bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential responses to maternal diabetes in embryo and visceral yolk sac
Authors: Salbaum J. Michael , Stone Kirsten P. , Kruger Claudia , Kappen Claudia
Published: October 2023

Introduction: Maternal diabetes during pregnancy is well known to be associated with a higher risk for structural birth defects in the offspring. Recent searches for underlying mechanisms have largely focused on aberrant processes in the embryo itself, although prior research in rodent models implicated dysfunction also of the visceral yolk sac. The objective of our research was to investigate both tissues within the conceptus simultaneously.

Methods: We conducted unbiased transcriptome profiling by RNA sequencing on pairs of individual yolk sacs and their cognate embryos, using the non-obese diabetic (NOD) mouse model. The analysis was performed at gestational day 8.5 on morphologically normal specimen to circumvent confounding by defective development.

Results: Even with large sample numbers (n = 33 in each group), we observed considerable variability of gene expression, primarily driven by exposure to maternal diabetes, and secondarily by developmental stage of the embryo. Only a moderate number of genes changed expression in the yolk sac, while in the embryo, the exposure distinctly influenced the relationship of gene expression levels to developmental progression, revealing a possible role for altered cell cycle regulation in the response. Also affected in embryos under diabetic conditions were genes involved in cholesterol biosynthesis and NAD metabolism pathways.

Discussion: Exposure to maternal diabetes during gastrulation changes transcriptomic profiles in embryos to a substantially greater effect than in the corresponding yolk sacs, indicating that despite yolk sac being of embryonic origin, different mechanisms control transcriptional activity in these tissues. The effects of maternal diabetes on expression of many genes that are correlated with developmental progression (i.e. somite stage) highlight the importance of considering developmental maturity in the interpretation of transcriptomic data. Our analyses identified cholesterol biosynthesis and NAD metabolism as novel pathways not previously implicated in diabetic pregnancies. Both NAD and cholesterol availability affect a wide variety of cellular signaling processes, and can be modulated by diet, implying that prevention of adverse outcomes from diabetic pregnancies may require broad interventions, particularly in the early stages of pregnancy.
Precipitation forecasting: from geophysical aspects to machine learning applications
Authors: Oliveira Ewerton Cristhian Lima de , Nogueira Neto Antonio Vasconcelos , Santos Ana Paula Paes dos , da Costa Claudia Priscila Wanzeler , Freitas Julio Cezar Gonçalves de , Souza-Filho Pedro Walfir Martins , Rocha Rafael de Lima , Alves Ronnie Cley , Franco Vânia dos Santos , Carvalho Eduardo Costa de , Tedeschi Renata Gonçalves
Published: October 2023

Intense precipitation events pose a significant threat to human life. Mathematical and computational models have been developed to simulate atmospheric dynamics to predict and understand these climates and weather events. However, recent advancements in artificial intelligence (AI) algorithms, particularly in machine learning (ML) techniques, coupled with increasing computer processing power and meteorological data availability, have enabled the development of more cost-effective and robust computational models that are capable of predicting precipitation types and aiding decision-making to mitigate damage. In this paper, we provide a comprehensive overview of the state-of-the-art in predicting precipitation events, addressing issues and foundations, physical origins of rainfall, potential use of AI as a predictive tool for forecasting, and computational challenges in this area of research. Through this review, we aim to contribute to a deeper understanding of precipitation formation and forecasting aided by ML algorithms.
Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids
Authors: Todo Hiroaki , Niki Rina , Okada Akie , Narita Ibuki , Inamura Kazuya , Ito Ayu , Itakura Shoko , Hijikuro Ichiro , Sugibayashi Kenji
Published: October 2023

Non-lamellar liquid crystal (NLLC) structures have gained increasing attention for the controlled release of entrapped drugs. In the present study, an in situ NLLC structure-forming depot formulation through contact with water was developed using a ternary mixture system of soya phosphatidyl choline (SPC), 1, 2-dioleoyl-sn-glycero-3-phosphoglycerol sodium salt (DOPG), and sorbitan trioleate (Span 85), and the long-term release of an entrapped model drug, leuprolide acetate (LA), was investigated using evaluation of in vitro release and in vivo blood concentration–time profiles. Polarized images and small angle X-ray scattering analysis were used to confirm the presence of NLLC structures by contacting the prepared formulation with water. In addition, LA release and blood concentration–time profiles were investigated using in vitro and in vivo experiments, respectively. In situ NLLC constructed formulations by contacting water were achieved using a ternary mixture of SPC, DOPG, and Span 85. In particular, negative curvature was increased with an increase in the amount of Span 85 in the formulation, and an Fd3m structure was obtained with a sustained release of LA. A maintained blood concentration of LA over 21 days was confirmed by subcutaneous (s.c.) administration of the formulation. No retained administered formulation at the injection site was confirmed 28 days after administration without any signs of irritation, inflammation, or other apparent toxicity confirmed by visual observation. This result may be helpful for the development of a lipid-based formulation of peptides and proteins with sustained drug release.
Numerical simulations of pure quasi-P-waves in orthorhombic anisotropic media
Authors: Wang Hao , Huang Jianping , Yang Jidong , Shen Yi
Published: October 2023

