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Neuroinflammation is implicated in the onset of postoperative cognitive dysfunction (POCD), with CD33 and triggering receptor expressed on myeloid cells 2 (TREM2) playing crucial roles in immune response modulation and neuroinflammatory processes. A total of 96 aged male C57/BL6 mice (9-12 months) were randomly assigned to one of four groups, each receiving an siRNA injection into the lateral ventricle. Subsequently, the mice underwent partial hepatectomy under general anesthesia. To assess cognitive function, the Morris water maze tests were conducted both pre- and post-surgery. Following behavioral assessments, hippocampal tissues were swiftly harvested. The regulation of CD33 and TREM2 expression was achieved through siRNA in the BV2 microglia cell line. Expression levels of CD33 and TREM2 were evaluated both in vitro and in vivo using quantitative RT-PCR and western blot analyses. This study explored the impact of CD33 and TREM2 on POCD in aged mice and revealed that surgery and anesthesia increased CD33 expression, leading to spatial learning and memory impairments. Inhibiting CD33 expression via siRNA administration ameliorated cognitive deficits and mitigated the neuroinflammatory response triggered by surgery. Additionally, CD33 inhibition reversed the surgery-induced decrease in synaptic-related proteins, highlighting its role in preserving synaptic integrity. Moreover, our experiments suggest that CD33 may influence neuroinflammation and cognitive function through mechanisms involving TREM2. This is evidenced by the suppression of pro-inflammatory cytokines following CD33 knockdown in microglia and the reversal of these effects when both CD33 and TREM2 are concurrently knocked down. These findings imply that CD33 might promote neuroinflammation by inhibiting TREM2. This study highlights the potential of targeting CD33 as a promising therapeutic strategy for preventing and treating POCD. It provides valuable insights into the intricate mechanisms underlying cognitive dysfunction following surgical procedures.
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BACKGROUND: Ovarian cancer (OC) is one of the cancers with a high incidence at present, which poses a severe threat to women's health. This study focused on identifying the heterogeneity among malignant epithelial cell OC and constructing an effective prognostic signature to predict prognosis and immunotherapy according to a multidisciplinary study. METHODS: The InterCNV algorithm was used to identify the heterogeneity of OC based on the scRNA-seq and bulk RNA-seq data. Six algorithms selected EMTscore. An effective prognostic signature was conducted using the COX and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The texting datasets were used to assess the accuracy of the prognostic signature. We evaluated different immune characteristics and immunotherapy response differences among other risk groups. RESULTS: A prognostic signature including 14 genes was established. The patients in the high-risk group have poor survival outcomes. We also found that the patients in the low-risk group have higher immune cell infiltration, enrichment of immune checkpoints, and immunotherapy response, suggesting that the patients in the low-risk group may be more sensitive to immunotherapy. Finally, the laboratory test results showed that KREMEN2 was identified as a novel biomarker and therapeutic target for OC patients. CONCLUSIONS: Our study established a GRG signature consisting of 16 genes based on the scRNA-seq and bulk RNA-seq data, which provides a new perspective on the prediction of prognosis and treatment strategy for OC.
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Biological membranes play a crucial role in actively hosting, modulating and coordinating a wide range of molecular events essential for cellular function. Membranes are organized into diverse domains giving rise to dynamic molecular patchworks. However, the very definition of membrane domains has been the subject of continuous debate. For example, in the plant field, membrane domains are often referred to as nanodomains, nanoclusters, microdomains, lipid rafts, membrane rafts, signalling platforms, foci or liquid-ordered membranes without any clear rationale. In the context of plant-microbe interactions, microdomains have sometimes been used to refer to the large area at the plant-microbe interface. Some of these terms have partially overlapping meanings at best, but they are often used interchangeably in the literature. This situation generates much confusion and limits conceptual progress. There is thus an urgent need for us as a scientific community to resolve these semantic and conceptual controversies by defining an unambiguous nomenclature of membrane domains. In this Review, experts in the field get together to provide explicit definitions of plasma membrane domains in plant systems and experimental guidelines for their study. We propose that plasma membrane domains should not be considered on the basis of their size alone but rather according to the biological system being considered, such as the local membrane environment or the entire cell.
