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1.
PLoS One ; 19(5): e0303235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728287

RESUMEN

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes-Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3-were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment.


Asunto(s)
Autofagia , Galectina 3 , Aprendizaje Automático , Neuronas , Animales , Neuronas/metabolismo , Ratas , Galectina 3/metabolismo , Galectina 3/genética , Ratas Sprague-Dawley , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/genética , Mapas de Interacción de Proteínas , Ácido Glutámico/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética
2.
Reproduction ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38744310

RESUMEN

Previous studies from our group and others have shown increased IncRNA H19 expression in both the eutopic endometrium and the ectopic endometriosis tissue during endometriosis. In this study, we use immunofluorescence, immunohistochemistry and protein quantification to determine that levels of aerobic glycolysis and histone lactylation; which we show are increased in endometriosis tissues. In HESC cells (Human Endometrial Stromal Cells), we found that high H19 expression resulted in abnormal glucose metabolism by examining the levels of glucose, lactate, and ATP and measuring protein levels of enzymes that participate in glycolysis. At the same time, immunofluorescence and western blotting demonstrated increased histone lactylation in H19 overexpressing cells. Altering aerobic glycolysis and histone lactylation levels through the addition of Nala (sodium lactate) and 2-DG demonstrated that increased aerobic glycolysis and histone lactylation levels resulted in enhanced cell proliferation and cell migration, contributing to endometriosis. To validate these findings in vivo, we constructed an endometriosis mouse model, demonstrating similar changes in endometriosis tissues in vivo. Both aerobic glycolysis and histone lactylation levels were elevated in endometriotic lesions. Taken together, these data demonstrate elevated expression levels of H19 in endometriosis patients promote abnormal glucose metabolism and elevated histone lactylation levels in vivo, enhancing cell proliferation and migration and promoting the progression of endometriosis. Our study provides a functional link between H19 expression and histone lactylation and glucose metabolism in endometriosis, providing new insights into disease mechanisms that could result in novel therapeutic approaches.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38709609

RESUMEN

Developing a distributed bipartite optimal consensus scheme while ensuring user-predefined performance is essential in practical applications. Existing approaches to this problem typically require a complex controller structure due to adopting an identifier-actor-critic framework and prescribed performance cannot be guaranteed. In this work, an adaptive critic learning (ACL)-based optimal bipartite consensus scheme is developed to bridge the gap. A newly designed error scaling function, which defines the user-predefined settling time and steady accuracy without relying on the initial conditions, is then integrated into a cost function. The backstepping framework combines the ACL and integral reinforcement learning (IRL) algorithm to develop the adaptive optimal bipartite consensus scheme, which contributes a critic-only controller structure by removing the identifier and actor networks in the existing methods. The adaptive law of the critic network is derived by the gradient descent algorithm and experience replay to minimize the IRL-based residual error. It is shown that a compute-saving learning mechanism can achieve the optimal consensus, and the error variables of the closed-loop system are uniformly ultimately bounded (UUB). Besides, in any bounded initial condition, the evolution of bipartite consensus is limited to a user-prescribed boundary under bounded initial conditions. The illustrative simulation results validate the efficacy of the approach.

4.
Front Public Health ; 12: 1385592, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721532

RESUMEN

Background: Widowhood is one of the most serious issues affecting the mental health of older persons. China currently has tens of millions of widowed older adult, which is a huge group. It is of great significance to study the impacts of widowhood on their mental health and put forward some measures for improvement. Method: We used China Family Panel Studies (CFPS) data in 2020, which included 4,184 older adults. Linear regression is used to examine the relationship among widowhood, mental health, and social capital. Results: Both short-term and medium- and long-term widowhood lead to a significant increase in depression, which seriously affects the mental health of older people. At the same time, community-level and family-level social capital have significant buffering effects on the loss of mental health caused by widowhood, but this effect is heterogeneous, with different types of social capital playing different roles among different gender groups. Conclusion: The provision of care support by children and good neighborhood relationships can help mitigate the psychological impact of widowhood, and these are areas where social policy can make a difference.


