The Insular Cortex: An Interface Between Sensation, Emotion and Cognition.

The insula is a complex brain region central to the orchestration of taste perception, interoception, emotion, and decision-making. Recent research has shed light on the intricate connections between the insula and other brain regions, revealing the crucial role of this area in integrating sensory, emotional, and cognitive information. The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain. We summarize its role in interoceptive and exteroceptive sensory processing, illustrating insular function as a bridge connecting internal and external experiences. Drawing on recent research, we delineate the insular involvement in emotional processes, highlighting its implications in psychiatric conditions, such as anxiety, depression, and addiction. We further discuss the insular contributions to cognition, focusing on its significant roles in time perception and decision-making. Collectively, the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes. Through this review, we hope to highlight the importance of the insula as an interface between sensation, emotion, and cognition, and to inspire further research into this fascinating brain region.

Enhancing the endo-activity of the thermophilic chitinase to yield chitooligosaccharides with high degrees of polymerization.

Thermophilic endo-chitinases are essential for production of highly polymerized chitooligosaccharides, which are advantageous for plant immunity, animal nutrition and health. However, thermophilic endo-chitinases are scarce and the transformation from exo- to endo-activity of chitinases is still a challenging problem. In this study, to enhance the endo-activity of the thermophilic chitinase Chi304, we proposed two approaches for rational design based on comprehensive structural and evolutionary analyses. Four effective single-point mutants were identified among 28 designed mutations. The ratio of (GlcNAc)3 to (GlcNAc)2 quantity (DP3/2) in the hydrolysates of the four single-point mutants undertaking colloidal chitin degradation were 1.89, 1.65, 1.24, and 1.38 times that of Chi304, respectively. When combining to double-point mutants, the DP3/2 proportions produced by F79A/W140R, F79A/M264L, F79A/W272R, and M264L/W272R were 2.06, 1.67, 1.82, and 1.86 times that of Chi304 and all four double-point mutants exhibited enhanced endo-activity. When applied to produce chitooligosaccharides (DP ≥ 3), F79A/W140R accumulated the most (GlcNAc)4, while M264L/W272R was the best to produce (GlcNAc)3, which was 2.28 times that of Chi304. The two mutants had exposed shallower substrate-binding pockets and stronger binding abilities to shape the substrate. Overall, this research offers a practical approach to altering the cutting pattern of a chitinase to generate functional chitooligosaccharides.

CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer.

Coiled-coil domain-containing 58 (CCDC58) is a member of the CCDC protein family. Similar to other members, CCDC58 exhibits potential tumorigenic roles in a variety of malignancies. However, there is no systematic and comprehensive pan-cancer analysis to investigate the diagnosis, prognosis, immune infiltration, and other related functions of CCDC58. We used several online websites and databases, such as TCGA, GTEx, UALCAN, HPA, CancerSEA, BioGRID, GEPIA 2.0, TIMER 2.0, and TISIDB, to extract CCDC58 expression data and clinical data of patients in pan-cancer. Then, the relationship between CCDC58 expression and diagnosis, prognosis, genetic alterations, DNA methylation, genomic heterogeneity, and immune infiltration level were determined. In addition, the biological function of CCDC58 in liver hepatocellular carcinoma (LIHC) was investigated. Pan-cancer analysis results showed that CCDC58 was differentially expressed in most tumors and showed excellent performance in diagnosis and prediction of prognosis. The expression of CCDC58 was highly correlated with genetic alterations, DNA methylation, and genomic heterogeneity in some tumors. In addition, the correlation analysis of CCDC58 with the level of immune infiltration and immune checkpoint marker genes indicated that CCDC58 might affect the composition of the tumor immune microenvironment. Enrichment analysis showed that CCDC58-related genes were mainly linked to mitosis, chromosome, and cell cycle. Finally, biological function experiments demonstrated that CCDC58 plays an important role in tumor cell proliferation and migration. CCDC58 was first identified as a pan-cancer biomarker. It may be used as a potential therapeutic target to improve the prognosis of patients in the future.

Unveiling aging dynamics in the hematopoietic system insights from single-cell technologies.

