly down-regulated.

Conclusion: CPT can inhibit the proliferation and migration of BRCA cells by regulating CDK1, CCNA2, and ESR1, especially in ER-positive BRCA samples. On the one hand, our research has discovered the possible mechanism that CPT can better interfere with ER+ BRCA; on the other hand, the combination of high-throughput data analysis and network pharmacology provides valuable information for identifying the mechanism of drug intervention in the disease.
Simultaneous Activation of Erk1/2 and Akt Signaling is Critical for Formononetin-Induced Promotion of Endothelial Function
Authors: Wu Jinjun , Kong Muyan , Lou Yanmei , Li Leyan , Yang Chunlin , Xu Huifang , Cui Yuqi , Hao Hong , Liu Zhenguo
Published: January 2021

Formononetin (FMNT) is a major bioactive compound from Astragalus membranaceus (Fisch.) Bunge, and has been widely used to treat conditions related to vascular insufficiency. However, the molecular mechanism for the therapeutic effect has not been well defined. This study aimed to investigate the effect and mechanism of FMNT on endothelial function. The potential targets and signaling pathways of FMNT in the setting of ischemia were predicted using network pharmacology analysis. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro studies and C57BL/6 mice were used for in vivo experiments. The results of the network pharmacology analysis showed that multiple signaling molecules including MAPK and PI3K-Akt pathways could be involved in the pharmacological actions of FMNT against ischemic diseases. The experimental validation data showed that FMNT significantly promoted the growth, proliferation, migration and tube formation of HUVECs in association with activation of endothelial nitric oxide synthase (eNOS) and promotion of intracellular nitric oxide (NO) production. FMNT also markedly activated Erk1/2 and Akt signaling in HUVECs. The enhanced endothelial function by FMNT was abolished when the cells were pre-treated with eNOS inhibitor. FMNT-induced eNOS/NO activation, endothelial function and angiogenesis was also effectively attenuated when Erk1/2 or Akt signaling pathway was inhibited. In addition, FMNT significantly promoted wound healing in C57BL/6 mice associated with activation of Erk1/2 and Akt signaling. Enhanced wound healing by FMNT in mice was prevented when eNOS-, Erk1/2, or Akt-medicated signaling was inhibited. Moreover, when Akt signaling was inhibited in HUVECs, FMNT was still able to activate Erk1/2 signaling without promotion of endothelial function. Similarly, FMNT could activate Akt signaling with no change in endothelial function when Erk1/2 signaling was attenuated in HUVECs. Conclusively, the present study demonstrated that FMNT significantly enhanced endothelial function and promoted angiogenesis in vitro and in vivo through activating Erk1/2- and Akt-mediated eNOS/NO signaling pathway. The data also suggested that simultaneous activation of Erk1/2 and Akt signaling was required for FMNT-induced promotion of endothelial function. Results from the present study might provide support and evidence for the application of FMNT during the clinical treatment of conditions related to vascular insufficiency.
miRNome profiling of LSC-enriched CD34+CD38−CD26+ fraction in Ph+ CML-CP samples from Argentinean patients: a potential new pharmacogenomic tool
Authors: Ruiz María Sol , Sánchez María Belén , Bonecker Simone , Furtado Carolina , Koile Daniel , Yankilevich Patricio , Cranco Santiago , Custidiano María del Rosario , Freitas Josefina , Moiraghi Beatriz , Pérez Mariel Ana , Pavlovsky Carolina , Varela Ana Inés , Ventriglia Verónica , Sánchez Ávalos Julio César , Larripa Irene , Zalcberg Ilana , Mordoh José , Valent Peter , Bianchini Michele
Published: January 2021

Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of LSC-enriched CD34+CD38−CD26+ and normal hematopoietic stem cells (HSC) fractions obtained from the same chronic phase (CP) CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC-enriched CD34+CD38−CD26+ and HSC fractions from CML-CP patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML-CP patients, despite the absence of BCR-ABL1 expression, showed an altered miRNome. We confirmed by RT-qPCR that the levels of miR-196a-5p were increased more than nine-fold in CD26+ (BCR-ABL1+) vs. CD26− (BCR-ABL1−) CD34+CD38− fractions from CML-CP patients at diagnosis, and in silico analysis revealed a significant association to lipid metabolism and hematopoiesis functions. In the light of recent descriptions of increased oxidative metabolism in CML LSC-enriched fractions, these results serve as a guide for future functional studies that evaluate the role of microRNAs in this process. Metabolic vulnerabilities in LSCs open the road for new therapeutic strategies. This is the first report of the miRNome of CML-CP CD34+CD38− fractions that distinguishes between CD26+ (BCR-ABL1+) and their CD26− (BCR-ABL1-) counterparts, providing valuable data for future studies.
Overview of OxLDL and Its Impact on Cardiovascular Health: Focus on Atherosclerosis
Authors: Poznyak Anastasia V. , Nikiforov Nikita G. , Markin Alexander M. , Kashirskikh Dmitry A. , Myasoedova Veronika A. , Gerasimova Elena V. , Orekhov Alexander N.
Published: January 2021

Cardiovascular pathologies maintain the leading position in mortality worldwide. Atherosclerosis is a chronic disease that can result in a variety of serious complications, such as myocardial infarction, stroke, and cardiovascular disease. Inflammation and lipid metabolism alterations play a crucial role in atherogenesis, but the details of relationships and causality of these fundamental processes remain not clear. The oxidation of LDL was considered the main atherogenic modification of LDL within the vascular wall for decades. However, recent investigations provided a growing body of evidence in support of the multiple LDL modification theory. It suggests that LDL particles undergo numerous modifications that change their size, density, and chemical properties within the blood flow and vascular wall. Oxidation is the last stage in this cascade resulting in the atherogenic properties. Moreover, recent investigations have discovered that oxLDL may have both anti-inflammatory and pro-inflammatory properties. Oxidized LDL can trigger inflammation through the activation of macrophages and other cells. After all, oxidized LDL is still a promising object for further investigations that have the potential to clarify the unknown parts of the atherogenic process. In this review, we discuss the role of oxLDL in atherosclerosis development on different levels.
Contributive Role of TNF-α to L-DOPA-Induced Dyskinesia in a Unilateral 6-OHDA Lesion Model of Parkinson’s Disease
Authors: dos Santos Pereira Maurício , Abreu Gabriel Henrique Dias , Rocca Jeremy , Hamadat Sabah , Raisman-Vozari Rita , Michel Patrick Pierre , Del Bel Elaine
Published: January 2021

Our present objective was to better characterize the mechanisms that regulate striatal neuroinflammation in mice developing L-DOPA-induced dyskinesia (LID). For that, we used 6-hydroxydopamine (6-OHDA)-lesioned mice rendered dyskinetic by repeated intraperitoneal injections of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) and quantified ensuing neuroinflammatory changes in the dopamine-denervated dorsal striatum. LID development was associated with a prominent astrocytic response, and a more moderate microglial cell reaction restricted to this striatal area. The glial response was associated with elevations in two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β. Treatment with the phytocannabinoid cannabidiol and the transient receptor potential vanilloid-1 (TRPV-1) channel antagonist capsazepine diminished LID intensity and decreased TNF-α levels without impacting other inflammation markers. To possibly reproduce the neuroinflammatory component of LID, we exposed astrocyte and microglial cells in culture to candidate molecules that might operate as inflammatory cues during LID development, i.e., L-DOPA, dopamine, or glutamate. Neither L-DOPA nor dopamine produced an inflammatory response in glial cell cultures. However, glutamate enhanced TNF-α secretion and GFAP expression in astrocyte cultures and promoted Iba-1 expression in microglial cultures. Of interest, the antidyskinetic treatment with cannabidiol + capsazepine reduced TNF-α release in glutamate-activated astrocytes. TNF-α, on its own, promoted the synaptic release of glutamate in cortical neuronal cultures, whereas cannabidiol + capsazepine prevented this effect. Therefore, we may assume that the release of TNF-α by glutamate-activated astrocytes may contribute to LID by exacerbating corticostriatal glutamatergic inputs excitability and maintaining astrocytes in an activated state through a self-reinforcing mechanism.
Investigating Inventory Strategy Under Demand Distribution Fluctuation in Dual-Channel Supply Chain
Authors: Xu Nai-Ru , Cheng Jie , Cai Zheng-Qun
Published: January 2021

