bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of COVID-19 Lockdown Measures and COVID-19 Infection on Cognitive Functions: A Review in Healthy and Neurological Populations
Authors: Manfredini Alessio , Pisano Francesca , Incoccia Chiara , Marangolo Paola
Published: March 2023

The COVID-19 pandemic severely affected people’s mental health all over the world. This review aims to present a comprehensive overview of the literature related to the effects of COVID-19 lockdown measures and COVID-19 infection on cognitive functioning in both healthy people and people with neurological conditions by considering only standardized tests. We performed a narrative review of the literature via two databases, PUBMED and SCOPUS, from December 2019 to December 2022. In total, 62 out of 1356 articles were selected and organized into three time periods: short-term (1–4 months), medium-term (5–8 months), and long-term (9–12 months), according to the time in which the tests were performed. Regardless of the time period, most studies showed a general worsening in cognitive performance in people with neurological conditions due to COVID-19 lockdown measures and in healthy individuals recovered from COVID-19 infection. Our review is the first to highlight the importance of considering standardized tests as reliable measures to quantify the presence of cognitive deficits due to COVID-19. Indeed, we believe that they provide an objective measure of the cognitive difficulties encountered in the different populations, while allowing clinicians to plan rehabilitation treatments that can be of great help to many patients who still, nowadays, experience post-COVID-19 symptoms.
Transcriptome and Metabolome Profiling Unveil Pigment Formation Variations in Brown Cotton Lines (Gossypium hirsutum L.)
Authors: Lv Yin-Ping , Zhao Gang , Xie Yong-Fei , Owusu Anane Gideon , Wu Yong , Gao Jun-Shan
Published: March 2023

Naturally brown colored cotton (NBCC) is becoming increasingly popular due to its natural properties of coloration. However, poor fiber quality and color fading are key issues that are hindering the cultivation of naturally colored cotton. In this study, based on transcriptome and metabolome of 18 days post-anthesis (DPA), we compared the variations of pigment formation in two brown cotton fibers (DCF and LCF), with white cotton fiber (WCF) belonging to a near-isogenic line. A transcriptome study revealed a total of 15,785 differentially expressed genes significantly enriched in the flavonoid biosynthesis pathway. Furthermore, for flavonoid biosynthesis-related genes, such as flavonoid 3′5′-hydroxylase (F3′5′H), anthocyanidin synthase (ANS), anthocyanidin reductase (ANR), chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR), and chalcone isomerase (CHI), their expressions significantly increased in LCF compared with DCF and WCF. Moreover, transcription factors MYB and bHLH were significantly expressed in LCF and DCF. Most flavonoid-related metabolites (myricetin naringenin, catechin, epicatechin-epiafzelechin, and epigallocatechin) were found to be more highly up-regulated in LCF and DCF than WCF. These findings reveal the regulatory mechanism controlling different brown pigmentation in cotton fibers and elucidate the need for the proper selection of high-quality brown cotton fiber breeding lines for promising fiber quality and durable brown color pigmentation.
Minocycline as Treatment for Psychiatric and Neurological Conditions: A Systematic Review and Meta-Analysis
Authors: Panizzutti Bruna , Skvarc David , Lin Sylvia , Croce Sarah , Meehan Alcy , Bortolasci Chiara Cristina , Marx Wolfgang , Walker Adam J. , Hasebe Kyoko , Kavanagh Bianca E. , Morris Margaret J. , Mohebbi Mohammadreza , Turner Alyna , Gray Laura , Berk Lesley , Walder Ken , Berk Michael , Dean Olivia M.
Published: March 2023

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer’s disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.
The Role of Light-Regulated Auxin Signaling in Root Development
Authors: Yun Fahong , Liu Huwei , Deng Yuzheng , Hou Xuemei , Liao Weibiao
Published: March 2023

The root is an important organ for obtaining nutrients and absorbing water and carbohydrates, and it depends on various endogenous and external environmental stimulations such as light, temperature, water, plant hormones, and metabolic constituents. Auxin, as an essential plant hormone, can mediate rooting under different light treatments. Therefore, this review focuses on summarizing the functions and mechanisms of light-regulated auxin signaling in root development. Some light-response components such as phytochromes (PHYs), cryptochromes (CRYs), phototropins (PHOTs), phytochrome-interacting factors (PIFs) and constitutive photo-morphorgenic 1 (COP1) regulate root development. Moreover, light mediates the primary root, lateral root, adventitious root, root hair, rhizoid, and seminal and crown root development via the auxin signaling transduction pathway. Additionally, the effect of light through the auxin signal on root negative phototropism, gravitropism, root greening and the root branching of plants is also illustrated. The review also summarizes diverse light target genes in response to auxin signaling during rooting. We conclude that the mechanism of light-mediated root development via auxin signaling is complex, and it mainly concerns in the differences in plant species, such as barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.), changes of transcript levels and endogenous IAA content. Hence, the effect of light-involved auxin signaling on root growth and development is definitely a hot issue to explore in the horticultural studies now and in the future.
Genetic Diversity and Phylogeography of a Turf-Forming Cosmopolitan Marine Alga, Gelidium crinale (Gelidiales, Rhodo-Phyta)
Authors: Boo Ga Hun , Bottalico Antonella , Le Gall Line , Yoon Hwan Su
Published: March 2023

