bluuebunny/crossref_metadata_2025 huggingface dataset:
Redefining Molecular Chaperones as Chaotropes
Authors: Macošek Jakub , Mas Guillaume , Hiller Sebastian
Published: June 2021

Molecular chaperones are the key instruments of bacterial protein homeostasis. Chaperones not only facilitate folding of client proteins, but also transport them, prevent their aggregation, dissolve aggregates and resolve misfolded states. Despite this seemingly large variety, single chaperones can perform several of these functions even on multiple different clients, thus suggesting a single biophysical mechanism underlying. Numerous recently elucidated structures of bacterial chaperone–client complexes show that dynamic interactions between chaperones and their client proteins stabilize conformationally flexible non-native client states, which results in client protein denaturation. Based on these findings, we propose chaotropicity as a suitable biophysical concept to rationalize the generic activity of chaperones. We discuss the consequences of applying this concept in the context of ATP-dependent and -independent chaperones and their functional regulation.
The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies
Authors: Xiu Mengxi , Wang Yongbo , Li Baoli , Wang Xifeng , Xiao Fan , Chen Shoulin , Zhang Lieliang , Zhou Bin , Hua Fuzhou
Published: June 2021

Aberrant Notch signaling profoundly affects cancer progression. Especially the Notch3 receptor was found to be dysregulated in cancer, where its expression is correlated with worse clinicopathological features and poor prognosis. The activation of Notch3 signaling is closely related to the activation of cancer stem cells (CSCs), a small subpopulation in cancer that is responsible for cancer progression. In addition, Notch3 signaling also contributes to tumor chemoresistance against several drugs, including doxorubicin, platinum, taxane, epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) and gemcitabine, through complex mechanisms. In this review, we mainly focus on discussing the molecular mechanisms by which Notch3 modulates cancer stemness and chemoresistance, as well as other cancer behaviors including metastasis and angiogenesis. What’s more, we propose potential treatment strategies to block Notch3 signaling, such as non-coding RNAs, antibodies and antibody-drug conjugates, providing a comprehensive reference for research on precise targeted cancer therapy.
Exploring the Key Genes and Identification of Potential Diagnosis Biomarkers in Alzheimer’s Disease Using Bioinformatics Analysis
Authors: Yu Wuhan , Yu Weihua , Yang Yan , Lü Yang
Published: June 2021

Background

Alzheimer’s disease (AD) is one of the major threats of the twenty-first century and lacks available therapy. Identification of novel molecular markers for diagnosis and treatment of AD is urgently demanded, and genetic biomarkers show potential prospects.

Method

We identify and intersected differentially expressed genes (DEGs) from five microarray datasets to detect consensus DEGs. Based on these DEGs, we conducted Gene Ontology (GO), performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, constructed a protein—protein interaction (PPI) network, and utilized Cytoscape to identify hub genes. The least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify potential diagnostic biomarkers. Gene set enrichment analysis (GSEA) was performed to investigate the biological functions of the key genes.

Result

We identified 608 consensus DEGs, several dysregulated pathways, and 18 hub genes. Sixteen hub genes dysregulated as AD progressed. The diagnostic model of 35 genes was constructed, which has a high area under the curve (AUC) value in both the validation dataset and combined dataset (AUC = 0.992 and AUC = 0.985, respectively). The model can also differentiate mild cognitive impairment and AD patients from controls in two blood datasets. Brain-derived neurotrophic factor (BDNF) and WW domain-containing transcription regulator protein 1 (WWTR1), which are associated with the Braak stage, Aβ 42 levels, and β-secretase activity, were identified as critical genes of AD.

Conclusion

Our study identified 16 hub genes correlated to the neuropathological stage and 35 potential biomarkers for the diagnosis of AD. WWTR1 were identified as candidate genes for future studies. This study deepens our understanding of the transcriptomic and functional features and provides new potential diagnostic biomarkers and therapeutic targets for AD.
Learning by Insight-Like Sudden Comprehension as a Potential Strategy to Improve Memory Encoding in Older Adults
Authors: Kizilirmak Jasmin M. , Fischer Larissa , Krause Justus , Soch Joram , Richter Anni , Schott Björn H.
Published: June 2021

Several cognitive functions show a decline with advanced age, most prominently episodic memory. Problem-solving by insight represents a special associative form of problem-solving that has previously been shown to facilitate long-term memory formation. Recent neuroimaging evidence suggests that the encoding network involved in insight-based memory formation is largely hippocampus-independent. This may represent a potential advantage in older adults, as the hippocampus is one of the earliest brain structures to show age-related volume loss and functional impairment. Here, we investigated the potential beneficial effects of learning by insight in healthy older (60–79 years) compared to young adults (19–28 years). To this end, we compared later memory performance for verbal riddles encoded incidentally via induced insight-like sudden comprehension in both age groups. We employed a variant of the Compound Remote Associate Task (CRAT) for incidental encoding, during which participants were instructed to judge the solvability of items. In a 24-h delayed surprise memory test, participants attempted to solve previously encountered items and additionally performed a recognition memory test. During this test, older adults correctly solved an equal proportion of new CRA items compared to young adults and both age groups reported a similar frequency of Aha! experiences. While overall memory performance was better in young participants (higher proportion of correctly solved and correctly recognized old CRA items), older participants exhibited a stronger beneficial effect of insight-like sudden comprehension on later recognition memory for CRA items. Our results suggest that learning via insight might constitute a promising approach to improve memory function in old age.
Targeting of Lysosomal Pathway Genes for Parkinson's Disease Modification: Insights From Cellular and Animal Models
Authors: Abe Tetsuro , Kuwahara Tomoki
Published: June 2021