When manufacturers construct a dual-channel distribution system, which includes online and offline sales channels, they need to solve the inventory management problem to ensure supply and reduce inventory costs of the supply chain system. The dual-channel supply chain is the research object, and the inventory decision model is designed to achieve optimal profit when market demand is divided into online and offline demands. The results of the numerical analysis and simulations, conducted using MATLAB, indicate that both the manufacturer and the retailer increase their inventories and that their profits decrease when demand uncertainty increases. Besides, the increase in the online demand ratio causes the increase in the manufacturer’s inventory and reduces the profits of the retailer and the entire supply chain.
Genome-Wide Association Study on Seminal and Nodal Roots of Wheat Under Different Growth Environments
Authors: Xu Fengdan , Chen Shulin , Yang Xiwen , Zhou Sumei , Chen Xu , Li Jie , Zhan Kehui , He Dexian
Published: January 2021

The root of wheat consists of seminal and nodal roots. Comparatively speaking, fewer studies have been carried out on the nodal root system because of its disappearance at the early seedling stage under indoor environments. In this study, 196 accessions from the Huanghuai Wheat Region (HWR) were used to identify the characteristics of seminal and nodal root traits under different growth environments, including indoor hydroponic culture (IHC), outdoor hydroponic culture (OHC), and outdoor pot culture (OPC), for three growing seasons. The results indicated that the variation range of root traits in pot environment was larger than that in hydroponic environment, and canonical coefficients were the greatest between OHC and OPC (0.86) than those in other two groups, namely, IHC vs. OPC (0.48) and IHC vs. OHC (0.46). Most root traits were negatively correlated with spikes per area (SPA), grains per spike (GPS), and grain yield (GY), while all the seminal root traits were positively correlated with thousand-kernel weight (TKW). Genome-wide association study (GWAS) was carried out on root traits by using a wheat 660K SNP array. A total of 35 quantitative trait loci (QTLs)/chromosomal segments associated with root traits were identified under OPC and OHC. In detail, 11 and 24 QTLs were significantly associated with seminal root and nodal root traits, respectively. Moreover, 13 QTLs for number of nodal roots per plant (NRP) containing 14 stable SNPs, were distributed on chromosomes 1B, 2B, 3A, 4B, 5D, 6D, 7A, 7B, and Un. Based on LD and bioinformatics analysis, these QTLs may contain 17 genes closely related to NRP. Among them, TraesCS2B02G552500 and TraesCS7A02G428300 were highly expressed in root tissues. Moreover, the frequencies of favorable alleles of these 14 SNPs were confirmed to be less than 70% in the natural population, suggesting that the utilization of these superior genes in wheat root is still improving.
Functional Diversity in Ferns Is Driven by Species Richness Rather Than by Environmental Constraints
Authors: Aros-Mualin Daniela , Noben Sarah , Karger Dirk N. , Carvajal-Hernández César I. , Salazar Laura , Hernández-Rojas Adriana , Kluge Jürgen , Sundue Michael A. , Lehnert Marcus , Quandt Dietmar , Kessler Michael
Published: January 2021

