bluuebunny/crossref_metadata_2025 huggingface dataset:
Duck Plague Virus Negatively Regulates IFN Signaling to Promote Virus Proliferation via JNK Signaling Pathway
Authors: Wu Liping , Tian Bin , Wang Mingshu , Cheng Anchun , Jia Renyong , Zhu Dekang , Liu Mafeng , Yang Qiao , Wu Ying , Huang Juan , Zhao XinXin , Chen Shun , Zhang Shaqiu , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Yu Yanling , Zhang Ling , Pan LeiCHang
Published: June 2022

Duck plague virus (DPV), a member of the alphaherpesvirus subfamily, can cause severe damage and immunosuppression in ducks and geese in China. Since lacking an available cell model, the antiviral signal transduction pathways induction and regulation mechanisms related to DPV infection in duck cells are still enigmatic. Our previous study developed a monocyte/macrophages cell model, which has been applied to study innate immunity with DPV. In the present study, we compared and analyzed transcriptome associated with the DPV infection of CHv (virulent strain) and CHa (avirulent strain) at 48hpi based on the duck monocyte/macrophages cell model and RNA-seq technology. Differentially expressed genes (DEGs) analysis showed 2,909 and 2,438 genes altered in CHv and CHa infected cells compared with control cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the DEGs were mainly involved in biological processes such as metabolic pathways, viral infectious diseases, immune system, and signal transduction. The CHv and CHa virus differentially regulated MAPK, NF-κB, and IFN signaling pathways based on transcriptome sequencing data and RT-qPCR results. The JNK inhibitor SP600125 enhanced the IFN signaling, but potentially reduced the VSV and DPV titers in the cell culture supernatant, indicating that JNK negatively regulates the IFN pathway and the inflammatory pathway to promote virus proliferation. The research results may provide promising information to understand the pathogenesis of DPV and provide a novel mechanism by which DPV modulates antiviral signaling and facilitate virus proliferation through hijacking the JNK pathway, which provides a new means for the prevention and control of DPV infection.
Application of Microalgae Assemblages’ Parameters for Ecological Monitoring in Mangrove Forest
Authors: Inyang Aniefiok Ini , Wang You-Shao , Cheng Hao
Published: June 2022

Although the relationship between biodiversity and ecological functioning is a vital issue in coastal water ecology, how this relationship is influenced by environmental conditions is still unknown. It was investigated for the dynamics of algal diversity and algal pollution indices, as well as their relationships with trophic state, in a mangrove forest along the Guangdong coast, South China. It is hypothesized that the phytoplankton alpha-diversity indices and algal pollution indices have the potential to provide a signal linking trophic state and water quality variation in the mangrove forest. The t-test showed that phytoplankton alpha-diversity indices and algal pollution indices varied significantly between the dry and wet seasons (p < 0.01 or p < 0.05). The trophic state index record confirmed that the mangrove forest was mesotrophic to eutrophic during study periods while the CCME: WQI revealed that the water quality in the forest was under poor and marginal conditions in both seasons. Multivariate analysis revealed that the dynamics of phytoplankton alpha-diversity and algal pollution indices was closely related to trophic states change and influenced by environmental conditions. The results indicated that pH, total dissolved solids, salinity, electrical conductivity, turbidity, nitrate, and phosphate were the main factors affecting algal assemblages in the mangrove forest. The indices were confirmed as a quicker, faster, and reliable approach to appropriately describe and measure the trophic state variations in the mangrove ecosystem, though an integrated approach may be required in the future.
Evaluation of Cytotoxicity of Pb2+ Ion-Adsorbed Amino-Functionalized Magnetic Mesoporous Silica Nanoparticles: An In Vitro Study
Authors: Chen Yu , Liu Miao
Published: June 2022

Application of amino-functionalized mesoporous silica-coated core-shell magnetic nanoparticles (Fe3O4@mSiO2-NH2 NPs) for adsorbing heavy metal ions has attracted intensive interest in recent years. Despite the cytotoxicity triggered by the co-exposure of nanoparticles (NPs) and metal ions in relatively high dosages being reported, the effect of the adsorbed heavy metal ions on the cytotoxicity to human cells remains unexplored. Herein, we demonstrated the effect of amino-functionalized Fe3O4@mSiO2 core-shell magnetic nanoparticles before and after adsorbing Pb2+ ions on the cytotoxicity of human kidney cells (HEK293). The surface morphology, viability, and oxidative stress (OS) induction of HEK293 cells incubated with Fe3O4@mSiO2-NH2 NPs and Pb2+ ion-adsorbed Fe3O4@mSiO2-NH2 NPs were assessed, respectively. Transmission electron microscopic (TEM) images of cell sections depicted that Fe3O4@mSiO2-NH2 NPs were internalized by HEK293 cells and gathered mainly in the cytoplasm. Cell viability (MTT) assays revealed the Fe3O4@mSiO2-NH2 NPs could enhance the cell viability to 119.9% and 108.2% compared to the control group, respectively. On contrast, the Pb2+ ion-adsorbed Fe3O4@mSiO2-NH2 NPs were toxic to the cell because when the Pb2+ ion contents were 5.0 and 7.5 μg mL−1, the viabilities of the samples decreased to 97.1% and 84.7%, respectively. Oxidative stress data proved that OS was negatively affected by both dissociative Pb2+ ions and the Pb2+ ion-adsorbed Fe3O4@mSiO2-NH2 NPs. Cytotoxicity may be attributed to the OS induced by Pb2+ ions leaked from the adsorbent. Under the same Pb2+ ion concentration, the cytotoxicity of the adsorbed Pb2+ ions was lower than that of the dissociative Pb2+ ions, indicating that the adsorption by NPs inhibited the cytotoxicity of Pb2+ ions. This work will provide new references for assessing the cytotoxicity of Pb2+-adsorbed nanoparticles.
Low Stroke Risk in Children With Sickle Cell Disease in French Guiana: A Retrospective Cohort Study
Authors: Gargot Julie , Parriault Marie-Claire , Adenis Antoine , Clouzeau Jérôme , Dinh Van Kim-Anh , Ntab Balthazar , Defo Antoine , Nacher Mathieu , Elenga Narcisse
Published: June 2022

