RESUMEN
T cells are the central players in antitumor immunity, and effective tumor killing depends on their ability to infiltrate into the tumor microenvironment (TME) while maintaining normal cytotoxicity. However, late-stage tumors develop immunosuppressive mechanisms that impede T cell movement and induce exhaustion. Investigating T cell migration in human tumors in vivo could provide novel insights into tumor immune escape, although it remains a challenging task. In this study, we developed ReMiTT, a computational method that leverages spatial transcriptomics data to track T cell migration patterns within tumor tissue. Applying ReMiTT to ovarian tumor samples, we identified key genes and pathways that enriched on algorithm-identified T cell migration trails, including leukocyte chemotaxis, cell-cell adhesion, and ECM remodeling. We also characterized the phenotypes of T cells on the migrating trails, suggesting that regulatory T cells may accompany cytotoxic T cells during migration. Our findings provide a novel approach to studying T cell migration and interactions within the TME, offering new insights into tumor-immune dynamics.
RESUMEN
Working memory, an essential component of cognitive function, can be improved through specific methods. This meta-analysis evaluates the effectiveness of transcranial alternating current stimulation (tACS), an emerging technique for enhancing working memory, and explores its efficacy, influencing factors, and underlying mechanisms. A PRISMA systematic search was conducted. Hedges's g was used to quantify effect sizes. We constructed a three-level meta-analytic model to account for all effect sizes and performed subgroup analyses to assess moderating factors. Recognizing the distinct neural underpinnings of various working memory processes, we separately assessed the effects on n-back tasks and traditional working memory tasks. A total of 39 studies with 405 effect sizes were included (170 from n-back tasks and 235 from other tasks). The overall analysis indicated a net benefit of g = 0.060 of tACS on working memory. Separate analyses showed that tACS had a small positive effect on n-back tasks (g = 0.102), but almost no effect on traditional working memory tasks (g = 0.045). Further analyses revealed mainly: A moderately positive effect of theta tACS (without anti-phase stimulation) on n-back tasks (g = 0.207); and a small effect of offline stimulation on working memory maintenance (g = 0.127). Overall, tACS has minimal impact on working memory improvement, but it shows potential under certain conditions. Specifically, both online and offline theta tACS can improve n-back task performance, while only offline stimulation enhances working memory maintenance. More research is needed to understand the mechanisms behind these effects to make tACS an effective method.
RESUMEN
BACKGROUND: The maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring. RESULTS: The microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly. CONCLUSIONS: Our study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome. Video Abstract.
Asunto(s)
Animales Recién Nacidos , Bacterias , Heces , Microbioma Gastrointestinal , Meconio , Rumen , Animales , Bovinos , Microbioma Gastrointestinal/genética , Heces/microbiología , Femenino , Rumen/microbiología , Meconio/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , EmbarazoRESUMEN
Virulence factor genes (VFGs) pose a potential threat to ecological security and animal health, and have attracted increasing attention in the livestock industry. As one of the primary livestock types, dairy cattle may be an important source of VFG transmission. However, the distribution, transmission, and evolution of VFGs in the gastrointestinal tract and surrounding environment of dairy cattle remain unclear. In the present study, a total of 263 samples were collected from cows, calves, colostrum, farm wastewater, and soil. Metagenomics was conducted to analyze changes in the microbiome and VFGs characteristics in these ecological niches. The VFGs of the cows showed distinct differences between the rumen and feces, and were influenced by the region. The dominant VFG hosts was regulated by their microbial structure. Colostrum administration of cows increased VFG abundance in their newborn calf feces sharply and Enterobacteriaceae became the primary host. While diet was the primary driving force for the temporal variation in calf VFGs. For samples of the surrounding environment, water and soil had higher VFG concentrations and were more structurally stable. Moreover, extensive interactions between the mobile genetic elements and VFGs and gene mobile analysis map based on metagenomic binning both displayed the potential horizontal transfer ability of VFGs in the cows and environment. Our study revealed the prevalence, diffusion, and regulatory factors of VFGs in dairy cattle production systems, providing novel insights into reducing livestock VFGs and limiting their spread.
