bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat Stress Decreases Intestinal Physiological Function and Facilitates the Proliferation of Harmful Intestinal Microbiota in Sturgeons
Authors: Yang Shiyong , Zhang Chaoyang , Xu Wenqiang , Li Datian , Feng Yang , Wu Jiayun , Luo Wei , Du Xiaogang , Du Zongjun , Huang Xiaoli
Published: March 2022

Heat is a common source of stress in aquatic environments and can alter the physiological and metabolic functions of aquatic animals, especially their intestinal function. Here, the effects of heat stress on the structure and function of the intestine and the characteristics of the intestinal microbiota were studied in sturgeon (Acipenser baerii ♀ × Acipenser schrenckii ♂ hybrid F1). Sturgeons were exposed to sub-extreme (24°C) and extreme (28°C) high water temperatures for 12 days. The heat stress caused systemic damage to the intestine of sturgeons, which displayed severe enteritis in the valve intestine. The microbial diversity analysis showed that heat stress led to the disorder in intestinal microbiota, manifesting as an explosive increase in the abundance of thermophilic intestinal pathogens such as Plesiomonas, Cetobacterium, and Aeromonas and causing physiological dysfunction in the sturgeons. The disorder was followed by significant inhibition of intestinal digestion with reduced chymotrypsin, α-amylase, and lipase activities in the valve intestine and of antioxidant function with reduced peroxidase (POD) and catalase (CAT) activities. Simultaneously, heat stress reduced the thermal tolerance of sturgeons by reducing Grp75 expression and damaged the valve intestine’s repair ability with increased Tgf-β expression. The results confirmed that heat stress damaged the sturgeon intestines obviously and disturbed the intestinal microbiota, resulting in serious physiological dysfunction. The present study investigated the mechanism of the effect of heat stress on the sturgeon intestine and will help develop strategies to improve the resistance to thermal stress for wild and cultured sturgeons.
Cytobacts: Abundant and Diverse Vertically Seed-Transmitted Cultivation-Recalcitrant Intracellular Bacteria Ubiquitous to Vascular Plants
Authors: Thomas Pious , Rajendran Thekepat P. , Franco Christopher M. M.
Published: March 2022

We have recently described ‘Cytobacts’ as abundant intracellular endophytic bacteria inhabiting live plant cells based on the observations with callus and cell suspension cultures of grapevine and other plant species with the origin ascribable to field explants. In this study, we investigated the prevalence of such cytoplasmic bacterial associations in field plants across different taxa, their cultivability, and the extent of taxonomic diversity and explored the possibility of their embryo-mediated vertical transmission. Over 100 genera of field plants were surveyed for ‘Cytobacts’ through bright-field live-cell imaging as per our previous experience using fresh tissue sections from surface-sterilized shoot-tissues with parallel cultivation-based assessments. This revealed widespread cellular bacterial associations visualized as copious motile micro-particles in the cytoplasm with no or sparse colony forming units (CFU) from the tissue-homogenates indicating their general non-cultivability. Based on the ease of detection and the abundance of ‘Cytobacts’ in fresh tissue sections, the surveyed plants were empirically classified into three groups: (i) motile bacteria detected instantly in most cells; (ii) motility not so widely observed, but seen in some cells; and (iii) only occasional motile units observed, but abundant non-motile bacterial cells present. Microscopy versus 16S-rRNA V3–V4 amplicon profiling on shoot-tip tissues of four representative plants—tomato, watermelon, periwinkle, and maize—showed high bacterial abundance and taxonomic diversity (11–15 phyla) with the dominance of Proteobacteria followed by Firmicutes/Actinobacteria, and several other phyla in minor shares. The low CFU/absence of bacterial CFU from the tissue homogenates on standard bacteriological media endorsed their cultivation-recalcitrance. Intracellular bacterial colonization implied that the associated organisms are able to transmit vertically to the next generation through the seed-embryos. Microscopy and 16S-rRNA V3–V4 amplicon/metagenome profiling of mature embryos excised from fresh watermelon seeds revealed heavy embryo colonization by diverse bacteria with sparse or no CFU. Observations with grapevine fresh fruit-derived seeds and seed-embryos endorsed the vertical transmission by diverse cultivation-recalcitrant endophytic bacteria (CREB). By and large, Proteobacteria formed the major phylum in fresh seed-embryos with varying shares of diverse phyla. Thus, we document ‘Cytobacts’ comprising diverse and vertically transmissible CREBs as a ubiquitous phenomenon in vascular plants.
Involvement of the Dorsal Vagal Complex in Alcohol-Related Behaviors
Authors: Keller Bailey N. , Hajnal Andras , Browning Kirsteen N. , Arnold Amy C. , Silberman Yuval
Published: March 2022

