bluuebunny/crossref_metadata_2025 huggingface dataset:
7SK Acts as an Anti-tumor Factor in Tongue Squamous Cell Carcinoma
Authors: Zhang Bowen , Min Sainan , Guo Qi , Huang Yan , Guo Yuzhu , Liang Xiaolin , Wu Li-ling , Yu Guang-yan , Wang Xiangting
Published: April 2021

Increasing evidence has shown the mechanistic insights about non-coding RNA 7SK in controlling the transcription. However, the biological function and mechanism of 7SK in cancer are largely unclear. Here, we show that 7SK is down-regulated in human tongue squamous carcinoma (TSCC) and acts as a TSCC suppressor through multiple cell-based assays including a migration assay and a xenograft mouse model. The expression level of 7SK was negatively correlated with the size of tumors in the 73 in-house collected TSCC patients. Through combined analysis of 7SK knockdown of RNA-Seq and available published 7SK ChIRP-seq data, we identified 27 of 7SK-regulated genes that were involved in tumor regulation and whose upstream regulatory regions were bound by 7SK. Motif analysis showed that the regulatory sequences of these genes were enriched for transcription factors FOXJ3 and THRA, suggesting a potential involvement of FOXJ3 and THRA in 7SK-regulated genes. Interestingly, the augmented level of FOXJ3 in TSCC patients and previous reports on THRA in other cancers have suggested that these two factors may promote TSCC progression. In support of this idea, we found that 21 out of 27 aforementioned 7SK-associated genes were regulated by FOXJ3 and THRA, and 12 of them were oppositely regulated by 7SK and FOXJ3/THRA. We also found that FOXJ3 and THRA dramatically promoted migration in SCC15 cells. Collectively, we identified 7SK as an antitumor factor and suggested a potential involvement of FOXJ3 and THRA in 7SK-mediated TSCC progression.
Analysis of the Phenotypic Variability as Well as Impact of Early Diagnosis and Treatment in Six Affected Families With ALDH7A1 Deficiency
Authors: Jiao Xianru , Gong Pan , Wu Ye , Zhang Yuehua , Yang Zhixian
Published: April 2021

Objective

To describe the clinical characteristics of 12 patients from six families with pyridoxine-dependent epilepsy (PDE) carryingALDH7A1mutations, and analyze the impact of early diagnosis and treatment, as well as possible genotype–phenotype relationship.

Methods

Clinical and genetics data of 12 patients were collected.

Results

Family 1–3 presented with symptoms in the neonatal period, while family 4-6 presented during early infancy. In the same family, the age of onset was similar. The focal motor seizure appeared in all patients. The affected identical twins from family 4 were diagnosed with infantile spasms. Mutation analysis identified nine differentALDH7A1mutations among six families. The neurodevelopment of siblings in family 1 was mild delay and normal separately due to the minor difference of delayed diagnosis time. Siblings in family 2 showed severely delayed and normal development respectively due to the significant difference of a delayed diagnosis for 4 years. In family 5, although the difference of the delayed diagnosis time is up to 7 years, the nearly normal psychomotor development in both patients might be due to infrequent seizures before the delayed diagnosis. A severe phenotype exhibited in family 3, 4, and 6. The survived affected patients presented with severe developmental delay or refractory seizures and their twins or older sisters presented a similar clinical history and died in the early days of life. Mutation analysis showed D511N and IVS11 + 1G > A in family 3, V188A and exon1 deletion in family 4, and Y354C and exon 8–13 deletion in family 6.

Conclusion

Patients from the same family often have the same phenotype, including onset age and seizure type. Early treatment with pyridoxine and infrequent seizures showed positive relationship with prognosis. The deletion of exon 1 and exon 8–13 might be associated with the severe phenotype.
Alteration of the Gut Microbiome in Chronic Kidney Disease Patients and Its Association With Serum Free Immunoglobulin Light Chains
Authors: Liu Fengping , Xu Xuefang , Chao Lin , Chen Ke , Shao Amo , Sun Danqin , Hong Yan , Hu Renjing , Jiang Peng , Zhang Nan , Xiao Yonghong , Yan Feng , Feng Ninghan
Published: April 2021

Objectives

Gut dysbiosis is associated with chronic kidney disease (CKD), and serum free immunoglobulin light chains (FLCs) are biomarkers for CKD. This study aims to assess the CKD gut microbiome and to determine its impact on serum FLC levels.

Methods

To control for confounders, 100 patients and sex- and age-matched healthy controls (HCs) were recruited. The gut microbiome was assessed by sequencing 16S rRNA gene V3-V4 hypervariable regions. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was applied to infer functional metabolic pathways. When observing group differences in the microbiome and predicted metabolic pathways, demographic confounders were adjusted using binary logistic regression; when examining impacts of the gut microbiome and metabolic pathways on serum FLCs, factors influencing FLC levels were adjusted using multiple regression.

