bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-Brain Functional Network Connectivity Abnormalities in Affective and Non-Affective Early Phase Psychosis
Authors: Fu Zening , Iraji Armin , Sui Jing , Calhoun Vince D.
Published: June 2021

Psychosis disorders share overlapping symptoms and are characterized by a wide-spread breakdown in functional brain integration. Although neuroimaging studies have identified numerous connectivity abnormalities in affective and non-affective psychoses, whether they have specific or unique connectivity abnormalities, especially within the early stage is still poorly understood. The early phase of psychosis is a critical period with fewer chronic confounds and when treatment intervention may be most effective. In this work, we examined whole-brain functional network connectivity (FNC) from both static and dynamic perspectives in patients with affective psychosis (PAP) or with non-affective psychosis (PnAP) and healthy controls (HCs). A fully automated independent component analysis (ICA) pipeline called “Neuromark” was applied to high-quality functional magnetic resonance imaging (fMRI) data with 113 early-phase psychosis patients (32 PAP and 81 PnAP) and 52 HCs. Relative to the HCs, both psychosis groups showed common abnormalities in static FNC (sFNC) between the thalamus and sensorimotor domain, and between subcortical regions and the cerebellum. PAP had specifically decreased sFNC between the superior temporal gyrus and the paracentral lobule, and between the cerebellum and the middle temporal gyrus/inferior parietal lobule. On the other hand, PnAP showed increased sFNC between the fusiform gyrus and the superior medial frontal gyrus. Dynamic FNC (dFNC) was investigated using a combination of a sliding window approach, clustering analysis, and graph analysis. Three reoccurring brain states were identified, among which both psychosis groups had fewer occurrences in one antagonism state (state 2) and showed decreased network efficiency within an intermediate state (state 1). Compared with HCs and PnAP, PAP also showed a significantly increased number of state transitions, indicating more unstable brain connections in affective psychosis. We further found that the identified connectivity features were associated with the overall positive and negative syndrome scale, an assessment instrument for general psychopathology and positive symptoms. Our findings support the view that subcortical-cortical information processing is disrupted within five years of the initial onset of psychosis and provide new evidence that abnormalities in both static and dynamic connectivity consist of shared and unique features for the early affective and non-affective psychoses.
Riboflavin Inhibits Histamine-Dependent Itch by Modulating Transient Receptor Potential Vanilloid 1 (TRPV1)
Authors: Lee Kihwan , Choi Young In , Im Sang-Taek , Hwang Sung-Min , Lee Han-Kyu , Im Jay-Zoon , Kim Yong Ho , Jung Sung Jun , Park Chul-Kyu
Published: June 2021

Riboflavin, also known as vitamin B2, isfound in foods and is used as a dietary supplement. Its deficiency (also called ariboflavinosis) results in some skin lesions and inflammations, such as stomatitis, cheilosis, oily scaly skin rashes, and itchy, watery eyes. Various therapeutic effects of riboflavin, such as anticancer, antioxidant, anti-inflammatory, and anti-nociceptive effects, are well known. Although some studies have identified the clinical effect of riboflavin on skin problems, including itch and inflammation, its underlying mechanism of action remains unknown. In this study, we investigated the molecular mechanism of the effects of riboflavin on histamine-dependent itch based on behavioral tests and electrophysiological experiments. Riboflavin significantly reduced histamine-induced scratching behaviors in mice and histamine-induced discharges in single-nerve fiber recordings, while it did not alter motor function in the rotarod test. In cultured dorsal root ganglion (DRG) neurons, riboflavin showed a dose-dependent inhibitory effect on the histamine- and capsaicin-induced inward current. Further tests wereconducted to determine whether two endogenous metabolites of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have similar effects to those of riboflavin. Here, FMN, but not FAD, significantly inhibited capsaicin-induced currents and itching responses caused by histamine. In addition, in transient receptor potential vanilloid 1 (TRPV1)-transfected HEK293 cells, both riboflavin and FMN blocked capsaicin-induced currents, whereas FAD did not. These results revealed that riboflavin inhibits histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how riboflavin exerts antipruritic effects and suggests that it might be a useful drug for the treatment of histamine-dependent itch.
Phosphorylation and O-GlcNAcylation of the PHF-1 Epitope of Tau Protein Induce Local Conformational Changes of the C-Terminus and Modulate Tau Self-Assembly Into Fibrillar Aggregates
Authors: Cantrelle François-Xavier , Loyens Anne , Trivelli Xavier , Reimann Oliver , Despres Clément , Gandhi Neha S. , Hackenberger Christian P. R. , Landrieu Isabelle , Smet-Nocca Caroline
Published: June 2021