RESUMEN
BACKGROUND: Pangolins are the only mammals that have overlapping scales covering most of their bodies, and they play a crucial role in the ecosystem, biological research, and human health and disease. Previous studies indicated pangolin scale might provide an important mechanical defense to themselves. The origin and exact functions of this unique trait remain a mystery. Using a multi-omics analysis approach, we report a novel functional explanation for how mammalian scales can provide host-pathogen defense. RESULTS: Our data suggest that pangolin scales have a sophisticated structure that could potentially trap pathogens. We identified numerous proteins and metabolites exhibiting antimicrobial activity, which could suggest a role for scales in pathogen defense. Notably, we found evidence suggesting the presence of exosomes derived from diverse cellular origins, including mesenchymal stem cells, immune cells, and keratinocytes. This observation suggests a complex interplay where various cell types may contribute to the release of exosomes and antimicrobial compounds at the interface between scales and viable tissue. These findings indicate that pangolin scales may serve as a multifaceted defense system, potentially contributing to innate immunity. Comparisons with human nail and hair revealed pangolin-specific proteins that were enriched in functions relating to sensing, immune responses, neutrophil degranulation, and stress responses. We demonstrated the antimicrobial activity of key pangolin scale components on pathogenic bacteria by antimicrobial assays. CONCLUSIONS: This study identifies a potential role of pangolin scales and implicates scales, as possible determinants of pathogen defense due to their structure and contents. We indicate for the first time the presence of exosomes in pangolin scales and propose the new functions of scales and their mechanisms. This new mechanism could have implications for multiple fields, including providing interesting new research directions and important insights that can be useful for synthesizing and implementing new biomimetic antimicrobial approaches.
Asunto(s)
Inmunidad Innata , Pangolines , Animales , Humanos , Interacciones Huésped-Patógeno/inmunología , Adaptación FisiológicaRESUMEN
Grain boundaries in noble metal catalysts have been identified as critical sites for enhancing catalytic activity in electrochemical reactions such as the oxygen reduction reaction. However, conventional methods to modify grain boundary density often alter particle size, shape, and morphology, obscuring the specific role of grain boundaries in catalytic performance. This study addresses these challenges by employing gold nanoparticle assemblies to control grain boundary density through the manipulation of nanoparticle collision frequency during synthesis. We demonstrate a direct correlation between increased grain boundary density and enhanced two-electron oxygen reduction reaction activity, achieving a significant improvement in both specific and mass activity. Additionally, the gold nanoparticle assemblies with high grain boundary density exhibit remarkable electrochemical stability, attributed to boron segregation at the grain boundaries, which prevents structural degradation. This work provides a promising strategy for optimizing the activity, selectivity, and stability of noble metal catalysts through precise grain boundary engineering.
RESUMEN
BACKGROUND: Spiroplasma eriocheiris has been proved to be a pathogen causing tremor disease of Eriocheir sinensis, it is also infectious to other aquatic crustaceans, resulting in a serious threat on the sustainable development of the aquaculture industry. S. eriocheiris is a helical-shaped microbe without a cell wall, and its motility is related to the cytoskeleton protein MreB which belongs to the actin superfamily and has five MreB homologs. RESULTS: In this study, we purified MreB3, MreB4 and MreB5, and successfully prepared monoclonal antibodies. After S. eriocheiris treated with actin stabilizator Phalloidin and inhibitors A22, we found that Phalloidin and A22 affect the S. eriocheiris morphology by altering MreB expression. We confirmed that the ability of S. eriocheiris to invade E. sinensis was increased after treatment with Phalloidin, including that the morphology of E. sinensis blood lymphocytes was deteriorated, blood lymphocytes viability was decreased, peroxidase activity and cell necrosis were increased. On the contrary, the pathogenicity of S. eriocheiris decreased after treatment with A22. CONCLUSIONS: Our findings suggest that the MreB protein in S. eriocheiris plays a crucial role in its morphology and pathogenicity, providing new insights into potential strategies for the prevention and control of S. eriocheiris infections.