The accurate simulation of anisotropic media is critical in seismic imaging and inversion. In recent years, some scholars have dedicated efforts to the study of precise elastic waves in anisotropic media; however, it is easy to separate P-wave and S-wave from elastic wave fields in isotropic media but difficult to separate them in anisotropic media. To address this issue, others have proposed pseudo-pure-wave equations based on the theory of wave-mode separation, but shear wave interference still exists. Therefore, we derived the first-order pure quasi-P-wave equation with no shear wave component in orthorhombic anisotropic media (ORT) which is common in the Earth’s crust and has very important research value. The presence of a pseudodifferential operator in the equation poses a challenge for solving. In order to solve the pure wave equation, we decomposed the original pseudodifferential operator into an elliptic differential operator and a scalar operator, both of which are easily solvable. In addition, we extended the equation from ORT media to tilted ORT (TORT) media. The example results indicate that our pure quasi-P-wave equation can yield a more stable and accurate P-wave field. The pure wave equation we propose can be applied in reverse time migration (RTM), the least squares RTM (LSRTM), and even the full waveform inversion (FWI).
Worry effect for COVID-19 transmission over depression, anxiety, and satisfaction with studies in Peruvian university students
Authors: Mamani-Benito Oscar , Carranza Esteban Renzo Felipe , Castillo-Blanco Ronald , Lingán-Huamán Susana K. , Gálvez-Díaz Norma del Carmen , Huancahuire-Vega Salomón , Corrales-Reyes Ibraín Enrique
Published: October 2023

Introduction

Concern about contracting COVID-19 has had repercussions on university students. The aim of this study was to determine its effect on depression, anxiety, and satisfaction with studies.

Methods

Using an explanatory cross-sectional design, 1,260 medical, nursing, and dentistry students from both public and private universities in Peru participated in this study. They were assessed using a scale for concern about contracting COVID-19, the Patient Health Questionnaire-2, the Generalized Anxiety Disorder-2 (GAD-2), and a brief scale for satisfaction with their studies.

Results

After analyzing the data using structural equation modeling, it was found that the explanatory model had an adequate fit. It showed that concern about COVID-19 had a direct and significant effect on anxiety (β = 0.46, p < 0.001) and depression (β = 0.38, p < 0.001). However, the same effect was not evident on satisfaction with studies (β = −0.06, p = 0.068).

Discussion

The uncertainty about contracting COVID-19 triggered symptoms of anxiety and depression among Peruvian university students. Still, it did not affect the satisfaction students felt when their academic expectations were met.
KRT17 from skin cells with high glucose stimulation promotes keratinocytes proliferation and migration
Authors: Zhou Peng , Feng Haijun , Qin Wenhui , Li Qin
Published: October 2023

Impaired diabetic wound healing is an important issue in diabetic complications. Proliferation and migration of keratinocytes are major processes of skin wound repair after injury. However, hyperkeratosis can affect the speed of wound healing. Based on the results of preliminary experiments on increased KRT17 expression after high glucose stimulation of human skin tissue cells, a cell model of human immortalized keratinocyte (HaCaT) stimulation with different concentrations of KRT17 was established in vitro, and the promotion in cell proliferation and migration were discovered. KRT17 silencing promoted diabetic wound healing in the db/db diabetic wound model. Transcriptome sequencing (RNA-seq) was performed on HaCaT cells after KRT17 stimulation, and analysis showed significant enrichment in the PI3K-AKT signaling pathway, in which the regulation of cell c-MYB mRNA, a key molecule regulating cell proliferation and migration, was significantly upregulated. In vitro assays showed increased c-MYB expression and enhanced pAKT activity after HaCaT cell stimulation by KRT17. We speculate that KRT17 is upregulated under high glucose and promotes keratinocyte proliferation and migration caused hyperkeratosis, through the c-MYB/PI3K-AKT pathway, contributing to delayed wound healing.
Empowering solar photovoltaic logistic operations through cloud-enabled blockchain technology: a sustainable approach
Authors: Pan HongYu , Bayanati Mahmonir , Vaseei Masoud , Chobar Adel Pourghader
Published: October 2023

In a world where renewable energy solutions are in high demand, solar photovoltaic (PV) systems are at the forefront, emphasizing the need for efficient and eco-friendly logistics. This coincides with the rise of blockchain technology as a game-changer in PV system management. Additionally, cloud computing is playing a pivotal role in transforming the IT landscape, providing seamless access to shared computing resources via the Internet. This research introduces a novel framework that utilizes cloud computing to enhance blockchain-based PV logistics. It employs a sophisticated mathematical model to optimize logistics components such as transportation, storage, inventory management, and supply chain coordination, with the goal of minimizing costs and improving overall efficiency. At the heart of this transformative paradigm lies a visionary cloud-based system, endowing PV logistic planners with the power of real-time access to mission-critical data. This infusion of data-driven decision-making capabilities fosters a seamless symphony of communication and enriches collaboration among stakeholders, setting the stage for monumental shifts in efficiency and management, ushering in a new era of sustainability and scalability within the photovoltaic industry. This technological synergy is not just about immediate gains. It is a testament to our commitment to improved energy sustainability and a testament to our shared vision of a greener future. In lockstep with the global pursuit of renewable energy solutions, this research lights the way toward a brighter, more sustainable tomorrow.
Features of the TCR repertoire associate with patients' clinical and molecular characteristics in acute myeloid leukemia
Authors: Pospiech Mateusz , Tamizharasan Mukund , Wei Yu-Chun , Kumar Advaith Maya Sanjeev , Lou Mimi , Milstein Joshua , Alachkar Houda
Published: October 2023