Previous genetic studies on hereditary Parkinson's disease (PD) have identified a set of pathogenic gene mutations that have strong impacts on the pathogenicity of PD. In addition, genome-wide association studies (GWAS) targeted to sporadic PD have nominated an increasing number of genetic variants that influence PD susceptibility. Although the clinical and pathological characteristics in hereditary PD are not identical to those in sporadic PD, α-synuclein, and LRRK2 are definitely associated with both types of PD, with LRRK2 mutations being the most frequent cause of autosomal-dominant PD. On the other hand, a significant portion of risk genes identified from GWAS have been associated with lysosomal functions, pointing to a critical role of lysosomes in PD pathogenesis. Experimental studies have suggested that the maintenance or upregulation of lysosomal activity may protect against neuronal dysfunction or degeneration. Here we focus on the roles of representative PD gene products that are implicated in lysosomal pathway, namely LRRK2, VPS35, ATP13A2, and glucocerebrosidase, and provide an overview of their disease-associated functions as well as their cooperative actions in the pathogenesis of PD, based on the evidence from cellular and animal models. We also discuss future perspectives of targeting lysosomal activation as a possible strategy to treat neurodegeneration.
Wnt-Frizzled Signaling Regulates Activity-Mediated Synapse Formation
Authors: Teo Samuel , Salinas Patricia C.
Published: June 2021

The formation of synapses is a tightly regulated process that requires the coordinated assembly of the presynaptic and postsynaptic sides. Defects in synaptogenesis during development or in the adult can lead to neurodevelopmental disorders, neurological disorders, and neurodegenerative diseases. In order to develop therapeutic approaches for these neurological conditions, we must first understand the molecular mechanisms that regulate synapse formation. The Wnt family of secreted glycoproteins are key regulators of synapse formation in different model systems from invertebrates to mammals. In this review, we will discuss the role of Wnt signaling in the formation of excitatory synapses in the mammalian brain by focusing on Wnt7a and Wnt5a, two Wnt ligands that play an in vivo role in this process. We will also discuss how changes in neuronal activity modulate the expression and/or release of Wnts, resulting in changes in the localization of surface levels of Frizzled, key Wnt receptors, at the synapse. Thus, changes in neuronal activity influence the magnitude of Wnt signaling, which in turn contributes to activity-mediated synapse formation.
Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation
Authors: Mezhibovsky Esther , Knowles Kim A. , He Qiyue , Sui Ke , Tveter Kevin M. , Duran Rocio M. , Roopchand Diana E.
Published: June 2021

A Western Diet (WD) low in fiber but high in fats and sugars contributes to obesity and non-alcoholic fatty liver disease (NAFLD). Supplementation with grape polyphenols (GPs) rich in B-type proanthocyanidins (PACs) can attenuate symptoms of cardiometabolic disease and alter the gut microbiota and its metabolites. We hypothesized that GP-mediated metabolic improvements would correlate with altered microbial metabolites such as short chain fatty acids (SCFAs). To more closely mimic a WD, C57BL/6J male mice were fed a low-fiber diet high in sucrose and butterfat along with 20% sucrose water to represent sugary beverages. This WD was supplemented with 1% GPs (WD-GP) to investigate the impact of GPs on energy balance, SCFA profile, and intestinal metabolism. Compared to WD-fed mice, the WD-GP group had higher lean mass along with lower fat mass, body weight, and hepatic steatosis despite consuming more calories from sucrose water. Indirect and direct calorimetry revealed that reduced adiposity in GP-supplemented mice was likely due to their greater energy expenditure, which resulted in lower energy efficiency compared to WD-fed mice. GP-supplemented mice had higher abundance of Akkermansia muciniphila, a gut microbe reported to increase energy expenditure. Short chain fatty acid measurements in colon content revealed that GP-supplemented mice had lower concentrations of butyrate, a major energy substrate of the distal intestine, and reduced valerate, a putrefactive SCFA. GP-supplementation also resulted in a lower acetate:propionate ratio suggesting reduced hepatic lipogenesis. Considering the higher sucrose consumption and reduced butyrate levels in GP-supplemented mice, we hypothesized that enterocytes would metabolize glucose and fructose as a replacement energy source. Ileal mRNA levels of glucose transporter-2 (GLUT2, SLC2A2) were increased indicating higher glucose and fructose uptake. Expression of ketohexokinase (KHK) was increased in ileum tissue suggesting increased fructolysis. A GP-induced increase in intestinal carbohydrate oxidation was supported by: (1) increased gene expression of duodenal pyruvate dehydrogenase (PDH), (2) a decreased ratio of lactate dehydrogenase a (LDHa): LDHb in jejunum and colon tissues, and (3) decreased duodenal and colonic lactate concentrations. These data indicate that GPs protect against WD-induced obesity and hepatic steatosis by diminishing portal delivery of lipogenic butyrate and sugars due to their increased intestinal utilization.
Validity and Reliability of a Water Frequency Questionnaire to Estimate Daily Total Water Intake in Adults
Authors: Colburn Abigail T. , Johnson Evan C. , Péronnet François , Jansen Lisa T. , Capitan-Jimenez Catalina , Adams J. D. , Guelinckx Isabelle , Perrier Erica T. , Mauromoustakos Andy , Kavouras Stavros A.
Published: June 2021

