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Infantile epileptic spasm syndrome (IESS) is a new concept proposed recently. IESS is a unique and age-specific refractory epilepsy syndrome. The recent advances in molecular biology, neuroimmunology and the in-depth study of anti-epileptic mechanism in antiepileptic drugs have led to the achievements in the definition and treatment of infantile epileptic spasm. At present, the use of traditional antiepileptic drugs is decreasing, while the use of new antiepileptic drugs is increasing. In this paper, based on the relevant literature in recent years, the authors discuss the pathogenesis, epidemiology, etiology, diagnosis, treatment, therapeutic drugs, clinical progress, efficacy, and safety of infantile epileptic spasm, hoping to introduce the latest status in research and achievements of IESS.

Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME. [ABSTRACT FROM AUTHOR]

Time-series Interferometric Synthetic Aperture Radar (InSAR) technology, renowned for its high-precision, wide coverage, and all-weather capabilities, has become an essential tool for Earth observation. However, the quality of the interferometric baseline network significantly influences the monitoring accuracy of InSAR technology. Therefore, optimizing the interferometric baseline is crucial for enhancing InSAR's monitoring accuracy. Surface vegetation changes can disrupt the coherence between SAR images, introducing incoherent noise into interferograms and reducing InSAR's monitoring accuracy. To address this issue, we propose and validate an optimization method for the InSAR baseline that considers changes in vegetation coverage (OM-InSAR-BCCVC) in the Yuanmou dry-hot valley. Initially, based on the imaging times of SAR image pairs, we categorize all interferometric image pairs into those captured during months of high vegetation coverage and those from months of low vegetation coverage. We then remove the image pairs with coherence coefficients below the category average. Using the Small Baseline Subset InSAR (SBAS-InSAR) technique, we retrieve surface deformation information in the Yuanmou dry-hot valley. Landslide identification is subsequently verified using optical remote sensing images. The results show that significant seasonal changes in vegetation coverage in the Yuanmou dry-hot valley lead to noticeable seasonal variations in InSAR coherence, with the lowest coherence in July, August, and September, and the highest in January, February, and December. The average coherence threshold method is limited in this context, resulting in discontinuities in the interferometric baseline network. Compared with methods without baseline optimization, the interferometric map ratio improved by 17.5% overall after applying the OM-InSAR-BCCVC method, and the overall inversion error RMSE decreased by 0.5 rad. From January 2021 to May 2023, the radar line of sight (LOS) surface deformation rate in the Yuanmou dry-hot valley, obtained after atmospheric correction by GACOS, baseline optimization, and geometric distortion region masking, ranged from −73.87 mm/year to 127.35 mm/year. We identified fifteen landslides and potential landslide sites, primarily located in the northern part of the Yuanmou dry-hot valley, with maximum subsidence exceeding 100 mm at two notable points. The OM-InSAR-BCCVC method effectively reduces incoherent noise caused by vegetation coverage changes, thereby improving the monitoring accuracy of InSAR. [ABSTRACT FROM AUTHOR]

Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of undifferentiated pancreatic ductal adenocarcinoma, with a generally poor prognosis and only sporadic cases reported worldwide. Histologically, the most notable feature of SCP is the presence of abundant of mesenchymatoid spindle tumor cells in the tumor, which lack glandular differentiation. Immunohistochemically, SCP is characterized by the expression of both mesenchymal and epithelial markers. With only a few reported cases, there is limited knowledge about its molecular and clinicopathological characteristics. Therefore, the present study performed a literature search to identify all relevant published studies. The present review provides an overview of the histogenesis, diagnosis, genetic features, prognosis and treatment of SCP, specifically focusing on the molecular alterations. Furthermore, a single-center experience is reported, which adds to the limited evidence available in the literature. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) actively reprogram their tumor microenvironment (TME) to sustain a supportive niche, which may have a dramatic impact on prognosis and immunotherapy. However, our knowledge of the landscape of the gastric cancer stem-like cell (GCSC) microenvironment needs to be further improved. A multi-step process of machine learning approaches was performed to develop and validate the prognostic and predictive potential of the GCSC-related score (GCScore). The high GCScore subgroup was not only associated with stem cell characteristics, but also with a potential immune escape mechanism. Furthermore, we experimentally demonstrated the upregulated infiltration of CD206+ tumor-associated macrophages (TAMs) in the invasive margin region, which in turn maintained the stem cell properties of tumor cells. Finally, we proposed that the GCScore showed a robust capacity for prediction for immunotherapy, and investigated potential therapeutic targets and compounds for patients with a high GCScore. The results indicate that the proposed GCScore can be a promising predictor of prognosis and responses to immunotherapy, which provides new strategies for the precision treatment of GCSCs. [ABSTRACT FROM AUTHOR]

RIG-I and MDA5 are cytoplasmic RNA sensors that mediate cell intrinsic immunity against viral pathogens. While it has been well-established that RIG-I and MDA5 recognize RNA viruses, their interactive network with DNA viruses, including herpes simplex virus 1 (HSV-1), remains less clear. Using a combination of RNA-deep sequencing and genetic studies, we show that the γ134.5 gene product, a virus-encoded virulence factor, enables HSV growth by neutralization of RIG-I dependent restriction. When expressed in mammalian cells, HSV-1 γ134.5 targets RIG-I, which cripples cytosolic RNA sensing and subsequently suppresses antiviral gene expression. Rather than inhibition of RIG-I K63-linked ubiquitination, the γ134.5 protein precludes the assembly of RIG-I and cellular chaperone 14-3-3ε into an active complex for mitochondrial translocation. The γ134.5-mediated inhibition of RIG-I-14-3-3ε binding abrogates the access of RIG-I to mitochondrial antiviral-signaling protein (MAVS) and activation of interferon regulatory factor 3. As such, unlike wild type virus HSV-1, a recombinant HSV-1 in which γ134.5 is deleted elicits efficient cytokine induction and replicates poorly, while genetic ablation of RIG-I expression, but not of MDA5 expression, rescues viral growth. Collectively, these findings suggest that viral suppression of cytosolic RNA sensing is a key determinant in the evolutionary arms race of a large DNA virus and its host. Author summary: Host cytosolic RNA sensing has been implicated in the recognition of herpesvirus infection. As such, herpesviruses likely have evolved strategies to escape this host surveillance mechanism; however, molecular insight into antagonism of RNA sensors by herpesviruses remains largely elusive. We show that the γ134.5 protein encoded by herpes simplex virus 1 inactivates the helicase RIG-I that serves as an RNA receptor. Viral γ134.5 hijacks RIG-I and selectively inhibits its engagement with the chaperone protein 14-3-3ε in the cytoplasm of infected cells. Targeting of RIG-I by γ134.5 blocks the cytosol-to-mitochondrial translocation of RIG-I, which ultimately dampens antiviral innate immunity. Finally, depletion of RIG-I enhances the growth of a recombinant HSV-1 in which γ134.5 was deleted. Our work provides insights into viral modulation of intracellular RNA recognition in herpesvirus infection, which in turn may guide the rational development of therapeutic agents. [ABSTRACT FROM AUTHOR]