Cosmopolitan species are rare in red algae, which have a low-dispersal capacity unless they are dispersed by human-mediated introductions. Gelidium crinale, a turf-forming red alga, has a widespread distribution in tropical and temperate waters. To decipher the genetic diversity and phylogeography of G. crinale, we analyzed mitochondrial COI-5P and plastid rbcL sequences from collections in the Atlantic, Indian, and Pacific Oceans. Phylogenies of both markers statistically supported the monophyly of G. crinale, with a close relationship to G. americanum and G. calidum from the Western Atlantic. Based on the molecular analysis from these materials, Pterocladia heteroplatos from India is here merged with G. crinale. Phylogeny and TCS networks of COI-5P haplotypes revealed a geographic structure of five groups: (i) Atlantic-Mediterranean, (ii) Ionian, (iii) Asian, (iv) Adriatic-Ionian, and (v) Australasia-India-Tanzania-Easter Island. The most common ancestor of G. crinale likely diverged during the Pleistocene. The Bayesian Skyline Plots suggested the pre-LGM population expansion. Based on geographical structure, lineage-specific private haplotypes, the absence of shared haplotypes between lineages, and AMOVA, we propose that the cosmopolitan distribution of G. crinale has been shaped by Pleistocene relicts. The survival of the turf species under environmental stresses is briefly discussed.
Neuroprotection: Rescue from Neuronal Death in the Brain 2.0
Authors: Lee Bae Hwan
Published: March 2023

The brain is vulnerable to endogenous or exogenous injuries [...]
KIT D816V Mast Cells Derived from Induced Pluripotent Stem Cells Recapitulate Systemic Mastocytosis Transcriptional Profile
Authors: de Toledo Marcelo A. S. , Fu Xuhuang , Maié Tiago , Buhl Eva M. , Götz Katrin , Schmitz Susanne , Kaiser Anne , Boor Peter , Braunschweig Till , Chatain Nicolas , Costa Ivan G. , Brümmendorf Tim H. , Koschmieder Steffen , Zenke Martin
Published: March 2023

Mast cells (MCs) represent a population of hematopoietic cells with a key role in innate and adaptive immunity and are well known for their detrimental role in allergic responses. Yet, MCs occur in low abundance, which hampers their detailed molecular analysis. Here, we capitalized on the potential of induced pluripotent stem (iPS) cells to give rise to all cells in the body and established a novel and robust protocol for human iPS cell differentiation toward MCs. Relying on a panel of systemic mastocytosis (SM) patient-specific iPS cell lines carrying the KIT D816V mutation, we generated functional MCs that recapitulate SM disease features: increased number of MCs, abnormal maturation kinetics and activated phenotype, CD25 and CD30 surface expression and a transcriptional signature characterized by upregulated expression of innate and inflammatory response genes. Therefore, human iPS cell-derived MCs are a reliable, inexhaustible, and close-to-human tool for disease modeling and pharmacological screening to explore novel MC therapeutics.
Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth
Authors: Zapletal Emilija , Vasiljevic Tea , Busson Pierre , Matijevic Glavan Tanja
Published: March 2023

Damage-associated molecular patterns (DAMPs) are endogenous molecules released from the necrotic cells dying after exposure to various stressors. After binding to their receptors, they can stimulate various signaling pathways in target cells. DAMPs are especially abundant in the microenvironment of malignant tumors and are suspected to influence the behavior of malignant and stromal cells in multiple ways often resulting in promotion of cell proliferation, migration, invasion, and metastasis, as well as increased immune evasion. This review will start with a reminder of the main features of cell necrosis, which will be compared to other forms of cell death. Then we will summarize the various methods used to assess tumor necrosis in clinical practice including medical imaging, histopathological examination, and/or biological assays. We will also consider the importance of necrosis as a prognostic factor. Then the focus will be on the DAMPs and their role in the tumor microenvironment (TME). We will address not only their interactions with the malignant cells, frequently leading to cancer progression, but also with the immune cells and their contribution to immunosuppression. Finally, we will emphasize the role of DAMPs released by necrotic cells in the activation of Toll-like receptors (TLRs) and the possible contributions of TLRs to tumor development. This last point is very important for the future of cancer therapeutics since there are attempts to use TLR artificial ligands for cancer therapeutics.
Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy
Authors: Shevlyakov Anton D. , Kolesnikova Tatiana O. , de Abreu Murilo S. , Petersen Elena V. , Yenkoyan Konstantin B. , Demin Konstantin A. , Kalueff Allan V.
Published: March 2023