The purpose of this investigation was to assess the validity and reliability of a seven-day water frequency questionnaire (TWI-FQ) to estimate daily total water intake (TWI) in comparison to a water turnover objective reference value via deuterium oxide (D2O). Data collection occurred over 3 weeks, with a wash-out period during week two. Healthy adults (n = 98; 52% female; 41 ± 14 y; BMI, 26.4 ± 5.5 kg·m−2) retrospectively self-reported consumption frequencies of 17 liquids and 35 foods with specified volumes/amounts for weeks one and three via TWI-FQ. Standard water content values were utilized to determine the volume of water consumed from each liquid and food for calculation of mean daily TWI for each week. Diet records were completed daily during week two to estimate metabolic water production. To assess validity of the TWI-FQ, participants consumed D2O at the start of each week and provided urine samples immediately before ingestion, the following day, and at the end of the week to calculate water turnover. Metabolic water was subtracted from water turnover to estimate TWI. TWI-FQ validity was assessed via Bland-Altman plot for multiple observations. Reliability was assessed via intraclass correlation and Pearson's correlation between weeks. TWI-FQ significantly underestimated D2O TWI by −350 ± 1,431 mL·d−1 (95% confidence interval (CI): −551, −149 mL·d−1). TWI-FQ TWI was significantly correlated (r = 0.707, P <0.01) and not different (198 ± 1,180 mL·d−1, 95% CI: −38, 435 mL·d−1) between weeks. TWI-FQ intraclass correlation = 0.706 was significant [95% CI: 0.591, 0.793; F(97, 98) = 5.799], indicating moderate test-retest reliability. While this tool would not be suitable for individual TWI assessment, the magnitude of bias may be acceptable for assessment at the sample-level.
Prognostic Value of Galectin-9 Relates to Programmed Death-Ligand 1 in Patients With Multiple Myeloma
Authors: Lee Byung-Hyun , Park Yong , Kim JI-Hea , Kang Ka-Won , Lee Seung-Jin , Kim Seok Jin , Kim Byung Soo
Published: June 2021

Galectin-9 (Gal-9) expression can be negatively or positively associated with cancer patient prognosis, depending on the cancer type. However, the nature of this relationship remains unclear in multiple myeloma. Therefore, we evaluated the prognostic value of Gal-9 and its relationship with the expression of PD-L1 molecule, the most widely studied immune checkpoint inhibitor, in patients with newly diagnosed multiple myeloma. Gal-9 and PD-L1 levels in bone marrow aspirate samples were evaluated using immunofluorescence assays. Gal-9 positivity was defined as having ≥1% Gal-9-expressing plasma cells. PD-L1 expression was categorized as low or high based on its median value. The median OS of patients with positive and negative Gal-9 expression was 42 months and not reached, respectively. However, no significant difference was observed in OS between the two groups (P = 0.10). Patients with high PD-L1 expression had OS times of 14 and 43 months in the positive and negative Gal-9 expression groups, respectively. In the high PD-L1 expression group, patients expressing Gal-9 had significantly worse OS than those negative for it (P = 0.019). Multivariable Cox analysis confirmed that Gal-9 expression could independently predict shortened OS (hazard ratio, 1.090; 95% confidence interval, 1.015–1.171; P = 0.018) in patients with high PD-L1 expression. However, in the low PD-L1 expression group, patients with high Gal-9 expression exhibited a trend toward better OS (P = 0.816). Our results indicate that the prognostic value of Gal-9 may be related to PD-L1 expression in patients with newly diagnosed multiple myeloma.
Implications of Habitual Alcohol Intake With the Prognostic Significance of Mean Corpuscular Volume in Stage II-III Colorectal Cancer
Authors: Liu Qi , Yang Yufei , Li Xinxiang , Zhang Sheng
Published: June 2021

Objective

To elucidate the prognostic significance of mean corpuscular volume (MCV), with implications of habitual alcohol intake in stage II-III colorectal cancer (CRC).

Background

MCV had the potential to become an ideal prognostic biomarker and be put into clinical application. Few studies, however, have explored whether habitual alcohol intake which greatly increased the value of MCV would affect the prognostic role of MCV.

Methods

Eligible patients were identified from the CRC database of Fudan University Shanghai Cancer Center (FUSCC) between January 2012 and December 2013. Survival analyses were constructed using the Kaplan–Meier method to evaluate the survival time distribution, and the log-rank test was used to determine the survival differences. Univariate and multivariate Cox proportional hazard models were built to calculate the hazard ratios of different prognostic factors.

Results

A total of 694 patients diagnosed with stage II-III CRC between January 2012 and December 2013 were identified from FUSCC. Low pretreatment MCV was independently associated with 72.0% increased risk of overall mortality compared with normal MCV (HR = 1.720, 95%CI =1.028-2.876, P =0.039, using normal MCV as the reference). In patients with habitual alcohol intake, however, pretreatment MCV positively correlated with the mortality (P = 0.02) and tumor recurrence (P = 0.002) after adjusting for other known prognostic factors.