The neurobiological mechanisms that regulate the development and maintenance of alcohol use disorder (AUD) are complex and involve a wide variety of within and between systems neuroadaptations. While classic reward, preoccupation, and withdrawal neurocircuits have been heavily studied in terms of AUD, viable treatment targets from this established literature have not proven clinically effective as of yet. Therefore, examination of additional neurocircuitries not classically studied in the context of AUD may provide novel therapeutic targets. Recent studies demonstrate that various neuropeptides systems are important modulators of alcohol reward, seeking, and intake behaviors. This includes neurocircuitry within the dorsal vagal complex (DVC), which is involved in the control of the autonomic nervous system, control of intake of natural rewards like food, and acts as a relay of interoceptive sensory information via interactions of numerous gut-brain peptides and neurotransmitter systems with DVC projections to central and peripheral targets. DVC neuron subtypes produce a variety of neuropeptides and transmitters and project to target brain regions critical for reward such as the mesolimbic dopamine system as well as other limbic areas important for the negative reinforcing and aversive properties of alcohol withdrawal such as the extended amygdala. This suggests the DVC may play a role in the modulation of various aspects of AUD. This review summarizes the current literature on neurotransmitters and neuropeptides systems in the DVC (e.g., norepinephrine, glucagon-like peptide 1, neurotensin, cholecystokinin, thyrotropin-releasing hormone), and their potential relevance to alcohol-related behaviors in humans and rodent models for AUD research. A better understanding of the role of the DVC in modulating alcohol related behaviors may lead to the elucidation of novel therapeutic targets for drug development in AUD.
G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation
Authors: Ham Hyeon Joo , Lee Yong Sun , Lee Hee Pom , Ham Young Wan , Yun Jaesuk , Han Sang Bae , Hong Jin Tae
Published: March 2022

Chronic stress is thought to be a major contributor to the onset of mental disorders such as anxiety disorders. Several studies have demonstrated a correlation between anxiety state and neuroinflammation, but the detailed mechanism is unclear. Chitinase-3-like 1 (CHI3L1) is expressed in several chronic inflammatorily damaged tissues and is well known to play a major role in mediating inflammatory responses. In the present study, we investigated the anxiolytic-like effect of N-Allyl-2-[(6-butyl-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl)sulfanyl]acetamide (G721-0282), an inhibitor of CHI3L1, on mice treated with chronic unpredictable mild stress (CUMS), as well as the mechanism of its action. We examined the anxiolytic-like effect of G721-0282 by conducting several behavioral tests with oral administration of G721-0282 to CUMS-treated BALB/c male mice. We found that administration of G721-0282 relieves CUMS-induced anxiety. Anxiolytic-like effects of G721-0282 have been shown to be associated with decreased expressions of CUMS-induced inflammatory proteins and cytokines in the hippocampus. The CUMS-elevated levels of CHI3L1 and IGFBP3 were inhibited by treatment with G721-0282 in vivo and in vitro. However, CHI3L1 deficiency abolished the anti-inflammatory effects of G721-0282 in microglial BV-2 cells. These results suggest that G721-0282 could lower CUMS-induced anxiety like behaviors by regulating IGFBP3-mediated neuroinflammation via inhibition of CHI3L1.
The Specific Role of Reactive Astrocytes in Stroke
Authors: Li Leiyang , Zhou Jinpeng , Han Liying , Wu Xun , Shi Yingwu , Cui Wenxing , Zhang Shenghao , Hu Qing , Wang Jin , Bai Hao , Liu Haixiao , Guo Wei , Feng Dayun , Qu Yan
Published: March 2022

Astrocytes are essential in maintaining normal brain functions such as blood brain barrier (BBB) homeostasis and synapse formation as the most abundant cell type in the central nervous system (CNS). After the stroke, astrocytes are known as reactive astrocytes (RAs) because they are stimulated by various damage-associated molecular patterns (DAMPs) and cytokines, resulting in significant changes in their reactivity, gene expression, and functional characteristics. RAs perform multiple functions after stroke. The inflammatory response of RAs may aggravate neuro-inflammation and release toxic factors to exert neurological damage. However, RAs also reduce excitotoxicity and release neurotrophies to promote neuroprotection. Furthermore, RAs contribute to angiogenesis and axonal remodeling to promote neurological recovery. Therefore, RAs’ biphasic roles and mechanisms make them an effective target for functional recovery after the stroke. In this review, we summarized the dynamic functional changes and internal molecular mechanisms of RAs, as well as their therapeutic potential and strategies, in order to comprehensively understand the role of RAs in the outcome of stroke disease and provide a new direction for the clinical treatment of stroke.
Past and Future Explanations for Depersonalization and Derealization Disorder: A Role for Predictive Coding
Authors: Gatus Andrew , Jamieson Graham , Stevenson Bruce
Published: March 2022

Depersonalization (DP) and derealization (DR) refer to states of dissociation in which one feels a sense of alienation in relation to one’s self and environment, respectively. Whilst transient episodes often diminish without treatment, chronic experiences of DP and DR may last for years, with common treatments lacking a strong evidence base for their efficacy. We propose a theoretical explanation of DP and DR based on interoceptive predictive coding, and discuss how transient experiences of DP and DR may be induced in the non-clinical population using virtual reality. Further, we review the use of heartbeat evoked potentials in detecting the neural correlates of DP and DR allowing for an objective measure of these experiences in the non-clinical population. Finally, we discuss how the induction and detection of transient experiences of DP and DR in the non-clinical population could shed light on how the brain constructs one’s sense of self and reality.
Software Bug Detection Causes a Shift From Bottom-Up to Top-Down Effective Connectivity Involving the Insula Within the Error-Monitoring Network
Authors: Castelhano Joao , Duarte Isabel C. , Couceiro Ricardo , Medeiros Julio , Duraes Joao , Afonso Sónia , Madeira Henrique , Castelo-Branco Miguel
Published: March 2022