One in every 227 babies born in French Guiana has sickle cell disease, which represents the greatest incidence in France. This study aimed to determine the incidence of stroke in children with sickle cell disease and its associated risk factors. This retrospective cohort study included all children with sickle cell disease diagnosed in the neonatal period who were born in French Guiana between 01/01/1992 and 12/31/2002. Of a total of 218 records, 122 patients were included. There were 70 HbSS/Sβ0 (58%), 40 HbSC (33%), and 11 Sβ + thalassemia (9%). The number of emergency admissions was significantly different between genotypes, with a higher number in SS/Sβ0 children (p = 0.004). There were significantly more acute chest syndromes (p = 0.006) and more elevated Lactate Dehydrogenase in SS/Sβ0 patients (p = 0.003). Three of these patients had ischemic strokes at a mean age of 6.9 years, and one had a hemorrhagic stroke at the age of 9,2 years. The incidence rate of ischemic stroke for SS/Sβ0 children was 3.1 (95% CI: 1.0–9.7) per 1,000 patient-years, and the clinically apparent stroke risk by the age of 15 years and 3 months was 6,4%. The incidence of hemorrhagic stroke was 1.1 (95% CI: 0.1–7.4) per 1,000 patients-years. No patient with SC or Sβ + thalassemia genotypes experienced any stroke.
Dialysis Duration and Glucose Exposure Amount Do Not Increase Mortality Risk in Peritoneal Dialysis Patients: A Population-Based Cohort Study From 2004 to 2012
Authors: Wu Pei-Yu , Lin Ming-Yen , Hwang Shang-Jyh , Chiu Yi-Wen
Published: June 2022

Background

Although the bio-incompatibility of glucose-based peritoneal dialysis (PD) solution is well documented, it is used worldwide. How PD duration and the amount of dialyzate glucose exposure affect survival in patients with end-stage renal disease remain inconclusive due to improper study designs in the extant literature.

Methods

All incident patients with PD from 2004 to 2007 who were older than 18 years in Taiwan were included. Patients were censored when they received a transplant or at the end of 2012. Glucose exposure through PD solution was calculated by the mean glucose contained per liter when receiving PD. For those who had already shifted to hemodialysis (HD) and survived longer than 2, 3, and 4 years (the index dates), the cause-specific Cox regression model was used to make the survival comparison by PD duration and mean glucose concentration in these three cohorts, respectively. The model was adjusted by demographics, case-mix, time cohort (2004–2005 vs. 2006–2007), peritonitis episode (none vs. ≥once), and mean PD solution glucose exposure (tertile).

Results

A total of 3,226 patients were included, with a mean age of 53.4 ± 15.2 years, 44.6% being male, and 34.2% having diabetes mellitus. The 1, 2, 3, and 4-year survival rates were 94, 87, 80, and 74%, while technical survival rates were 86, 70, 56, and 45%, respectively. The overall transplant events were 309 (9.6%) only. There were 389, 495, and 553 incident patients with PD shifting to HD included in 2-, 3-, and 4-year cohort, respectively. The population with moderate glucose concentration exposure had the highest mortality, and the high glucose concentration exposure had non-significant lower mortality in each cohort. In various fixed time-window cohorts, the duration of PD treatment did not increase mortality risk after adjustments. In addition, glucose exposure did not affect the mortality rate.

Conclusion

For incident PD patients with PD duration no longer than 4 years, neither PD duration nor glucose exposure amount increases the long-term mortality risk.
Optical Coherence Tomography Angiography Analysis of Vessel Density Indices in Early Post-COVID-19 Patients
Authors: Chiosi Flavia , Campagna Giuseppe , Rinaldi Michele , Manzi Gianluigi , dell'Omo Roberto , Fiorentino Giuseppe , Toro Mario , Tranfa Fausto , D'Andrea Luca , Rejdak Magdalena , Costagliola Ciro
Published: June 2022

Purpose

A hypercoagulable state has been reported to cause potential sight-threatening ischemia in patients suffering from Coronavirus disease 2019 (COVID-19). This study aimed to determine whether vessel density (VD), as measured by optical coherence tomography angiography (OCT-A), has insights into retinal and choriocapillaris vascular changes in patients affected by SARS-CoV-2 infection.

