bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential impact of environmental factors on systemic and localized autoimmunity
Authors: Touil Hanane , Mounts Kristin , De Jager Philip Lawrence
Published: May 2023

The influence of environmental factors on the development of autoimmune disease is being broadly investigated to better understand the multifactorial nature of autoimmune pathogenesis and to identify potential areas of intervention. Areas of particular interest include the influence of lifestyle, nutrition, and vitamin deficiencies on autoimmunity and chronic inflammation. In this review, we discuss how particular lifestyles and dietary patterns may contribute to or modulate autoimmunity. We explored this concept through a spectrum of several autoimmune diseases including Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE) and Alopecia Areata (AA) affecting the central nervous system, whole body, and the hair follicles, respectively. A clear commonality between the autoimmune conditions of interest here is low Vitamin D, a well-researched hormone in the context of autoimmunity with pleiotropic immunomodulatory and anti-inflammatory effects. While low levels are often correlated with disease activity and progression in MS and AA, the relationship is less clear in SLE. Despite strong associations with autoimmunity, we lack conclusive evidence which elucidates its role in contributing to pathogenesis or simply as a result of chronic inflammation. In a similar vein, other vitamins impacting the development and course of these diseases are explored in this review, and overall diet and lifestyle. Recent work exploring the effects of dietary interventions on MS showed that a balanced diet was linked to improvement in clinical parameters, comorbid conditions, and overall quality of life for patients. In patients with MS, SLE and AA, certain diets and supplements are linked to lower incidence and improved symptoms. Conversely, obesity during adolescence was linked with higher incidence of MS while in SLE it was associated with organ damage. Autoimmunity is thought to emerge from the complex interplay between environmental factors and genetic background. Although the scope of this review focuses on environmental factors, it is imperative to elaborate the interaction between genetic susceptibility and environment due to the multifactorial origin of these disease. Here, we offer a comprehensive review about the influence of recent environmental and lifestyle factors on these autoimmune diseases and potential translation into therapeutic interventions.
Socs3 expression in myeloid cells modulates the pathogenesis of dextran sulfate sodium (DSS)-induced colitis
Authors: Zhou Lianna , Yan Zhaoqi , Yang Wei , Buckley Jessica A. , Al Diffalha Sameer , Benveniste Etty N. , Qin Hongwei
Published: May 2023

Introduction

Myeloid cells play a critical role in the pathogenesis of Inflammatory Bowel Diseases (IBDs), including Ulcerative Colitis (UC) and Crohn’s Disease (CD). Dysregulation of the JAK/STAT pathway is associated with many pathological conditions, including IBD. Suppressors Of Cytokine Signaling (SOCS) are a family of proteins that negatively regulate the JAK/STAT pathway. Our previous studies identified that mice lacking Socs3 in myeloid cells developed a hyper-activated phenotype of macrophages and neutrophils in a pre-clinical model of Multiple Sclerosis.

Methods

To better understand the function of myeloid cell Socs3 in the pathogenesis of colitis, mice with Socs3 deletion in myeloid cells (Socs3ΔLysM) were utilized in a DSS-induced colitis model.

Results

Our results indicate that Socs3 deficiency in myeloid cells leads to more severe colitis induced by DSS, which correlates with increased infiltration of monocytes and neutrophils in the colon and increased numbers of monocytes and neutrophils in the spleen. Furthermore, our results demonstrate that the expression of genes related to the pathogenesis and diagnosis of colitis such as Il1β, Lcn2, S100a8 and S100a9 were specifically enhanced in Socs3-deficient neutrophils localized to the colon and spleen. Conversely, there were no observable differences in gene expression in Ly6C+ monocytes. Depletion of neutrophils using a neutralizing antibody to Ly6G significantly improved the disease severity of DSS-induced colitis in Socs3-deficient mice.

Discussion

Thus, our results suggest that deficiency of Socs3 in myeloid cells exacerbates DSS-induced colitis and that Socs3 prevents overt activation of the immune system in IBD. This study may provide novel therapeutic strategies to IBD patients with hyperactivated neutrophils.
Integrated bioinformatics identifies key mediators in cytokine storm and tissue remodeling during Vibrio mimicus infection in yellow catfish (Pelteobagrus fulvidraco)
Authors: Feng Yang , Wang Jiao , Fan Wei , Geng Yi , Huang Xiaoli , Ouyang Ping , Chen Defang , Guo Hongrui , Deng Huidan , Lai Weimin , Zuo Zhicai
Published: May 2023

Introduction

The pathogenesis of Vibrio mimicus infection in yellow catfish (Pelteobagrus fulvidraco) remains poorly understood, particularly regarding the impact of infection with the pathogen on primary target organs such as the skin and muscle.

Methods

In this study, we aim to analyze the pathological intricacies of the skin and muscle of yellow catfish after being infected with V. mimicus using a 1/10 LC50 seven-day post-infection model. Furthermore, we have utilized integrated bioinformatics to comprehensively elucidate the regulatory mechanisms and identify the key regulatory genes implicated in this phenomenon.

