RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown. METHODS: Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2. RESULTS: We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1). CONCLUSION: BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.

Migration time correction for dual pressure capillary electrophoresis in semi-targeted metabolomics study.

Migration time fluctuation strongly affects peak alignment and identification of unknown compounds, making migration time correction an essential step in capillary electrophoresis (CE)-based metabolomics. To obtain more reliable information, metabolites with different apparent mobilities are analyzed by tandem mass spectrometry. Applying a small pressure is a common practice for reducing the analysis time of anions in a positive mode CE, known as the pressure-assisted CE. However, applying pressure may reduce the separation efficiency and can be undesirable for cation analysis. A simple way to address this issue is to increase the pressure after a certain time, during the separation. We term this practice as dual pressure CE. However, changing the pressure during the CE separation complicates migration time correction. Previous migration time correction methods were established based on a consistent electroosmotic flow and a constant pressure-driven bulk-flow velocity. We proposed a new correction method to support the peak alignment when dual pressure CE is used. A Python-based script was developed to implement dual pressure CE migration time correction for semi-targeted metabolomics study performed by a multiple reaction monitoring-based method. This script can help select suitable endogenous metabolites as correction markers, perform migration time correction, and conduct peak alignment. A case study showed that migration time precision of 156 metabolites in 32 samples can be improved from 4.8 to 11.4%RSD (relative standard deviation) to less than 1.8%RSD.

Exploring the Mediating Effect of Physical Activities on Built Environment and Obesity for Elderly People: Evidence From Shanghai, China.

There is still a scarcity of literature on the specific mechanisms of the linkage between the built environment and obesity. As a result, this study investigated whether and how physical activities mediate the associations between the objective built environment and the BMI of elderly people. To investigate the effect of the duration and intensity of physical activity on the effect of the built environment, the study made use of the bootstrap method. In general, we discovered that physical activity duration has a huge mediating effect on the elderly people in Shanghai, especially with respect to the density and accessibility of facilities (gyms, parks, fast-food restaurants) that can greatly stimulate physical activity in elderly people to reduce their BMI. There were both direct and indirect effects on their BMI, which means that the health benefits of green spaces for older people may be more complicated than first thought.

Integrating GWAS and transcriptomics to identify candidate genes conferring heat tolerance in rice.

Introduction: Rice (Oryza sativa L.) production is being challenged by global warming. Identifying new loci and favorable alleles associated with heat tolerance is crucial to developing rice heat-tolerant varieties. Methods: We evaluated the heat tolerance at the seedling stage using 620 diverse rice accessions. A total of six loci associated with heat tolerance were identified by a genome-wide association study (GWAS) with ~2.8 million single nucleotide polymorphisms (SNPs). Results: Among the six detected loci, qHT7 harbored the strongest association signal and the most associated SNPs. By comparing the transcriptomes of two representative accessions with contrasting heat tolerance, LOC_Os07g48710 (OsVQ30) was selected as a promising candidate gene in qHT7 due to the significant difference in its expression level between the two accessions. Haplotype 4 (Hap4) of LOC_Os07g48710 was determined as the favorable haplotype for heat tolerance via the gene-based haplotype analysis. The heat-tolerant haplotype LOC_Os07g48710Hap4 is highly enriched in the tropical Geng/Japonica accessions, and its frequency has decreased significantly during the improvement process of rice varieties. Discussion: Based on the GWAS and transcriptomics integrated results, a hypothetical model modulated by qHT7 in response to heat stress was proposed. Our results provide valuable candidate genes for improving rice heat tolerance through molecular breeding.

Multimodal Medical Image Fusion using Rolling Guidance Filter with CNN and Nuclear Norm Minimization.