The neural correlates of software programming skills have been the target of an increasing number of studies in the past few years. Those studies focused on error-monitoring during software code inspection. Others have studied task-related cognitive load as measured by distinct neurophysiological measures. Most studies addressed only syntax errors (shallow level of code monitoring). However, a recent functional MRI (fMRI) study suggested a pivotal role of the insula during error-monitoring when challenging deep-level analysis of code inspection was required. This raised the hypothesis that the insula is causally involved in deep error-monitoring. To confirm this hypothesis, we carried out a new fMRI study where participants performed a deep source-code comprehension task that included error-monitoring to detect bugs in the code. The generality of our paradigm was enhanced by comparison with a variety of tasks related to text reading and bugless source-code understanding. Healthy adult programmers (N = 21) participated in this 3T fMRI experiment. The activation maps evoked by error-related events confirmed significant activations in the insula [p(Bonferroni) < 0.05]. Importantly, a posterior-to-anterior causality shift was observed concerning the role of the insula: in the absence of error, causal directions were mainly bottom-up, whereas, in their presence, the strong causal top-down effects from frontal regions, in particular, the anterior cingulate cortex was observed.
F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
Authors: Liu Xiao-zhou , Jin Yuan , Chen Sen , Xu Kai , Xie Le , Qiu Yue , Wang Xiao-hui , Sun Yu , Kong Wei-jia
Published: March 2022

Mutations in the GJB2 gene encoding connexin26 (Cx26) protein are one of the most common causes of hereditary deafness. Previous studies have found that different Cx26-null mouse models have severe hearing loss and deformity of the organ of Corti (OC) as well as a reduction in microtubules in pillar cells (PCs). To explore the underlying mechanism of OC deformity caused by Cx26 downregulation further, we established Cx26 knockdown (KD) mouse models at postnatal days (P)0 and P8. The actin filaments contained in the pillar cells of mice in the P0 KD group were reduced by 54.85% and vinculin was increased by 22%, while the outer hair cells (OHCs) showed normal F-actin content. In the P8 KD group, PCs and OHCs of mice also showed almost normal F-actin content. The G-actin/F-actin ratio increased by 38% in the P0 KD group. No significant change was found in the mRNA or protein expression level of G-actin or the cadherin–catenin core complex in the P0 KD group at P6. Moreover, immunofluorescence showed that the intensity of LRRK2 was reduced by 97% in the P0 KD group at P6. Our results indicate that Cx26 is involved in the maturation of the cytoskeleton during the development of the OC at the early postnatal stage. The polymerization of G-actin into F-actin is prevented in Cx26 KD mice.
Slc6a20a Heterozygous and Homozygous Mutant Mice Display Differential Behavioral and Transcriptomic Changes
Authors: Kim Junhyung , Roh Junyeop Daniel , Kim Seongbin , Kang Hyojin , Bae Mihyun , Kim Eunjoon
Published: March 2022

SLC6A20A is a proline and glycine transporter known to regulate glycine homeostasis and NMDA receptor (NMDAR) function in the brain. A previous study found increases in ambient glycine levels and NMDA receptor-mediated synaptic transmission in the brains of Slc6a20a-haploinsufficient mice, but it remained unknown whether Slc6a20a deficiency leads to disease-related behavioral deficits in mice. Here, we report that Slc6a20a heterozygous and homozygous mutant mice display differential behavioral phenotypes in locomotor, repetitive behavioral, and spatial and fear memory domains. In addition, these mice show differential transcriptomic changes in synapse, ribosome, mitochondria, autism, epilepsy, and neuron-related genes. These results suggest that heterozygous and homozygous Slc6a20a deletions in mice lead to differential changes in behaviors and transcriptomes.
APOBEC Mutational Signature and Tumor Mutational Burden as Predictors of Clinical Outcomes and Treatment Response in Patients With Advanced Urothelial Cancer
Authors: Natesan Divya , Zhang Li , Martell Henry J. , Jindal Tanya , Devine Patrick , Stohr Bradley , Espinosa-Mendez Carlos , Grenert James , Van Ziffle Jessica , Joseph Nancy , Umetsu Sarah , Onodera Courtney , Turski Michelle , Chan Emily , Desai Arpita , Aggarwal Rahul , Wong Anthony , Porten Sima , Chou Jonathan , Friedlander Terence , Fong Lawrence , Small Eric J. , Sweet-Cordero Alejandro , Koshkin Vadim S.
Published: March 2022

Introduction

Tumor mutational burden (TMB) and APOBEC mutational signatures are potential prognostic markers in patients with advanced urothelial carcinoma (aUC). Their utility in predicting outcomes to specific therapies in aUC warrants additional study.

Methods

We retrospectively reviewed consecutive UC cases assessed with UCSF500, an institutional assay that uses hybrid capture enrichment of target DNA to interrogate 479 common cancer genes. Hypermutated tumors (HM), defined as having TMB ≥10 mutations/Mb, were also assessed for APOBEC mutational signatures, while non-HM (NHM) tumors were not assessed due to low TMB. The logrank test was used to determine if there were differences in overall survival (OS) and progression-free survival (PFS) among patient groups of interest.