Phosphorylation of the neuronal microtubule-associated Tau protein plays a critical role in the aggregation process leading to the formation of insoluble intraneuronal fibrils within Alzheimer’s disease (AD) brains. In recent years, other posttranslational modifications (PTMs) have been highlighted in the regulation of Tau (dys)functions. Among these PTMs, the O-β-linked N-acetylglucosaminylation (O-GlcNAcylation) modulates Tau phosphorylation and aggregation. We here focus on the role of the PHF-1 phospho-epitope of Tau C-terminal domain that is hyperphosphorylated in AD (at pS396/pS404) and encompasses S400 as the major O-GlcNAc site of Tau while two additional O-GlcNAc sites were found in the extreme C-terminus at S412 and S413. Using high resolution NMR spectroscopy, we showed that the O-GlcNAc glycosylation reduces phosphorylation of PHF-1 epitope by GSK3β alone or after priming by CDK2/cyclin A. Furthermore, investigations of the impact of PTMs on local conformation performed in small peptides highlight the role of S404 phosphorylation in inducing helical propensity in the region downstream pS404 that is exacerbated by other phosphorylations of PHF-1 epitope at S396 and S400, or O-GlcNAcylation of S400. Finally, the role of phosphorylation and O-GlcNAcylation of PHF-1 epitope was probed in in-vitro fibrillization assays in which O-GlcNAcylation slows down the rate of fibrillar assembly while GSK3β phosphorylation stimulates aggregation counteracting the effect of glycosylation.
Persistent Response and Prolonged Survival Following Pembrolizumab Discontinuation Due to Long-Lasting Autoimmune Colitis in Advanced NSCLC: A Case Report
Authors: Damato Angela , De Marco Loredana , Serra Silvia , Larocca Mario , Arias Alicia Garcia , Rondini Ermanno , Pinto Carmine
Published: June 2021

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies including non-small-cell lung cancer (NSCLC). Immune-mediated colitis is a known adverse effect of pembrolizumab which can lead to the treatment interruption, although not compromising the control of the oncological disease. Herein, we report the case of a 59-year-old woman on pembrolizumab for advanced NSCLC which developed a severe and persistent colitis treated with infliximab for several months following anti-PD-1 antibody discontinuation. This strategy resulted in an improvement but not complete recovery of the gastrointestinal toxicity despite revealed sustained response and control of the oncological disease with prolonged survival over 24 months.
Sunitinib Treatment for Advanced Paraganglioma: Case Report of a Novel SDHD Gene Mutation Variant and Systematic Review of the Literature
Authors: Sesti Franz , Feola Tiziana , Puliani Giulia , Centello Roberta , Di Vito Valentina , Bagni Oreste , Lenzi Andrea , Isidori Andrea M. , Cantisani Vito , Faggiano Antongiulio , Giannetta Elisa
Published: June 2021

Background

Paragangliomas (PGLs) are neuroendocrine neoplasms arising from chromaffin cells of sympathetic or parasympathetic paraganglia. Systemic therapies have been used only in metastatic PGLs. Antiangiogenic agents, such as sunitinib, could be a viable therapeutic choice in the subgroup of patients with SDH-positive PGLs. We describe the case of a man with Familial Paraganglioma Syndrome type 1 (FPGL) related to a novel mutation in SDHD gene treated with sunitinib. Furthermore, we performed a systematic review of the literature aimed to address the following question: is sunitinib treatment effective in patients with advanced/progressive/metastatic PGL?

Methods

We performed a data search using MEDLINE, Cochrane Library, and Scopus between April 2019 and September 2020. We included studies reporting data on clinical or biological characteristics, or clinical outcomes of patients with PGLs treated with sunitinib.

Results

The search leaded to the selection of 25 publications. Data from case reports and case series showed that disease control rate (DCR = stable disease + partial response + complete response) was achieved in 34.7% of cases under sunitinib treatment. In 39% of patients DCR was followed by progressive disease (PD) or tumor relapse, 26.1% patients showed PD. Data from clinical trials showed that DCR was 83%, and the median progression free survival was 13.4 months.

Discussion

Data from the present literature review suggested that sunitinib could be a viable therapeutic option in advanced/progressive/metastatic inoperable PGLs. However, further trials on the efficacy of sunitinib in FPGL and sporadic PGL are needed.
Association of Mu-Opioid Receptor(MOR) Expression and Opioids Requirement With Survival in Patients With Stage I-III Pancreatic Ductal Adenocarcinoma
Authors: Zhang Hao , Qu Mengdi , Gorur Aysegul , Sun Zhirong , Cata Juan P. , Chen Wankun , Miao Changhong
Published: June 2021

Background

The use of opioids in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is associated with shorter survival and not dependent on the expression of the mu-opioid receptor (MOR). The role of opioid use and MOR expression in stage I-III PDAC has not been investigated.

Methods

We conducted retrospective study in patients with stage I-III PDAC. MOR expression and OPRM1 gene expression in tumour tissue and non-tumour tissue was measured. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints included perineural invasion, intraoperative sufentanil consumption, and length of stay. We performed a subgroup group analysis to evaluate the interaction between levels of MOR expression, amount of opioids use (high versus low) and its association with survival.

Results

A total of 236 patients were enrolled in this study.There were no significantly difference in OS rates in patients with high versus low levels of MOR (1-year OS: 65.2% versus 70.6%, P=0.064; 3-year: 31.4% versus 35.8%, P=0.071; 5-year: 19.4% versus. 16.2%, P=0.153, respectively) in the tumours. The DFS rates between the groups were no significantly difference. Of note, a high expression of MOR combined with high opioid consumption was associated with poor prognosis in stage I-III PDAC patients. Tumor expressing high levels of MOR show higher rates of perineural invasion.