Epilepsy is a highly prevalent, severely debilitating neurological disorder characterized by seizures and neuronal hyperactivity due to an imbalanced neurotransmission. As genetic factors play a key role in epilepsy and its treatment, various genetic and genomic technologies continue to dissect the genetic causes of this disorder. However, the exact pathogenesis of epilepsy is not fully understood, necessitating further translational studies of this condition. Here, we applied a computational in silico approach to generate a comprehensive network of molecular pathways involved in epilepsy, based on known human candidate epilepsy genes and their established molecular interactors. Clustering the resulting network identified potential key interactors that may contribute to the development of epilepsy, and revealed functional molecular pathways associated with this disorder, including those related to neuronal hyperactivity, cytoskeletal and mitochondrial function, and metabolism. While traditional antiepileptic drugs often target single mechanisms associated with epilepsy, recent studies suggest targeting downstream pathways as an alternative efficient strategy. However, many potential downstream pathways have not yet been considered as promising targets for antiepileptic treatment. Our study calls for further research into the complexity of molecular mechanisms underlying epilepsy, aiming to develop more effective treatments targeting novel putative downstream pathways of this disorder.
Genetics of Multiple System Atrophy and Progressive Supranuclear Palsy: A Systemized Review of the Literature
Authors: Bougea Anastasia
Published: March 2023

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are uncommon multifactorial atypical Parkinsonian syndromes, expressed by various clinical features. MSA and PSP are commonly considered sporadic neurodegenerative disorders; however, our understanding is improving of their genetic framework. The purpose of this study was to critically review the genetics of MSA and PSP and their involvement in the pathogenesis. A systemized literature search of PubMed and MEDLINE was performed up to 1 January 2023. Narrative synthesis of the results was undertaken. In total, 43 studies were analyzed. Although familial MSA cases have been reported, the hereditary nature could not be demonstrated. COQ2 mutations were involved in familial and sporadic MSA, without being reproduced in various clinical populations. In terms of the genetics of the cohort, synuclein alpha (SNCA) polymorphisms were correlated with an elevated likelihood of manifesting MSA in Caucasians, but a causal effect relationship could not be demonstrated. Fifteen MAPT mutations were linked with PSP. Leucine-rich repeat kinase 2 (LRRK2) is an infrequent monogenic mutation of PSP. Dynactin subunit 1 (DCTN1) mutations may imitate the PSP phenotype. GWAS have noted many risk loci of PSP (STX6 and EIF2AK3), suggesting pathogenetic mechanisms related to PSP. Despite the limited evidence, it seems that genetics influence the susceptibility to MSA and PSP. MAPT mutations result in the MSA and PSP pathologies. Further studies are crucial to elucidate the pathogeneses of MSA and PSP, which will support efforts to develop novel drug options.
Antennal Transcriptome Analysis of Olfactory Genes and Characterization of Odorant Binding Proteins in Odontothrips loti (Thysanoptera: Thripidae)
Authors: Liu Yanqi , Luo Yingning , Du Lixiao , Ban Liping
Published: March 2023

To identify odors in complex environments accurately, insects have evolved multiple olfactory proteins. In our study, various olfactory proteins of Odontothrips loti Haliday, an oligophagous pest that primarily affects Medicago sativa (alfalfa), were explored. Specifically, 47 putative olfactory candidate genes were identified in the antennae transcriptome of O. loti, including seven odorant-binding proteins (OBPs), nine chemosensory proteins (CSPs), seven sensory neuron membrane proteins (SNMPs), eight odorant receptors (ORs), and sixteen ionotropic receptors (IRs). PCR analysis further confirmed that 43 out of 47 genes existed in O. loti adults, and O.lotOBP1, O.lotOBP4, and O.lotOBP6 were specifically expressed in the antennae with a male-biased expression pattern. In addition, both the fluorescence competitive binding assay and molecular docking showed that p-Menth-8-en-2-one, a component of the volatiles of the host, had strong binding ability to the O.lotOBP6 protein. Behavioral experiments showed that this component has a significant attraction to both female and male adults, indicating that O.lotOBP6 plays a role in host location. Furthermore, molecular docking reveals potential active sites in O.lotOBP6 that interact with most of the tested volatiles. Our results provide insights into the mechanism of O. loti odor-evoked behavior and the development of a highly specific and sustainable approach for thrip management.
A Polyaminobiaryl-Based β-secretase Modulator Alleviates Cognitive Impairments, Amyloid Load, Astrogliosis, and Neuroinflammation in APPSwe/PSEN1ΔE9 Mice Model of Amyloid Pathology
Authors: Tautou Marie , Descamps Florian , Larchanché Paul-Emmanuel , Buée Luc , El Bakali Jamal , Melnyk Patricia , Sergeant Nicolas
Published: March 2023

