bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling Ribonucleotide and Deoxyribonucleotide Pools Perturbed by Remdesivir in Human Bronchial Epithelial Cells
Authors: Li Yan , Zhang Hui-Xia , Luo Wen-Di , Lam Christopher Wai Kei , Wang Cai-Yun , Bai Li-Ping , Wong Vincent Kam Wai , Zhang Wei , Jiang Zhi-Hong
Published: April 2021

Remdesivir (RDV) has generated much anticipation for its moderate effect in treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the unsatisfactory survival rates of hospitalized patients limit its application to the treatment of coronavirus disease 2019 (COVID-19). Therefore, improvement of antiviral efficacy of RDV is urgently needed. As a typical nucleotide analog, the activation of RDV to bioactive triphosphate will affect the biosynthesis of endogenous ribonucleotides (RNs) and deoxyribonucleotides (dRNs), which are essential to RNA and DNA replication in host cells. The imbalance of RN pools will inhibit virus replication as well. In order to investigate the effects of RDV on cellular nucleotide pools and on RNA transcription and DNA replication, cellular RNs and dRNs concentrations were measured by the liquid chromatography-mass spectrometry method, and the synthesis of RNA and DNA was monitored using click chemistry. The results showed that the IC50 values for BEAS-2B cells at exposure durations of 48 and 72 h were 25.3 ± 2.6 and 9.6 ± 0.7 μM, respectively. Ten (10) μM RDV caused BEAS-2B arrest at S-phase and significant suppression of RNA and DNA synthesis after treatment for 24 h. In addition, a general increase in the abundance of nucleotides and an increase of specific nucleotides more than 2 folds were observed. However, the variation of pyrimidine ribonucleotides was relatively slight or even absent, resulting in an obvious imbalance between purine and pyrimidine ribonucleotides. Interestingly, the very marked disequilibrium between cytidine triphosphate (CTP) and cytidine monophosphate might result from the inhibition of CTP synthase. Due to nucleotides which are also precursors for the synthesis of viral nucleic acids, the perturbation of nucleotide pools would block viral RNA replication. Considering the metabolic vulnerability of endogenous nucleotides, exacerbating the imbalance of nucleotide pools imparts great promise to enhance the efficacy of RDV, which possibly has special implications for treatment of COVID-19.
Mogroside IIe Ameliorates Cardiomyopathy by Suppressing Cardiomyocyte Apoptosis in a Type 2 Diabetic Model
Authors: Cai Xin , He Lingmin , Zhou Guoao , Li Shenghua , Liao Xinghua
Published: May 2021

Mogroside IIe is primarily present in the unripe fruit of Siraitia grosvenorii (Swingle) C. Jeffrey, and it is the predominant saponin component. The purpose of this study was to investigate the effects of mogroside IIe (MGE IIe) on myocardial cell apoptosis in diabetic cardiomyopathy (DCM) rats by establishing a high-sugar and high-fat diet–induced model of type 2 diabetes (T2D) in SD rats and a homocysteine (Hcy)-induced apoptotic model in rat H9c2 cardiomyocytes. The results showed that MGE IIe decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, but increased the levels of high-density lipoprotein (HDL) in the SD rat model. Furthermore, MGE IIe decreased the levels of lactate dehydrogenase 2 (LDH2), creatine phosphokinase isoenzyme (CKMB), and creatine kinase (CK), and improved heart function. Additionally, MGE IIe inhibited the secretion of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α), improved myocardial morphology, and reduced myocardial apoptosis in the SD rat model. Furthermore, MGE IIe inhibited the mRNA and protein expression of active-caspase-3, -8, -9, -12, and Bax and Cyt-C, and promoted the mRNA and protein expression of Bcl-2 in the SD rat model. Furthermore, MGE IIe suppressed homocysteine-induced apoptosis of H9c2 cells by inhibiting the activity of caspases-3, -8, -9, and -12. In conclusion, MGE IIe inhibits the apoptotic pathway, thereby relieving DCM in vivo and in vitro.
Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine
Authors: Micaglio Emanuele , Locati Emanuela T. , Monasky Michelle M. , Romani Federico , Heilbron Francesca , Pappone Carlo
Published: April 2021

Adverse drug reactions (ADRs) are an important and frequent cause of morbidity and mortality. ADR can be related to a variety of drugs, including anticonvulsants, anaesthetics, antibiotics, antiretroviral, anticancer, and antiarrhythmics, and can involve every organ or apparatus. The causes of ADRs are still poorly understood due to their clinical heterogeneity and complexity. In this scenario, genetic predisposition toward ADRs is an emerging issue, not only in anticancer chemotherapy, but also in many other fields of medicine, including hemolytic anemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency, aplastic anemia, porphyria, malignant hyperthermia, epidermal tissue necrosis (Lyell’s Syndrome and Stevens-Johnson Syndrome), epilepsy, thyroid diseases, diabetes, Long QT and Brugada Syndromes. The role of genetic mutations in the ADRs pathogenesis has been shown either for dose-dependent or for dose-independent reactions. In this review, we present an update of the genetic background of ADRs, with phenotypic manifestations involving blood, muscles, heart, thyroid, liver, and skin disorders. This review aims to illustrate the growing usefulness of genetics both to prevent ADRs and to optimize the safe therapeutic use of many common drugs. In this prospective, ADRs could become an untoward “stress test,” leading to new diagnosis of genetic-determined diseases. Thus, the wider use of pharmacogenetic testing in the work-up of ADRs will lead to new clinical diagnosis of previously unsuspected diseases and to improved safety and efficacy of therapies. Improving the genotype-phenotype correlation through new lab techniques and implementation of artificial intelligence in the future may lead to personalized medicine, able to predict ADR and consequently to choose the appropriate compound and dosage for each patient.
Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug–Induced Acute Urticaria/Angioedema
Authors: Jurado-Escobar Raquel , Doña Inmaculada , Triano-Cornejo José , Perkins James R. , Pérez-Sánchez Natalia , Testera-Montes Almudena , Labella Marina , Bartra Joan , Laguna José J. , Estravís Miguel , Agúndez José A. G. , Torres María J. , Cornejo-García José A.
Published: April 2021

