bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha-7 Nicotinic Receptor Dampens Murine Osteoblastic Response to Inflammation and Age-Related Osteoarthritis
Authors: Courties Alice , Petit Juliette , Do Ariane , Legris Manon , Kouki Inès , Pigenet Audrey , Sacitharan Pradeep K. , Ehkirch Francois-Paul , Berenbaum Francis , Sellam Jérémie
Published: April 2022

Introduction

Osteoarthritis (OA) is a whole-joint disease characterized by a low-grade inflammation that is involved in both cartilage degradation and subchondral bone remodeling. Since subchondral bone has a cholinergic innervation and that acetylcholine (Ach) might have an anti-inflammatory effect through the α7 nicotinic Ach receptor (α7nAchR), we aimed (i) to determine the expression of non-neuronal cholinergic system and nicotinic receptor subunits by murine and human osteoblasts, (ii) to address the role of α7nAchR in osteoblastic response to inflammation, and (iii) to study the role of α7nAchR in a spontaneous aging OA model.

Methods

Primary cultures of WT and α7nAchR knock-out mice (Chrna7-/-) murine osteoblasts and of subchondral bone human OA osteoblasts were performed. The expressions of the non-neuronal cholinergic system and of the nAchR subunits were assessed by PCR. In vitro, IL1β-stimulated WT, Chrna7-/-, and human osteoblasts were pretreated with nicotine. At 24 h, expressions of interleukin-6 (IL6) and metalloproteinase-3 and -13 (MMP), RANK-ligand (RANKL), and osteoprotegerin (OPG) were quantified by qPCR and ELISA. Spontaneous aging OA was evaluated and compared between male WT and Chrna7-/- mice of 9 and 12 months.

Results

Murine WT osteoblasts express the main components of the cholinergic system and α7 subunit composing α7nAchR. Nicotine partially prevented the IL1β-induced expression and production of IL6, MMP3, and RANKL in WT osteoblasts. The effect for IL6 and MMP was mediated by α7nAchR since nicotine had no effect on Chrna7-/- osteoblasts while the RANKL decrease persisted. Chrna7-/- mice displayed significantly higher cartilage lesions than their WT counterparts at 9 and 12 months, without difference in subchondral bone remodeling. Human OA osteoblasts also expressed the non-neuronal cholinergic system and α7 subunit as well as CHRFAM7A, the dominant negative duplicate of Chrna7. Nicotine pretreatment did not significantly reduce IL6 and MMP3 production in IL-1β-stimulated human osteoarthritic osteoblasts (n = 4), possibly due to CHRFAM7A.

Conclusion

Cholinergic system counteracts murine osteoblastic response to IL-1β through α7nAchR. Since α7nAchR deletion may limit cartilage degradation during murine age-related OA, enhancing cholinergic system could be a new therapeutic target in OA but may depend on CHRFAM7A expression.
Neutrophil Percentage-to-Albumin Ratio: A Good Parameter for the Evaluation of the Severity of Anti-NMDAR Encephalitis at Admission and Prediction of Short-Term Prognosis
Authors: Tang Yao , Hou Haiman , Li Lanjun , Yong Liuliang , Zhang Shuang , Yan Lulu , Huang Xiaoxue , Wu Jun
Published: April 2022

Objectives

The purpose of this study was to investigate the association of neutrophil percentage-to-albumin ratio (NPAR) with the severity at admission and discharge (short-term prognosis) in patients with anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis.

Methods

Multivariable logistic regression models such as NPAR were constructed based on univariable regression results. Receiver operating characteristic (ROC) curves, nomograms, and concordance index (c-index) were used to evaluate the efficacy of the models in assessing disease severity at admission and predicting short-term prognosis, validated by bootstrap, Hosmer–Lemeshow goodness-of-fit test, calibration curves, and decision curve analysis.

Results

A total of 181 patients with anti-NMDAR encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University were included. The results showed that NPAR had good sensitivity and specificity in assessing disease severity at admission and predicting short-term prognosis. The multivariable logistic regression models based on NPAR and other influencing factors had good discrimination, consistency, accuracy, calibration ability, applicability, and validity in assessing the severity at admission and predicting short-term prognosis.

Conclusion

NPAR has good clinical value in assessing disease severity at admission and predicting short-term prognosis of patients with anti-NMDAR encephalitis.
Epigenetic Regulation of Immune and Inflammatory Responses in Rheumatoid Arthritis
Authors: Chen Qi , Li Hao , Liu Yusi , Zhao Min
Published: April 2022

Purpose

Rheumatoid arthritis (RA) is a disease associated with multiple factors. Epigenetics can affect gene expression without altering the DNA sequence. In this study, we aimed to comprehensively analyze epigenetic regulation in RA.

Methods

Using the Gene Expression Omnibus database, we identified a methylation chip, RNA-sequencing, and miRNA microarray for RA. First, we searched for DNA methylation, genes, and miRNAs associated with RA using differential analysis. Second, we determined the regulatory networks for RA-specific methylation, miRNA, and m6A using cross-analysis. Based on these three regulatory networks, we built a comprehensive epigenetic regulatory network and identified hub genes.

