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1.
J Ment Health ; : 1-9, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602358

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms after natural disaster can have a detrimental effect on marital relationships, which may be through parenting-related factor. AIMS: The study aimed to examine the mechanism underlying the long-term effects of PTSD symptoms on marital satisfaction via coparenting, and its differences between men and women following the Super Typhoon Lekima. METHODS: Participants were 465 married victims with children. They reported their PTSD, coparenting, and marital satisfaction at three and fifteen months after the tropical cyclone. RESULTS: The results showed that for women, only higher negative cognitive and emotional alterations (NCEA) symptoms were associated with lower marital satisfaction through conflict coparenting. For men, higher intrusion, NCEA, and hyperarousal symptoms were associated with marital satisfaction through different coparenting. To be specific, for men, higher intrusion symptoms were associated with lower marital satisfaction via less reprimand coparenting; higher NCEA symptoms were associated with lower marital satisfaction via less integrity coparenting, and associated with higher marital satisfaction via less conflict coparenting; higher hyperarousal symptoms were associated with lower marital satisfaction via more conflict coparenting. CONCLUSIONS: These findings suggested that the long-term effect of PTSD symptoms on marital satisfaction via coparenting mainly showed for men.

2.
Mol Pain ; : 17448069241249455, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597175

RESUMO

Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.

3.
IEEE Trans Med Imaging ; PP2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587959

RESUMO

Multimodal machine learning models are being developed to analyze pathology images and other modalities, such as gene expression, to gain clinical and biological insights. However, most frameworks for multimodal data fusion do not fully account for the interactions between different modalities. Here, we present an attention-based fusion architecture that integrates a graph representation of pathology images with gene expression data and concomitantly learns from the fused information to predict patient-specific survival. In our approach, pathology images are represented as undirected graphs, and their embeddings are combined with embeddings of gene expression signatures using an attention mechanism to stratify tumors by patient survival. We show that our framework improves the survival prediction of human non-small cell lung cancers, outperforming existing state-of-the-art approaches that leverage multimodal data. Our framework can facilitate spatial molecular profiling to identify tumor heterogeneity using pathology images and gene expression data, complementing results obtained from more expensive spatial transcriptomic and proteomic technologies.

4.
Adv Mater ; : e2312341, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567889

RESUMO

Noncentrosymmetric transition metal dichalcogenide (TMD) monolayers offer a fertile platform for exploring unconventional Ising superconductivity (SC) and charge density waves (CDWs). However, the vulnerability of isolated monolayers to structural disorder and environmental oxidation often degrade their electronic coherence. Herein, an alternative approach is reported for fabricating stable and intrinsic monolayers of 1H-TaS2 sandwiched between SnS blocks in a (SnS)1.15TaS2 van der Waals (vdW) superlattice. The SnS block layers not only decouple individual 1H-TaS2 sublayers to endow them with monolayer-like electronic characteristics, but also protect the 1H-TaS2 layers from electronic degradation. The results reveal the characteristic 3 × 3 CDW order in 1H-TaS2 sublayers associated with electronic rearrangement in the low-lying sulfur p band, which uncovers a previously undiscovered CDW mechanism rather than the conventional Fermi surface-related framework. Additionally, the (SnS)1.15TaS2 superlattice exhibits a strongly enhanced Ising-like SC with a layer-independent Tc of ≈3.0 K, comparable to that of the isolated monolayer 1H-TaS2 sample, presumably attributed to their monolayer-like characteristics and retained Fermi states. These results provide new insights into the long-debated CDW order and enhanced SC of monolayer 1H-TaS2, establishing bulk vdW superlattices as promising platforms for investigating exotic collective quantum phases in the 2D limit.

5.
Nat Commun ; 15(1): 3029, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589456

RESUMO

The discovery of various primary ferroic phases in atomically-thin van der Waals crystals have created a new two-dimensional wonderland for exploring and manipulating exotic quantum phases. It may also bring technical breakthroughs in device applications, as evident by prototypical functionalities of giant tunneling magnetoresistance, gate-tunable ferromagnetism and non-volatile ferroelectric memory etc. However, two-dimensional multiferroics with effective magnetoelectric coupling, which ultimately decides the future of multiferroic-based information technology, has not been realized yet. Here, we show that an unconventional magnetoelectric coupling mechanism interlocked with heterogeneous ferrielectric transitions emerges at the two-dimensional limit in van der Waals multiferroic CuCrP2S6 with inherent antiferromagnetism and antiferroelectricity. Distinct from the homogeneous antiferroelectric bulk, thin-layer CuCrP2S6 under external electric field makes layer-dependent heterogeneous ferrielectric transitions, minimizing the depolarization effect introduced by the rearrangements of Cu+ ions within the ferromagnetic van der Waals cages of CrS6 and P2S6 octahedrons. The resulting ferrielectric phases are characterized by substantially reduced interlayer magnetic coupling energy of nearly 50% with a moderate electric field of 0.3 V nm-1, producing widely-tunable magnetoelectric coupling which can be further engineered by asymmetrical electrode work functions.