Conclusions

In CRC patients without habitual alcohol intake, low (<80 fL) level of pretreatment MCV was a predictor of poor prognosis. In patients with habitual alcohol intake, however, pretreatment MCV showed the opposite prognostic role, which would elicit many fundamental studies to elucidate the mechanisms behind.
A Novel Prognostic Signature Based on Metabolism-Related Genes to Predict Survival and Guide Personalized Treatment for Head and Neck Squamous Carcinoma
Authors: Li Ying , Weng Youliang , Pan Yuhui , Huang Zongwei , Chen Xiaochuan , Hong Wenquan , Lin Ting , Wang Lihua , Liu Wei , Qiu Sufang
Published: June 2021

Metabolic reprogramming contributes to patient prognosis. Here, we aimed to reveal the comprehensive landscape in metabolism of head and neck squamous carcinoma (HNSCC), and establish a novel metabolism-related prognostic model to explore the clinical potential and predictive value on therapeutic response. We screened 4752 metabolism-related genes (MRGs) and then identified differentially expressed MRGs in HNSCC. A novel 10-MRGs risk model for prognosis was established by the univariate Cox regression analysis and the least absolute shrinkage and selection operator (Lasso) regression analysis, and then verified in both internal and external validation cohort. Kaplan-Meier analysis was employed to explore its prognostic power on the response of conventional therapy. The immune cell infiltration was also evaluated and we used tumor immune dysfunction and exclusion (TIDE) algorithm to estimate potential response of immunotherapy in different risk groups. Nomogram model was constructed to further predict patients’ prognoses. We found the MRGs-related prognostic model showed good prediction performance. Survival analysis indicated that patients suffered obviously poorer survival outcomes in high-risk group (p < 0.001). The metabolism-related signature was further confirmed to be the independent prognostic value of HNSCC (HR = 6.387, 95% CI = 3.281-12.432, p < 0.001), the efficacy of predictive model was also verified by internal and external validation cohorts. We observed that HNSCC patients would benefit from the application of chemotherapy in the low-risk group (p = 0.029). Immunotherapy may be effective for HNSCC patients with high risk score (p < 0.01). Furthermore, we established a predictive nomogram model for clinical application with high performance. Our study constructed and validated a promising 10-MRGs signature for monitoring outcome, which may provide potential indicators for metabolic therapy and therapeutic response prediction in HNSCC.
Safety and Success of Lumbar Puncture in Young Infants: A Prospective Observational Study
Authors: Bedetti Luca , Lugli Licia , Marrozzini Lucia , Baraldi Alessandro , Leone Federica , Baroni Lorenza , Lucaccioni Laura , Rossi Cecilia , Roversi Maria F. , D'Amico Roberto , Iughetti Lorenzo , Berardi Alberto
Published: June 2021

Objective:This study aims to evaluate safety and success rates of lumbar puncture (LP) and to identify factors associated with adverse events or failure of LP in infants.

Methods:This two-center prospective observational study investigated infants younger than 90 days of age who underwent LP. Need for resuscitation oxygen desaturation (SpO2< 90%), bradycardia and intraventricular hemorrhage were considered adverse events. LP failed if cerebrospinal spinal fluid was not collected or had traces of blood. Logistic regression analysis was used to evaluate whether corrected gestational age (GA), body weight at LP, position, and any respiratory support during LP affected SpO2desaturation or failure of LP.

Results:Among 204 LPs, 134 were performed in full-term and 70 in pre-term born infants. SpO2desaturations occurred during 45 (22.4%) LPs. At multivariate analysis, lower GA at LP (p< 0.001), non-invasive respiratory support (p0.007) and mechanical ventilation (p0.004) were associated with SpO2desaturations. Transient, self-resolving bradycardia occurred in 7 (3.4%) infants. Two infants had intraventricular hemorrhage detected within 72 h of LP. No further adverse events were registered. Failure of LP occurred in 38.2% of cases and was not associated with any of the factors evaluated.

Conclusions:LP was safe in most infants. Body weight or GA at LP did not affect LP failure. These data are useful to clinicians, providing information on the safety of the procedure.
iTRAQ-Based Proteomics Reveals Gu-Ben-Fang-Xiao Decoction Alleviates Airway Remodeling via Reducing Extracellular Matrix Deposition in a Murine Model of Chronic Remission Asthma
Authors: Xing Qiongqiong , You Yannan , Zhao Xia , Ji Jianjian , Yan Hua , Dong Yingmei , Ren Lishun , Ding Yuanyuan , Hou Shuting
Published: June 2021

Airway remodeling is a primary pathological feature of asthma. The current therapy for asthma mainly targets reducing inflammation but not particularly airway remodeling. Therefore, it is worthwhile to develop alternative and more effective therapies to attenuate remodeling. Gu-Ben-Fang-Xiao Decoction (GBFXD) has been used to effectively and safely treat asthma for decades. In this study, GBFXD regulated airway inflammation, collagen deposition, and the molecules relevant to airway remodeling such as Vimentin, α-SMA, hydroxyproline, and E-cadherin in chronic remission asthma (CRA) murine model. Proteomic analysis indicated that the overlapping differentially expressed proteins (DEPs) (Model/Control and GBFXD/Model) were mainly collagens and laminins, which were extracellular matrix (ECM) proteins. In addition, the KEGG analysis showed that GBFXD could regulate pathways related to airway remodeling including ECM-receptor interactions, focal adhesion, and the PI3K/AKT signaling pathway, which were the top three significantly enriched pathways containing the most DEPs for both Model/Control and GBFXD/Model. Further validation research showed that GBFXD regulated reticulon-4 (RTN4) and suppressed the activation of the PI3K/AKT pathway to alleviate ECM proteins deposition. In conclusion, our findings indicate that GBFXD possibly regulate the PI3K/AKT pathway via RTN4 to improve airway remodeling, which provides a new insight into the molecular mechanism of GBFXD for the treatment of CRA.
Forsythiasides-Rich Extract From Forsythiae Fructus Inhibits Mast Cell Degranulation by Enhancing Mitochondrial Ca2+ Uptake
Authors: Qi Ruijuan , Kang Yuan , Li Ximeng , Zhang Xiaoyu , Han Yixin , Cai Runlan , Gao Yuan , Qi Yun
Published: June 2021