Results

Principal coordinate analysis revealed a significantly different bacterial community between the CKD and HC groups (P < 0.05). After adjusting for confounders, lower Chao 1, observed species and Shannon indices based on binary logistic regression predicted CKD prevalence. Actinobacteria, Alistipes, Bifidobacterium and Bifidobacterium longum enrichment, upregulation of metabolic pathways of bacterial toxin, chloroalkane and chloroalkene degradation, and Staphylococcus aureus infection also predicted CKD prevalence (P < 0.05). Furthermore, depletion of Actinobacteria and Bifidobacterium and reduced chloroalkane and chloroalkene degradation predicted high levels of FLC λ (P < 0.05).

Conclusions

Gut dysbiosis in CKD patients was confirmed by controlling for confounders in the present study. Additionally, the association between gut dysbiosis and FLC λ levels demonstrates the existence of crosstalk between the microbiome and immune response in CKD.
Revisiting the Coreceptor Function of Complement Receptor Type 2 (CR2, CD21); Coengagement With the B-Cell Receptor Inhibits the Activation, Proliferation, and Antibody Production of Human B Cells
Authors: Kovács Kristóf G. , Mácsik-Valent Bernadett , Matkó János , Bajtay Zsuzsa , Erdei Anna
Published: April 2021

The positive coreceptor function of complement receptor type 2 [CR2 (CD21)] on B cells is generally accepted, although its role in the enhancement of antibody production had only been proven in mice. The importance of this phenomenon prompted reinvestigation of the functional consequences of coclustering CD21 and the B cell receptor (BCR) on primary human cells. We found that, at non-stimulatory concentrations of anti-IgG/A/M, coclustering the BCR and CR2 enhanced the Ca2+response, while activation marker expression, cytokine production, proliferation, and antibody production were all inhibited upon the coengagement of CR2 and BCR on human B cells. Thus, the “textbook dogma” claiming that C3d acts as an adjuvant to enhance humoral immunity is relevant only to mice and not to humans.
The Functional and Antiviral Activity of Interferon Alpha-Inducible IFI6 Against Hepatitis B Virus Replication and Gene Expression
Authors: Sajid Muhammad , Ullah Hafiz , Yan Kun , He Miao , Feng Jiangpeng , Shereen Muhammad Adnan , Hao Ruidong , Li Qiaohong , Guo Deyin , Chen Yu , Zhou Li
Published: April 2021

Hepatitis B virus is an enveloped DNA virus, that infects more than three hundred and sixty million people worldwide and leads to severe chronic liver diseases. Interferon-alpha inducible protein 6 (IFI6) is an IFN-stimulated gene (ISG) whose expression is highly regulated by the stimulation of type I IFN-alpha that restricts various kinds of virus infections by targeting different stages of the viral life cycle. This study aims to investigate the antiviral activity of IFI6 against HBV replication and gene expression. The IFI6 was highly induced by the stimulation of IFN-α in hepatoma cells. The overexpression of IFI6 inhibited while knockdown of IFI6 elevated replication and gene expression of HBV in HepG2 cells. Further study determined that IFI6 inhibited HBV replication by reducing EnhII/Cp of the HBV without affecting liver enriched transcription factors that have significant importance in regulating HBV enhancer activity. Furthermore, deletion mutation of EnhII/Cp and CHIP analysis revealed 100 bps (1715-1815 nt) putative sites involved in IFI6 mediated inhibition of HBV. Detailed analysis with EMSA demonstrated that 1715-1770 nt of EnhII/Cp was specifically involved in binding with IFI6 and restricted EnhII/Cp promoter activity. Moreover, IFI6 was localized mainly inside the nucleus to involve in the anti-HBV activity of IFI6. In vivo analysis based on the hydrodynamic injection of IFI6 expression plasmid along with HBV revealed significant inhibition of HBV DNA replication and gene expression. Overall, our results suggested a novel mechanism of IFI6 mediated HBV regulation that could develop potential therapeutics for efficient HBV infection treatment.
Double Insurance for OC: miRNA-Mediated Platinum Resistance and Immune Escape
Authors: Zou Xueqin , Zhao Yangjing , Liang Xiuting , Wang Hui , Zhu Yanling , Shao Qixiang
Published: April 2021

Ovarian cancer (OC) is still the leading cause of death among all gynecological malignancies, despite the recent progress in cancer therapy. Immune escape and drug resistance, especially platinum-based chemotherapy, are significant factors causing disease progression, recurrence and poor prognosis in OC patients. MicroRNAs(miRNAs) are small noncoding RNAs, regulating gene expression at the transcriptional level. Accumulating evidence have indicated their crucial roles in platinum resistance. Importantly, they also act as mediators of tumor immune escape/evasion. In this review, we summarize the recent study of miRNAs involved in platinum resistance of OC and systematically analyses miRNAs involved in the regulation of OC immune escape. Further understanding of miRNAs roles and their possible mechanisms in platinum resistance and tumor escape may open new avenues for improving OC therapy.
Assessing Habitat Suitability Models for the Deep Sea: Is Our Ability to Predict the Distributions of Seafloor Fauna Improving?
Authors: Bowden David A. , Anderson Owen F. , Rowden Ashley A. , Stephenson Fabrice , Clark Malcolm R.
Published: April 2021