Conclusion

MOR is not an independent predictor of poor survival in stage I-III PDAC but associated with perineural invasion. Patients requiring high amounts of opioids intraoperatively show worse outcome if they are expressing high levels of MOR.
Validity of Random Triglyceride Levels in Infants Receiving Parenteral Nutrition
Authors: Bader Mohammad Y. , Lam Melanie A. , Munoz Fernando , Thompson Leslie , Kylat Ranjit I.
Published: June 2021

Background: Intravenous lipid emulsions (IL) are an important part of parenteral nutrition (PN) to meet essential fatty acid (EFA) requirements and metabolic demands of neonates and preterm infants. Some critically-ill neonates may not metabolize IL effectively which can lead to hypertriglyceridemia. Risks associated with this include increased pulmonary vascular resistance, displaced bilirubins, and platelet or macrophage dysfunction. Serum triglyceride (TG) concentration is used as a marker for lipid tolerance and predictor of potential complications involved with IL administration, but the clinical significance of this is still debated. Management of TG levels with regard to timing of laboratory tests, the ideal goal range, and duration of infusion of IL varies across institutions and is not standardized.

Methods: Single-center, retrospective study of newborn infants receiving parenteral nutrition (PN). Fasting and non-fasting TG levels were drawn during the same lipid infusion of 2–3g/kg/day. The primary outcome was the difference between fasting and non-fasting TG levels. Statistical assessment of continuous data was done with student t-test and nominal data was evaluated using X2-test and logistic regression.

Results: Forty infants were included with mean gestational age at birth of 29.5 ± 3.4 weeks and mean birth weight of 1.3 ± 0.5 kg. Mean time between lab draws while on same IL dose was 11.6 ± 0.2 h with resulting mean fasting and non-fasting (random) TG levels 82 ± 40 mg/dL (95% CI 68.4, 97.6) and 101 ± 40 mg/dL (95% CI 88.5, 115.8), respectively. Mean difference between TG levels during lipid-free interval and during infusion was −18.6 ± 51.2 mg/dL (95% CI −35.0, −2.3; p = 0.03).

Conclusion: We concluded there is no difference in the management of IL, when TG level was drawn randomly or as fasting sample. Obtaining TG level during routine lab draws is appropriate. We extrapolated that the administration of IL over 24 h will not interfere with TG level.
Low-Dose Antibiotic Prophylaxis Induces Rapid Modifications of the Gut Microbiota in Infants With Vesicoureteral Reflux
Authors: Morello William , D'Amico Federica , Serafinelli Jessica , Turroni Silvia , Abati Isabella , Fiori Jessica , Baskin Esra , Yalcinkaya Fatos , Jankauskiene Augustina , Pennesi Marco , Zurowska Aleksandra , Becherucci Francesca , Drozdz Dorota , Mekahli Djalila , Krzemien Grazyna , La Scola Claudio , Taranta-Janusz Katarzyna , Mehls Otto , Schaefer Franz , Candela Marco , Montini Giovanni
Published: June 2021

Background and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants.

Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed.

Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels.

Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks.
Comparison of Two Types of Staged Laparoscopic Orchiopexy for High Intra-Abdominal Testes in Children: A Retrospective Study From a Single Center
Authors: Liu Jie , Tang Rui , Wang Xiao , Sui Bangzhi , Jin Zhiyuan , Xu Xudong , Zhu Qinghua , Chen Jin , Ma Honglong , Duan Guangqi
Published: June 2021

Background: To evaluate the efficacy and safety of 2nd-stage laparoscopic traction orchiopexy (Shehata technique) compared to Fowler-Stephens (F-S technique) for high intra-abdominal testes (IATs) in children.

Patients and Methods: We performed a retrospective review of all children (<14 years old) who underwent laparoscopic treatment of high IAT in the pediatric surgery center of Yijishan Hospital of Wannan Medical College from April 2016 to April 2020. Participants were divided into the Fowler-Stephens (F-S) group and Shehata group according to the surgical method. We collected the medical records of all children and analyzed them statistically.

Results: In this study, 43 patients in our center received 2nd-stage laparoscopic surgical treatment. The results showed that there were 23 high IATs in 22 patients in the F-S group and 22 IATs in 21 patients in the Shehata group. All patients completed the operation successfully. No significant difference in operation time was noted between the two groups. There was no significant difference in the testicular atrophy rate between the two groups (P = 0.323). The testicular retraction rate of the F-S group was greater than that of the Shehata group (P = 0.04).

Conclusion:The results of this study indicate that the application of assisted laparoscopic testicular traction technology can effectively retain the main blood supply of the testis and vas deferens with a high survival rate and clear advantages. The preliminary results show that the Shehata technique is safe, reliable and effective in the treatment of high IAT in children.
Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting Mpro and Ameliorates Pulmonary Inflammation
Authors: Xiao Ting , Cui Mengqi , Zheng Caijuan , Wang Ming , Sun Ronghao , Gao Dandi , Bao Jiali , Ren Shanfa , Yang Bo , Lin Jianping , Li Xiaoping , Li Dongmei , Yang Cheng , Zhou Honggang
Published: June 2021