Asunto(s)
Spiroplasma , Spiroplasma/patogenicidad , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Braquiuros/microbiología , VirulenciaRESUMEN
Jujube (Ziziphus jujuba Mill.), belonging to the Rhamnaceae family, is gaining increasing prominence as a perennial fruit crop with significant economic and medicinal values. Here, we conduct de novo assembly of four reference-grade genomes, encompassing one wild and three cultivated jujube accessions. We present insights into the population structure, genetic diversity, and genomic variations within a diverse collection of 1059 jujube accessions. Analyzes of the jujube pan-genome, based on our four assemblies and four previously released genomes, reveal extensive genomic variations within domestication-associated regions, potentially leading to the discovery of a candidate gene that regulates flowering and fruit ripening. By leveraging the pan-genome and a large-scale resequencing population, we identify two candidate genes involved in domestication traits, including the seed-setting rate, the bearing-shoot length and the leaf size in jujube. These genomic resources will accelerate evolutionary and functional genomics studies of jujube.
Asunto(s)
Domesticación , Variación Genética , Genoma de Planta , Ziziphus , Ziziphus/genética , Frutas/genética , Frutas/anatomía & histología , Frutas/crecimiento & desarrollo , Genómica/métodos , Polimorfismo de Nucleótido SimpleRESUMEN
Characterization and comparison of the chemical compositions and biological activities of Lactarius volemus of three different sizes (large size, medium size, small size) were investigated in this work. By comparing three sizes of Lactarius volemus, the small-sized Lactarius volemus had the highest content of crude fiber, fat, crude protein, total sugar, reducing sugar, polyphenols, and total flavonoids, whereas medium-sized Lactarius volemus showed the highest content of ash and total amino acids. Meanwhile, the small-sized Lactarius volemus also exhibited the best 2,2-Diphenyl-1-picrylhy drazyl (DPPH) radical scavenging ability, α-amylase inhibitory activity, α-glucosidase inhibitory activity, and xanthine oxidase inhibitory activity. The small-sized Lactarius volemus had the highest chemical composition content and the best biological activities among the three different sizes. This work might provide basic data support for guiding the development of Lactarius volemus and also instruct consumers in selecting and purchasing high-quality Lactarius volemus.
RESUMEN
The advent of the digital economy has brought new opportunities to food marketing. In China, many food businesses have begun to use interactions under specific social media topics to open up new sales channels. Green food, as a representative of environmentally related topics, is increasingly influencing consumer choices through online interactions. In light of this, this study collected data from a large group of participants engaged in online green interactions to explore the psychological mechanisms behind consumers' choices of green food in an online context. The findings indicate that online green interactions positively influence the willingness to purchase green food, with environmental self-efficacy and flow experience serving as mediators in this relationship. Information trust and consumer traits act as boundary conditions. This study not only deepens the understanding of food consumer behavior in the digital context, but also provides important references for food companies on how to more effectively utilize online interaction to promote the market expansion of green food.
RESUMEN
BACKGROUND: The deficit in cognitive reappraisal capacity is a key factor in developing and maintaining emotional disorders such as anxiety disorders and depressive disorders. However, the results from both neuroimaging and behavioral studies are mixed. Therefore, we systematically conducted a series of meta-analyses based on behavioral and neuroimaging studies to clarify this issue. METHODS: In behavioral meta-analyses, we used three-level random-effects models to summarize the overall effect sizes based on Hedges' g. In neuroimaging meta-analyses, we used SDM-PSI to summarize the brain activation patterns. RESULTS: Behavioral meta-analyses found that individuals with anxiety disorders or depressive disorders could reduce negative reactivity through reappraisal; the reduction of negative emotions through reappraisal by individuals with anxiety disorders was similar to that by healthy individuals; the reduction by depressive disorders was lower than that of healthy individuals. Neuroimaging meta-analyses showed that individuals with anxiety disorders or depressive disorders activated regions of cognitive control during cognitive reappraisal; the activation in individuals with anxiety disorders was lower than in healthy individuals; while the activation in individuals with depressive disorders was similar to that in healthy individuals. CONCLUSION: Individuals with anxiety and depressive disorders showed dissociation in behaviour and neuroimaging patterns of cognitive reappraisal capacity deficit.