Results

Our histopathological examination revealed significant pathological changes in the skin and muscle, characterized by necrosis and inflammation. Moreover, tissue remodeling occurred, with perimysium degeneration and lesion invasion into the muscle along the endomysium, accompanied by a transformation of type I collagen into a mixture of type I and type III collagens in the perimysium and muscle bundles. Our eukaryotic transcriptomic and 4D label-free analyses demonstrated a predominantly immune pathway response in both the skin and muscle, with downregulation observed in several cell signaling pathways that focused on focal adhesion-dominated cell signaling pathways. The upregulated genes included interleukins (IL)-1 and -6, chemokines, and matrix metallopeptidases (mmp)-9 and -13, while several genes were significantly downregulated, including col1a and col1a1a. Further analysis revealed that these pathways were differentially regulated, with mmp-9 and mmp-13 acting as the potential core regulators of cytokine and tissue remodeling pathways. Upregulation of NF-κB1 and FOSL-1 induced by IL-17C and Nox 1/2-based NADPH oxidase may have held matrix metallopeptidase and cytokine-related genes. Also, we confirmed these relevant regulatory pathways by qPCR and ELISA in expanded samples.

Discussion

Our findings unequivocally illustrate the occurrence of a cytokine storm and tissue remodeling, mediated by interleukins, chemokines, and MMPs, in the surface of yellow catfish infected with V. mimicus. Additionally, we unveil the potential bidirectional regulatory role of MMP-9 and MMP-13. These results provide novel perspectives on the intricate immune response to V. mimicus infection in yellow catfish and highlight potential targets for developing therapies.
CD44 targeted delivery of oncolytic Newcastle disease virus encapsulated in thiolated chitosan for sustained release in cervical cancer: a targeted immunotherapy approach
Authors: Kousar Kousain , Naseer Faiza , Abduh Maisa Siddiq , Anjum Sadia , Ahmad Tahir
Published: May 2023

Introduction

Cervical cancer accounts for one of most common cancers among women of reproductive age. Oncolytic virotherapy has emerged as a promising immunotherapy modality but it comes with several drawbacks that include rapid clearance of virus from body due to immune-neutralization of virus in host. To overcome this, we encapsulated oncolytic Newcastle disease virus (NDV) in polymeric thiolated chitosan nanoparticles. For active targeting of virus loaded nanoformulation against CD44 (cluster of differentiation 44) receptors which are overly expressed on cancer cells, these nanoparticles were surface functionalized with hyaluronic acid (HA).

Methods

Using half dose of NDV (TCID50 (50% tissue culture infective dose) single dose 3 × 105), virus loaded nanoparticles were prepared by green synthesis approach through ionotropic gelation method. Zeta analysis was performed to analyse size and charge on nanoparticles. Nanoparticles (NPs) shape and size were analysed by SEM (scanning electron microscope) and TEM (transmission electron microscope) while functional group identification was done by FTIR (fourier transform infrared) and XRD (X-ray diffraction). Viral quantification was done by TCID50 and Multiplicity of infection (MOI) determination while oncolytic potential of NPs encapsulated virus was analysed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and cell morphology analysis.

Results

Zeta analysis showed that average size of NDV loaded thiolated chitosan nanoparticles surface functionalized with HA (HA-ThCs-NDV) was 290.4nm with zeta potential of 22.3 mV and 0.265 PDI (polydispersity index). SEM and TEM analysis showed smooth surface and spherical features of nanoparticles. FTIR and XRD confirmed the presence of characteristic functional groups and successful encapsulation of the virus. In vitro release showed continuous but sustained release of NDV for up to 48 hours. TCID50 for HA-ThCs-NDV nanoparticles was 2.63x 106/mL titter and the nanoformulation exhibited high oncolytic potential in cell morphology analysis and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay as compared to naked virus, in dose dependent manner.

Discussion

These findings suggest that virus encapsulation in thiolated chitosan nanoparticles and surface functionalization with HA is not only helpful in achieving active targeting while masking virus from immune system but, it also gives sustained release of virus in tumor microenvironment for longer period of time that increases bioavailability of virus.
Elevated sHLA-G plasma levels post chemotherapy combined with ILT-2 rs10416697C allele status of the sHLA-G-related receptor predict poorest disease outcome in early triple-negative breast cancer patients
Authors: Hoffmann Oliver , Wormland Sebastian , Bittner Ann-Kathrin , Hölzenbein Julian , Schwich Esther , Schramm Sabine , Rohn Hana , Horn Peter A. , Kimmig Rainer , Kasimir-Bauer Sabine , Rebmann Vera
Published: May 2023

Introduction

Triple negative breast cancer (TNBC) shows an aggressive growing and spreading behavior and has limited treatment options, often leading to inferior disease outcome. Therefore, surrogate markers are urgently needed to identify patients at high risk of recurrence and more importantly, to identify additional therapeutic targets enabling further treatment options. Based on the key role of the non-classical human leukocyte antigen G (HLA-G) and its related receptor immunoglobulin-like transcript receptor-2 (ILT-2) in immune evasion mechanisms of tumors, members of this ligand-receptor axis appear to be promising tool for both, defining risk groups and potential therapeutic targets.

Materials and methods

To follow this, sHLA-G levels before and after chemotherapy (CT), HLA-G 3’ UTR haplotypes, and allele variations rs10416697 at the distal gene promoter region of ILT-2 were defined in healthy female controls and early TNBC patients. The results obtained were associated with clinical status, presence of circulating tumor cell (CTC) subtypes, and disease outcome of patients in terms of progression-free or overall survival.