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BACKGROUND: In recent years, the incidence of thyroid nodules has increased significantly. There are various ways to treat thyroid nodules, and ablation therapy is one of the important ways to treat thyroid nodules. However, there are many complications and deficiencies in the current ablation treatment of thyroid nodules, especially the incomplete ablation of thyroid cancer nodules, which limits the further application of ablation technology. In this paper, we report two cases of incomplete ablation of thyroid nodules, one of which underwent surgical treatment due to anxiety after ablation, and the postoperative pathology confirmed that there was still residual papillary thyroid carcinoma, and the other patient underwent an operation after ablation, but visited our medical institution again due to cervical lymph node metastasis in a short period of time, and after radical cervical lymph node dissection, pathology confirmed multiple cervical lymph node metastasis. Radionuclide therapy was performed after surgery, and two patients are currently receiving endocrine suppression therapy, and their condition is stable with no signs of recurrence. CONCLUSION: The incomplete ablation of thyroid cancer nodules limits the development of ablation therapy, making ablation treatment a double-edged sword. Guidelines and expert consensus can guide their development, but they need to evolve with the times, and a multidisciplinary diagnostic team can help screen the most suitable patients. Only by using this technology more standardly, using the most appropriate technology, and treating the most suitable patients, can benefit more and more patients.
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Tumeurs de la thyroïde , Humains , Tumeurs de la thyroïde/chirurgie , Tumeurs de la thyroïde/anatomopathologie , Femelle , Adulte d'âge moyen , Mâle , Adulte , Radio-isotopes de l'iode/usage thérapeutique , Cancer papillaire de la thyroïde/chirurgie , Cancer papillaire de la thyroïde/anatomopathologie , Nodule thyroïdien/chirurgie , Nodule thyroïdien/anatomopathologie , Techniques d'ablation/méthodes , Métastase lymphatiqueRÉSUMÉ
Euphorbiabietane F (1), a novel abietane diterpenoid with the unprecedented 6/6/5/6/5 carbon skeleton, one new strobane diterpenoid (2), together with one new pimarane diterpenoid (3) were isolated from the roots of Euphorbia fischeriana. The structures were elucidated by the extensive spectroscopic data, gauge-independent atomic orbital (GIAO) NMR calculations, the comparison of experimental and calculated ECD spectra, as well as single crystal X-ray diffraction. The cytotoxicity result suggested the moderate inhibition rate of 1 on the cell lines of HepG2 and A549.
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Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo2(OCOCH3)4] complexes, the nuclear magnetic resonance calculation with DP4 + probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 µM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis.
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Directional auxin transport and formation of auxin maxima are critical for embryogenesis, organogenesis, pattern formation, and growth coordination in plants, but the mechanisms underpinning the initiation and establishment of these auxin dynamics are not fully understood. Here we show that a self-initiating and -terminating transient auxin flow along the marginal cells (MCs) contributes to the formation of an auxin maximum at the tip of Arabidopsis cotyledon that globally coordinates the interdigitation of puzzle-shaped pavement cells in the cotyledon epidermis. Prior to the interdigitation, indole butyric acid (IBA) is converted to indole acetic acid (IAA) to induce PIN2 accumulation and polarization in the marginal cells, leading to auxin flow toward and accumulation at the cotyledon tip. When IAA levels at the cotyledon tip reaches a maximum, it activates pavement cell interdigitation as well as the accumulation of the IBA transporter TOB1 in MCs, which sequesters IBA to the vacuole and reduces IBA availability and IAA levels. The reduction of IAA levels results in PIN2 down-regulation and cessation of the auxin flow. Hence, our results elucidate a self-activating and self-terminating transient polar auxin transport system in cotyledons, contributing to the formation of localized auxin maxima that spatiotemporally coordinate pavement cell interdigitation.