6.
Lancet ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38643776

RESUMO

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

7.
bioRxiv ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38559216

RESUMO

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.

8.
mBio ; : e0075124, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591890

RESUMO

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly, BA.2.87.1 is more resistant to neutralization by XBB.1.5-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines. IMPORTANCE: This study investigates the recently emerged SARS-CoV-2 variants, BA.2.87.1 and JN.1, in comparison to earlier variants and the parental D614G. Varied infectivity and cell-cell fusion activity among these variants suggest potential disparities in their ability to infect target cells and possibly pathogenesis. BA.2.87.1 exhibits lower nAb escape from bivalent mRNA vaccinee and BA.2.86/JN.1-infected sera than JN.1 but is relatively resistance to XBB.1.5-vaccinated hamster sera, revealing distinct properties in immune reason and underscoring the significance of continuing surveillance of variants and reformulation of vaccines. Antigenic differences between BA.2.87.1 and other earlier variants yield critical information not only for antibody evasion but also for viral evolution. In conclusion, this study furnishes timely insights into the spike biology and immune escape of the emerging variants BA.2.87.1 and JN.1, thus guiding effective vaccine development and informing public health interventions.

9.
Redox Rep ; 29(1): 2332038, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38563333

RESUMO

OBJECTIVES: Gentamicin is one of the most common ototoxic drugs that can lower patients' quality of life. Oxidative stress is a key factors inducing sensory hair cell death during gentamicin administration. So far, there are no effective drugs to prevent or treat gentamicin- induced hearing loss. A recent study found cystic fibrosis transmembrane conductance regulator (CFTR) as a new target to modulate cellular oxidative balance. The objective of this study was to estimate the effect of the CFTR activator ivacaftor on gentamicin-induced ototoxicity and determine its mechanism. METHODS: The hair cell count was analyzed by Myosin 7a staining. Apoptosis was analyzed by TUNEL Apoptosis Kit. Cellular reactive oxygen species (ROS) level was detected by DCFH-DA probes. The Nrf2 related proteins expression levels were analyzed by western blot. RESULTS: An in vitro cochlear explant model showed that gentamicin caused ROS accumulation in sensory hair cells and induced apoptosis, and this effect was alleviated by pretreatment with ivacaftor. Western blotting showed that ivacaftor administration markedly increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO1), and NAD(P)H:quinone oxidoreductase 1 (NQO1). The protective effect of ivacaftor was abolished by the Nrf2 inhibitor ML385. DISCUSSION: Our results indicate the protective role of the CFTR-Nrf2-HO1/NQO1 pathway in gentamicin-induced ototoxicity. Ivacaftor may be repositioned or repurposed towards aminoglycosides-induced hearing loss.


Assuntos
Aminofenóis , Perda Auditiva , Ototoxicidade , Quinolonas , Humanos , Gentamicinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/farmacologia , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/farmacologia , Qualidade de Vida , Estresse Oxidativo , Apoptose , NAD(P)H Desidrogenase (Quinona)/metabolismo , NAD(P)H Desidrogenase (Quinona)/farmacologia
10.
World J Gastrointest Oncol ; 16(3): 630-642, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577463

RESUMO

As important messengers of intercellular communication, exosomes can regulate local and distant cellular communication by transporting specific exosomal contents and can also promote or suppress the development and progression of gastric cancer (GC) by regulating the growth and proliferation of tumor cells, the tumor-related immune response and tumor angiogenesis. Exosomes transport bioactive molecules including DNA, proteins, and RNA (coding and noncoding) from donor cells to recipient cells, causing reprogramming of the target cells. In this review, we will describe how exosomes regulate the cellular immune response, tumor angiogenesis, proliferation and metastasis of GC cells, and the role and mechanism of exosome-based therapy in human cancer. We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treatment of GC and their relationship with drug resistance.