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity reactions, probably due to their high consumption worldwide. The most frequent type of NSAID hypersensitivity is NSAID cross-hypersensitivity, in which patients react to NSAIDs from different chemical groups in the absence of a specific immunological response. The underlying mechanism of NSAID cross-hypersensitivity has been linked to cyclooxygenase (COX)-1 inhibition causing an imbalance in the arachidonic acid pathway. Despite NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype, most studies have focused on NSAID-exacerbated respiratory disease. As NSAID cross-hypersensitivity reactions are idiosyncratic, only appearing in some subjects, it is believed that individual susceptibility is under the influence of genetic factors. Although associations with polymorphisms in genes from the AA pathway have been described, no previous study has evaluated the potential role of cytosolic phospholipase A2 (cPLA2) variants. This enzyme catalyzes the initial hydrolysis of membrane phospholipids to release AA, which can be subsequently metabolized into eicosanoids. Here, we analyzed for the first time the overall genetic variation in the cPLA2 gene (PLA2G4A) in NIUA patients. For this purpose, a set of tagging single nucleotide polymorphisms (tagSNPs) in PLA2G4A were selected using data from Europeans subjects in the 1,000 Genomes Project, and genotyped with the iPlex Sequenom MassArray technology. Two independent populations, each comprising NIUA patients and NSAID-tolerant controls, were recruited in Spain, for the purposes of discovery and replication, comprising a total of 1,128 individuals. Fifty-eight tagSNPs were successfully genotyped in the discovery cohort, of which four were significantly associated with NIUA after Bonferroni correction (rs2049963, rs2064471, rs12088010, and rs12746200). These polymorphisms were then genotyped in the replication cohort: rs2049963 was associated with increased risk for NIUA after Bonferroni correction under the dominant and additive models, whereas rs12088010 and rs12746200 were protective under these two inheritance models. Our results suggest a role for PLA2G4A polymorphisms in NIUA. However, further studies are required to replicate our findings, elucidate the mechanistic role, and evaluate the participation of PLA2G4A variants in other phenotypes induced by NSAID cross-hypersensitivity.
Store-Operated Calcium Channels as Drug Target in Gastroesophageal Cancers
Authors: Chang Yan , Roy Souvik , Pan Zui
Published: May 2021

Gastroesophageal cancers, including tumors occurring in esophagus and stomach, usually have poor prognosis and lack effective chemotherapeutic drugs for treatment. The association between dysregulated store-operated calcium entry (SOCE), a key intracellular Ca2+signaling pathway and gastroesophageal cancers are emerging. This review summarizes the recent advances in understanding the contribution of SOCE-mediated intracellular Ca2+signaling to gastroesophageal cancers. It assesses the pathophysiological role of each component in SOCE machinery, such as Orais and STIMs in the cancer cell proliferation, migration, and invasion as well as stemness maintenance. Lastly, it discusses efforts towards development of more specific and potent SOCE inhibitors, which may be a new set of chemotherapeutic drugs appearing at the horizon, to provide either targeted therapy or adjuvant treatment to overcome drug resistance for gastroesophageal cancers.
Crocetin and Its Glycoside Crocin, Two Bioactive Constituents From Crocus sativus L. (Saffron), Differentially Inhibit Angiogenesis by Inhibiting Endothelial Cytoskeleton Organization and Cell Migration Through VEGFR2/SRC/FAK and VEGFR2/MEK/ERK Signaling Pathways
Authors: Zhao Chen , Kam Hio-Tong , Chen Yan , Gong Guiyi , Hoi Maggie Pui-Man , Skalicka-Woźniak Krystyna , Dias Alberto Carlos Pires , Lee Simon Ming-Yuen
Published: April 2021

Crocetin and crocin are two important carotenoids isolated from saffron (Crocus sativus L.), which have been used as natural biomedicines with beneficial effects for improving the suboptimal health status associated with abnormal angiogenesis. However, the anti-angiogenic effects and underlying mechanisms of the effects of crocetin and crocin have not been investigated and compared. The anti-angiogenic effects of crocetin and crocin were tested on human umbilical vein endothelial cells (HUVECs) in vitro, and in zebrafish in vivo. In vivo, crocetin (20 μM) and crocin (50 and 100 μM) significantly inhibited subintestinal vein vessels formation, and a conversion process between them existed in zebrafish, resulting in a difference in their effective concentrations. In the HUVEC model, crocetin (10, 20 and 40 μM) and crocin (100, 200 and 400 μM) inhibited cell migration and tube formation, and inhibited the phosphorylation of VEGFR2 and its downstream pathway molecules. In silico analysis further showed that crocetin had a higher ability to bind with VEGFR2 than crocin. These results suggested that crocetin was more effective than crocin in inhibiting angiogenesis through regulation of the VEGF/VEGFR2 signaling pathway. These compounds, especially crocetin, are potential candidate natural biomedicines for the management of diseases associated with abnormal blood vessel growth, such as age-related macular degeneration.
Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
Authors: Liu Xing , Zhou Pingsheng , He Keqing , Wen Zhili , Gao Yong
Published: May 2021