Functional traits determine how species interact with their abiotic and biotic environment. In turn, functional diversity describes how assemblages of species as a whole are adapted to their environment, which also determines how they might react to changing conditions. To fully understand functional diversity, it is fundamental to (a) disentangle the influences of environmental filtering and species richness from each other, (b) assess if the trait space saturates at high levels of species richness, and (c) understand how changes in species numbers affect the relative importance of the trait niche expansion and packing. In the present study, we determined functional diversity of fern assemblages by describing morphological traits related to resource acquisition along four tropical elevational transects with different environmental conditions and species richness. We used several functional diversity indices and their standardized effect size to consider different aspects of functional diversity. We contrasted these aspects of functional diversity with climate data and species richness using linear models and linear mixed models. Our results show that functional morphological trait diversity was primarily driven by species richness and only marginally by environmental conditions. Moreover, increasing species richness contributed progressively to packing of the morphological niche space, while at the same time decreasing morphological expansion until a saturation point was reached. Overall, our findings suggest that the density of co-occurring species is the fundamental driving force of morphological niche structure, and environmental conditions have only an indirect influence on fern resource acquisition strategies.
Effects of Statistical and Narrative Health Claims on Consumer Food Product Evaluation
Authors: Lin Hung-Chou , Lee Sheng-Hsien
Published: January 2021

This research aims at exploring the underlying mechanisms how consumers respond to statistical and narrative health claims when they evaluate food products. Moreover, personality traits and product-related information are also incorporated to discuss their effects on the relationship between message types and consumers’ food product evaluation. The results indicate that statistical health claims are more persuasive than narrative health claims. In addition, the results show that individuals’ health knowledge, NFC moderate the relationship between message types and product evaluation. It argues that individuals with limited health knowledge evaluate food product more favorably when statistical health claims are used, while individuals with more health knowledge evaluate food product more favorably when narrative health claims are used. Moreover, it reveals that individuals with high NFC evaluate food product more favorably when statistical health claims are used, while individuals with low NFC evaluate food product more favorably when narrative health claims are used.
Mobile-Aware Deep Learning Algorithms for Malaria Parasites and White Blood Cells Localization in Thick Blood Smears
Authors: Nakasi Rose , Mwebaze Ernest , Zawedde Aminah
Published: January 2021

Effective determination of malaria parasitemia is paramount in aiding clinicians to accurately estimate the severity of malaria and guide the response for quality treatment. Microscopy by thick smear blood films is the conventional method for malaria parasitemia determination. Despite its edge over other existing methods of malaria parasitemia determination, it has been critiqued for being laborious, time consuming and equally requires expert knowledge for an efficient manual quantification of the parasitemia. This pauses a big challenge to most low developing countries as they are not only highly endemic but equally low resourced in terms of technical personnel in medical laboratories This study presents an end-to-end deep learning approach to automate the localization and count of P.falciparum parasites and White Blood Cells (WBCs) for effective parasitemia determination. The method involved building computer vision models on a dataset of annotated thick blood smear images. These computer vision models were built based on pre-trained deep learning models including Faster Regional Convolutional Neural Network (Faster R-CNN) and Single Shot Multibox Detector (SSD) models that help process the obtained digital images. To improve model performance due to a limited dataset, data augmentation was applied. Results from the evaluation of our approach showed that it reliably detected and returned a count of parasites and WBCs with good precision and recall. A strong correlation was observed between our model-generated counts and the manual counts done by microscopy experts (posting a spear man correlation of ρ = 0.998 for parasites and ρ = 0.987 for WBCs). Additionally, our proposed SSD model was quantized and deployed on a mobile smartphone-based inference app to detect malaria parasites and WBCs in situ. Our proposed method can be applied to support malaria diagnostics in settings with few trained Microscopy Experts yet constrained with large volume of patients to diagnose.
Quantitative Spectral Data Analysis Using Extreme Learning Machines Algorithm Incorporated with PCA
Authors: Li Michael , Wibowo Santoso , Li Wei , Li Lily D.
Published: January 2021