Results

Among 75 aUC patients who had UCSF500 testing, 46 patients were evaluable for TMB, of which 19 patients (41%) had HM tumors and the rest had NHM tumors (27 patients). An additional 29 patients had unknown TMB status. Among 19 HM patients, all 16 patients who were evaluable for analysis had APOBEC signatures. HM patients (N=19) were compared with NHM patients (N=27) and had improved OS from diagnosis (125.3 months vs 35.7 months, p=0.06) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.04). Patients with APOBEC (N=16) were compared with remaining 56 patients, comprised of 27 NHM patients and 29 patients with unknown TMB, showing APOBEC patients to have improved OS from diagnosis (125.3 months vs 44.5 months, p=0.05) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.05). Neither APOBEC nor HM status were associated with response to immunotherapy.

Conclusions

In a large, single-institution aUC cohort assessed with UCSF500, an institutional NGS panel, HM tumors were common and all such tumors that were evaluated for mutational signature analysis had APOBEC signatures. APOBEC signatures and high TMB were prognostic of improved OS from diagnosis and both analyses also predicted inferior outcomes with chemotherapy treatment.
Management of Chronic Myeloid Leukemia and Pregnancy: A Bibliometric Analysis (2000-2020)
Authors: Wang Yue , Jiang Liqing , Li Baoxuan , Zhao Yan
Published: March 2022

Background

Given the increasing number and survival rates of reproductive-age patients with chronic myeloid leukemia (CML), several studies aimed to elucidate optimum disease management in pregnancy. This study aimed to use bibliometric analysis to assess focus and reported insights, as well as future trends, in CML and pregnancy research.

Methods

We extracted all studies related to CML and pregnancy from the Web of Science database from 2001 to 2020. VOS Viewer, CiteSpace, Python, and R-bibliometrix were used for bibliometric analysis, revealing the leading research countries, institutions, and authors, as well as distribution of keywords (frequency greater than five).

Results

A total of 196 records, published in 137 journals by 1,105 authors from 421 research institutes in 50 countries, were identified for analysis. The United States was the leader in the number of publications. Imperial College London and National Research Center for Hematology were the most influential institutions. In addition, Apperley J, Cortes J, Abruzzese E and Kantarjian H were the leading authors in the field. Keyword analysis identified four research hotspot clusters.

Conclusions

This study systematically analyzed the progress in CML and pregnancy research in the last 20 years. The present findings suggest that the management of planned and unplanned pregnancies in patients with CML will remain a research focus, as further evidence is required for the development of treatment guidelines.
A Systematic Review of Candidate miRNAs, Its Targeted Genes and Pathways in Chronic Myeloid Leukemia–An Integrated Bioinformatical Analysis
Authors: Elias Marjanu Hikmah , Syed Mohamad Syarifah Faezah , Abdul Hamid Nazefah
Published: March 2022

Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully used to treat CML, there are still cases of resistance. The resistance occurred mainly due to the mutation in the tyrosine kinase domain of the BCR-ABL1 gene. However, there are still many cases with unknown causes of resistance as the etiopathology of CML are not fully understood. Thus, it is crucial to figure out the complete pathogenesis of CML, and miRNA can be one of the essential pathogeneses. The objective of this study was to systematically review the literature on miRNAs that were differentially expressed in CML cases. Their target genes and downstream genes were also explored. An electronic search was performed via PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct. The following MeSH (Medical Subject Heading) terms were used: chronic myeloid leukaemia, genes and microRNAs in the title or abstract. From 806 studies retrieved from the search, only clinical studies with in-vitro experimental evidence on the target genes of the studied miRNAs in CML cells were included. Two independent reviewers independently scrutinised the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. Study design, sample size, sampling type, and the molecular method used were identified for each study. The pooled miRNAs were analysed using DIANA tools, and target genes were analysed with DAVID, STRING and Cytoscape MCODE. Fourteen original research articles on miRNAs in CML were included, 26 validated downstream genes and 187 predicted target genes were analysed and clustered into 7 clusters. Through GO analysis, miRNAs’ target genes were localised throughout the cells, including the extracellular region, cytosol, and nucleus. Those genes are involved in various pathways that regulate genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration of CML cells.
To Wrap or Not? Utility of Anti-reflux Procedure in Infants Needing Gastrostomy Tubes
Authors: Khan Faraz A. , Nestor Kelsey , Hashmi Asra , Islam Saleem
Published: March 2022

Purpose

Gastrostomy tube (GT) insertion is commonly performed in children with failure to thrive. Pediatric patients' frequently have gastroesophageal reflux (GER) and discerning pathological GER can be challenging. Moreover, there is some evidence that GT insertion may lead to worsening GER and to avoid a subsequent anti-reflux procedure (ARP), though controversial some surgeons advocate considering an ARP concomitantly. The purpose of this report is to assess outcomes in infants who underwent a GT vs. GT with ARP.

Methods

Retrospective review of all infants who had a GT placed at a single institution from 2009–2014. The patients were then divided into two cohorts based on the index operation i.e., GT vs GT with ARP and outcomes compared.

Results

226 operations (104 GT, 122 GT with ARP) were performed. The cohorts were similar in gender, gestational age, race, weight, median age, LOS, and proportion of neurologically impaired patients. Preoperative GER was significantly higher in the GT with ARP cohort (91 vs. 18%). No difference in the rate of immediate complications was noted between the two groups. Postoperative increase in anti-reflux medications was significantly higher in the GT cohort (p = 0.01). Post-op GER needing a secondary procedure (ARP or GJ tube) was noted in 21/104 (20%) patients. Those needing an additional procedure vs. those with GT alone were similar in the proportion of patients with pre-op GER, neurologic impairment, type of feeds, and age.