Results

Using a differential analysis, we identified 16,852 differentially methylated sites, 4877 differentially expressed genes, and 32 differentially expressed miRNAs. The methylation-expression regulatory network was mainly associated with the PI3K-Akt and T-cell receptor signaling pathways. The miRNA expression regulatory network was mainly related to the MAPK and chemokine signaling pathways. M6A regulatory network was mainly associated with the MAPK signaling pathway. Additionally, five hub genes were identified in the epigenetic regulatory network: CHD3, SETD1B, FBXL19, SMARCA4, and SETD1A. Functional analysis revealed that these five genes were associated with immune cells and inflammatory responses.

Conclusion

We constructed a comprehensive epigenetic network associated with RA and identified core regulatory genes. This study provides a new direction for future research on the epigenetic mechanisms of RA.
Ontogenetic and Spatiotemporal Changes in Isotopic Niche of Jumbo Squid (Dosidicus gigas) in the Southeastern Pacific
Authors: Hu Guanyu , Boenish Robert , Zhao Zhenfang , Li Jianhua , Chen Xinjun
Published: April 2022

Jumbo squid (Dosidicus gigas) plays an important role in food webs throughout the eastern Pacific; however, its trophic ecology is complex, because it is a highly migratory and opportunistic predator. In this study, δ13C and δ15N values were measured along the lateral wall of lower beak to investigate the ontogenetic and spatiotemporal feeding strategy shifts of jumbo squid, respectively. Both year and area had significant influences on δ13C (p < 0.01), while sex and stage had no significant influence on δ13C (p > 0.05). All explanatory variables (sex, stage, year, and area) had significant influences on δ15N (p < 0.05). The differences of niche among life stages indicated that the habitat and feeding habit were likely changed with the growth of individuals. Compared with normal years, the habitat of squids might change during the El Niño year. However, during the strong El Niño year, habitat location changed and niche size decreased compared to normal years. The trophic niche of D. gigas differed between different areas. Stable isotopes in early life stages were most effective for distinguishing different geographic populations. Females and males were likely to inhabit similar geographic areas throughout ontogeny. Unexpectedly, we found evidence to suggest females may have larger habitats and wider trophic niche than males. This study revealed the ontogenetic and spatiotemporal plasticity of habitat and feeding strategy of D. gigas.
Directed Energy Deposition of Multi-Principal Element Alloys
Authors: Sreeramagiri Praveen , Balasubramanian Ganesh
Published: April 2022

As efforts associated with the exploration of multi-principal element alloys (MPEAs) using computational and data-intensive methods continue to rise, experimental realization and validation of the predicted material properties require high-throughput and combinatorial synthesis of these alloys. While additive manufacturing (AM) has emerged as the leading pathway to address these challenges and for rapid prototyping through part fabrication, extensive research on developing and understanding the process-structure-property correlations is imminent. In particular, directed energy deposition (DED) based AM of MPEAs holds great promise because of the boundless compositional variations possible for functionally graded component manufacturing as well as surface cladding. We analyze the recent efforts in DED of MPEAs, the microstructural evolution during the laser metal deposition of various transition and refractory elements, and assess the effects of various processing parameters on the material phase and properties. Our efforts suggest that the development of robust predictive approaches for process parameter selection and modifying the synthesis mechanisms are essential to enable DED platforms to repeatedly produce defect free, stable and designer MPEAs.
Polyglycerol/Polydopamine-Coated Nanoparticles for Biomedical Applications
Authors: Sotoma Shingo
Published: April 2022

Nanoparticles play an active role in biomedical science due to their unique properties, which cannot be obtained from bulk materials. Therefore, understanding and controlling the physicochemical properties of nanoparticles are gaining increasing importance for their practical applications. Surface coating is an important technique that controls the physical properties of nanoparticles since the coating is the first part of the nanoparticle that is in contact with the environment. Additionally, the coating creates robust targeting, therapy, imaging, and sensing opportunities. This review first introduced two recently developed outstanding coatings, namely, hyperbranched polyglycerol and polydopamine, and the research achieved by the polyglycerol/polydopamine-coated nanoparticles was then highlighted.
Efficacy and Safety of Pleural Cryobiopsy vs. Forceps Biopsy for Evaluation of Undiagnosed Pleural Effusion: A Systematic Review and Meta-Analysis
Authors: Giri Mohan , Dai Haiyun , Guo Shuliang , Li Yishi , He Lin , Zhuang Rongjuan
Published: April 2022

Background

Pleural cryobiopsy is a novel technique for the diagnosis of pleural pathologies. However, the safety and feasibility of this modality compared to standard forceps for pleural biopsy has not been fully elucidated. This systematic review and meta-analysis aims to establish the efficacy and safety of cryobiopsy for evaluation of undiagnosed pleural effusion.

Methods

For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and Web of science databases up to December 16, 2021 to identify relevant articles. We included randomized controlled trials, cohort studies, retrospectives studies and case series that compared pleural cryobiopsy and forceps biopsy. A qualitative assessment was performed using the QUADAS-2 tool.

Results

Of the 365 articles identified by our search, 15 studies were eligible for inclusion. The specimen sizes obtained with cryobiopsy were significantly larger compared with forceps biopsy (Standard mean difference 1.16; 95 % CI: 0.51–1.82; P < 0.01). Furthermore, the cryobiopsy tissue specimens were deeper (OR 2.68; 95 % CI: 1.39–5.16; P < 0.01) and qualitatively better with less crush artifacts (OR 0.06; 95 % CI: 0.01–0.26; P < 0.01). There was no significant difference in diagnostic yield (OR 1.32; 95 % CI: 0.79–2.21; P = 0.29) and mild to moderate bleeding events (OR 1.21; 95 % CI: 0.64–2.29; P = 0.57) between pleural cryobiopsy and forceps biopsy. No publication bias was observed among these studies.