Mast cells (MCs) activated via IgE/FcεRI or MAS-related G protein coupled receptor (Mrgpr)-mediated pathway can release granules that play prominent roles in hypersensitivity reactions. Forsythiae Fructus, a well-known traditional Chinese medicine, has been clinically used for allergic diseases. Although previous studies indicated that Forsythiae Fructus extract inhibited compound 48/80-induced histamine release from MCs, its effect on IgE-dependent MC degranulation and possible underlying mechanisms remain to be explored. Herein, we prepared the forsythiasides-rich extract (FRE) and investigated its action on MC degranulation and explored its underlying mechanism. Our data showed that FRE could dampen IgE/FcεRI- and Mrgpr-mediated MC degranulation in vitro and in vivo. Mechanism study indicated that FRE decreased cytosolic Ca2+ (Ca2+[c]) level rapidly and reversibly. Moreover, FRE decreased Ca2+[c] of MCs independent of plasma membrane Ca2+-ATPase (PMCA), sarco/endoplasmic Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger (NCX). While, along with Ca2+[c] decrease, the increase of mitochondrial Ca2+ (Ca2+[m]) occurred simultaneously in FRE-treated RBL-2H3 cells. In the isolated mitochondria, FRE also promoted the subcellular organelle to uptake more extramitochondrial Ca2+. In conclusion, by increasing Ca2+[m] uptake, FRE decreases Ca2+[c] level to suppress MC degranulation. Our findings may provide theoretical support for the clinical application of Forsythiae Fructus on allergy and other MC-involved diseases.
Petunia Performance Under Application of Animal-Based Protein Hydrolysates: Effects on Visual Quality, Biomass, Nutrient Content, Root Morphology, and Gas Exchange
Authors: Cristiano Giuseppe , De Lucia Barbara
Published: June 2021

Sustainable plant production practices have been implemented to reduce the use of synthetic fertilizers and other agrochemicals. One way to reduce fertilizer use without negatively impacting plant nutrition is to enhance crop uptake of nutrients with biostimulants. As the effectiveness of a biostimulant can depend on the origin, species, dose, and application method, the aim of this research was to evaluate the effect of a commercial animal-based protein hydrolysate (PH) biostimulant on the visual quality, biomass, macronutrient content, root morphology, and leaf gas exchange of a petunia (Petunia × hybrida Hort. “red”) under preharvest conditions. Two treatments were compared: (a) three doses of an animal-based PH biostimulant: 0 (D0 = control), 0.1 (D0.1 = normal), and 0.2 g L–1 (D0.2 = high); (b) two biostimulant application methods: foliar spray and root drenching. The dose × method interaction effect of PH biostimulant on the plants was significant in terms of quality grade and fresh and dry biomass. The high dose applied as foliar spray produced petunias with extra-grade visual quality (number of flowers per plant 161, number of leaves per plant 450, and leaf area per plant 1,487 cm2) and a total aboveground dry weight of 35 g, shoots (+91%), flowers (+230%), and leaf fresh weight (+71%). P and K contents were higher than in untreated petunias, when plants were grown with D0.2 and foliar spray. With foliar spray at the two doses, SPAD showed a linear increase (+21.6 and +41.0%) with respect to untreated plants. The dose × method interaction effect of biostimulant application was significant for root length, projected and total root surface area, and number of root tips, forks, and crossings. Concerning leaf gas exchange parameters, applying the biostimulant at both doses as foliar spray resulted in a significant improvement in net photosynthesis (D0.1: 22.9 μmol CO2 m–2 s–1 and D0.2: 22.4 μmol CO2 m–2 s–1) and stomatal conductance (D0.1: 0.42 mmol H2O m–2 s–1 and D0.2: 0.39 mmol H2O m–2 s–1) compared to control. These results indicate that application of PH biostimulant at 0.2 g L–1 as foliar spray helped to achieve extra-grade plants and that this practice can be exploited in sustainable greenhouse conditions for commercial production of petunia.
Regulation of Dual Activity of Ascorbate Peroxidase 1 From Arabidopsis thaliana by Conformational Changes and Posttranslational Modifications
Authors: Kaur Shubhpreet , Prakash Prapti , Bak Dong-Ho , Hong Sung Hyun , Cho Chuloh , Chung Moon-Soo , Kim Jin-Hong , Lee Sungbeom , Bai Hyoung-Woo , Lee Sang Yeol , Chung Byung Yeoup , Lee Seung Sik
Published: June 2021