Background

Allogeneic hematopoietic stem cell transplant remains the most effective strategy for patients with high-risk acute myeloid leukemia (AML). Leukemia-specific neoantigens presented by the major histocompatibility complexes (MHCs) are recognized by the T cell receptors (TCR) triggering the graft-versus-leukemia effect. A unique TCR signature is generated by a complex V(D)J rearrangement process to form TCR capable of binding to the peptide-MHC. The generated TCR repertoire undergoes dynamic changes with disease progression and treatment.

Method

Here we applied two different computational tools (TRUST4 and MIXCR) to extract the TCR sequences from RNA-seq data from The Cancer Genome Atlas (TCGA) and examine the association between features of the TCR repertoire in adult patients with AML and their clinical and molecular characteristics.

Results

We found that only ~30% of identified TCR CDR3s were shared by the two computational tools. Yet, patterns of TCR associations with patients’ clinical and molecular characteristics based on data obtained from either tool were similar. The numbers of unique TCR clones were highly correlated with patients’ white blood cell counts, bone marrow blast percentage, and peripheral blood blast percentage. Multivariable regressions of TCRA and TCRB median normalized number of unique clones with mutational status of AML patients using TRUST4 showed significant association of TCRA or TCRB with WT1 mutations, WBC count, %BM blast, and sex (adjusted in TCRB model). We observed a correlation between TCRA/B number of unique clones and the expression of T cells inhibitory signal genes (TIGIT, LAG3, CTLA-4) and foxp3, but not IL2RA, CD69 and TNFRSF9 suggestive of exhausted T cell phenotypes in AML.

Conclusion

Benchmarking of computational tools is needed to increase the accuracy of the identified clones. The utilization of RNA-seq data enables identification of highly abundant TCRs and correlating these clones with patients’ clinical and molecular characteristics. This study further supports the value of high-resolution TCR-Seq analyses to characterize the TCR repertoire in patients.
A gonadal gap junction INX-14/Notch GLP-1 signaling axis suppresses gut defense through an intestinal lysosome pathway
Authors: Zhang Xiumei , Wang Yirong , Cai Zixin , Wan Zhiqing , Aihemaiti Yilixiati , Tu Haijun
Published: October 2023

Gap junctions mediate intercellular communications across cellular networks in the nervous and immune systems. Yet their roles in intestinal innate immunity are poorly understood. Here, we show that the gap junction/innexin subunit inx-14 acts in the C. elegans gonad to attenuate intestinal defenses to Pseudomonas aeruginosa PA14 infection through the PMK-1/p38 pathway. RNA-Seq analyses revealed that germline-specific inx-14 RNAi downregulated Notch/GLP-1 signaling, while lysosome and PMK-1/p38 pathways were upregulated. Consistently, disruption of inx-14 or glp-1 in the germline enhanced resistance to PA14 infection and upregulated lysosome and PMK-1/p38 activity. We show that lysosome signaling functions downstream of the INX-14/GLP-1 signaling axis and upstream of PMK-1/p38 pathway to facilitate intestinal defense. Our findings expand the understanding of the links between the reproductive system and intestinal defense, which may be evolutionarily conserved in higher organism.
Combinatorial blockade for cancer immunotherapy: targeting emerging immune checkpoint receptors
Authors: Roy Dia , Gilmour Cassandra , Patnaik Sachin , Wang Li Lily
Published: October 2023

The differentiation, survival, and effector function of tumor-specific CD8+ cytotoxic T cells lie at the center of antitumor immunity. Due to the lack of proper costimulation and the abundant immunosuppressive mechanisms, tumor-specific T cells show a lack of persistence and exhausted and dysfunctional phenotypes. Multiple coinhibitory receptors, such as PD-1, CTLA-4, VISTA, TIGIT, TIM-3, and LAG-3, contribute to dysfunctional CTLs and failed antitumor immunity. These coinhibitory receptors are collectively called immune checkpoint receptors (ICRs). Immune checkpoint inhibitors (ICIs) targeting these ICRs have become the cornerstone for cancer immunotherapy as they have established new clinical paradigms for an expanding range of previously untreatable cancers. Given the nonredundant yet convergent molecular pathways mediated by various ICRs, combinatorial immunotherapies are being tested to bring synergistic benefits to patients. In this review, we summarize the mechanisms of several emerging ICRs, including VISTA, TIGIT, TIM-3, and LAG-3, and the preclinical and clinical data supporting combinatorial strategies to improve existing ICI therapies.
Learning from Caretta caretta (Linnaeus, 1758) epibionts: a study from the Adriatic Sea
Authors: Baruffaldi Matilde , Rubini Silva , Ignoto Sara , Angelini Valeria , Tiralongo Francesco
Published: October 2023

