Background: Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. Methods: To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated in vitro and in vivo . Results: Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion via the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. Conclusion: This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion via M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.

Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed m 6 A RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering was applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between m 6 A regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and m 6 A cluster 1/2 groups were utilized for the hub genes, and four genes ( TAGLN2, PDPN, TIMP1, EMP3) were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76–0.83) and 0.72 (0.68–0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found PDPN and TIMP1 were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.

Stroke is a disastrous neurological disease with high morbidity and mortality. The mechanism of the pathological process is extremely complicated and unclear.Although many basic studies have confirmed molecular mechanism of brain injury after stroke, these studies have not yet translated into treatment and clinical application. Ferroptosis is a form of cell death that is distinct from necrosis, apoptosis, and autophagy morphologically and biochemically and is characterized by iron-dependent accumulation of lipid peroxides. Despite ferroptosis being first identified in cancer cells, it was recently revealed to also be a significant factor in the pathological process of stroke. A better understanding of ferroptosis in stroke may provide us with better therapeutic targets to treat this devastating disease. Here, we systematically summarized the current mechanism of ferroptosis and reviewed the current studies regarding the relationship between ferroptosis and stroke.

No abstract

Planar digital image sensors facilitate broad applications in a wide range of areas1–5, and the number of pixels has scaled up rapidly in recent years2,6. However, the practical performance of imaging systems is fundamentally limited by spatially nonuniform optical aberrations originating from imperfect lenses or environmental disturbances7,8. Here we propose an integrated scanning light-field imaging sensor, termed a meta-imaging sensor, to achieve high-speed aberration-corrected three-dimensional photography for universal applications without additional hardware modifications. Instead of directly detecting a two-dimensional intensity projection, the meta-imaging sensor captures extra-fine four-dimensional light-field distributions through a vibrating coded microlens array, enabling flexible and precise synthesis of complex-field-modulated images in post-processing. Using the sensor, we achieve high-performance photography up to a gigapixel with a single spherical lens without a data prior, leading to orders-of-magnitude reductions in system capacity and costs for optical imaging. Even in the presence of dynamic atmosphere turbulence, the meta-imaging sensor enables multisite aberration correction across 1,000 arcseconds on an 80-centimetre ground-based telescope without reducing the acquisition speed, paving the way for high-resolution synoptic sky surveys. Moreover, high-density accurate depth maps can be retrieved simultaneously, facilitating diverse applications from autonomous driving to industrial inspections.

The hematopoietic cell kinase (HCK), a member of the Src family protein-tyrosine kinases (SFKs), is primarily expressed in cells of the myeloid and B lymphocyte lineages. Nevertheless, the roles of HCK in glioblastoma (GBM) remain to be examined. Thus, we aimed to investigate the effects of HCK on GBM development both in vitro and in vivo, as well as the underlying mechanism. The present study found that HCK was highly expressed in both tumor tissues from patients with GBM and cancer cell lines. HCK enhanced cell viability, proliferation, and migration, and induced cell apoptosis in vitro. Tumor xenografts results also demonstrated that HCK knockdown significantly inhibited tumor growth. Interestingly, gene set enrichment analysis (GSEA) showed HCK was closed associated with epithelial mesenchymal transition (EMT) and TGFβ signaling in GBM. In addition, we also found that HCK accentuates TGFβ-induced EMT, suggesting silencing HCK inhibited EMT through the inactivation of Smad signaling pathway. In conclusion, our findings indicated that HCK is involved in GBM progression via mediating EMT process, and may be served as a promising therapeutic target for GBM.

Purpose Glioma is the most prevalent malignant form of brain tumors, with a dismal prognosis. Currently, cancer immunotherapy has emerged as a revolutionary treatment for patients with advanced highly aggressive therapy-resistant tumors. However, there is no effective biomarker to reflect the response to immunotherapy in glioma patient so far. So we aim to assess the clinical predictive value of FCER1G in patients with glioma. Methods The expression level and correlation between clinical prognosis and FER1G levels were analyzed with the data from CGGA, TCGA, and GEO database. Univariate and multivariate cox regression model was built to predict the prognosis of glioma patients with multiple factors. Then the correlation between FCER1G with immune cell infiltration and activation was analyzed. At last, we predict the immunotherapeutic response in both high and low FCER1G expression subgroups. Results FCER1G was significantly higher in glioma with greater malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio of FCER1G expression (Low versus High) was 0.66 and 95 % CI is 0.54 to 0.79 (P < 0.001), whereas age (HR = 1.26, 95 % CI  1.04–1.52), grade (HR = 2.75, 95 % CI 2.06–3.68), tumor recurrence (HR = 2.17, 95 % CI  1.81–2.62), IDH mutant (HR = 2.46, 95 % CI 1.97–3.01) and chemotherapeutic status (HR = 1.4, 95 % CI  1.20–1.80) are also included. Furthermore, we illustrated that gene FCER1G stratified glioma cases into high and low FCER1G expression subgroups that demonstrated with distinct clinical outcomes and T cell activation. At last, we demonstrated that high FCER1G levels presented great immunotherapeutic response in glioma patients. Conclusions This study demonstrated FCER1G as a novel predictor for clinical diagnosis, prognosis, and response to immunotherapy in glioma patient. Assess expression of FCER1G is a promising method to discover patients that may benefit from immunotherapy.

Cabergoline is a dopamine agonist that has been used as the first-line treatment option for prolactin-secreting pituitary adenomas for several decades. It not only suppresses hormone production from these prolactinomas, but also causes tumour shrinkage. Recent studies revealed some novel mechanisms by which cabergoline suppresses tumour cell proliferation and induces cell death. In this article, we review the most recent findings in cabergoline studies, focusing on its anti-tumour function. These studies suggest the potential broader clinical use of cabergoline in the treatment of other tumours such as breast cancer, pancreatic neuroendocrine tumours, and lung cancer.