Methods that predict the distributions of species and habitats by developing statistical relationships between observed occurrences and environmental gradients have become common tools in environmental research, resource management, and conservation. The uptake of model predictions in practical applications remains limited, however, because validation against independent sample data is rarely practical, especially at larger spatial scales and in poorly sampled environments. Here, we use a quantitative dataset of benthic invertebrate faunal distributions from seabed photographic surveys of an important fisheries area in New Zealand as independent data against which to assess the usefulness of 47 habitat suitability models from eight published studies in the region. When assessed against the independent data, model performance was lower than in published cross-validation values, a trend of increasing performance over time seen in published metrics was not supported, and while 74% of the models were potentially useful for predicting presence or absence, correlations with prevalence and density were weak. We investigate the reasons underlying these results, using recently proposed standards to identify areas in which improvements can best be made. We conclude that commonly used cross-validation methods can yield inflated values of prediction success even when spatial structure in the input data is allowed for, and that the main impediments to prediction success are likely to include unquantified uncertainty in available predictor variables, lack of some ecologically important variables, lack of confirmed absence data for most taxa, and modeling at coarse taxonomic resolution.
What Is Refractory Organic Matter in the Ocean?
Authors: Baltar Federico , Alvarez-Salgado Xosé A. , Arístegui Javier , Benner Ronald , Hansell Dennis A. , Herndl Gerhard J. , Lønborg Christian
Published: April 2021

About 20% of the organic carbon produced in the sunlit surface ocean is transported into the ocean’s interior as dissolved, suspended and sinking particles to be mineralized and sequestered as dissolved inorganic carbon (DIC), sedimentary particulate organic carbon (POC) or “refractory” dissolved organic carbon (rDOC). Recently, the physical and biological mechanisms associated with the particle pumps have been revisited, suggesting that accepted fluxes might be severely underestimated (Boyd et al., 2019; Buesseler et al., 2020). Perhaps even more poorly understood are the mechanisms driving rDOC production and its potential accumulation in the ocean. On the basis of recent conflicting evidence about the relevance of DOC degradation in the deep ocean, we revisit the concept of rDOC in terms of its “refractory” nature in order to understand its role in the global carbon cycle. Here, we address the problem of various definitions and approaches used to characterize rDOC (such as turnover time in relation to the ocean transit time, molecule abundance, chemical composition and structure). We propose that rDOC should be operationally defined. However, we recognize there are multiple ways to operationally define rDOC; thus the main focus for unifying future studies should be to explicitly state how rDOC is being defined and the analytical window used for measuring rDOC, rather than adhering to a single operational definition. We also conclude, based on recent evidence, that the persistence of rDOC is fundamentally dependent on both intrinsic (chemical composition and structure, e.g., molecular properties), and extrinsic properties (amount or external factors, e.g., molecular concentrations, ecosystem properties). Finally, we suggest specific research questions aimed at stimulating research on the nature, dynamics, and role of rDOC in Carbon sequestration now and in future scenarios of climate change.
Photophysiological Tolerance and Thermal Plasticity of Genetically Different Symbiodiniaceae Endosymbiont Species of Cnidaria
Authors: Russnak Vanessa , Rodriguez-Lanetty Mauricio , Karsten Ulf
Published: April 2021

Coral reefs are endangered by constantly rising water temperature due to global warming. This triggers a breakdown of the nutritional symbiosis between cnidarian hosts and their Symbiodiniaceae symbionts, resulting in the loss of the algal partner. In the Symbiodiniaceae exists a high genetic diversity with broad physiological plasticity within and between species, resulting in large thermal tolerance. While these variations have been studied in individual taxa, comprehensive comparative experimental data on numerous species are still rare. In the present study, the photosynthetic performance and tolerance as function of light and temperature of nine Symbiodiniaceae genetic types of four different clades were determined. The data indicate significant differences in the response patterns. Almost all algal isolates exhibited low to moderate light requirements for photosynthesis without photoinhibition, and a photosynthetic efficiency between 20 and 80% in the temperature range 20–34°C, indicating a broad thermal tolerance to temperature fluctuations in tropical regions. The presented data clearly point to a broad photophysiological tolerance and thermal plasticity of genetically different Symbiodiniaceae, which contributes as an important finding to a better understanding of host-symbiont response to an increasing sea surface temperature.
Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis
Authors: Wan Minjie , Han Jiawen , Ding Lili , Hu Feng , Gao Pujun
Published: April 2021

