bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodiversity Patterns and Ecological Preferences of the Photobionts Associated With the Lichen-Forming Genus Parmelia
Authors: Moya Patricia , Molins Arantzazu , Škaloud Pavel , Divakar Pradeep K. , Chiva Salvador , Dumitru Cristina , Molina Maria Carmen , Crespo Ana , Barreno Eva
Published: December 2021

The worldwide, ecologically relevant lichen-forming genusParmeliacurrently includes 41 accepted species, of which theParmelia sulcatagroup (PSULgp) and theParmelia saxatilisgroup (PSAXgp) have received considerable attention over recent decades; however, phycobiont diversity is poorly known inParmelias. lat. Here, we studied the diversity ofTrebouxiamicroalgae associated with 159 thalli collected from 30 locations, including nineParmeliaspp.:P. barrenoae, P. encryptata, P. ernstiae, P. mayi, P. omphalodes, P. saxatilis, P. serrana, P. submontana, andP. sulcata. The mycobionts were studied by carrying out phylogenetic analyses of the nrITS. Microalgae genetic diversity was examined by using both nrITS and LSU rDNA markers. To evaluate putative species boundaries, three DNA species delimitation analyses were performed onTrebouxiaandParmelia. All analyses clustered the mycobionts into two main groups: PSULgp and PSAXgp. Species delimitation identified 13 fungal and 15 algal species-level lineages. To identify patterns in specificity and selectivity, the diversity and abundance of the phycobionts were identified for eachParmeliaspecies. High specificity of eachParmeliagroup for a givenTrebouxiaclade was observed; PSULgp associated only with clade I and PSAXgp with clade S. However, the degree of specificity is different within each group, since the PSAXgp mycobionts were less specific and associated with 12Trebouxiaspp., meanwhile those of PSULgp interacted only with threeTrebouxiaspp. Variation-partitioning analyses were conducted to detect the relative contributions of climate, geography, and symbiotic partner to phycobiont and mycobiont distribution patterns. Both analyses explained unexpectedly high portions of variability (99 and 98%) and revealed strong correlations between the fungal and algal diversity. Network analysis discriminated seven ecological clusters. Even though climatic conditions explained the largest proportion of the variation among these clusters, they seemed to show indifference relative to climatic parameters. However, the cluster formed byP. saxatilisA/P. saxatilisB/Trebouxiasp. 2/Trebouxiasp. S02/Trebouxiasp. 3A was identified to prefer cold-temperate as well as humid summer environments.
Transcriptomics of Listeria monocytogenes Treated With Olive Leaf Extract
Authors: Liu Yanhong , Fang Ting , Suo Yujuan , Gao Shigang , Baranzoni Gian Marco , Armstrong Cheryl M.
Published: December 2021

Listeria monocytogenes is a regulated foodborne pathogen that is known to cause listeriosis, a disease associated with high mortality rates in humans. Olive leaf extract (OLE) has been shown to act as a plant antimicrobial and inhibit the growth of pathogens, such as L. monocytogenes, although its mode of action has not been defined. To help identify the cellular mechanisms important for conveying these beneficial traits, RNA-Seq was used to study the transcriptome of L. monocytogenes upon exposure to a sublethal level of OLE. Results obtained from cells cultured both with and without OLE at two different time points (3.5-h and 24-h) revealed 661 genes that were differentially expressed. Of the differentially expressed genes (DEGs) identified, transcription was altered for 171 genes in response to the 3.5-h OLE treatment while 490 genes were altered in response to the 24-h OLE treatment. These DEGs included but were not limited to genes encoding for signal transduction, ATP-binding cassette (ABC) transporters, and the phosphotransferase system. Interestingly, several virulence-related genes were downregulated including an ABC transporter permease previously shown to negatively regulate biofilm formation, genes involved in flagella assembly and binding/entry into host cells as well as those regulating acid resistance suggesting that OLE may decrease the virulence potential of L. monocytogenes. Furthermore, quantitative reverse-transcription PCR was used to validate the data obtained via RNA-Seq. Our study provides insight into the mode of action of OLE treatment against L. monocytogenes and may aid in identifying synergetic strategies to inhibit L. monocytogenes in food.
Organic Carbon Mineralization and Bacterial Community of Active Layer Soils Response to Short-Term Warming in the Great Hing’an Mountains of Northeast China
Authors: Dong Xingfeng , Liu Chao , Ma Dalong , Wu Yufei , Man Haoran , Wu Xiangwen , Li Miao , Zang Shuying
Published: December 2021