RESUMEN
BACKGROUND: Instead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of "blood-activating and stasis-resolving" formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. PURPOSE: To study the underlying mechanisms of a classical "blood-activating and stasis-resolving" formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. STUDY DESIGN: HUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. RESULTS: Our data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206+ macrophages and increased number of CD86+ macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. CONCLUSION: This study demonstrated for the first time that TSD as a classical Chinese formula can enhance the drug efficacy and reduce the side effects of doxorubicin. These findings can support that TSD could be used as an adjuvant therapy in combination with conventional chemotherapy for the future breast cancer treatment.
Asunto(s)
Doxorrubicina , Medicamentos Herbarios Chinos , Células Endoteliales de la Vena Umbilical Humana , Neovascularización Patológica , Pez Cebra , Animales , Doxorrubicina/farmacología , Medicamentos Herbarios Chinos/farmacología , Humanos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Femenino , Ratones , Neovascularización Patológica/tratamiento farmacológico , Ratones Endogámicos BALB C , Animales Modificados Genéticamente , Microambiente Tumoral/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Apoptosis/efectos de los fármacosRESUMEN
Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently through the introduction of spatially resolved transcriptomics (SRT) technologies, especially those that achieve single-cell resolution. Nevertheless, substantial challenges remain to analyze such highly complex data properly. Here, we introduce a multiple-instance learning framework, Spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight Spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates and, most importantly, the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of Spacia for three commercialized single-cell resolution SRT technologies: MERSCOPE/Vizgen, CosMx/NanoString and Xenium/10x. Overall, Spacia represents a notable step in advancing quantitative theories of cellular communications.
Asunto(s)
Comunicación Celular , Perfilación de la Expresión Génica , Análisis de la Célula Individual , Transcriptoma , Análisis de la Célula Individual/métodos , Humanos , Comunicación Celular/genética , Perfilación de la Expresión Génica/métodos , AnimalesRESUMEN
In solids, chemical short-range order (CSRO) refers to the self-organization of atoms of certain species occupying specific crystal sites. CSRO is increasingly being envisaged as a lever to tailor the mechanical and functional properties of materials. Yet quantitative relationships between properties and the morphology, number density, and atomic configurations of CSRO domains remain elusive. Herein, it is showcased how machine learning-enhanced atom probe tomography (APT) can mine the near-atomically resolved APT data and jointly exploit the technique's high elemental sensitivity to provide a 3D quantitative analysis of CSRO in a CoCrNi medium-entropy alloy. Multiple CSRO configurations are revealed, with their formation supported by state-of-the-art Monte-Carlo simulations. Quantitative analysis of these CSROs allows establishing relationships between processing parameters and physical properties. The unambiguous characterization of CSRO will help refine strategies for designing advanced materials by manipulating atomic-scale architectures.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMS) is a common gynecological disease that causes dysmenorrhea, chronic pelvic pain and infertility. Luoshi Neiyi Prescription (LSNYP), a traditional Chinese medicine (TCM) formula, is used to relieve EMS in the clinic. AIMS: This study aimed to examine the active components of LSNYP and the possible mechanism involved in its treatment of EMS. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to identify the chemical components of LSNYP. Human primary ectopic endometrial stromal cells (ecESCs) and eutopic endometrial stromal cells (euESCs) were isolated, and the expression levels of hypoxia inducible factor 1A (HIF1A), enhancer of zeste homolog 2 (EZH2) and steroidogenic factor 1 (SF-1) were detected by immunofluorescence and qPCR. Cobalt chloride (CoCl2) was utilized to construct an in vitro hypoxic environment, and lentiviruses were engineered to downregulate HIF1A and EZH2 and upregulate EZH2. Subsequently, the expression levels of HIF1A, EZH2, and SF-1 were measured using qPCR or western blotting. The binding of EZH2 to the SF-1 locus in ESCs was examined via ChIP. Furthermore, the effects of LSNYP on the HIF1A/EZH2/SF-1 pathway were evaluated both in vitro and in vivo. RESULTS: A total of 185 components were identified in LSNYP. The protein and gene expression levels of HIF1A