Epibiont communities can be used as useful ecological indicators, providing information on the ecology and health conditions of their hosts. In this study, we analyzed the cirriped community from a total of 117 dead specimens of Caretta caretta (Linnaeus, 1758) collected in the north Adriatic between the years 2020 and 2022. We recorded a total of six different species distributed in five genera of cirripeds. The two most abundant species were Chelonibia testudinaria (Linnaeus, 1758) and Platylepas hexastylos (Linnaeus, 1758), located in different areas of the body; the former mainly on the carapace, while the latter mainly on the skin. We analyzed their abundance and distribution pattern on the sea turtle’s body and used the findings to deduce the health conditions and ecological aspects of stranded specimens of C. caretta, providing new data on this threatened and vulnerable species and its epibionts. A total of 11 specimens of C. caretta were affected by DTS (Debilitative Turtle Syndrome), these specimens exhibited a significant barnacle infestation on all body parts, markedly higher than the specimens of C. caretta not affected by DTS. Studies of associated barnacles in sea turtles should be encouraged among researchers as complementary tool to infer habitat use and health status of sea turtle species.
Flow cytometry methods for targeted isolation of ctenophore cells
Authors: Dieter Abigail C. , True Aliyah B. K. , Gilbertson Emily A. , Snyder Grace , Lacy-Hulbert Adam , Traylor-Knowles Nikki , Browne William E. , Vandepas Lauren E.
Published: October 2023

Cell suspension fluidics, such as flow cytometry (FCS) and fluorescence-activated cell sorting (FACS), facilitates the identification and precise separation of individual cells based on phenotype. Since its introduction, flow cytometry has been used to analyze cell types and cellular processes in diverse non-vertebrate taxa, including cnidarians, molluscs, and arthropods. Ctenophores, which diverged very early from the metazoan stem lineage, have emerged as an informative clade for the study of metazoan cell type evolution. We present standardized methodologies for flow cytometry-mediated identification and analyses of cells from the model ctenophore Mnemiopsis leidyi that can also be applied to isolate targeted cell populations. Here we focus on the identification and isolation of ctenophore phagocytes. Implementing flow cytometry methods in ctenophores allows for fine scale analyses of fundamental cellular processes conserved broadly across animals, as well as potentially revealing novel cellular phenotypes and behaviors restricted to the ctenophore lineage.
From modern-day parasitology to paleoparasitology: the elusive past record and evolution of Cryptosporidium
Authors: Roche Kévin , Dalle Frédéric , Capelli Nicolas , Borne Romain , Jouffroy-Bapicot Isabelle , Valot Benoit , Grenouillet Frédéric , Le Bailly Matthieu
Published: October 2023

Recent efforts have been made to review the state of the art on a variety of questions and targets in paleoparasitology, including protozoan taxa. Meanwhile, these efforts seemed to let aside Cryptosporidium, and we then intended to review its paleoparasitological record to assess its past distribution and favored detection methods, and eventually highlight needed research trajectories. This review shows that contrary to other parasites, most of the positive results came from South-American sites and coprolites rather than sediment samples, highlighting the need to test this kind of material, notably in Europe where many negative results were reported in the published literature from sediment samples. Moreover, aDNA-based detections are nearly absent from the paleoparasitological record of this parasite, though punctually shown successful. With their potential to address the evolutionary history of Cryptosporidium species, notably through their 18S rRNA tree, aDNA-based approaches should be encouraged in the future. In sum, and though the limits of currently used methods and materials remain unclear, this review highlights the potential role of coprolites and aDNA for the study of Cryptosporidium species in the past and how this history shaped their current diversity and distribution, notably among human populations but also farm animals.
Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?
Authors: Shapiro Leland , Scherger Sias , Franco-Paredes Carlos , Gharamti Amal , Henao-Martinez Andrés F.
Published: October 2023

Introduction

The European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) announced conditions for using recombinant human interleukin-1 receptor antagonist (rhIL-1ra) to treat hospitalized patients with Coronavirus disease 2019 (COVID-19) and risk for progression. These decisions followed publication of the suPAR-guided Anakinra treatment for Validation of the risk and early Management OF seveRE respiratory failure by COVID-19 (SAVE- MORE) phase 3 clinical trial that yielded positive results.

Methods

We conducted a literature review and theoretical analysis of IL-1 blockade as a therapy to treat COVID-19. Using a stepwise analysis, we assessed clinical applicability of the SAVE-MORE results and evaluated conceptual support for interleukin-1 suppression as a suitable approach to COVID-19 treatment. This therapeutic approach was then examined as an example of inflammation-suppressing measures used to treat sepsis.

Results

Anakinra use as a COVID-19 therapy seems to rely on a view of pathogenesis that incorrectly reflects human disease. Since COVID-19 is an example of sepsis, COVID-19 benefit due to anti-inflammatory therapy contradicts an extensive history of unsuccessful clinical study. Repurposing rhIL-1ra to treat COVID-19 appears to exemplify a cycle followed by inflammation-suppressing sepsis treatments. A landscape of treatment failures is interrupted by a successful clinical trial. However, subsequent confirmatory study fails to replicate the positive data.