Methods

Hundred and fifty two patients positive for SARS-CoV-2 infection were enrolled in this observational, retrospective, controlled study. A control group of 60 healthy subjects was selected for statistical comparisons. Raw OCT and OCT-A data were exported and 3D datasets were analyzed to determine VD.

Results

Hundred and forty eyes (92.1%) were included for final analysis. The VD of the superficial capillary plexus (SCP) did not differ between the two groups. The mean VD of the deep capillary plexus (DCP) and the choriocapillaris (CC) was significantly lower in the foveal sector of the COVID-19 group compared to healthy controls. Within the post-COVID-19 group, the lowest DCP and CC foveal VD values were recorded in patients treated with antiviral therapy; no differences were observed among COVID-19 patients with other comorbidities (hypertension, diabetes, thyroid disease) or taking antiplatelet therapy. DCP and CC foveal VD were significantly lower in patients hospitalized in an intensive care unit (ICU) than asymptomatic patients.

Conclusion

Foveal vessel density at the level of DCP and CC was reduced in post-COVID-19 patients. Further studies evaluating these changes over time will be needed to corroborate the hypothesis of a microvascular retinal impairment in individuals who have recently recovered from SARS-CoV-2 infection.
Composition and Biogeography of Planktonic Pro- and Eukaryotic Communities in the Atlantic Ocean: Primer Choice Matters
Authors: Milke Felix , Sanchez-Garcia Selene , Dlugosch Leon , McNichol Jesse , Fuhrman Jed , Simon Meinhard , Wagner-Döbler Irene
Published: June 2022

Basin-scale biogeographic observations of marine pelagic pro- and eukaryotic communities are necessary to understand forces driving community composition and for providing a baseline to monitor global change. Deep sequencing of rRNA genes provides community composition at high resolution; yet, it is unclear how the choice of primers affects biogeographic patterns. Here, we re-amplified 16S rRNA genes from DNA sampled during R/V Polarstern Cruise ANT28-5 over a latitudinal transect across the Atlantic Ocean from 52°S to 47°N using universal V4-V5 primers and compared the results with those obtained previously with V5-V6 bacteria-specific primers. For validation of our results, we inferred community composition based on 16S rRNA genes of metagenomes from the same stations and single amplified genomes (SAGs) from the Global Ocean Reference Genome (GORG) database. We found that the universal V4-V5 primers retrieved SAR11 clades with similar relative proportions as those found in the GORG database while the V5-V6 primers recovered strongly diverging clade abundances. We confirmed an inverse bell-shaped distance-decay relationship and a latitudinal diversity gradient that did not decline linearly with absolute latitude in the Atlantic Ocean. Patterns were modified by sampling depth, sequencing depth, choice of primers, and abundance filtering. Especially richness patterns were not robust to methodological change. This study offers a detailed picture of the Atlantic Ocean microbiome using a universal set of PCR primers that allow for the conjunction of biogeographical patterns among organisms from different domains of life.
Mixed-Mode Bacterial Transmission via Eggshells in an Oviparous Reptile Without Parental Care
Authors: Li Teng , Yang Yang , Li Huijun , Li Chunkai
Published: June 2022

Symbiotic microorganisms play important roles in maintaining health and facilitating the adaptation of the host. We know little about the origin and transgenerational transmission of symbiotic bacteria, especially in egg-laying species without parental care. Here, we investigated the transmission of bacterial symbionts in the Chinese three-keeled pond turtle (Mauremys reevesii), a species with no post-oviposition parental care, by evaluating contributions from potential maternal and environmental sources to eggshell bacterial communities. Using 16S rRNA amplicon sequencing, we established that the bacterial communities of eggshells were similar to those of the maternal cloaca, maternal skin, and nest soil, but distinct from those of surface soil around nest and pond water. Phylogenetic structure analysis and source-tracking models revealed the deterministic assembly process of eggshell microbiota and high contributions of the maternal cloaca, maternal skin, and nest soil microbiota to eggshell bacterial communities. Moreover, maternal cloaca showed divergent contribution to eggshell microbiota compared with two other main sources in phylogenesis and taxonomic composition. The results demonstrate a mixture of horizontal and vertical transmission of symbiotic bacteria across generations in an oviparous turtle without parental care and provide insight into the significance of the eggshell microbiome in embryo development.
A Microtitre Plate Dilution Method for Minimum Killing Concentration Is Developed to Evaluate Metabolites-Enabled Killing of Bacteria by β-lactam Antibiotics
Authors: Tao Jian-jun , Xiang Juan-juan , Jiang Ming , Kuang Su-fang , Peng Xuan-xian , Li Hui
Published: June 2022