Conclusion

Identifying patients who would benefit from a concomitant ARP remains challenging. A fifth of GT patients needed a subsequent procedure despite most high-risk patients having already undergone an ARP. Since the overall rate of complications remained similar, initial GT approach can be considered reasonable.
Isolation and Pharmacological Characterization of α-Elapitoxin-Oh3a, a Long-Chain Post-Synaptic Neurotoxin From King Cobra (Ophiophagus hannah) Venom
Authors: Huynh Tam M. , Silva Anjana , Isbister Geoffrey K. , Hodgson Wayne C.
Published: March 2022

The King Cobra (Ophiophagus hannah) is the world’s largest venomous snake and has a widespread geographical distribution throughout Southeast Asia. Despite proteomic studies indicating the presence of postsynaptic neurotoxins in O. hannah venom, there are few pharmacological investigations of these toxins. We isolated and characterized α-elapitoxin-Oh3a (α-EPTX-Oh3a; 7,938 Da), a long-chain postsynaptic neurotoxin, which constitutes 5% of O. hannah venom. α-EPTX-Oh3a (100–300 nM) caused concentration-dependent inhibition of indirect twitches and inhibited contractile responses of tissues to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The prior incubation of tissues with Thai Red Cross Society King Cobra antivenom (1 ml/0.8 mg) prevented the in vitro neurotoxic effects of α-EPTX-Oh3a (100 nM). The addition of Thai Red Cross Society King Cobra antivenom (1 ml/0.8 mg), at the t90 time point partially reversed the in vitro neurotoxicity of α-EPTX-Oh3a (100 nM). Repeatedly washing the tissue did not allow significant recovery from the in vitro neurotoxic effects of α-EPTX-Oh3a (100 nM). α-EPTX-Oh3a demonstrated pseudo-irreversible antagonism of concentration-response curves to carbachol, with a pA2 of 8.99. De novo sequencing of α-EPTX-Oh3a showed a long-chain postsynaptic neurotoxin with 72 amino acids, sharing 100% sequence identity with Long neurotoxin OH-55. In conclusion, the antivenom is useful for reversing the clinically important long-chain α-neurotoxin-mediated neuromuscular paralysis.
17α-Hydroxyprogesterone Caproate Inhibits Cytokine Production via Suppression of NF-κB Activation
Authors: Hu Tao , Tang Chengjifu , Stern Sydney , Yang Luan , Du Tom
Published: March 2022

Cytokine release syndrome (CRS) is one of the leading causes of morbidity and mortality in COVID-19 patients with elevated levels of circulating cytokines contributing to various clinical symptoms. Favorable control of CRS represents a promising and effective strategy to mitigate the clinical outcomes of hospitalized patients with moderate to severe pneumonia. Usingin vivocytokine release assay in human peripheral blood mononuclear cell (PBMC)-engrafted immunodeficient mice, we reported that 17α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestogen, exhibited significant inhibition of OKT-3-stimulated production of numerous cytokines including TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, and GM-CSF. Furthermore, 17-OHPC inhibitedin vitroproduction of IFN-γ, IL-1β, IL-2, IL-6, and IL-10 in human PBMCs stimulated with OKT3, while exhibiting down-regulation of the mRNA levels of TNF-α, IFN-γ, IL-2, IL-6, and IL-10. Using the same human PBMCs, additional stimulators anti-CD28 antibody or PHA treatments led to substantial cytokine production, which was also attenuated by 17-OHPC. OKT3-stimulated phosphorylation of IκBα and nuclear translocation of NF-κB p65 in human PBMCs were also reversed by 17-OHPC, suggesting its inhibition on NF-κB signaling in immune cells. Taken together, this work reported bothin vivoandin vitroinhibition of cytokine production by 17-OHPC, presumably by virtue of its suppression of NF-κB signaling. These findings provide pharmacological evidence to support the potential application of 17-OHPC in treating CRS associated with COVID-19.
Lactobacillus plantarum RS-09 Induces M1-Type Macrophage Immunity Against Salmonella Typhimurium Challenge via the TLR2/NF-κB Signalling Pathway
Authors: Zhao Chenpei , Chen Huan , Liang Hao , Zhao Xiaoyu , Tang Wenli , Wei Maolian , Li Youzhi , Zhang Jianlong , Yu Xin , Chen Guozhong , Zhu Hongwei , Jiang Linlin , Zhang Xingxiao
Published: March 2022