Liver fibrosis is a pathological process caused by persistent chronic injury of the liver. Kupffer cells, natural killer (NK) cells, NKT cells, and dendritic cells (DCs), which are in close contact with T and B cells, serve to bridge innate and adaptive immunity in the liver. Meanwhile, an imbalanced inflammatory response constitutes a challenge in liver disease. The dichotomous roles of novel immune cells, including T helper 17 (Th17), regulatory T cells (Tregs), mucosa-associated invariant T cells (MAIT), and innate lymphoid cells (ILCs) in liver fibrosis have gradually been revealed. These cells not only induce damage during liver fibrosis but also promote tissue repair. Hence, immune cells have unique, and often opposing, roles during the various stages of fibrosis. Due to this heterogeneity, the treatment, or reversal of fibrosis through the target of immune cells have attracted much attention. Moreover, activation of hepatic stellate cells (HSCs) constitutes the core of fibrosis. This activation is regulated by various immune mediators, including Th17, Th22, and Th9, MAIT, ILCs, and γδ T cells, as well as their related cytokines. Thus, liver fibrosis results from the complex interaction of these immune mediators, thereby complicating the ability to elucidate the mechanisms of action elicited by each cell type. Future developments in biotechnology will certainly aid in this feat to inform the design of novel therapeutic targets. Therefore, the aim of this review was to summarize the role of specific immune cells in liver fibrosis, as well as biomarkers and treatment methods related to these cells.
Microbially-Enhanced Vanadium Mining and Bioremediation Under Micro- and Mars Gravity on the International Space Station
Authors: Cockell Charles S. , Santomartino Rosa , Finster Kai , Waajen Annemiek C. , Nicholson Natasha , Loudon Claire-Marie , Eades Lorna J. , Moeller Ralf , Rettberg Petra , Fuchs Felix M. , Van Houdt Rob , Leys Natalie , Coninx Ilse , Hatton Jason , Parmitano Luca , Krause Jutta , Koehler Andrea , Caplin Nicol , Zuijderduijn Lobke , Mariani Alessandro , Pellari Stefano , Carubia Fabrizio , Luciani Giacomo , Balsamo Michele , Zolesi Valfredo , Ochoa Jon , Sen Pia , Watt James A. J. , Doswald-Winkler Jeannine , Herová Magdalena , Rattenbacher Bernd , Wadsworth Jennifer , Everroad R. Craig , Demets René
Published: April 2021

As humans explore and settle in space, they will need to mine elements to support industries such as manufacturing and construction. In preparation for the establishment of permanent human settlements across the Solar System, we conducted the ESA BioRock experiment on board the International Space Station to investigate whether biological mining could be accomplished under extraterrestrial gravity conditions. We tested the hypothesis that the gravity (g) level influenced the efficacy with which biomining could be achieved from basalt, an abundant material on the Moon and Mars, by quantifying bioleaching by three different microorganisms under microgravity, simulated Mars and Earth gravitational conditions. One element of interest in mining is vanadium (V), which is added to steel to fabricate high strength, corrosion-resistant structural materials for buildings, transportation, tools and other applications. The results showed that Sphingomonas desiccabilis and Bacillus subtilis enhanced the leaching of vanadium under the three gravity conditions compared to sterile controls by 184.92 to 283.22%, respectively. Gravity did not have a significant effect on mean leaching, thus showing the potential for biomining on Solar System objects with diverse gravitational conditions. Our results demonstrate the potential to use microorganisms to conduct elemental mining and other bioindustrial processes in space locations with non-1 × g gravity. These same principles apply to extraterrestrial bioremediation and elemental recycling beyond Earth.
Identification of Epithelial-Mesenchymal Transition-Related lncRNAs that Associated With the Prognosis and Immune Microenvironment in Colorectal Cancer
Authors: Liu Chuan , Hu Chuan , Li Jianyi , Jiang Liqing , Zhao Chengliang
Published: April 2021

Background: The expression of long non-coding RNA (lncRNA) is associated with the epithelial-mesenchymal transition (EMT) in tumorigenicity, but the role of EMT-related lncRNA in colorectal cancer (CRC) remains unclear.

Methods: The clinical data and gene expression profile of CRC patients were obtained from The Cancer Genome Atlas database. Differential expression analysis, Cox regression model, and Kaplan-Meier analysis were used to study the relationship between EMT-related lncRNAs and the prognosis of CRC. Functional analysis and unsupervised clustering analysis were performed to explore the influence of certain lncRNAs on CRC. Finally, Cytoscape was used to construct mRNA-lncRNA networks.

Results: Two signatures incorporating six and ten EMT-related lncRNAs were constructed for predicting the overall survival (OS) and disease-free survival (DFS), respectively. Kaplan-Meier survival curves indicated that patients in the high-risk group had a poorer prognosis than those in the low-risk group. The results of the functional analysis suggested that the P53 and ECM-receptor pathways affect the prognosis of CRC, and AL591178.1 is a key prognostic EMT-related lncRNA, which is negatively related to immune cells, P53 pathway, and ECM-receptor pathway.