Discussion

We suggest further experimentation is not a promising pathway to discover game-changing sepsis therapies. A different kind of approach may be necessary.
Lignan-containing maple products inhibit Listeria monocytogenes biofilms on fresh produce
Authors: Elbakush Ahmed M. , Fulano Alex M. , Gomelsky Mark
Published: October 2023

Major listeriosis outbreaks have been associated with fresh produce contaminated with Listeria monocytogenes. Strains that synthesize the Pss exopolysaccharide (EPS) have an estimated 102 to 104-fold advantage over nonsynthesizing strains in causing listeriosis. They more readily attach to the surfaces of fruit and vegetables forming EPS-biofilms that better withstand stresses associated with produce storage and consumption. Here, we show that the threat to fresh produce safety posed by the listerial EPS-biofilms may be countered by broadly available maple products. We serendipitously discovered that aqueous extracts of wood from several Acer (maple) and Carya (pecan, hickory) species inhibit the formation of listerial EPS-biofilms without affecting bacterial viability. One active ingredient in maple wood was identified as nortrachelogenin-8’-O-β-D-glucopyranoside (NTG). At 120 μM, this lignan decreased colonization of the EPS-synthesizing L. monocytogenes on cantaloupe pieces by approximately 150-fold, and on cut celery and lettuce by 10 to 11-fold. Another lignan, lariciresinol, which is abundant in a common food sweetener, maple syrup, had antibiofilm activity comparable to that of NTG. Diluted in the range of 1:200 to 1:800 maple syrup from two random manufacturers prevented formation of listeiral EPS-biofilms. Importantly, not only did maple products drastically decrease colonization of fresh produce by the EPS-synthesizing strains, they also decreased, by 6 to 30-fold, colonization by the L. monocytogenes strains that do not synthesize measurable EPS, including strains from the infamous 2011 cantaloupe listeriosis outbreak. Inhibition of surface colonization by various listerial strains, broad availability of maple sap and syrup as well as maple lumber processing waste position maple products as potential antibiofilm agents for protecting fresh produce from L. monocytogenes.
Human tumor viruses: induction of three-dimensional alterations in the host genome structure
Authors: Minarovits Janos
Published: October 2023

Certain viruses called tumor viruses or oncoviruses are capable to change the gene expression pattern of distinct human or animal cell types in tissue culture, resulting in uncontrolled proliferation as well as a change in the social behavior of the infected cells: the oncovirus-transformed, immortalized cells are capable to form malignant neoplasms in suitable animal models. At present, seven human viruses are categorized as causative agents of distinct human malignancies. The genomes of human tumor viruses, typically encode viral oncoproteins and non– translated viral RNAs that affect the gene expression pattern of their target cells or induce genetic and epigenetic alterations contributing to oncogenesis. Recently, the application of chromatin conformation capture technologies and three-dimensional (3D) molecular imaging techniques revealed how the gene products or genomes of certain human tumor viruses interact with and induce alterations in the 3D host genome structure. This Mini Review aims to cover selected aspects of these developments. The papers, discussed briefly, describe how insertion of a novel viral binding site for the 3D genome organizer cellular protein CCCTC-binding factor (CTCF) into the DNA of T cells infected by human T-cell lymphotropic virus type 1 (HTLV-1) may contribute to lymphomagenesis, as well as how integration of high risk human papillomavirus genome into the host cell DNA may facilitate cervical carcinogenesis. Recent results regarding the interactions of cellular genomes with the episomal, chromatinized DNA genomes of oncogenic human herpesvirus, Epstein–Barr virus (EBV) will also be summarized, similarly to available data regarding contacts formed by episomal or integrated hepatitis B virus (HBV) DNA with host chromatin. Finally, a putative mechanism of hepatitis C virus (HCV) induced chromatin alterations will be presented, which may solve the riddle, how a cytoplasmic RNA virus without a viral oncogene could induce malingnant transfrormation of hepatocytes.
The role of chicken eggs in modulating sarcopenic obesity and gut microbiota in db/db mice
Authors: Okamura Takuro , Hasegawa Yuka , Hamaguchi Masahide , Sasano Ryoichi , Fukui Michiaki
Published: October 2023

Background

Sarcopenia obesity, in which loss of muscle mass and fat accumulation occur simultaneously, is the pathological basis of type 2 diabetes mellitus. The usefulness of chicken eggs in sarcopenia prevention has been reported in several previous studies. The purpose of this study was to determine the beneficial effects of chicken eggs in the prevention of sarcopenic obesity in db/db mice.

Methods

We raised 8-week-old db/db male mice, a model of sarcopenia obesity, for 8 weeks and fed them a diet mixed with dried whole eggs. The fecal microbiota transplant (FMT) group was treated with antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age.

Results

Eggs administered to db/db mice showed increased grip strength (p = 0.022) and muscle mass (p = 0.013), decreased visceral fat mass (p = 0.005), and significantly increased physical activity (p < 0.001). The FMT group of egg-fed mice showed a significant improvement in glucose intolerance and sarcopenic obesity. Sequencing of gene expression in the small intestine showed that the gene expression of amino acid transporters such as Slc6a18, Slc6a19, and Slc38a6 was increased in egg-fed mice. 16S rRNA sequencing of the gut microbiota showed an increase in the genus Vampirovibrio in both the egg-fed and FMT groups compared to that in egg-fed mice.