Conclusions

Compared to flexible forceps biopsy pleural cryobiopsy obtained larger and deeper tissue specimens with less crush artifacts but does not show superiority for diagnostic yield. Further studies are still needed to verify these findings.
Gut Microbiota of Ostrinia nubilalis Larvae Degrade Maize Cellulose
Authors: Li Junfeng , Wang Siran , Zhao Jie , Dong Zhihao , Shao Tao
Published: April 2022

Most arthropod guts harbor diverse microbiota for symbiotic digestion. The European corn borer (ECB), Ostrinia nubilalis (Hübner), is a devastating pest that feeds the lignocellulose-rich tissues of maize plants. However, the potential role of ECB gut microbes in degrading maize cellulose remains largely unexplored. Here, we investigated the gut microbiota of ECB fed with different diets and their potential function in maize lignocellulose degradation. The diversity and composition of gut bacterial communities varied dramatically between the ECB larva fed with artificial diets (ECB-D) and maize plants (ECB-M). Draft genomes of the microbial consortia from ECB-D and ECB-M showed that the principal degraders of cellulose mainly belonged to Firmicutes or Proteobacteria and they were primarily found in the midgut. The cellulolytic microbial consortia contained genes encoding various carbohydrate-active enzymes (CAZyme). Furthermore, scanning electron microscopy revealed significant breakdown of lignocellulose in maize treated by the two microbial consortia for 9 days in vitro. Metabolomic analyses show that maize particles treated by two microbial consortia generate distinctive metabolomic profiles, with enrichment for different monosaccharides (i.e., Glucose, Rhamnofuranose, Isomaltose, and Cellobiose) and amino acids (i.e., Threonine, Histidine, and Lysine). The results indicated that the diet of the host impacted the composition and function of its gut microbiota and ECB exploited specific gut microbes to digest maize lignocellulose with distinctive products. Our study provides valuable microbiota resources for lignocellulose bioconversion.
Effects of Host Plant and Insect Generation on Shaping of the Gut Microbiota in the Rice Leaffolder, Cnaphalocrocis medinalis
Authors: Yang Yajun , Liu Xiaogai , Xu Hongxing , Liu Yinghong , Lu Zhongxian
Published: April 2022

Gut microbes in insects may play an important role in the digestion, immunity and protection, detoxification of toxins, development, and reproduction. The rice leaffolder Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Crambidae) is a notorious insect pest that can damage rice, maize, and other gramineous plants. To determine the effects of host plants and generations on the gut microbiota of C. medinalis, we deciphered the bacterial configuration of this insect pest fed rice or maize for three generations by Illumina MiSeq technology. A total of 16 bacterial phyla, 34 classes, 50 orders, 101 families, 158 genera, and 44 species were identified in C. medinalis fed rice or maize for three generations. Host plants, insect generation, and their interaction did not influence the alpha diversity indices of the gut microbiota of C. medinalis. The dominant bacterial taxa were Proteobacteria and Firmicutes at the phylum level and Enterococcus and unclassified Enterobacteriaceae at the genus level. A number of twenty genera coexisted in the guts of C. medinalis fed rice or maize for three generations, and their relative abundances occupied more than 90% of the gut microbiota of C. medinalis. A number of two genera were stably found in the gut of rice-feeding C. medinalis but unstably found in the gut microbiota of maize-feeding C. medinalis, and seven genera were stably found in the gut of maize-feeding C. medinalis but unstably found in the gut of rice-feeding C. medinalis. In addition, many kinds of microbes were found in some but not all samples of the gut of C. medinalis fed on a particular host plant. PerMANOVA indicated that the gut bacteria of C. medinalis could be significantly affected by the host plant and host plant × generation. We identified 47 taxa as the biomarkers for the gut microbiota of C. medinalis fed different host plants by LEfSe. Functional prediction suggested that the most dominant role of the gut microbiota in C. medinalis is metabolism, followed by environmental information processing, cellular processes, and genetic information processing. Our findings will enrich the understanding of gut bacteria in C. medinalis and reveal the differences in gut microbiota in C. medinalis fed on different host plants for three generations.
Complex Chronic Wound Biofilms Are Inhibited in vitro by the Natural Extract of Capparis spinose
Authors: Di Lodovico Silvia , Bacchetti Tiziana , D’Ercole Simonetta , Covone Sara , Petrini Morena , Di Giulio Mara , Di Fermo Paola , Diban Firas , Ferretti Gianna , Cellini Luigina
Published: April 2022