Lactobacillus plantarumcan interact with macrophages against bacterial enteropathy due to its potential ability to modulate macrophage polarization. However, this mechanism is not completely understood. TLR2 can recognize microbial components and trigger macrophage cytokine responses to different gram-positive strains. The aim of this study was to investigate whether probioticLactobacillus plantarumRS-09 can induce macrophage polarization againstSalmonellaTyphimurium infection via TLR2 signalling. BALB/c mice were preadministered RS-09 continuously for 7 days and then infected withSalmonellaTyphimurium ATCC14028. Mouse RAW264.7 mononuclear macrophages were stimulated with RS-09 and coincubated with ATCC14028 or PBS controls. The results of thein vivostudy indicated that RS-09 could relieveS. Typhimurium-induced splenomegaly, body weight loss and death rate. RS-09 also limited the colonization and translocation ofS. Typhimurium in the gastrointestinal tract and thereby protected against infection. We also observed that RS-09 upregulated the production of M1 macrophage characteristics (e.g., CD11c and IL-6) againstS. Typhimurium. Furthermore, RS-09 induced the expression of TLR2 in macrophages. In anin vitrostudy, treatment of RAW264.7 cells with RS-09 either concurrently with or beforeS. Typhimurium challenge enhanced the secretion of Reactive oxygen species and Nitric oxide. This effect was related to TLR2 and NF-κB activation. Based on these findings,Lactobacillus plantarumRS-09 was shown to modulate M1 macrophage polarization and induce TLR2-linked NF-κB signalling activity in the innate immune response toS. Typhimurium infection.
Lipidated Calcitonin Gene-Related Peptide (CGRP) Peptide Antagonists Retain CGRP Receptor Activity and Attenuate CGRP Action In Vivo
Authors: Jamaluddin Aqfan , Chuang Chia-Lin , Williams Elyse T. , Siow Andrew , Yang Sung Hyun , Harris Paul W. R. , Petersen Jakeb S. S. M. , Bower Rebekah L. , Chand Shanan , Brimble Margaret A. , Walker Christopher S. , Hay Debbie L. , Loomes Kerry M.
Published: March 2022

Signaling through calcitonin gene-related peptide (CGRP) receptors is associated with pain, migraine, and energy expenditure. Small molecule and monoclonal antibody CGRP receptor antagonists that block endogenous CGRP action are in clinical use as anti-migraine therapies. By comparison, the potential utility of peptide antagonists has received less attention due to suboptimal pharmacokinetic properties. Lipidation is an established strategy to increase peptide half-life in vivo. This study aimed to explore the feasibility of developing lipidated CGRP peptide antagonists that retain receptor antagonist activity in vitro and attenuate endogenous CGRP action in vivo. CGRP peptide analogues based on the archetypal CGRP receptor antagonist, CGRP8-37, were palmitoylated at the N-terminus, position 24, and near the C-terminus at position 35. The antagonist activities of the lipidated peptide analogues were tested in vitro using transfected Cos-7 cells expressing either the human or mouse CGRP receptor, amylin subtype 1 (AMY1) receptor, adrenomedullin (AM) receptors, or calcitonin receptor. Antagonist activities were also evaluated in SK-N-MC cells that endogenously express the human CGRP receptor. Lipidated peptides were then tested for their ability to antagonize endogenous CGRP action in vivo using a capsaicin-induced dermal vasodilation (CIDV) model in C57/BL6J mice. All lipidated peptides except for the C-terminally modified analogue retained potent antagonist activity compared to CGRP8-37 towards the CGRP receptor. The lipidated peptides also retained, and sometimes gained, antagonist activities at AMY1, AM1 and AM2 receptors. Several lipidated peptides produced robust inhibition of CIDV in mice. This study demonstrates that selected lipidated peptide antagonists based on αCGRP8-37 retain potent antagonist activity at the CGRP receptor and are capable of inhibition of endogenous CGRP action in vivo. These findings suggest that lipidation can be applied to peptide antagonists, such as αCGRP8-37 and are a potential strategy for antagonizing CGRP action.
A Novel 3D Image Encryption Based on the Chaotic System and RNA Crossover and Mutation
Authors: Chu Ran , Zhang Shufang , Gao Xianpeng
Published: March 2022

In this paper, a novel 3D image encryption based on the memristive chaotic system and RNA crossover and mutation is proposed. Firstly, the dynamic characteristics of the nonlinear system with two memristors are analyzed, including phase diagrams, Lyapunov exponential spectrums, and bifurcation diagrams. According to the merged image of three 3D images, the initial values of the memristive chaotic system are generated by SHA-256. Then the vertex coordinates are scrambled and diffused by 3D Arnold matrix and chaotic sequences. Finally, according to the dynamical encoding and decoding rules, crossover and RNA mutation are designed to confuse and diffuse the vertex coordinates. Throughout the encryption process, the Arnold matrix, RNA encoding and decoding rules, and crossover and mutation algorithms are determined by the memristive chaotic system. The experimental results verify that the proposed cryptosystem could encrypt three 3D images at the same time and resist various attacks effectively, and has good security performance.
Elevated CO2 Improves the Physiology but Not the Final Yield in Spring Wheat Genotypes Subjected to Heat and Drought Stress During Anthesis
Authors: Abdelhakim Lamis Osama Anwar , Mendanha Thayna , Palma Carolina Falcato Fialho , Vrobel Ondřej , Štefelová Nikola , Ćavar Zeljković Sanja , Tarkowski Petr , De Diego Nuria , Wollenweber Bernd , Rosenqvist Eva , Ottosen Carl-Otto
Published: March 2022