Conclusion: Six OS-related and ten DFS-related EMT-related lncRNAs were correlated with the prognosis of CRC by potentially affecting the immune microenvironment, and AL591178.1 plays a key role as a prognostic factor.
A Novel Defined Risk Signature of the Ferroptosis-Related Genes for Predicting the Prognosis of Ovarian Cancer
Authors: Ye Ying , Dai Qinjin , Li Shuhong , He Jie , Qi Hongbo
Published: April 2021

Ferroptosis is an iron-dependent, regulated form of cell death, and the process is complex, consisting of a variety of metabolites and biological molecules. Ovarian cancer (OC) is a highly malignant gynecologic tumor with a poor survival rate. However, the predictive role of ferroptosis-related genes in ovarian cancer prognosis remains unknown. In this study, we demonstrated that the 57 ferroptosis-related genes were expressed differently between ovarian cancer and normal ovarian tissue, and based on these genes, all OC cases can be well divided into 2 subgroups by applying consensus clustering. We utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to develop a multigene risk signature from the TCGA cohort and then validated it in an OC cohort from the GEO database. A 5-gene signature was built and reveals a favorable predictive efficacy in both TCGA and GEO cohort (P < 0.001 and P = 0.03). The GO and KEGG analysis revealed that the differentially expressed genes (DEGs) between the low- and high-risk subgroup divided by our risk model were associated with tumor immunity, and lower immune status in the high-risk group was discovered. In conclusion, ferroptosis-related genes are vital factors predicting the prognosis of OC and could be a novel potential treatment target.
Development of a Classical Conditioning Task for Humans Examining Phasic Heart Rate Responses to Signaled Appetitive Stimuli: A Pilot Study
Authors: Sayão Alessandra , Alves Heloisa , Furukawa Emi , Schultz Wenk Thomas , Cagy Mauricio , Gutierrez-Arango Samantha , Tripp Gail , Caparelli-Dáquer Egas
Published: April 2021

Cardiac responses to appetitive stimuli have been studied as indices of motivational states and attentional processes, the former being associated with cardiac acceleration and latter deceleration. Very few studies have examined heart rate changes in appetitive classical conditioning in humans. The current study describes the development and pilot testing of a classical conditioning task to assess cardiac responses to appetitive stimuli and cues that reliably precede them. Data from 18 adults were examined. They were shown initially neutral visual stimuli (putative CS) on a computer screen followed by pictures of high-caloric food (US). Phasic cardiac deceleration to food images was observed, consistent with an orienting response to motivationally significant stimuli. Similar responses were observed to non-appetitive stimuli when they were preceded by the cue associated with the food images, suggesting that attentional processes were engaged by conditioned stimuli. These autonomic changes provide significant information about classical conditioning effects in humans.
The Role of Mitochondrial Dysfunction and ER Stress in TDP-43 and C9ORF72 ALS
Authors: Dafinca Ruxandra , Barbagallo Paola , Talbot Kevin
Published: April 2021

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system with complex determinants, including genetic and non-genetic factors. Despite this heterogeneity, a key pathological signature is the mislocalization and aggregation of specific proteins in the cytoplasm, suggesting that convergent pathogenic mechanisms focusing on disturbances in proteostasis are important in ALS. In addition, many cellular processes have been identified as potentially contributing to disease initiation and progression, such as defects in axonal transport, autophagy, nucleocytoplasmic transport, ER stress, calcium metabolism, the unfolded protein response and mitochondrial function. Here we review the evidence from in vitro and in vivo models of C9ORF72 and TDP-43-related ALS supporting a central role in pathogenesis for endoplasmic reticulum stress, which activates an unfolded protein response (UPR), and mitochondrial dysfunction. Disruption in the finely tuned signaling between the ER and mitochondria through calcium ions may be a crucial trigger of mitochondrial deficits and initiate an apoptotic signaling cascade, thus acting as a point of convergence for multiple upstream disturbances of cellular homeostasis and constituting a potentially important therapeutic target.
Rethinking the Mechanisms Underlying the McGurk Illusion
Authors: Gonzales Mariel G. , Backer Kristina C. , Mandujano Brenna , Shahin Antoine J.
Published: April 2021