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BACKGROUND: Obstructive Sleep Apnea (OSA) is a widespread sleep disturbance linked to metabolic and cardiovascular conditions. The Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratios (NHHR) has been proposed as being a potential biomarker to gauge cardiovascular risk. However, its relationship with OSA remains unclear. METHODS: This survey investigated the link NHHR to OSA in American citizens aged 20 and older using information collected via the National Health and Nutrition Examination Survey (NHANES) during the years 2017 to 2020. Logistic regression models with multivariable adjustments were employed to assess this relationship. Nonlinear associations were explored using smooth curve fitting, with a two-part linear regression model identifying a threshold effect. Subgroup analyses were conducted to evaluate population-specific differences. RESULTS: The survey encompassed 6763 participants, with an average age of 50.75 ± 17.32. The average NHHR stood at 2.74, accompanied by a standard deviation of 1.34, while the average frequency of OSA was 49.93%. Upon adjusting for covariates, each unit increase in NHHR may be associated with a 9% rise in OSA incidence. (95% confidence intervals 1.04-1.14; P < 0.0001). Notably, a U-shaped curve depicted the NHHR-OSA relationship, with an inflection point at 4.12. Subgroup analyses revealed consistent associations, with educational attainment and diabetes status modifying the NHHR-OSA relationship. CONCLUSION: The study highlights NHHR as a potential tool for OSA prediction, presenting avenues for advanced risk evaluation, tailored interventions, personalized treatment approaches, and preventive healthcare.
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Cholestérol HDL , Enquêtes nutritionnelles , Syndrome d'apnées obstructives du sommeil , Humains , Syndrome d'apnées obstructives du sommeil/sang , Syndrome d'apnées obstructives du sommeil/épidémiologie , Adulte d'âge moyen , Mâle , Femelle , Études transversales , Adulte , Cholestérol HDL/sang , Sujet âgé , Facteurs de risque , Marqueurs biologiques/sang , Maladies cardiovasculaires/sang , Maladies cardiovasculaires/épidémiologieRÉSUMÉ
Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ-δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.
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Athérosclérose , Marqueurs biologiques , Chimiokine CXCL9 , Stéatose hépatique non alcoolique , Humains , Stéatose hépatique non alcoolique/génétique , Stéatose hépatique non alcoolique/diagnostic , Stéatose hépatique non alcoolique/métabolisme , Stéatose hépatique non alcoolique/épidémiologie , Stéatose hépatique non alcoolique/anatomopathologie , Athérosclérose/génétique , Athérosclérose/métabolisme , Athérosclérose/diagnostic , Marqueurs biologiques/métabolisme , Chimiokine CXCL9/génétique , Chimiokine CXCL9/métabolisme , Réseaux de régulation génique , Comorbidité , Cellules endothéliales de la veine ombilicale humaine/métabolisme , Analyse de profil d'expression de gènesRÉSUMÉ
The development of multicellular tissues requires both local and global coordination of cell polarization, however, the mechanisms underlying their interplay are poorly understood. In Arabidopsis, leaf epidermal pavement cells (PC) develop a puzzle-piece shape locally coordinated through apoplastic auxin signaling. Here we show auxin also globally coordinates interdigitation by activating the TIR1/AFB-dependent nuclear signaling pathway. This pathway promotes a transient maximum of auxin at the cotyledon tip, which then moves across the leaf activating local PC polarization, as demonstrated by locally uncaged auxin globally rescuing defects in tir1;afb1;afb2;afb4;afb5 mutant but not in tmk1;tmk2;tmk3;tmk4 mutants. Our findings show that hierarchically integrated global and local auxin signaling systems, which respectively depend on TIR1/AFB-dependent gene transcription in the nucleus and TMK-mediated rapid activation of ROP GTPases at the cell surface, control PC interdigitation patterns in Arabidopsis cotyledons, revealing a mechanism for coordinating a local cellular process with the development of whole tissues.