Extreme learning machine (ELM) is a popular randomization-based learning algorithm that provides a fast solution for many regression and classification problems. In this article, we present a method based on ELM for solving the spectral data analysis problem, which essentially is a class of inverse problems. It requires determining the structural parameters of a physical sample from the given spectroscopic curves. We proposed that the unknown target inverse function is approximated by an ELM through adding a linear neuron to correct the localized effect aroused by Gaussian basis functions. Unlike the conventional methods involving intensive numerical computations, under the new conceptual framework, the task of performing spectral data analysis becomes a learning task from data. As spectral data are typical high-dimensional data, the dimensionality reduction technique of principal component analysis (PCA) is applied to reduce the dimension of the dataset to ensure convergence. The proposed conceptual framework is illustrated using a set of simulated Rutherford backscattering spectra. The results have shown the proposed method can achieve prediction inaccuracies of less than 1%, which outperform the predictions from the multi-layer perceptron and numerical-based techniques. The presented method could be implemented as application software for real-time spectral data analysis by integrating it into a spectroscopic data collection system.
Genetic Diversity and Population Structure of Serbian Barley (Hordeum vulgare L.) Collection during a 40-Year Long Breeding Period
Authors: Brbaklić Ljiljana , Trkulja Dragana , Mikić Sanja , Mirosavljević Milan , Momčilović Vojislava , Dudić Branislav , Procházková Lenka , Aćin Vladimir
Published: January 2021

Determination of genetic diversity and population structure of breeding material is an important prerequisite for discovering novel and valuable alleles aimed at crop improvement. This study’s main objective was to characterize genetic diversity and population structure of a collection representing a 40-year long historical period of barley (Hordeum vulgare L.) breeding, using microsatellites, pedigree, and phenotypic data. The set of 90 barley genotypes was phenotyped during three growing seasons and genotyped with 338 polymorphic alleles. The indicators of genetic diversity showed differentiation changes throughout the breeding periods. The population structure discriminated the breeding material into three distinctive groups. The principal coordinate analysis grouped the genotypes according to their growth habit and row type. An analysis of phenotypic variance (ANOVA) showed that almost all investigated traits varied significantly between row types, seasons, and breeding periods. A positive effect on yield progress during the 40-year long breeding period could be partly attributed to breeding for shorter plants, which reduced lodging and thus provided higher yield stability. The breeding material revealed a considerable diversity level based on microsatellite and phenotypic data without a tendency of genetic erosion throughout the breeding history and implied dynamic changes in genetic backgrounds, providing a great gene pool suitable for further barley improvement.
Effects of Soil Types and Irrigation Modes on Rice Root Morphophysiological Traits and Grain Quality
Authors: Zhao Can , Chen Mengyun , Li Xiaofeng , Dai Qigen , Xu Ke , Guo Baowei , Hu Yajie , Wang Weiling , Huo Zhongyang
Published: January 2021

Soil moisture plays an important role in rice (Oryza sativa L.) root development and grain quality. However, little is known about the effects of soil type on rice root morphophysiological traits (RMTs) and grain quality under different irrigation modes. A soil-grown experiment was conducted during the 2016–2017 rice growing seasons in Yangzhou city with three soil types, namely, clay soil, loamy soil, and sandy soil, and three irrigation regimes, namely, conventional irrigation (CI, 0 kPa), alternate wetting and moderate drying (AWMD, −15 kPa), and alternate wetting and severe drying (AWSD, −25 kPa). The AWMD regime improved the RMT by 3.05–48.95% when compared with the CI and AWSD regimes, and the RMTs in loamy were 7.38–93.67% higher than those in clay and sandy soil under AWMD across 2016 and 2017. The AWMD regime improved the rice milling quality and appearance quality both in clay and loamy soil by 2.88–10.08% and 15.43–45.77%, respectively. The CI regime improved the processing quality and nutritional quality of rice in sandy soil. Both loamy and clay soils improved the rice RMTs and grain quality under an AWMD regime. The RMTs were very significantly correlated with water use efficiency, rice milling, and cooking quality and were negatively correlated with rice appearance quality. The AWMD regime can affect the rice RMT and can improve the rice grain quality in loamy soil. Our results provide a theoretical basis for the design of water-saving rice irrigation regimes and for an improvement in rice grain quality in the process of rice cultivation.
Can Nitrogen Fertilizer Management Improve Grain Iron Concentration of Agro-Biofortified Crops in Zimbabwe?
Authors: Manzeke-Kangara Muneta G. , Mtambanengwe Florence , Watts Michael J. , Broadley Martin R. , Lark R. Murray , Mapfumo Paul
Published: January 2021