Because, as of yet, there are few new antibiotics active against multidrug-resistant bacteria are being explored, compounds including metabolites that might help us tide over this crisis are greatly expected. A recently adopted method to evaluate the potentiation of metabolites is the plate-counting test. However, the method is time-consuming, strenuous, and unfeasible for a large scale of screening. A minimum inhibitory concentration (MIC) test by using a microtitre plate dilution method is convenient and economic for a large scale of identification, but it cannot be used to detect the potentiation. Here, the microtitre plate dilution method was modified to develop a novel test for evaluating metabolites that enable the killing of bacterial pathogens by antibiotics, designed as minimum killing concentration (MKC). To do this, bacterial number, incubation time, ionic strength of M9 medium, and inosine concentration are optimized using Escherichia coli. Different from the MIC test, which uses 5 × 104 CFU cells and performed in LB medium, the MKC test needed 1 × 107 CFU - 2 × 107 CFU cells and was carried out in M9 medium. Moreover, MKC test was suitable for bactericidal antibiotics such as cephalosporins, penicillins and carbapenems and was proportional to the plate-counting test. The developed MKC test was feasible for different metabolites and clinically multidrug-resistant pathogens, and measurement of minimum bactericidal concentration (MBC). Therefore, the MKC test was developed to accelerate the identification of compounds that promote antibiotic-mediated killing efficacy.
The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer’s Disease
Authors: Weng Shiting , Lai Qi-Lun , Wang Junjun , Zhuang Liying , Cheng Lin , Mo Yejia , Liu Lu , Zhao Zexian , Zhang Ying , Qiao Song
Published: June 2022

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of β–amyloid peptide 1–42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of β-amyloid peptide 1–42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.
Obesity, Weight Gain, and Fluid Overload in Peritoneal Dialysis
Authors: Ng Jack Kit-Chung , Than Win Hlaing , Szeto Cheuk Chun
Published: June 2022

Obesity is a global epidemic that has a complicated pathogenesis as well as impact on the outcome of peritoneal dialysis (PD) patients. In this review, the prevalence of obesity in incident PD patients as well as the phenomenon of new-onset glucose intolerance after PD will be reviewed. Published literature on the effect of obesity on the survival and incidence of cardiovascular disease in PD patients will be discussed. Particular emphasis would be put on literature that compared the impact of obesity on the outcome of hemodialysis and PD, and the confounding effect of dialysis adequacy. Next, the complex concept of obesity and its relevance for PD will be explored. The focus would be put on the methods of assessment and clinical relevance of central versus general obesity, as well as visceral versus subcutaneous adipose tissue. The relation between obesity and systemic inflammation, as well as the biological role of several selected adipokines will be reviewed. The confounding effects of metabolic syndrome and insulin resistance will be discussed, followed by the prevalence and prognostic impact of weight gain during the first few years of PD. The differences between weight gain due to fluid overload and accumulation of adipose tissue will be discussed, followed by the current literature on the change in body composition after patients are put on chronic PD. The methods of body composition will be reviewed, and the clinical relevance of individual body component (fluid, fat, muscle, and bone) will be discussed. The review will conclude by highlighting current gaps of knowledge and further research directions in this area.
Role of HMGB1/TLR4 and IL-1β/IL-1R1 Signaling Pathways in Epilepsy
Authors: Zhang Shaohui , Chen Feng , Zhai Feng , Liang Shuli
Published: June 2022

Epilepsy is a chronic disorder of the nervous system characterized by recurrent seizures. Inflammation is one of the six major causes of epilepsy, and its role in the pathogenesis of epilepsy is gaining increasing attention. Two signaling pathways, the high mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4) and interleukin-1β (IL-1β)/interleukin-1 receptor 1 (IL-1R1) pathways, have become the focus of research in recent years. These two signaling pathways have potential as biomarkers in the prediction, prognosis, and targeted therapy of epilepsy. This review focuses on the association between epilepsy and the neuroinflammatory responses mediated by these two signaling pathways. We hope to contribute further in-depth studies on the role of HMGB1/TLR4 and IL-1β/IL-1R1 signaling in epileptogenesis and provide insights into the development of specific agents targeting these two pathways.
The Role of Graph Theory in Evaluating Brain Network Alterations in Frontotemporal Dementia
Authors: Nigro Salvatore , Filardi Marco , Tafuri Benedetta , De Blasi Roberto , Cedola Alessia , Gigli Giuseppe , Logroscino Giancarlo
Published: June 2022

Frontotemporal dementia (FTD) is a spectrum of clinical syndromes that affects personality, behavior, language, and cognition. The current diagnostic criteria recognize three main clinical subtypes: the behavioral variant of FTD (bvFTD), the semantic variant of primary progressive aphasia (svPPA), and the non-fluent/agrammatic variant of PPA (nfvPPA). Patients with FTD display heterogeneous clinical and neuropsychological features that highly overlap with those presented by psychiatric syndromes and other types of dementia. Moreover, up to now there are no reliable disease biomarkers, which makes the diagnosis of FTD particularly challenging. To overcome this issue, different studies have adopted metrics derived from magnetic resonance imaging (MRI) to characterize structural and functional brain abnormalities. Within this field, a growing body of scientific literature has shown that graph theory analysis applied to MRI data displays unique potentialities in unveiling brain network abnormalities of FTD subtypes. Here, we provide a critical overview of studies that adopted graph theory to examine the topological changes of large-scale brain networks in FTD. Moreover, we also discuss the possible role of information arising from brain network organization in the diagnostic algorithm of FTD-spectrum disorders and in investigating the neural correlates of clinical symptoms and cognitive deficits experienced by patients.
Electroacupuncture on Hemifacial Spasm and Temporomandibular Joint Pain Co-Morbidity: A Case Report
Authors: Huang Jian-peng , Liang Zhan-mou , Zou Qi-wen , Zhan Jie , Li Wen-ting , Li Sheng , Li Kai , Fu Wen-bin , Liu Jian-hua
Published: June 2022