11.
Anal Chem ; 96(16): 6170-6179, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38616610

RESUMO

Despite their many important physiological functions, past work on the diverse sequences of human milk oligosaccharides (HMOs) has been focused mainly on the highly abundant HMOs with a relatively low degree of polymerization (DP) due to the lack of efficient methods for separation/purification and high-sensitivity sequencing of large-sized HMOs with DP ≥ 10. Here we established an ultrahigh-temperature preparative HPLC based on a porous graphitized carbon column at up to 145 °C to overcome the anomeric α/ß splitting problem and developed further the negative-ion ESI-CID-MS/MS into multistage MSn using a combined product-ion scanning of singly charged molecular ion and doubly charged fragment ion of the branching Gal and adjacent GlcNAc residues. The separation and sequencing method allows efficient separation of a neutral fraction with DP ≥ 10 into 70 components, among which 17 isomeric difucosylated nona- and decasaccharides were further purified and sequenced. As a result, novel branched difucosyl heptaose and octaose backbones were unambiguously identified in addition to the conventional linear and branched octaose backbones. The novel structures of difucosylated DF-novo-heptaose, DF-novo-LNO I, and DF-novo-LNnO I were corroborated by NMR. The various fucose-containing Lewis epitopes identified on different backbones were confirmed by oligosaccharide microarray analysis.


Assuntos
Leite Humano , Oligossacarídeos , Espectrometria de Massas por Ionização por Electrospray , Humanos , Leite Humano/química , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Temperatura
12.
Pest Manag Sci ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625031

RESUMO

BACKGROUND: To discover novel fungicide candidates, five series of novel norbornene hydrazide, bishydrazide, oxadiazole, carboxamide and acylthiourea derivatives (2a-2t, 3a-3f, 4a-4f, 5a-5f and 7a-7f) were designed, synthesized and assayed for their antifungal activity toward seven representative plant fungal pathogens. RESULTS: In the in vitro antifungal assay, some title norbornene derivatives presented good antifungal activity against Botryosphaeria dothidea, Sclerotinia sclerotiorum and Fusarium graminearum. Especially, compound 2b exhibited the best inhibitory activity toward B. dothidea with the median effective concentration (EC50) of 0.17 mg L-1, substantially stronger than those of the reference fungicides boscalid and carbendazim. The in vivo antifungal assay on apples revealed that 2b had significant curative and protective effects, both of which were superior to boscalid. In the preliminary antifungal mechanism study, 2b was able to injure the surface morphology of hyphae, destroy the cell membrane integrity and increase the intracellular reactive oxygen species (ROS) level of B. dothidea. In addition, 2b could considerably inhibit the laccase activity with the median inhibitory concentration (IC50) of 1.02 µM, much stronger than that of positive control cysteine (IC50 = 35.50 µM). The binding affinity and interaction mode of 2b with laccase were also confirmed by molecular docking. CONCLUSION: This study presented a promising lead compound for the study of novel laccase inhibitors as fungicidal agrochemicals, which demonstrate significant anti-B. dothidea activity and laccase inhibitory activity. © 2024 Society of Chemical Industry.

13.
Am J Pathol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588853

RESUMO

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperforms existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor (normal) lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heat maps. The network was further tested using endobronchial biopsies from two data cohorts, containing normal to carcinoma in situ histology, and it demonstrated a unique capability to differentiate carcinoma in situ lung squamous PMLs based on their progression status to invasive carcinoma. The network may have utility in stratifying PMLs for chemoprevention trials or more aggressive follow-up.

14.
Prog Neurobiol ; : 102612, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642602

RESUMO

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.

15.
Sensors (Basel) ; 24(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38610392

RESUMO

The decipherment of ancient Chinese scripts, such as oracle bone and bronze inscriptions, holds immense significance for understanding ancient Chinese history, culture, and civilization. Despite substantial progress in recognizing oracle bone script, research on the overall recognition of ancient Chinese characters remains somewhat lacking. To tackle this issue, we pioneered the construction of a large-scale image dataset comprising 9233 distinct ancient Chinese characters sourced from images obtained through archaeological excavations. We propose the first model for recognizing the common ancient Chinese characters. This model consists of four stages with Linear Embedding and Swin-Transformer blocks, each supplemented by a CoT Block to enhance local feature extraction. We also advocate for an enhancement strategy, which involves two steps: firstly, conducting adaptive data enhancement on the original data, and secondly, randomly resampling the data. The experimental results, with a top-one accuracy of 87.25% and a top-five accuracy of 95.81%, demonstrate that our proposed method achieves remarkable performance. Furthermore, through the visualizing of model attention, it can be observed that the proposed model, trained on a large number of images, is able to capture the morphological characteristics of ancient Chinese characters to a certain extent.