Background: The etiology and carcinogenesis of hepatocellular carcinoma (HCC) are associated with various risk factors. Saponins extracted from Dioscorea zingiberensis C. H. Wright exhibit antitumor activity against HCC. This study aimed to investigate the effect and the underlying mechanism of Dioscorea Zingiberensis new saponin (ZnS) on HCC.

Methods: Human HCC cell lines, Huh7 and SMMC-7721, were treated with different concentrations of ZnS. Cell apoptosis was determined via flow cytometry assay. Differentially expressed lncRNAs (DElncRNAs) in ZnS-treated SMMC-7721 cells were determined through RNA-sequence. The role of lncRNA TCONS-00026762 in HCC was investigated gain of function analysis, along with cell proliferation, apoptosis, and invasion in HCC cells. A subcutaneous xenograft of SMMC-7721 cell lines was established to study the effects of TCONS-00026762 in vivo. The expression of apoptosis-related proteins was detected in vivo and in vitro via western blotting.

Results: ZnS inhibited the proliferation of HCC cell in a dose-dependent manner. ZnS could induce apoptosis in HCC cells. Illumina sequencing results showed that 493 DElncRNAs were identified in ZnS-treated SMMC-7721 cells. TCONS-00026762 expression was down-regulated in the ZnS-treated SMMC-7721 cells. TCONS-00026762 inhibited the effect of ZnS on the proliferation, apoptosis, and invasion of HCC cells. ZnS inhibited the tumor growth, while, TCONS-00026762 promoted tumor growth in vivo. Furthermore, ZnS and TCONS-00026762 regulated cell apoptotic pathways.

Conclusion: ZnS significantly inhibits the viability, apoptosis, invasion, and tumorigenicity of HCC cells by regulating the expression of TCONS-00026,762. Our findings provide novel insights into the potential role of lncRNA in HCC therapy.
On the Stabilization of Breather-type Solutions of the Damped Higher Order Nonlinear Schrödinger Equation
Authors: Schober C. M. , Islas A. L.
Published: April 2021

Spatially periodic breather solutions (SPBs) of the nonlinear Schrödinger (NLS) equation are frequently used to model rogue waves and are typically unstable. In this paper we study the effects of dissipation and higher order nonlinearities on the stabilization of N-mode SPBs, 1≤N≤3, in the framework of a damped higher order NLS (HONLS) equation. We observe the onset of novel instabilities associated with the development of critical states resulting from symmetry breaking in the damped HONLS system. We develop a broadened Floquet characterization of instabilities of solutions of the NLS equation by showing that instabilities are associated with degenerate complex elements of not only the discrete, but also the continuous Floquet spectrum. As a result, the Floquet criteria for the stabilization of a solution of the damped HONLS centers around the elimination of all complex degenerate elements of the spectrum. For a given initial N-mode SPB, a short-time perturbation analysis shows that the complex double points associated with resonant modes split under the damped HONLS while those associated with nonresonant modes remain closed. The corresponding /damped HONLS numerical experiments corroborate that instabilities associated with nonresonant modes persist on a longer time scale than the instabilities associated with resonant modes.
Tooth Removal in the Leopard Gecko and the de novo Formation of Replacement Teeth
Authors: Brink Kirstin S. , Henríquez Joaquín Ignacio , Grieco Theresa M. , Martin del Campo Jesus Rodolfo , Fu Katherine , Richman Joy M.
Published: May 2021

Many reptiles are able to continuously replace their teeth through life, an ability attributed to the existence of epithelial stem cells. Tooth replacement occurs in a spatially and temporally regulated manner, suggesting the involvement of diffusible factors, potentially over long distances. Here, we locally disrupted tooth replacement in the leopard gecko (Eublepharis macularius) and followed the recovery of the dentition. We looked at the effects on local patterning and functionally tested whether putative epithelial stem cells can give rise to multiple cell types in the enamel organs of new teeth. Second generation teeth with enamel and dentine were removed from adult geckos. The dental lamina was either left intact or disrupted in order to interfere with local patterning cues. The dentition began to reform by 1 month and was nearly recovered by 2–3 months as shown in μCT scans and eruption of teeth labeled with fluorescent markers. Microscopic analysis showed that the dental lamina was fully healed by 1 month. The deepest parts of the dental lamina retained odontogenic identity as shown by PITX2 staining. A pulse-chase was carried out to label cells that were stimulated to enter the cell cycle and then would carry BrdU forward into subsequent tooth generations. Initially we labeled 70–78% of PCNA cells with BrdU. After a 1-month chase, the percentage of BrdU + PCNA labeled cells in the dental lamina had dropped to 10%, consistent with the dilution of the label. There was also a population of single, BrdU-labeled cells present up to 2 months post surgery. These BrdU-labeled cells were almost entirely located in the dental lamina and were the likely progenitor/stem cells because they had not entered the cell cycle. In contrast fragmented BrdU was seen in the PCNA-positive, proliferating enamel organs. Homeostasis and recovery of the gecko dentition was therefore mediated by a stable population of epithelial stem cells in the dental lamina.
Recent Advances of MicroRNAs, Long Non-coding RNAs, and Circular RNAs in Preeclampsia
Authors: Chen Ailing , Yu Renqiang , Jiang Shiwen , Xia Yankai , Chen Ying
Published: April 2021

