bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a novel reactive oxygen species (ROS)-related genes model combined with RT-qPCR experiments for prognosis and immunotherapy in gastric cancer
Authors: Cen Kenan , Wu Zhixuan , Mai Yifeng , Dai Ying , Hong Kai , Guo Yangyang
Published: April 2023

Reactive oxygen species play a crucial role in the prognosis and tumor microenvironment (TME) of malignant tumors. An ROS-related signature was constructed in gastric cancer (GC) samples from TCGA database. ROS-related genes were obtained from the Molecular Signatures Database. Consensus clustering was used to establish distinct ROS-related subtypes related to different survival and immune cell infiltration patterns. Sequentially, prognostic genes were identified in the ROS-related subtypes, which were used to identify a stable ROS-related signature that predicted the prognosis of GC. Correlation analysis revealed the significance of immune cell iniltration, immunotherapy, and drug sensitivity in gastric cancers with different risks. The putative molecular mechanisms of the different gastric cancer risks were revealed by functional enrichment analysis. A robust nomogram was established to predict the outcome of each gastric cancer. Finally, we verified the expression of the genes involved in the model using RT-qPCR. In conclusion, the ROS-related signature in this study is a novel and stable biomarker associated with TME and immunotherapy responses.
Association of gut microbiome and metabolites with onset and treatment response of patients with pemphigus vulgaris
Authors: Wang Yiyi , Xia Xuyang , Zhou Xingli , Zhan Tongying , Dai Qinghong , Zhang Yan , Zhang Wei , Shu Yang , Li Wei , Xu Heng
Published: April 2023

Background

Gut dysbiosis and gut microbiome-derived metabolites have been implicated in both disease onset and treatment response, but this has been rarely demonstrated in pemphigus vulgaris (PV). Here, we aim to systematically characterize the gut microbiome to assess the specific microbial species and metabolites associated with PV.

Methods

We enrolled 60 PV patients and 19 matched healthy family members, and collected 100 fecal samples (60 treatment-naïve, 21 matched post-treatment, and 19 controls). Metagenomic shotgun sequencing and subsequent quality control/alignment/annotation were performed to assess the composition and microbial species, in order to establish the association between gut microbiome with PV onset and treatment response. In addition, we evaluated short-chain fatty acids (SCFAs) in PV patients through targeted metabolomics analysis.

Results

The diversity of the gut microbiome in PV patients deviates from the healthy family members but not between responder and non-responder, or before and after glucocorticoid treatment. However, the relative abundance of several microbial species, including the pathogenic bacteria (e.g., Escherichia coli) and some SCFA-producing probiotics (e.g., Eubacterium ventriosum), consistently differed between the two groups in each comparison. Escherichia coli was enriched in PV patients and significantly decreased after treatment in responders. In contrast, Eubacterium ventriosum was enriched in healthy family members and significantly increased particularly in responders after treatment. Consistently, several gut microbiome-derived SCFAs were enriched in healthy family members and significantly increased after treatment (e.g., butyric acid and valeric acid).

Conclusions

This study supports the association between the gut microbiome and PV onset, possibly through disrupting the balance of gut pathogenic bacteria and probiotics and influencing the level of gut microbiome-derived SCFAs. Furthermore, we revealed the potential relationship between specific microbial species and glucocorticoid treatment.
TIGAR deficiency induces caspase-1-dependent trophoblasts pyroptosis through NLRP3-ASC inflammasome
Authors: Guo Junjun , Zhou Meijuan , Zhao Man , Li Shuxian , Fang Zhenya , Li Anna , Zhang Meihua
Published: April 2023

Introduction

Gestational diabetes mellitus (GDM), a common complication of pregnancy, is risky for both mother and fetus. Previous studies about TP53-induced glycolysis and apoptosis regulator (TIGAR) focused on the occurrence and development of cancer, cardiovascular disease, and neurological disease, however, it is still unclear whether TIGAR plays a regulatory role in gestational diabetes mellitus (GDM).

Methods

Utilizing HG exposure, we explored the role of TIGAR in oxidative stress limitation, excessive inflammatory toxicity defense, and pyroptosis prevention.

Results

TIGAR was up-regulated in vivo and in vitro under HG condition, and loss of TIGAR increased ROS in trophoblast cells which drove a phenotypic switch and hindered the capacity of migration, invasion, and tube formation. This switch depended on the increased activation of NLRP3-ASC-caspase-1 signaling, which caused a distinctive characteristic of pyroptosis, and these findings could finally be reverted by antioxidant treatment (NAC) and receptor block (MCC950). Collectively, trophoblast pyroptosis is an upstream event of TIGAR deficiency-induced inflammation, which is promoted by ROS accumulation through NLRP3-ASC inflammasome.

Conclusion

Taken together, our results uncovered that, as the upstream event of TIGAR deficiency-induced inflammation, pyroptosis is stimulated by ROS accumulation through NLRP3-ASC inflammasome.
Establishing the role of the FES tyrosine kinase in the pathogenesis, pathophysiology, and severity of sepsis and its outcomes
Authors: Laight Brian J. , Jawa Natasha A. , Tyryshkin Kathrin , Maslove David M. , Boyd J. Gordon , Greer Peter A.
Published: April 2023

Introduction

Sepsis is a result of initial over-activation of the immune system in response to an infection or trauma that results in reduced blood flow and life-threatening end-organ damage, followed by suppression of the immune system that prevents proper clearance of the infection or trauma. Because of this, therapies that not only limit the activation of the immune system early on, but also improve blood flow to crucial organs and reactivate the immune system in late-stage sepsis, may be effective treatments. The tyrosine kinase FES may fulfill this role. FES is present in immune cells and serves to limit immune system activation. We hypothesize that by enhancing FES in early sepsis and inhibiting its effects in late sepsis, the severity and outcome of septic illness can be improved.