BACKGROUND: Medical image fusion is very important for the diagnosis and treatment of diseases. In recent years, there have been a number of different multi-modal medical image fusion algorithms that can provide delicate contexts for disease diagnosis more clearly and more conveniently. Recently, nuclear norm minimization and deep learning have been used effectively in image processing. METHODS: A multi-modality medical image fusion method using a rolling guidance filter (RGF) with a convolutional neural network (CNN) based feature mapping and nuclear norm minimization (NNM) is proposed. At first, we decompose medical images to base layer components and detail layer components by using RGF. In the next step, we get the basic fused image through the pretrained CNN model. The CNN model with pre-training is used to obtain the significant characteristics of the base layer components. And we can compute the activity level measurement from the regional energy of CNN-based fusion maps. Then, a detail fused image is gained by NNM. That is, we use NNM to fuse the detail layer components. At last, the basic and detail fused images are integrated into the fused result. RESULTS: From the comparison with the most advanced fusion algorithms, the results of experiments indicate that this fusion algorithm has the best effect in visual evaluation and objective standard. CONCLUSION: The fusion algorithm using RGF and CNN-based feature mapping, combined with NNM, can improve fusion effects and suppress artifacts and blocking effects in the fused results.

Does acculturation really matter for internal migrants' health?Evidence from eight cities in China.

It is widely recognized that China has experienced the largest internal migration in its history and that these internal migrants are largely excluded from urban services, posing major challenges to their health outcomes. This paper attempts to address this issue from a socio-ecological lens, examining John W. Berry's conceptual framework of acculturation on internal migrants' health in China. We employed the National Migrant Dynamic Monitoring Survey (MDMS; 2014) data, with around 16,000 samples from eight cities. Our results showed that compared to their hometown culture, where migrants can successfully integrate into the mainstream culture of the destination area, mental health stress can be prevented and self-assessed health status is improved. Well-integrated migrants showed the best self-reported health (SRH) and mental health status, while segregated or marginalized migrants received lower health scores. It was interesting to see that the origin culture only protected SRH whereas the local culture could promote both mental health and SRH. This evidence may be alarming. Local government must respect origin cultures when carrying out social integration policy. In addition, macro-migration policies should encourage local mobility within the same cultural areas to minimize the negative effects of migration.

High gravimetric and volumetric sodium storage in a functionalized coal-based microcrystal/CNT binder-free electrode.

Abundant oxygen functional groups in coal-based microcrystals, especially for carboxylic anhydrides and quinone groups with two Na+ storage sites, provide plentiful active sites to adsorb Na+. The carboxyl groups serve as the binder connecting active material with a current collector. High gravimetric and volumetric sodium storage was achieved in this binder-free electrode.

Pseudocapacitive Na+ Insertion in Ti-O-C Channels of TiO2-C Nanofibers with High Rate and Ultrastable Performance.

Ti-O-C channels for ultrafast sodium storage were constructed in N/S-co-doped TiO2-C nanofibers, which deliver a high rate performance of 181.9 mAh g-1 at 5 A g-1 after 3000 cycles. The existence of Ti-O-C bonds at the interface of TiO2-C phases was revealed by synchrotron radiation X-ray absorption spectra. Based on this, first-principles calculations further verified the low energy barrier for Na+ insertion/extraction in the Ti-O-C channels formed by the intimately integrated graphite layer with TiO2 near the surface. In addition, surface defects induced by heteroatoms accelerate the Na+ mass transfer through the pathway from the carbon surface to the Ti-O-C channel.

Exploring the Impacts of Housing Condition on Migrants' Mental Health in Nanxiang, Shanghai: A Structural Equation Modelling Approach.

Although rapid urbanization and associated rural-to-urban migration has brought in enormous economic benefits in Chinese cities, one of the negative externalities include adverse effects upon the migrant workers' mental health. The links between housing conditions and mental health are well-established in healthy city and community planning scholarship. Nonetheless, there has thusfar been no Chinese study deciphering the links between housing conditions and mental health accounting for macro-level community environments, and no study has previously examined the nature of the relationships in locals and migrants. To overcome this research gap, we hypothesized that housing conditions may have a direct and indirect effects upon mental which may be mediated by neighbourhood satisfaction. We tested this hypothesis with the help of a household survey of 368 adult participants in Nanxiang Town, Shanghai, employing a structural equation modeling approach. Our results point to the differential pathways via which housing conditions effect mental health in locals and migrants. For locals, housing conditions have direct effects on mental health, while as for migrants, housing conditions have indirect effects on mental health, mediated via neighborhood satisfaction. Our findings have significant policy implications on building an inclusive and harmonious society. Upstream-level community interventions in the form of sustainable planning and designing of migrant neighborhoods can promote sense of community, social capital and support, thereby improving mental health and overall mental capital of Chinese cities.