Results

sHLA-G plasma levels were increased in TNBC patients post-CT compared to levels of patients pre-CT or controls. High post-CT sHLA-G levels were associated with the development of distant metastases, the presence of ERCC1 or PIK3CA-CTC subtypes post-CT, and poorer disease outcome in uni- or multivariate analysis. HLA-G 3’ UTR genotypes did not influence disease outcome but ILT-2 rs10416697C allele was associated with AURKA-positive CTC and with adverse disease outcome by uni- and multivariate analysis. The prognostic value of the combined risk factors (high sHLA-G levels post-CT and ILT-2 rs10416697C allele carrier status) was an even better independent indicator for disease outcome in TNBC than the lymph nodal status pre-CT. This combination allowed the identification of patients with high risk of early progression/death with positive nodal status pre-CT or with non-pathological complete therapy response

Conclusion

The results of this study highlight for the first time that the combination of high levels of sHLA-G post-CT with ILT-2 rs10416697C allele receptor status is a promising tool for the risk assessment of TNBC patients and support the concept to use HLA-G/ILT-2 ligand-receptor axis as therapeutic targets.
Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome
Authors: Jandl Katharina , Berg Johannes Lorenz , Birnhuber Anna , Fliesser Elisabeth , Borek Izabela , Seeliger Benjamin , David Sascha , Schmidt Julius J. , Gorkiewicz Gregor , Zacharias Martin , Welte Tobias , Olschewski Horst , Heinemann Akos , Wygrecka Malgorzata , Kwapiszewska Grazyna
Published: May 2023

Background

Immune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragments is mostly unknown. Here, we investigate the role of endostatin, a fragment of the BM protein collagen XVIIIα1, on ARDS associated cellular functions such as neutrophil recruitment, endothelial cell barrier integrity, and platelet aggregation in vitro.

Methods

In our study we analyzed endostatin in plasma and post-mortem lung specimens of patients with COVID-19 and non-COVID-19 ARDS. Functionally, we investigated the effect of endostatin on neutrophil activation and migration, platelet aggregation, and endothelial barrier function in vitro. Additionally, we performed correlation analysis for endostatin and other critical plasma parameters.

Results

We observed increased plasma levels of endostatin in our COVID-19 and non-COVID-19 ARDS cohort. Immunohistochemical staining of ARDS lung sections depicted BM disruption, alongside immunoreactivity for endostatin in proximity to immune cells, endothelial cells, and fibrinous clots. Functionally, endostatin enhanced the activity of neutrophils, and platelets, and the thrombin-induced microvascular barrier disruption. Finally, we showed a positive correlation of endostatin with soluble disease markers VE-Cadherin, c-reactive protein (CRP), fibrinogen, and interleukin (IL)-6 in our COVID-19 cohort.

Conclusion

The cumulative effects of endostatin on propagating neutrophil chemotaxis, platelet aggregation, and endothelial cell barrier disruption may suggest endostatin as a link between those cellular events in ARDS pathology.
A case report of early diagnosis of asymptomatic hairy cell leukemia using flow cytometry
Authors: Tadros James , Davis Amanda , Awoleye Oreoluwa , Vassiliou Evros
Published: May 2023

Hairy Cell Leukemia is an infrequent leukemia that can be recognized both microscopically and flow cytometrically once the patient develops symptoms. We present a case where early diagnosis was achieved using flow cytometry long before the patient became symptomatic. This was achieved by focusing on a small percentage (0.9%) of total leukocytes that exhibited a higher side scatter and brighter CD19/CD20 than the remaining lymphocytes. A bone marrow aspirate three weeks later confirmed the presence of malignant B-cells. Shortly after, the patient presented splenomegaly and complained of fatigue.
Growth variability in Atlantic horse mackerel Trachurus trachurus (Linneus, 1758) across the central Mediterranean Sea: contrasting latitudinal gradient and different ecosystems
Authors: Basilone Gualtiero , Ferreri Rosalia , Aronica Salvatore , Bonanno Angelo , Genovese Simona , Rumolo Paola , Carbonara Pierluigi , Barra Marco
Published: May 2023

Data on Atlantic horse mackerel Trachurus trachurus (Linneus, 1758) were collected along 8-year acoustic surveys (2011-2018). Age and growth variability of horse mackerel from the Central Mediterranean Sea were investigated within different, contrasting habitats, from the south of Sicily to the north Tyrrhenian (Ligurian Sea). Data from satellite provided the habitat features along the study period over the whole surveyed area. For comparison purposes, according to the ecosystems difference the study area has been split into four subareas: Strait of Sicily (SoS), North of Sicily (NS), south Tyrrhenian Sea (ST) and north Tyrrhenian Sea (NT). In terms of the FAO Geographical Sub-Area definition the SoS corresponding to GSA15 and 16, NS to GSA 10 south, ST to GSA10 north and NT to GSA 9. Results showed a growth homogeneity in the study area, suggesting a unique stock inhabiting these waters. The only exception was recorded for juveniles (Age 0 class) in the SoS, where a lower size at age was detected compared to other areas. A multiple linear modelling analyses suggested that variability in length at age 0 was mainly linked to the oceanographic differences between an upwelling driven system (Strait of Sicily) and the other ecosystems, where enrichment processes are mainly due to river runoff (relevant in ST and NT). Namely, Absolute Dynamic Topography (ADT) and body condition factor (Kn) were significantly related to differences in length at age 0. Results revealed that currents (and gyres) are among the principal abiotic factors controlling Atlantic horse mackerel growth in its first year of life, suggesting that circulation and food-related processes (i.e., zooplankton concentration) are of major importance for this species. Finally preliminary observations suggest the Strait of Sicily may be the main spawning area among those analyzed.
A new procedure for autonomous acquisition of photosynthesis-irradiance curves on a microphytobenthic biofilm
Authors: Meresse Marvin , Gevaert François , Duong Gwendoline , Denis Lionel
Published: May 2023