Resistant wound microorganisms are becoming an extremely serious challenge in the process of treating infected chronic wounds, leading to impaired healing. Thus, additional approaches should be taken into consideration to improve the healing process. The use of natural extracts can represent a valid alternative to treat/control the microbial infections in wounds. This study investigates the antimicrobial/antivirulence effects of Capparis spinose aqueous extract against the main chronic wound pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The extract shows phenolic characterization with rutin (1.8 ± 0.14 μg/mg) as the major compound and antibacterial effect against bacteria (S. aureus PECHA 10 MIC 6.25%; P. aeruginosa PECHA 4 MIC 12.50%) without action against C. albicans (MIC and MFC ≥ 50%). Capparis spinose also shows a significant antivirulence effect in terms of antimotility/antibiofilm actions. In particular, the extract acts (i) on P. aeruginosa both increasing its swimming and swarming motility favoring the planktonic phenotype and reducing its adhesive capability, (ii) on S. aureus and P. aeruginosa biofilm formation reducing both the biomass and CFU/ml. Furthermore, the extract significantly displays the reduction of a dual-species S. aureus and P. aeruginosa Lubbock chronic wound biofilm, a complex model that mimics the realistic in vivo microbial spatial distribution in wounds. The results suggest that C. spinose aqueous extract could represent an innovative eco-friendly strategy to prevent/control the wound microbial infection.
Genomic Characterization of a Uropathogenic Escherichia coli ST405 Isolate Harboring blaCTX-M-15-Encoding IncFIA-FIB Plasmid, blaCTX-M-24-Encoding IncI1 Plasmid, and Phage-Like Plasmid
Authors: Yao Mianzhi , Zhu Qianhui , Zou Jin , Shenkutie Abebe Mekuria , Hu Songnian , Qu Jiuxin , He Zilong , Leung Polly H. M.
Published: April 2022

Escherichia coli sequence type 405 is an emerging antibiotic-resistant clonal group associated with the global dissemination of extended-spectrum β-lactamase-producing E. coli. In this study, we report the genome assembly and characterization of a uropathogenic E. coli ST405 strain, SZESBLEC201, based on long and short reads obtained from the Nanopore and Illumina sequencing platforms, respectively. Whole-genome sequencing revealed that SZESBLEC201 harbors a 5,020,403 bp chromosome and three plasmids, namely, pSZESBLEC201-1, pSZESBLEC201-2, and pSZESBLEC201-3. pSZESBLEC201-1 (111,621 bp) belongs to the IncFIA-FIB type and harbors blaCTX-M-15. However, this plasmid does not harbor conjugative transfer-associated genes, rendering pSZESBLEC201-1 unable to be conjugatively transferred. pSZESBLEC201-2 (95,138 bp) is a phage-like plasmid that shows a strong genome synteny with Escherichia phage P1 but with the absence of mobile genetic elements and some regulatory genes. pSZESBLEC201-3 (92,865 bp) belongs to the IncI1 type and carries blaCTX-M-24. In contrast to pSZESBLEC201-1, pSZESBLEC201-3 retains its full active conjugation machinery and can be transferred via conjugation. The genetic features of the genome show that the SZESBLEC201 has a unique virulence pattern compared with genetically similar strains found in the same country (China). The plasmid backbones exhibit a high degree of similarity to those of geographically distant isolates, highlighting the global spread of blaCTX-M genes and the genome plasticity of this clonal group. The coexistence of two blaCTX-M variants in the same strain increases the risk of the emergence of new blaCTX-M variants. Further studies on phage-like plasmids are necessary to provide insights into their biological activities and clinical significance.
Secretome Analysis of Macrophomina phaseolina Identifies an Array of Putative Virulence Factors Responsible for Charcoal Rot Disease in Plants
Authors: Sinha Nilanjan , Patra Sourav Kumar , Ghosh Sanjay
Published: April 2022

Macrophomina phaseolina is a global devastating necrotrophic fungal pathogen. It causes charcoal rot disease in more than 500 host plants including major food crops, pulse crops, fiber crops, and oil crops. Despite having the whole-genome sequence of M. phaseolina, understanding the M. phaseolina genome-based plant–pathogen interactions is limited in the absence of direct experimental proof of secretion. Thus, it is essential to understand the host–microbe interaction and the disease pathogenesis, which can ensure global agricultural crop production and security. An in silico–predicted secretome of M. phaseolina is unable to represent the actual secretome. We could identify 117 proteins present in the secretome of M. phaseolina using liquid chromatography–electrospray ionization–tandem mass spectrometry. Data are available via ProteomeXchange with identifier PXD032749. An array of putative virulence factors of M. phaseolina were identified in the present study using solid-state culture. Similar virulence factors have been reported in other plant pathogenic fungi also. Among the secretory fungal proteins with positive economic impacts, lignocellulolytic enzymes are of prime importance. Further, we validated our results by detecting the cell wall–degrading enzymes xylanase, endoglucanase, and amylase in the secretome of M. phaseolina. The present study may provide a better understanding about the necrotrophic fungi M. phaseolina, which modulate the host plant defense barriers using secretory proteins.
The Minimal Translation Machinery: What We Can Learn From Naturally and Experimentally Reduced Genomes
Authors: Garzón María José , Reyes-Prieto Mariana , Gil Rosario
Published: April 2022