Hemifacial spasm (HFS) and temporomandibular joint (TMJ) pain are common facial diseases which cause depression, anxiety, insomnia, and poor quality of life. However, currently there are still no effective therapies to treat HFS and TMJ. Electroacupuncture (EA) has advantages of safety, rapid work, easy operation and convenience. Here, we reported a case of a 50-year-old woman who presented with irregular spasm of eyelids and facial muscles on the left side, and TMJ pain on the right side. The patient had been treated with carbamazepine (20mg per day) and alternative therapies for a year, but still not much improvement in the symptoms. The scores of the Jankovic Rating Scale (JRS), global rating scale (GRS), and visual analog scale (VAS) were 7, 60, and 7 points, respectively. The EMG test showed that the spastic side had higher R1 amplitude, longer R2 duration, and larger R2 area than the non-spasmodic side, and the occurrence rate of the lateral spread responses (LSR) in the Orbicularis oris and the Orbicularis oculi muscle was 60% and 40%, respectively. We considered this patient had left HFS and right TMJ pain. EA was successfully undertaken for two periods over 30 weeks. After EA, JRS and VAS were reduced sharply, and the symptoms of HFS were stable without recurrence. However, the frequency of the lower eyelid increased gradually during the 6-month follow-up. These findings reveal that EA with the frequency of 2 Hz and intensity of ~ 1–2 mA may be a benefit for alleviating symptoms of HFS and TMJ pain without adverse reaction. The potential mechanisms of EA in HFS and TMJ pain co-morbidity involve brain stem mechanism and DNIC mechanism for distal acupuncture and segmental mechanism for local acupuncture analgesia.
Differences in Alpha Diversity of Gut Microbiota in Neurological Diseases
Authors: Li Zhuoxin , Zhou Jie , Liang Hao , Ye Li , Lan Liuyan , Lu Fang , Wang Qing , Lei Ting , Yang Xiping , Cui Ping , Huang Jiegang
Published: June 2022

Background

Neurological diseases are difficult to diagnose in time, and there is currently a lack of effective predictive methods. Previous studies have indicated that a variety of neurological diseases cause changes in the gut microbiota. Alpha diversity is a major indicator to describe the diversity of the gut microbiota. At present, the relationship between neurological diseases and the alpha diversity of the gut microbiota remains unclear.

Methods

We performed a systematic literature search of Pubmed and Bioproject databases up to January 2021. Six indices were used to measure alpha diversity, including community richness (observed species, Chao1 and ACE), community diversity (Shannon, Simpson), and phylogenetic diversity (PD). Random-effects meta-analyses on the standardized mean difference (SMD) were carried out on the alpha diversity indices. Subgroup analyses were performed to explore the sources of interstudy heterogeneity. Meta-analysis was performed on articles by matching the age, sex, and body mass index (BMI) of the disease group with the control group. Meanwhile, subgroup analysis was performed to control the variability of the sequencing region, platform, geographical region, instrument, and diseases. The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was calculated to assess the prediction effectiveness of the microbial alpha diversity indices.

Results

We conducted a meta-analysis of 24 published studies on 16S rRNA gene amplified sequencing of the gut microbiota and neurological diseases from the Pubmed and Bioproject database (patients, n = 1,469; controls, n = 1,289). The pooled estimate demonstrated that there was no significant difference in the alpha diversity between patients and controls (P < 0.05). Alpha diversity decreased only in Parkinson's disease patients, while it increased in anorexia nervosa patients compared to controls. After adjusting for age, sex, BMI, and geographical region, none of the alpha diversity was associated with neurological diseases. In terms of Illumina HiSeq 2000 and the V3-V5 sequencing region, the results showed that alpha diversity increased significantly in comparison with the controls, while decreased in Illumina HiSeq 2500. ROC curves suggested that alpha diversity could be used as a biomarker to predict the AD (Simpson, AUC= 0.769, P = 0.0001), MS (observed species, AUC= 0.737, P = 0.001), schizophrenia (Chao1, AUC = 0.739, P = 0.002).

Conclusions

Our review summarized the relationship between alpha diversity of the gut microbiota and neurological diseases. The alpha diversity of gut microbiota could be a promising predictor for AD, schizophrenia, and MS, but not for all neurological diseases.
Functional Plasticity Coupled With Structural Predispositions in Auditory Cortex Shape Successful Music Category Learning
Authors: Mankel Kelsey , Shrestha Utsav , Tipirneni-Sajja Aaryani , Bidelman Gavin M.
Published: June 2022

