bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted escape of SARS-CoV-2 in vitro from monoclonal antibody S309, the precursor of sotrovimab
Authors: Magnus Clara Luzia , Hiergeist Andreas , Schuster Philipp , Rohrhofer Anette , Medenbach Jan , Gessner André , Peterhoff David , Schmidt Barbara
Published: August 2022

Class 1 and 2 monoclonal antibodies inhibit SARS-CoV-2 entry by blocking the interaction of the viral receptor-binding domain with angiotensin-converting enzyme 2 (ACE2), while class 3 antibodies target a highly conserved epitope outside the ACE2 binding site. We aimed to investigate the plasticity of the spike protein by propagating wild-type SARS-CoV-2 in the presence of class 3 antibody S309. After 12 weeks, we obtained a viral strain that was completely resistant to inhibition by S309, due to successively evolving amino acid exchanges R346S and P337L located in the paratope of S309. The antibody lost affinity to receptor-binding domains carrying P337L or both amino acid exchanges, while ACE2 binding was not affected. The resistant strain replicated efficiently in human CaCo-2 cells and was more susceptible to inhibition of fusion than the original strain. Overall, SARS-CoV-2 escaped inhibition by class 3 antibody S309 through a slow, but targeted evolution enabling immune escape and altering cell entry. This immune-driven enhancement of infectivity and pathogenicity could play an important role in the future evolution of SARS-CoV-2, which is under increasing immunological pressure from vaccination and previous infections.
Inactivated tick-borne encephalitis vaccine elicits several overlapping waves of T cell response
Authors: Sycheva Anastasiia L. , Komech Ekaterina A. , Pogorelyy Mikhail V. , Minervina Anastasia A. , Urazbakhtin Shamil Z. , Salnikova Maria A. , Vorovitch Mikhail F. , Kopantzev Eugene P. , Zvyagin Ivan V. , Komkov Alexander Y. , Mamedov Ilgar Z. , Lebedev Yuri B.
Published: August 2022

The development and implementation of vaccines have been growing exponentially, remaining one of the major successes of healthcare over the last century. Nowadays, active regular immunizations prevent epidemics of many viral diseases, including tick-borne encephalitis (TBE). Along with the generation of virus-specific antibodies, a highly effective vaccine should induce T cell responses providing long-term immune defense. In this study, we performed longitudinal high-throughput T cell receptor (TCR) sequencing to characterize changes in individual T cell repertoires of 11 donors immunized with an inactivated TBE vaccine. After two-step immunization, we found significant clonal expansion of both CD4+ and CD8+ T cells, ranging from 302 to 1706 vaccine-associated TCRβ clonotypes in different donors. We detected several waves of T cell clonal expansion generated by distinct groups of vaccine-responding clones. Both CD4+ and CD8+ vaccine-responding T cell clones formed 17 motifs in TCRβ sequences shared by donors with identical HLA alleles. Our results indicate that TBE vaccination leads to a robust T cell response due to the production of a variety of T cell clones with a memory phenotype, which recognize a large set of epitopes.
Variable frequencies of peripheral T-lymphocyte subsets in the diabetes spectrum from type 1 diabetes through latent autoimmune diabetes in adults (LADA) to type 2 diabetes
Authors: Tan Tingting , Xiang Yufei , Deng Chao , Cao Chuqing , Ren Zhihui , Huang Gan , Zhou Zhiguang
Published: August 2022

T lymphocytes are key players in the pathogenesis of autoimmune diabetes. We recruited subjects with T1D (n=81), LADA (n=82), T2D (n=95) and NGT (n=218) and analyzed the percentages of T-lymphocyte subsets, including T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), T cytotoxic 1 (Tc1), regulatory T cells (Tregs), effector T (Teff), naïve T, central memory T (Tcm), and effector memory T (Tem) cells by flow cytometry. LADA patients possessed similar frequencies of IFN-γ+CD4+ T (Th1), IFN-γ+CD8+ T and CD4+ Teff cells compared with T1D patients, but much lower than those of NGT subjects. Like T2D patients, LADA patients had increased frequencies of CD4+ Tem and CD8+ Tem cells with respect to T1D and NGT subjects. In LADA patients, Th2 cells were decreased while CD4+ Tcm cells were increased compared with NGT subjects. Notably, we observed significant negative correlations between the CD4+ Tcm cell frequency and C-peptide in LADA subjects. These data demonstrates that LADA patients possess T-cell subset changes resembling both T1D and T2D and represent the middle of the diabetes spectrum between T1D and T2D. Based on these T-cell subset alterations, we speculate that autoimmunity-induced β-cell destruction and inflammation-induced insulin resistance might both be involved in the pathogenesis of LADA.
Global scientific trends on the immunomodulation of mesenchymal stem cells in the 21st century: A bibliometric and visualized analysis
Authors: Wang Zhongqing , Sun Yuqiang , Shen Rou , Tang Xia , Xu Yingxin , Zhang Ye , Liu Yao
Published: August 2022

Background

Since the discovery of the immunomodulatory functions of mesenchymal stem cells (MSCs), their application in immunomodulation has attracted considerable attention, and an increasing number of studies have been conducted worldwide. Our research aimed to investigate the global status and trends in this field.