Preeclampsia is a clinical syndrome characterized by multiple-organ dysfunction, such as maternal hypertension and proteinuria, after 20 weeks of gestation. It is a common cause of fetal growth restriction, fetal malformation, and maternal death. At present, termination of pregnancy is the only way to prevent the development of the disease. Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are involved in important pathological and physiological functions in life cycle activities including ontogeny, reproduction, apoptosis, and cell reprogramming, and are closely associated with human diseases. Accumulating evidence suggests that non-coding RNAs are involved in the pathogenesis of preeclampsia through regulation of various physiological functions. In this review, we discuss the current evidence of the pathogenesis of preeclampsia, introduce the types and biological functions of non-coding RNA, and summarize the roles of non-coding RNA in the pathophysiological development of preeclampsia from the perspectives of oxidative stress, hypoxia, angiogenesis, decidualization, trophoblast invasion and proliferation, immune regulation, and inflammation. Finally, we briefly discuss the potential clinical application and future prospects of non-coding RNA as a biomarker for the diagnosis of preeclampsia.
Elucidating Mitochondrial DNA Markers of Ogura-Based CMS Lines in Indian Cauliflowers (Brassica oleracea var. botrytis L.) and Their Floral Abnormalities Due to Diversity in Cytonuclear Interactions
Authors: Singh Saurabh , Bhatia Reeta , Kumar Raj , Behera Tusar K. , Kumari Khushboo , Pramanik Achintya , Ghemeray Hemant , Sharma Kanika , Bhattacharya R. C. , Dey Shyam S.
Published: April 2021

Mitochondrial markers can be used to differentiate diverse mitotypes as well as cytoplasms in angiosperms. In cauliflower, cultivation of hybrids is pivotal in remunerative agriculture and cytoplasmic male sterile lines constitute an important component of the hybrid breeding. In diversifying the source of male sterility, it is essential to appropriately differentiate among the available male sterile cytoplasms in cauliflower. PCR polymorphism at the key mitochondrial genes associated with male sterility will be instrumental in analyzing, molecular characterization, and development of mitotype-specific markers for differentiation of different cytoplasmic sources. Presence of auto- and alloplasmic cytonuclear combinations result in complex floral abnormalities. In this context, the present investigation highlighted the utility of organelle genome-based markers in distinguishing cytoplasm types in Indian cauliflowers and unveils the epistatic effects of the cytonuclear interactions influencing floral phenotypes. In PCR-based analysis using a set of primers targeted to orf-138, 76 Indian cauliflower lines depicted the presence of Ogura cytoplasm albeit the amplicons generated exhibited polymorphism within the ofr-138 sequence. The polymorphic fragments were found to be spanning over 200–280 bp and 410–470 bp genomic regions of BnTR4 and orf125, respectively. Sequence analysis revealed that such cytoplasmic genetic variations could be attributed to single nucleotide polymorphisms and insertion or deletions of 31/51 nucleotides. The cytoplasmic effects on varying nuclear-genetic backgrounds rendered an array of floral abnormalities like reduction in flower size, fused flowers, splitted style with the exposed ovule, absence of nonfunctional stamens, and petaloid stamens. These floral malformations caused dysplasia of flower structure affecting female fertility with inefficient nectar production. The finding provides an important reference to ameliorate understanding of mechanism of cytonuclear interactions in floral organ development in Brassicas. The study paves the way for unraveling developmental biology of CMS phenotypes in eukaryotic organisms and intergenomic conflict in plant speciation.
Transcriptome Profile Reveals Drought-Induced Genes Preferentially Expressed in Response to Water Deficit in Cultivated Peanut (Arachis hypogaea L.)
Authors: Wang Xu , Yang Xinlei , Feng Yucheng , Dang Phat , Wang Wenwen , Graze Rita , Clevenger Josh P. , Chu Ye , Ozias-Akins Peggy , Holbrook Corley , Chen Charles
Published: April 2021

Cultivated peanut (Arachis hypogaea) is one of the most widely grown food legumes in the world, being valued for its high protein and unsaturated oil contents. Drought stress is one of the major constraints that limit peanut production. This study’s objective was to identify the drought-responsive genes preferentially expressed under drought stress in different peanut genotypes. To accomplish this, four genotypes (drought tolerant: C76-16 and 587; drought susceptible: Tifrunner and 506) subjected to drought stress in a rainout shelter experiment were examined. Transcriptome sequencing analysis identified that all four genotypes shared a total of 2,457 differentially expressed genes (DEGs). A total of 139 enriched gene ontology terms consisting of 86 biological processes and 53 molecular functions, with defense response, reproductive process, and signaling pathways, were significantly enriched in the common DEGs. In addition, 3,576 DEGs were identified only in drought-tolerant lines in which a total of 74 gene ontology terms were identified, including 55 biological processes and 19 molecular functions, mainly related to protein modification process, pollination, and metabolic process. These terms were also found in shared genes in four genotypes, indicating that tolerant lines adjusted more related genes to respond to drought. Forty-three significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were also identified, and the most enriched pathways were those processes involved in metabolic pathways, biosynthesis of secondary metabolites, plant circadian rhythm, phenylpropanoid biosynthesis, and starch and sucrose metabolism. This research expands our current understanding of the mechanisms that facilitate peanut drought tolerance and shed light on breeding advanced peanut lines to combat drought stress.
Introgression of Maize Lethal Necrosis Resistance Quantitative Trait Loci Into Susceptible Maize Populations and Validation of the Resistance Under Field Conditions in Naivasha, Kenya
Authors: Awata Luka A. O. , Ifie Beatrice E. , Danquah Eric , Jumbo MacDonald Bright , Suresh L. Mahabaleswara , Gowda Manje , Marchelo-Dragga Philip W. , Olsen Michael Scott , Shorinola Oluwaseyi , Yao Nasser Kouadio , Boddupalli Prasanna M. , Tongoona Pangirayi B.
Published: May 2021