The coronavirus disease 2019 (COVID-19) has spread widely around the world and has seriously affected the human health of tens of millions of people. In view of lacking anti-virus drugs target to SARS-CoV-2, there is an urgent need to develop effective new drugs. In this study, we reported our discovery of SARS-CoV-2 Mpro inhibitors. We selected 15 natural compounds, including 7 flavonoids, 3 coumarins, 2 terpenoids, one henolic, one aldehyde and one steroid compound for molecular docking and enzymatic screening. Myricetin were identified to have potent inhibit activity with IC50 3.684 ± 0.076 μM in the enzyme assay. The binding pose of Myricetin with SARS-CoV-2 Mpro was identified using molecular docking method. In the binding pocket of SARS-CoV-2 Mpro, the chromone ring of Myricetin interacts with His41 through π-π stacking, and the 3’-, 4’- and 7-hydroxyl of Myricetin interact with Phe140, Glu166and Asp187 through hydrogen bonds. Significantly, our results showed that Myricetin has potent effect on bleomycin-induced pulmonary inflammation by inhibiting the infiltration of inflammatory cells and the secretion of inflammatory cytokines IL-6, IL-1α, TNF-α and IFN-γ. Overall, Myricetin may be a potential drug for anti-virus and symptomatic treatment of COVID-19.
Exploration of the Modulatory Property Mechanism of ELeng Capsule in the Treatment of Endometriosis Using Transcriptomics Combined With Systems Network Pharmacology
Authors: Zheng Weilin , Wang Jie , Wu Jiayi , Wang Tao , Huang Yangxue , Liang Xuefang , Cao Lixing
Published: June 2021

Endometriosis is a common gynecological disease and causes severe chronic pelvic pain and infertility. Growing evidence showed that traditional Chinese medicine (TCM) plays an active role in the treatment of endometriosis. ELeng Capsule (ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. However, the mechanisms of ELC have not been fully characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC. As a result, 40 compounds are identified, and 75 targets overlapped with endometriosis-related proteins. The mechanism of ELC for the treatment of endometriosis is based on the function modules of inducing apoptosis, inhibiting angiogenesis, and regulating immunity mainly through signaling molecules and interaction (neuroactive ligand–receptor interaction), immune system–associated pathways (toll-like receptor signaling pathway), vascular endothelial growth factor (VEGF) signaling, and MAPK signaling pathway based on network pharmacology. In addition, based on RNA-sequence analysis, we found that the mechanism of ELC was predominantly associated with the regulation of the function modules of actin and cytoskeleton, epithelial–mesenchymal transition (EMT), focal adhesion, and immunity-associated pathways. In conclusion, ELC exerted beneficial effects on endometriosis, and the potential mechanism could be realized through functional modules, such as inducing apoptosis and regulating angiogenesis, cytoskeleton, and EMT. This work not only provides insights into the therapeutic mechanism of TCM for treating endometriosis but also offers an efficient way for drug discovery and development from herbal medicine.
Pharmacokinetics of Acetaminophen and Metformin Hydrochloride in Rats After Exposure to Simulated High Altitude Hypoxia
Authors: Zhu Jun-bo , Yang Jian-xin , Nian Yong-qiong , Liu Gui-qin , Duan Ya-bin , Bai Xue , Wang Qian , Zhou Yang , Wang Xue-jun , Qu Ning , Li Xiang-yang
Published: June 2021

The pharmacokinetic characteristics of drugs were altered under high altitude hypoxia, thereby affecting the absorption, distribution, metabolism, and excretion of drug. However, there are few literatures on the pharmacokinetic changes of antipyretic and pain-relieving drugs and cardiovascular system drugs at high altitude. This study aimed to evaluate the pharmacokinetics of acetaminophen and metformin hydrochloride in rats under simulated high altitude hypoxia condition. Mechanically, the protein and mRNA expression of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) and organic cation transporter 2 (OCT2) were investigated by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Compared with the normoxia group, the t1/2 and AUC of acetaminophen were significantly increased, and the CL/F was significantly decreased in rats after exposure to simulated high altitude hypoxia. The t1/2 of metformin hydrochloride was significantly increased by simulated high altitude hypoxia. No significant differences in AUC and CL/F of metformin hydrochloride were observed when comparing the hypoxia group with the normoxia group. The protein and mRNA expression of UGT1A1 and OCT2 were decreased significantly under hypoxia in rats. This study found obvious changes in the pharmacokinetics of acetaminophen and metformin hydrochloride in rats after exposure to simulated high altitude hypoxia, and they might be due to significant decreases in the expressions of UGT1A1 and OCT2. To sum up, our data suggested that the pharmacokinetics of acetaminophen and metformin hydrochloride should be reexamined, and the optimal dose should be reassessed under hypoxia exposure.
Suppression of Inflammatory Cardiac Cytokine Network in Rats with Untreated Obesity and Pre-Diabetes by AT2 Receptor Agonist NP-6A4
Authors: Gavini Madhavi P. , Mahmood Abuzar , Belenchia Anthony M. , Beauparlant Paige , Kumar Senthil A. , Ardhanari Sivakumar , DeMarco Vincent G. , Pulakat Lakshmi
Published: June 2021