Methods

Publications on the immunomodulatory functions of MSCs from 1 January 2000 to 7 March 2022 were retrieved from the Web of Science Core Collection. The data were studied and indexed using the bibliometric methodology. Visualization analysis, co-authorship, co-occurrence analysis, and publication trends in MSC immunomodulation were conducted using the VOSviewer software.

Results

In total, 4,227 papers were included in the study. The number of publications and research interests has significantly increased globally. China published the highest number of related articles, while the US published articles with the highest number of citations. Stem Cell Research & Therapy had the highest number of publications. Sun Yat-sen University, Shanghai Jiao Tong University, Harvard University, and Seoul National University were the most contributive institutions. Furthermore, the studies were divided into four research hotspots for MSC immunomodulation: MSC immunomodulation in regenerative medicine, the effects and mechanisms of MSC immunomodulation, MSC therapy for immune diseases, and the cell source of MSCs.

Conclusion

This study indicates that the number of publications on MSC immunomodulation will increase in the future, and MSC immunomodulation mechanisms and clinical applications of MSC immunotherapy should be the next hotspots in this research field.
Adipose tissue macrophages in remote modulation of hepatic glucose production
Authors: Tao Yan , Jiang Quanhong , Wang Qun
Published: August 2022

Hepatic glucose production (HGP) is fine-regulated via glycogenolysis or gluconeogenesis to maintain physiological concentration of blood glucose during fasting-feeding cycle. Aberrant HGP leads to hyperglycemia in obesity-associated diabetes. Adipose tissue cooperates with the liver to regulate glycolipid metabolism. During these processes, adipose tissue macrophages (ATMs) change their profiles with various physio-pathological settings, producing diverse effects on HGP. Here, we briefly review the distinct phenotypes of ATMs under different nutrition states including feeding, fasting or overnutrition, and detail their effects on HGP. We discuss several pathways by which ATMs regulate hepatic gluconeogenesis or glycogenolysis, leading to favorable or unfavorable metabolic consequences. Furthermore, we summarize emerging therapeutic targets to correct metabolic disorders in morbid obesity or diabetes based on ATM-HGP axis. This review puts forward the importance and flexibility of ATMs in regulating HGP, proposing ATM-based HGP modulation as a potential therapeutic approach for obesity-associated metabolic dysfunction.
Coastal aquaculture farms for the sea cucumber Apostichopus japonicus provide spawning and first-year nursery grounds for wild black rockfish, Sebastes schlegelii: A case study from the Luanhe River estuary, Bohai bay, the Bohai Sea, China
Authors: Xu Min , Qi Zun-li , Liu Zun-lei , Quan Wei-min , Zhao Qi , Zhang Yun-ling , Liu Hui , Yang Lin-lin
Published: August 2022

Aquaculture farms are known to attract wild organisms from nearby areas. Sea cucumber Apostichopus japonicus aquaculture farms in Bohai Bay, the Bohai Sea, China, might provide spawning and nursery grounds for wild black rockfish Sebastes schlegelii populations. To identify the above, we studied the variation in the numbers of S. schlegelii larvae (and length-categories as a percentage of the natural population) via ichthyoplankton surveys by months from January to October 2020, and assessed the food web structure and energy flow distribution of the farm and trophic links of S. schlegelii natural stock by using Ecopath modeling in July 2016 to August 2017. Larvae with a length between 3.90-5.80 mm were observed in the farm in May 2020, the juveniles with an estimated trophic level of 4.31. Juveniles used the farms as first-year nursery ground, and then they swam into deeper waters in August of the following year. MTI analysis showed increasing biomass of S. schlegelii might result in a decrease in the biomass of crustacea, and had positive and negative impacts on mollusk and Hexagrammos otakii biomass. We argued that aquacultural infrastructures constructed by artificial reefs could be used as a fisheries management tool to enhance S. schlegelii stocks and that monitoring of other marine organisms, such as oysters, Rapana venosa, Charybdis japonica, and Asterias spp. etc., was necessary to maintain sustainable exploitations of aquacultural farm ecosystems. A paucity of knowledge surrounding the interactions between aquaculture farms and wild organisms needs furthermore researches.
Compound Raman microscopy for rapid diagnosis and antimicrobial susceptibility testing of pathogenic bacteria in urine
Authors: Zhang Weifeng , Sun Hongyi , He Shipei , Chen Xun , Yao Lin , Zhou Liqun , Wang Yi , Wang Pu , Hong Weili
Published: August 2022