The McGurk illusion occurs when listeners hear an illusory percept (i.e., “da”), resulting from mismatched pairings of audiovisual (AV) speech stimuli (i.e., auditory/ba/paired with visual/ga/). Hearing a third percept—distinct from both the auditory and visual input—has been used as evidence of AV fusion. We examined whether the McGurk illusion is instead driven by visual dominance, whereby the third percept, e.g., “da,” represents a default percept for visemes with an ambiguous place of articulation (POA), like/ga/. Participants watched videos of a talker uttering various consonant vowels (CVs) with (AV) and without (V-only) audios of/ba/. Individuals transcribed the CV they saw (V-only) or heard (AV). In the V-only condition, individuals predominantly saw “da”/“ta” when viewing CVs with indiscernible POAs. Likewise, in the AV condition, upon perceiving an illusion, they predominantly heard “da”/“ta” for CVs with indiscernible POAs. The illusion was stronger in individuals who exhibited weak/ba/auditory encoding (examined using a control auditory-only task). In Experiment2, we attempted to replicate these findings using stimuli recorded from a different talker. The V-only results were not replicated, but again individuals predominately heard “da”/“ta”/“tha” as an illusory percept for various AV combinations, and the illusion was stronger in individuals who exhibited weak/ba/auditory encoding. These results demonstrate that when visual CVs with indiscernible POAs are paired with a weakly encoded auditory/ba/, listeners default to hearing “da”/“ta”/“tha”—thus, tempering the AV fusion account, and favoring a default mechanism triggered when both AV stimuli are ambiguous.
Spontaneous Activity in Primary Visual Cortex Relates to Visual Creativity
Authors: Wang Yibo , Li Junchao , Wang Zengjian , Liang Bishan , Jiao Bingqing , Zhang Peng , Huang Yingying , Yang Hui , Yu Rengui , Yu Sifang , Zhang Delong , Liu Ming
Published: April 2021

Cognitive and neural processes underlying visual creativity have attracted substantial attention. The current research uses a critical time point analysis (CTPA) to examine how spontaneous activity in the primary visual area (PVA) is related to visual creativity. We acquired the functional magnetic resonance imaging (fMRI) data of 16 participants at the resting state and during performing a visual creative synthesis task. According to the CTPA, we then classified spontaneous activity in the PVA into critical time points (CTPs), which reflect the most useful and important functional meaning of the entire resting-state condition, and the remaining time points (RTPs). We constructed functional brain networks based on the brain activity at two different time points and then subsequently based on the brain activity at the task state in a separate manner. We explore the relationship between resting-state and task-fMRI (T-fMRI) functional brain networks. Our results found that: (1) the pattern of spontaneous activity in the PVA may associate with mental imagery, which plays an important role in visual creativity; (2) in comparison with the RTPs-based brain network, the CTP-network showed an increase in global efficiency and a decrease in local efficiency; (3) the regional integrated properties of the CTP-network could predict the integrated properties of the creative-network while the RTP-network could not. Thus, our findings indicated that spontaneous activity in the PVA at CTPs was associated with a visual creative task-evoked brain response. Our findings may provide an insight into how the visual cortex is related to visual creativity.
Delaying Broccoli Floret Yellowing by Phytosulfokine α Application During Cold Storage
Authors: Aghdam Morteza Soleimani , Alikhani-Koupaei Majid , Khademian Raheleh
Published: April 2021

During postharvest life, broccoli suffers from floret yellowing confining its economic and nutritional value. The objective of the present study was to explore the mechanisms employed by phytosulfokine α (PSKα) at 150 nM for delaying floret yellowing in broccoli during storage at 4°C for 28 days. Our results showed that the higher endogenous accumulation of hydrogen sulfide (H2S) resulting from the higher gene expression and activities of l-cysteine desulfhydrase (LCD) and d-cysteine desulfhydrase (DCD) in broccoli floret treated with 150 nM PSKα may serve as an endogenous signaling molecule for delaying senescence. Moreover, the suppressed ethylene biosynthesis in broccoli floret treated with 150 nM PSKα might be ascribed to lower gene expression and activities of ACC synthase (ACS) and ACC oxidase (ACO). Furthermore, lower gene expression and activities of Mg2+ dechelatase (MDC), pheophytinase (PPH), and pheophorbide a oxygenase (PaO) might be the reasons for the higher accumulation of chlorophyll in broccoli floret treated with 150 nM PSKα. Based on our findings, exogenous PSKα application could be employed as signaling bioactive hormone for retarding floret yellowing of broccoli during storage at 4°C for 28 days.
Central Nervous System Inflammation Induced by Lipopolysaccharide Up-Regulates Hepatic Hepcidin Expression by Activating the IL-6/JAK2/STAT3 Pathway in Mice
Authors: Zhang Fali , Zhao Peng , Qian Zhongming , Zhong Mingkang
Published: April 2021

It is known that lipopolysaccharide (LPS) triggers inflammatory response after intracerebroventricular (ICV) injection and elevates the expression of hepcidin through the interleukin 6/janus kinase 2/transducer and activator of the transcription 3 (IL-6/JAK2/STAT3) signaling pathway in the brain. This study was conducted to determine whether LPS ICV injection can regulate peripheral hepatic hepcidin expression and iron metabolism. Here, we studied the hepcidin expression in the liver, as well as serum iron and transferrin saturation, after LPS ICV injection. We also demonstrated the role of the IL-6/JAK2/STAT3 pathway in hepcidin expression in the livers of IL-6 knockout (IL-6–/– mice) and IL-6+/+ mice. AG490 was used to verify the effect of the IL-6/JAK2/STAT3 pathway on hepatic hepcidin expression. Our present study demonstrated that LPS ICV injection up-regulated hepatic hepcidin expression. This finding provides further evidence for highlighting the importance of the central inflammation on hepatic hepcidin expression and peripheral iron metabolism.
Radiographic Features and Clinical Factor for Preoperative Prediction in the Bulging Duodenal Papilla With Malignancy
Authors: Wang Xiao-Jie , Ke Jun-Li , Xu Jian-Xia , Zhou Jia-Ping , Lu Yuan-Fei , Zhou Qiao-Mei , Shi Dan , Yu Ri-Sheng
Published: April 2021