The progress in Alzheimer’s disease (AD) treatment suggests a combined therapeutic approach targeting the two lesional processes of AD, which include amyloid plaques made of toxic Aβ species and neurofibrillary tangles formed of aggregates of abnormally modified Tau proteins. A pharmacophoric design, novel drug synthesis, and structure-activity relationship enabled the selection of a polyamino biaryl PEL24-199 compound. The pharmacologic activity consists of a non-competitive β-secretase (BACE1) modulatory activity in cells. Curative treatment of the Thy-Tau22 model of Tau pathology restores short-term spatial memory, decreases neurofibrillary degeneration, and alleviates astrogliosis and neuroinflammatory reactions. Modulatory effects of PEL24-199 towards APP catalytic byproducts are described in vitro, but whether PEL24-199 can alleviate the Aβ plaque load and associated inflammatory counterparts in vivo remains to be elucidated. We investigated short- and long-term spatial memory, Aβ plaque load, and inflammatory processes in APPSwe/PSEN1ΔE9 PEL24-199 treated transgenic model of amyloid pathology to achieve this objective. PEL24-199 curative treatment induced the recovery of spatial memory and decreased the amyloid plaque load in association with decreased astrogliosis and neuroinflammation. The present results underline the synthesis and selection of a promising polyaminobiaryl-based drug that modulates both Tau and, in this case, APP pathology in vivo via a neuroinflammatory-dependent process.
Biomarker-Development Proteomics in Kidney Transplantation: An Updated Review
Authors: Sirolli Vittorio , Piscitani Luca , Bonomini Mario
Published: March 2023

Kidney transplantation (KT) is the optimal therapeutic strategy for patients with end-stage renal disease. The key to post-transplantation management is careful surveillance of allograft function. Kidney injury may occur from several different causes that require different patient management approaches. However, routine clinical monitoring has several limitations and detects alterations only at a later stage of graft damage. Accurate new noninvasive biomarker molecules are clearly needed for continuous monitoring after KT in the hope that early diagnosis of allograft dysfunction will lead to an improvement in the clinical outcome. The advent of “omics sciences”, and in particular of proteomic technologies, has revolutionized medical research. Proteomic technologies allow us to achieve the identification, quantification, and functional characterization of proteins/peptides in biological samples such as urine or blood through supervised or targeted analysis. Many studies have investigated proteomic techniques as potential molecular markers discriminating among or predicting allograft outcomes. Proteomic studies in KT have explored the whole transplant process: donor, organ procurement, preservation, and posttransplant surgery. The current article reviews the most recent findings on proteomic studies in the setting of renal transplantation in order to better understand the effective potential of this new diagnostic approach.
Transcriptome and Co-Expression Network Analysis Reveals the Molecular Mechanism of Rice Root Systems in Response to Low-Nitrogen Conditions
Authors: Wang Weiping , Xin Wei , Chen Ning , Yang Fan , Li Jia , Qu Guize , Jiang Xingdong , Xu Lu , Zhao Shijiao , Liu Hualong , Yang Luomiao , Zheng Hongliang , Zou Detang , Wang Jingguo
Published: March 2023

Nitrogen is an important nutrient for plant growth and essential metabolic processes. Roots integrally obtain nutrients from soil and are closely related to the growth and development of plants. In this study, the morphological analysis of rice root tissues collected at different time points under low-nitrogen and normal nitrogen conditions demonstrated that, compared with normal nitrogen treatment, the root growth and nitrogen use efficiency (NUE) of rice under low-nitrogen treatment were significantly improved. To better understand the molecular mechanisms of the rice root system’s response to low-nitrogen conditions, a comprehensive transcriptome analysis of rice seedling roots under low-nitrogen and control conditions was conducted in this study. As a result, 3171 differentially expressed genes (DEGs) were identified. Rice seedling roots enhance NUE and promote root development by regulating the genes related to nitrogen absorption and utilization, carbon metabolism, root growth and development, and phytohormones, thereby adapting to low-nitrogen conditions. A total of 25,377 genes were divided into 14 modules using weighted gene co-expression network analysis (WGCNA). Two modules were significantly associated with nitrogen absorption and utilization. A total of 8 core genes and 43 co-expression candidates related to nitrogen absorption and utilization were obtained in these two modules. Further studies on these genes will contribute to the understanding of low-nitrogen adaptation and nitrogen utilization mechanisms in rice.
Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein
Authors: Fairley Lauren H. , Lejri Imane , Grimm Amandine , Eckert Anne
Published: March 2023

Abnormal tau build-up is a hallmark of Alzheimer’s disease (AD) and more than 20 other serious neurodegenerative diseases. Mitochondria are paramount organelles playing a predominant role in cellular bioenergetics, namely by providing the main source of cellular energy via adenosine triphosphate generation. Abnormal tau impairs almost every aspect of mitochondrial function, from mitochondrial respiration to mitophagy. The aim of our study was to investigate the effects of spermidine, a polyamine which exerts neuroprotective effects, on mitochondrial function in a cellular model of tauopathy. Recent evidence identified autophagy as the main mechanism of action of spermidine on life-span prolongation and neuroprotection, but the effects of spermidine on abnormal tau-induced mitochondrial dysfunction have not yet been investigated. We used SH-SY5Y cells stably expressing a mutant form of human tau protein (P301L tau mutation) or cells expressing the empty vector (control cells). We showed that spermidine improved mitochondrial respiration, mitochondrial membrane potential as well as adenosine triphosphate (ATP) production in both control and P301L tau-expressing cells. We also showed that spermidine decreased the level of free radicals, increased autophagy and restored P301L tau-induced impairments in mitophagy. Overall, our findings suggest that spermidine supplementation might represent an attractive therapeutic approach to prevent/counteract tau-related mitochondrial impairments.
Global Analysis of Dark- and Heat-Regulated Alternative Splicing in Arabidopsis
Authors: Zhang Di , Chen Mo-Xian , Muhammad Aslam Mehtab , Liu Ying-Gao , Zhang Jianhua
Published: March 2023