Maize lethal necrosis (MLN), resulting from co-infection by maize chlorotic mottle virus (MCMV) and sugarcane mosaic virus (SCMV) can cause up to 100% yield losses in maize in Africa under serious disease conditions. Maize improvement through conventional backcross (BC) takes many generations but can significantly be shortened when molecular tools are utilized in the breeding process. We used a donor parent (KS23-6) to transfer quantitative trait loci (QTL) for resistance to MLN into nine adapted but MLN susceptible lines. Nurseries were established in Kiboko, Kenya during 2015–2017 seasons and BC3F2 progeny were developed using marker assisted backcrossing (MABC) approach. Six single nucleotide polymorphism (SNP) markers linked to QTL for resistance to MLN were used to genotype 2,400 BC3F2 lines using Kompetitive Allele Specific PCR (KASP) platform. We detected that two of the six QTL had major effects for resistance to MLN under artificial inoculation field conditions in 56 candidate BC3F2 lines. To confirm whether these two QTL are reproducible under different field conditions, the 56 BC3F2 lines including their parents were evaluated in replicated trials for two seasons under artificial MLN inoculations in Naivasha, Kenya in 2018. Strong association of genotype with phenotype was detected. Consequently, 19 superior BC3F2 lines with favorable alleles and showing improved levels of resistance to MLN under artificial field inoculation were identified. These elite lines represent superior genetic resources for improvement of maize hybrids for resistance to MLN. However, 20 BC3F2 lines were fixed for both KASP markers but were susceptible to MLN under field conditions, which could suggest weak linkage between the KASP markers and target genes. The validated two major QTL can be utilized to speed up the breeding process but additional loci need to be identified between the KASP markers and the resistance genes to strengthen the linkage.
Appropriate NH4+/NO3– Ratio Triggers Plant Growth and Nutrient Uptake of Flowering Chinese Cabbage by Optimizing the pH Value of Nutrient Solution
Authors: Zhu Yunna , Qi Baifu , Hao Yanwei , Liu Houcheng , Sun Guangwen , Chen Riyuan , Song Shiwei
Published: April 2021

Compared with sole nitrogen (N), the nutrition mixture of ammonium (NH4+) and nitrate (NO3–) is known to better improve crop yield and quality. However, the mechanism underlying this improvement remains unclear. In the present study, we analyzed the changes in nutrient solution composition, content of different N forms in plant tissues and exudates, and expression of plasma membrane (PM) H+-ATPase genes (HAs) under different NH4+/NO3– ratios (0/100, 10/90, 25/75, 50/50 as control, T1, T2, and T3) in flowering Chinese cabbage. We observed that compared with the control, T1 and T2 increased the economical yield of flowering Chinese cabbage by 1.26- and 1.54-fold, respectively, whereas T3 significantly reduced plant yield. Compared with the control, T1–T3 significantly reduced the NO3– content and increased the NH4+, amino acid, and soluble protein contents of flowering Chinese cabbage to varying extents. T2 significantly increased the N use efficiency (NUE), whereas T3 significantly decreased it to only being 70.25% of that of the control. Owing to the difference in N absorption and utilization among seedlings, the pH value of the nutrient solution differed under different NH4+/NO3– ratios. At harvest, the pH value of T2 was 5.8; in the control and T1, it was approximately 8.0, and in T3 it was only 3.6. We speculated that appropriate NH4+/NO3– ratios may improve N absorption and assimilation and thus promote the growth of flowering Chinese cabbage, owing to the suitable pH value. On the contrary, addition of excessive NH4+ may induce rhizosphere acidification and ammonia toxicity, causing plant growth inhibition. We further analyzed the transcription of PM H+-ATPase genes (HAs). HA1 and HA7 transcription in roots was significantly down-regulated by the addition of the mixture of NH4+ and NO3–, whereas the transcription of HA2, HA9 in roots and HA7, HA8, and HA10 in leaves was sharply up-regulated by the addition of the mixture; the transcription of HA3 was mainly enhanced by the highest ratio of NH4+/NO3–. Our results provide valuable information about the effects of treatments with different NH4+/NO3– ratios on plant growth and N uptake and utilization.
Diverged Early From CtpB and CtpC, CtpA Has Evolved to Process D1 Precursor in Oxygenic Photosynthetic Organisms
Authors: Chang Weidong , Li Chenggang , Cui Zheng , Li Wei , Song Haifeng , Chang Han , Fu Weihan , Wang Chunyu , Huang Ting , Luo Yixin , Shan Yelin , Wang Yuhua , Wang Fei , Xu Min , Fu Aigen
Published: April 2021