Improving iron (Fe) concentration in staple grain crops could help reduce Fe-deficiency anaemia in communities dependent on plant-based diets. Co-application of nitrogen (N) and zinc (Zn) fertilizers has been reported to improve both yield and grain Zn concentration of crops in smallholder farming systems. This study was conducted to determine if similar effects are observed for grain Fe concentration. Field experiments were conducted in two years, in two contrasting agro-ecologies in Zimbabwe, on maize (Zea mays L.), cowpea (Vigna unguiculata [L.] Walp) and two finger millet (Eleusine coracana (L.) Gaertn.) “seed pools”. The two finger millet “seed pools” were collected during previous farmer surveys to represent “high” and “low” Fe concentrations. All plots received foliar Fe-ethylene diamine tetra-acetic acid (EDTA) fertilizer and one of seven N treatments, representing mineral or organic N sources, and combinations thereof. Higher grain yields were observed in larger N treatments. Grain Fe concentration increased according to species: maize < finger millet < cowpea but varied widely according to treatment. Significant effects of N-form on grain Fe concentration were observed in the low finger millet “seed pool”, for which mineral N fertilizer application increased grain Fe concentration to a greater extent than other N forms, but not for the other species. Whilst good soil fertility management is essential for yield and grain quality, effects on grain Fe concentration are less consistent than reported previously for Zn.
Quantitative Ethnomedicinal Status and Phytochemical Analysis of Berberis lyceum Royle
Authors: Nazir Nausheen , Rahman Abdur , Uddin Faheem , Khan Khalil Atif Ali , Zahoor Muhammad , Nisar Mohammad , Ullah Saeed , Ullah Riaz , Ezzeldin Essam , Mostafa Gamal A. E.
Published: January 2021

Berberis lyceum Royle has such pronounced medicinal values that it is used as cure of many diseases and has exhibited great therapeutic effects among the local communities throughout the world. The present research was carried out to evaluate the quantitative ethnobotanical status and phytochemical analysis of B. lyceum. Regular field trips were arranged to the study area (Shangla District) in August 2017 to October 2019 and interviews with 100 residents (age range: 30 to 50 years) were conducted. The approach adopted for ethnobotanical data was semi-scientific as the inhabitants were not aware about the modern names of some diseases and therefore physician prescriptions were also consulted. Ethnobotanical data were examined using relative frequency of citation and % use value. The % use value of B. lyceum indicates that the people of District Shangla mostly used it for curing of different diseases. In spite of tremendous uses the plant still survived in this area mainly due to the non-accessibility for humans of the mountain tops; otherwise, increase in anthropogenic activities even in these hilly areas poses a threat of the eradication of this plant. To correlate the folkloric uses with its phytochemical composition, HPLC (high performance liquid chromatography) analysis was performed and a total of six phenolic compounds (quercetin, chlorogenic acid, berberine, rutin, mandellic acid, and hydroxy benzoic acid) were identified in its root. As most of the health complications are correlated to oxidative stress therefore in vitro antioxidant activity were also performed using DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethyl benzo thiazoline-6-sulfonic acid) assays. The observed antioxidant potential may most probably be due to berberine and chlorogenic acid that were present in highest concentration in the analyzed extract. The effectiveness of the selected plant as remedy for a number of diseases (that were pointed out by the local community) may be due to its phytochemical composition especially berberine and chlorogenic acid as oxidative stress is the root cause of many diseases. The plant extract exhibited high antioxidant potential (DPPH IC50 = 165µg/mL; ABTSIC50 = 110µg/mL) in relation to the detected concentration of berberine and chlorogenic acid. It can be inferred from experimental results that the ethnopharmacological efficacy of this endangered species may be due to its phytochemical composition and antioxidant activities. This case study helps to revive the importance of B. lyceum in local communities and emphasizes the need for its conservation.