and SF-1 were increased, whereas those of EZH2 were decreased in ecESCs. After treating euESCs with 50 µmol L-1 CoCl2 for 24 h, cell viability and estradiol (E2) production were enhanced. Hypoxia decreased EZH2 protein expression, while si-HIF1A increased it. SF-1 was increased when EZH2 was downregulated in normal and hypoxic environments, whereas the overexpression of EZH2 led to a decrease in SF-1 expression. ChIP revealed that hypoxia reduced EZH2 binding to the SF-1 locus in euESCs. In vitro, LSNYP-containing serum decreased E2 and prostaglandin E2 (PGE2) production, inhibited cell proliferation and invasion, and reduced the expression of HIF1A, SF-1, steroidogenic acute regulatory protein (StAR), and aromatase cytochrome P450 (P450arom). In vivo, LSNYP suppressed inflammation and adhesion and inhibited the HIF1A/EZH2/SF-1 pathway in endometriotic tissues. CONCLUSIONS: LSNYP may exert pharmacological effects on EMS by inhibiting E2 synthesis and inflammation through regulation of the HIF1A/EZH2/SF-1 pathway. These results suggest that LSNYP may be a promising candidate for the treatment of EMS.
Asunto(s)
Medicamentos Herbarios Chinos , Endometriosis , Proteína Potenciadora del Homólogo Zeste 2 , Estradiol , Subunidad alfa del Factor 1 Inducible por Hipoxia , Adulto , Animales , Femenino , Humanos , Ratones , Células Cultivadas , Medicamentos Herbarios Chinos/farmacología , Endometriosis/tratamiento farmacológico , Endometriosis/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Estradiol/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Inflamación/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Factor Esteroidogénico 1/genética , Factor Esteroidogénico 1/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismoRESUMEN
Helical nanostructures fabricated via the self-assembly of artificial motifs have been a captivating subject because of their structural aesthetics and multiple functionalities. Herein, we report the facile construction of a self-assembled nanohelix (NH) by leveraging an achiral aggregation-induced emission (AIE) luminogen (G) and pillar[5]arene (H), driven by host-guest interactions and metal coordination. Inspired by the "sergeants and soldiers" effect and "majority rule" principle, the host-guest complexation between G and H is employed to fixate the twisted conformation of G for the generation of "contortion sites", which further induced the emergence of helicity as the 1D assemblies are formed via Ag(I) coordination and hexagonally packed into nano-sized fibers. The strategy has proved feasible in both homogeneous and heterogeneous syntheses. Along with the formation of NH, boosted luminescence and enhanced productivity of reactive oxygen species (ROS) are afforded because of the efficient restriction on G, indicating the concurrent regulation of NH's morphology and photophysical properties by supramolecular assembly. In addition, NH also exhibits the capacity for bacteria imaging and photodynamic antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).
RESUMEN
Geological sequestration of carbon dioxide is a critical strategy to combat global warming, playing a significant role in the reduction of greenhouse gas emissions and preservation of the global ecosystem. Over more than three decades, this domain has expanded to encompass myriad research avenues and nuanced sub-fields. Proficiency in navigating the dynamic developments and prominent challenges in this arena is imperative for promoting scholarly advancement. In this investigation, bibliometric techniques are applied to perform a comprehensive qualitative and quantitative investigation of the progression of studies on CO2 geological sequestration. The analysis incorporates a thorough review and synthesis of the accumulated literature, comprising 34,392 articles sourced from the Web of Science Core Collection. The assessment primarily scrutinizes the chronological dispersal of research outputs, geographical and institutional representation, principal journals of publication, and patterns of authorship to highlight burgeoning areas of concentrated research endeavors and prospective future research frontiers. The data reveals a pronounced surge in academic literature focusing on CO2 geological storage post-2009, which underscores the increasing value of this research sector. Investigations of CO2 geological sequestration are characterized by widespread international engagement, with notable contributions from the United States, China, and the United Kingdom substantially steering the research discourse. The core investigative themes comprise comprehensive inquiries into the physical and chemical dynamics of CO2 containment, environmental repercussions, safety assessments, evaluation methods, and technological assessments of carbon storage, along with stringent scrutiny of geological contexts for their viability and efficacy as sequestration sites.