As a buffer layer for the energy and water exchange between atmosphere and permafrost, the active layer is sensitive to climate warming. Changes in the thermal state in active layer can alter soil organic carbon (SOC) dynamics. It is critical to identify the response of soil microbial communities to warming to better predict the regional carbon cycle under the background of global warming. Here, the active layer soils collected from a wetland-forest ecotone in the continuous permafrost region of Northeastern China were incubated at 5 and 15°C for 45 days. High-throughput sequencing of the 16S rRNA gene was used to examine the response of bacterial community structure to experimental warming. A total of 4148 OTUs were identified, which followed the order 15°C > 5°C > pre-incubated. Incubation temperature, soil layer and their interaction have significant effects on bacterial alpha diversity (Chao index). Bacterial communities under different temperature were clearly distinguished. Chloroflexi, Actinobacteria, Proteobacteria, and Acidobacteria accounted for more than 80% of the community abundance at the phylum level. Warming decreased the relative abundance of Chloroflexi and Acidobacteria, while Actinobacteria and Proteobacteria exhibited increasing trend. At family level, the abundance of norank_o__norank_c__AD3 and Ktedonobacteraceae decreased significantly with the increase of temperature, while Micrococcaccac increased. In addition, the amount of SOC mineralization were positively correlated with the relative abundances of most bacterial phyla and SOC content. SOC content was positively correlated with the relative abundance of most bacterial phyla. Results indicate that the SOC content was the primary explanatory variable and driver of microbial regulation for SOC mineralization. Our results provide a new perspective for understanding the microbial mechanisms that accelerates SOC decomposition under warming conditions in the forest-wetland ecotone of permafrost region.
Swine Influenza Virus Infection Decreases the Protective Immune Responses of Subunit Vaccine Against Porcine Circovirus Type 2
Authors: Sun Yuhang , Zhang Jinlong , Liu Zixuan , Zhang Ying , Huang Kehe
Published: December 2021

Porcine circovirus type 2 (PCV2) is the primary pathogen of porcine circovirus diseases and porcine circovirus associated diseases. Immunization with a vaccine is considered an effective measure to control these diseases. However, it is still unknown whether PCV2 vaccines have protective immune responses on the animals infected with swine influenza virus (SIV), a pandemic virus in swine herds. In this study, we first compared the effects of 2 different PCV2 vaccines on normal mice and SIV-infected mice, respectively. The results showed that these two vaccines had protective immune responses in normal mice, and the subunit vaccine (vaccine S) had better effects. However, the inactivated vaccine (vaccine I) instead of vaccine S exhibited more immune responses in the SIV-infected mice. SIV infection significantly decreased the immune responses of vaccine S in varying aspects including decreased PCV2 antibody levels and increased PCV2 replication. Mechanistically, further studies showed that SIV infection increased IL-10 expression and M2 macrophage percentage, but decreased TNF-α expression and M1 macrophage percentage in the mice immunized with vaccine S; on the contrary, macrophage depleting by using clodronate-containing liposomes significantly alleviated the SIV infection-induced decrease in the protective immune responses of vaccine S against PCV2. This study indicates that SIV infection decreases the protective immune responses of vaccine S against PCV2. The macrophage polarization induced by SIV infection might facilitate decreased immune responses to vaccine S, which provides new insight into vaccine evaluation and a reference for the analysis of immunization failure.
The Role of Unfolded Protein Response in Coronavirus Infection and Its Implications for Drug Design
Authors: Xue Mei , Feng Li
Published: December 2021

Coronavirus is an important pathogen with a wide spectrum of infection and potential threats to humans and animals. Its replication occurs in the cytoplasm and is closely related to the endoplasmic reticulum (ER). Studies reported that coronavirus infection causes ER stress, and cells simultaneously initiate unfolded protein response (UPR) to alleviate the disturbance of ER homeostasis. Activation of the three branches of UPR (PERK, IRE1, and ATF6) modulates various signaling pathways, such as innate immune response, microRNA, autophagy, and apoptosis. Therefore, a comprehensive understanding of the relationship between coronavirus and ER stress is helpful to understand the replication and pathogenesis of coronavirus. This paper summarizes the current knowledge of the complex interplay between coronavirus and UPR branches, focuses on the effect of ER stress on coronavirus replication and coronavirus resistance to host innate immunity, and summarizes possible drug targets to regulate the impact of coronavirus infection.
Environmental Tuning of Homologs of the Orange Carotenoid Protein-Encoding Gene in the Cyanobacterium Fremyella diplosiphon
Authors: Petrescu D. Isabel , Dilbeck Preston L. , Montgomery Beronda L.
Published: December 2021