Background

To investigate characteristic clinical and imaging features and establish a scoring system for preoperative prediction of malignancy in the bulging duodenal papilla.

Methods

A total of 147 patients with bulging duodenal papilla (Benign enlargement n = 67; malignant enlargement n = 80) from our hospital between 2010 and 2020 were retrospectively analyzed. We investigated meaningful clinical and CT imaging features and established the score model through logistic regression and weighted. The calibration test, the ROC, AUC, and cut-off points were performed in score model. The model was also divided into three score ranges for convenient clinical evaluation.

Results

Three clinical and CT imaging features were finally included in the score model including direct bilirubin (DBil) increase >7 umol/L (3 points), pancreatic duct (PD) dilation >5 mm (2 points), and irregular shape (2 points). The AUCs of the primary predictive model and score model were 0.896 (95% CI, 0.835–0.940) and 0.896 (95% CI, 0.835–0.940), respectively. This scoring system presented with a sensitivity of 78.8% and a specificity of 88.1% when using 2.5 points as cutoff value. Three score ranges were also proposed for convenient clinical use as follows: 0–2 points; 3–4 points; 5–7 points. The number of patients with malignant duodenal papillary enlargement increased with the increasing scores.

Conclusions

We proposed a convenient scoring system to preoperative predict malignancy in the bulging duodenal papilla.
Multimodal Treatment With Orbital Organ Preservation in Adult Patients With Locally Advanced Small-Round-Cell Malignancy of the Nasal Cavity and Paranasal Sinus
Authors: Chen Nanxiang , Yuan Hu , Fan Wenjun , Ma Lin , Liu Kun , Chen Lei , Yang Shiming , Zhang Xinxin
Published: April 2021

Background

To investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in adult patients with locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life.

Methods

The clinical data of 49 patients with orbital involvement of locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between December 2009 and January 2019 were retrospectively analyzed. Treatment efficacy and side effects were assessed. The study included three different pathological types. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 3. The overall survival (OS) rate, progression-free survival (PFS) rate, and orbital preservation rate were calculated using the Kaplan-Meier method.

Results

After multimodal treatment, the 3- and 5-year OS rates of the 49 patients were 63.8% and 54.5%, respectively, and the 3- and 5-year total PFS rates were 66.8% and 63.1%, respectively.

Conclusions

Multimodal treatment can preserve the orbital organs of adult patients with small-round-cell malignancy of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates, and improve quality of life, thus providing a new treatment option for these patients.
Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review
Authors: Mondello Cristina , Roccuzzo Salvatore , Malfa Orazio , Sapienza Daniela , Gualniera Patrizia , Ventura Spagnolo Elvira , Di Nunno Nunzio , Salerno Monica , Pomara Cristoforo , Asmundo Alessio
Published: April 2021

Introduction:The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs.

Methods:A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations.

Results:A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung.

Discussion:The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.
Contribution of Population Pharmacokinetics of Glycopeptides and Antifungals to Dosage Adaptation in Paediatric Onco-hematological Malignancies: A Review
Authors: Leroux Stéphanie , Mechinaud-Heloury Françoise , Jacqz-Aigrain Evelyne
Published: April 2021

The response to medications in children differs not only in comparison to adults but also between children of the different age groups and according to the disease. This is true for anti-infectives that are widely prescribed in children with malignancy. In the absence of pharmacokinetic/pharmacodynamic paediatric studies, dosage is frequently based on protocols adapted to adults. After a short presentation of the drugs, we reviewed the population pharmacokinetic studies available for glycopeptides (vancomycin and teicoplanin, n = 5) and antifungals (voriconazole, posaconazole, and amphotericin B, n = 9) currently administered in children with onco-hematological malignancies. For each of them, we reported the main study characteristics including identified covariates affecting pharmacokinetics and proposed paediatric dosage recommendations. This review highlighted the very limited amount of data available, the lack of consensus regarding PK/PD targets used for dosing optimization and regarding dosage recommendations when available. Additional PK studies are urgently needed in this specific patient population. In addition to pharmacokinetics, efficacy may be altered in immunocompromised patients and prospective clinical evaluation of new dosage regimen should be provided as they are missing in most cases.
The Thermoregulatory and Thermal Responses of Individuals With a Spinal Cord Injury During Exercise, Acclimation and by Using Cooling Strategies–A Systematic Review
Authors: Grossmann Fabian , Flueck Joelle Leonie , Perret Claudio , Meeusen Romain , Roelands Bart
Published: April 2021

Background:In individuals with a spinal cord injury thermoregulatory mechanisms are fully or partially interrupted. This could lead to exercise-induced hyperthermia in temperate conditions which can be even more distinct in hot conditions. Hyperthermia has been suggested to impair physiological mechanisms in athletes, which could negatively influence physical performance and subjective well-being or cause mild to severe health issues.