Categorizing sounds into meaningful groups helps listeners more efficiently process the auditory scene and is a foundational skill for speech perception and language development. Yet, how auditory categories develop in the brain through learning, particularly for non-speech sounds (e.g., music), is not well understood. Here, we asked musically naïve listeners to complete a brief (∼20 min) training session where they learned to identify sounds from a musical interval continuum (minor-major 3rds). We used multichannel EEG to track behaviorally relevant neuroplastic changes in the auditory event-related potentials (ERPs) pre- to post-training. To rule out mere exposure-induced changes, neural effects were evaluated against a control group of 14 non-musicians who did not undergo training. We also compared individual categorization performance with structural volumetrics of bilateral Heschl’s gyrus (HG) from MRI to evaluate neuroanatomical substrates of learning. Behavioral performance revealed steeper (i.e., more categorical) identification functions in the posttest that correlated with better training accuracy. At the neural level, improvement in learners’ behavioral identification was characterized by smaller P2 amplitudes at posttest, particularly over right hemisphere. Critically, learning-related changes in the ERPs were not observed in control listeners, ruling out mere exposure effects. Learners also showed smaller and thinner HG bilaterally, indicating superior categorization was associated with structural differences in primary auditory brain regions. Collectively, our data suggest successful auditory categorical learning of music sounds is characterized by short-term functional changes (i.e., greater post-training efficiency) in sensory coding processes superimposed on preexisting structural differences in bilateral auditory cortex.
The Enhanced Interhemispheric Functional Connectivity in the Striatum Is Related to the Cognitive Impairment in Individuals With White Matter Hyperintensities
Authors: Zhu Huahong , Qin Ruomeng , Cheng Yue , Huang Lili , Shao Pengfei , Xu Hengheng , Xu Yun , Ye Qing
Published: June 2022

Objective

The cognitive performance of individuals with white matter hyperintensities (WMH) tends to vary considerably. This study aimed to explore the relationship of the synchronous spontaneous activities in homotopic areas across hemispheres, named as voxel-mirrored homotopic connectivity (VMHC), with the cognitive performance of individuals with WMH.

Materials and Methods

Eighty-two WMH subjects without cognitive impairment (CI), 56 WMH subjects with CI, and 92 healthy subjects (HS) underwent neuropsychological tests and multimodal magnetic resonance imaging scans. VMHC maps were analyzed among the three groups. Correlative analyses were performed between VMHC values and cognitive function.

Results

No significant difference in WMH volume, brain volume, or gray matter atrophy rate was shown between WMH subjects with and without CI. In contrast, those with CI displayed lower VMHC in the bilateral cuneus and calcarine and higher VMHC in the lentiform nucleus and caudate nucleus (LNCN) than those without CI. Furthermore, the VMHC in the LNCN was negatively associated with the global function and the memory function in WMH subjects.

Conclusion

The enhanced VMHC in the LNCN was associated with the development of CI in individuals with WMH. This finding may contribute to the exploration of surrogate markers for the CI caused by WMH.
Establish a New Diagnosis of Sarcopenia Based on Extracted Radiomic Features to Predict Prognosis of Patients With Gastric Cancer
Authors: Chen Xiao-Dong , Chen Wen-Jing , Huang Ze-Xin , Xu Li-Bin , Zhang Hui-Hui , Shi Ming-Ming , Cai Yi-Qi , Zhang Wei-Teng , Li Zhao-Shen , Shen Xian
Published: June 2022

Background

Preoperative sarcopenia is a prognostic risk factor for gastric cancer (GC). This study aimed to determine whether radiomic sarcopenia features on computed tomography (CT) could be used to diagnose sarcopenia preoperatively, and whether they could be used to accurately predict the postoperative survival and complication prognosis of patients with GC.

Methods

We retrospectively analyzed data of 550 patients with GC who underwent radical gastrectomy. The patients were divided into training (2014–2016) and validation (2017–2019) cohorts. We established a radiomics-based diagnosis tool for sarcopenia. Thereafter, univariate and multivariate analyses of diagnostic factors were carried out. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were used to compare different diagnostic models. The Kaplan–Meier method was used to estimate the survival curve.

Results

Radiomic sarcopenia correlated with complications and long-term survival. Skeletal muscle index, grip strength, and walking speed were correlated with postoperative complications in both cohorts (AUCs: 0.632, 0.577, and 0.614, respectively in the training cohort; 0.570, 0.605, 0.546, respectively, in the validation cohort), and original sarcopenia was more accurate than any of these indicators. However, radiomic sarcopenia has a higher AUC in predicting short-term complications than original sarcopenia in both groups (AUCs: 0.646 vs. 0.635 in the training cohort; 0.641 vs. 0.625 in the validation cohort). In the training cohort, the overall survival time of patients with original sarcopenia was shorter than normal patients (hazard ratio, HR = 1.741; 95% confidence interval [CI], 1.044–2.903; p = 0.031). While radiomic sarcopenia had a greater prognostic significance, the overall survival time of patients with radiomic sarcopenia was significantly worse than normal patients (HR, 1.880; 95% CI, 1.225–2.885, p = 0.003).