The orange carotenoid protein (OCP) family of proteins are light-activated proteins that function in dissipating excess energy absorbed by accessory light-harvesting complexes, i.e., phycobilisomes (PBSs), in cyanobacteria. Some cyanobacteria contain multiple homologs of the OCP-encoding gene (ocp). Fremyella diplosiphon, a cyanobacterium studied for light-dependent regulation of PBSs during complementary chromatic acclimation (CCA), contains several OCP homologs – two full-length OCPs, three Helical Carotenoid Proteins (HCPs) with homology to the N-terminus of OCP, and one C-terminal domain-like carotenoid protein (CCP) with homology to the C-terminus of OCP. We examined whether these homologs are distinctly regulated in response to different environmental factors, which could indicate distinct functions. We observed distinct patterns of expression for some OCP, HCP, and CCP encoding genes, and have evidence that light-dependent aspects of ocp homolog expression are regulated by photoreceptor RcaE which controls CCA. RcaE-dependent transcriptional regulator RcaC is also involved in the photoregulation of some hcp genes. Apart from light, additional environmental factors associated with cellular redox regulation impact the mRNA levels of ocp homologs, including salt, cold, and disruption of electron transport. Analyses of conserved sequences in the promoters of ocp homologs were conducted to gain additional insight into regulation of these genes. Several conserved regulatory elements were found across multiple ocp homolog promoters that potentially control differential transcriptional regulation in response to a range of environmental cues. The impact of distinct environmental cues on differential accumulation of ocp homolog transcripts indicates potential functional diversification of this gene family in cyanobacteria. These genes likely enable dynamic cellular protection in response to diverse environmental stress conditions in F. diplosiphon.
A Review on the Role of miR-1290 in Cell Proliferation, Apoptosis and Invasion
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Taheri Mohammad , Samadian Mohammad
Published: December 2021

MicroRNAs (miRNAs) have been shown to affect expression of several genes contributing in important biological processes. miR-1290 a member of this family with crucial roles in the carcinogenesis. This miRNA is transcribed from MIR1290 gene on chromosome 1p36.13. This miRNA has interactions with a number of mRNA coding genes as well as non-coding RNAs SOCS4, GSK3, BCL2, CCNG2, KIF13B, INPP4B, hMSH2, KIF13B, NKD1, FOXA1, IGFBP3, CCAT1, FOXA1, NAT1, SMEK1, SCAI, ZNF667-AS1, ABLIM1, Circ_0000629 and CDC73. miR-1290 can also regulate activity of JAK/STAT3, PI3K/AKT, Wnt/β-catenin and NF-κB molecular pathways. Most evidence indicates the oncogenic roles of miR-1290, yet controversial evidence also exists. In the present review, we describe the results of in vitro, animal and human investigations about the impact of miR-1290 in the development of malignancies.
Beyond the Liver: Liver-Eye Communication in Clinical and Experimental Aspects
Authors: Yuan Tian-Hao , Yue Zhen-Sheng , Zhang Guo-Heng , Wang Lin , Dou Guo-Rui
Published: December 2021

The communication between organs participates in the regulation of body homeostasis under physiological conditions and the progression and adaptation of diseases under pathological conditions. The communication between the liver and the eyes has been received more and more attention. In this review, we summarized some molecular mediators that can reflect the relationship between the liver and the eye, and then extended the metabolic relationship between the liver and the eye. We also summarized some typical diseases and phenotypes that have been able to reflect the liver-eye connection in the clinic, especially non-alcoholic fatty liver disease (NAFLD) and diabetic retinopathy (DR). The close connection between the liver and the eye is reflected through multiple pathways such as metabolism, oxidative stress, and inflammation. In addition, we presented the connection between the liver and the eye in traditional Chinese medicine, and introduced the fact that artificial intelligence may use the close connection between the liver and the eye to help us solve some practical clinical problems. Paying attention to liver-eye communication will help us have a deeper and more comprehensive understanding of certain communication between liver diseases and eyes, and provide new ideas for their potential therapeutic strategy.
Predefined-Time Stability/Synchronization of Coupled Memristive Neural Networks With Multi-Links and Application in Secure Communication
Authors: Zhao Hui , Liu Aidi , Wang Qingjié , Zheng Mingwen , Chen Chuan , Niu Sijie , Li Lixiang
Published: December 2021

This paper explores the realization of a predefined-time synchronization problem for coupled memristive neural networks with multi-links (MCMNN) via nonlinear control. Several effective conditions are obtained to achieve the predefined-time synchronization of MCMNN based on the controller and Lyapunov function. Moreover, the settling time can be tunable based on a parameter designed by the controller, which is more flexible than fixed-time synchronization. Then based on the predefined-time stability criterion and the tunable settling time, we propose a secure communication scheme. This scheme can determine security of communication in the aspect of encrypting the plaintext signal with the participation of multi-links topology and coupled form. Meanwhile, the plaintext signals can be recovered well according to the given new predefined-time stability theorem. Finally, numerical simulations are given to verify the effectiveness of the obtained theoretical results and the feasibility of the secure communication scheme.
Differential Rearrangement of Excitatory Inputs to the Medial Prefrontal Cortex in Chronic Pain Models
Authors: Jefferson Taylor , Kelly Crystle J. , Martina Marco
Published: December 2021