Despite their high productivity and their key role in coastal processes, microphytobenthic biofilm studies remain relatively scarce because in situ, meteorological hazards make it difficult to acquire reproducible measurements, also due to difficulties in properly reproducing field conditions in the laboratory. Therefore, in order to better understand the processes of microphytobenthic primary production, we have developed an automated laboratory system and procedure with variable light intensity, with a large number of replicates. This article aims to provide a description of the creation of a P-I curve based on a total of 128 vertical profiles recorded on a sediment core taken in situ, placed in the automated system and studied under controlled conditions of temperature and air humidity while light intensity was varied automatically, thus allowing to work in standard and replicable conditions. With measured production levels of up to 14.68 ± 3.70 mmol O2.m-2.h-1 and a productivity of 0.06 ± 0.01 mmol O2.m-2.h-1 per gram of Chl a corresponding to what is generally found in temperate environments, we have shown that our system is suitable for high frequency measurements and, by combining surficial measurements of modulated fluorescence and oxygen microprofiling in sediments, complementary information from a large dataset on photosynthetic and microphytobenthic migratory activity may be obtained under standard conditions. The development of this tool has made it possible to highlight a stabilization time for oxygen fluxes. For our study conducted in a temperate environment, we observed a time lag of a few minutes that should be considered when acquiring PE curves in the laboratory to study microphytobenthic photosynthetic capacities. This tool also allowed to describe microphytobenthic migration in response to light exposure, with successive steps observed through fluorescence and oxygen profiles. First, microphytobenthos migrated towards the surface until the optimal intensity of production at 475 µmol photons.m-2.s-1, then from this intensity as well as towards 780 µmol photons.m-2.s-1, downwards migratory movements were detected. This system is a working basis which can open interesting perspectives for the study of the effect of other abiotic (or biotic) parameters.
A bioenergetics approach to modelling tolerance limits under acute thermal stress in farmed finfish
Authors: Stavrakidis-Zachou Orestis , Papandroulakis Nikos , Lika Konstadia
Published: May 2023

Pinpointing thermal tolerance thresholds for commercially important species, such as aquaculture finfish, under acute and chronic thermal stress is becoming increasingly relevant in the context of climate change. While experimental research, traditionally quantified by the determination of the Critical Thermal Maximum (CTmax), offers valuable insights, it is necessary to further develop appropriate tools to provide predictions and shed light on the underlying mechanisms of thermal tolerance. Bioenergetic models have long been used to study the effects of temperature on fish metabolism under chronic, but rarely under acute, scales. In this study, we present a modelling approach based on the Dynamic Energy Budget (DEB) theory that describes the tolerance limits of fish under acute thermal stress in bioenergetics terms. It adopts the notion of an energy-dependent tolerance to stress and defines acute tolerance limits at the intersection of fundamental energy fluxes, namely those relating to the mobilization of energy and to maintenance costs. To showcase this approach, DEB models for two finfish, the European sea bass (Dicentrarchus labrax) and the meagre (Argyrosomus regius) were used to run acute thermal challenge simulations and study shifts in the critical temperature achieved by the fish. The results suggest that the model can adequately capture the general tolerance patterns observed experimentally for the two species as well as pinpoint the parameters that may influence them. In particular, the simulations showed a positive relation between acclimation temperature and tolerance while the opposite stands for the body size of the fish, with smaller fish achieving higher critical temperatures than their larger counterparts. Also, tolerance limits were affected by the state of internal reserves, with well-fed fish exhibiting higher values. Finally, the potential application of this modelling approach on higher taxonomic scales was evaluated, by running simulations on species belonging to major fish orders. The preliminary results suggest that the method can capture differences among groups that are consistent with literature, suggesting it may be a realistic mechanistic approach for studying thermal tolerance in ectotherms.
A standardised ecosystem services framework for the deep sea
Authors: La Bianca Giulia , Rees Sian , Attrill Martin J. , Lombard Amanda T. , McQuaid Kirsty A. , Niner Holly J. , van Rein Henk , Sink Kerry J. , Howell Kerry L.
Published: May 2023