Conclusion

Extracted sarcopenia features based on CT can predict long-term survival and short-term complications of GC patients after surgery, and its accuracy has been verified by training and validation groups. Compared with original sarcopenia, radiomic sarcopenia can effectively improve the accuracy of survival and complication prediction and also shorten the time and steps of traditional screening, thereby reducing the subjectivity effects of sarcopenia assessment.
Folic Acid Preconditioning Alleviated Radiation-Induced Ovarian Dysfunction in Female Mice
Authors: Zhang Qianyu , Wei Zhifu , Weng Huinan , Chen Ye , Zhang Jie , Mei Shiwei , Wei Jiahui , Zhu Xiulan , Nong Yingqi , Ruan Jianxing , Liu Wenjuan , Zhou Ruiqiong , Wang Fang , Xie Yanni , Huang Junjiu , Zhang Xiqian , Liu Fenghua
Published: June 2022

Radiological therapy/examination is the primary source of artificial radiation exposure in humans. While its application has contributed to major advances in disease diagnosis and treatment, ionizing radiation exposure is associated with ovarian damage. The use of natural products, either alone or as an adjunct, has become increasingly common for reducing the side effects of radiological therapy during disease treatment. Herein, we explored the protective effect of folic acid (FA), a widely used B vitamin, against radiation-induced ovarian injury and its mechanism of action. Female mice with normal ovarian function were randomly divided into control, FA, radiation, and radiation + FA groups. The intervention strategy included daily intragastric administration of FA (5 mg/kg) for 3 weeks prior to radiation exposure. Mice in the radiation and radiation + FA groups received a single dose of 5 Gy X-ray irradiation. Changes in the estrous cycle were then recorded, and ovarian tissues were collected. Pathophysiological changes as well as reproductive and endocrine-related indexes were determined via H&E staining, immunohistochemistry, Western blot, and ELISA. The reproductive performance and emotional symptoms of animals were also monitored. Our results indicated that FA intervention effectively alleviated ovarian damage, leading to more regular estrous cycles, lesser impairment of follicular morphology and endocrine status, as well as greater germ cell preservation. Reduced levels of oxidative stress, inflammation, and enhanced DNA repair were associated these changes. FA pre-administration improved the reproductive performance, leading to higher pregnancy rates and greater litter sizes. Further, the anxiety levels of animals were significantly reduced. Our results indicate that FA pre-administration significantly alleviates radiation-induced ovarian damage in rodents, highlighting its potential as a protective strategy against radiation exposure in the female population.
Induction of Ferroptosis by Ophiopogonin-B Through Regulating the Gene Signature AURKA in NSCLC
Authors: Li Liqiu , Gao Qian , Wang Jin , Gu Ling , Li Zhihui , Zhang Shiping , Hu Cheng , He Menglin , Wang Yulin , Wang Zixuan , Yi Yongxiang , Fu Jin , Zhang Xiongfei , Ge Fei , Chen Meijuan , Zhang Xu
Published: June 2022

Ferroptosis is a new type of iron-dependent programmed cell death. In recent years, its role in the diagnosis and treatment of multiple tumors, including non-small cell lung cancer (NSCLC), has been continuously observed. The relationship between the ferroptosis-related genes and the prognosis of patients with NSCLC needs to be clarified. In this study, The Cancer Genome Atlas (TCGA) and the Gene Expression Synthesis database (Gene Expression Omnibus, GEO) were used to build a model of ferroptosis-related differentially expressed genes (DEGs). A total of 101 ferroptosis-related DEGs were screened using R language, and a 12-gene signature was finally established through univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. According to the risk scores, the patients were divided into a high-risk or a low-risk group, with patients in the low-risk group showing better prognosis. AURKA, one of the genes in the 12-gene signature, was found to be highly expressed in tumors. In addition, further study verified AURKA to be a negative regulator of ferroptosis in NSCLC cells. Ophiopogonin B (OP-B) had been reported to induce apoptosis, mitotic catastrophe, and autophagy in NSCLC cells. Herein, proteomic sequencing analysis and OP-B administration revealed the upregulation of AURKA and the downregulation of PHKG2 and SLC7A5 in the 12-gene signature, indicating that OP-B induced ferroptosis in NSCLC. Determination of the concentrations of malondialdehyde (MDA), glutathione (GSH), and intracellular iron and the mitochondrial membrane potential (MMP) confirmed the induction of ferroptosis by OP-B in vitro. Furthermore, transmission electron microscopy (TEM) examination of lung cancer xenotransplantation in nude mice confirmed that OP-B induced ferroptosis in vivo. Further study of the molecular mechanism showed that the ferroptosis effect caused by OP-B can be partially reversed by the overexpression of AURKA. Overall, our study established a new ferroptosis-related risk prediction model for the prognosis of patients with NSCLC, revealed the enrichment pathways of ferroptosis in NSCLC, and discovered the negative regulation of AURKA in ferroptosis. On this basis, we demonstrated that OP-B can induce ferroptosis in NSCLC and clarified the specific molecular mechanism of OP-B inducing ferroptosis by regulating the expression of AURKA.
The Diagnostic Potential of SHOX2 and RASSF1A DNA Methylation in Early Lung Adenocarcinoma
Authors: Gao Hong , Yang Jun , He Lu , Wang Wei , Liu Yanhong , Hu Yue , Ge Meiling , Ding Jie , Ye Qing
Published: June 2022

Objective

Methylation of the promoters of SHOX2 and RASSF1A are potentially informative biomarkers for the diagnosis of early lung adenocarcinoma (LUAD). Abnormal methylation of SHOX2 and RASSF1A promoters may promote the occurrence and facilitate the progression of LUAD.