Alternative splicing (AS) is one of the major post-transcriptional regulation mechanisms that contributes to plant responses to various environmental perturbations. Darkness and heat are two common abiotic factors affecting plant growth, yet the involvement and regulation of AS in the plant responses to these signals remain insufficiently examined. In this study, we subjected Arabidopsis seedlings to 6 h of darkness or heat stress and analyzed their transcriptome through short-read RNA sequencing. We revealed that both treatments altered the transcription and AS of a subset of genes yet with different mechanisms. Dark-regulated AS events were found enriched in photosynthesis and light signaling pathways, while heat-regulated AS events were enriched in responses to abiotic stresses but not in heat-responsive genes, which responded primarily through transcriptional regulation. The AS of splicing-related genes (SRGs) was susceptible to both treatments; while dark treatment mostly regulated the AS of these genes, heat had a strong effect on both their transcription and AS. PCR analysis showed that the AS of the Serine/Arginine-rich family gene SR30 was reversely regulated by dark and heat, and heat induced the upregulation of multiple minor SR30 isoforms with intron retention. Our results suggest that AS participates in plant responses to these two abiotic signals and reveal the regulation of splicing regulators during these processes.
The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies
Authors: Krop Juliette , Tian Xuezi , van der Hoorn Marie-Louise , Eikmans Michael
Published: March 2023

Pregnancy is a fascinating immunological paradox: the semi-allogeneic fetus generally grows without any complications. In the placenta, fetal trophoblast cells come into contact with maternal immune cells. Inaccurate or inadequate adaptations of the maternal immune system could lead to problems with the functioning of the placenta. Macrophages are important for tissue homeostasis, cleanup, and the repair of damaged tissues. This is crucial for a rapidly developing organ such as the placenta. The consensus on macrophages at the maternal-fetal interface in pregnancy is that a major proportion have an anti-inflammatory, M2-like phenotype, that expresses scavenger receptors and is involved in tissue remodeling and the dampening of the immune reactions. Recent multidimensional analyses have contributed to a more detailed outlook on macrophages. The new view is that this lineage represents a highly diverse phenotype and is more prevalent than previously thought. Spatial-temporal in situ analyses during gestation have identified unique interactions of macrophages both with trophoblasts and with T cells at different trimesters of pregnancy. Here, we elaborate on the role of macrophages during early human pregnancy and at later gestation. Their possible effect is reviewed in the context of HLA incompatibility between mother and fetus, first in naturally conceived pregnancies, but foremost in pregnancies after oocyte donation. The potential functional consequences of macrophages for pregnancy-related immune reactions and the outcome in patients with recurrent pregnancy loss are also discussed.
microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation
Authors: Desantis Vanessa , Potenza Maria Assunta , Sgarra Luca , Nacci Carmela , Scaringella Antonietta , Cicco Sebastiano , Solimando Antonio Giovanni , Vacca Angelo , Montagnani Monica
Published: March 2023

The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. Despite the currently available treatment approaches, the progression of AF, its recurrence rate, and the high mortality risk of related complications underlay the need for more advanced prognostic and therapeutic strategies. There is increasing attention on the molecular mechanisms controlling AF onset and progression points to the complex cell to cell interplay that triggers fibroblasts, immune cells and myofibroblasts, enhancing atrial fibrosis. In this scenario, endothelial cell dysfunction (ED) might play an unexpected but significant role. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level. In the cardiovascular compartment, both free circulating and exosomal miRNAs entail the control of plaque formation, lipid metabolism, inflammation and angiogenesis, cardiomyocyte growth and contractility, and even the maintenance of cardiac rhythm. Abnormal miRNAs levels may indicate the activation state of circulating cells, and thus represent a specific read-out of cardiac tissue changes. Although several unresolved questions still limit their clinical use, the ease of accessibility in biofluids and their prognostic and diagnostic properties make them novel and attractive biomarker candidates in AF. This article summarizes the most recent features of AF associated with miRNAs and relates them to potentially underlying mechanisms.
Metformin May Alter the Metabolic Reprogramming in Cancer Cells by Disrupting the L-Arginine Metabolism: A Preliminary Computational Study
Authors: Espinosa-Rodriguez Bryan Alejandro , Treviño-Almaguer Daniela , Carranza-Rosales Pilar , Ramirez-Cabrera Monica Azucena , Ramirez-Estrada Karla , Arredondo-Espinoza Eder Ubaldo , Mendez-Lopez Luis Fernando , Balderas-Renteria Isaias
Published: March 2023

Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin’s anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.
Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode
Authors: Burke Adam , Di Filippo Mara , Spiccio Silvia , Schito Anna Maria , Caviglia Debora , Brullo Chiara , Baumann Marcus
Published: March 2023