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In this study, we conducted an in-depth exploration of Alzheimer's Disease (AD) by integrating state-of-the-art methodologies, including single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and a convolutional neural network (CNN) model. Focusing on the pivotal role of microglia in AD pathology, our analysis revealed 11 distinct microglial subclusters, with 4 exhibiting obviously alterations in AD and HC groups. The investigation of cell-cell communication networks unveiled intricate interactions between AD-related microglia and various cell types within the central nervous system (CNS). Integration of WGCNA and scRNA-seq facilitated the identification of critical genes associated with AD-related microglia, providing insights into their involvement in processes such as peptide chain elongation, synapse-related functions, and cell adhesion. The identification of 9 hub genes, including USP3, through the least absolute shrinkage and selection operator (LASSO) and COX regression analyses, presents potential therapeutic targets. Furthermore, the development of a CNN-based model showcases the application of deep learning in enhancing diagnostic accuracy for AD. Overall, our findings significantly contribute to unraveling the molecular intricacies of microglial responses in AD, offering promising avenues for targeted therapeutic interventions and improved diagnostic precision.
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Maladie d'Alzheimer , Microglie , , Analyse sur cellule unique , Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/anatomopathologie , Maladie d'Alzheimer/métabolisme , Analyse sur cellule unique/méthodes , Microglie/métabolisme , Microglie/anatomopathologie , Humains , Réseaux de régulation génique , Analyse de profil d'expression de gènes , Apprentissage profondRÉSUMÉ
Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 µg/mL of GML enhanced the phagocytic activity of HD11 cells (P < 0.05) without affecting cell viability (P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes (P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-ß1 and IL-10 genes (P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1ß and IL-6) induced by LPS (P < 0.05). GML also promoted the expression of TGF-ß1 and IL-10 (P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS (P < 0.05), as well as the phosphorylation of NF-κB p65 (P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway.
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Apoptose , Poulets , Inflammation , Laurate , Lipopolysaccharides , Macrophages , Monoglycérides , Facteur de transcription NF-kappa B , Espèces réactives de l'oxygène , Animaux , Espèces réactives de l'oxygène/métabolisme , Apoptose/effets des médicaments et des substances chimiques , Macrophages/effets des médicaments et des substances chimiques , Facteur de transcription NF-kappa B/métabolisme , Lipopolysaccharides/pharmacologie , Inflammation/médecine vétérinaire , Inflammation/induit chimiquement , Monoglycérides/pharmacologie , Laurate/pharmacologie , Lignée cellulaire , Anti-inflammatoires/pharmacologie , Protéines aviaires/génétique , Protéines aviaires/métabolismeRÉSUMÉ
The incidence of thyroid nodules is rising annually. Surgical treatment is effective, but often results in significant trauma, recurrent laryngeal nerve injury, hypoparathyroidism, and other complications. Recent years have seen significant breakthroughs in thyroid nodule ablation for treating thyroid diseases, although its application remains controversial. The objective was to review the development history and current research status of thyroid nodule ablation to provide a reference for future studies. The literature on thyroid nodule ablation was reviewed, analysing its advantages and disadvantages. The therapeutic effect of thyroid nodule ablation in treating benign thyroid lesions is noteworthy, but issues such as lax treatment indications and excessive medical treatment persist. Initial success has been achieved in treating thyroid malignant lesions, particularly papillary thyroid microcarcinoma (PTMC). However, the curative effect requires further follow-up verification.
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Nodule thyroïdien , Humains , Nodule thyroïdien/chirurgie , Nodule thyroïdien/anatomopathologie , Tumeurs de la thyroïde/chirurgie , Tumeurs de la thyroïde/anatomopathologie , Femelle , Techniques d'ablation/méthodes , Mâle , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVE: To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). METHODS: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. RESULTS: Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia. CONCLUSION: Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.