Objective:The aim was to evaluate the literature on the thermoregulatory and thermal responses of individuals with a spinal cord injury during exercise in temperate and hot conditions taking the effects of cooling techniques and heat acclimation into account.

Data sources:Two electronic databases, PubMed and Web of Science were searched. Studies were eligible if they observed the influence of exercise on various thermoregulatory parameters (e.g., core and skin temperature, sweat rate, thermal sensation) in individuals with a spinal cord injury.

Results:In total 32 articles were included of which 26 were of strong, 3 of moderate and 3 of weak quality. Individuals with a high lesion level, especially those with a tetraplegia, reached a higher core and skin temperature with a lower sweat rate. The use of cooling techniques before and during exercise can positively affect the burden of the impaired thermoregulatory system in all individuals with a spinal cord injury.

Conclusion:Due to the absence of normal thermoregulatory abilities, individuals with a high-level spinal cord injury need special attention when they are exercising in temperate and hot conditions to prevent them from potential heat related issues. The use of cooling techniques can reduce this risk.
Age-Related Decline in Vertical Jumping Performance in Masters Track and Field Athletes: Concomitant Influence of Body Composition
Authors: Alvero-Cruz José R. , Brikis Mieszko , Chilibeck Phil , Frings-Meuthen Petra , Vico Guzmán Jose F. , Mittag Uwe , Michely Sarah , Mulder Edwin , Tanaka Hirofumi , Tank Jens , Rittweger Jörn
Published: April 2021

Vertical jumping power declines with advancing age, which is theoretically explicable by loss of muscle mass and increases in body fat. However, the results of previous cross-sectional studies remain inconsistent on these relationships. The present study included 256 masters athletes who competed at the 2018 track and field world championships in Málaga, Spain. We assessed body composition with bioelectrical impedance (Inbody S10) and vertical jumping power with a Leonardo ground reaction force platform. Relationships between age, jumping power, and body composition were analyzed by correlation and regression analyses. Hierarchical multiple regression analysis was used to evaluate effects of each factor on vertical jumping power. Age-related rates of decreases in maximal power and jump height were similar between male and female athletes. Percent fat-free mass and percent body fat were negatively and positively, respectively, associated with age in masters athletes and were comparable to those previously observed in the general population. Moreover, these effects in body composition can, to a great extent, explain the age-related decline in jumping power, an effect that seems at least partly independent of age. Finally, the multiple regression model to determine independent predictors of vertical jump performance yielded an overall R2 value of 0.75 with the inclusion of (1) athletic specialization in power events, (2) percent fat-free mass, and (3) phase angle. However, partial regression yielded significant effects of age, but not gender, on peak power, even when adjusting for athletic specialization, percent fat-free mass, and phase angle. We concluded that loss of skeletal muscle mass and changes in bio-impedance phase angle are important contributors to the age-related reduction in anaerobic power, even in adults who maintain high levels of physical activity into old age. However, age per se remains a significant predictor of vertical jump performance, further demonstrating deteriorated muscle quality at old age (sarcosthenia).
RETRACTED: MiR-22 Inhibition Alleviates Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy by Targeting the sirt1/PGC-1α Pathway
Authors: Wang Runze , Xu Yuerong , Niu Xiaolin , Fang Yexian , Guo Dong , Chen Jiangwei , Zhu Hanzhao , Dong Jiaying , Zhao Ran , Wang Ying , Qi Bingchao , Ren Gaotong , Li Xue , Liu Li , Zhang Mingming
Published: April 2021

Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function and gain-of-function experiments to identify the role of miR-22 in doxorubicin-induced cardiomyopathy. Our data suggested that inhibiting miR-22 alleviated cardiac fibrosis and cardiac dysfunction induced by doxorubicin. In addition, inhibiting miR-22 mitigated mitochondrial dysfunction through the sirt1/PGC-1α pathway. Knocking out miR-22 enhanced mitochondrial biogenesis, as evidenced by increased PGC-1α, TFAM, and NRF-1 expression in vivo. Furthermore, knocking out miR-22 rescued mitophagy, which was confirmed by increased expression of PINK1 and parkin and by the colocalization of LC3 and mitochondria. These protective effects were abolished by overexpressing miR-22. In conclusion, miR-22 may represent a new target to alleviate cardiac dysfunction in doxorubicin-induced cardiomyopathy and improve prognosis in patients receiving chemotherapy.