Methods and analysis

In vitro and in vivo modeling will be performed to determine the degree of inflammatory signaling, cytokine production, and neutrophil extracellular trap (NET) formation that occurs in wild-type (WT) and FES knockout (FES-/-) mice. Clinically available treatments known to enhance or inhibit FES expression (lorlatinib and decitabine, respectively), will be used to explore the impact of early vs. late FES modulation on outcomes in WT mice. Bioinformatic analysis will be performed to examine FES expression levels in RNA transcriptomic data from sepsis patient cohorts, and correlate FES expression data with clinical outcomes (diagnosis of sepsis, illness severity, hospital length-of-stay).

Ethics and dissemination

Ethics approval pending from the Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board. Results will be disseminated through scientific publications and through lay summaries to patients and families.
Exhausted T cells hijacking the cancer-immunity cycle: Assets and liabilities
Authors: Brunell Anna E. , Lahesmaa Riitta , Autio Anu , Thotakura Anil K.
Published: April 2023

T cell exhaustion is an alternative differentiation path of T cells, sometimes described as a dysfunction. During the last decade, insights of T cell exhaustion acting as a bottle neck in the field of cancer immunotherapy have undoubtedly provoked attention. One of the main drivers of T cell exhaustion is prolonged antigen presentation, a prerequisite in the cancer-immunity cycle. The umbrella term “T cell exhaustion” comprises various stages of T cell functionalities, describing the dynamic, one-way exhaustion process. Together these qualities of T cells at the exhaustion continuum can enable tumor clearance, but if the exhaustion acquired timeframe is exceeded, tumor cells have increased possibilities of escaping immune system surveillance. This could be considered a tipping point where exhausted T cells switch from an asset to a liability. In this review, the contrary role of exhausted T cells is discussed.
The first crystal structure of CD8αα from a cartilaginous fish
Authors: Jia Zhao , Feng Jianhua , Dooley Helen , Zou Jun , Wang Junya
Published: April 2023

Introduction

Cartilaginous fishes are the most evolutionary-distant vertebrates from mammals and possess an immunoglobulin (Ig)- and T cell-mediated adaptive immunity. CD8 is the hallmark receptor of cytotoxic T cells and is required for the formation of T cell receptor-major histocompatibility complex (TCR-MHC) class I complexes.

Methods

RACE PCR was used to obtain gene sequences. Direct dilution was applied for the refolding of denatured recombinant CD8 protein. Hanging-drop vapor diffusion method was performed for protein crystallization.

Results

In this study, CD8α and CD8β orthologues (termed ScCD8α and ScCD8β) were identified in small-spotted catshark (Scyliorhinus canicula). Both ScCD8α and ScCD8β possess an extracellular immunoglobulin superfamily (IgSF) V domain as in previously identified CD8 proteins. The genes encoding CD8α and CD8β are tandemly linked in the genomes of all jawed vertebrates studied, suggesting that they were duplicated from a common ancestral gene before the divergence of cartilaginous fishes and other vertebrates. We determined the crystal structure of the ScCD8α ectodomain homodimer at a resolution of 1.35 Å and show that it exhibits the typical topological structure of CD8α from endotherms. As in mammals, the homodimer formation of ScCD8αα relies upon interactions within a hydrophobic core although this differs in position and amino acid composition. Importantly, ScCD8αα shares the canonical cavity required for interaction with peptide-loaded MHC I in mammals. Furthermore, it was found that ScCD8α can co-immunoprecipitate with ScCD8β, indicating that it can form both homodimeric and heterodimeric complexes.

Conclusion

Our results expand the current knowledge of vertebrate CD8 dimerization and the interaction between CD8α with p/MHC I from an evolutionary perspective.
The role of group 3 innate lymphoid cell in intestinal disease
Authors: Li Minghui , Wang Zehui , Jiang Wei , Lu Yihan , Zhang Jun
Published: April 2023

Group 3 innate lymphoid cells (ILC3s), a novel subpopulation of lymphocytes enriched in the intestinal mucosa, are currently considered as key sentinels in maintaining intestinal immune homeostasis. ILC3s can secrete a series of cytokines such as IL-22 to eliminate intestinal luminal antigens, promote epithelial tissue repair and mucosal barrier integrity, and regulate intestinal immunity by integrating multiple signals from the environment and the host. However, ILC3 dysfunction may be associated with the development and progression of various diseases in the gut. Therefore, in this review, we will discuss the role of ILC3 in intestinal diseases such as enteric infectious diseases, intestinal inflammation, and tumors, with a focus on recent research advances and discoveries to explore potential therapeutic targets.
Case report: Complete response of an anaplastic thyroid carcinoma patient with NRAS Q61R/BRAF D594N mutations to the triplet of dabrafenib, trametinib and PD-1 antibody
Authors: Gui Lin , Zhu Yiming , Li Xiaomo , He Xiaohui , Ma Tonghui , Cai Yi , Liu Shaoyan
Published: April 2023