Heat and drought events often occur concurrently as a consequence of climate change and have a severe impact on crop growth and yield. Besides, the accumulative increase in the atmospheric CO2 level is expected to be doubled by the end of this century. It is essential to understand the consequences of climate change combined with the CO2 levels on relevant crops such as wheat. This study evaluated the physiology and metabolite changes and grain yield in heat-sensitive (SF29) and heat-tolerant (LM20) wheat genotypes under individual heat stress or combined with drought applied during anthesis at ambient (aCO2) and elevated CO2 (eCO2) levels. Both genotypes enhanced similarly the WUE under combined stresses at eCO2. However, this increase was due to different stress responses, whereas eCO2 improved the tolerance in heat-sensitive SF29 by enhancing the gas exchange parameters, and the accumulation of compatible solutes included glucose, fructose, β-alanine, and GABA to keep water balance; the heat-tolerant LM20 improved the accumulation of phosphate and sulfate and reduced the lysine metabolism and other metabolites including N-acetylornithine. These changes did not help the plants to improve the final yield under combined stresses at eCO2. Under non-stress conditions, eCO2 improved the yield of both genotypes. However, the response differed among genotypes, most probably as a consequence of the eCO2-induced changes in glucose and fructose at anthesis. Whereas the less-productive genotype LM20 reduced the glucose and fructose and increased the grain dimension as the effect of the eCO2 application, the most productive genotype SF29 increased the two carbohydrate contents and ended with higher weight in the spikes. Altogether, these findings showed that the eCO2 improves the tolerance to combined heat and drought stress but not the yield in spring wheat under stress conditions through different mechanisms. However, under non-stress conditions, it could improve mainly the yield to the less-productive genotypes. Altogether, the results demonstrated that more studies focused on the combination of abiotic stress are needed to understand better the spring wheat responses that help the identification of genotypes more resilient and productive under these conditions for future climate conditions.
Photosynthetic Light Harvesting and Thylakoid Organization in a CRISPR/Cas9 Arabidopsis Thaliana LHCB1 Knockout Mutant
Authors: Sattari Vayghan Hamed , Nawrocki Wojciech J. , Schiphorst Christo , Tolleter Dimitri , Hu Chen , Douet Véronique , Glauser Gaëtan , Finazzi Giovanni , Croce Roberta , Wientjes Emilie , Longoni Fiamma
Published: March 2022

Light absorbed by chlorophylls of Photosystems II and I drives oxygenic photosynthesis. Light-harvesting complexes increase the absorption cross-section of these photosystems. Furthermore, these complexes play a central role in photoprotection by dissipating the excess of absorbed light energy in an inducible and regulated fashion. In higher plants, the main light-harvesting complex is trimeric LHCII. In this work, we used CRISPR/Cas9 to knockout the five genes encoding LHCB1, which is the major component of LHCII. In absence of LHCB1, the accumulation of the other LHCII isoforms was only slightly increased, thereby resulting in chlorophyll loss, leading to a pale green phenotype and growth delay. The Photosystem II absorption cross-section was smaller, while the Photosystem I absorption cross-section was unaffected. This altered the chlorophyll repartition between the two photosystems, favoring Photosystem I excitation. The equilibrium of the photosynthetic electron transport was partially maintained by lower Photosystem I over Photosystem II reaction center ratio and by the dephosphorylation of LHCII and Photosystem II. Loss of LHCB1 altered the thylakoid structure, with less membrane layers per grana stack and reduced grana width. Stable LHCB1 knockout lines allow characterizing the role of this protein in light harvesting and acclimation and pave the way for future in vivo mutational analyses of LHCII.
The Life Crafting Scale: Development and Validation of a Multi-Dimensional Meaning-Making Measure
Authors: Chen Shi , van der Meij Leander , van Zyl Llewellyn E. , Demerouti Evangelia
Published: March 2022

Finding meaning in our lives is a central tenet to the human experience and a core contributor to mental health. Individuals tend to actively seek the sources of meaning in their lives or consciously enact efforts to create or “craft” meaning in different life domains. These overall “Life Crafting” behaviors refer to the conscious efforts individuals exert to create meaning in their lives through (a) cognitively (re-)framing how they view life, (b) seeking social support systems to manage life challenges, and (c) actively seeking challenges to facilitate personal growth. Specifically, these behaviors are actioned to better align life goals, personal needs, values, and capabilities. However, no psychological assessment instrument currently exists to measure overall life crafting. As such, the purpose of this paper was twofold: to conceptualize life crafting and to develop, validate and evaluate a robust measure of overall life crafting. A mixed-method, multi-study research design was employed. First, nine participants were interviewed to determine the methods or techniques used to craft meaningful life experiences. These methods/techniques were used as indicators to create an initial item pool which was then reviewed by a panel of experts to ensure face validity. Second, in Study 1, the factorial structure of the instrument was explored by gathering data from a convenience sample (N = 331), with the results showing support for a three-factor structure of life crafting, consisting of (a) cognitive crafting, (b) seeking social support, and (c) seeking challenges. Finally, in Study 2 (N = 362), the aim was to confirm the factorial structure of the Life Crafting scale and to determine its level of internal consistency, partial measurement invariance across genders, and criterion validity [meaning in life (β = 0.91), mental health (β = 0.91), work engagement (β = 0.54), and job burnout (β = −0.42)]. The results supported a second-order factorial model of Life Crafting, which comprised of three first-order factors (cognitive crafting, seeking social support, and seeking challenges). Therefore, the Life Crafting Scale can be used as a valid and reliable instrument to measure- and track the effectiveness of life crafting interventions.
Relationships Between Mathematics Performance and Attitude to Mathematics: Influences of Gender, Test Anxiety, and Working Memory
Authors: Dowker Ann , Sheridan Hannah
Published: March 2022