Rapid identification and antimicrobial susceptibility testing (AST) of bacteria are key interventions to curb the spread and emergence of antimicrobial resistance. The current gold standard identification and AST methods provide comprehensive diagnostic information but often take 3 to 5 days. Here, a compound Raman microscopy (CRM), which integrates Raman spectroscopy and stimulated Raman scattering microscopy in one system, is presented and demonstrated for rapid identification and AST of pathogens in urine. We generated an extensive bacterial Raman spectral dataset and applied deep learning to identify common clinical bacterial pathogens. In addition, we employed stimulated Raman scattering microscopy to quantify bacterial metabolic activity to determine their antimicrobial susceptibility. For proof-of-concept, we demonstrated an integrated assay to diagnose urinary tract infection pathogens, S. aureus and E. coli. Notably, the CRM system has the unique ability to provide Gram-staining classification and AST results within ~3 h directly from urine samples and shows great potential for clinical applications.
Different feeding strategies can affect growth performance and rumen functions in Gangba sheep as revealed by integrated transcriptome and microbiome analyses
Authors: Jize Zhang , Zhuoga Deqing , Xiaoqing Zhang , Na Ta , Jiacuo Gesang , Cuicheng Luosang , Bandan Pingcuo
Published: August 2022

Due to the harsh environment in the Tibetan Plateau, traditional grazing greatly limits the growth potential of local animals and causes severe ecosystem degradation. This is an urgent issue to be solved, which requires alternative strategies for grazing animals in the Tibetan alpine pastoral livestock systems. This study aimed to investigate the effects of different feeding strategies on growth performance and ruminal microbiota-host interactions in the local breed of sheep (Gangba sheep). Thirty 9-month old Gangba sheep (n = 10 per group) were assigned to natural grazing (G), semi-grazing with supplementation (T), and barn feeding (F) groups (supplementation of concentrate and oat hay) based on body weight. At the end of the experiment (75 d), all sheep were weighed, rumen fluid was obtained from six sheep per group, and ruminal epithelium was obtained from 3 sheep per group. The results showed that: (1) Compared with the G and T groups, the F group significantly increased dry matter intake, average daily gain, and feed conversion ratio of animals. Additionally, Gangba sheep in the F group had higher concentrations of ruminal short-chain volatile fatty acids (VFAs), especially propionate and butyrate (P <0.05) than sheep in the G and T groups. (2) The principal coordinates analysis indicated a significant difference in bacterial composition among different feed strategies. More specifically, the relative abundance of propionate (unidentified F082 and Succiniclasticum) and butyrate-producing (Eubacterium_coprostanoligenes_group) genera were also observed to be increased in the F group, in which unidentified F082 was identified as a differential biomarker among the three groups according to linear discriminant analysis effect size analysis. (3) The dynamics of the rumen epithelial transcriptome revealed that ECM-receptor interactions, focal adhesion, and PI3K-Akt signaling pathways, which are critical in mediating many aspects of cellular functions such as cell proliferation and motility, were upregulated in the F group. In conclusion, under harsh conditions in the Tibetan alpine meadow, barn feeding increased ruminal VFAs concentrations (especially propionate and butyrate), which stimulated gene expression related to cell proliferation in rumen epithelium, appearing to be superior to natural grazing and semi-grazing in gaining body weight of the local Gangba sheep.
Characterization and genomic analysis of two novel psychrotolerant Acidithiobacillus ferrooxidans strains from polar and subpolar environments
Authors: Muñoz-Villagrán Claudia , Grossolli-Gálvez Jonnathan , Acevedo-Arbunic Javiera , Valenzuela Ximena , Ferrer Alonso , Díez Beatriz , Levicán Gloria
Published: August 2022

The bioleaching process is carried out by aerobic acidophilic iron-oxidizing bacteria that are mainly mesophilic or moderately thermophilic. However, many mining sites are located in areas where the mean temperature is lower than the optimal growth temperature of these microorganisms. In this work, we report the obtaining and characterization of two psychrotolerant bioleaching bacterial strains from low-temperature sites that included an abandoned mine site in Chilean Patagonia (PG05) and an acid rock drainage in Marian Cove, King George Island in Antarctic (MC2.2). The PG05 and MC2.2 strains showed significant iron-oxidation activity and grew optimally at 20°C. Genome sequence analyses showed chromosomes of 2.76 and 2.84 Mbp for PG05 and MC2.2, respectively, and an average nucleotide identity estimation indicated that both strains clustered with the acidophilic iron-oxidizing bacterium Acidithiobacillus ferrooxidans. The Patagonian PG05 strain had a high content of genes coding for tolerance to metals such as lead, zinc, and copper. Concordantly, electron microscopy revealed the intracellular presence of polyphosphate-like granules, likely involved in tolerance to metals and other stress conditions. The Antarctic MC2.2 strain showed a high dosage of genes for mercury resistance and low temperature adaptation. This report of cold-adapted cultures of the At. ferrooxidans species opens novel perspectives to satisfy the current challenges of the metal bioleaching industry.
Crop-type-driven changes in polyphenols regulate soil nutrient availability and soil microbiota
Authors: Fan Dongmei , Zhao Zhumeng , Wang Yu , Ma Junhui , Wang Xiaochang
Published: August 2022