Obesity affects over 42% of the United States population and exacerbates heart disease, the leading cause of death in men and women. Obesity also increases pro-inflammatory cytokines that cause chronic tissue damage to vital organs. The standard-of-care does not sufficiently attenuate these inflammatory sequelae. Angiotensin II receptor AT2R is an anti-inflammatory and cardiovascular protective molecule; however, AT2R agonists are not used in the clinic to treat heart disease. NP-6A4 is a new AT2R peptide agonist with an FDA orphan drug designation for pediatric cardiomyopathy. NP-6A4 increases AT2R expression (mRNA and protein) and nitric oxide generation in human cardiovascular cells. AT2R-antagonist PD123319 and AT2RSiRNA suppress NP-6A4-effects indicating that NP-6A4 acts through AT2R. To determine whether NP-6A4 would mitigate cardiac damage from chronic inflammation induced by untreated obesity, we investigated the effects of 2-weeks NP-6A4 treatment (1.8 mg/kg delivered subcutaneously) on cardiac pathology of male Zucker obese (ZO) rats that display obesity, pre-diabetes and cardiac dysfunction. NP-6A4 attenuated cardiac diastolic and systolic dysfunction, cardiac fibrosis and cardiomyocyte hypertrophy, but increased myocardial capillary density. NP-6A4 treatment suppressed tubulointerstitial injury marker urinary β-NAG, and liver injury marker alkaline phosphatase in serum. These protective effects of NP-6A4 occurred in the presence of obesity, hyperinsulinemia, hyperglycemia, and hyperlipidemia, and without modulating blood pressure. NP-6A4 increased expression of AT2R (consistent with human cells) and cardioprotective erythropoietin (EPO) and Notch1 in ZO rat heart, but suppressed nineteen inflammatory cytokines. Cardiac miRNA profiling and in silico analysis showed that NP-6A4 activated a unique miRNA network that may regulate expression of AT2R, EPO, Notch1 and inflammatory cytokines, and mitigate cardiac pathology. Seventeen pro-inflammatory and pro-fibrotic cytokines that increase during lethal cytokine storms caused by infections such as COVID-19 were among the cytokines suppressed by NP-6A4 treatment in ZO rat heart. Thus, NP-6A4 activates a novel anti-inflammatory network comprised of 21 proteins in the heart that was not reported previously. Since NP-6A4’s unique mode of action suppresses pro-inflammatory cytokine network and attenuates myocardial damage, it can be an ideal adjuvant drug with other anti-glycemic, anti-hypertensive, standard-of-care drugs to protect the heart tissues from pro-inflammatory and pro-fibrotic cytokine attack induced by obesity.
Equivalence of Approaches to Relational Quantum Dynamics in Relativistic Settings
Authors: Höhn Philipp A. , Smith Alexander R. H. , Lock Maximilian P. E.
Published: June 2021

We have previously shown that three approaches to relational quantum dynamics—relational Dirac observables, the Page-Wootters formalism and quantum deparametrizations—are equivalent. Here we show that this “trinity” of relational quantum dynamics holds in relativistic settings per frequency superselection sector. Time according to a clock subsystem is defined via a positive operator-valued measure (POVM) that is covariant with respect to the group generated by its (quadratic) Hamiltonian. This differs from the usual choice of a self-adjoint clock observable conjugate to the clock momentum. It also resolves Kuchař's criticism that the Page-Wootters formalism yields incorrect localization probabilities for the relativistic particle when conditioning on a Minkowski time operator. We show that conditioning instead on the covariant clock POVM results in a Newton-Wigner type localization probability commonly used in relativistic quantum mechanics. By establishing the equivalence mentioned above, we also assign a consistent conditional-probability interpretation to relational observables and deparametrizations. Finally, we expand a recent method of changing temporal reference frames, and show how to transform states and observables frequency-sector-wise. We use this method to discuss an indirect clock self-reference effect and explore the state and temporal frame-dependence of the task of comparing and synchronizing different quantum clocks.
The Transition From MoS2 Single-Layer to Bilayer Growth on the Au(111) Surface
Authors: Ewert Moritz , Buß Lars , Braud Nicolas , Kundu Asish K. , Sheverdyaeva Polina M. , Moras Paolo , Genuzio Francesca , Menteş Tevfik Onur , Locatelli Andrea , Falta Jens , Flege Jan Ingo
Published: June 2021

The transition from single-layer to bilayer growth of molybdenum disulfide on the Au(111) surface is investigated by in situ low-energy electron and photoemission microscopy. By mapping the film morphology with nanometer resolution, we show that a MoS2 bilayer forms at the boundaries of single-layer single-domain MoS2 islands and next to merging islands whereas bilayer nucleation at the island centers is found to be suppressed, which may be related to the usage of dimethyl disulfide as sulfur precursor in the growth process. This approach, which may open up the possibility of growing continuous films over large areas while delaying bilayer formation, is likely transferable to other transition metal dichalcogenide model systems.
Acute Effect of Enhanced External Counterpulsation on the Carotid Hemodynamic Parameters in Patients With High Cardiovascular Risk Factors
Authors: Zhang Yahui , Mai Zhouming , Du Jianhang , Zhou Wenjuan , Wei Wenbin , Wang Hui , Yao Chun , Zhang Xinxia , Huang Hui , Wu Guifu
Published: June 2021

Purpose

Enhanced external counterpulsation (EECP) can improve carotid circulation in patients with coronary artery disease. However, the response of carotid hemodynamic parameters induced by EECP in patients with high cardiovascular risk factors remains to be clarified. This study aimed to investigate the acute effect of EECP on the hemodynamic parameters in the carotid arteries before, during, and immediately after EECP in patients with hypertension, hyperlipidemia, and type 2 diabetes.