The current theoretical proposals of minimal genomes have not attempted to outline the essential machinery for proper translation in cells. Here, we present a proposal of a minimal translation machinery based on (1) a comparative analysis of bacterial genomes of insects’ endosymbionts using a machine learning classification algorithm, (2) the empiric genomic information obtained from Mycoplasma mycoides JCVI-syn3.0 the first minimal bacterial genome obtained by design and synthesis, and (3) a detailed functional analysis of the candidate genes based on essentiality according to the DEG database (Escherichia coli and Bacillus subtilis) and the literature. This proposed minimal translational machinery is composed by 142 genes which must be present in any synthetic prokaryotic cell designed for biotechnological purposes, 76.8% of which are shared with JCVI-syn3.0. Eight additional genes were manually included in the proposal for a proper and efficient translation.
A One-Health Approach to Investigating an Outbreak of Alimentary Tick-Borne Encephalitis in a Non-endemic Area in France (Ain, Eastern France): A Longitudinal Serological Study in Livestock, Detection in Ticks, and the First Tick-Borne Encephalitis Virus Isolation and Molecular Characterisation
Authors: Gonzalez Gaëlle , Bournez Laure , Moraes Rayane Amaral , Marine Dumarest , Galon Clémence , Vorimore Fabien , Cochin Maxime , Nougairède Antoine , Hennechart-Collette Catherine , Perelle Sylvie , Leparc-Goffart Isabelle , Durand Guillaume André , Grard Gilda , Bénet Thomas , Danjou Nathalie , Blanchin Martine , Lacour Sandrine A. , Franck Boué , Chenut Guillaume , Mainguet Catherine , Simon Catherine , Brémont Laurence , Zientara Stephan , Moutailler Sara , Martin-Latil Sandra , Dheilly Nolwenn M. , Beck Cécile , Lecollinet Sylvie
Published: April 2022

Tick-borne encephalitis virus’ (TBEV) geographic range and the human incidence are increasing throughout Europe, putting a number of non-endemic regions and countries at risk of outbreaks. In spring 2020, there was an outbreak of tick-born encephalitis (TBE) in Ain, Eastern France, where the virus had never been detected before. All patients but one had consumed traditional unpasteurised raw goat cheese from a local producer. We conducted an investigation in the suspected farm using an integrative One Health approach. Our methodology included (i) the detection of virus in cheese and milk products, (ii) serological testing of all animals in the suspected farm and surrounding farms, (iii) an analysis of the landscape and localisation of wooded area, (iv) the capture of questing ticks and small mammals for virus detection and estimating enzootic hazard, and (v) virus isolation and genome sequencing. This approach allowed us to confirm the alimentary origin of the TBE outbreak and witness in real-time the seroconversion of recently exposed individuals and excretion of virus in goat milk. In addition, we identified a wooded focus area where and around which there is a risk of TBEV exposure. We provide the first TBEV isolate responsible for the first alimentary-transmitted TBE in France, obtained its full-length genome sequence, and found that it belongs to the European subtype of TBEV. TBEV is now a notifiable human disease in France, which should facilitate surveillance of its incidence and distribution throughout France.
Identification of Tumor Mutation Burden, Microsatellite Instability, and Somatic Copy Number Alteration Derived Nine Gene Signatures to Predict Clinical Outcomes in STAD
Authors: Chen Chuanzhi , Chen Yi , Jin Xin , Ding Yongfeng , Jiang Junjie , Wang Haohao , Yang Yan , Lin Wu , Chen Xiangliu , Huang Yingying , Teng Lisong
Published: April 2022

Genomic features, including tumor mutation burden (TMB), microsatellite instability (MSI), and somatic copy number alteration (SCNA), had been demonstrated to be involved with the tumor microenvironment (TME) and outcome of gastric cancer (GC). We obtained profiles of TMB, MSI, and SCNA by processing 405 GC data from The Cancer Genome Atlas (TCGA) and then conducted a comprehensive analysis though “iClusterPlus.” A total of two subgroups were generated, with distinguished prognosis, somatic mutation burden, copy number changes, and immune landscape. We revealed that Cluster1 was marked by a better prognosis, accompanied by higher TMB, MSIsensor score, TMEscore, and lower SCNA burden. Based on these clusters, we screened 196 differentially expressed genes (DEGs), which were subsequently projected into univariate Cox survival analysis. We constructed a 9-gene immune risk score (IRS) model using LASSO-penalized logistic regression. Moreover, the prognostic prediction of IRS was verified by receiver operating characteristic (ROC) curve analysis and nomogram plot. Another independent Gene Expression Omnibus (GEO) contained specimens from 109 GC patients was designed as an external validation. Our works suggested that the 9‐gene‐signature prediction model, which was derived from TMB, MSI, and SCNA, was a promising predictive tool for clinical outcomes in GC patients. This novel methodology may help clinicians uncover the underlying mechanisms and guide future treatment strategies.
Small Heat Shock Proteins in Retinal Diseases
Authors: Rajeswaren Vivian , Wong Jeffrey O. , Yabroudi Dana , Nahomi Rooban B. , Rankenberg Johanna , Nam Mi-Hyun , Nagaraj Ram H.
Published: April 2022

This review summarizes the latest findings on small heat shock proteins (sHsps) in three major retinal diseases: glaucoma, diabetic retinopathy, and age-related macular degeneration. A general description of the structure and major cellular functions of sHsps is provided in the introductory remarks. Their role in specific retinal diseases, highlighting their regulation, role in pathogenesis, and possible use as therapeutics, is discussed.
Network Reconfiguration Among Cerebellar Visual, and Motor Regions Affects Movement Function in Spinocerebellar Ataxia Type 3
Authors: Chen Hui , Dai Limeng , Zhang Yuhan , Feng Liu , Jiang Zhenzhen , Wang Xingang , Xie Dongjing , Guo Jing , Chen Huafu , Wang Jian , Liu Chen
Published: April 2022

Background

Spinocerebellar ataxia type 3 (SCA3) is a rare movement disorder characterized with ataxia. Previous studies on movement disorders show that the whole-brain functional network tends to be more regular, and these reconfigurations correlate with genetic and clinical variables.