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Hyperthermie provoquée , Épanchement pleural malin , Humains , Épanchement pleural malin/thérapie , Hyperthermie provoquée/méthodes , Résultat thérapeutique , Perfusion régionale de chimiothérapie anticancéreuse/méthodes , Perfusion régionale de chimiothérapie anticancéreuse/effets indésirables , Antinéoplasiques/administration et posologie , Antinéoplasiques/effets indésirablesRÉSUMÉ
Coherent and dissipative interactions between different quantum systems are essential for the construction of hybrid quantum systems and the investigation of novel quantum phenomena. Here, we propose and analyze a magnon-skyrmion hybrid quantum system, consisting of a micromagnet and nearby magnetic skyrmions. We predict a strong-coupling mechanism between the magnonic mode of the micromagnet and the quantized helicity degree of freedom of the skyrmion. We show that with this hybrid setup it is possible to induce magnon-mediated nonreciprocal interactions and responses between distant skyrmion qubits or between skyrmion qubits and other quantum systems like superconducting qubits. This work provides a quantum platform for the investigation of diverse quantum effects and quantum information processing with magnetic microstructures.
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Recent advancements in our understanding of cell membrane dynamics have shed light on the importance of plasma membrane (PM) nanodomains in plant cell signaling. Nevertheless, many aspects of membrane nanodomains, including their regulatory mechanisms and biological functions, remain enigmatic. To address this knowledge gap, our review article proposes a novel perspective wherein signaling pathways target endoplasmic reticulum (ER)-based lipid metabolism to exert control over the formation and function of membrane nanodomains. Subsequently, these nanodomains reciprocate by influencing the localization and activity of signaling molecules at the PM. We place a specific emphasis on ER-based enzymatic reactions, given the ER's central role in membrane lipid biosynthesis and its capacity to directly impact PM lipid composition, particularly with regard to saturation levels - an essential determinant of nanodomain properties. The interplay among cell signaling, glycerolipid metabolism, and PM nanodomain may create feedforward/feedback loops that fine-tune cellular responses to developmental and environmental cues.
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Membrane cellulaire , Réticulum endoplasmique , Métabolisme lipidique , Transduction du signal , Réticulum endoplasmique/métabolisme , Membrane cellulaire/métabolisme , Microdomaines membranaires/métabolisme , Lipides membranaires/métabolismeRÉSUMÉ
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies. Lactate dehydrogenase family genes (LDHs) play a critical role in tumor metabolism, but their functions in HNSCC have not been investigated thoroughly. Thus, we aimed to explore the value of LDHs in HNSCC. METHODS: The association between LDHs expression and mutations, methylation, copy number variations (CNVs), alternative splicing (AS) and competing endogenous RNA (ceRNA) was investigated in The Cancer Genome Atlas (TCGA). The expression level of LDHs in OSCC tissues and adjacent normal tissues was verified by qPCR. Algorithms, such as ssGSEA, ESTIMATE, xCell and TIDE were utilized to analyze the characteristics of immune infiltration. Pathway alternations were enriched by GO, GSEA and KEGG analysis. The Mantel test was employed to elucidate the correlation between metabolism and the tumor microenvironment (TME). Subsequently, MTT and colony formation assays were utilized to assess the impact of LDHB knockdown on cellular proliferation. Additionally, ATP and lactate assays were performed to examine metabolic alterations. Co-culture experiments further investigated the effect of LDHB knockdown on T cell differentiation. RESULTS: LDHs were completely analyzed in multiple databases, among which LDHB was differentially expressed in HNSCC and significantly associated with prognosis. Low LDHB expression had better clinicopathological characteristics. Downregulated LDHB expression was associated with enhanced immune cell infiltration and could influence tumor metabolism. Despite having worse cytotoxic T lymphocyte dysfunction, the LDHBlow group was predicted to respond more favorably to immune checkpoint inhibitors (ICIs) therapy. Moreover, the correlation between metabolism and TME was depicted. In vitro, LDHB knockdown resulted in inhibited cell proliferation, increased lactate levels and decreased ATP levels, while promoted the Th1 differentiation of T cells. CONCLUSIONS: Our study provided a comprehensive analysis of the LDHs and illustrated low LDHB expression could inhibit tumor cell proliferation and ATP production by influencing metabolism, with improved immune cell infiltration and better response to immunotherapy.