Methods

Eighty-three subjects were recruited into this study to receive 45-min EECP, including patients with simple hypertension (n = 21), hyperlipidemia (n = 23), type 2 diabetes (n = 18), and healthy subjects (n = 21). Hemodynamic parameters in both common carotid arteries (CCAs) were measured and calculated from Doppler ultrasound images. Peak systolic velocity (PSV), end-diastolic velocity (EDV), mean inner diameter (ID), systolic/diastolic flow velocity ratio (VS/VD), flow rate (FR), and resistance index (RI) were monitored before, during, and immediately after 45-min EECP.

Results

EDV and VS/VD were significantly reduced, while RI of CCAs was significantly increased among four groups during EECP (all P < 0.01). Additionally, the ID of CCAs and the FR of left CCA increased in patients with hyperlipidemia during EECP (P < 0.05). PSV of left CCA was reduced in patients with type 2 diabetes (P < 0.05). Moreover, immediately after EECP, ID was significantly higher in patients with hyperlipidemia. The RI of patients with hypertension and PSV and VS/VD of patients with type 2 diabetes were significantly lower compared with baseline (all P < 0.05).

Conclusion

EECP created an acute reduction in EDV, PSV, and VS/VD, and an immediate increase in the RI, FR, and ID of CCAs among the four groups. Additionally, a single 45-min session of EECP produced immediate improvement in the ID of patients with hyperlipidemia, the RI of patients with hypertension, and the PSV and VS/VD of patients with type 2 diabetes. The different hemodynamic responses induced by EECP may provide theoretical guidance for making personalized plans in patients with different cardiovascular risk factors.
Transcriptomic and Metabolomic Data Reveal the Key Metabolic Pathways Affecting Streltzoviella insularis (Staudinger) (Lepidoptera: Cossidae) Larvae During Overwintering
Authors: Pei Jiahe , Xu Yabei , Zong Shixiang , Ren Lili
Published: June 2021

Streltzoviella insularis (Staudinger) (Lepidoptera: Cossidae) is a woodboring insect feeding on Fraxinus pennsylvanica, Sophora japonica, and Ginkgo biloba, as well as many other species used for urban greening and plain afforestation in northern China, including the temperate north. There is also a risk that S. insularis could spread through the transportation of seedlings, thereby increasing urban greening costs. However, how S. insularis increases the cold tolerance then reduces it to survive winter temperature below 0°C remains unclear. In the transcriptomic of S. insularis, we identified three profiles (profile 25, 27, and 13) whose trends related to the cold tolerance. We detected 1,783 differentially expressed genes (in profile 25) and identified 522 genes enriched in the AMPK signaling pathway. The metabolome analysis identified 122 differential metabolites. We identified four co-pathways, among which “Glycerophospholipid metabolism” was the pathway most enriched in differentially expressed genes and differential metabolites. The AMPK signaling and glycerophospholipid metabolism pathways play key roles in the natural overwintering physiological process of S. insularis larvae.
Overexpression of the Peach Transcription Factor Early Bud-Break 1 Leads to More Branches in Poplar
Authors: Zhao Xuehui , Wen Binbin , Li Chen , Tan Qiuping , Liu Li , Chen Xiude , Li Ling , Fu Xiling
Published: June 2021

Shoot branching is an important adaptive trait that determines plant architecture. In a previous study, the Early bud-break 1 (EBB1) gene in peach (Prunus persica var. nectarina) cultivar Zhongyou 4 was transformed into poplar (Populus trichocarpa). PpEBB1-oe poplar showed a more branched phenotype. To understand the potential mechanisms underlying the EBB1-mediated branching, transcriptomic and proteomics analyses were used. The results showed that a large number of differentially expressed genes (DEGs)/differentially expressed proteins (DEPs) associated with light response, sugars, brassinosteroids (BR), and nitrogen metabolism were significantly enriched in PpEBB1-oe poplar. In addition, contents of sugars, BR, and amino acids were measured. Results showed that PpEBB1 significantly promoted the accumulation of fructose, glucose, sucrose, trehalose, and starch. Contents of brassinolide (BL), castasterone (CS), and 6-deoxocathasterone (6-deoxoCS) were all significantly changed with overexpressing PpEBB1. Various types of amino acids were measured and four of them were significantly improved in PpEBB1-oe poplar, including aspartic acid (Asp), arginine (Arg), cysteine (Cys), and tryptohpan (Trp). Taken together, shoot branching is a process controlled by a complex regulatory network, and PpEBB1 may play important roles in this process through the coordinating multiple metabolic pathways involved in shoot branching, including light response, phytohormones, sugars, and nitrogen.
Transcriptomic and Weighted Gene Co-expression Correlation Network Analysis Reveal Resveratrol Biosynthesis Mechanisms Caused by Bud Sport in Grape Berry
Authors: Leng Feng , Ye Yunling , Zhou Jialing , Jia Huijuan , Zhu Xiaoheng , Shi Jiayu , Zhang Ziyue , Shen Nan , Wang Li
Published: June 2021