Methods

To test whether the brain network in patients with SCA3 follows a similar reconfiguration course to other movement disorders, we recruited 41 patients with SCA3 (mean age = 40.51 ± 12.13 years; 23 male) and 41 age and sex-matched healthy individuals (age = 40.10 ± 11.56 years; 24 male). In both groups, the whole-brain network topology of resting-state functional magnetic resonance imaging (rs-fMRI) was conducted using graph theory, and the relationships among network topologies, cytosine-adenine-guanine (CAG) repeats, clinical symptoms, and functional connectivity were explored in SCA3 patients using partial correlation analysis, controlling for age and sex.

Results

The brain networks tended to be more regular with a higher clustering coefficient, local efficiency, and modularity in patients with SCA3. Hubs in SCA3 patients were reorganized as the number of hubs increased in motor-related areas and decreased in cognitive areas. At the global level, small-worldness and normalized clustering coefficients were significantly positively correlated with clinical motor symptoms. At the nodal level, the clustering coefficient and local efficiency increased significantly in the visual (bilateral cuneus) and sensorimotor (right cerebellar lobules IV, V, VI) networks and decreased in the cognitive areas (right middle frontal gyrus). The clustering coefficient and local efficiency in the bilateral cuneus gyrus were negatively correlated with clinical motor symptoms. The functional connectivity between right caudate nucleus and bilateral calcarine gyrus were negatively correlated with disease duration, while connectivity between right posterior cingulum gyrus and left cerebellar lobule III, left inferior occipital gyrus and right cerebellar lobule IX was positively correlated.

Conclusion

Our results demonstrate that a more regular brain network occurred in SCA3 patients, with motor and visual-related regions, such as, cerebellar lobules and cuneus gyrus, both forayed neighbor nodes as “resource predators” to compensate for normal function, with motor and visual function having the higher priority comparing with other high-order functions. This study provides new information about the neurological mechanisms underlying SCA3 network topology impairments in the resting state, which give a potential guideline for future clinical treatments.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [ChiCTR1800019901].
Cognitive Dysfunction in Repeat Expansion Diseases: A Review
Authors: Zhang Sizhe , Shen Lu , Jiao Bin
Published: April 2022

With the development of the sequencing technique, more than 40 repeat expansion diseases (REDs) have been identified during the past two decades. Moreover, the clinical features of these diseases show some commonality, and the nervous system, especially the cognitive function was affected in part by these diseases. However, the specific cognitive domains impaired in different diseases were inconsistent. Here, we survey literature on the cognitive consequences of the following disorders presenting cognitive dysfunction and summarizing the pathogenic genes, epidemiology, and different domains affected by these diseases. We found that the cognitive domains affected in neuronal intranuclear inclusion disease (NIID) were widespread including the executive function, memory, information processing speed, attention, visuospatial function, and language. Patients with C9ORF72-frontotemporal dementia (FTD) showed impairment in executive function, memory, language, and visuospatial function. While in Huntington's disease (HD), the executive function, memory, and information processing speed were affected, in the fragile X-associated tremor/ataxia syndrome (FXTAS), executive function, memory, information processing speed, and attention were impaired. Moreover, the spinocerebellar ataxias showed broad damage in almost all the cognitive domains except for the relatively intact language ability. Some other diseases with relatively rare clinical data also indicated cognitive dysfunction, such as myotonic dystrophy type 1 (DM1), progressive myoclonus epilepsy (PME), Friedreich ataxia (FRDA), Huntington disease like-2 (HDL2), and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We drew a cognitive function landscape of the related REDs that might provide an aspect for differential diagnosis through cognitive domains and effective non-specific interventions for these diseases.
Reinforcement History Dependent Effects of Low Dose Ethanol on Reward Motivation in Male and Female Mice
Authors: Bryant Kathleen G. , Singh Binay , Barker Jacqueline M.
Published: April 2022

Alcohol use disorders (AUDs) are more prevalent in men than in women, though AUD diagnoses in women are growing rapidly, making an understanding of sex differences in alcohol-related behaviors increasingly important. The development of AUDs involves the transition from casual, low levels of alcohol drinking to higher, maladaptive levels. The ability of low dose alcohol to drive reward and drug seeking may differ in males and females, and this could underlie differences in susceptibility to AUD. In this study we sought to determine whether a history of chronic, low dose ethanol exposure (0.5 g/kg; i.p.) could drive sucrose reward seeking and motivation, and whether this differed between male and female mice. Adult mice were trained to lever press for a liquid sucrose reward on two reinforcement schedules: a random interval (RI) schedule and a variable ratio (VR) schedule. After training, mice were tested on each of these levers for reward motivation using a progressive ratio test. We found that a history of low dose ethanol exposure increased sucrose reward motivation in male mice, but only on the RI lever and only when exposure occurred proximal to learning. Female mice were more motivated for sucrose on the RI lever than the VR lever regardless of ethanol exposure condition. These findings indicate that training on different reinforcement schedules affects reward motivation. Further, we show that males are more susceptible to the effects of low dose ethanol on sucrose reward motivation than females. These data broaden our understanding of sex differences in reward seeking as a result of ethanol exposure.
Transcriptome and Proteome Analysis in LUHMES Cells Overexpressing Alpha-Synuclein
Authors: Höllerhage Matthias , Stepath Markus , Kohl Michael , Pfeiffer Kathy , Chua Oscar Wing ho , Duan Linghan , Hopfner Franziska , Eisenacher Martin , Marcus Katrin , Höglinger Günter U.
Published: April 2022