As the demographic structure shifts towards an aging society, strategies aimed at slowing down or reversing the aging process become increasingly essential. Aging is a major predisposing factor for many chronic diseases in humans. The hematopoietic system, comprising blood cells and their associated bone marrow microenvironment, intricately participates in hematopoiesis, coagulation, immune regulation and other physiological phenomena. The aging process triggers various alterations within the hematopoietic system, serving as a spectrum of risk factors for hematopoietic disorders, including clonal hematopoiesis, immune senescence, myeloproliferative neoplasms and leukemia. The emerging single-cell technologies provide novel insights into age-related changes in the hematopoietic system. In this review, we summarize recent studies dissecting hematopoietic system aging using single-cell technologies. We discuss cellular changes occurring during aging in the hematopoietic system at the levels of the genomics, transcriptomics, epigenomics, proteomics, metabolomics and spatial multi-omics. Finally, we contemplate the future prospects of single-cell technologies, emphasizing the impact they may bring to the field of hematopoietic system aging research.

Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack of a detailed understanding of oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. The role of protein lactylation, a newly unraveled post-translational modification that orchestrates gene expression, remains largely elusive in the pathogenesis of iCCA. METHODS: Proteomics analysis of clinical iCCA specimens and adjacent tissues was performed to screen for proteins aberrantly lactylated in iCCA. Mass spectrometry, macromolecule interaction and cell behavioral studies were employed to identify the specific lactylation sites on the candidate protein(s) and to decipher the downstream mechanisms responsible for iCCA development, which were subsequently validated using a xenograft tumor model and clinical samples. RESULTS: Nucleolin (NCL), the most abundant RNA-binding protein in the nucleolus, was identified as a functional lactylation target that correlates with iCCA occurrence and progression. NCL was lactylated predominantly at lysine 477 by the acyltransferase P300 in response to a hyperactivity of glycolysis, and promoted the proliferation and invasion of iCCA cells. Mechanistically, lactylated NCL bound to the primary transcript of MAP kinase-activating death domain protein (MADD) and warranted an efficient translation of MADD by circumventing alternative splicing that generates a premature termination codon. NCL lactylation, MADD and subsequent ERK activation promoted xenograft tumor growth, and were found to associate with the overall survival of iCCA patients. CONCLUSION: NCL is lactylated to upregulate MADD through an RNA splicing-dependent mechanism, which potentiates iCCA pathogenesis via the MAPK pathway. Our findings reveal a novel link between metabolic reprogramming and canonical tumor-initiating events, and provide biomarkers that can be potentially used for prognostic evaluation or targeted treatment of iCCA. IMPACT AND IMPLICATION: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive liver malignancy with largely uncharacterized pathogenetic mechanisms. Herein, we demonstrated that glycolysis promotes P300-catalyzed lactylation of NCL, which upregulates MAP kinase-activating death domain protein (MADD) through precise mRNA splicing, and activates ERK signaling to drive iCCA development. These findings unravel a novel link between metabolic rewiring and canonical oncogenic pathways, and provide new biomarkers for prognostic assessment and targeting of clinical iCCA.

Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy.

INTRODUCTION: As one of the major components of the tumor microenvironment, tumor-associated macrophages (TAMs) possess profound inhibitory activity against T cells and facilitate tumor escape from immune checkpoint blockade therapy. Converting this pro-tumorigenic toward the anti-tumorigenic phenotype thus is an important strategy for enhancing adaptive immunity against cancer. However, a plethora of mechanisms have been described for pro-tumorigenic differentiation in cancer, metabolic switches to program the anti-tumorigenic property of TAMs are elusive. MATERIALS AND METHODS: From an unbiased analysis of single-cell transcriptome data from multiple tumor models, we discovered that anti-tumorigenic TAMs uniquely express elevated levels of a specific fatty acid receptor, G-protein-coupled receptor 84 (GPR84). Genetic ablation of GPR84 in mice leads to impaired pro-inflammatory polarization of macrophages, while enhancing their anti-inflammatory phenotype. By contrast, GPR84 activation by its agonist, 6-n-octylaminouracil (6-OAU), potentiates pro-inflammatory phenotype via the enhanced STAT1 pathway. Moreover, 6-OAU treatment significantly retards tumor growth and increases the anti-tumor efficacy of anti-PD-1 therapy. CONCLUSION: Overall, we report a previously unappreciated fatty acid receptor, GPR84, that serves as an important metabolic sensing switch for orchestrating anti-tumorigenic macrophage polarization. Pharmacological agonists of GPR84 hold promise to reshape and reverse the immunosuppressive TME, and thereby restore responsiveness of cancer to overcome resistance to immune checkpoint blockade.

Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions. METHODS: CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity. RESULTS: This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively. CONCLUSION: EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.

Different cortical connectivities in human females and males relate to differences in strength and body composition, reward and emotional systems, and memory.