Anaplastic thyroid carcinoma, BRAF non-V600, NRAS, combination immunotherapy and targeted therapy, case report. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with a mortality rate near 100%. BRAF V600 and NRAS mutations are the most common drivers of ATC. While patients with BRAF V600-mutated ATC can be treated with BRAF-targeted therapy, there is no effective treatment for ATC driven by NRAS or non-V600 BRAF mutations. For patients with untargetable driver mutations, immunotherapy provides an alternative treatment option. Here, we present a metastatic ATC patient with PD-L1 positive (tumor proportion score of 60%) tumor and NRAS Q61R/BRAF D594N mutations, who progressed on PD-1 antibody sintilimab plus angiogenesis inhibitor anlotinib. The class 3 BRAF mutant D594N is sensitive to the inhibition of MEK inhibitor trametinib, and its oncogenic activity also depends on CRAF, which can be inhibited by BRAF inhibitor dabrafenib. For these reasons, the patient received a salvage treatment regime of dabrafenib, trametinib, and sintilimab, which resulted in a complete pathological response. To our best knowledge, this is the first report of successful treatment of ATC patients with concurrent NRAS/BRAF non-V600 mutations with the combination of immunotherapy and targeted therapy. Further investigation is required to decipher the mechanism by which the combination of dabrafenib/trametinib with PD-1 antibody overcomes initial immunotherapy resistance likely mediated by concurrent BRAF and NRAS mutations.
Melittin derived peptide-drug conjugate, M-DM1, inhibits tumor progression and induces effector cell infiltration in melanoma by targeting M2 tumor-associated macrophages
Authors: Jeong Chanmi , Kim Jeongdong , Han Ik-Hwan , Kim Soyoung , Choi Ilseob , Kim Hongsung , Jeong Jin-Hyun , Bae Hyunsu
Published: April 2023

Background

Melanoma has the highest mortality rate among all the types of skin cancer. In melanoma, M2-like tumor-associated macrophages (TAMs) are associated with the invasiveness of tumor cells and a poor prognosis. Hence, the depletion or reduction of M2-TAMs is a therapeutic strategy for the inhibition of tumor progression. The aim of this study was to evaluate the therapeutic effects of M-DM1, which is a conjugation of melittin (M), as a carrier for M2-like TAMs, and mertansine (DM1), as a payload to induce apoptosis of TAMs, in a mouse model of melanoma.

Methods

Melittin and DM1 were conjugated and examined for the characterization of M-DM1 by high-performance liquid chromatography and electrospray ionization mass spectrometry. Synthesized M-DM1 were examined for in vitro cytotoxic effects. For the in vivo study, we engrafted murine B16-F10 into right flank of C57BL/6 female mice and administered an array of treatments (PBS, M, DM1, or M-DM1 (20 nmol/kg)). Subsequently, the tumor growth and survival rates were analyzed, as well as examining the phenotypes of tumor-infiltrating leukocytes and expression profiles.

Results

M-DM1 was found to specifically reduce M2-like TAMs in melanoma, which potentially leads to the suppression of tumor growth, migration, and invasion. In addition, we also found that M-DM1 improved the survival rates in a mouse model of melanoma compared to M or DM1 treatment alone. Flow cytometric analysis revealed that M-DM1 enhanced the infiltration of CD8+ cytotoxic T cells and natural killer cells (NK cells) in the tumor microenvironment.

Conclusion

Taken together, our findings highlight that M-DM1 is a prospective agent with enhanced anti-tumor effects.
Abacavir use is associated with increased prothrombin conversion
Authors: Yan Qiuting , Huang Shengshi , van der Heijden Wouter , Ninivaggi Marisa , van de Wijer Lisa , de Laat-Kremers Romy , Van der Ven Andre J. , de Laat Bas , de Mast Quirijn
Published: April 2023

There is ongoing debate as to whether abacavir (ABC) increases the risk for cardiovascular disease(CVD) in people living with HIV (PLHIV) and the mechanisms underlying this possible association. We recently showed that the use of an ABC-containing regimen was independently associated with increased thrombin generation (TG). In the present study, we aim to explore these findings further, by studying the mechanistical processes that underly the global thrombin generation test via thrombin dynamics analysis. Thrombin dynamics analysis can pinpoint the cause of increased thrombin generation associated with ABC-use either to the procoagulant prothrombin conversion pathway or the anticoagulant thrombin inactivation pathway. In this cross-sectional study, 208 virally suppressed PLHIV were included, of whom 94 were on a ABC-containing regimen, 92 on a tenofovir disoproxil fumarate (TDF)-containing regimen, and the remainder on other regimens. We used Calibrated Automated Thrombinography to measure thrombin generation and perform thrombin dynamics analysis. The total amount of prothrombin conversion, as well as the maximum rate of prothrombin conversion were significantly increased in PLHIV on an ABC containing regimen compared to other treatment regimens. The levels of pro- and anticoagulant factors were comparable, indicating that the ABC-induced changes affect the kinetics of prothrombin conversion rather than procoagulant factor levels. Moreover, Von Willebrand Factor (VWF), active VWF and VWF pro-peptide levels were significantly higher in PLHIV than controls without HIV. However, they did not differ between ABC and non-ABC treated participants.
Local ecological knowledge can support improved management of small-scale fisheries in the Bay of Bengal
Authors: Ullah Hadayet , Wahab Md Abdul , Rahman Md Jalilur , Al Mamun Shaheed Nasrullah , Kumar Uttam , Rahman Muhammad Arifur , Souhardya Sazeed Mehrab , Kabir Ilias Ebne , Hussain Monayem , Rahman Md. Bokthier , Chishty Sk Md Saeef Ul Hoque
Published: April 2023