Ascorbate peroxidase (APX) is an important reactive oxygen species (ROS)-scavenging enzyme, which catalyzes the removal of hydrogen peroxide (H2O2) to prevent oxidative damage. The peroxidase activity of APX is regulated by posttranslational modifications (PTMs), such as S-nitrosylation, tyrosine nitration, and S-sulfhydration. In addition, it has been recently reported that APX functions as a molecular chaperone, protecting rice against heat stress. In this study, we attempted to identify the various functions of APX in Arabidopsis and the effects of PTMs on these functions. Cytosol type APX1 from Arabidopsis thaliana (AtAPX1) exists in multimeric forms ranging from dimeric to high-molecular-weight (HMW) complexes. Similar to the rice APX2, AtAPX1 plays a dual role behaving both as a regular peroxidase and a chaperone molecule. The dual activity of AtAPX1 was strongly related to its structural status. The main dimeric form of the AtAPX1 protein showed the highest peroxidase activity, whereas the HMW form exhibited the highest chaperone activity. Moreover, in vivo studies indicated that the structure of AtAPX1 was regulated by heat and salt stresses, with both involved in the association and dissociation of complexes, respectively. Additionally, we investigated the effects of S-nitrosylation, S-sulfhydration, and tyrosine nitration on the protein structure and functions using gel analysis and enzymatic activity assays. S-nitrosylation and S-sulfhydration positively regulated the peroxidase activity, whereas tyrosine nitration had a negative impact. However, no effects were observed on the chaperone function and the oligomeric status of AtAPX1. Our results will facilitate the understanding of the role and regulation of APX under abiotic stress and posttranslational modifications.
Comprehensive Lower Extremities Joints Range of Motion Profile in Futsal Players
Authors: Cejudo Antonio , Ruiz-Pérez Iñaki , Hernández-Sánchez Sergio , De Ste Croix Mark , Sainz de Baranda Pilar , Ayala Francisco
Published: June 2021

The purposes of this study were to describe the lower extremities joints range of motion (ROM) profile using a comprehensive approach in futsal players and to examine potential player position (goalkeepers vs. outfield players), competitive level (first [top] division vs. second division), number of playing years, sex (males vs. females), and bilateral (dominant limb vs. non-dominant limb) differences. A total of 72 male and 67 female elite futsal players from 11 clubs were measured of passive hip (flexion with knee flexed [HFKF] and extended [HFKE], extension [HE], abduction [HA], external [HER], and internal [HIR] rotation), knee (flexion [KF]) and ankle (dorsiflexion with knee flexed [ADFKF] and extended [ADFKE]) ROMs. Bayesian inferences exploring differences between player position, competitive level, sex and limb were made. A Bayesian correlation analysis was conducted to explore the influence of playing years on joints ROMs. The results showed no significant player position or competitive level related differences in any average ROM score. However, statistically significant sex-related differences were documented whereby female players reported higher hip and knee joints ROM average values than their male counterparts. Especially relevant were the proportions of males (72%) and players from teams engaged in the second division (61%) displaying limited HFKE ROMs. Likewise, around 35% of all players showed restricted ADFKF ROMs. In addition, approximately 21, 18, 22, and 25% of the futsal players were identified as having bilateral asymmetries (≥8°) for HA, HIR, HER, and KF ROMs, respectively. Finally, Bayesian correlation analysis did not report any significant association between years of playing futsal and ROM measures (all r values < 0.34). The implications that these restricted HFKE and ADFKF ROMs and bilateral asymmetries in hip (abduction, internal and external rotation) and knee (flexion) ROMs caused by the practice of futsal may have on physical performance and injury risk warrant future research.
Effects of Pandemic on Feelings of Depression in Italy: The Role of Age, Gender, and Individual Experiences During the First Lockdown
Authors: Arpino Bruno , Pasqualini Marta
Published: June 2021

The restrictions to physical contacts that have been imposed in different countries to deal with the coronavirus disease 2019 (COVID-19) pandemic may have contributed to an increase in feelings of depression on top of other negative consequences of the pandemic. This study examines the consequences of the COVID-19 pandemic on feelings of depression using original data collected in Italy between April 14 and 24, 2020. Quota sampling (N = 3,026) was performed to target the population of 18+ and, together with post-stratification weights, permitted obtaining a representative sample of the Italian population with respect to key sociodemographic factors. We find that 47% of the respondents have increased depressive feelings during the Covid-19 lockdown. Adopting a life-course perspective, we revealed great heterogeneity in feelings of depression consequences by age, gender, and difficulties experienced during the first national lockdown. Identifying groups of population at higher risk of suffering from feelings of depression as a result of COVID-19 is crucial to limit indirect long-term consequences of the pandemic.
Anxiety Impacts Consent Capacity to Treatment in Alzheimer's Disease
Authors: Kato Yuka , Matsuoka Teruyuki , Eguchi Yoko , Iiboshi Kiyoko , Koumi Hiroyuki , Nakamura Kaeko , Okabe Kayoko , Nakaaki Shutaro , Furukawa Toshiaki A. , Mimura Masaru , Narumoto Jin
Published: June 2021