Conclusion

The results of this study indicate that egg consumption not only increases the intake of amino acids and other nutrients but also alters the intestinal microbiota and increases amino acid absorption from the intestinal tract, suggesting that eggs might contribute to the ameliorative mechanism of sarcopenic obesity.
The causality between gut microbiome and anorexia nervosa: a Mendelian randomization analysis
Authors: Xia Xuan , He Shu-yang , Zhang Xiao-Lin , Wang Decheng , He Qian , Xiao Qing-Ao , Yang Yong
Published: October 2023

Background and aim

Nutrient production by intestinal microbiota corresponds to regulate appetite while gut microbial composition was influenced by diet ingestion. However, the causal relationship between gut microbial taxa and anorexia nervosa (AN) remains unclear. Mendelian Randomization (MR) is a novel research method that effectively eliminates the interference of confounding factors and allows for the exploration of the direct causal effects between exposure and outcome. This study employs MR to explore the causal effect between AN and specific gut microbiome.

Methods

Large-scale Genome Wide Association Study (GWAS) data of AN and 211 gut microbes were obtained from the IEU open GWAS project and Mibiogen Consortium. Two-sample MR was performed to determine the causal relationship between gut microbiota and AN. Furthermore, a bi-directional MR analysis was to examine the direction of the causal relations. The Bonferroni correction test was used to adjust potential correlations among microbial taxa.

Result

In forward MR analysis, 10specific gut microbial taxa have an impact on the occurrence of AN (the p value of IVW <0.05). The high abundance of Genus Eubacteriumnodatumgroup ID: 11297 (OR:0.78, 95% CI:0.62–0.98, p = 0.035) and Class Melainabacteria ID: 1589 (OR:0.72, 95% CI:0.51–0.99, p = 0.045) may be considered protective factors for AN. But after Bonferroni correction, only Class Actinobacteria ID:419 (OR:1.53, 95% CI:1.19–1.96, p = 0.00089) remained significantly associated and high abundance of Class Actinobacteria ID:419 considered as a risk factor for AN. In the reverse MR analysis, AN influences 8 gut microbial taxa with none-statistically significant associations after adjustment.

Conclusion

We identified a significant correlation between AN and 18 microbial taxa which have not been previously reported. Among them, 10 kinds of gut bacteria may affect the occurrence of AN, and the status of AN would affect 8 kinds of gut bacteria. After correction, the Class Actinobacteria ID:419 continued to exert an influence on AN.
Live-cell imaging of endocytosed synaptophysin around individual hippocampal presynaptic active zones
Authors: Tanaka Hiromitsu , Funahashi Junichiro , Hirano Tomoo
Published: October 2023

In presynaptic terminals 4 types of endocytosis, kiss-and-run, clathrin-mediated, bulk and ultrafast endocytosis have been reported to maintain repetitive exocytosis of neurotransmitter. However, detailed characteristics and relative contribution of each type of endocytosis still need to be determined. Our previous live-cell imaging study demonstrated individual exocytosis events of synaptic vesicle within an active-zone-like membrane (AZLM) formed on glass using synaptophysin tagged with a pH-sensitive fluorescent protein. On the other hand, individual endocytosis events of postsynaptic receptors were recorded with a rapid extracellular pH exchange method. Combining these methods, here we live-cell imaged endocytosed synaptophysin with total internal reflection fluorescence microscopy in rat hippocampal culture preparations. Clathrin-dependent and -independent endocytosis, which was seemingly bulk endocytosis, occurred within several seconds after electrical stimulation at multiple locations around AZLM at room temperature, with the locations varying trial to trial. The contribution of clathrin-independent endocytosis was more prominent when the number of stimulation pulses was large. The skewness of synaptophysin distribution in intracellular vesicles became smaller after addition of a clathrin inhibitor, which suggests that clathrin-dependent endocytosis concentrates synaptophysin. Ultrafast endocytosis was evident immediately after stimulation only at near physiological temperature and was the predominant endocytosis when the number of stimulation pulses was small.
Containment control of multiple unmanned surface vessels with NN control via reconfigurable hierarchical topology
Authors: Liu Wei , Teng Fei , Xiao Huiyu , Wang Chen
Published: October 2023

This paper investigates the containment control of multiple unmanned surface vessels with nonlinear dynamics. To solve the leader-follower synchronization problem in a containment control system, a hierarchical control framework with a topology reconfiguration mechanism is proposed, and the process of containment control is converted into the tracking of a reference signal for each vessel on its respective target heading by means of the light-of-sight (LOS) guidance. In a control system, the neural networks (NNs) are adopted to consider the uncertainty. In the follower layer, a connectivity controller with a topology reconfiguration mechanism is embedded, to change the converging positions of followers so as to avoid collision within the system, and to maintain the system connectivity when the communication equality is poor. The effectiveness of the hierarchical control framework proposed in this paper is valid by simulation.
Interacting information streams on the nephron arterial network
Authors: Marsh Donald J. , Wexler Anthony S. , Holstein-Rathlou Niels-Henrik
Published: October 2023