Fishers’ local ecological knowledge (LEK) can be used to reconstruct or supplement long-term trends in heavily exploited population or poorly assessed species with low biomass. We used historical memories of small-scale fishers to understand their perceptions of changes in catch trends in marine fisheries over the last 20 years. The study aimed at evaluating how fishers could provide consistent and reliable data on major fish species/groups comparable with official catch data and to explore the potential of increasing their participation in fishery management. We conducted focus group discussions (FGDs) and key informant interviews with experienced fishers and stakeholders, using a structured template related to the catch and effort data. Using FGD data, we systematically compared changes in fish catch rates and effort over time and space. Data were collected on major groups of species that had reasonable landing over time. Overall, the analysis revealed changes in catch rate, monthly landings per landing center, factors that likely influence the catch trends, and the spatial expansion of fisheries. Our study provides insight into species’ abundance over time. Fishers’ LEK shows declining catch rates for major species and groups, but monthly harvests at landing centers have increased over two decades because of increased fishing efforts. Small-scale fishers are catching more fish from deeper waters over time, indicating a geographical expansion and/or development of fisheries beyond traditionally exploited areas. Such expansions of nearshore fisheries may result from the overfishing of nearby areas. On the contrary, this could be viewed as a positive indication of the potential for growth and development of small-scale fisheries in the region, especially in the context of the blue economy. The agreement between official statistics and fishers’ data on species catch trends over time suggests that fishers have a good understanding of their fishing system. This indicates that fishers’ knowledge could be invaluable, especially in data-poor areas. LEK integration into policy and management is thus expected to facilitate the efficient management of small-scale fisheries.
Stimulus material selection for the Dutch famous faces test for older adults
Authors: van den Elzen Evi H. T. , Brehmer Yvonne , Van Deun Katrijn , Mark Ruth E.
Published: April 2023

Worldwide, approximately 22% of all individuals aged 50 years and older are currently estimated to fall somewhere on the Alzheimer’s disease (AD) continuum, which can be roughly divided into preclinical AD, mild cognitive impairment (MCI), and AD dementia. While episodic memory loss (among other aspects) is typically required for a diagnosis of AD dementia, MCI is said to have occurred when cognitive impairment (including memory loss) is worse than expected for the person’s age but not enough to be classified as dementia. On the other hand, preclinical AD can currently only be detected using biomarkers; clinical symptoms are not apparent using traditional neuropsychological tests. The main aim of the current paper was to explore the possibility of a test which could distinguish preclinical AD from normal aging. Recent scientific evidence suggests that the Famous Faces Test (FFT) could differentiate preclinical AD from normal aging up to 5 years before a clinical AD diagnosis. Problematic with existing FFTs is the selection of stimulus material. Faces famous in a specific country and a specific decade might not be equally famous for individuals in another country or indeed for people of different ages. The current article describes how famous faces were systematically selected and chosen for the Dutch older (60+) population using five steps. The goal was to design and develop short versions of the FFT for Dutch older adults of equivalent mean difficulty. In future work, these nine parallel versions will be necessary for (a) cross-sectional comparison as well as subsequent longitudinal assessment of cognitively normal and clinical groups and (b) creating personalized norms for the normal aged controls that could be used to compare performance within individuals with clinical diagnoses. The field needs a simple, cognitive test which can distinguish the earliest stages of the dementia continuum from normal aging.
A glance at the gut microbiota and the functional roles of the microbes based on marmot fecal samples
Authors: Chen Chuizhe , Chen Shu , Wang Bo
Published: April 2023

Research on the gut microbiota, which involves a large and complex microbial community, is an important part of infectious disease control. In China, few studies have been reported on the diversity of the gut microbiota of wild marmots. To obtain full details of the gut microbiota, including bacteria, fungi, viruses and archaea, in wild marmots, we have sequenced metagenomes from five sample-sites feces on the Hulun Buir Grassland in Inner Mongolia, China. We have created a comprehensive database of bacterial, fungal, viral, and archaeal genomes and aligned metagenomic sequences (determined based on marmot fecal samples) against the database. We delineated the detailed and distinct gut microbiota structures of marmots. A total of 5,891 bacteria, 233 viruses, 236 fungi, and 217 archaea were found. The dominant bacterial phyla were Firmicutes, Proteobacteria, Bacteroidetes, and Actinomycetes. The viral families were Myoviridae, Siphoviridae, Phycodnaviridae, Herpesviridae and Podoviridae. The dominant fungi phyla were Ascomycota, Basidiomycota, and Blastocladiomycota. The dominant archaea were Biobacteria, Omoarchaea, Nanoarchaea, and Microbacteria. Furthermore, the gut microbiota was affected by host species and environment, and environment was the most important factor. There were 36,989 glycoside hydrolase genes in the microbiota, with 365 genes homologous to genes encoding β-glucosidase, cellulase, and cellulose β-1,4-cellobiosidase. Additionally, antibiotic resistance genes such as macB, bcrA, and msbA were abundant. To sum up, the gut microbiota of marmot had population diversity and functional diversity, which provides a basis for further research on the regulatory effects of the gut microbiota on the host. In addition, metagenomics revealed that the gut microbiota of marmots can degrade cellulose and hemicellulose.
Volatiles of fungal cultivars act as cues for host-selection in the fungus-farming ambrosia beetle Xylosandrus germanus
Authors: Gugliuzzo Antonio , Kreuzwieser Jürgen , Ranger Christopher M. , Tropea Garzia Giovanna , Biondi Antonio , Biedermann Peter H. W.
Published: April 2023