Despite its remoteness, human activity has impacted the deep sea and changes to the structure and function of deep-sea ecosystems are already noticeable. In terrestrial and shallow water marine environments, demonstrating how ecosystems support human well-being has been instrumental in setting policy and management objectives for sustainable resource use. Foundational to this approach is a framework of ecosystem service (ES) classification and a synthesis of the knowledge base, which can then be used to structure decision-support tools such as ecosystem accounts or Environmental Impact Assessments. At present, no such framework exists for the deep sea. There is thus an urgent need to determine and assess the ES provided by deep-sea habitats and species before (potentially irreversible) decisions are made about deep-sea habitat use and governance. As a first step towards the incorporation of ES in such decision-making, we undertake two systematic reviews of the scientific literature based on the principles of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) systematic process. This was to define a comparative ES framework and synthesise the current evidence base for how deep-sea habitats support ecosystem services. Our framework proposes four supporting services, three regulating services, four provisioning services and three cultural services for which there is an established and growing body of evidence for the role of deep-sea habitats. The ES framework presented here provides a structure for deep-sea ecosystem services. In its next phase of development, this could provide the foundation for the development of habitat-ecosystem service matrices, which are a critical component for truly accounting for ES in decision-making, particularly spatial management. This framework has significant implications for deep-sea management, conservation and policy, as it provides an ecosystem services-based tool that can be used in any deep-sea ecosystems management across the planet, and it also shows how critical these data gaps are for today’s decisions and how seriously they should be considered in decision-making processes.
Establishment and validation of a clinical nomogram model based on serum YKL-40 to predict major adverse cardiovascular events during hospitalization in patients with acute ST-segment elevation myocardial infarction
Authors: Fang Caoyang , Li Jun , Wang Wei , Wang Yuqi , Chen Zhenfei , Zhang Jing
Published: May 2023

Objective

This study aimed to investigate the predictive value of a clinical nomogram model based on serum YKL-40 for major adverse cardiovascular events (MACE) during hospitalization in patients with acute ST-segment elevation myocardial infarction (STEMI).

Methods

In this study, 295 STEMI patients from October 2020 to March 2023 in the Second People’s Hospital of Hefei were randomly divided into a training group (n = 206) and a validation group (n = 89). Machine learning random forest model was used to select important variables and multivariate logistic regression was included to analyze the influencing factors of in-hospital MACE in STEMI patients; a nomogram model was constructed and the discrimination, calibration, and clinical effectiveness of the model were verified.

Results

According to the results of random forest and multivariate analysis, we identified serum YKL-40, albumin, blood glucose, hemoglobin, LVEF, and uric acid as independent predictors of in-hospital MACE in STEMI patients. Using the above parameters to establish a nomogram, the model C-index was 0.843 (95% CI: 0.79–0.897) in the training group; the model C-index was 0.863 (95% CI: 0.789–0.936) in the validation group, with good predictive power; the AUC (0.843) in the training group was greater than the TIMI risk score (0.648), p < 0.05; and the AUC (0.863) in the validation group was greater than the TIMI risk score (0.795). The calibration curve showed good predictive values and observed values of the nomogram; the DCA results showed that the graph had a high clinical application value.

Conclusion

In conclusion, we constructed and validated a nomogram based on serum YKL-40 to predict the risk of in-hospital MACE in STEMI patients. This model can provide a scientific reference for predicting the occurrence of in-hospital MACE and improving the prognosis of STEMI patients.
Role of melatonin in enhancing arbuscular mycorrhizal symbiosis and mitigating cold stress in perennial ryegrass (Lolium perenne L.)
Authors: Wei Hongjian , Wang Jiajin , Wang Qi , He Wenyuan , Liao Songkai , Huang Jiahao , Hu Wentao , Tang Ming , Chen Hui
Published: May 2023

Melatonin is a biomolecule that affects plant development and is involved in protecting plants from environmental stress. However, the mechanisms of melatonin’s impact on arbuscular mycorrhizal (AM) symbiosis and cold tolerance in plants are still unclear. In this research, AM fungi inoculation and exogenous melatonin (MT) were applied to perennial ryegrass (Lolium perenne L.) seedlings alone or in combination to investigate their effect on cold tolerance. The study was conducted in two parts. The initial trial examined two variables, AM inoculation, and cold stress, to investigate the involvement of the AM fungus Rhizophagus irregularis in endogenous melatonin accumulation and the transcriptional levels of its synthesis genes in the root system of perennial ryegrass under cold stress. The subsequent trial was designed as a three-factor analysis, encompassing AM inoculation, cold stress, and melatonin application, to explore the effects of exogenous melatonin application on plant growth, AM symbiosis, antioxidant activity, and protective molecules in perennial ryegrass subjected to cold stress. The results of the study showed that compared to non-mycorrhizal (NM) plants, cold stress promoted an increase in the accumulation of melatonin in the AM-colonized counterparts. Acetylserotonin methyltransferase (ASMT) catalyzed the final enzymatic reaction in melatonin production. Melatonin accumulation was associated with the level of expression of the genes, LpASMT1 and LpASMT3. Treatment with melatonin can improve the colonization of AM fungi in plants. Simultaneous utilization of AM inoculation and melatonin treatment enhanced the growth, antioxidant activity, and phenylalanine ammonia-lyase (PAL) activity, while simultaneously reducing polyphenol oxidase (PPO) activity and altering osmotic regulation in the roots. These effects are expected to aid in the mitigation of cold stress in Lolium perenne. Overall, melatonin treatment would help Lolium perenne to improve growth by promoting AM symbiosis, improving the accumulation of protective molecules, and triggering in antioxidant activity under cold stress.
Metagenomic analysis reveals gut plasmids as diagnosis markers for colorectal cancer
Authors: Cai Zhiyuan , Li Ping , Zhu Wen , Wei Jingyue , Lu Jieyu , Song Xiaoyi , Li Kunwei , Li Sikai , Li Man
Published: May 2023

Background

Colorectal cancer (CRC) is linked to distinct gut microbiome patterns. The efficacy of gut bacteria as diagnostic biomarkers for CRC has been confirmed. Despite the potential to influence microbiome physiology and evolution, the set of plasmids in the gut microbiome remains understudied.