C-terminal peptidase (Ctp) cleaves the C-terminal extension of the D1 precursor (pD1) to form mature D1. Among the three homologs CtpA, CtpB, and CtpC in photosynthetic organisms only the first is capable of processing pD1 while the roles of CtpB and CtpC remain elusive. Phylogenetic analysis of Ctps from photosynthetic organisms revealed that CtpA has diverged early from CtpB and CtpC during evolution implying distinct roles for the Ctps. Analysis of Arabidopsis Ctp-deficient mutants revealed that pD1 processing was not affected in atctpb, atctpc, or atctpbatctpc mutants, demonstrating that AtCtpA, not AtCtpB or AtCtpC, is responsible for cleaving the pD1 C-terminal extension. Ectopic expression of CtpAs from Synechococcus elongatus, Chlamydomonas reinhardtii, and Physcomitrella patens in atctpa rescued the lethal phenotype of the mutant indicating that SeCtpA, CrCtpA, and PpCtpA could process pD1 in Arabidopsis. Enzyme activity assays showed that PpCtpA and CrCtpA could convert pD1 into mature D1 in vitro. In contrast, expressing CtpB or CtpC from Arabidopsis, C. reinhardtii, or P. patens in atctpa did not rescue its D1 maturation deficiency, and enzyme activity assays also showed that neither CtpB nor CtpC could process pD1 in vitro. Taken together, we conclude that the function of pD1 processing by CtpA is conserved in photosynthetic organisms. It is possible that among other factors CtpA developed this function to initiate the formation of the oxygenic D1/D2 type PSII complex during evolution whereas CtpB or CtpC have other roles that are still unclear.
Couples Coping With the Serious Illness of One of the Partners
Authors: Riazuelo Hélène
Published: April 2021

Chronic kidney failure is a serious somatic disease. Addressing the issue of living with a chronic disease means fully considering the patients’ entourage, their families, and those close to them, especially their children and spouses.

Objectives: The present paper focuses on the couple’s psychological experience when one of them suffers from a chronic disease, in this instance kidney disease. In particular, how is the spouse affected by the treatment provided? The aim is not only to see how care for sick people can be improved, but also, more specifically, how relatives and especially partners can receive attention.

Methodology: A qualitative approach is not only adopted, being based on the psychotherapeutic follow-up of the partners of patients with chronic kidney disease, but also of the patients themselves, addressing the matter of their life as a couple. Three couples were considered, and two case studies are presented here. The issues that cut across these different situations are examined.

Results and Discussion: Some couples show considerable resourcefulness. However, over the years, that capacity for adaptation and inventiveness can also be interrupted by the periods of greater suffering and even despair, especially when the somatic pathology becomes chronic. Many spouses talk about how living with a sick partner weighs down on them, causing severe fatigue. Some aspects of the illness can also become traumatic. The disease regularly disrupts the daily life of the couple and the family. This leads to a reworking of family relations. Each couple has its own history with the condition. As it emerges, it can disrupt the bonds of filiation, especially when the illness is hereditary. Making psychological care more accessible to the partners involved constitutes a major challenge for our hospital care systems.
Depression and Suicidal Ideation in a Sample of Malaysian Healthcare Workers: A Preliminary Study During the COVID-19 Pandemic
Authors: Sahimi Hajar Mohd Salleh , Mohd Daud Tuti Iryani , Chan Lai Fong , Shah Shamsul Azhar , Rahman Farynna Hana Ab , Nik Jaafar Nik Ruzyanei
Published: April 2021

Objective: The burden of suicidal behavior is anticipated to increase as a sequela of the COVID-19 pandemic. However, there is limited evidence on suicidal behavior among healthcare workers, an at-risk population. Our study aimed to investigate suicidal ideation in terms of the rate and associated factors in a sample of Malaysian healthcare workers during the early-phase of the COVID-19 pandemic.

Methods: A subpopulation analysis (N = 171) was conducted within a larger, nation-wide cross-sectional study of Malaysian healthcare worker psychological distress from March 18–21, 2020. Current suicidal ideation was measured with item 9 of the Patient Health Questionnaire-9 (PHQ-9). The following independent variables were assessed: socio-demographic profile, occupation and service-related factors, health-anxiety (Health Anxiety Inventory, HAI), lifetime anxiety disorder and severity of depression (PHQ-9).

Results: The proportion of healthcare workers with current suicidal ideation (19/171) and clinical depression (17/171) were 11.1 and 9.9%, respectively. Multivariable analysis showed that clinical depression was the most significant factor associated with current suicidal ideation (p < 0.001, OR = 55.983, 95% CI = 9.015–347.671) followed by mild (subthreshold) depression (p = 0.001, OR = 115.984, 95% CI = 2.977–85.804). Service duration of more than 10 years was associated with significantly less suicidal ideation (p = 0.049, OR = 0.072, 95% CI = 0.005–0.993).