Many wood-boring insects use aggregation pheromones during mass colonization of host trees. Bark beetles (Curculionidae: Scolytinae) are a model system, but much less is known about the role of semiochemicals during host selection by ambrosia beetles. As an ecological clade within the bark beetles, ambrosia beetles are obligately dependent on fungal mutualists for their sole source of nutrition. Mass colonization of trees growing in horticultural settings by exotic ambrosia beetles can occur, but aggregation cues have remained enigmatic. To elucidate this mechanism, we first characterized the fungal associates of the exotic, mass-aggregating ambrosia beetleXylosandrus germanusin Southern Germany. Still-air olfactometer bioassays documented the attraction ofX. germanusto its primary nutritional mutualistAmbrosiella grosmanniaeand to a lesser extent another common fungal isolate (Acremoniumsp.). During two-choice bioassays,X. germanuswas preferentially attracted to branch sections (i.e., bolts) that were either pre-colonized by conspecifics or pre-inoculated withA. grosmanniae. Subsequent analyses identified microbial volatile organic compounds (MVOCs) that could potentially function as aggregation pheromones forX. germanus. To our knowledge, this is the first evidence for fungal volatiles as attractive cues during host selection byX. germanus. Adaptive benefits of responding to fungal cues associated with an infestation of conspecifics could be a function of locating a suitable substrate for cultivating fungal symbionts and/or increasing the likelihood of mating opportunities with the flightless males. However, this requires solutions for evolutionary conflict arising due to potential mixing of vertically transmitted and horizontally acquired symbiont strains, which are discussed.
DNA repair enzymes of the Antarctic Dry Valley metagenome
Authors: Rzoska-Smith Elizabeth , Stelzer Ronja , Monterio Maria , Cary Stephen C. , Williamson Adele
Published: April 2023

Microbiota inhabiting the Dry Valleys of Antarctica are subjected to multiple stressors that can damage deoxyribonucleic acid (DNA) such as desiccation, high ultraviolet light (UV) and multiple freeze-thaw cycles. To identify novel or highly-divergent DNA-processing enzymes that may enable effective DNA repair, we have sequenced metagenomes from 30 sample-sites which are part of the most extensive Antarctic biodiversity survey undertaken to date. We then used these to construct wide-ranging sequence similarity networks from protein-coding sequences and identified candidate genes involved in specialized repair processes including unique nucleases as well as a diverse range of adenosine triphosphate (ATP) -dependent DNA ligases implicated in stationary-phase DNA repair processes. In one of the first direct investigations of enzyme function from these unique samples, we have heterologously expressed and assayed a number of these enzymes, providing insight into the mechanisms that may enable resident microbes to survive these threats to their genomic integrity.
Soil bacterial communities of paddy are dependent on root compartment niches but independent of growth stages from Mollisols of Northeast China
Authors: Liu Kai , Wang Qiuju , Sun Minglong , Gao Shiwei , Liu Qing , Shan Lili , Guo Junxiang , Bian Jingyang
Published: April 2023

Introduction

Deep insights into adhering soil of root zones (rhizosphere and rhizoplane) microbial community could provide a better understanding of the plant-microbe relationship. To better understand the dynamics of these microbial assemblies over the plant life cycle in rhizodeposition along rice roots.

Methods

Here, we investigated bacterial distribution in bulk, rhizosphere, and rhizoplane soils at tillering, heading, and mature stage, from rice (Oryza sativa) fields of the Northeast China.

Results and Discussion

Our results revealed that soil bacterial α-diversity and community composition were significantly affected by root compartment niches but not by temporal change. Compared to rhizoplane soils in the same period, bulk in the heading and rhizosphere in the mature had the largest increase in Shannon’s index, with 11.02 and 14.49% increases, respectively. Proteobacteria, Chloroflexi, Bacteroidetes, and Acidobacteria are predominant across all soil samples, bulk soil had more phyla increased across the growing season than that of root related-compartments. Deterministic mechanisms had a stronger impact on the bacterial community in the compartments connected to the roots, with the relative importance of the bulk soil, rhizoplane and rhizosphere at 83, 100, and 56%, respectively. Because of ecological niche drivers, the bacterial networks in bulk soils exhibit more complex networks than rhizosphere and rhizoplane soils, reflected by more nodes, edges, and connections. More module hub and connector were observed in bulk (6) and rhizoplane (5) networks than in rhizosphere (2). We also detected shifts from bulk to rhizoplane soils in some functional guilds of bacteria, which changed from sulfur and nitrogen utilization to more carbon and iron cycling processes. Taken together, our results suggest distinct bacterial network structure and distribution patterns among rhizosphere, rhizoplane, and bulk soils, which could possibly result in potential functional differentiation. And the potential functional differentiation may be influenced by plant root secretions, which still needs to be further explored.
The cognitive dysfunction of claustrum on Alzheimer’s disease: A mini-review
Authors: Chen Chun-Yan , Yang Guang-Yi , Tu Hai-Xia , Weng Xu-Chu , Hu Chun , Geng Hong-Yan
Published: April 2023