Sex differences in human brain structure and function are important, partly because they are likely to be relevant to the male-female differences in behavior and in mental health. To analyse sex differences in cortical function, functional connectivity was measured in 36,531 participants (53% female) in the UK Biobank (mean age 69) using the Human Connectome Project multimodal parcellation atlas with 360 well-specified cortical regions. Most of the functional connectivities were lower in females (Bonferroni corrected), with the mean Cohen's d = - 0.18. Removing these as covariates reduced the difference of functional connectivities for females-males from d = - 0.18 to - 0.06. The lower functional connectivities in females were especially of somatosensory/premotor regions including the insula, opercular cortex, paracentral lobule and mid-cingulate cortex, and were correlated with lower maximum workload (r = 0.17), and with higher whole body fat mass (r = - 0.17). But some functional connectivities were higher in females, involving especially the ventromedial prefrontal cortex and posterior cingulate cortex, and these were correlated with higher liking for some rewards such as sweet foods, higher happiness/subjective well-being, and with better memory-related functions. The main findings were replicated in 1000 individuals (532 females, mean age 29) from the Human Connectome Project. This investigation shows the cortical systems with different functional connectivity between females and males, and also provides for the first time a foundation for understanding the implications for behavior of these differences between females and males.

Qualitative Proteome-wide Lysine Crotonylation Profiling Reveals Protein Modification Alteration in the Leukocyte Extravasation Pathway in Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a severe systemic autoimmune disease with multiple manifestations. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification epigenetic pattern that may affect gene expression and is linked to diseases causally. METHODS: We collected blood samples from 11 SLE individuals and 36 healthy subjects. Then, we used highly sensitive liquid chromatography-mass spectrometry technology to carry out proteomics and quantitative crotonylome analysis of SLE peripheral blood mononuclear cells in this investigation, which indicated the unique etiology of SLE. Finally, we verified the expression of critical protein in the leukocyte extravasation pathway by online database analysis and Western blot. RESULTS: There were 618 differentially expressed proteins (DEPs), and 612 crotonylated lysine sites for 272 differentially modified proteins (DMPs) found. These DEPs and DMPs are primarily enriched in the leukocyte extravasation signaling pathway, such as MMP8, MMP9, and ITGAM. CONCLUSIONS: This is the first study of crotonylated modification proteomics in SLE. The leukocyte extravasation signaling pathway had a considerable concentration of DEPs and DMPs, indicating that this pathway may be involved in the pathogenic development of SLE.

Familiarity of teaching skills among general practitioners transfer training trainers in China: a cross-sectional survey.

BACKGROUND: The insufficient number of general practitioners (GPs) is a major challenge facing China's healthcare system. The purpose of the GP transfer training programme was to provide training for experienced doctors to transition to general practice. However, research on the competencies of GP transfer training trainers in teaching skills in China is limited. This cross-sectional study aimed to examine the baseline familiarity with teaching skills among Chinese GP transfer training trainers. METHODS: An online survey was conducted among trainers who participated in the 2021 Sichuan Province General Practice Training Trainer Program. The survey collected data on participants' characteristics and familiarity with 20 skills in three essential teaching knowledge areas: the core functions of primary care (five questions), preparation for lesson plan (four questions), and teaching methods (11 questions). RESULTS: In total, 305 participants completed the survey. Familiarity rates were generally low across all three essential teaching knowledge areas. No significant differences were observed in familiarity rates between the tertiary and secondary hospitals. CONCLUSION: This study revealed gaps in the teaching skills of GP transfer training trainers in China. These results suggest the necessity for targeted training programs to enhance the teaching skills and competencies of trainers.

Proteomic analysis of lysine 2-hydroxyisobutyryl in SLE reveals protein modification alteration in complement and coagulation cascades and platelet activation Pathways.