Crop rotation is a typical agronomic practice to mitigate soil deterioration caused by continuous cropping. However, the mechanisms of soil biotic and abiotic factors in response to different cropping patterns in acidic and polyphenol-rich tea nurseries remain unclear. In this study, the composition and function of microbial communities were comparatively investigated in soils of tea seedlings continuously planted for 2 years (AC: autumn-cutting; SC: summer-cutting) and in soils rotation with strawberries alternately for 3 years (AR: autumn-cutting). The results showed that AR significantly improved the survival of tea seedlings but greatly reduced the contents of soil polyphenols. The lower soil polyphenol levels in AR were associated with the decline of nutrients (SOC, TN, Olsen-P) availability, which stimulates the proliferation of nutrient cycling-related bacteria and mixed-trophic fungi, endophytic fungi and ectomycorrhizal fungi, thus further satisfying the nutrient requirements of tea seedlings. Moreover, lower levels of polyphenols facilitated the growth of plant beneficial microorganisms (Bacillus, Mortierella, etc.) and suppressed pathogenic fungi (Pseudopestalotiopsis, etc.), creating a more balanced microbial community that is beneficial to plant health. Our study broadens the understanding of the ecological role of plant secondary metabolites and provides new insights into the sustainability of tea breeding.
Effects of frequency and amount of stover mulching on soil nitrogen and the microbial functional guilds of the endosphere and rhizosphere
Authors: Song Wenchen , Wang Jing , Hou Lei
Published: August 2022

Stover mulching as a conservation and sustainable agricultural practice is beneficial for maintaining soil nitrogen (N) requirements and plant health. The microbial functional guilds of the root and rhizosphere are important factors in the soil nitrogen cycle. However, it is unclear how the frequency and amount of stover mulching influence microbial functional guilds in the root and rhizosphere. Therefore, we investigated the responses of the microbial functional guilds in the endosphere and rhizosphere to maize stover mulching amounts (0, 1/3, 2/3, and total stover mulching every year) and frequencies (once every 3 years and twice every 3 years) under 10-year no-till management. The bacterial functional guilds of nitrogen fixation, nitrification, and anaerobic nitrate oxidation displayed the significantly correlation with C/N, total nitrogen, NO3−, and NH4+. The fungal functional guilds of plant pathogens and saprotrophs showed significantly correlations with C/N, total nitrogen, and NO3−. Moreover, we found that bacterial guilds play a pivotal role in maintaining N requirements at the jointing stage, whereas root endophytic fungal guilds play a more important role than bacterial guilds in regulating plant health at the mature stage. The frequency and amount of stover mulching had significant effects on the microbial functional guilds in the root and rhizosphere. Our data suggest that stover mulch application twice every 3 years is the optimal mulching frequency because it yielded the lowest abundance of nitrifying and anaerobic nitrate-oxidising bacteria and the highest abundance of nitrogen-fixing bacteria at the jointing stage, as well as the lowest abundance of fungal plant pathogens in roots at the mature stage.
Genomic characteristics of clinical multidrug-resistant Proteus isolates from a tertiary care hospital in southwest China
Authors: Li Ying , Liu Qian , Qiu Yichuan , Fang Chengju , Zhou Yungang , She Junping , Chen Huan , Dai Xiaoyi , Zhang Luhua
Published: August 2022

Multidrug-resistant (MDR) Proteus, especially those strains producing extended-spectrum β-lactamases (ESBL) and carbapenemases, represents a major public health concern. In the present work, we characterized 27 MDR Proteus clinical isolates, including 23 Proteus mirabilis, three Proteus terrae, and one Proteus faecis, by whole-genome analysis. Among the 27 isolates analyzed, SXT/R391 ICEs were detected in 14 strains, and the complete sequences of nine ICEs were obtained. These ICEs share a common backbone structure but also have different gene contents in hotspots and variable regions. Among them, ICEPmiChn2826, ICEPmiChn2833, ICEPmiChn3105, and ICEPmiChn3725 contain abundant antibiotic resistance genes, including the ESBL gene blaCTX-M-65. The core gene phylogenetic analysis of ICEs showed their genetic diversity, and revealed the cryptic dissemination of them in Proteus strains from food animals and humans on a China-wide scale. One of the isolates, FZP3105, acquired an NDM-1-producing MDR plasmid, designated pNDM_FZP3105, which is a self-transmissible type 1/2 hybrid IncC plasmid. Analysis of the genetic organization showed that pNDM_FZP3105 has two novel antibiotic resistance islands bearing abundant antibiotic resistance genes, among which blaNDM-1 is located in a 9.0 kb ΔTn125 bracketed by two copies of IS26 in the same direction. In isolates FZP2936 and FZP3115, blaKPC-2 was detected on an IncN plasmid, which is identical to the previously reported pT211 in Zhejiang province of China. Besides, a MDR genomic island PmGRI1, a variant of PmGRI1-YN9 from chicken in China, was identified on their chromosome. In conclusion, this study demonstrates abundant genetic diversity of mobile genetic elements carrying antibiotic resistance genes, especially ESBL and carbapenemase genes, in clinical Proteus isolates, and highlights that the continuous monitoring on their transmission and further evolution is needed.
Pseudomonas aeruginosa inhibits quorum-sensing mechanisms of soft rot pathogen Lelliottia amnigena RCE to regulate its virulence factors and biofilm formation
Authors: Kapadia Chintan , Kachhdia Rinkal , Singh Susheel , Gandhi Kelvin , Poczai Peter , Alfarraj Saleh , Ansari Mohammad Javed , Gafur Abdul , Sayyed R. Z.
Published: August 2022