Methods

We investigated the essential features of gut plasmid using metagenomic data of 1,242 samples from eight distinct geographic cohorts. We identified 198 plasmid-related sequences that differed in abundance between CRC patients and controls and screened 21 markers for the CRC diagnosis model. We utilize these plasmid markers combined with bacteria to construct a random forest classifier model to diagnose CRC.

Results

The plasmid markers were able to distinguish between the CRC patients and controls [mean area under the receiver operating characteristic curve (AUC = 0.70)] and maintained accuracy in two independent cohorts. In comparison to the bacteria-only model, the performance of the composite panel created by combining plasmid and bacteria features was significantly improved in all training cohorts (mean AUCcomposite = 0.804 and mean AUCbacteria = 0.787) and maintained high accuracy in all independent cohorts (mean AUCcomposite = 0.839 and mean AUCbacteria = 0.821). In comparison to controls, we found that the bacteria-plasmid correlation strength was weaker in CRC patients. Additionally, the KEGG orthology (KO) genes in plasmids that are independent of bacteria or plasmids significantly correlated with CRC.

Conclusion

We identified plasmid features associated with CRC and showed how plasmid and bacterial markers could be combined to further enhance CRC diagnosis accuracy.
Time-restricted feeding affects colonic nutrient substrates and modulates the diurnal fluctuation of microbiota in pigs
Authors: Wang Hongyu , Li Qiuke , Xu Rongying , Su Yong , Zhu Weiyun
Published: May 2023

Introduction

Studies demonstrate that time-restricted feeding (TRF) can regulate gut microbiota composition. However, it is unclear whether TRF could affect the gut microbial rhythmicity in growing pigs. Therefore, the present study aimed to explore the effects of TRF on the dynamic fluctuation of the gut microbiota.

Methods

A total of 10 healthy growing pigs equipped with T cannula were employed. Pigs were randomly allotted to the free access (FA) and the TRF groups with 5 replicates (1 pig/replicates). Pigs in the FA group were fed free access during the whole experimental period, whereas pigs in the TRF group were fed free access three times per day within limited times (7:00–8:00, 12:00–13:00, 17:00–18:00). The experiment lasted for 15 days, at 06:00 a.m. of the day 16, colonic digesta were collected at a 6-h interval for consecutive 24 h marked as T06 (06:00), T12 (12:00), T18 (18:00), T24 (24:00), T30 (06:00), respectively.

Results

Results showed that TRF altered the distribution of feed intake without changing the total feed intake within a day (p = 0.870). TRF decreased the overall concentration of colonic cellulose and altered their oscillating patterns. All alpha-diversity indexes of different time points showed significant differences regardless of feeding pattern with a trough at T18 or T24. TRF shifted the trough of the alpha-diversity index Simpson and Invsimpson. TRF lost the rhythmicity of Prevotellaceae, Ruminococcaceae, Bacteroidales_S24-7_group, and Peptococcaceae and gained the rhythmicity of Pasteurellaceae, Clostridiaceae_1, Veillonellaceae, and Peptostreptococcaceae. Also, TRF altered the interaction pattern by increasing the microbes involved in the co-occurrence network and their crosstalk, especially at T24. Interestingly, the microbial variation at T24 could largely explained by colonic substrates starch (R2 = 0.369; p = 0.001), cellulose (R2 = 0.235; p = 0.009) and NH4-N (R2 = 0.489; p = 0.001).

Conclusion

In conclusion, TRF has changed the concentrates of cellulose and the relative abundance of specific microbes and certain microbial metabolites. In addition, TRF has more powerful effects on the fluctuation modes of these nutrient substrates, microbes, and metabolites by shifting their peaks or troughs. This knowledge facilitates the development of precision regulation targeting gut microbial rhythmicity.
Pilot testing the EARS-Vet surveillance network for antibiotic resistance in bacterial pathogens from animals in the EU/EEA
Authors: Lagrange Justine , Amat Jean-Philippe , Ballesteros Cristina , Damborg Peter , Grönthal Thomas , Haenni Marisa , Jouy Eric , Kaspar Heike , Kenny Kevin , Klein Babette , Lupo Agnese , Madec Jean-Yves , Salomonsen Charlotte Mark , Müller Elisabeth , Madero Cristina Muñoz , Nilsson Oskar , Norström Madelaine , Nykäsenoja Suvi , Overesch Gudrun , Pedersen Karl , Pohjanvirta Tarja , Slowey Rosemarie , Justo Cristiana Teixeira , Urdahl Anne Margrete , Zafeiridis Christos , Zini Eric , Cazeau Géraldine , Jarrige Nathalie , Collineau Lucie
Published: May 2023

Introduction

As part of the EU Joint Action on Antimicrobial Resistance (AMR) and Healthcare-Associated Infections, an initiative has been launched to build the European AMR Surveillance network in veterinary medicine (EARS-Vet). So far, activities included mapping national systems for AMR surveillance in animal bacterial pathogens, and defining the EARS-Vet objectives, scope, and standards. Drawing on these milestones, this study aimed to pilot test EARS-Vet surveillance, namely to (i) assess available data, (ii) perform cross-country analyses, and (iii) identify potential challenges and develop recommendations to improve future data collection and analysis.