Multi-drug resistant bacterial strains (MDR) have become an increasing challenge to our health system, resulting in multiple classical antibiotics being clinically inactive today. As the de-novo development of effective antibiotics is a very costly and time-consuming process, alternative strategies such as the screening of natural and synthetic compound libraries is a simple approach towards finding new lead compounds. We thus report on the antimicrobial evaluation of a small collection of fourteen drug-like compounds featuring indazoles, pyrazoles and pyrazolines as key heterocyclic moieties whose synthesis was achieved in continuous flow mode. It was found that several compounds possessed significant antibacterial potency against clinical and MDR strains of the Staphylococcus and Enterococcus genera, with the lead compound (9) reaching MIC values of 4 µg/mL on those species. In addition, time killing experiments performed on compound 9 on Staphylococcus aureus MDR strains highlight its activity as bacteriostatic. Additional evaluations regarding the physiochemical and pharmacokinetic properties of the most active compounds are reported and showcased, promising drug-likeness, which warrants further explorations of the newly identified antimicrobial lead compound.
Integral Equations of the First Kind for Calculating Electro- and Magnetostatic Fields Perturbed by Conductors and Ferro-Magnets
Authors: Plugatar Yurij , Filippov Dmitriy , Chabanov Vladimir , Kazak Anatoliy , Korzin Vadim , Oleinikov Nikolay , Mayorova Angela , Nekhaychuk Dmitry
Published: March 2023

The aim of the study was to develop a methodology for calculating and optimizing devices for the magnetic exploration of fossils containing materials with a high magnetic permeability. The proposed technique is based on the calculation of electrostatic fields perturbed by conducting bodies and of magnetic fields perturbed by ferromagnets with a high magnetic permeability. It uses an integral equation of the first kind. This technique is preferable to the technique consisting in the use of an integral equation of the second kind, since in the situation under consideration, the latter does not have a unique solution and requires transformation. Prospects for the development of this area allow one to bring geophysical services to the service market on a new scientific and technical production level; reduce the environmental burden on nature by replacing magnetometric measurements with energy-saving, environmentally safe technology; and ensure the export potential of magnetometric equipment.
Practical Pharmacological Treatment of Heart Failure: Does Ejection Fraction Matter Anymore?
Authors: Chan Jonathan C. H. , Cowley Emily , Chan Michael
Published: March 2023

Heart failure (HF) is a complex clinical syndrome involving structural and/or functional abnormalities of the heart. Heart failure is often classified based on left ventricular ejection fraction, which serves as a predictor of mortality. The majority of the data supporting disease-modifying pharmacological therapies are from patients with reduced ejection fraction (less than 40%). However, with the recent results from the sodium glucose cotransporter-2 inhibitor trials, there is renewed interest in identifying potential beneficial pharmacological therapies. This review focuses on and includes pharmacological HF therapies across the spectrum of ejection fraction, providing an overview of the novel trials. We also examined the effects of the treatments on mortality, hospitalization, functional status, and biomarker levels to further investigate the interplay between ejection fraction and HF.
Telepsychology in Europe since COVID-19: How to Foster Social Telepresence?
Authors: Haddouk Lise , Milcent Carine , Schneider Benoît , Van Daele Tom , De Witte Nele A. J.
Published: March 2023

All over the world, measures were taken to prevent the spread of COVID-19. Social distancing not only had a strong influence on mental health, but also on the organization of care systems. It changed existing practices, as we had to rapidly move from face-to-face contact to remote contact with patients. These changes have prompted research into the attitudes of mental healthcare professionals towards telepsychology. Several factors affect these attitudes: at the institutional and organizational level, but also the collective and personal experience of practitioners. This paper is based on an original European survey conducted by the EFPA (European Federation of Psychologists’ Associations) Project Group on eHealth in 2020, which allowed to observe the variability in perceptions of telepsychology between countries and mental healthcare professionals. This study highlights different variables that contributed to the development of attitudes, such as motivations, acquired experience, or training. We found the “feeling of telepresence”—which consists of forgetting to some extent that we are at a distance, in feeling together—and social telepresence in particular as main determinants of the perception and the practice of telepsychology.
A Novel CT Perfusion-Based Fractional Flow Reserve Algorithm for Detecting Coronary Artery Disease
Authors: Gao Xuelian , Wang Rui , Sun Zhonghua , Zhang Hongkai , Bo Kairui , Xue Xiaofei , Yang Junjie , Xu Lei
Published: March 2023