The quorum-sensing (QS) cascade is responsible for the colonization and phenotypic behavior of the pathogenic organism and the regulation of diverse signal molecules. The disruption of the quorum-sensing system is an effective strategy to overcome the possibility of antibiotic resistance development in the pathogen. The quorum quenching does not kill the microbes. Instead, it hinders the expression of pathogenic traits. In the present experiment, Pseudomonas aeruginosa RKC1 was used to extract the metabolites responsible for quorum-sensing inhibition in soft rot pathogen Lelliottia amnigena RCE. During the initial screening, P. aeruginosa RKC1 was found to be most promising and inhibits violacein of Chromobacterium violaceum MTCC2656 pyocyanin, swarming-swimming motility of P. aeruginosa MTCC2297. The characterization of metabolites produced by the microbes which are responsible for quorum-sensing inhibition through GC-MS is very scarce in scientific literature. The ethyl acetate extract of P. aeruginosa RKC1 inhibits biofilm formation of L. amnigena RCE while inhibiting growth at higher concentrations. The GC-MS analysis suggested that Cyclic dipeptides (CDPs) such as Cyclo (L-prolyl-L-valine), Cyclo (Pro-Leu), and Cyclo(D-phenylalanyl-L-prolyl) were predominantly found in the ethyl acetate extract of the P. aeruginosa RKC1 (93.72%). This diketopiperazine (DKPs) exhibited quorum-sensing inhibition against the pathogen in liquid media during the active growth phase and regulated diverse metabolites of the pathogen. Moreover, the metabolites data from the clear zone around wells showed a higher concentration of DKSs (9.66%) compared to other metabolites. So far, very few reports indicate the role of DKPs or CDPs in inhibiting the quorum-sensing system in plant pathogenic bacteria. This is one such report that exploits metabolites of P. aeruginosa RKC1. The present investigation provided evidence to use quorum-sensing inhibitor metabolites, to suppress microbes' pathogenesis and thus develop an innovative strategy to overcome antibiotic resistance.
The protein kinase CK1: Inhibition, activation, and possible allosteric modulation
Authors: Sunkari Yashoda Krishna , Meijer Laurent , Flajolet Marc
Published: August 2022

Protein kinases play a vital role in biology and deregulation of kinases is implicated in numerous diseases ranging from cancer to neurodegenerative diseases, making them a major target class for the pharmaceutical industry. However, the high degree of conservation that exists between ATP-binding sites among kinases makes it difficult for current inhibitors to be highly specific. In the context of neurodegeneration, several groups including ours, have linked different kinases such as CK1 and Alzheimer’s disease for example. Strictly CK1-isoform specific regulators do not exist and known CK1 inhibitors are inhibiting the enzymatic activity, targeting the ATP-binding site. Here we review compounds known to target CK1, as well as other inhibitory types that could benefit CK1. We introduce the DNA-encoded library (DEL) technology that might represent an interesting approach to uncover allosteric modulators instead of ATP competitors. Such a strategy, taking into account known allosteric inhibitors and mechanisms, might help designing modulators that are more specific towards a specific kinase, and in the case of CK1, toward specific isoforms.
Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy
Authors: Liang Xiaolin , Zhang Simeng , Zhang Difei , Hu Liang , Zhang La , Peng Yu , Xu Yuan , Hou Haijing , Zou Chuan , Liu Xusheng , Chen Yang , Lu Fuhua
Published: August 2022

Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN.

Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman’s analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively.

Results:Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by Bacteroides was closely related to the IgAN patients. Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. Spearman’s correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients.

Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.
Mechanisms of ferroptosis in chronic kidney disease
Authors: Zhuo Wen-Qing , Wen Yi , Luo Hui-Jun , Luo Zhu-Lin , Wang Li
Published: August 2022

Ferroptosis is a newly identified form of regulated cell death characterized by iron accumulation and lipid peroxidation. Ferroptosis plays an essential role in the pathology of numerous diseases and has emerged as a key area of focus in studies of chronic kidney disease (CKD). CKD is a major public health problem with high incidence and mortality that is characterized by a gradual loss of kidney function over time. The severity and complexity of CKD combined with the limited knowledge of its underlying molecular mechanism(s) have led to increased interest in this disease area. Here, we summarize recent advances in our understanding of the regulatory mechanism(s) of ferroptosis and highlight recent studies describing its role in the pathogenesis and progression of CKD. We further discuss the potential therapeutic benefits of targeting ferroptosis for the treatment of CKD and the major hurdles to overcome for the translation of in vitro studies into the clinic.
Exploring the role of non-coding RNAs as potential candidate biomarkers in the cross-talk between diabetes mellitus and Alzheimer’s disease
Authors: Ghiam Shokoofeh , Eslahchi Changiz , Shahpasand Koorosh , Habibi-Rezaei Mehran , Gharaghani Sajjad
Published: August 2022

Background

Recent research has investigated the connection between Diabetes Mellitus (DM) and Alzheimer’s Disease (AD). Insulin resistance plays a crucial role in this interaction. Studies have focused on dysregulated proteins to disrupt this connection. Non-coding RNAs (ncRNAs), on the other hand, play an important role in the development of many diseases. They encode the majority of the human genome and regulate gene expression through a variety of mechanisms. Consequently, identifying significant ncRNAs and utilizing them as biomarkers could facilitate the early detection of this cross-talk. On the other hand, computational-based methods may help to understand the possible relationships between different molecules and conduct future wet laboratory experiments.