Methods

Eleven partners from nine EU/EEA countries participated and shared available data for the period 2016–2020, representing a total of 140,110 bacterial isolates and 1,302,389 entries (isolate-antibiotic agent combinations).

Results

Collected data were highly diverse and fragmented. Using a standardized approach and interpretation with epidemiological cut-offs, we were able to jointly analyze AMR trends of 53 combinations of animal host-bacteria–antibiotic categories of interest to EARS-Vet. This work demonstrated substantial variations of resistance levels, both among and within countries (e.g., between animal host species).

Discussion

Key issues at this stage include the lack of harmonization of antimicrobial susceptibility testing methods used in European surveillance systems and veterinary diagnostic laboratories, the absence of interpretation criteria for many bacteria–antibiotic combinations of interest, and the lack of data from a lot of EU/EEA countries where little or even surveillance currently exists. Still, this pilot study provides a proof-of-concept of what EARS-Vet can achieve. Results form an important basis to shape future systematic data collection and analysis.
Investigation of brain iron levels in Chinese patients with Alzheimer’s disease
Authors: Huang Chuanbin , Li Jing , Liu Chang , Zhang Yong , Tang Qiqiang , Lv Xinyi , Ruan Mengyue , Deng Kexue
Published: May 2023

Introduction

We aimed (i) to explore the diagnostic value of deep gray matter magnetic susceptibility in Alzheimer’s disease (AD) in China and (ii) to analyze its correlation with neuropsychiatric scales. Moreover, we conducted subgroup analysis based on the presence of the APOE-ε4 gene to improve the diagnosis of AD.

Methods

From the prospective studies of the China Aging and Neurodegenerative Initiative (CANDI), a total of 93 subjects who could undergo complete quantitative magnetic susceptibility imaging and APOE-ε4 gene detection were selected. Differences in quantitative susceptibility mapping (QSM) values between and within groups, including AD patients, individuals with mild cognitive impairment (MCI), and healthy controls (HCs), both APOE-ε4 carriers and non-carriers, were analyzed.

Results

In primary analysis, the magnetic susceptibility values of the bilateral caudate nucleus and right putamen in the AD group and of the right caudate nucleus in the MCI group were significantly higher than those in the HCs group (P < 0.05). In APOE-ε4 non-carriers, there were significant differences in more regions between the AD, MCI, and HCs groups, such as the left putamen and the right globus pallidus (P < 0.05). In subgroup analysis, the correlation between QSM values in some brain regions and neuropsychiatric scales was even stronger.

Discussion

Exploration of the correlation between deep gray matter iron levels and AD may provide insight into the pathogenesis of AD and facilitate early diagnosis in elderly Chinese. Further subgroup analysis based on the presence of the APOE-ε4 gene may further improve the diagnostic efficiency and sensitivity.
Association of age of adverse childhood experiences with thalamic volumes and post-traumatic stress disorder in adulthood
Authors: Huffman Nickelas , Shih Chia-Hao , Cotton Andrew S. , Lewis Terrence J. , Grider Stephen , Wall John T. , Wang Xin , Xie Hong
Published: May 2023

Background

Adverse childhood experiences (ACEs) have been linked to brain development and mental disorders, however, the impact of the age of occurrence of ACEs on thalamic volume and post-traumatic stress disorder (PTSD) after adult trauma remains unclear. This study assessed associations between ACEs at different ages to thalamic volumes and PTSD development following acute adult trauma.

Methods

Seventy-nine adult trauma survivors were recruited immediately after trauma. Within 2 weeks of the traumatic event, participants completed the PTSD Checklist (PCL) to assess PTSD symptoms, the Childhood Trauma Questionnaire (CTQ) and Childhood Age Range Stress Scale (CARSS) to evaluate ACEs and perceived stress level at preschool (<6 years old) and school (6–13 years old) ages, and structural magnetic resonance imaging (sMRI) to measure thalamic volumes. Participants were divided into three groups: those who experienced no childhood trauma or stress (non-ACEs), those who experienced childhood trauma and stress onset at preschool ages (Presch-ACEs), and those who experienced childhood trauma and stress onset at school ages (Sch-ACEs). At 3 months, participants underwent PTSD symptom evaluation using the Clinician Administered PTSD Scale (CAPS).

Results

Adult trauma survivors in the Presch-ACEs group had higher CTQ and CAPS scores. In addition, survivors in the Presch-ACEs group had smaller thalamic volume compared to survivors in the non-ACEs and Sch-ACEs groups. Furthermore, smaller thalamic volume moderated a positive association between post-trauma 2-week PCL and subsequent 3-month CAPS scores.