Asunto(s)
Salud Mental , Capital Social , Viudez , Humanos , Viudez/psicología , Viudez/estadística & datos numéricos , Femenino , Masculino , Anciano , Salud Mental/estadística & datos numéricos , China , Persona de Mediana Edad , Depresión/psicología , Anciano de 80 o más Años , Apoyo Social
5.
Acc Chem Res ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38723018

RESUMEN

ConspectusLithium ion batteries (LIBs) with inorganic intercalation compounds as electrode active materials have become an indispensable part of human life. However, the rapid increase in their annual production raises concerns about limited mineral reserves and related environmental issues. Therefore, organic electrode materials (OEMs) for rechargeable batteries have once again come into the focus of researchers because of their design flexibility, sustainability, and environmental compatibility. Compared with conventional inorganic cathode materials for Li ion batteries, OEMs possess some unique characteristics including flexible molecular structure, weak intermolecular interaction, being highly soluble in electrolytes, and moderate electrochemical potentials. These unique characteristics make OEMs suitable for applications in multivalent ion batteries, low-temperature batteries, redox flow batteries, and decoupled water electrolysis. Specifically, the flexible molecular structure and weak intermolecular interaction of OEMs make multivalent ions easily accessible to the redox sites of OEMs and facilitate the desolvation process on the redox site, thus improving the low-temperature performance, while the highly soluble nature enables OEMs as redox couples for aqueous redox flow batteries. Finally, the moderate electrochemical potential and reversible proton storage and release of OEMs make them suitable as redox mediators for water electrolysis. Over the past ten years, although various new OEMs have been developed for Li-organic batteries, Na-organic batteries, Zn-organic batteries, and other battery systems, batteries with OEMs still face many challenges, such as poor cycle stability, inferior energy density, and limited rate capability. Therefore, previous reviews of OEMs mainly focused on organic molecular design for organic batteries or strategies to improve the electrochemical performance of OEMs. A comprehensive review to explore the characteristics of OEMs and establish the correlation between these characteristics and their specific application in energy storage and conversion is still lacking.In this Account, we initially provide an overview of the sustainability and environmental friendliness of OEMs for energy storage and conversion. Subsequently, we summarize the charge storage mechanisms of the different types of OEMs. Thereafter, we explore the characteristics of OEMs in comparison with conventional inorganic intercalation compounds including their structural flexibility, high solubility in the electrolyte, and appropriate electrochemical potential in order to establish the correlations between their characteristics and potential applications. Unlike previous reviews that mainly introduce the electrochemical performance progress of different organic batteries, this Account specifically focuses on some exceptional applications of OEMs corresponding to the characteristics of organic electrode materials in energy storage and conversion, as previously published by our groups. These applications include monovalent ion batteries, multivalent ion batteries, low-temperature batteries, redox flow batteries with soluble OEMs, and decoupled water electrolysis employing organic electrodes as redox mediators. We hope that this Account will make an invaluable contribution to the development of organic electrode materials for next-generation batteries and help to unlock a world of potential energy storage applications.

6.
J Phys Chem Lett ; 15(18): 5008-5015, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38695764

RESUMEN

Second-harmonic generation (SHG) has rapidly advanced with the miniaturization of on-chip devices and has found many applications, including optical frequency conversion, nonlinear imaging, and quantum technology. However, owing to the obvious phase-matching constraints involved in nonlinear optical interactions in bulk crystals and the decrease in the length and strength of nonlinear interactions in nanophotonic and surface/interface systems, improving the SHG efficiency and manipulating its optical properties at the nanoscale are challenging tasks. Herein, a monocrystalline silver microplate and nanocube-coupled nanocavity with double-resonance plasmonic modes and an ultrasmall gap were constructed, resulting in efficiently enhanced SHG. In particular, the SHG from the silver microplate (111) is polarization-dependent, and the anisotropy of the SHG in the plasmonic nanocavity can be further controlled via the superposition of symmetries at the interface and plasmonic waveguide-cavity modes. The interfacial SHG provides technology for developing lattice surface atomic arrangement and nanostructure rapid characterization, nonlinear light sources, and on-chip nonlinear nanophotonic devices.