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Tumeurs de la tête et du cou , Immunothérapie , L-Lactate dehydrogenase , Carcinome épidermoïde de la tête et du cou , Humains , Carcinome épidermoïde de la tête et du cou/métabolisme , Carcinome épidermoïde de la tête et du cou/génétique , L-Lactate dehydrogenase/métabolisme , L-Lactate dehydrogenase/génétique , Tumeurs de la tête et du cou/métabolisme , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/thérapie , Microenvironnement tumoral , Marqueurs biologiques tumoraux/métabolisme , Marqueurs biologiques tumoraux/génétique , Lignée cellulaire tumorale , Prolifération cellulaire , Régulation de l'expression des gènes tumoraux , Différenciation cellulaire , IsoenzymesRÉSUMÉ
Cortical spreading depression (CSD) is a slow wave of cortical depolarization closely associated with migraines with an aura. Previously, it was thought that CSD depolarization was mainly driven by neurons, with characteristic changes in neuronal swelling and increased extracellular potassium (K+) and glutamate. However, the role of astrocytes, a member of the neurovascular unit, in migraine with CSD has recently received increasing attention. In the early stages of CSD, astrocytes provide neurons with energy support and clear K+ and glutamate from synaptic gaps. However, in the late stages of CSD, astrocytes release large amounts of lactic acid to exacerbate hypoxia when the energy demand exceeds the astrocytes' compensatory capacity. Astrocyte endfoot swelling is a characteristic of CSD, and neurons are not similarly altered. It is primarily due to K+ influx and abnormally active calcium (Ca2+) signaling. Aquaporin 4 (AQP-4) only mediates K+ influx and has little role as an aquaporin. Astrocytes endfoot swelling causes perivascular space closure, slowing the glymphatic system flow and exacerbating neuroinflammation, leading to persistent CSD. Astrocytes are double-edged swords in migraine with CSD and may be potential targets for CSD interventions.
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OBJECTIVE: Growing attention has been paid recently to electrocardiogram (ECG) based obstructive sleep apnea (OSA) detection, with some progresses been made on this topic. However, the lack of data, low data quality, and incomplete data labeling hinder the application of deep learning to OSA detection, which in turn affects the overall generalization capacity of the network. METHODS: To address these issues, we propose the ResT-ECGAN framework. It uses a one-dimensional generative adversarial network (ECGAN) for sample generation, and integrates it into ResT-Net for OSA detection. ECGAN filters the generated ECG signals by incorporating the concept of fuzziness, effectively increasing the amount of high-quality data. ResT-Net not only alleviates the problems caused by deepening the network but also utilizes multi-head attention mechanisms to parallelize sequence processing and extract more valuable OSA detection features by leveraging contextual information. RESULTS: Through extensive experiments, we verify that ECGAN can effectively improve the OSA detection performance of ResT-Net. Using only ResT-Net for detection, the accuracy on the Apnea-ECG and private databases is 0.885 and 0.837, respectively. By adding ECGAN-generated data augmentation, the accuracy is increased to 0.893 and 0.848, respectively. CONCLUSION AND SIGNIFICANCE: Comparing with the state-of-the-art deep learning methods, our method outperforms them in terms of accuracy. This study provides a new approach and solution to improve OSA detection in situations with limited labeled samples.