Materials and Methods

We selected 54 patients with early LUAD and 31 patients with benign lung nodules as a NJDT cohort and evaluated their DNA methylation and mRNA sequencing levels. The DNA methylation sequencing, mRNA sequencing, and clinical data for patients with LUAD were obtained from The Cancer Genome Atlas, and served as a TCGA cohort. We evaluated the diagnostic potential of a SHOX2 and RASSF1A combined promoter methylation assay for detection of early LUAD in the NJDT cohort. Then we explored the promoter methylation levels of SHOX2 and RASSF1A and their gene expression between normal and tumor samples at different stages in both cohorts. Pathways enriched between tumor and normal samples of methylation-positive patients in the NJDT cohort were analyzed.

Results

In the NJDT cohort, the sensitivity of the combined promoter methylation assay on tumor samples was 74.07%, the sensitivity on paired tumor and paracancerous samples was 77.78%, and the specificities in both contexts were 100%. The combined promoter methylation-positive patients had clinicopathologic features including older age, larger tumors, deeper invasion, and higher Ki-67 expression. In both cohorts, SHOX2 expression increased and RASSF1A expression decreased in tumor samples. The promoter methylation level of SHOX2 and RASSF1A was significantly higher in tumor samples at stage I-II than that in normal samples. The promoter methylation levels of these two genes were both negative associated with their expression in early tumor samples. In the NJDT cohort, methylation-positive patients of both individual SHOX2 and RASSF1A assays exhibited upregulation of folate acid metabolism and nucleotide metabolism in tumor samples. The SHOX2 methylation-positive and RASSF1A methylation-positive patients showed the downregulation of pathways related to cell proliferation and apoptosis and pathways involved in DNA repair, cell growth and cell adhesion, respectively.

Conclusion

The combined promoter methylation assay for SHOX2 and RASSF1A can be used for screening and diagnosis of early LUAD, with good sensitivity and specificity. The promoter methylation levels of SHOX2 and RASSF1A were associated with their abnormal mRNA expression, and affected DNA instability, cell proliferation, apoptosis and tumor microenvironment in patients with LUAD.
Development of a Multicellular 3D Tumor Model to Study Cellular Heterogeneity and Plasticity in NSCLC Tumor Microenvironment
Authors: Arora Leena , Kalia Moyna , Dasgupta Suman , Singh Navneet , Verma Anita K. , Pal Durba
Published: June 2022

Heterogeneity is a characteristic feature of solid tumors. Intra-tumor heterogeneity includes phenotypic diversity, epigenetic abnormalities, cell proliferation, and plasticity that eventually drives disease progression. Studying tumor heterogeneity in 2D culture is challenging as it cannot simulate the microenvironmental features, such as hypoxia, nutrient unavailability, and cell-ECM interactions. We propose the development of multicellular (tri-culture) 3D spheroids using a hanging drop method to study the non-tumorigenic (BEAS-2B) vs. tumorigenic NSCLC (A549/NCI-H460)cells’ interaction with lung fibroblasts (MRC-5) and monocytes (THP-1). Unlike the non-tumorigenic model, the tumorigenic 3D spheroids show significant induction of cell proliferation, hypoxia, pluripotency markers, notable activation of cancer-associated fibroblasts, and tumor-associated macrophages. CD68+ macrophages isolated from tumorigenic spheroids exhibited profound induction of phenotypic endothelial characteristics. The results are zebrafish tumor xenograft model and by using human patient samples. This multicellular 3D tumor model is a promising tool to study tumor-stroma interaction and cellular plasticity, targeting tumor heterogeneity, and facilitating cancer therapy success against NSCLC.
Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia
Authors: Li Yang , Xiao Jun , Zhang Tiancheng , Zheng Yanying , Jin Hailin
Published: June 2022

Background

Early colorectal cancer (ECRC) refers to any size of colorectal cancer (CRC) whose depth of invasion is limited to the mucosa and submucosa. About 10% of patients with ECRC die from cancer after surgery. KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) are considered diagnostic and prognostic markers in CRC. However, their characteristics in ECRC and whether postoperative chemotherapy based on them will benefit ECRC patients or not remain unknown.

Patients and Methods

Patients with ECRC and 298 patients with advanced colorectal cancer (ACRC) were collected in our hospital from January 2013 to December 2015. The Amplification Refractory Mutation System (ARMS)-PCR was used to perform the KRAS, NRAS, and BRAF mutant tests.

Results

In ECRC patients, 43 cases of KRAS mutation were found, accounting for 69.35%. Interestingly, among KRAS mutations, there were 10 KRAS multi-site mutation patients (16.13% in 62 ECRC patients). Moreover, the NRAS mutation rate was 3.23% but no BRAF mutation was found and only 1 case of MSI-High was detected. KRAS mutation was only related to the depth of tumor invasion whereas KRAS multi-site mutations were related to mucus components and tumor size. As far as NRAS is concerned, mutations were associated with elevated CEA, mucus components, and the depth of tumor invasion. Notably, compared with 2.35% KRAS multi-site mutation in ACRC, the rate of KRAS multi-site mutation in ECRC was much higher. Furthermore, Cox regression analysis revealed that KRAS mutation could be an independent prognostic factor of ECRC in patients who have undergone endoscopic resection or surgery.

Conclusion

Patients with ECRC might benefit from KRAS mutation testing but not from postoperative chemotherapy.