7.
Sci Total Environ ; 932: 173117, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38734097

RESUMEN

2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 µg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.

8.
Int Microbiol ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38740654

RESUMEN

INTRODUCTION: Sulfur-oxidizing bacteria (SOB) play a key role in the biogeochemical cycling of sulfur. OBJECTIVES: To explore SOB diversity, distribution, and physicochemical drivers in five volcanic lakes and two springs in the Wudalianchi volcanic field, China. METHODS: This study analyzed microbial communities in samples via high-throughput sequencing of the soxB gene. Physical-chemical parameters were measured, and QIIME 2 (v2019.4), R, Vsearch, MEGA7, and Mothur processed the data. Alpha diversity indices and UPGMA clustering assessed community differences, while heat maps visualized intra-sample variations. Canoco 5.0 analyzed community-environment correlations, and NMDS, Adonis, and PcoA explored sample dissimilarities and environmental factor correlations. SPSS v.18.0 tested for statistical significance. RESULTS: The diversity of SOB in surface water was higher than in springs (more than 7.27 times). We detected SOB affiliated to ß-proteobacteria (72.3 %), α-proteobacteria (22.8 %), and γ-proteobacteria (4.2 %) distributed widely in these lakes and springs. Rhodoferax and Cupriavidus were most frequent in all water samples, while Rhodoferax and Bradyrhizobium are dominant in surface waters but rare in springs. SOB genera in both habitats were positively correlated. Co-occurrence analysis identified Bradyrhizobium, Blastochloris, Methylibium, and Metyhlobacterium as potential keystone taxa. Redundancy analysis (RDA) revealed positive correlations between SOB diversity and total carbon (TC), Fe2+, and total nitrogen (TN) in all water samples. CONCLUSION: The diversity and community structure of SOB in volcanic lakes and springs in the Wudalianchi volcanic group were clarified. Moreover, the diversity and abundance of SOB decreased with the variation of water openness, from open lakes to semi-enclosed lakes and enclosed lakes.

9.
Front Immunol ; 15: 1357072, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638435

RESUMEN

Introduction: Clostridium perfringens α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear. Methods: In vivo, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). In vitro, IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms. Results and discussion: The results showed that in vivo, arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin (IL)-1ß, IL-6 and IL-17 mRNA expression. Clostridium perfringens α toxin significantly decreased jejunal mechanistic target of rapamycin (mTOR) and solute carrier family 38 member 9 (SLC38A9) mRNA expression, while arginine supplementation significantly increased mTOR and SLC38A9 mRNA expression. In vitro, arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines IL-6, C-X-C motif chemokine ligand (CXCL)10, CXCL11 and transforming growth factor-ß (TGF-ß), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-XL) and cysteinyl aspartate specific proteinase 3 (Caspase-3) and the ratio of Bax to Bcl-2. Arginine pretreatment significantly increased the α toxin-induced decrease in mTOR, SLC38A9, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (S6K) mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mTOR mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury in vivo and in vitro, which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.