Materials and methods

In this study, we retrieved Genome-Wide Association Study (GWAS, 2008) results from the United Kingdom Biobank database using the keywords “Alzheimer’s” and “Diabetes Mellitus.” After excluding low confidence variants, statistical analysis was performed, and adjusted p-values were determined. Using the Linkage Disequilibrium method, 127 significant shared Single Nucleotide Polymorphism (SNP) were chosen and the SNP-SNP interaction network was built. From this network, dense subgraphs were extracted as signatures. By mapping each signature to the reference genome, genes associated with the selected SNPs were retrieved. Then, protein-microRNA (miRNA) and miRNA-long non-coding RNA (lncRNA) bipartite networks were built and significant ncRNAs were extracted. After the validation process, by applying the scoring function, the final protein-miRNA-lncRNA tripartite network was constructed, and significant miRNAs and lncRNAs were identified.

Results

Hsa-miR-199a-5p, hsa-miR-199b-5p, hsa-miR-423-5p, and hsa-miR-3184-5p, the four most significant miRNAs, as well as NEAT1, XIST, and KCNQ1OT1, the three most important lncRNAs, and their interacting proteins in the final tripartite network, have been proposed as new candidate biomarkers in the cross-talk between DM and AD. The literature review also validates the obtained ncRNAs. In addition, miRNA/lncRNA pairs; hsa-miR-124-3p/KCNQ1OT1, hsa-miR-124-3p/NEAT1, and hsa-miR-124-3p/XIST, all expressed in the brain, and their interacting proteins in our final network are suggested for future research investigation.

Conclusion

This study identified 127 shared SNPs, 7 proteins, 15 miRNAs, and 11 lncRNAs involved in the cross-talk between DM and AD. Different network analysis and scoring function suggested the most significant miRNAs and lncRNAs as potential candidate biomarkers for wet laboratory experiments. Considering these candidate biomarkers may help in the early detection of DM and AD co-occurrence.
Number-time interaction: Search for a common magnitude system in a cross-modal setting
Authors: Shukla Anuj , Bapi Raju S.
Published: August 2022

A theory of magnitude (ATOM) suggests that a generalized magnitude system in the brain processes magnitudes such as space, time, and numbers. Numerous behavioral and neurocognitive studies have provided support to ATOM theory. However, the evidence for common magnitude processing primarily comes from the studies in which numerical and temporal information are presented visually. Our current understanding of such cross-dimensional magnitude interactions is limited to visual modality only. However, it is still unclear whether the ATOM-framework accounts for the integration of cross-modal magnitude information. To examine the cross-modal influence of numerical magnitude on temporal processing of the tone, we conducted three experiments using a temporal bisection task. We presented the numerical magnitude information in the visual domain and the temporal information in the auditory either simultaneously with duration judgment task (Experiment-1), before duration judgment task (Experiment-2), and before duration judgment task but with numerical magnitude also being task-relevant (Experiment-3). The results suggest that the numerical information presented in the visual domain affects temporal processing of the tone only when the numerical magnitudes were task-relevant and available while making a temporal judgment (Experiments-1 and 3). However, numerical information did not interfere with temporal information when presented temporally separated from the duration information (Experiments-2). The findings indicate that the influence of visual numbers on temporal processing in cross-modal settings may not arise from the common magnitude system but instead from general cognitive mechanisms like attention and memory.
Global and local feature fusion via long and short-term memory mechanism for dance emotion recognition in robot
Authors: Lyu Yin , Sun Yang
Published: August 2022

In recent years, there are more and more intelligent machines in people's life, such as intelligent wristbands, sweeping robots, intelligent learning machines and so on, which can simply complete a single execution task. We want robots to be as emotional as humans. In this way, human-computer interaction can be more natural, smooth and intelligent. Therefore, emotion research has become a hot topic that researchers pay close attention to. In this paper, we propose a new dance emotion recognition based on global and local feature fusion method. If the single feature of audio is extracted, the global information of dance cannot be reflected. And the dimension of data features is very high. In this paper, an improved long and short-term memory (LSTM) method is used to extract global dance information. Linear prediction coefficient is used to extract local information. Considering the complementarity of different features, a global and local feature fusion method based on discriminant multi-canonical correlation analysis is proposed in this paper. Experimental results on public data sets show that the proposed method can effectively identify dance emotion compared with other state-of-the-art emotion recognition methods.
Topological relationships between perivascular spaces and progression of white matter hyperintensities: A pilot study in a sample of the Lothian Birth Cohort 1936
Authors: Barnes Abbie , Ballerini Lucia , Valdés Hernández Maria del C. , Chappell Francesca M. , Muñoz Maniega Susana , Meijboom Rozanna , Backhouse Ellen V. , Stringer Michael S. , Duarte Coello Roberto , Brown Rosalind , Bastin Mark E. , Cox Simon R. , Deary Ian J. , Wardlaw Joanna M.
Published: August 2022

Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH) are features of cerebral small vessel disease which can be seen in brain magnetic resonance imaging (MRI). Given the associations and proposed mechanistic link between PVS and WMH, they are hypothesized to also have topological proximity. However, this and the influence of their spatial proximity on WMH progression are unknown. We analyzed longitudinal MRI data from 29 out of 32 participants (mean age at baseline = 71.9 years) in a longitudinal study of cognitive aging, from three waves of data collection at 3-year intervals, alongside semi-automatic segmentation masks for PVS and WMH, to assess relationships. The majority of deep WMH clusters were found adjacent to or enclosing PVS (waves−1: 77%; 2: 76%; 3: 69%), especially in frontal, parietal, and temporal regions. Of the WMH clusters in the deep white matter that increased between waves, most increased around PVS (waves−1–2: 73%; 2–3: 72%). Formal statistical comparisons of severity of each of these two SVD markers yielded no associations between deep WMH progression and PVS proximity. These findings may suggest some deep WMH clusters may form and grow around PVS, possibly reflecting the consequences of impaired interstitial fluid drainage via PVS. The utility of these relationships as predictors of WMH progression remains unclear.
Direct cerebello-striatal loop in dystonia as a possible new target for deep brain stimulation: A revised view of subcortical pathways involved
Authors: Kaji Ryuji
Published: August 2022

Dystonia is the second most common movement disorder next to tremor, but its pathophysiology remains unsettled. Its therapeutic measures include anti-cholingerics and other medications, in addition to botulinum neurotoxin injections, and stereotaxic surgery including deep brain stimulation (DBS), but there still remain a number of patients resistant to the therapy. Evidence has been accumulating suggesting that basal ganglia in association with the cerebellum are playing a pivotal role in pathogenesis. Clinical observations such as sensory tricks and the effects of muscle afferent stimulation and blockage suggest the conflict between the cortical voluntary motor plan and the subcortical motor program or motor subroutine controlling the intended action semi-automatically. In this review, the current understanding of the possible pathways or loops involved in dystonia is presented, and we review promising new targets for Deep Brain Stimulation (DBS) including the cerebellum.
Change of mortality of patients with acute ischemic stroke before and after 2015
Authors: Park Sang-Won , Lee Ji Young , Heo Nam Hun , Han James Jisu , Lee Eun Chae , Hong Dong-Yong , Lee Dong-Hun , Lee Byung Cheol , Lim Young Wha , Kim Gui Ok , Lee Man Ryul , Oh Jae Sang
Published: August 2022

Introduction

Advances in the diagnosis and management of acute ischemic stroke (AIS) and the increased use of mechanical thrombectomy (MT) have improved the quality of care and prognosis of patients with AIS since 2015. We investigated the changing trends in mortality of patients with AIS in Korea before and after 2015.

Materials and methods

A retrospective cohort study was conducted using combined anonymized data from the Acute Stroke Assessment Registry of Korea and the Health Insurance Review & Assessment Service database. Patients with ischemic stroke with precise onset time and initial National Institute of Health Stroke Scale records were included.

Results

Patients receiving MT treatment increased from 256 (2.7%) pre-2015 to 1,037 (3.9%) post-2015 (p < 0.001). Overall mortality significantly decreased from pre-2015 to post-2015. In pre-2015, intravenous thrombolysis (IVT) administered within 2 h significantly reduced 3-month mortality when compared with non-IVT. While, in post-2015, IVT administered within 2 h significantly reduced the 3-month, 1-year, 2-year, and 4-year mortality (p < 0.05). MT only reduced 1-year mortality pre-2015; however, MT significantly reduced the 3-month, 1-year, and 2-year mortality post-2015 (p < 0.05). Post-stroke antiplatelet and anticoagulant drugs significantly reduced the 3-month, 1-year, 2-year, and 4-year mortality post-2015.

Discussion

Since 2015, faster IVT has significantly reduced the short- and long-term mortality in patients with AIS; MT reduced the 3-month, 1-year, and 2-year mortality. Post-stroke antithrombotic medication has significantly lowered the 2- and 4-year mortality since 2015.

Conclusions

Changing trends in AIS management since 2015 have improved the prognosis of patients with AIS.
A single-center retrospective study with 1-year follow-up after CEA in patients with severe carotid stenosis with contralateral carotid artery occlusion
Authors: Yuan Wanzhong , Huo Ran , Ma Kaiming , Han Yunfeng , Yin Xiaoliang , Yang Jun , Zhao Xihai , Wang Tao
Published: August 2022

Objective

To analyze the risk factors associated with adverse events after carotid endarterectomy (CEA) in patients with unilateral severe carotid stenosis and contralateral occlusion.