BACKGROUND: Post-translational modifications (PTMs) are considered to be an important factor in the pathogenesis of Systemic lupus erythematosus (SLE). Lysine 2-hydroxyisobutyryl (Khib), as an emerging post-translational modification of proteins, is involved in some important biological metabolic activities. However, there are poor studies on its correlation with diseases, especially SLE. OBJECTIVE: We performed quantitative, comparative, and bioinformatic analysis of Khib proteins in Peripheral blood mononuclear cells (PBMCs) of SLE patients and PBMCs of healthy controls. Searching for pathways related to SLE disease progression and exploring the role of Khib in SLE. METHODS: Khib levels in SLE patients and healthy controls were compared based on liquid chromatography tandem mass spectrometry, then proteomic analysis was conducted. RESULTS: Compared with healthy controls, Khib in SLE patients was up-regulated at 865 sites of 416 proteins and down-regulated at 630 sites of 349 proteins. The site abundance, distribution and function of Khib protein were investigated further. Bioinformatics analysis showed that Complement and coagulation cascades and Platelet activation in immune-related pathways were significantly enriched, suggesting that differentially modified proteins among them may affect SLE. CONCLUSION: Khib in PBMCs of SLE patients was significantly up- or down-regulated compared with healthy controls. Khib modification of key proteins in the Complement and coagulation cascades and Platelet activation pathways affects platelet activation and aggregation, coagulation functions in SLE patients. This result provides a new direction for the possible significance of Khib in the pathogenesis of SLE patients.

A Fast Evolutionary Knowledge Transfer Search for Multiscale Deep Neural Architecture.

The emergence of neural architecture search (NAS) algorithms has removed the constraints on manually designed neural network architectures, so that neural network development no longer requires extensive professional knowledge, trial and error. However, the extremely high computational cost limits the development of NAS algorithms. In this article, in order to reduce computational costs and to improve the efficiency and effectiveness of evolutionary NAS (ENAS) is investigated. In this article, we present a fast ENAS framework for multiscale convolutional networks based on evolutionary knowledge transfer search (EKTS). This framework is novel, in that it combines global optimization methods with local optimization methods for search, and searches a multiscale network architecture. In this article, evolutionary computation is used as a global optimization algorithm with high robustness and wide applicability for searching neural architectures. At the same time, for fast search, we combine knowledge transfer and local fast learning to improve the search speed. In addition, we explore a multiscale gray-box structure. This gray box structure combines the Bandelet transform with convolution to improve network approximation, learning, and generalization. Finally, we compare the architectures with more than 40 different neural architectures, and the results confirmed its effectiveness.

Does the Pro-Environmental Behavior of Household PV Installation Contribute to the Shaping of Users' Green Purchasing Behavior?-Evidence from China.

In order to achieve the "dual carbon goal", the Chinese government is actively encouraging the adoption of household photovoltaic (PV) systems. While there has been considerable research on residents' inclination to install PV, limited attention has been given to understanding how the installation and utilization of PV systems influence pro-environmental behaviors. Therefore, this paper aims to investigate the potential impact of pro-environmental behavior resulting from household PV installation on users' green purchasing behavior. Based on the "learning by doing" theory, a survey was conducted with 1249 participants, and the generalized structural equation model was employed as our analytical approach. The findings of this research indicate that the adoption and utilization of household photovoltaic (PV) systems have a positive impact on green consumption. The test results demonstrate that the overall effect coefficient is 0.03, indicating that current PV promotion policies have an indirect impact on green consumption. Moreover, economic incentive policies have a more substantial influence than environmental publicity policies, with total indirect effect coefficients of 0.005 and 0.002, respectively. Based on the findings above, the following recommendations are proposed: (1) It is recommended to maintain stable economic incentives to promote the adoption of household PV systems. (2) Emphasizing the dissemination of knowledge and skills for promoting environmental protection should be prioritized. (3) Efforts should be made to align personal interests and societal interests with low-carbon policies.

Risk factors analysis of surgical complications of hepatic hemangioma: a modified Clavien-Dindo classification-based study.

PURPOSE: There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment. METHODS: The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications. RESULTS: A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22-75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL. CONCLUSIONS: Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars.

Quality of life and its influencing factors in patients with schizophrenia. / ç²¾ç¥žåˆ†è£‚ç—‡æ‚£è€ ç”Ÿæ´»è´¨é‡åŠå ¶å½±å“å› ç´ .

Schizophrenia is a chronic mental disease. With the change of medical model, quality of life has gradually become an important prognostic indicator for patients with schizophrenia. People with schizophrenia have a lower quality of life than the general population or people with other chronic diseases, Sociodemographic factors such as age, gender, employment, education level, income and living situation; clinical factors such as psychiatric symptoms, medication compliance and insight; and psychosocial factors such as social support, cognition, stigma, self-esteem and needs are the main influencing factors for schizophrenia patients. Medication and psychological interventions such as social skills training, family intervention, cognitive correction and cognitive behavioral therapy can be used to improve the quality of life of patients with schizophrenia. Understanding the factors affecting the quality of life of schizophrenia patients and the improvement measures helps to provide reference for improving their quality of life.