Discussion

Earlier occurrence of ACEs was associated with smaller thalamic volume, which appears to moderate a positive association between early posttraumatic stress symptom severity and PTSD development after adult trauma. This raises the possibility that early occurrence of ACEs may impact thalamic structure, specifically a reduction in thalamic volume, and that smaller thalamic volume may contribute to susceptibility to PTSD development after adult trauma.
Multimodal transformer augmented fusion for speech emotion recognition
Authors: Wang Yuanyuan , Gu Yu , Yin Yifei , Han Yingping , Zhang He , Wang Shuang , Li Chenyu , Quan Dou
Published: May 2023

Speech emotion recognition is challenging due to the subjectivity and ambiguity of emotion. In recent years, multimodal methods for speech emotion recognition have achieved promising results. However, due to the heterogeneity of data from different modalities, effectively integrating different modal information remains a difficulty and breakthrough point of the research. Moreover, in view of the limitations of feature-level fusion and decision-level fusion methods, capturing fine-grained modal interactions has often been neglected in previous studies. We propose a method named multimodal transformer augmented fusion that uses a hybrid fusion strategy, combing feature-level fusion and model-level fusion methods, to perform fine-grained information interaction within and between modalities. A Model-fusion module composed of three Cross-Transformer Encoders is proposed to generate multimodal emotional representation for modal guidance and information fusion. Specifically, the multimodal features obtained by feature-level fusion and text features are used to enhance speech features. Our proposed method outperforms existing state-of-the-art approaches on the IEMOCAP and MELD dataset.
Neural Synchronization, Chimera States and Sleep Asymmetry
Authors: Glaze Tera A. , Bahar Sonya
Published: May 2023

We model the dynamics of sleep states in two connected model brain hemispheres, using groups of coupled individual Hindmarsh-Rose neural oscillators. In a single isloated hemisphere, sleep-promoting neurons and wake-promoting neurons exhibit alternating levels of within-group mean field activity, as well as alternating levels of stochastic phase synchronization, as the system moves between simulated day and night. In a two-hemisphere model, we find differences in the behavior of the sleep-promototing or wake-promoting regions between hemispheres, indicative of chimera-like behavior. We observe phase-cluster states, in which different hemispheres exhibit different bursting dynamics, as well as differences in synchronization between hemispheres. This provides a basis for modeling unihemispheric sleep, which occurs naturally in cetaceans and some bird species, among others, as well as asymmetric sleep, which occurs in human subjects suffering from sleep apnea or experiencing the “first night effect” induced by sleeping in a novel environment.
Epileptic seizure detection with deep EEG features by convolutional neural network and shallow classifiers
Authors: Zeng Wei , Shan Liangmin , Su Bo , Du Shaoyi
Published: May 2023

Introduction

In the clinical setting, it becomes increasingly important to detect epileptic seizures automatically since it could significantly reduce the burden for the care of patients suffering from intractable epilepsy. Electroencephalography (EEG) signals record the brain's electrical activity and contain rich information about brain dysfunction. As a non-invasive and inexpensive tool for detecting epileptic seizures, visual evaluation of EEG recordings is labor-intensive and subjective and requires significant improvement.

Methods

This study aims to develop a new approach to recognize seizures automatically using EEG recordings. During feature extraction of EEG input from raw data, we construct a new deep neural network (DNN) model. Deep feature maps derived from layers placed hierarchically in a convolution neural network are put into different kinds of shallow classifiers to detect the anomaly. Feature maps are reduced in dimensionality using Principal Component Analysis (PCA).

Results

By analyzing the EEG Epilepsy dataset and the Bonn dataset for epilepsy, we conclude that our proposed method is both effective and robust. These datasets vary significantly in the acquisition of data, the formulation of clinical protocols, and the storage of digital information, making processing and analysis challenging. On both datasets, extensive experiments are performed using a cross-validation by 10 folds strategy to demonstrate approximately 100% accuracy for binary and multi-category classification.

Discussion

In addition to demonstrating that our methodology outperforms other up-to-date approaches, the results of this study also suggest that it can be applied in clinical practice as well.
Temporal dynamics of Na/K pump mediated memory traces: insights from conductance-based models of Drosophila neurons
Authors: Megwa Obinna F. , Pascual Leila May , Günay Cengiz , Pulver Stefan R. , Prinz Astrid A.
Published: May 2023

Sodium potassium ATPases (Na/K pumps) mediate long-lasting, dynamic cellular memories that can last tens of seconds. The mechanisms controlling the dynamics of this type of cellular memory are not well understood and can be counterintuitive. Here, we use computational modeling to examine how Na/K pumps and the ion concentration dynamics they influence shape cellular excitability. In a Drosophila larval motor neuron model, we incorporate a Na/K pump, a dynamic intracellular Na+ concentration, and a dynamic Na+ reversal potential. We probe neuronal excitability with a variety of stimuli, including step currents, ramp currents, and zap currents, then monitor the sub- and suprathreshold voltage responses on a range of time scales. We find that the interactions of a Na+-dependent pump current with a dynamic Na+ concentration and reversal potential endow the neuron with rich response properties that are absent when the role of the pump is reduced to the maintenance of constant ion concentration gradients. In particular, these dynamic pump-Na+ interactions contribute to spike rate adaptation and result in long-lasting excitability changes after spiking and even after sub-threshold voltage fluctuations on multiple time scales. We further show that modulation of pump properties can profoundly alter a neuron’s spontaneous activity and response to stimuli by providing a mechanism for bursting oscillations. Our work has implications for experimental studies and computational modeling of the role of Na/K pumps in neuronal activity, information processing in neural circuits, and the neural control of animal behavior.