LUHMES cells share many characteristics with human dopaminergic neurons in the substantia nigra, the cells, the demise of which is responsible for the motor symptoms in Parkinson's disease (PD). LUHMES cells can, therefore, be used bona fide as a model to study pathophysiological processes involved in PD. Previously, we showed that LUHMES cells degenerate after 6 days upon overexpression of wild-type alpha-synuclein. In the present study, we performed a transcriptome and proteome expression analysis in alpha-synuclein-overexpressing cells and GFP-expressing control cells in order to identify genes and proteins that are differentially regulated upon overexpression of alpha-synuclein. The analysis was performed 4 days after the initiation of alpha-synuclein or GFP overexpression, before the cells died, in order to identify processes that preceded cell death. After adjustments for multiple testing, we found 765 genes being differentially regulated (439 upregulated, 326 downregulated) and 122 proteins being differentially expressed (75 upregulated, 47 downregulated). In total, 21 genes and corresponding proteins were significantly differentially regulated in the same direction in both datasets, of these 13 were upregulated and 8 were downregulated. In total, 13 genes and 9 proteins were differentially regulated in our cell model, which had been previously associated with PD in recent genome-wide association studies (GWAS). In the gene ontology (GO) analysis of all upregulated genes, the top terms were “regulation of cell death,” “positive regulation of programmed cell death,” and “regulation of apoptotic signaling pathway,” showing a regulation of cell death-associated genes and proteins already 2 days before the cells started to die. In the GO analysis of the regulated proteins, among the strongest enriched GO terms were “vesicle,” “synapse,” and “lysosome.” In total, 33 differentially regulated proteins were associated with synapses, and 12 differentially regulated proteins were associated with the “lysosome”, suggesting that these intracellular mechanisms, which had been previously associated with PD, also play an important role in our cell model.
The Effect of Inclines on Joint Angles in Stroke Survivors During Treadmill Walking
Authors: Zhang Xin , Lu Yanting , Chien Jung Hung , Fu Chenlei , Zhou Zhe , Li Hua , Hu Gongwei , Sun Tianbao
Published: April 2022

Stroke severely affects the quality of life, specifically in walking independently. Thus, it is crucial to understand the impaired gait pattern. This gait pattern has been widely investigated when walking on a level treadmill. However, knowledge about the gait pattern when walking on inclines is scarce. Therefore, this study attempted to fulfill this knowledge gap. In this study, 15 stroke survivors and 15 age/height/weight healthy controls were recruited. The participants were instructed to walk on three different inclines: 0°, 3°, and 6°. The participants were required to walk on each incline for 2 min and needed to complete each incline two times. The dependent variables were the peak values for ankle/knee/hip joint angles and the respective variability of these peak values. The results showed that an increment of the incline significantly increased the peak of the hip flexion and the peak of the knee flexion but did not affect the peak values of the ankle joints in the paretic leg in these stroke survivors. In comparison with the healthy controls, lower hip extension, lower hip flexion, lower knee flexion, and lower ankle plantar flexion were observed in stroke survivors. A clinical application of this work might assist the physical therapists in building an effective treadmill training protocol.
Intellectual Structure and Emerging Trends of White Matter Hyperintensity Studies: A Bibliometric Analysis From 2012 to 2021
Authors: Shi Yanan , Zhao Zehua , Tang Huan , Huang Shijing
Published: April 2022

White matter hyperintensities (WMHs), which have a significant effect on human health, have received increasing attention since their number of publications has increased in the past 10 years. We aimed to explore the intellectual structure, hotspots, and emerging trends of publications on WMHs using bibliometric analysis from 2012 to 2021. Publications on WMHs from 2012 to 2021 were retrieved from the Web of Science Core Collection. CiteSpace 5.8.R3, VOSviewer 1.6.17, and an online bibliometric analysis platform (Bibliometric. com) were used to quantitatively analyze the trends of publications from multiple perspectives. A total of 29,707 publications on WMHs were obtained, and the number of annual publications generally increased from 2012 to 2021. Neurology had the most publications on WMHs. The top country and institution were the United States and Harvard University, respectively. Massimo Filippi and Stephen M. Smith were the most productive and co-cited authors, respectively. Thematic concentrations primarily included cerebral small vessel disease, diffusion magnetic resonance imaging (dMRI), schizophrenia, Alzheimer’s disease, multiple sclerosis, microglia, and oligodendrocyte. The hotspots were clustered into five groups: white matter and diffusion tensor imaging, inflammation and demyelination, small vessel disease and cognitive impairment, MRI and multiple sclerosis, and Alzheimer’s disease. Emerging trends mainly include deep learning, machine learning, perivascular space, convolutional neural network, neurovascular unit, and neurite orientation dispersion and density imaging. This study presents an overview of publications on WMHs and provides insights into the intellectual structure of WMH studies. Our study provides information to help researchers and clinicians quickly and comprehensively understand the hotspots and emerging trends within WMH studies as well as providing direction for future basic and clinical studies on WMHs.
Engineered Biofilm: Innovative Nextgen Strategy for Quality Enhancement of Fermented Foods
Authors: Ghosh Sreejita , Nag Moupriya , Lahiri Dibyajit , Sarkar Tanmay , Pati Siddhartha , Kari Zulhisyam Abdul , Nirmal Nilesh P. , Edinur Hisham Atan , Ray Rina Rani
Published: April 2022