Resveratrol is a natural polyphenol compound produced in response to biotic and abiotic stresses in grape berries. However, changes in resveratrol caused by bud sport in grapes are scarcely reported. In this study, trans-resveratrol and cis-resveratrol were identified and quantified in the grape berries of ‘Summer Black’ and its bud sport ‘Nantaihutezao’ from the veraison to ripening stages using ultra performance liquid chromatography-high resolution tandem mass spectrometry (UPLC-HRMS). We found that bud sport accumulates the trans-resveratrol earlier and increases the contents of cis-resveratrol in the earlier stages but decreases its contents in the later stages. Simultaneously, we used RNA-Seq to identify 51 transcripts involved in the stilbene pathways. In particular, we further identified 124 and 19 transcripts that negatively correlated with the contents of trans-resveratrol and cis-resveratrol, respectively, and four transcripts encoding F3'5'H that positively correlated with the contents of trans-resveratrol by weighted gene co-expression network analysis (WGCNA). These transcripts may play important roles in relation to the synergistic regulation of metabolisms of resveratrol. The results of this study can provide a theoretical basis for the genetic improvement of grapes.
Overcoming Bottlenecks for Metabolic Engineering of Sesquiterpene Production in Tomato Fruits
Authors: Gutensohn Michael , Henry Laura K. , Gentry Scott A. , Lynch Joseph H. , Nguyen Thuong T. H. , Pichersky Eran , Dudareva Natalia
Published: June 2021

Terpenoids are a large and diverse class of plant metabolites that also includes volatile mono- and sesquiterpenes which are involved in biotic interactions of plants. Due to the limited natural availability of these terpenes and the tight regulation of their biosynthesis, there is strong interest to introduce or enhance their production in crop plants by metabolic engineering for agricultural, pharmaceutical and industrial applications. While engineering of monoterpenes has been quite successful, expression of sesquiterpene synthases in engineered plants frequently resulted in production of only minor amounts of sesquiterpenes. To identify bottlenecks for sesquiterpene engineering in plants, we have used two nearly identical terpene synthases, snapdragon (Antirrhinum majus) nerolidol/linalool synthase-1 and -2 (AmNES/LIS-1/-2), that are localized in the cytosol and plastids, respectively. Since these two bifunctional terpene synthases have very similar catalytic properties with geranyl diphosphate (GPP) and farnesyl diphosphate (FPP), their expression in target tissues allows indirect determination of the availability of these substrates in both subcellular compartments. Both terpene synthases were expressed under control of the ripening specific PG promoter in tomato fruits, which are characterized by a highly active terpenoid metabolism providing precursors for carotenoid biosynthesis. As AmNES/LIS-2 fruits produced the monoterpene linalool, AmNES/LIS-1 fruits were found to exclusively produce the sesquiterpene nerolidol. While nerolidol emission in AmNES/LIS-1 fruits was 60- to 584-fold lower compared to linalool emission in AmNES/LIS-2 fruits, accumulation of nerolidol-glucosides in AmNES/LIS-1 fruits was 4- to 14-fold lower than that of linalool-glucosides in AmNES/LIS-2 fruits. These results suggest that only a relatively small pool of FPP is available for sesquiterpene formation in the cytosol. To potentially overcome limitations in sesquiterpene production, we transiently co-expressed the key pathway-enzymes hydroxymethylglutaryl-CoA reductase (HMGR) and 1-deoxy-D-xylulose 5-phosphate synthase (DXS), as well as the regulator isopentenyl phosphate kinase (IPK). While HMGR and IPK expression increased metabolic flux toward nerolidol formation 5.7- and 2.9-fold, respectively, DXS expression only resulted in a 2.5-fold increase.
Genome-Wide Profiling of WRKY Genes Involved in Benzylisoquinoline Alkaloid Biosynthesis in California Poppy (Eschscholzia californica)
Authors: Yamada Yasuyuki , Nishida Shohei , Shitan Nobukazu , Sato Fumihiko
Published: June 2021

Transcription factors of the WRKY family play pivotal roles in plant defense responses, including the biosynthesis of specialized metabolites. Based on the previous findings of WRKY proteins regulating benzylisoquinoline alkaloid (BIA) biosynthesis, such as CjWRKY1—a regulator of berberine biosynthesis in Coptis japonica—and PsWRKY1—a regulator of morphine biosynthesis in Papaver somniferum—we performed genome-wide characterization of the WRKY gene family in Eschscholzia californica (California poppy), which produces various BIAs. Fifty WRKY genes were identified by homology search and classified into three groups based on phylogenetic, gene structure, and conserved motif analyses. RNA sequencing showed that several EcWRKY genes transiently responded to methyl jasmonate, a known alkaloid inducer, and the expression patterns of these EcWRKY genes were rather similar to those of BIA biosynthetic enzyme genes. Furthermore, tissue expression profiling suggested the involvement of a few subgroup IIc EcWRKYs in the regulation of BIA biosynthesis. Transactivation analysis using luciferase reporter genes harboring the promoters of biosynthetic enzyme genes indicated little activity of subgroup IIc EcWRKYs, suggesting that the transcriptional network of BIA biosynthesis constitutes multiple members. Finally, we investigated the coexpression patterns of EcWRKYs with some transporter genes and discussed the diversified functions of WRKY genes based on a previous finding that CjWRKY1 overexpression in California poppy cells enhanced BIA secretion into the medium.
The Role of User Behaviour in Improving Cyber Security Management
Authors: Moustafa Ahmed A. , Bello Abubakar , Maurushat Alana
Published: June 2021