RESUMEN
ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25's biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.
Asunto(s)
Apoptosis , Neoplasias Óseas , Proliferación Celular , Biología Computacional , Metilación de ADN , Proteínas Activadoras de GTPasa , Regulación Neoplásica de la Expresión Génica , Osteosarcoma , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , Humanos , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Biología Computacional/métodos , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/mortalidad , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Pronóstico , Masculino , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Relevancia ClínicaRESUMEN
Layered double hydroxides (LDHs) have garnered significant attention from researchers in the field of adsorption due to their unique laminated structures and ion exchange properties. LDHs with various anion intercalation showed different adsorption effects on adsorbing ions, but the corresponding adsorption mechanisms are ambiguous. In this study, three types of NiAl-LDHs were synthesized, utilizing NO3-, CO32-, or Cl- as the interlayer anions. Batch tests were conducted to study their adsorption performances for Br-. Among them, the LDH with a NO3- intercalation layer exhibited the highest adsorption capacity for Br-, reaching up to 1.40 mmol g-1. The adsorption kinetics, mechanism, and renewability of these NiAl-LDHs were systematically compared. As a result, the type of Br- adsorption by all three materials was single molecular layer chemisorption. Moreover, the thermodynamic results of adsorption suggested that the adsorption of Br- was a spontaneous exothermic process. X-ray photoelectron spectroscopy, X-ray diffraction, and point of zero charge analysis collectively indicated that the adsorption of Br- by LDHs primarily occurred through interlayer ion exchange and electrostatic interactions. Structural characterizations of the adsorbents revealed that Br- entered the interlayers of the three LDHs, causing varying degrees of reduction in the interlayer spacing. Density functional theory calculations indicated that the interlayer binding energy of LDH with NO3- intercalation was the lowest, thereby making it more susceptible NO3- to be exchanged with Br-. Finally, the stability of the NiAl-LDHs was studied. The NiAl-LDHs retains a high removal efficiency of Br- even after 5 cycles of adsorption and desorption.
RESUMEN
INTRODUCTION: Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns and macrophages play a crucial role. However, the interaction of these mediators, the exact cause, and the treatment of knee osteoarthritis (KOA) are still unclear. Moreover, the interaction of interleukin (IL)-33, platelet-derived growth factor-BB (PDGF-BB), and matrix metalloproteinase-9 (MMP-9) with other factors in the pathogenesis of KOA has not been elaborately explored. METHOD: Therefore, in this study, we analyzed the expression of IL-33, PDGF-BB, and MMP-9 in the knee cartilage tissue of model mice, murine KOA was induced by using the destabilization of the medial meniscus (DMM) model. RESULTS: Compared with the sham operation control group, the expression levels of PDGF-BB, IL-33, and MMP-9 were increased significantly, and the pathological sections showed obvious cartilage damage. Additionally, we assessed the levels of IL-33 and MMP-9 expression in the knee joint of KOA model mice following intervention with PDGF-BB antibody, and we found that the expression level of MMP-9 was reduced following intervention with IL-33 antibody. When the effects of the three antibodies were compared in a mouse disease model, it was discovered that the IL-33 antibody could dramatically lower the relative expression level of MMP-9, resulting in the least amount of cartilage damage and improved protection. In conclusion, inhibiting IL-33 can significantly lower inflammatory factor levels in the knee joint, including IL-33 and MMP-9, and it can improve cartilage breakdown in osteoarthritis of the knee. CONCLUSION: Overall, the results indicate that IL-33 has a therapeutic function in the treatment of knee osteoarthritis and may be a novel target for treatment of the underlying causes of KOA. Additionally, PDGF-BB might be an upstream pathway of IL-33, and KOA's MMP-9 is an downstream pathway of IL-33.