Asunto(s)
Arginina , Toxinas Bacterianas , Proteínas de Unión al Calcio , Interleucina-6 , Fosfolipasas de Tipo C , Animales , Masculino , Arginina/farmacología , Toxinas Bacterianas/toxicidad , Proteína X Asociada a bcl-2 , Pollos/genética , Inflamación , Diana Mecanicista del Complejo 1 de la Rapamicina , ARN Mensajero/genética , Serina-Treonina Quinasas TOR/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo
10.
Cell Death Discov ; 10(1): 193, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664375

RESUMEN

Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

11.
Biofabrication ; 16(3)2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38569491

RESUMEN

Regenerative healing of spinal cord injury (SCI) poses an ongoing medical challenge by causing persistent neurological impairment and a significant socioeconomic burden. The complexity of spinal cord tissue presents hurdles to successful regeneration following injury, due to the difficulty of forming a biomimetic structure that faithfully replicates native tissue using conventional tissue engineering scaffolds. 3D bioprinting is a rapidly evolving technology with unmatched potential to create 3D biological tissues with complicated and hierarchical structure and composition. With the addition of biological additives such as cells and biomolecules, 3D bioprinting can fabricate preclinical implants, tissue or organ-like constructs, andin vitromodels through precise control over the deposition of biomaterials and other building blocks. This review highlights the characteristics and advantages of 3D bioprinting for scaffold fabrication to enable SCI repair, including bottom-up manufacturing, mechanical customization, and spatial heterogeneity. This review also critically discusses the impact of various fabrication parameters on the efficacy of spinal cord repair using 3D bioprinted scaffolds, including the choice of printing method, scaffold shape, biomaterials, and biological supplements such as cells and growth factors. High-quality preclinical studies are required to accelerate the translation of 3D bioprinting into clinical practice for spinal cord repair. Meanwhile, other technological advances will continue to improve the regenerative capability of bioprinted scaffolds, such as the incorporation of nanoscale biological particles and the development of 4D printing.


Asunto(s)
Bioimpresión , Impresión Tridimensional , Traumatismos de la Médula Espinal , Andamios del Tejido , Traumatismos de la Médula Espinal/terapia , Bioimpresión/métodos , Humanos , Animales , Andamios del Tejido/química , Ingeniería de Tejidos , Materiales Biocompatibles/química
12.
Cancer Cell ; 42(4): 552-567.e6, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38593781

RESUMEN

Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL.


Asunto(s)
Leucemia , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Asparaginasa/farmacología , Farmacología en Red , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Transducción de Señal , Leucemia/tratamiento farmacológico
13.
J Burn Care Res ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38616525

RESUMEN

Animal experiments are important in trauma-related studies because they simulate in vivo effects. Rodents are a good choice for preparing trauma models; however, contractile healing in rodents results in a healing pattern that differs considerably from that in humans. Therefore, this study developed a new rodent model that avoids contractile healing of the skin around the wound using an anti-contraction ring, and the skin in the wound's center remains intact and acts as a source for epithelialized diffusion healing. Cell proliferation, migration, revascularization, and collagen secretion did not differ between the novel and conventional full-skin defect trauma models. However, the healing rate at various stages significantly differed between the two groups owing to differences in the healing patterns. And without effective treatment, the experimental group cannot heal. The stabilities of the novel and conventional methods were good regardless of operator or batch. In summary, this new animal trauma model provides a stable experimental environment similar to that in humans, which may promote trauma-related research.

14.
Genes (Basel) ; 15(4)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38674346

RESUMEN

Ketosis is a common metabolic disorder in the early lactation of dairy cows. It is typically diagnosed by measuring the concentration of ß-hydroxybutyrate (BHB) in the blood. This study aimed to estimate the genetic parameters of blood BHB and conducted a genome-wide association study (GWAS) based on the estimated breeding value. Phenotypic data were collected from December 2019 to August 2023, comprising blood BHB concentrations in 45,617 Holstein cows during the three weeks post-calving across seven dairy farms. Genotypic data were obtained using the Neogen Geneseek Genomic Profiler (GGP) Bovine 100 K SNP Chip and GGP Bovine SNP50 v3 (Illumina Inc., San Diego, CA, USA) for genotyping. The estimated heritability and repeatability values for blood BHB levels were 0.167 and 0.175, respectively. The GWAS result detected a total of ten genome-wide significant associations with blood BHB. Significant SNPs were distributed in Bos taurus autosomes (BTA) 2, 6, 9, 11, 13, and 23, with 48 annotated candidate genes. These potential genes included those associated with insulin regulation, such as INSIG2, and those linked to fatty acid metabolism, such as HADHB, HADHA, and PANK2. Enrichment analysis of the candidate genes for blood BHB revealed the molecular functions and biological processes involved in fatty acid and lipid metabolism in dairy cattle. The identification of novel genomic regions in this study contributes to the characterization of key genes and pathways that elucidate susceptibility to ketosis in dairy cattle.