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aβ) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment.
The interaction of peptide inhibitors and Aβ protein: Binding mode analysis, inhibition of the formation of Aβ aggregates, and then exert neuroprotective effects
Authors: Wu Yuchen , Guo Shuang , Wang Kunli , Kang Jingjing
Published: April 2023

Introduction

The misfolding and aggregation of β-amyloid (Aβ) easily form Aβ fibers, which are continuously deposited in the brain, leading to the massive generation of amyloid plaques, severely destroying neuronal connections, and promoting Alzheimer’s disease (AD) The occurrence and development of AD is one of the pathogenesis of AD. There is an urgent need to develop inhibitors against Aβ aggregation, which is hopefully a potential way to treat AD.

Methods

In this study, we first found the crystal structure of the Aβ1–42 receptor protein from the RCSB PDB protein structure database and used the SYBYL X2.0 software for molecular docking, and then used the Peptide Ranker, Innovagen, DPL, and ToxinPred online websites to perform peptides. Predict the activity score, toxicity and water solubility, and then calculate the affinity constant KD value of polypeptide and Aβ through Surface Plasmon Resonance (SPR) experiment. Subsequently, the CCK-8 kit method was used to determine the toxicity of different concentrations of peptides (3.125, 6.25, 12.5, 25, 50, 100, 200 μM) to PC12 cells, and then the peptides and Aβ according to different concentration ratios (1:4, 1:2, 1:1, 1:0.5, 1:0.25, 0:4), this method is also used to detect the effect of peptides on Aβ-induced neurotoxicity. The thioflavin T (ThT) fluorescence method was used to detect the effects of peptides (50 μM) on Aβ (25 μM) aggregation inhibitory effect.

Results

The results showed that the CScore of YVRHLKYVRHLK peptide molecule docking was 10.0608, the predicted activity score was 0.20, and the KD value was 5.385 × 10−5. The ThT and CCK-8 kit method found that the peptide itself is less toxic to PC12 cells at a concentration of 50 μM, and it has a significant inhibitory effect on the formation of Aβ1–42 aggregates when incubated with Aβ1–42 at a ratio of 1:1 (p < 0.05) and can significantly reduce the PC12 cytotoxicity induced by Aβ1–42 (p < 0.05).

Conclusion

In conclusion, the polypeptide YVRHLKYVRHLK designed in this study has a neuroprotective effect on PC12 cytotoxicity induced by Aβ1–42.

Graphical Abstract
Cognitive inhibition deficit in long COVID-19: An exploratory study
Authors: Saucier Jacob , Jose Caroline , Beroual Zaynab , Al-Qadi Mohammad , Chartrand Simon , Libert Eméraldine , Losier Marie-Claire , Cooling Kendra , Girouard Gabriel , Jbilou Jalila , Chamard-Witkowski Ludivine
Published: April 2023

Background and objectives

An increasing number of research studies point toward the importance and prevalence of long-term neurocognitive symptoms following infection with COVID-19. Our objectives were to capture the prevalence of cognitive impairments from 1 to 16 months post-COVID-19 infection, assess the changes in neuropsychological functions over time, and identify factors that can predict long-term deficits in cognition.

Methodology

A cross-sectional research design was adopted to compare four sub-samples recruited over a 16-month timeframe (1–4, 5–8, 9–12, and 13–16 months). Phone interviews were conducted at least 6 weeks after being infected by COVID-19. Sociodemographic and clinical questionnaires were administered followed by standardized neurocognitive and psychological tests and health questionnaires screening cognitive symptoms, anxiety, depression, fatigue, and autonomy.

Results

Regarding general health questionnaires, 55.2% of the 134 participants had symptoms of psychiatric illness, while 21.6% of patients had moderate-to-severe anxiety or depression. Cognitive efficiency was diminished in 19.4% of our population. Executive dysfunction was screened in 56% of patients, and an impairment of cognitive flexibility and inhibition was revealed in 38.8%. Depression, hospital or intensive care unit (ICU) admission, and the duration of hospital or ICU stay were associated with an inhibition deficit. The duration elapsed from the initial infection, and the neurocognitive assessment was not associated with a decrease in inhibition deficit. The prevalence of cognitive impairments, other than inhibition deficit, tended to decrease during the study period.