Background: The diagnostic accuracy of fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFR-CT) needs to be further improved despite promising results available in the literature. While an innovative myocardial computed tomographic perfusion (CTP)-derived fractional flow reserve (CTP-FFR) model has been initially established, the feasibility of CTP-FFR to detect coronary artery ischemia in patients with suspected coronary artery disease (CAD) has not been proven. Methods: This retrospective study included 93 patients (a total of 103 vessels) who received CCTA and CTP for suspected CAD. Invasive coronary angiography (ICA) was performed within 2 weeks after CCTA and CTP. CTP-FFR, CCTA (stenosis ≥ 50% and ≥70%), ICA, FFR-CT and CTP were assessed by independent laboratory experts. The diagnostic ability of the CTP-FFR grouped by quantitative coronary angiography (QCA) in mild (30–49%), moderate (50–69%) and severe stenosis (≥70%) was calculated. The effect of calcification of lesions, grouped by FFR on CTP-FFR measurements, was also assessed. Results: On the basis of per-vessel level, the AUCs for CTP-FFR, CTP, FFR-CT and CCTA were 0.953, 0.876, 0.873 and 0.830, respectively (all p < 0.001). The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CTP-FFR for per-vessel level were 0.87, 0.88, 0.87, 0.85 and 0.89 respectively, compared with 0.87, 0.54, 0.69, 0.61, 0.83 and 0.75, 0.73, 0.74, 0.70, 0.77 for CCTA ≥ 50% and ≥70% stenosis, respectively. On the basis of per-vessel analysis, CTP-FFR had higher specificity, accuracy and AUC compared with CCTA and also higher AUC compared with FFR-CT or CTP (all p < 0.05). The sensitivity and accuracy of CTP-FFR + CTP + FFR-CT were also improved over FFR-CT alone (both p < 0.05). It also had improved specificity compared with FFR-CT or CTP alone (p < 0.01). A strong correlation between CTP-FFR and invasive FFR values was found on per-vessel analysis (Pearson’s correlation coefficient 0.89). The specificity of CTP-FFR was higher in the severe calcification group than in the low calcification group (p < 0.001). Conclusions: A novel CTP-FFR model has promising value to detect myocardial ischemia in CAD, particularly in mild-to-moderate stenotic lesions.
After SARS-CoV-2 Pandemics: New Insights into ICU-Acquired Pneumonia
Authors: Timsit Jean-Francois
Published: March 2023

SARS-CoV-2 pandemics profoundly modified the process of hospital care [...]
Suppression of Fusarium Wilt in Watermelon by Bacillus amyloliquefaciens DHA55 through Extracellular Production of Antifungal Lipopeptides
Authors: Al-Mutar Dhabyan Mutar Kareem , Alzawar Noor Salih Abduljaleel , Noman Muhammad , Azizullah  , Li Dayong , Song Fengming
Published: March 2023

Fusarium wilt caused by Fusarium oxysporum f. sp. niveum is one of the most devastating fungal diseases affecting watermelon (Citrullus lanatus L.). The present study aimed to identify potent antagonistic bacterial strains with substantial antifungal activity against F. oxysporum f. sp. niveum and to explore their potential for biocontrol of Fusarium wilt in watermelon. Out of 77 isolates from watermelon rhizosphere, six bacterial strains—namely, DHA4, DHA6, DHA10, DHA12, DHA41, and DHA55—exhibited significant antifungal activity against F. oxysporum f. sp. niveum, as well as other phytopathogenic fungi, including Didymella bryoniae, Sclerotinia sclerotiorum, Fusarium graminearum, and Rhizoctonia solani. These Gram-positive, rod-shaped, antagonistic bacterial strains were able to produce exo-enzymes (e.g., catalase, protease, and cellulase), siderophore, and indole-3-acetic acid and had the ability to solubilize phosphate. In greenhouse experiments, these antagonistic bacterial strains not only promoted plant growth but also suppressed Fusarium wilt in watermelon. Among these strains, DHA55 was the most effective, achieving the highest disease suppression of 74.9%. Strain DHA55 was identified as Bacillus amyloliquefaciens based on physiological, biochemical, and molecular characterization. B. amyloliquefaciens DHA55 produced various antifungal lipopeptides, including iturin, surfactin, and fengycin, that showed significant antifungal activities against F. oxysporum f. sp. niveum. Microscopic observations revealed that B. amyloliquefaciens DHA55 exhibited an inhibitory effect against F. oxysporum f. sp. niveum on the root surface of watermelon plants. These results demonstrate that B. amyloliquefaciens DHA55 can effectively promote plant growth and suppress the development of watermelon Fusarium wilt, providing a promising agent for the biocontrol of Fusarium wilt in watermelon.
TIPE2 Inhibits MGD Inflammation by Regulating Macrophage Polarization
Authors: Zhao Songjiao , Shen Yankun , Wu Shinan , Shao Yi , Shi Ruize , Yan Yan , Zhao Hui
Published: March 2023