Blood flow and glomerular filtration in the kidney are regulated by two mechanisms acting on the afferent arteriole of each nephron. The two mechanisms operate as limit cycle oscillators, each responding to a different signal. The myogenic mechanism is sensitive to a transmural pressure difference across the wall of the arteriole, and tubuloglomerular feedback (TGF) responds to the NaCl concentration in tubular fluid flowing into the nephron’s distal tubule,. The two mechanisms interact with each other, synchronize, cause oscillations in tubular flow and pressure, and form a bimodal electrical signal that propagates into the arterial network. The electrical signal enables nephrons adjacent to each other in the arterial network to synchronize, but non-adjacent nephrons do not synchronize. The arteries supplying the nephrons have the morphologic characteristics of a rooted tree network, with 3 motifs characterizing nephron distribution. We developed a model of 10 nephrons and their afferent arterioles in an arterial network that reproduced these structural characteristics, with half of its components on the renal surface, where experimental data suitable for model validation is available, and the other half below the surface, from which no experimental data has been reported. The model simulated several interactions: TGF-myogenic in each nephron with TGF modulating amplitude and frequency of the myogenic oscillation; adjacent nephron-nephron with strong coupling; non-adjacent nephron-nephron, with weak coupling because of electrical signal transmission through electrically conductive arterial walls; and coupling involving arterial nodal pressure at the ends of each arterial segment, and between arterial nodes and the afferent arterioles originating at the nodes. The model predicted full synchronization between adjacent nephrons pairs and partial synchronization among weakly coupled nephrons, reproducing experimental findings. The model also predicted aperiodic fluctuations of tubular and arterial pressures lasting longer than TGF oscillations in nephrons, again confirming experimental observations. The model did not predict complete synchronization of all nephrons.
The value of computed tomography perfusion deficit volumes in acute isolated brainstem infarction
Authors: Chen Pengjun , Pan Yiying , Wang Jingke , Hui Junguo , Gao Ruijie , Lin Guihan , Li Bingrong , Rao Jie , Xia Shuiwei , Ji Jiansong
Published: October 2023

Purpose

Diagnosis of acute isolated brainstem infarction is challenging owing to non-specific, variable symptoms, and the effectiveness of non-contrast computed tomography (NCCT) is poor owing to limited spatial resolution and artifacts. Computed tomography perfusion (CTP) imaging parameters are significantly associated with functional outcomes in posterior circulation acute ischemic stroke; however, the role of CTP in isolated brainstem infarction remains unclear. We aimed to determine the value of CTP imaging parameters in predicting functional outcomes for affected patients.

Methods

In total, 116 consecutive patients with isolated pontine/midbrain hypoperfusion who underwent CTP and follow-up by magnetic resonance imaging (MRI) between January 2018 and March 2022, were retrospectively analyzed. Perfusion deficit volumes on all maps, and the final infarction volume (FIV) on MRI were quantified. “Good” functional outcome was defined as a 90-day modified Rankin Scale score of 0 and 1. Statistical analysis included uni- and multivariate regression analyses, binary logistic regressions, and receiver operating characteristics (ROC) analyses.

Results

In total, 113 patients had confirmed isolated pontine/midbrain infarction on follow-up MRI. Onset-to-scan time, visibility of ischemic lesions on NCCT, the baseline National Institutes of Health Stroke Scale (NIHSS) score, and perfusion deficit volumes on all CTP maps were significantly associated with FIV (p < 0.05). In a multivariate linear regression model, adjusted for age, sex, NIHSS score, onset-to-scan time, and visibility of NCCT, perfusion deficit volumes remained significantly associated with FIV. In binary logistic regression analyses, perfusion deficit volumes on all CTP maps remained independent predictors of a good functional outcome. In ROC analyses, the cerebral blood flow deficit volume showed a slightly higher discriminatory value with the largest area under the curve being 0.683 [(95% CI, 0.587–0.780), p = 0.001].

Conclusion

Perfusion deficit volumes of CTP imaging could reflect the FIV and contain prognostic information on functional outcomes in patients with acute isolated brainstem infarction.
Case report: Successful autologous hematopoietic stem cell transplantation in a patient with GAD antibody-spectrum disorder with rapidly progressive dementia
Authors: Disserol Caio César Diniz , Kowacs Dora Pedroso , Nabhan Samir Kanaan , Teive Hélio Afonso Ghizoni , Kowacs Pedro André
Published: October 2023

The prevalence of neurological syndromes associated with antibodies to glutamic acid decarboxylase is increasing. While cognitive impairment is a common feature of this condition, it seldom emerges as the primary symptom. In this study, we discuss a case of refractory dementia associated with the glutamic acid decarboxylase spectrum disorder. Interestingly, this case showed a favorable outcome following autologous hematopoietic stem cell transplantation. We also provide an in-depth review of the current literature on the use of this therapeutic approach for the treatment of this disease.
Effect of acupuncture on pain and substance P levels in middle-aged women with chronic neck pain
Authors: Ko Jade Heejae , Kim Seung-Nam
Published: October 2023