Conclusions: Depression (subthreshold and especially within the clinical range) and early-career status (<10 years in service) may be target areas of early intervention for reduction of suicidal ideation amongst healthcare workers who have served during the COVID-19 pandemic. Further research is warranted to elucidate specific occupational stressors related to COVID-19 work conditions to tailor appropriate suicide preventive strategies in this population.
Perceived Social Norms as Determinants of Adherence to Public Health Measures Related to COVID-19 in Bali, Indonesia
Authors: Indrayathi Putu Ayu , Januraga Pande Putu , Pradnyani Putu Erma , Gesesew Hailay Abrha , Ward Paul Russel
Published: April 2021

Introduction: Before the widespread availability of an effective COVID-19 vaccine, it is crucial to control the rate of transmission by ensuring adherence to behavioral modifications, such as wearing masks, physical distancing, and washing hands, all of which can be implemented as public health measures. Focusing on the conditions in Bali, this study explored the level of compliance to public health measures targeted at COVID-19 and identified the determinants of compliance via the values, rules, and knowledge approach.

Materials and Methods: This cross-sectional study conducted an online survey using the Google Form application from June 29 to July 5, 2020. The minimum required sample size was 664. Inclusion criteria were set as follows: 18 years of age or older and residing in Bali during the data collection period. Adherence was measured based on nine protocol indicators that were rated using a four-point Likert scale. A multiple linear regression analysis was then conducted to determine the associated factors of adherence to public health measures.

Results: Of the 954 survey respondents, data from 743 were included for analysis. The average level of adherence to public health measures was 32.59 (range of 20–36). The linear regression analysis showed that perceived health benefits from public health measures, being female, and having COVID-19 test histories were significantly associated with adherence to public health measures.

Conclusions: For public health measures targeted at COVID-19, adherence was strongly associated with perceived social norms, in which individuals played social community roles by adapting to standardized public health measures. It is thus imperative for governments to support and monitor public health measures during the COVID-19 pandemic.
The Prevalence of Metabolic Disease Multimorbidity and Its Associations With Spending and Health Outcomes in Middle-Aged and Elderly Chinese Adults
Authors: Zhao Yang , Zhang Puhong , Lee John Tayu , Oldenburg Brian , Heusden Alexander van , Haregu Tilahun Nigatu , Wang Haipeng
Published: May 2021

Objective: Metabolic diseases have been a clinical challenge worldwide and a major public health issue. Very few studies from China investigated the impact of metabolic multimorbidity on healthcare and health outcomes at the national level. This study aims to examine the association of metabolic multimorbidity with health service utilization, spending, functional and mental health.

Materials and Methods: This is a nationally representative cross-sectional study, utilizing the data from the China Health and Retirement Longitudinal Study in 2015, including 11,377 participants aged 45 years and older. Multivariable regression models were used to assess the association of metabolic multimorbidity with healthcare, out-of-pocket expenditure (OOPE), the activities of daily living (ADL) limitation, the instrumental activities of daily living (IADL) limitation, and depression.

Results: Overall, 30.50% of total participants had metabolic multimorbidity in 2015 in China. Compared with single disease, metabolic multimorbidity were associated with the number of outpatient visits [incident rate ratio (IRR) = 1.30, 95% CI = 1.05, 1.62] and days of inpatient care (IRR = 1.52, 95% CI = 1.28, 1.81). Metabolic multimorbidity was positively associated with the OOPE on outpatient care (coefficient = 82.99, 95% CI = 17.70, 148.27) and physical functional difficulties, including ADL limitation (odds ratio = 1.36, 95% CI = 1.18, 1.57).

Conclusions: Metabolic multimorbidity is associated with higher levels of health-care service use, greater expenditure for outpatient care, and more difficulties in ADL among Chinese adults. China's health-care systems need to shift from single-disease models to new financing and service delivery models to effectively manage metabolic multimorbidity.
Occupational Characteristics and Management Measures of Sporadic COVID-19 Outbreaks From June 2020 to January 2021 in China: The Importance of Tracking Down “Patient Zero”
Authors: Feng Maohui , Ling Qiong , Xiong Jun , Manyande Anne , Xu Weiguo , Xiang Boqi
Published: April 2021

There are occupational disparities in the risk of contracting COVID-19. Occupational characteristics and work addresses play key roles in tracking down “patient zero.” The present descriptive analysis for occupational characteristics and management measures of sporadic COVID-19 outbreaks from June to December 2020 in China offers important new information to the international community at this stage of the pandemic. These data suggest that Chinese measures including tracking down “patient zero,” launching mass COVID-19 testing in the SARS-CoV-2-positive areas, designating a new high- or medium-risk area, locking down the corresponding community or neighborhood in response to new COVID-19 cases, and basing individual methods of protection on science are effective in reducing the transmission of the highly contagious SARS-CoV-2 across China.
Ethical Questions Raised by AI-Supported Mentoring in Higher Education
Authors: Köbis Laura , Mehner Caroline
Published: April 2021