Chronic pain patients suffer a disrupted quality of life not only from the experience of pain itself, but also from comorbid symptoms such as depression, anxiety, cognitive impairment, and sleep disturbances. The heterogeneity of these symptoms support the idea of a major involvement of the cerebral cortex in the chronic pain condition. Accordingly, abundant evidence shows that in chronic pain the activity of the medial prefrontal cortex (mPFC), a brain region that is critical for executive function and working memory, is severely impaired. Excitability of the mPFC depends on the integrated effects of intrinsic excitability and excitatory and inhibitory inputs. The main extracortical sources of excitatory input to the mPFC originate in the thalamus, hippocampus, and amygdala, which allow the mPFC to integrate multiple information streams necessary for cognitive control of pain including sensory information, context, and emotional salience. Recent techniques, such as optogenetic methods of circuit dissection, have made it possible to tease apart the contributions of individual circuit components. Here we review the synaptic properties of these main glutamatergic inputs to the rodent mPFC, how each is altered in animal models of chronic pain, and how these alterations contribute to pain-associated mPFC deactivation. By understanding the contributions of these individual circuit components, we strive to understand the broad spectrum of chronic pain and comorbid pathologies, how they are generated, and how they might be alleviated.
SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis
Authors: Ding Jiangwei , Li Xinxiao , Tian Haiyan , Wang Lei , Guo Baorui , Wang Yangyang , Li Wenchao , Wang Feng , Sun Tao
Published: December 2021

Background:SCN1A is one of the most common epilepsy genes. About 80% of SCN1A gene mutations cause Dravet syndrome (DS), which is a severe and catastrophic epileptic encephalopathy. More than 1,800 mutations have been identified in SCN1A. Although it is known that SCN1A is the main cause of DS and genetic epilepsy with febrile seizures plus (GEFS+), there is a dearth of information on the other related diseases caused by mutations of SCN1A.

Objective: The aim of this study is to systematically review the literature associated with SCN1A and other non-DS-related disorders.

Methods: We searched PubMed and SCOPUS for all the published cases related to gene mutations of SCN1A until October 20, 2021. The results reported by each study were summarized narratively.

Results: The PubMed and SCOPUS search yielded 2,889 items. A total of 453 studies published between 2005 and 2020 met the final inclusion criteria. Overall, 303 studies on DS, 93 on GEFS+, three on Doose syndrome, nine on the epilepsy of infancy with migrating focal seizures (EIMFS), six on the West syndrome, two on the Lennox–Gastaut syndrome (LGS), one on the Rett syndrome, seven on the nonsyndromic epileptic encephalopathy (NEE), 19 on hemiplegia migraine, six on autism spectrum disorder (ASD), two on nonepileptic SCN1A-related sudden deaths, and two on the arthrogryposis multiplex congenital were included.

Conclusion: Aside from DS, SCN1A also causes other epileptic encephalopathies, such as GEFS+, Doose syndrome, EIMFS, West syndrome, LGS, Rett syndrome, and NEE. In addition to epilepsy, hemiplegic migraine, ASD, sudden death, and arthrogryposis multiplex congenital can also be caused by mutations of SCN1A.
Age-Stratified Risk of Dementia in Parkinson's Disease: A Nationwide, Population-Based, Retrospective Cohort Study in Taiwan
Authors: Chang Ting-Ya , Yang Chun-Pai , Chen Yi-Huei , Lin Ching-Heng , Chang Ming-Hong
Published: December 2021

Introduction: Parkinson's disease (PD) manifests with dominant motor symptoms and a wide range of non-motor symptoms (NMS). Dementia is one of the most disabling and exhausting NMS throughout the clinical course. We conducted a population-based, age-stratified, retrospective cohort study to investigate the incidence rate and risk of dementia of patients with newly diagnosed PD, and linked to the clinicopathological PD subtypes.

Methods: Patients with newly diagnosed PD (PD group, n = 760) and control subjects (non-PD group, n = 3,034) were selected from the Taiwan's National Health Insurance Research Database from January 2001 to December 2005. The dementia incidence rate and dementia-free survival rate were calculated.

Results: The overall dementia incidence rate was 17.5 and 5.7 per 1,000 person-years in PD and non-PD groups, respectively. The PD group had a significantly higher overall risk of dementia than controls (p < 0.001). The younger PD patients had a lower dementia incidence rate than the older PD patients, but a higher dementia risk compared to the same age of controls (<60 years, adjusted HR 6.55, 95% CI 1.56–27.48, p = 0.010). The dementia-free survival rate was significantly lower in the PD group compared to the non-PD group during follow-up (p < 0.001).

Conclusion: In our study, the older age of onset in PD patients resulted in a higher incidence rate of dementia. In the young age of PD patients, the incidence rate of dementia was lower than the older PD patients, but the dementia risk was higher than controls of the same age. These findings possibly implied that there were different pathogenesis and pathologies causing dementia in younger and older PD patients.
Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis
Authors: Zaidan Bruna Cunha , Cardoso Ingrid Carolina da Silva , Campos Brunno Machado de , Silva Luciana Ramalho Pimentel da , Coelho Vanessa C. Mendes , Silveira Kairo Alexandre Alves , Amorim Bárbara Juarez , Alvim Marina Koutsodontis Machado , Tedeschi Helder , Yasuda Clarissa Lin , Ghizoni Enrico , Cendes Fernando , Rogerio Fabio
Published: December 2021