Chronic neck pain is a leading health issue affecting a significant proportion of the global population. Multiple treatment options for chronic neck pain include anti-inflammatory drugs and analgesics. Acupuncture has been widely used for the treatment of chronic pain. In this study, we aimed to determine the efficacy of acupuncture for female patients with chronic neck pain. Twenty-three participants were enrolled in the study, and participants waited 4 weeks without acupuncture treatment and then received 4 weeks of treatment. One-way ANOVA with repeated measures was used to determine differences in the visual analogue scale (VAS), neck disability index (NDI), and substance P (SP) over time. The subjects’ pain intensity and degree of disability due to neck pain were measured as primary outcomes. SP in the blood was also analyzed as a secondary outcome. There was no significant difference between the VAS score and NDI value of baseline and after 4 weeks waiting. However, there was an improvement in both VAS and NDI after 4 weeks treatment. SP level was decreased after 4 weeks treatment. We could conclude that acupuncture is effective in alleviating chronic neck pain. Moreover, our findings revealed the efficacy of acupuncture on chronic pain with potential underlying biological mechanisms.
Structural–functional coupling abnormalities in temporal lobe epilepsy
Authors: Huang Xiaoting , Du Yangsa , Guo Danni , Xie Fangfang , Zhou Chunyao
Published: October 2023

Background

Nowadays, researchers are using advanced multimodal neuroimaging techniques to construct the brain network connectome to elucidate the complex relationship among the networks of brain functions and structure. The objective of this study was to evaluate the coupling of structural connectivity (SC) and functional connectivity (FC) in the entire brain of healthy controls (HCs), and to investigate modifications in SC–FC coupling in individuals suffering from temporal lobe epilepsy (TLE).

Methods

We evaluated 65 patients with TLE matched for age and gender with 48 healthy controls. The SC–FC coupling between regions was determined, based on which whole-brain nodes were clustered. Differences in the coupling among the three groups of nodes were compared. To further validate the results obtained, the within-cluster coupling indices of the three groups were compared to determine the inter-group differences.

Results

Nodes were divided into five clusters. Cluster 1 was primarily located in the limbic system (n = 9/27), whereas cluster 5 was mainly within the visual network (n = 12/29). By comparing average cluster SC–FC coupling in each cluster of the three groups, we identified marked discrepancies within the three cohorts in Cluster 3 (p = 0.001), Cluster 4 (p < 0.001), and Cluster 5 (p < 0.001). Post-hoc analysis revealed that the SC–FC coupling strengths in LTLE and RTLE were significantly lower than that in HCs in Cluster 3 (PL = 0.001/PR = 0.003), Cluster 4 (PL = 0.001/PR < 0.001), and Cluster 5 (PL < 0.001/PR < 0.001). We also observed that the within-cluster SC–FC coupling in cluster 5 of left- and right TLE was significantly lower than in HCs (PL = 0.0001, PR = 0.0005).

Conclusion

The SC and FC are inconsistently coupled across the brain with spatial heterogeneity. In the fifth cluster with the highest degree of coupling in HCs, the average SC–FC coupling index of individuals with TLE was notably less than that of HCs, manifesting that brain regions with high coupling may be more delicate and prone to pathological disruption.
Non-invasive brain stimulation for fibromyalgia: current trends and future perspectives
Authors: Zhang Jia-Hao , Liang Jian , Yang Zhong-Wei
Published: October 2023

Fibromyalgia, a common and enduring pain disorder, ranks as the second most prevalent rheumatic disease after osteoarthritis. Recent years have witnessed successful treatment using non-invasive brain stimulation. Transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsion therapy have shown promise in treating chronic pain. This article reviews the literature concerning non-invasive stimulation for fibromyalgia treatment, its mechanisms, and establishes a scientific basis for rehabilitation, and discusses the future directions for research and development prospects of these techniques are discussed.
Synapse-associated protein 102 – a highly mobile MAGUK predominate in early synaptogenesis
Authors: De Los Reyes Dominique Alexandra , Karkoutly Mohammad Yaman , Zhang Yonghong
Published: October 2023

Neurodevelopmental and neurodegenerative disorders are primarily characterized by serious structural and functional changes in excitatory glutamatergic synapses in the brain, resulting in many synaptic deficits and aberrant synapse loss. It is a big challenge to reverse these synaptic impairments as a treatment for neurological diseases in the field. Extensive research on glutamate receptors as therapeutic targets has been done but with little success shown in human trials. PSD-95-like MAGUK proteins perform a pivotal role in regulating the trafficking and stability of glutamate receptors that are important to postsynaptic structure and function. MAGUK and MAGUK-modulated synaptic pathways are becoming promising candidates for developing therapeutic targets. As a MAGUK protein, SAP102 is not understood well compared to PSD-95. Here, we review the current research on SAP102 including its synaptic functions and regulation, especially its expression and functions in the early stage of synaptogenesis and the association with neurodevelopmental disorders. This review presents valuable information for future structural and functional studies of SAP102 to reveal its roles in young and mature neurons. It provides clues for developing potential remedies to reverse synaptic impairments and strategies to grow new neurons.