Microbial communities within fermented food (beers, wines, distillates, meats, fishes, cheeses, breads) products remain within biofilm and are embedded in a complex extracellular polymeric matrix that provides favorable growth conditions to the indwelling species. Biofilm acts as the best ecological niche for the residing microbes by providing food ingredients that interact with the fermenting microorganisms' metabolites to boost their growth. This leads to the alterations in the biochemical and nutritional quality of the fermented food ingredients compared to the initial ingredients in terms of antioxidants, peptides, organoleptic and probiotic properties, and antimicrobial activity. Microbes within the biofilm have altered genetic expression that may lead to novel biochemical pathways influencing their chemical and organoleptic properties related to consumer acceptability. Although microbial biofilms have always been linked to pathogenicity owing to its enhanced antimicrobial resistance, biofilm could be favorable for the production of amino acids like l-proline and L-threonine by engineered bacteria. The unique characteristics of many traditional fermented foods are attributed by the biofilm formed by lactic acid bacteria and yeast and often, multispecies biofilm can be successfully used for repeated-batch fermentation. The present review will shed light on current research related to the role of biofilm in the fermentation process with special reference to the recent applications of NGS/WGS/omics for the improved biofilm forming ability of the genetically engineered and biotechnologically modified microorganisms to bring about the amelioration of the quality of fermented food.
Nutritional Diversity in Native Germplasm of Maize Collected From Three Different Fragile Ecosystems of India
Authors: Langyan Sapna , Bhardwaj Rakesh , Kumari Jyoti , Jacob Sherry Rachel , Bisht Ishwari Singh , Pandravada Someswara Rao , Singh Archna , Singh Pratap Bhan , Dar Zahoor Ahmed , Kumar Ashok , Rana Jai Chand
Published: April 2022

Native germplasm resources are adapted to specific ecological niches. They have sustained over generations owing to the preference of local communities for their unique taste, the utility to particular dishes, and the low cost of cultivation. They may help eradicate malnutrition and act as a source for trait-linked genes. The present dataset comprises thirty-three native germplasm of maize collected from Rajasthan, Himachal Pradesh, and Andhra Pradesh states of India with an altitudinal variation of 386–2,028 m. They were evaluated for proximate composition, minerals, nutritional attributes, and antioxidant activity and compared with the standard values reported in the Indian Food Composition Table 2017 (IFCT2017). The nutritional profile showed moisture content in the range of 7.16–10.9%, ash 0.73–1.93%, crude protein 8.68–12.0%, crude fat 3.72–8.03%, dietary fiber 5.21–11.2%, and available carbohydrates 60.6–69.8%. Three accessions, namely, Malan 11 (7.06%), Malan 24 (7.20%), and Yellow Chamba Local 02 (8.03%) exhibited almost double the crude fat content as compared with the values notified in IFCT2017 (3.77). Total sugar content obtained was in the range of 5.00–11.3%, whereas the starch content was found between 50.9 and 64.9%. All the germplasm except Yellow Chamba Local reflected a higher protein content than reported values in IFCT2017 (8.80). Sathi, Safed Chamba Local, and Ragal Makka had nearly 12% protein content. Mineral malnutrition, mainly due to iron (Fe) deficiency, is a worldwide issue to science, humanity, and society. The mineral profile revealed that most germplasm had a higher iron content. Accessions with the iron content of nearly three times of IFCT2017 reported value were identified in germplasm belonging to three states. A negative relationship was observed between the altitude of the sample collection site and available carbohydrate content. In contrast, available carbohydrate showed inverse correlations with dietary fiber, protein, and fat content. The information generated in this study can be utilized to promote these germplasm as nutrifood, nutritional surveillance, labeling, and crop improvement programs.
The Correlation of Prediabetes and Type 2 Diabetes With Adiposity in Adults
Authors: Sun Juan , Liu Zhen , Zhang Zimu , Zeng Ziyang , Kang Weiming
Published: April 2022

Background

Fat metabolism is associated with prediabetes and type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the detailed correlation of diabetes status with adiposity among adults.

Methods

Briefly, 28,429 adults aged ≥18 years from both sexes in the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were included in this study. Multivariable linear regression models were used to examine associations of prediabetes and diabetes status, disease duration of T2DM, serum glucose, glycohemoglobin (HbA1c) with total percent fat (TPF), and fat mass distribution.

Results

After adjusting for sociodemographic covariates, health behaviors, hypertension, hypercholesterolemia, there were direct associations of prediabetes and T2DM status with TPF, trunk fat mass, android fat mass, gynoid fat mass and android to gynoid ratio compared with non-diabetes. But the fat mass decreased with the increase of the disease duration in patients with T2DM. Besides, when stratifying by diabetes status, we found direct associations of serum glucose and HbA1c with TPF, trunk fat mass, android fat mass, gynoid fat mass, and android to gynoid ratio in non-diabetic and prediabetic participants. But in patients with T2DM, inverse associations of serum glucose and HbA1c with fat mass were observed.

Conclusions

This study indicated that adults with prediabetes and T2DM had significantly higher TPF, trunk fat mass, android fat mass, gynoid fat mass, and android to gynoid ratio compared with those without diabetes. Moreover, fat mass decreased as the disease duration increased in patients with T2DM. The associations of serum glucose and HbA1c with TPF and fat mass distribution in patients with T2DM were opposite to the relationships observed in non-diabetic and prediabetic participants.