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE–HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.
Case Report: Takotsubo Cardiomyopathy in Bickerstaff Brainstem Encephalitis Triggered by COVID-19
Authors: Kimura Mizuki , Hashiguchi Shunta , Tanaka Kenichi , Hagiwara Manato , Takahashi Keita , Miyaji Yosuke , Joki Hideto , Doi Hiroshi , Koga Michiaki , Takeuchi Hideyuki , Tanaka Fumiaki
Published: December 2021

Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy triggered by critical illness including severe neurological disorders. However, an association between TCM and Bickerstaff brainstem encephalitis (BBE) has rarely been described. During the current coronavirus disease 2019 (COVID-19) pandemic, growing evidence indicates that COVID-19 often leads to various neurological disorders, but there are few reports of an association between COVID-19 and BBE. Here we report a case of TCM associated with BBE triggered by COVID-19, which subsided with immunotherapy for BBE. Both transthoracic echocardiography and electrocardiography led to early and accurate diagnosis of TCM. Sustained hemodynamic instability due to TCM was immediately lessened with immunotherapy whereas additional plasmapheresis and immunotherapy were required to treat BBE. This case indicates that BBE might follow COVID-19 and TCM should be considered when hemodynamic status remains unstable in a patient with BBE.
Embedding Functional Brain Networks in Low Dimensional Spaces Using Manifold Learning Techniques
Authors: Casanova Ramon , Lyday Robert G. , Bahrami Mohsen , Burdette Jonathan H. , Simpson Sean L. , Laurienti Paul J.
Published: December 2021

Background: fMRI data is inherently high-dimensional and difficult to visualize. A recent trend has been to find spaces of lower dimensionality where functional brain networks can be projected onto manifolds as individual data points, leading to new ways to analyze and interpret the data. Here, we investigate the potential of two powerful non-linear manifold learning techniques for functional brain networks representation: (1) T-stochastic neighbor embedding (t-SNE) and (2) Uniform Manifold Approximation Projection (UMAP) a recent breakthrough in manifold learning.

Methods: fMRI data from the Human Connectome Project (HCP) and an independent study of aging were used to generate functional brain networks. We used fMRI data collected during resting state data and during a working memory task. The relative performance of t-SNE and UMAP were investigated by projecting the networks from each study onto 2D manifolds. The levels of discrimination between different tasks and the preservation of the topology were evaluated using different metrics.

Results: Both methods effectively discriminated the resting state from the memory task in the embedding space. UMAP discriminated with a higher classification accuracy. However, t-SNE appeared to better preserve the topology of the high-dimensional space. When networks from the HCP and aging studies were combined, the resting state and memory networks in general aligned correctly.

Discussion: Our results suggest that UMAP, a more recent development in manifold learning, is an excellent tool to visualize functional brain networks. Despite dramatic differences in data collection and protocols, networks from different studies aligned correctly in the embedding space.
DW-Net: Dynamic Multi-Hierarchical Weighting Segmentation Network for Joint Segmentation of Retina Layers With Choroid Neovascularization
Authors: Wang Lianyu , Wang Meng , Wang Tingting , Meng Qingquan , Zhou Yi , Peng Yuanyuan , Zhu Weifang , Chen Zhongyue , Chen Xinjian
Published: December 2021

Choroid neovascularization (CNV) is one of the blinding factors. The early detection and quantitative measurement of CNV are crucial for the establishment of subsequent treatment. Recently, many deep learning-based methods have been proposed for CNV segmentation. However, CNV is difficult to be segmented due to the complex structure of the surrounding retina. In this paper, we propose a novel dynamic multi-hierarchical weighting segmentation network (DW-Net) for the simultaneous segmentation of retinal layers and CNV. Specifically, the proposed network is composed of a residual aggregation encoder path for the selection of informative feature, a multi-hierarchical weighting connection for the fusion of detailed information and abstract information, and a dynamic decoder path. Comprehensive experimental results show that our proposed DW-Net achieves better performance than other state-of-the-art methods.
The Repression of the HMGB1-TLR4-NF-κB Signaling Pathway by Safflower Yellow May Improve Spinal Cord Injury
Authors: Wang Lu , Botchway Benson O. A. , Liu Xuehong
Published: December 2021

Spinal cord injury (SCI) often results in abnormal sensory and motor functions. Current interventions for SCI in the clinical setting are not effective partly due to the complexity concerning its pathophysiological mechanism. In the wake of SCI, considerable inflammatory cells assemble around the injured area that induces a series of inflammatory reactions and aggravates tissue lesions, thereby affecting the recovery of the damaged nerve tissue. Therefore, the inhibition of inflammatory responses can improve the repair of the injured spinal cord tissue. Safflower Yellow (SY) is the main active ingredient of Carthamus tinctorius. SY has anti-inflammatory effect, as it can inhibit IκBα phosphorylation to impede the NF-κB signaling pathway and p53 nuclear translocation. Besides, SY can limit the release of pro-inflammatory factors, which in turn may alleviate secondary SCI and prevent further complications. In this report, we analyze the pathophysiological mechanism of SCI, the role of inflammatory responses, and how SY interferes with the HMGB1-TLR-4-NF-κB signaling pathway to attenuate inflammatory responses in SCI.
Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies
Authors: Nhu Nguyen Thanh , Li Qing , Liu Yijie , Xu Jian , Xiao Shu-Yun , Lee Shin-Da
Published: December 2021