Background: The aim of this study was to decide the role of the polarization of macrophages regulated by tumor necrosis factor-α (TNF-α)-induced protein 8-like 2 (TIPE2) in meibomian gland dysfunction (MGD). Methods: Firstly, the secretory function of the meibomian gland (MG) in apolipoprotein E knockout (ApoE-/-) MGD mice and normal mice was detected by oil red staining. Then, the expression levels of markers of M1 and M2 macrophages were detected by immunofluorescence staining in MGD, normal mice, and mild and severe MGD corpses to decide the role of M1 and M2 macrophages in MGD inflammation. Meanwhile, the expression levels of TIPE2 in MGD mice and MGD patients were detected by immunofluorescence staining, and the correlations among TIPE2, M1 and M2 macrophages were analyzed by immunofluorescence double staining in MGD mice and MGD patients. Furthermore, lipopolysaccharide (LPS) and interleulkin-4 (IL-4) were used to induce M1 and M2 polarization of macrophages, and the mRNA level of TIPE2 was detected in M1 and M2 macrophages. Results: Oil red staining showed that eyelid fat congestion was more severe in (ApoE-/-) MGD mice than in normal mice, and the M1 macrophage was the primary inflammatory cell infiltrated in (ApoE-/-) MGD mice (p < 0.05). The results of the immunofluorescence staining showed that the infiltration of macrophages in MGD mice was more obvious than that in the normal group, and M1 macrophage was the dominant group (p < 0.05). Similar to the results of the MGD mouse model, more macrophage infiltration was observed in MGD patients’ MG tissues, and there were more M1 cells in the severe group than in the mild group (p < 0.05). Moreover, the expression of TIPE2 was positively correlated with the expression of M2 macrophages in MGD patients and mice MG tissues (p < 0.05). The expression of TIPE2 mRNA in LPS-induced M1 macrophages declined, while the expression of TIPE2 mRNA in IL-4-induced M2 macrophages increased (p < 0.05). Conclusion: M1 macrophage was the dominant group infiltrated in the MG tissue of MGD, and TIPE2 is a potential anti-inflammatory target for preventing the development of MGD by promoting the M2 polarization of macrophages.
Endoscopic and Image Analysis of the Airway in Patients with Mucopolysaccharidosis Type IVA
Authors: Lee Yi-Hao , Su Chin-Hui , Lin Che-Yi , Lin Hsiang-Yu , Lin Shuan-Pei , Chuang Chih-Kuang , Lee Kuo-Sheng
Published: March 2023

Mucopolysaccharidosis (MPS) is a hereditary disorder arising from lysosomal enzymes deficiency, with glycosaminoglycans (GAGs) storage in connective tissues and bones, which may compromise the airway. This retrospective study evaluated patients with MPS type IVA with airway obstruction detected via endoscopy and imaging modalities and the effects of surgical interventions based on symptoms. The data of 15 MPS type IVA patients (10 males, 5 females, mean age 17.8 years) were reviewed in detail. Fiberoptic bronchoscopy (FB) was used to distinguish adenotonsillar hypertrophy, prolapsed soft palate, secondary laryngomalacia, vocal cord granulation, cricoid thickness, tracheal stenosis, shape of tracheal lumen, nodular deposition, tracheal kinking, tracheomalacia with rigid tracheal wall, and bronchial collapse. Computed tomography (CT) helped to measure the deformed sternal angle, the cross-sectional area of the trachea, and its narrowest/widest ratio (NW ratio), while angiography with 3D reconstruction delineated tracheal torsion, kinking, or framework damage and external vascular compression of the trachea. The NW ratio correlated negatively with age (p < 0.01), showing that airway obstruction progressed gradually. Various types of airway surgery were performed to correct the respiratory dysfunction. MPS type IVA challenges the management of multifactorial airway obstruction. Preoperative airway evaluation with both FB and CT is strongly suggested to assess both intraluminal and extraluminal factors causing airway obstruction.
The Naive Estimator of a Poisson Regression Model with a Measurement Error
Authors: Wada Kentarou , Kurosawa Takeshi
Published: March 2023

We generalize the naive estimator of a Poisson regression model with a measurement error as discussed in Kukush et al. in 2004. The explanatory variable is not always normally distributed as they assume. In this study, we assume that the explanatory variable and measurement error are not limited to a normal distribution. We clarify the requirements for the existence of the naive estimator and derive its asymptotic bias and asymptotic mean squared error (MSE). The requirements for the existence of the naive estimator can be expressed using an implicit function, which the requirements can be deduced by the characteristic of the Poisson regression models. In addition, using the implicit function obtained from the system of equations of the Poisson regression models, we propose a consistent estimator of the true parameter by correcting the bias of the naive estimator. As illustrative examples, we present simulation studies that compare the performance of the naive estimator and new estimator for a Gamma explanatory variable with a normal error or a Gamma error.
On Asymmetric Correlations and Their Applications in Financial Markets
Authors: Cao Linyu , Sun Ruili , Ma Tiefeng , Liu Conan
Published: March 2023

Progress on asymmetric correlations of asset returns has recently advanced considerably. Asymmetric correlations can cause problems in hedging effectiveness and overstate the value of diversification. Furthermore, considering the asymmetric correlations in portfolio construction significantly enhances performance. The purpose of this paper is to trace developments and identify areas that require further research. We examine three aspects of asymmetric correlations: first, the existence of asymmetric correlations between asset returns and their significance tests; second, the test on the existence of asymmetric correlations between different markets and financial assets; and third, the root cause analysis of asymmetric correlations. In the first part, the contents of extreme value theory, the H statistic and a model-free test are covered. In the second part, commonly used models such as copula and GARCH are included. In addition to the GARCH and copula formulations, many other methods are included, such as regime switching, the Markov switching model, and the multifractal asymmetric detrend cross-correlation analysis method. In addition, we compare the advantages and differences between the models. In the third part, the causes of asymmetry are discussed, for example, higher common fundamental risk, correlation of individual fundamental risk, and so on.