This study aimed to clarify how behavioral and psychological symptoms of dementia (BPSD) and cognitive function affect the decision-making capacity of persons with Alzheimer's disease (AD) in a real informed consent situation about anti-dementia drug prescriptions. The participants were 76 patients with AD. We used the MacArthur Competence Assessment Tool to assess the capacity for consent to treatment (MacCAT-T). We simultaneously used the Mini-Mental State Examination, Executive Interview, Executive Clock Drawing Task, Logical Memory I of the Wechsler Memory Scale-Revised (LM I), LM II, and Neuropsychiatric Inventory (NPI) to assess cognitive function and psychiatric symptoms. We calculated the correlations between the MacCAT-T scores and the demographic, neuropsychological, and psychiatric variables. Once the univariable correlations were determined, we performed simple linear regression analyses to examine if the regression equations were significant. In the final analyses, we incorporated significant variables into stepwise multiple linear regression analyses to determine the most significant predictors of mental capacity. Age (β = −0.34), anxiety (β = −0.27), and LM I (β = 0.26) were significant predictors of “understanding” (adjustedR2= 0.29). LM II (β = 0.39), anxiety (β = −0.29), and education (β = 0.21) were significant predictors of “understanding of alternative treatments” (adjustedR2= 0.30). Anxiety (β = −0.36) and age (β = −0.22) were significant predictors of “appreciation” (adjustedR2= 0.18). Age (β = −0.31) and anxiety (β = −0.28) were significant predictors of explained variance in “reasoning” (adjustedR2= 0.17). Patients with anxiety had lower scores on all five MacCAT-T subscales: “understanding,” without 3.8 [SD= 1.2] vs. with 2.6 [SD= 1.1]; “understanding of alternative treatments,” without 2.9 [SD= 2.2] vs. with 1.3 [SD= 1.8]; “appreciation,” without 2.9 [SD= 1.1] vs. with 1.9 [SD= 1.2]; “reasoning,” without 4.0 [SD= 2.0] vs. with 2.7 [SD= 1.7]; and “expressing a choice,” without 1.9 [SD= 0.4] vs. with 1.5 [SD= 0.6]. Considering the effects of BPSD, cognitive function, and age/education when assessing consent capacity in persons with AD is important. Reducing anxiety may contribute to improved capacity in persons with AD.
Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China
Authors: Liu Shuang , Han Wei , Shen Chenyu , Zhu Changju , Wang Qiaofang , Liang Xianquan , He Xiangxi , Xie Qin , Wei Jie , Wu Miao , Zhao Xiaodong , Liu Hongsheng , Liu Danping , Guo Xiaowang , Nie Shinan , Cao Liping , Lu Linxin , Fang Yaqin , Lu Zhongqiu , Wu Yixu , Zhao Min , Han Jun , Zhang Xinchao , Chang Jie , Xu Shuogui , Ma Wenjie , Si Junli , Qi Suxia , Peng Peng , Chai Yage , Cao Yu , Jiang Yaowen , Yin Wen , Wang Yanjun , Zhan Hong , Huang Yingxiong , Deng Ying , Song Juanjuan , Yang Lishan , Wu Jiali , Ding Banghan , Zheng Danwen , Qian Chuanyun , Huang Rui , Lin Jiyan , Xu Zhihong , Zhang Guoxiu , Hu Yingying , Dou Qingli , Zhang Xiaoming , Tian Yingping , Yao Dongqi , Walline Joseph Harold , Zhu Huadong , Xu Jun , Li Yi , Yu Xuezhong
Published: June 2021

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1–15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31–45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.
Problematic Use of Alcohol and Online Gaming as Coping Strategies During the COVID-19 Pandemic: A Mini Review
Authors: Xu Shijie , Park Minkyung , Kang Ung Gu , Choi Jung-Seok , Koo Ja Wook
Published: June 2021

The COVID-19 (coronavirus disease 2019) pandemic has dramatically changed our daily lives and activities, including those originally intended to serve for leisure and pleasure. Drinking and online gaming became coping behaviors used to rescue ourselves from the stress and restricted lifestyle during the COVID-19 pandemic. However, frequent drinking and gaming can result in the pathological consequences of addiction. Those affected use the stimuli not to obtain pleasure, but rather to avoid the displeasure induced by stress and previous use, often unsuccessfully. This review aims to provide an overview of recent longitudinal cohort studies on alcohol and gaming use during the COVID-19 pandemic, as well as to analyze how the pandemic has affected alcohol and gaming use. There was a substantial risk of alcohol and online gaming overuse during the lockdown, which may depend on the pandemic's duration or overuse patterns. Previous studies have shown that increased alcohol consumption and online gaming are associated with heightened stress and anxiety levels caused by social isolation/quarantine. Over time, frequent or excessive alcohol consumption and gaming could lead to an increased risk of more serious mental health problems. Every effort should be made to mitigate mental health problems and ensure adequate adaptation to these exceptional circumstances. Therefore, it would be helpful to encourage physical activity, social interaction, and collaboration to facilitate psychological and physical health.
Sex-Related Differences in White Matter Asymmetry and Its Implications for Verbal Working Memory in Psychosis High-Risk State
Authors: Steinmann Saskia , Lyall Amanda E. , Langhein Mina , Nägele Felix L. , Rauh Jonas , Cetin-Karayumak Suheyla , Zhang Fan , Mussmann Marius , Billah Tashrif , Makris Nikos , Pasternak Ofer , O'Donnell Lauren J. , Rathi Yogesh , Kubicki Marek , Leicht Gregor , Shenton Martha E. , Mulert Christoph
Published: June 2021

Objective: Sexual dimorphism has been investigated in schizophrenia, although sex-specific differences among individuals who are at clinical high-risk (CHR) for developing psychosis have been inconclusive. This study aims to characterize sexual dimorphism of language areas in the brain by investigating the asymmetry of four white matter tracts relevant to verbal working memory in CHR patients compared to healthy controls (HC). HC typically show a leftward asymmetry of these tracts. Moreover, structural abnormalities in asymmetry and verbal working memory dysfunctions have been associated with neurodevelopmental abnormalities and are considered core features of schizophrenia.