Asunto(s)
Ácido 3-Hidroxibutírico , Estudio de Asociación del Genoma Completo , Lactancia , Polimorfismo de Nucleótido Simple , Animales , Bovinos/genética , Ácido 3-Hidroxibutírico/sangre , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/veterinaria , Femenino , Lactancia/genética , Cetosis/veterinaria , Cetosis/genética , Cetosis/sangre , Antecedentes Genéticos , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/sangre , Genotipo
15.
Materials (Basel) ; 17(3)2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38591663

RESUMEN

The stress distribution in prestressed filament wound components plays a crucial role in determining the quality of these components during their operational lifespan. This article proposes a physical model to analyze the stress and deformation of prestressed wound composite components with arch-shaped sections. Drawing upon the principles of beam theory, we delve into the analysis of prestressed wound components with metal liners featuring arch-shaped sections. Our investigation revealed a noteworthy phenomenon termed the "additional bending moment effect" within prestressed wound components with arch-shaped sections. Furthermore, this study establishes a relationship between this additional bending moment and the external pressure. In addition, a 3D finite element (FE) model for prestressed wound components with arch-shaped sections incorporating metal liners was developed. The model's accuracy was validated through a comparison with prestressed wound experiments, showcasing an error margin of less than 2%. In comparison with prestressed wound components with circular cross-sections under identical load and dimensional parameters, it was observed that prestressed wound components with arch-shaped sections exhibit stress distributions in the arc segments akin to their circular counterparts, with differences not exceeding 5%. Notably, when the ratio of the straight segment length to the inner diameter of the arc segment inner is less than 4, the deformation on the symmetric plane of the arc segment in an arch-shaped component can be effectively considered as the summation of deformations in equivalent-sized arc and straight segments under identical loading conditions. This yields an equivalent physical model and a streamlined analysis and design methodology for describing the deformation characteristics of prestressed wound components with arch-shaped sections.

16.
Sci Rep ; 14(1): 8125, 2024 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-38582956

RESUMEN

CD74 is a type-II transmembrane glycoprotein that has been linked to tumorigenesis. However, this association was based only on phenotypic studies, and, to date, no in-depth mechanistic studies have been conducted. In this study, combined with a multi-omics study, CD74 levels were significantly upregulated in most cancers relative to normal tissues and were found to be predictive of prognosis. Elevated CD74 expression was associated with reduced levels of mismatch-repair genes and homologous repair gene signatures in over 10 tumor types. Multiple fluorescence staining and bulk, spatial, single-cell transcriptional analyses indicated its potential as a marker for M1 macrophage infiltration in pan-cancer. In addition, CD74 expression was higher in BRCA patients responsive to conventional chemotherapy and was able to predict the prognosis of these patients. Potential CD74-activating drugs (HNHA and BRD-K55186349) were identified through molecular docking to CD74. The findings indicate activation of CD74 may have potential in tumor immunotherapy.