Mentoring is a highly personal and individual process, in which mentees take advantage of expertise and experience to expand their knowledge and to achieve individual goals. The emerging use of AI in mentoring processes in higher education not only necessitates the adherence to applicable laws and regulations (e.g., relating to data protection and non-discrimination) but further requires a thorough understanding of ethical norms, guidelines, and unresolved issues (e.g., integrity of data, safety, and security of systems, and confidentiality, avoiding bias, insuring trust in and transparency of algorithms). Mentoring in Higher Education requires one of the highest degrees of trust, openness, and social–emotional support, as much is at the stake for mentees, especially their academic attainment, career options, and future life choices. However, ethical compromises seem to be common when digital systems are introduced, and the underlying ethical questions in AI-supported mentoring are still insufficiently addressed in research, development, and application. One of the challenges is to strive for privacy and data economy on the one hand, while Big Data is the prerequisite of AI-supported environments on the other hand. How can ethical norms and general guidelines of AIED be respected in complex digital mentoring processes? This article strives to start a discourse on the relevant ethical questions and in this way raise awareness for the ethical development and use of future data-driven, AI-supported mentoring environments in higher education.
Design and Modelling of a Continuum Robot for Distal Lung Sampling in Mechanically Ventilated Patients in Critical Care
Authors: Mitros Zisos , Thamo Balint , Bergeles Christos , da Cruz Lyndon , Dhaliwal Kevin , Khadem Mohsen
Published: May 2021

In this paper, we design and develop a novel robotic bronchoscope for sampling of the distal lung in mechanically-ventilated (MV) patients in critical care units. Despite the high cost and attributable morbidity and mortality of MV patients with pneumonia which approaches 40%, sampling of the distal lung in MV patients suffering from range of lung diseases such as Covid-19 is not standardised, lacks reproducibility and requires expert operators. We propose a robotic bronchoscope that enables repeatable sampling and guidance to distal lung pathologies by overcoming significant challenges that are encountered whilst performing bronchoscopy in MV patients, namely, limited dexterity, large size of the bronchoscope obstructing ventilation, and poor anatomical registration. We have developed a robotic bronchoscope with 7 Degrees of Freedom (DoFs), an outer diameter of 4.5 mm and inner working channel of 2 mm. The prototype is a push/pull actuated continuum robot capable of dexterous manipulation inside the lung and visualisation/sampling of the distal airways. A prototype of the robot is engineered and a mechanics-based model of the robotic bronchoscope is developed. Furthermore, we develop a novel numerical solver that improves the computational efficiency of the model and facilitates the deployment of the robot. Experiments are performed to verify the design and evaluate accuracy and computational cost of the model. Results demonstrate that the model can predict the shape of the robot in <0.011s with a mean error of 1.76 cm, enabling the future deployment of a robotic bronchoscope in MV patients.
Soft Adaptive Mechanical Metamaterials
Authors: Khajehtourian Romik , Kochmann Dennis M.
Published: May 2021

Soft materials are inherently flexible and make suitable candidates for soft robots intended for specific tasks that would otherwise not be achievable (e.g., smart grips capable of picking up objects without prior knowledge of their stiffness). Moreover, soft robots exploit the mechanics of their fundamental building blocks and aim to provide targeted functionality without the use of electronics or wiring. Despite recent progress, locomotion in soft robotics applications has remained a relatively young field with open challenges yet to overcome. Justly, harnessing structural instabilities and utilizing bistable actuators have gained importance as a solution. This report focuses on substrate-free reconfigurable structures composed of multistable unit cells with a nonconvex strain energy potential, which can exhibit structural transitions and produce strongly nonlinear transition waves. The energy released during the transition, if sufficient, balances the dissipation and kinetic energy of the system and forms a wave front that travels through the structure to effect its permanent or reversible reconfiguration. We exploit a triangular unit cell’s design space and provide general guidelines for unit cell selection. Using a continuum description, we predict and map the resulting structure’s behavior for various geometric and material properties. The structural motion created by these strongly nonlinear metamaterials has potential applications in propulsion in soft robotics, morphing surfaces, reconfigurable devices, mechanical logic, and controlled energy absorption.
Perceptions and Experiences of Frontline Urban Indian Organization Healthcare Workers With Infection Prevention and Control During the COVID-19 Pandemic
Authors: Collins Noah , Crowder Jolie , Ishcomer-Aazami Jamie , Apedjihoun Dionne
Published: April 2021

Coronavirus disease 2019 (COVID-19) has created significant challenges for outpatient healthcare providers and patients across the United States (U.S.). Forty-one Urban Indian Organizations (UIOs), who provide a wide spectrum of health services for American Indian and Alaska Native (AI/AN) populations and other underinsured and uninsured populations in urban areas across the country, are no exception. The National Council of Urban Indian Health (NCUIH), in collaboration with the U.S. Centers for Disease Control and Prevention (CDC), set out to understand the needs, challenges, and opportunities for improvement in infection prevention and control (IPC) training and systems from the perspective of UIO frontline healthcare workers. As part of the CDC's Project Firstline, NCUIH was chosen as a partner in a national collaborative. The first task was to conduct listening sessions with frontline UIO staff to learn more about IPC practices in the context of the COVID-19 pandemic. Thirty staff from 16 UIOs, representing full ambulatory, limited ambulatory, outreach and referral, and outpatient and residential treatment programs participated in virtual video focus groups in July of 2020. Thematic and content analysis protocols guided data analysis and coding. Analysis of findings generated four major themes: staff adaptation in the context of resilience; responsibility and duty to protect patients, families, and coworkers; mental and emotional issues for UIO staff; and IPC challenges in the context of COVID-19. Participants' challenges ranged from lack of access to personal protective equipment (PPE) to the absence of standardized training. Significant disparities in social determinants of health experienced by Native American and non-Native populations served by UIOs create additional challenges to the delivery of and access to care during the pandemic. The diverse array of tribal cultural values and contexts of the people and communities served by UIOs reportedly serve as both facilitators and barriers to care, awareness, and uptake of infectious disease public health practices.