Methods: Twenty-nine subjects with CHR (17 female/12 male) for developing psychosis and twenty-one HC (11 female/10 male) matched for age, sex, and education were included in the study. Two-tensor unscented Kalman filter tractography, followed by an automated, atlas-guided fiber clustering approach, were used to identify four fiber tracts related to verbal working memory: the superior longitudinal fasciculi (SLF) I, II and III, and the superior occipitofrontal fasciculus (SOFF). Using fractional anisotropy (FA) of tissue as the primary measure, we calculated the laterality index for each tract.

Results: There was a significantly greater right>left asymmetry of the SLF-III in CHR females compared to HC females, but no hemispheric difference between CHR vs. HC males. Moreover, the laterality index of SLF-III for CHR females correlated negatively with Backward Digit Span performance, suggesting a greater rightward asymmetry was associated with poorer working memory functioning.

Conclusion: This study suggests increased rightward asymmetry of the SLF-III in CHR females. This finding of sexual dimorphism in white matter asymmetry in a language-related area of the brain in CHR highlights the need for a deeper understanding of the role of sex in the high-risk state. Future work investigating early sex-specific pathophysiological mechanisms, may lead to the development of novel personalized treatment strategies aimed at preventing transition to a more chronic and difficult-to-treat disorder.
A Rare Case of Mesenteric Chylous Cyst in Infant: Case Report and Review of Literature
Authors: Salatto Alessia , Indrio Flavia , Campanella Vittoria , Curci Marina , Maggipinto Cosetta , Cocomazzi Raffaella , Canale Francesco , Nobili Maria , Bartoli Fabio
Published: June 2021

The occurrence of a mesenteric cyst (MC) is common in adults while in children and in infants is rare. In adults mesenteric cysts are often asymptomatic and discovered incidentally; however, in children they commonly present with symptoms of abdominal pain or distension with fever and leucocytosis. We report on a rare case, in our experience, of Mesenteric Chylous cyst (MCC) in an infant with signs and symptoms of intestinal obstruction. Discussion of literature is also reported.
The Behavior of Consumers and Producers of Food of Animal Origin and Their Impacts in One Health
Authors: Nespolo Natália Maramarque
Published: June 2021

Most people consume animal foods, for example meats, but few are concerned with the quality and origin of these products. Many studies point out hygiene problems of these foods after production; however, the lack of knowledge of the consumers of animal products about the importance of hygienic-sanitary control during the production process can lead them to a bad choice when buying these products and, consequently, expose themselves to the risk of acquiring many diseases, such as zoonosis. In this perspective, the objective of this work is to reflect about the consumers' role in the production of safe food of animal origin and to show that the population's health education is necessary and urgent. Only by helping the consumers to obtain knowledge about the production of animal products origin will there be a change in consumption habits, preventing the ingestion of contaminated foods that can cause damage to human health and to the environment, consequently, promoting one's health.
Addressing the Antimicrobial Resistance of Ruminant Mycoplasmas Using a Clinical Surveillance Network
Authors: Jaÿ Maryne , Poumarat François , Colin Adélie , Tricot Agnès , Tardy Florence
Published: June 2021

Antimicrobial resistance (AMR) surveillance of mycoplasmas of veterinary importance has been held back for years due to lack of harmonized methods for antimicrobial susceptibility testing (AST) and interpretative criteria, resulting in a crucial shortage of data. To address AMR in ruminant mycoplasmas, we mobilized a long-established clinical surveillance network called “Vigimyc.” Here we describe our surveillance strategy and detail the results obtained during a 2-year monitoring period. We also assess how far our system complies with current guidelines on AMR surveillance and how it could serve to build epidemiological cut-off values (ECOFFs), as a first attainable criterion to help harmonize monitoring efforts and move forward to clinical breakpoints. Clinical surveillance through Vigimyc enables continuous collection, identification and preservation of Mycoplasma spp. isolates along with metadata. The most frequent pathogens, i.e., M. bovis and species belonging to M. mycoides group, show stable clinicoepidemiological trends and were included for annual AST. In the absence of interpretative criteria for ruminant mycoplasmas, we compared yearly minimum inhibitory concentration (MIC) results against reference datasets. We also ran a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis on the overall service provided by our AMR surveillance strategy. Results of the 2018–2019 surveillance campaign were consistent with the reference datasets, with M. bovis isolates showing high MIC values for all antimicrobial classes except fluoroquinolones, and species of the Mycoides group showing predominantly low MIC values. A few new AMR patterns were detected, such as M. bovis with lower spectinomycin MICs. Our reference dataset partially complied with European Committee on Antimicrobial Susceptibility Testing (EUCAST) requirements, and we were able to propose tentative epidemiological cut-off values (TECOFFs) for M. bovis with tilmicosin and spectinomycin and for M. mycoides group with tilmicosin and lincomycin. These TECOFFs were consistent with other published data and the clinical breakpoints of Pasteurellaceae, which are often used as surrogates for mycoplasmas. SWOT analysis highlighted the benefit of pairing clinical and antimicrobial resistance surveillance despite the AST method-related gaps that remain. The international community should now direct efforts toward AST method harmonization and clinical interpretation.