Discussion

This study supports the extensive literature on the cognitive and neuropsychiatric sequelae of COVID-19 and highlights long-lasting inhibition deficits, while other cognitive functions seemed to improve over time. The severity of infection could interact as a catalyst in the complex interplay between depression and executive functions. The absence of a relation between inhibition deficits and sociodemographic or medical factors reinforces the need for cognitive screening in all COVID-19 patients. Future research should focus on inhibition deficits longitudinally to assess the progression of this impairment.
The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study
Authors: Lv Xiaofeng , Xu Bojun , Tang Xiurong , Liu Shanshan , Qian Jun-Hui , Guo Julan , Luo Jian
Published: April 2023

Background

Previous epidemiological and other studies have shown an association between major depressive disorder (MDD) and migraine. However, the causal relationship between them remains unclear. Therefore, this study aimed to investigate the causal relationship between MDD and migraine using a bidirectional, two-sample Mendelian randomization (MR) approach.

Methods

Data on MDD and migraine, including subtypes with aura migraine (MA) and without aura migraine (MO), were gathered from a publicly available genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) utilized as instrumental variables (IVs) were then screened by adjusting the intensity of the connection and removing linkage disequilibrium. To explore causal effects, inverse variance weighting (IVW) was used as the primary analysis method, with weighted median, MR-Egger, simple mode, and weighted mode used as supplementary analytic methods. Furthermore, heterogeneity and pleiotropy tests were carried out. Cochran’s Q-test with IVW and MR-Egger was used to assess heterogeneity. Pleiotropy testing was carried out using the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was also used to evaluate the stability of the findings. Finally, we used migraine (MA and MO) levels to deduce reverse causality with MDD risk.

Results

Random effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (CI), 1.324–1.949, p = 1.52E-06; MDD-MA: OR, 1.400, 95%CI, 1.067–1.8378, p = 0.015; MDD-MO: OR, 1.814, 95%CI, 1.277–2.578, p = 0.0008), indicating a causal relationship between MDD levels and increased risk of migraine (including MA and MO). In the inverse MR analysis, the findings were all negative, while in sensitivity analyses, the results were robust except for the study of MA with MDD.

Conclusion

Our study confirms a causal relationship between MDD levels and increased risk of migraine, MA, and MO. There was little evidence in the reverse MR analysis to suggest a causal genetic relationship between migraine (MA and MO) and MDD risk levels.
Temperature variability increases the onset risk of ischemic stroke: A 10-year study in Tianjin, China
Authors: Chen Zhuangzhuang , Liu Peilin , Xia Xiaoshuang , Wang Lin , Li Xin
Published: April 2023

Background

Epidemiological evidence suggests a correlation between ambient temperature and ischemic stroke. However, evidence on the impact of daily temperature variability on the onset of ischemic stroke is lacking and limited.

Objective

We aimed to investigate the short-term association between temperature variability and ischemic stroke occurrence in Tianjin.

Methods

We performed a 10-year analysis of ischemic stroke patients hospitalized in two affiliated hospitals of Tianjin Medical University from 2011 to 2020. Daily meteorological data were collected from the Tianjin Meteorological Bureau. Temperature variability was calculated from the standard deviation (SD) of daily minimum and maximum temperatures over exposure days. A quasi-Poisson generalized linear regression combined with distributed lag non-linear model (DLNM) was used to estimate the effect of temperature variability on daily stroke onset, while controlling for daily mean temperature, relative humidity, long-term trend and seasonality, public holiday, and day of the week.

Results

Temperature variability was positively associated with ischemic stroke. A 1°C increase in temperature variability at 0–1 days (TV0–1) was associated with a 4.1% (1.9–6.3%) increase of ischemic stroke onset. In a stratified analysis, men, people aged ≤65 years, and individuals with pre-existing hypertension, hyperlipidemia, hyperhomocysteinemia were more susceptible to temperature variability. Furthermore, the influence pattern of temperature variability on ischemic stroke was different in the cold season (November–April) and the warm season (May–October).

Conclusion

Our findings suggested that short-term temperature variability exposure could increase the risk of ischemic stroke, which may provide new insights into the impact of climate change on health.
Additive prognostic impact of the cerebrospinal fluid arginine/ornithine ratio to established clinical scores in aneurysmal subarachnoid hemorrhage
Authors: Weller Johannes , Lampmann Tim , Asoglu Harun , Schneider Matthias , Ehrentraut Stefan Felix , Lehmann Felix , Güresir Erdem , Dorn Franziska , Petzold Gabor C. , Vatter Hartmut , Zimmermann Julian
Published: April 2023

Cerebrospinal fluid (CSF) metabolites are increasingly recognized as prognostic factors in aneurysmal subarachnoid hemorrhage (SAH). The CSF arginine/ornithine ratio (Arg/Orn) was shown to predict cerebral vasospasms and clinical outcome in SAH. The additive prognostic value of Arg/Orn over established prognostic scores has not been investigated. CSF Arg/Orn and the established prognostic scores SAH, FRESH, SAH-PDS, HAIR, Rosen–McDonald, Hunt and Hess, WFNS and modified Fisher scale were determined in a prospective cohort of patients with aneurysmal SAH. Logistic regression models to predict a favorable outcome, defined as a modified Rankin Scale score of 0–3 at 3  months follow-up, were constructed for each score, both with and without the addition of Arg/Orn. The impact of Arg/Orn was assessed comparing logistic regression models containing the respective score with and without Arg/Orn with the likelihood ratio chi-squared test. CSF Arg/Orn and clinical scores were determined in 38 SAH patients. Arg/Orn was an independent predictor of clinical outcome when added to established prognostic scores (p < 0.05) with the exception of HAIR (p = 0.078). All models were significantly improved if Arg/Orn was added as a covariable (p < 0.05). The results of this study confirm Arg/Orn as an independent prognostic factor and its addition improves established prognostic models in SAH.
Should we offer deep brain stimulation to Parkinson’s disease patients with GBA mutations?
Authors: Artusi Carlo Alberto , Lopiano Leonardo
Published: April 2023

