Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The molecular understanding of ALS is hampered by the lack of experimental models recapitulating disease heterogeneity and analytical framework integrating multi-omics datasets. Here, we developed a pipeline integrating machine learning and consensus clustering to analyze a large-scale dataset of patient-derived motor neuron models from Answer ALS.
View Article and Find Full Text PDFCell Oncol (Dordr)
August 2025
Background: Non-small cell lung cancer (NSCLC) mainly includes lung squamous cell carcinoma and lung adenocarcinoma, and its extremely high morbidity and mortality are the main causes of poor prognosis in NSCLC patients. Therefore, it is particularly important to study the mechanisms associated with tumor proliferation and metastasis and explore new molecular targets of NSCLC. Studies have shown that Guanosine monophosphate synthase (GMPS) may serve as a potential drug target, but its biological function and molecular mechanism in NSCLC are still unknown.
View Article and Find Full Text PDFThe molecular continuum of premalignant-to-malignant transition remains elusive in carcinogenesis, primarily due to the difficulty in sampling transitional lesions. Here, we present comprehensive genomic and immunological profiling of 21 very early hepatocellular carcinomas (veHCCs) arising within 17 cancer-prone DNs. Surprisingly, 82% of cancer-prone DNs harbored alterations, suggesting a predisposing rather than causative role in malignancy transition.
View Article and Find Full Text PDFGlioblastoma (GBM) is the most lethal primary brain tumor with intra-tumoral hierarchy of glioblastoma stem cells (GSCs). The heterogeneity of GSCs within GBM inevitably leads to treatment resistance and tumor recurrence. Molecular mechanisms of different cellular state GSCs remain unclear.
View Article and Find Full Text PDFBackground: Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear.
Methods: We determined immune-cell signatures of PICS after sepsis at single-cell resolution.
The central nervous system (CNS) is increasingly recognized as a critical modulator in the oncogenesis of glioblastoma multiforme (GBM), with interactions between cancer and local neuronal circuits frequently leading to epilepsy; however, the relative contributions of these factors remain unclear. Here, we report a coordinated intratumor shift among distinct cancer subtypes within progenitor-like families of epileptic GBM patients, revealing an accumulation of oligodendrocyte progenitor (OPC)-like subpopulations at the cancer-neuron interface along with heightened electrical signaling activity in the surrounding neuronal networks. The OPC-like cells associated with epilepsy express KCND2, which encodes the voltage-gated K channel K4.
View Article and Find Full Text PDFGlioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion.
View Article and Find Full Text PDFLong noncoding RNAs (lncRNAs) have been demonstrated to participate in neuroblastoma cisplatin resistance and tumorigenesis. LncRNA LINC00460 was previously reported to play a critical regulatory role in many cancer development. Nevertheless, its role in modulating neuroblastoma cisplatin resistance has not been explored till now.
View Article and Find Full Text PDFBackground: Early stage lung adenocarcinomas manifested as ground-glass nodules (GGNs) are increasingly being detected, but screening and diagnosis for GGN-featured lung adenocarcinomas in different risk populations reach no agreement.
Objectives: To analyze the clinical, pathological, imaging and genetic features of GGN-featured lung adenocarcinomas on high-resolution computed tomography (HRCT) in different risk groups.
Methods: Include patients with GGNs on HRCT surgically diagnosed as lung adenocarcinoma in the West China Hospital, Sichuan University from 2009 to 2021, and their clinical, pathological, imaging and gene sequencing data.
Clin Cancer Res
September 2023
Purpose: The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state.
View Article and Find Full Text PDFIt is important to describe lineages before they go extinct, as we can only protect what we know. This is especially important in the case of microendemic species likely to be relict populations, such as salamanders in southern China. Here, we unexpectedly sampled individuals in Fujian province, China, and then worked on determining their taxonomic status.
View Article and Find Full Text PDFAnimals (Basel)
March 2023
The quality and yield of cashmere closely affect the economic benefits of cashmere goat farming. Studies have shown that controlling light can have an important impact on cashmere but can also affect the concentration of harmful gases. In order to explore the impact of a short photoperiod on the growth of cashmere and harmful gases in goat houses, 130 female (non-pregnant) Shanbei white cashmere goats, aged 4-5 years with similar body weights, were randomly divided into a control group and a treatment group, with 65 goats in each group.
View Article and Find Full Text PDFAnthropogenic activities pose a more significant threat to the environment than natural phenomena by contaminating the environment with heavy metals. Cadmium (Cd), a highly poisonous heavy metal, has a protracted biological half-life and threatens food safety. Plant roots absorb Cd due to its high bioavailability through apoplastic and symplastic pathways and translocate it to shoots through the xylem with the help of transporters and then to the edible parts via the phloem.
View Article and Find Full Text PDFGlioblastoma is the most malignant primary brain tumor, the prognosis of which remains dismal even with aggressive surgical, medical, and radiation therapies. Glioblastoma stem cells (GSCs) promote therapeutic resistance and cellular heterogeneity due to their self-renewal properties and capacity for plasticity. To understand the molecular processes essential for maintaining GSCs, we performed an integrative analysis comparing active enhancer landscapes, transcriptional profiles, and functional genomics profiles of GSCs and non-neoplastic neural stem cells (NSCs).
View Article and Find Full Text PDFUnlabelled: Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single-cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia.
View Article and Find Full Text PDFThe immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed.
View Article and Find Full Text PDFJ Clin Invest
January 2023
Glioblastoma ranks among the most aggressive and lethal of all human cancers. Self-renewing, highly tumorigenic glioblastoma stem cells (GSCs) contribute to therapeutic resistance and maintain cellular heterogeneity. Here, we interrogated superenhancer landscapes of primary glioblastoma specimens and patient-derived GSCs, revealing a kelch domain-containing gene, specifically Kelch domain containing 8A (KLHDC8A) with a previously unknown function as an epigenetically driven oncogene.
View Article and Find Full Text PDFSmall Methods
November 2022
Although many studies have investigated functional molecules in extracellular vesicles (EVs), the exact number of ribonucleic acid molecules in a single-EV is unknown. Therefore, it is critical to explore the transcriptomic features and heterogeneity at the level of a single-EV. Here, using the 10x Genomics platform, the RNA cargos are profiled in single EVs derived from human K562 and mesenchymal stem cells.
View Article and Find Full Text PDFOpen Life Sci
August 2022
fusion genes are diverse. Approximately 30 different fusion protein partners have been described previously, and some of these fusion proteins have been reported to be effective against -tyrosine kinase inhibitor (TKI). rearrangements often occur at a common breakpoint in exon 20 of the genome.
View Article and Find Full Text PDFUnlabelled: Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that β2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-β1 (TGFβ1).
View Article and Find Full Text PDFTwo new quaternary selenides AAgGaSe, (A = Rb, 1; Cs, 2) were synthesised solid-state reaction in sealed silica tubes. Compounds 1 and 2 crystallised in the monoclinic space group (no. 8) and their three-dimensional [AgGaSe] anionic frameworks were comprised of AgSe and GaSe tetrahedrons.
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