Prognostic value of the pretreatment systemic immune-inflammation index in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The systemic immune-inflammation index (SII) is a novel biomarker to predict the prognosis of some malignant tumors based on neutrophil, platelet, and lymphocyte counts. Evidence is scarce about the prognostic value of SII for prostate cancer patients. This systematic review and meta-analysis was conducted to explore the prognostic value of the SII in prostate cancer. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL) databases were searched to determine eligible studies from inception to August 15, 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to pool the results. Statistical analyses were conducted by using Stata 17.0 software. RESULTS: A total of 12 studies with 8083 patients were included. The quantitative synthesis showed that a high SII was related to poor overall survival (OS) (HR = 1.44, 95% CI 1.23-1.69, p < 0.001). Furthermore, a subgroup analysis showed that a high SII was associated with poor OS in the groups of any ethnicity, tumor type, and cutoff value. An increased SII was also associated with inferior progression-free survival (PFS) (HR = 1.80, 95% CI 1.27-2.56, p = 0.001). In the subgroup analysis, a high SII value was related to poor PFS in Asian patients (HR = 4.03, 95% CI 1.07-15.17, p = 0.04) and a cutoff value > 580 (HR = 1.19, 95% CI 1.04-1.36, p = 0.01). CONCLUSION: Based on the current evidence, a high pretreatment SII may be associated with poor OS and PFS. The SII may serve as an important prognostic indicator in patients with prostate cancer. More rigorously designed studies are needed to explore the SII and the prognosis of prostate cancer.

Evolutionary Dual-Stream Transformer.

Vision transformers (ViTs) are rapidly evolving and are widely used in computer vision. However, high-performance ViTs require many computations, which limit their further development in the vision field. In this article, a novel evolutionary dual-stream transformer (E-DST) model is proposed to alleviate the computational resource demand problem. A hybrid attention mechanism structure is proposed for a DST model. The DST model uses a dual-branch structure to fuse convolutional and transformer features. Combining the features learned by the transformer and convolution effectively saves model computational resources. In addition, an evolutionary optimizer is proposed to optimize the parameters of the model. The excellent search ability of the evolutionary algorithm is utilized to optimize the transformer model parameters. The convergence of the evolutionary optimizer is proved in this article. In addition, the proposed E-DST model is experimentally compared with a variety of classic models and their deformations based on three datasets. And, the evolutionary optimizer proves its generality in convolutional and recurrent neural networks. The experimental results show that the E-DST model can effectively reduce computational resources and that the evolutionary optimizer can solve large-scale optimization problems. In conclusion, our proposed method is feasible and effective.

Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.

Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM's natural evolutionary trajectory by using rare multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES transition potentially via activation of the HIF1A-FOSL2 axis. High-NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T-cell activity and accelerate NES transition in tumor cells. Moreover, the polarized macrophages could upregulate CCL2 to induce tumor cell migration. SIGNIFICANCE: GBM progression could be induced by hypoxia via the HIF1A-FOSL2 axis. Tumor-derived ANXA1 is associated with recruitment and polarization of bone marrow-derived macrophages to suppress the immunoenvironment. The polarized macrophages promote tumor cell NES transition and migration. This article is highlighted in the In This Issue feature, p. 2711.

Hydrophobic and Rapid-Response Sensor Inks: Array-Based Fingerprinting of Perfumes.

Counterfeited perfumes mixed with inexpensive additives for commercial purposes pose a great threat to cosmetic market competition and human health. Herein, a 24-element, solid-state colorimetric sensor array employing chemo-responsive dye inks for accurate discrimination of a variety of fragrance bases and "sniffing out" real perfumes from adulterated samples was first reported. The physiochemical robustness and gas response kinetics of the sensor array were optimized with the streamlined design of the channel geometry and hydrophobic modification of the sensor substrate. A unique and distinguishable color change profile was obtained within 2 min exposure of diluted vapor that enabled clear fingerprinting of chemically similar perfume samples. Four commercial perfume products were successfully distinguished and categorized according to their similarity to relevant perfume bases using chemometric methods including hierarchical clustering and principal component analysis. The sensor array also allows the discrimination of ethanol-diluted fragrance bases from the pristine sample, revealing its potential for quality assurance of perfumes and other cosmetics. Such easy-to-use, disposable, and miniaturized chemical sensing detectors therefore prove exceptionally valuable for fast analysis of luxuries such as perfumes and other industrial products with complex chemical compositions.