This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in ischemia/reperfusion (I/R) injury after ischemic stroke. Pubmed, Web of Science, and EMBASE databases were searched through July 2021. The studies published in English language that mentioned the effects of Mdivi-1 on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in I/R-induced brain injury were included. The CAMARADES checklist (for in vivo studies) and the TOXRTOOL checklist (for in vitro studies) were used for study quality evaluation. Twelve studies were included (median CAMARADES score = 6; TOXRTOOL scores ranging from 16 to 18). All studies investigated neural mitochondrial functions, providing that Mdivi-1 attenuated the mitochondrial membrane potential dissipation, ATP depletion, and complexes I-V abnormalities; enhanced mitochondrial biogenesis, as well as inactivated mitochondrial fission and mitophagy in I/R-induced brain injury. Ten studies analyzed neural mitochondria-mediated apoptosis, showing that Mdivi-1 decreased the levels of mitochondria-mediated proapoptotic factors (AIF, Bax, cytochrome c, caspase-9, and caspase-3) and enhanced the level of antiapoptotic factor (Bcl-2) against I/R-induced brain injury. The findings suggest that Mdivi-1 can protect neural mitochondrial functions, thereby attenuating neural mitochondria-mediated apoptosis in I/R-induced brain injury. Our review supports Mdivi-1 as a potential therapeutic compound to reduce brain damage in ischemic stroke (PROSPERO protocol registration ID: CRD42020205808).

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020205808].
The Hallucinogenic Serotonin2A Receptor Agonist, 2,5-Dimethoxy-4-Iodoamphetamine, Promotes cAMP Response Element Binding Protein-Dependent Gene Expression of Specific Plasticity-Associated Genes in the Rodent Neocortex
Authors: Desouza Lynette A. , Benekareddy Madhurima , Fanibunda Sashaina E. , Mohammad Farhan , Janakiraman Balaganesh , Ghai Utkarsha , Gur Tamar , Blendy Julie A. , Vaidya Vidita A.
Published: December 2021

Psychedelic compounds that target the 5-HT2A receptor are reported to evoke psychoplastogenic effects, including enhanced dendritic arborization and synaptogenesis. Transcriptional regulation of neuronal plasticity-associated genes is implicated in the cytoarchitectural effects of serotonergic psychedelics, however, the transcription factors that drive this regulation are poorly elucidated. Here, we addressed the contribution of the transcription factor cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) in the regulation of neuronal plasticity-associated genes by the hallucinogenic 5-HT2A receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI). In vitro studies with rat cortical neurons indicated that DOI enhances the phosphorylation of CREB (pCREB) through mitogen-activated protein (MAP) kinase and calcium/calmodulin dependent kinase II (CaMKII) pathways, with both cascades contributing to the DOI-evoked upregulation of Arc, Bdnf1, Cebpb, and Egr2 expression, whilst the upregulation of Egr1 and cFos mRNA involved the MAP kinase and CaMKII pathway respectively. We observed a robust DOI-evoked increase in the expression of several neuronal plasticity-associated genes in the rat neocortex in vivo. This DOI-evoked upregulation of neuronal plasticity-associated genes was completely blocked by the 5-HT2A receptor antagonist MDL100,907 in vitro and was also abrogated in the neocortex of 5-HT2A receptor deficient mice. Further, 5-HT2A receptor stimulation enhanced pCREB enrichment at putative cAMP response element (CRE) binding sites in the Arc, Bdnf1, Cebpb, cFos, but not Egr1 and Egr2, promoters in the rodent neocortex. The DOI-mediated transcriptional induction of Arc, cFos and Cebpb was significantly attenuated in the neocortex of CREB deficient/knockout (CREBαδ KO) mice. Collectively, these results indicate that the hallucinogenic 5-HT2A receptor agonist DOI leads to a rapid transcriptional upregulation of several neuronal plasticity-associated genes, with a subset of them exhibiting a CREB-dependent regulation. Our findings raise the intriguing possibility that similar to slow-acting classical antidepressants, rapid-action serotonergic psychedelics that target the 5-HT2A receptor may also recruit the transcription factor CREB to enhance the expression of neuronal plasticity-associated genes in the neocortex, which could in turn contribute to the rapid psychoplastogenic changes evoked by these compounds.
Infant Appetitive Phenotypes: A Group-Based Multi-Trajectory Analysis
Authors: Russell Catherine G. , Appleton Jessica , Burnett Alissa J. , Rossiter Chris , Fowler Cathrine , Denney-Wilson Elizabeth , Jansen Elena
Published: December 2021

Background: Examining appetitive traits with person-centered analytical approaches can advance the understanding of appetitive phenotype trajectories across infancy, their origins, and influences upon them. The objective of the present study was to empirically describe appetitive phenotype trajectories in infancy and examine the associations with infant and parent factors.