Parkinson’s disease (PD) patients who are carriers of glucosylceramidase β1 (GBA1) gene mutations typically have an earlier age at onset and a more aggressive disease course, with a higher burden of neuropsychological issues. The use of deep brain stimulation (DBS) in PD patients with disabling motor fluctuations and absence of dementia is a widespread therapeutic option, often with good results in terms of improvement in activities of daily living and quality of life. Although all PD patients, when fulfilling the common selection criteria for DBS, can benefit from this intervention, some studies have raised attention toward the fact that PD patients who are carriers of GBA1 variants may have a worse DBS outcome possibly due to an accelerated progression of cognitive decline. From this viewpoint, we summarize the current literature, highlighting the knowledge gaps and proposing suggestions for further research as well as for clinical practice in this timeframe of uncertainty related to using DBS in PD patients who are carriers of GBA1 variants.
Deep learning-based algorithm accurately classifies sleep stages in preadolescent children with sleep-disordered breathing symptoms and age-matched controls
Authors: Somaskandhan Pranavan , Leppänen Timo , Terrill Philip I. , Sigurdardottir Sigridur , Arnardottir Erna Sif , Ólafsdóttir Kristín A. , Serwatko Marta , Sigurðardóttir Sigurveig Þ. , Clausen Michael , Töyräs Juha , Korkalainen Henri
Published: April 2023

Introduction

Visual sleep scoring has several shortcomings, including inter-scorer inconsistency, which may adversely affect diagnostic decision-making. Although automatic sleep staging in adults has been extensively studied, it is uncertain whether such sophisticated algorithms generalize well to different pediatric age groups due to distinctive EEG characteristics. The preadolescent age group (10–13-year-olds) is relatively understudied, and thus, we aimed to develop an automatic deep learning-based sleep stage classifier specifically targeting this cohort.

Methods

A dataset (n = 115) containing polysomnographic recordings of Icelandic preadolescent children with sleep-disordered breathing (SDB) symptoms, and age and sex-matched controls was utilized. We developed a combined convolutional and long short-term memory neural network architecture relying on electroencephalography (F4-M1), electrooculography (E1-M2), and chin electromyography signals. Performance relative to human scoring was further evaluated by analyzing intra- and inter-rater agreements in a subset (n = 10) of data with repeat scoring from two manual scorers.

Results

The deep learning-based model achieved an overall cross-validated accuracy of 84.1% (Cohen’s kappa κ = 0.78). There was no meaningful performance difference between SDB-symptomatic (n = 53) and control subgroups (n = 52) [83.9% (κ = 0.78) vs. 84.2% (κ = 0.78)]. The inter-rater reliability between manual scorers was 84.6% (κ = 0.78), and the automatic method reached similar agreements with scorers, 83.4% (κ = 0.76) and 82.7% (κ = 0.75).

Conclusion

The developed algorithm achieved high classification accuracy and substantial agreements with two manual scorers; the performance metrics compared favorably with typical inter-rater reliability between manual scorers and performance reported in previous studies. These suggest that our algorithm may facilitate less labor-intensive and reliable automatic sleep scoring in preadolescent children.
Impact of Donepezil on Brain Glucose Metabolism Assessed Using [18F]2-Fluoro-2-deoxy-D-Glucose Positron Emission Tomography Imaging in a Mouse Model of Alzheimer’s Disease Induced by Intracerebroventricular Injection of Amyloid-Beta Peptide
Authors: Hugon Gaëlle , Goutal Sébastien , Sarazin Marie , Bottlaender Michel , Caillé Fabien , Droguerre Marine , Charvériat Mathieu , Winkeler Alexandra , Tournier Nicolas
Published: April 2023

Graphical Abstract

[18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET imaging was performed in a mouse model of Alzheimer’s disease to investigate the impact of donepezil on brain glucose metabolism.
Peripheral focused ultrasound stimulation and its applications: From therapeutics to human–computer interaction
Authors: Bao Shi-Chun , Li Fei , Xiao Yang , Niu Lili , Zheng Hairong
Published: April 2023

Peripheral focused ultrasound stimulation (pFUS) has gained increasing attention in the past few decades, because it can be delivered to peripheral nerves, neural endings, or sub-organs. With different stimulation parameters, ultrasound stimulation could induce different modulation effects. Depending on the transmission medium, pFUS can be classified as body-coupled US stimulation, commonly used for therapeutics or neuromodulation, or as an air-coupled contactless US haptic system, which provides sensory inputs and allows distinct human-computer interaction paradigms. Despite growing interest in pFUS, the underlying working mechanisms remain only partially understood, and many applications are still in their infancy. This review focused on existing applications, working mechanisms, the latest progress, and future directions of pFUS. In terms of therapeutics, large-sample randomized clinical trials in humans are needed to translate these state of art techniques into treatments for specific diseases. The airborne US for human-computer interaction is still in its preliminary stage, but further efforts in task-oriented US applications might provide a promising interaction tool soon.