Information security has for long time been a field of study in computer science, software engineering, and information communications technology. The term ‘information security’ has recently been replaced with the more generic term cybersecurity. The goal of this paper is to show that, in addition to computer science studies, behavioural sciences focused on user behaviour can provide key techniques to help increase cyber security and mitigate the impact of attackers’ social engineering and cognitive hacking methods (i.e., spreading false information). Accordingly, in this paper, we identify current research on psychological traits and individual differences among computer system users that explain vulnerabilities to cyber security attacks and crimes. Our review shows that computer system users possess different cognitive capabilities which determine their ability to counter information security threats. We identify gaps in the existing research and provide possible psychological methods to help computer system users comply with security policies and thus increase network and information security.
Age and Education Effects on a Novel Syntactic Assessment Battery for Elderly Adults
Authors: Sung Jee Eun , Ahn Heekyung , Choi Sujin , Lee Kiseop
Published: June 2021

The purpose of this study was to delineate the properties of a novel syntactic assessment battery and to present descriptive data on normal elderly individuals. We administered the Syntactic Assessment Battery (hereinafter SAB) using a sentence-picture paradigm to 195 normal elderly adults in three age groups (60–69, 70–79, and 80–90) and five educational levels (No formal education, Elementary School Graduation, Middle School Graduation, High School Graduation, College Graduation and Above). A multiple linear regression model was applied to verify the age and education effects. A summary of results indicated that the SAB effectively detected age and education effects. People generally demonstrated worse performance as they aged but better performance as their educational levels increased. People with high school education and above generally demonstrated stronger performance on the test, although educational effects were not significantly different between elementary and middle school graduation groups. The current novel syntactic assessment battery can serve as a screening measure that sensitively detects age and education effects.
Different Placement Practices for Different Families? Children’s Adjustment in LGH Adoptive Families
Authors: Costa Pedro Alexandre , Tasker Fiona , Leal Isabel Pereira
Published: June 2021

Objective

The purpose of this study was to examine the characteristics of children placed with lesbian, gay, and heterosexual adopters, and to examine children’s problem behaviors and positive psychosocial adjustment across the three family types.

Background

There is evidence that children with hard-to-place profiles may be more likely to be matched with lesbian and gay parents. In addition, children adopted from care face greater developmental difficulties than children raised by their birth families, although adoptive parents may buffer the negative effects of early adversity on their children’s psychosocial adjustment.

Method

A final sample of 149 adoptive families from across the United Kingdom was recruited: 71 heterosexual parented, 39 lesbian parented, and 39 gay parented.

Results

The results showed that gay and lesbian parents were more likely than heterosexual parents to be matched with hard-to-place children, partially because they were more open to being matched with children with hard-to-place profiles. However, no differences among the three family types on children’s psychosocial adjustment were found, when controlling for children’s early adversity.

Conclusion

Adopted children displayed similar levels of problem behaviors and positive adjustment in lesbian, gay, and heterosexual parented families. Early adversity and having a physical problem/disability accounted for much of the variance in problem behaviors whereas parenting did not. In contrast, it was suggested that parenting processes, namely, parental closeness, may help to explain children’s positive adjustment.
First Impression Formation Based on Valenced Self-Disclosure in Social Media Profiles
Authors: Qin Yuren , Cho Hichang , Li Pengxiang , Zhang Lianshan
Published: June 2021

This study aims to understand how the valence of self-disclosure (operationalized as the dominantly positive vs. balanced vs. dominantly negative social media posts of a future collaborator) influences first impression formation on social media. We also focus on trustworthiness as a mediator and perceived homophily as a moderator to specify the underlying mechanisms through which self-disclosure valence affects first impression formation. The results from an online experiment (N = 204) suggest that self-disclosure valence has a significant effect on perceived trustworthiness and likability when individuals evaluate an unknown future collaborator using the social media profile. Trustworthiness mediates the effect of self-disclosure valence on likability when the individuals feel that they are dissimilar or even slightly similar to strangers. At that time, individuals tend to seek cues from both self-disclosure valence and perceived homophily to form the trustworthiness perception, and the influence of self-disclosure depends on the level of perceived homophily.
Conspiracy Mentality Predicts Public Opposition to Foreign Trade
Authors: Jedinger Alexander
Published: June 2021

The proliferation of protectionist sentiments and policies has raised questions about the psychological sources of trade openness among the public. The current research investigated the effects of a previously neglected factor on attitudes toward international trade: conspiracy mentality. Conspiracy mentality describes the generalized belief that political and economic events are controlled by powerful malevolent forces acting in secret. Using data from a cross-sectional survey of German adults (N = 391), I hypothesized and found that conspiracy mentality is uniquely associated with the perceived threat posed by foreign trade and opposition to international trade. These findings suggest that individual differences in conspiracy mentality make an important contribution to understanding the fears associated with economic globalization.