Materials and Methods: In this longitudinal cohort study of Australian infants, parents completed three online surveys ~3 months apart, beginning when the infant was <6 months. Appetitive traits were assessed with the Baby Eating Behavior Questionnaire (BEBQ) and parent feeding practices with the Feeding Practices and Structure Questionnaire (FPSQ) infant and toddler version. Parent demographics and cognitions were also collected. Infant weight and length were transcribed from health records and converted to a BMI z-score. Group-based trajectory modeling identified appetitive phenotype trajectories using the BEBQ. Multilevel modeling examined change in feeding practices and child BMI z-score over time by appetitive phenotype trajectories.

Results: At time 1, 380 participants completed the survey (mean infant age 98 days), 178 at time 2 (mean infant age 198 days), and 154 at time 3 (mean infant age 303 days). Three multi-trajectory appetitive phenotype groups were identified and labeled as (Phenotype 1) food avoidant trending toward low food approach (21.32% of infants), (Phenotype 2) persistently balanced (50.53% of infants), and (Phenotype 3) high and continuing food approach (28.16% of infants). Formula feeding was more common in Phenotype 1 (p = 0.016). Parents of infants in Phenotype 1 were more likely to rate them as being more difficult than average, compared to infants with phenotypes 2 or 3. Phenotype 2 had the greatest increase in persuasive feeding over time [0.30; 95% CI (0.12, −0.47)].

Conclusions: Distinct multi-trajectory appetitive phenotype groups emerge early in infancy. These trajectories appear to have origins in both infant and parent characteristics as well as parent behaviors and cognitions. The infant multi-trajectory appetitive phenotype groups suggest that for some infants, difficulties in self-regulating appetite emerge early in life. Investigation of infant multi-trajectory appetitive phenotype groups that utilize a range of measures, examine relationships to key covariates and outcomes, and extend from infancy into childhood are needed.
As a Staple Food Substitute, Oat and Buckwheat Compound Has Health-Promoting Effects for Diabetic Rats
Authors: Liu Siqi , Yin Xueqian , Hou Chao , Liu Xinran , Ma Huijuan , Zhang Xiaoxuan , Xu Meihong , Xie Ying , Li Yong , Wang Junbo
Published: December 2021

Dietary intervention is crucial for the prevention and control of diabetes. China has the largest diabetic population in the world, yet no one dietary strategy matches the eating habits of the Chinese people. To explore an effective and acceptable dietary pattern, this study uses oat and buckwheat compound (OBC) as a staple food substitute and explored its effects on diabetic Sprague–Dawley rats. The model of diabetic rats was established by combining high-calorie feed and streptozotocin (STZ) injection. The dietary intervention for the seven groups, including a normal control group, a model control group, a metformin control group, a wheat flour control group, and three OBC groups with different doses, started from the beginning of the experiment and lasted for 11 weeks, two consecutive injections of STZ in small doses were operated at the 6th week. General states, glucose metabolism, and lipid metabolism indexes were measured. Antioxidant and inflammatory indexes and pathologic changes of kidney and liver tissues were tested. Changes in kidney and ileum ultramicrostructure were detected. What's more, ileal epithelial tight junction proteins and gut microbiota were analyzed. Significant decreases in fasting blood glucose (FBG), glucose tolerance, serum insulin, and insulin resistance were observed in rats intervened with OBC, and these rats also showed a higher level of superoxide dismutase (SOD) together with improved lipid metabolism, attenuated inflammation, and liver and kidney injuries. In addition, in OBC groups, the intestinal barrier was improved, and the disturbance of gut microbiota was reduced. These results suggest that OBC has health-promoting effects for diabetic rats, and since oat and buckwheat are traditionally consumed grains in China, OBC could be a potential and easy-to-accept staple food substitute for the dietary pattern for Chinese.
Orange Juice Attenuates Circulating miR-150-5p, miR-25-3p, and miR-451a in Healthy Smokers: A Randomized Crossover Study
Authors: Dorna Mariana S. , Barbosa Elizabete M. S. , Callegari Matheus A. , Tanni Suzana E. , Chiuso-Minicucci Fernanda , Felix Tainara F. , Seneda Ana L. , Correa Camila R. , Fernandes Ana A. H. , Azevedo Paula S. , Polegato Bertha F. , Rogero Marcelo M. , Paiva Sergio A. R. , Zornoff Leonardo A. M. , Reis Patricia P. , Minicucci Marcos F.
Published: December 2021

Introduction: Tobacco smoke is associated with oxidative and inflammatory pathways, increasing the risk of chronic-degenerative diseases. Our goal was to evaluate the effects of acute “Pera” and “Moro” orange juice consumption on inflammatory processes and oxidative stress in microRNA (miRNA) expression in plasma from healthy smokers.