Many studies have indicated that mathematics anxiety, and other negative attitudes and emotions toward mathematics, are pervasive and are associated with lower mathematical performance. Some previous research has suggested that working memory is related to both mathematics anxiety and mathematics. Moreover, both gender and chosen course of study (sciences vs. humanities) appeared likely to influence students’ attitudes to mathematics. In the present study, 40 university undergraduates completed a battery of assessments investigating working memory, attitude to mathematics, test anxiety. and mental and written arithmetic. Attitudes to mathematics were significantly associated with the other variables: working memory, test anxiety, and both measures of mathematical performance. The other variables were not strongly associated with one another. There were no gender differences in mathematical performance, but females exhibited more negative attitudes to mathematics and higher test anxiety than males. After controlling for test anxiety, there ceased to be significant gender differences in attitudes to mathematics. Science students had more positive attitudes to mathematics than humanities students, but the groups did not differ in test anxiety, Science students were better at written but not mental arithmetic. They were also better at working memory, but this was not a significant covariate when the groups were compared on mathematical performance and attitudes to mathematics The results are discussed, with particular focus on implications for future research on influences on mathematics anxiety.
Confirming the Validity of the School-Refusal Assessment Scale—Revised in a Sample of Children With Attention-Deficit/Hyperactivity Disorder
Authors: Orm Stian , Orm Cathrine , Mebostad Mette I. , Dechsling Anders , Nordahl-Hansen Anders
Published: March 2022

Children with developmental disorders, such as attention-deficit/hyperactivity disorder (ADHD), are at high risk of school-refusal behavior (SRB) compared with their peers. One of the most used scales to assess SRB is the school refusal behavior scale – revised (SRAS-R). The SRAS-R has demonstrated good psychometric properties when used with the general population of children, but, recently, its validity has been questioned when used with children with developmental disorders. We tested the psychometric properties of the SRAS-R parental reports in 96 children with ADHD (Mage = 12.4; SD = 1.7, 61.5% boys). Results showed good model fit and internal consistency for the original four-factor structure. Three of the factors were strongly correlated, suggesting that SRB among children with ADHD is caused by several factors.
Influencing Factors, Formation Mechanism, and Pre-control Methods of Coal Miners′ Unsafe Behavior: A Systematic Literature Review
Authors: Yang Li , Wang Xue , Zhu Junqi , Qin Zhiyuan
Published: March 2022

Coal mine accidents are mainly caused by the unsafe behavior of workers. Studying workers' unsafe behaviors can help in regulating such behaviors and reducing the incidence of accidents. However, there is a dearth of systematic literature review in this area, which has hindered mine managers from fully understanding the unsafe behavior of workers. This study aims to address this research gap based on the literature retrieved from the Web of Science. First, a descriptive statistical analysis is conducted on the year, quantity, publications, and keywords of the literature. Second, the influencing factors, formation mechanism, and pre-control methods of coal miners' unsafe behavior are determined and discussed, and the research framework and future research directions of this study are proposed. The study results will help mine safety managers fully understand the influencing factors, formation mechanism, and pre-control methods of workers' unsafe behavior, and lay a theoretical foundation for the future research direction in this field.
A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage
Authors: Lizzo Giulia , Migliavacca Eugenia , Lamers Daniela , Frézal Adrien , Corthesy John , Vinyes-Parès Gerard , Bosco Nabil , Karagounis Leonidas G. , Hövelmann Ulrike , Heise Tim , von Eynatten Maximilian , Gut Philipp
Published: March 2022

Glycine and cysteine are non-essential amino acids that are required to generate glutathione, an intracellular tripeptide that neutralizes reactive oxygen species and prevents tissue damage. During aging glutathione demand is thought to increase, but whether additional dietary intake of glycine and cysteine contributes towards the generation of glutathione in healthy older adults is not well understood. We investigated supplementation with glycine and n-acetylcysteine (GlyNAC) at three different daily doses for 2 weeks (low dose: 2.4 g, medium dose: 4.8 g, or high dose: 7.2 g/day, 1:1 ratio) in a randomized, controlled clinical trial in 114 healthy volunteers. Despite representing a cohort of healthy older adults (age mean = 65 years), we found significantly higher baseline levels of markers of oxidative stress, including that of malondialdehyde (MDA, 0.158 vs. 0.136 µmol/L, p < 0.0001), total cysteine (Cysteine-T, 314.8 vs. 276 µM, p < 0.0001), oxidized glutathione (GSSG, 174.5 vs. 132.3 µmol/L, p < 0.0001), and a lower ratio of reduced to oxidized glutathione (GSH-F:GSSG) (11.78 vs. 15.26, p = 0.0018) compared to a young reference group (age mean = 31.7 years, n = 20). GlyNAC supplementation was safe and well tolerated by the subjects, but did not increase levels of GSH-F:GSSG (end of study, placebo = 12.49 vs. 7.2 g = 12.65, p-value = 0.739) or that of total glutathione (GSH-T) (end of study, placebo = 903.5 vs. 7.2 g = 959.6 mg/L, p-value = 0.278), the primary endpoint of the study. Post-hoc analyses revealed that a subset of subjects characterized by high oxidative stress (above the median for MDA) and low baseline GSH-T status (below the median), who received the medium and high doses of GlyNAC, presented increased glutathione generation (end of study, placebo = 819.7 vs. 4.8g/7.2 g = 905.4 mg/L, p-value = 0.016). In summary GlyNAC supplementation is safe, well tolerated, and may increase glutathione levels in older adults with high glutathione demand.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05041179, NCT05041179.