16.
Chem Biodivers ; : e202302033, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616167

RESUMO

To explore more potential fungicides with new scaffolds, thirty-seven norbornene carboxamide/sulfonamide derivatives were designed, synthesized, and assayed for inhibitory activity against six plant pathogenic fungi and oomycetes. The preliminary antifungal assay suggested that the title derivatives showed moderate to good antifungal activity against six plant pathogens. Especially, compound 6e presented excellent in vitro antifungal activity against Sclerotinia sclerotiorum (EC50 = 0.71 mg/L), which was substantially stronger than pydiflumetofen. In vivo antifungal assay indicated 6e displayed prominent protective and curative effects on rape leaves infected by S. sclerotiorum. The preliminary mechanism research displayed that 6e could damage the surface morphology and inhibit the sclerotia formation of S. sclerotiorum. In addition, the in vitro enzyme inhibition bioassay indicated that 6e displayed pronounced laccase inhibition activity (IC50 = 0.63 µM), much stronger than positive control cysteine. Molecular docking elucidated the binding modes between 6e and laccase. The bioassay results and mechanism investigation demonstrated that this class of norbornene carboxamide/sulfonamide derivatives could be promising laccase inhibitors for novel fungicide development.

17.
Cell Death Differ ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605168

RESUMO

Myddosome is an oligomeric complex required for the transmission of inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for the self-assemble of Myddosome proteins and regulation of intracellular signaling remains poorly understood. Here, we identify OTUD5 acts as an essential regulator for MyD88 oligomerization and Myddosome formation. OTUD5 directly interacts with MyD88 and cleaves its K11-linked polyubiquitin chains at Lys95, Lys231 and Lys250. This polyubiquitin cleavage enhances MyD88 oligomerization after LPS stimulation, which subsequently promotes the recruitment of downstream IRAK4 and IRAK2 to form Myddosome and the activation of NF-κB and MAPK signaling and production of inflammatory cytokines. Consistently, Otud5-deficient mice are less susceptible to LPS- and CLP-induced sepsis. Taken together, our findings reveal a positive regulatory role of OTUD5 in MyD88 oligomerization and Myddosome formation, which provides new sights into the treatment of inflammatory diseases.

18.
Front Immunol ; 15: 1381340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633246

RESUMO

Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/metabolismo , Baço/metabolismo , Camundongos Endogâmicos C57BL , Inflamação , Camundongos Knockout
19.
World J Clin Cases ; 12(11): 1857-1862, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660559

RESUMO

In this editorial, we comment on an article by Ruan et al published in a recent issue of the World Journal of Clinical Case. Pulmonary meningothelial proliferative lesions, including primary pulmonary meningiomas, minute pulmonary meningothelial-like nodules, and metastatic pulmonary meningiomas are rare pulmonary lesions. These lesions are difficult to differentiate from lung cancers based on clinical and imaging manifestations. Herein, we briefly introduce the clinical, imaging, and pathological characteristics of these lesions and discuss their pathogenesis to strengthen the current understanding of pulmonary meningothelial proliferative lesions in clinical diagnosis and therapy.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38651571

RESUMO

PURPOSE: To investigate the validity of using tibial capsular reflection and septum in the posterior compartment as landmark during posterior cruciate ligament (PCL) reconstruction (PCLR). METHODS: Anatomic measurements were obtained for 12 fresh human cadaveric knee specimens to observe the spatial position of the tibial insertion of the PCL in relation to the posterior septum and the capsular reflection in the posterior compartment. Sixty patients who underwent reconstruction of the PCL between 2020 and 2023 were also retrospectively investigated. The tibial tunnel was replaced in all patients using the same method (with reference to the tibial capsular reflection and the posterior septum). The placement of the tibial tunnel was assessed using X-ray fluoroscopy intraoperatively and computed tomography and three-dimensional reconstruction postoperatively. RESULTS: All fibres in the tibial insertion of the PCL in the 12 cadaveric specimens were located in the posteromedial compartment, adjacent to the posterior septum. The inferior border of the PCL insertion is adjacent to the tibial capsular reflection, which is attached at the champagne glass drop-off of the posterior tibia. In our previous cases, none of the patients experienced postoperative or intraoperative complications such as neurovascular injury, and the angle between the pin and the PCL facet was 93.1 ± 3.9° as measured on intraoperative radiographs. The mean distance from the centre of the tibial tunnel outlet to the inferior border of the PCL insertion was 5.6 ± 1.1 mm, and the distance from the centre of the tibial tunnel outlet to the outer border of the PCL insertion as a percentage of the length of the inferior border of PCL insertion was 42.2 ± 6.3%. CONCLUSION: The tibial capsular reflection and septum in the posterior compartment are safe and reliable soft-tissue landmark for tibial tunnel drilling in PCLR. LEVEL OF EVIDENCE: Level Ⅳ.

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