Methods: This was a randomized crossover study that included healthy smokers over 18 years old. Blood samples were collected before and 11 h after beverage ingestion. Participants were instructed to drink 400 mL of Pera orange juice (Citrus sinensis), Moro orange juice (Citrus sinensis L. Osbeck), or water. Each subject drank the beverages in a 3-way crossover study design. Inflammatory and oxidative stress biomarkers and circulating miRNA expression profiles were determined. The subjects maintained their usual tobacco exposure during the experiment.

Results: We included 18 individuals (12 men and 6 women), with 37.0 ± 12.0 years old. All subjects received the 3 interventions. Increased expression of circulating miRNAs (miR-150-5p, miR-25-3p, and miR-451a) was verified after cigarette smoking, which were attenuated after intake of both types of orange juice. There was no difference regarding serum levels of TNF-α, IL-6, MMP-9, and C-reactive protein. Despite the increased activity of serum superoxide dismutase and glutathione peroxidase after “Pera” or “Moro” orange juice intake, respectively, no changes in lipid hydroperoxide levels were detected.

Conclusion: Tobaccos smokers showed increased expression of miR-150-5p, miR-25-3p, and miR-451a was noted, and attenuated by orange juice intake. miRNAs were predicted to regulate 244 target genes with roles in oxidative stress, PI3K-Akt, and MAPK signaling, which are pathways frequently involved in smoking-related cardiovascular diseases and cancer.
Vitamin D Enhances Anticancer Properties of Cediranib, a VEGFR Inhibitor, by Modulation of VEGFR2 Expression in Melanoma Cells
Authors: Piotrowska Anna , Beserra Fernando Pereira , Wierzbicka Justyna Marta , Nowak Joanna Irena , Żmijewski Michał Aleksander
Published: December 2021

Regardless of the recent groundbreaking introduction of personalized therapy, melanoma continues to be one of the most lethal skin malignancies. Still, a substantial proportion of patients either fail to respond to the therapy or will relapse over time, representing a challenging clinical problem. Recently, we have shown that vitamin D enhances the effectiveness of classical chemotherapeutics in the human malignant melanoma A375 cell line. In search for new combination strategies and adjuvant settings to improve melanoma patient outcomes in the current study, the effects of cediranib (AZD2171), an oral tyrosine kinase inhibitor of VEGFR1-3, PDGFR, and c-KIT, used in combination either with 1,25(OH)2D3 or with low-calcemic analog calcipotriol were tested on four human malignant melanoma cell lines (A375, MNT-1, RPMI-7951, and SK-MEL-28). Melanoma cells were pretreated with vitamin D and subsequently exposed to cediranib. We observed a marked decrease in melanoma cell proliferation (A375 and SK-MEL-28), G2/M cell cycle arrest, and a significant decrease in melanoma cell mobility in experimental conditions used (A375). Surprisingly, concurrently with a very desirable decrease in melanoma cell proliferation and mobility, we noticed the upregulation of VEGFR2 at both protein and mRNA levels. No effect of vitamin D was observed in MNT-1 and RPMI-7951 melanoma cells. It seems that vitamin D derivatives enhance cediranib efficacy by modulation of VEGFR2 expression in melanoma cells expressing VEGFR2. In conclusion, our experiments demonstrated that vitamin D derivatives hold promise as novel adjuvant candidates to conquer melanoma, especially in patients suffering from vitamin D deficiency. However, further extensive research is indispensable to reliably assess their potential benefits for melanoma patients.
A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy
Authors: Zhang Chao , Zhao Shutao , Wang Xudong
Published: December 2021

Background

The perioperative treatment model for locally advanced rectosigmoid junction cancer (LARSC) has not been finalized; whether this model should refer to the treatment model for rectal cancer remains controversial.

Methods

We screened 10,188 patients with stage II/III rectosigmoid junction adenocarcinoma who underwent surgery between 2004 and 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Among them, 4,960 did not receive adjuvant chemotherapy, while 5,228 did receive adjuvant chemotherapy. Propensity score matching was used to balance the two groups for confounding factors, and the Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to identify independent prognostic factors and build a predictive nomogram of survival for LARSC. X-tile software was used to divide the patients into three groups (low, medium, and high) according to their risk scores. 726 patients in our hospital were included for external validation.

Results

LARSC patients did not show a benefit from neoadjuvant radiotherapy (P>0.05). After further excluding patients who received neoadjuvant radiotherapy, multivariate analysis found that age, grade, tumor size, T stage, and log odds of positive lymph nodes were independent prognostic factors for patients without adjuvant chemotherapy and were included in the nomogram. The C-index of the model was 0.690 (95% confidence interval: 0.668–0.712). We divided the patients into low, moderate, and high risk subgroups based on prediction scores of the nomogram. We found that adjuvant chemotherapy did not improve the prognosis of low risk patients, while moderate and high risk patients benefited from adjuvant therapy. External validation data found that moderate, and high risk patients also benefited from AT.

Conclusion

Direct surgery plus adjuvant chemotherapy may be the best perioperative treatment for LARSC. Moreover, adjuvant chemotherapy is only recommended for moderate and high risk patients as it did not benefit low risk patients.