Asunto(s)
Macrófagos , Neoplasias , Humanos , Pronóstico , Simulación del Acoplamiento Molecular , Macrófagos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo
17.
J Ethnopharmacol ; 331: 118233, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38685365

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. AIM OF THE STUDY: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. MATERIALS AND METHODS: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. RESULTS: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. CONCLUSION: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

18.
Skin Res Technol ; 30(5): e13701, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38682785

RESUMEN

BACKGROUND: Dermatomyositis (DM) is a rare inflammatory disease. Our research focuses on predicting poor prognosis in DM patients and evaluating the prognostic significance of ferritin and Salivary Sugar Chain Antigen-6 (KL-6) through multivariate logistic regression analysis. METHODS: Between February 2018 and April 2020, 80 DM patients at our hospital were categorized into MDA5 positive (n = 20) and negative (n = 60) groups. We conducted multivariate logistic regression to determine DM's poor prognosis risk factors and evaluate ferritin/KL-6's predictive value for prognosis. RESULTS: Analysis showed no gender, age, body mass index (BMI), or lifestyle (smoking, drinking) differences, nor in dyspnea, muscle weakness, skin ulcers, and acetylcysteine treatment effects (p > 0.05). Significant differences emerged in arrhythmias, interstitial pneumonia, C-reactive protein, albumin, and lactate dehydrogenase levels (p < 0.05). Before treatment, differences were negligible (p > 0.05), but post-treatment, serum KL-6 and ferritin levels dropped. MDA5 positive patients had elevated serum KL-6 and ferritin levels than survivors (p < 0.05), with a strong correlation to DM. Combined diagnosis using serum KL-6 and ferritin for DM prognosis showed area under curves of 0.716 and 0.634, significantly outperforming single-index diagnoses with an area under curve (AUC) of 0.926 (p < 0.05). CONCLUSION: Serum KL-6 and ferritin show marked abnormalities in DM, useful as indicators for evaluating polymyositis and DM conditions. However, the study's small sample size is a drawback. Expanding the sample size is essential to monitor serum KL-6 and ferritin changes in DM patients under treatment more closely, aiming to improve clinical assessment and facilitate detailed research.


Asunto(s)
Dermatomiositis , Ferritinas , Mucina-1 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Dermatomiositis/sangre , Dermatomiositis/diagnóstico , Ferritinas/sangre , Helicasa Inducida por Interferón IFIH1 , Modelos Logísticos , Mucina-1/sangre , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo
20.
Chemosphere ; 353: 141635, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38447897

RESUMEN

The performance of bacterial strains in executing degradative functions under the coexistence of heavy metals/heavy metal-like elements and organic contaminants is understudied. In this study, we isolated a fluorene-degrading bacterium, highly arsenic-resistant, designated as strain 2021, from contaminated soil at the abandoned site of an old coking plant. It was identified as a member of the genus Rhodococcus sp. strain 2021 exhibited efficient fluorene-degrading ability under optimal conditions of 400 mg/L fluorene, 30 °C, pH 7.0, and 250 mg/L trivalent arsenic. It was noted that the addition of arsenic could promote the growth of strain 2021 and improve the degradation of fluorene - a phenomenon that has not been described yet. The results further indicated that strain 2021 can oxidize As3+ to As5+; here, approximately 13.1% of As3+ was converted to As5+ after aerobic cultivation for 8 days at 30 °C. The addition of arsenic could greatly up-regulate the expression of arsR/A/B/C/D and pcaG/H gene clusters involved in arsenic resistance and aromatic hydrocarbon degradation; it also aided in maintaining the continuously high expression of cstA that codes for carbon starvation protein and prmA/B that codes for monooxygenase. These results suggest that strain 2021 holds great potential for the bioremediation of environments contaminated by a combination of arsenic and polycyclic aromatic hydrocarbons. This study provides new insights into the interactions among microbes, as well as inorganic and organic pollutants.


Asunto(s)
Arsénico , Hidrocarburos Policíclicos Aromáticos , Rhodococcus , Contaminantes del Suelo , Arsénico/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Fluorenos/metabolismo , Biodegradación Ambiental , Contaminantes del Suelo/metabolismo , Microbiología del Suelo
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