Methods

Patients were recruited for CEA between August 2014 and February 2020. CEA was performed under general anesthesia. The carotid clamp time (CCT; long CCT: >20 min) is defined as the period between clamp-on and clamp-off for the stenotic carotid artery. The perioperative factors and postoperative adverse events were recorded. All patients were followed up for 1 year after CEA.

Results

Sixty subjects (65.8 ± 7.2 years; 54 males) were included. Patients with adverse events had significantly longer CCT than those without adverse events (60% vs. 40%, P = 0.013). Univariate logistic regression analysis showed that a history of diabetes was significantly associated with adverse events (OR, 0.190; 95% CI, 0.045–0.814; P = 0.025); long CCT was significantly associated with adverse events (OR, 8.500; 95% CI, 1.617–44.682; P = 0.011). After adjusting for confounding factors, including age, sex, BMI, diabetes, PSV, long CCT, non–use of shunt, and history of stroke or TIA, the associations between diabetes and adverse events (OR, 0.113; 95% CI, 0.013–0.959; P = 0.046) were statistically significant; the associations between long CCT and adverse events (OR, 1.301; 95% CI, 1.049–1.613; P = 0.017) were statistically significant.

Conclusions

A longer carotid clamp time (>20 min) and a history of diabetes may increase the risk of adverse events in patients with unilateral severe carotid stenosis and contralateral occlusion after CEA. With good preoperative evaluation and intraoperative monitoring, the use of shunts may not be needed intraoperatively in patients with unilateral severe carotid stenosis and contralateral occlusion.
Training peripheral vision to read: Using stimulus exposure and identity priming
Authors: Yu Deyue
Published: August 2022

Reading in the periphery can be improved with perceptual learning. A conventional training paradigm involves repeated practice on a character-based task (e.g., recognizing random letters/words). While the training is effective, the hours of strenuous effort required from the trainees makes it difficult to implement the training in low-vision patients. Here, we developed a training paradigm utilizing stimulus exposure and identity priming to minimize training effort and improve training accessibility while maintaining the active engagement of observers through a stimulus visibility task. Twenty-one normally sighted young adults were randomly assigned to three groups: a control group, a with-repetition training group, and a without-repetition training group. All observers received a pre-test and a post-test scheduled 1 week apart. Each test consisted of measurements of reading speed, visual-span profile, the spatial extent of crowding, and isolated-letter profiles at 10° eccentricity in the lower visual field. Training consists of five daily sessions (a total of 7,150 trials) of viewing trigram stimuli (strings of three letters) with identity priming (prior knowledge of target letter identity). The with-repetition group was given the option to replay each stimulus (averaged 0.4 times). In comparison to the control group, both training groups showed significant improvements in all four performance measures. Stimulus replay did not yield a measurable benefit on learning. Learning transferred to various untrained tasks and conditions, such as the reading task and untrained letter size. Reduction in crowding was the main basis of the training-related improvement in reading. We also found that the learning can be partially retained for a minimum of 3 months and that complete retention is attainable with additional monthly training. Our findings suggest that conventional training task that requires recognizing random letters or words is dispensable for improving peripheral reading. Utilizing stimulus exposure and identity priming accompanied by a stimulus visibility task, our novel training procedure offers effective intervention, simple implementation, capability for remote and self-administration, and an easy translation into low-vision reading rehabilitation.
A touchscreen-based paradigm to measure visual pattern separation and pattern completion in mice
Authors: Wang Hao , Sun Na , Wang Xinyue , Han Jinyuan , Zhang Yongxiang , Huang Yan , Zhou Wenxia
Published: August 2022

Memory accuracy involves two major processes: pattern separation and pattern completion. Pattern separation refers to the ability to reduce overlap among similar inputs to avoid interference, and pattern completion refers to the ability to retrieve the whole information from partial or degraded cues. Impairments in pattern separation/pattern completion contribute to cognitive deficits in several diseases of the nervous system. Therefore, it is better to evaluate both pattern separation and pattern completion in one apparatus. However, few tools are available to assess pattern separation and pattern completion within the same apparatus for rodents. In this study, we designed a series of images with varying degrees of similarity to the correct image to evaluate pattern separation and pattern completion. First, mice were trained to discriminate between two totally different images, and once the correct percentage reached above 77% for two consecutive days, the images with different degrees of similarity were used to measure pattern separation and pattern completion. The results showed the mice performed progressively worse from S0 to S4 (increasing similarity) when discriminating similar images in pattern separation, and the mice performed progressively worse from C0 to C4 (decreasing cues information) when recalling the correct image according to partial cues in pattern completion, implying a good image similarity-dependent manner for memory accuracy evaluation. In sum, we designed a convenient, effective paradigm to evaluate pattern separation and pattern completion based on a touchscreen pairwise discrimination task, which may provide a new method for the studies of the effects and mechanisms of memory accuracy enhancing drugs.