The comparison of EGFR-TKI failure modes and subsequent management between exon 19 deletion and exon 21 L858R mutation in advanced non-small-cell lung cancer.

Background: Advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion (19 Del) and exon 21 L858R mutation (L858R) might be distinct diseases. Therefore, it is necessary to take EGFR mutation subgroups into consideration for making choices of subsequent treatment after tyrosine kinase inhibitors (TKIs) failure. Patients and methods: 174 patients who developed to EGFR-TKI failure were categorized into three cohorts of dramatic progression, gradual progression and local progression. Chi-square was used to compare the distribution of failure modes between 19 Del and L858R. Kaplan-Meier method and Cox Regression were performed for analyses of survival in different subsequent treatments. Results: The distribution of EGFR-TKI failure modes showed no significant difference between 19 Del and L858R. Patients in gradual progression had a longer progression-free survival (PFS) and overall survival (OS) compared with other failure modes in whole population, 19 Del cohort and L858R cohort. 19 Del patients with dramatic progression would obtain survival benefit from chemotherapy, while those with gradual progression got no survival benefit neither from chemotherapy nor previous TKI continuation. However, patients with dramatic or gradual progression would benefit from previous TKI continuation in L858R cohort. Conclusion: For advanced EGFR-positive NSCLC patients with acquired resistance to EGFR-TKI, subsequent treatment should be personalized according to EGFR-TKI failure modes & EGFR mutation subtypes.

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis.

BACKGROUND: The first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, have become the standard first-line treatment for non-small-cell lung cancer (NSCLC) patients with EGFR mutation. However, there was no pooled analysis focused on the usage of the second-generation TKI, afatinib, in advanced EGFR-positive NSCLC patients after failure of first generation TKIs. Therefore, a meta-analysis was conducted to solve the above question. METHODS: Electronic databases were searched for eligible literatures. ORR (objective response rate), DCR (disease controlled rate), PFS (progression-free survival), OS (overall survival) and primary grade 3/4 adverse events were pooled with the corresponding 95% confidence interval using R software. Sensitivity analyses and heterogeneity were quantitatively evaluated. RESULTS: A total of 545 EGFR-positive patients were available for analysis from five studies after detailed screening from 909 relevant studies. The pooled ORR and DCR of afatinib in EGFR-positive patients after failure of the first generation EGFR-TKIs were 0.12 (0.08-0.19) and 0.60 (0.53-0.68), respectively. Besides, the 6 m-PFS rate, 1 y-PFS rate and 6 m-OS rate were 0.26 (0.22-0.30), 0.08 (0.06-0.10) and 0.74 (0.56-0.86). The grade 3/4 rate of diarrhea and that of skin deformity were 0.23 (0.10-0.46) and 0.14 (0.05-0.33), respectively. Sensitivity analyses revealed similar results with lower heterogeneity. CONCLUSIONS: Considering the efficacy, toxicity and current availability, afatinib could be a therapeutic option for advanced EGFR mutated NSCLC patients after the failure of 1st-generation TKIs.

Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

BACKGROUND: Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. METHODS: Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. RESULTS: Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. CONCLUSION: Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib).

A large, single-center, real-world study of clinicopathological characteristics and treatment in advanced ALK-positive non-small-cell lung cancer.

Crizotinib has achieved astonishing success in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real-world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat-sen University Cancer Center. Chi-square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan-Meier methods and multivariable analyses were used to estimate progression-free survival (PFS). A total of 291 advanced NSCLC patients (ALK (+), N = 97; both ALK & epidermal growth factor receptor (EGFR) (-), N = 194) were enrolled. The occurrence of brain metastasis in ALK-positive patients was significantly higher than double-negative ones both at baseline (26.5% vs. 16.5%, P = 0.038) and during treatment (25.8% vs. 11.9%, P = 0.003), but opposite for pleural effusion (6.2% vs. 26.9%, P < 0.001 at baseline; 3.1% vs. 10.3%, P = 0.031 during treatment). ALK-positive patients of 53.6% used crizotinib, whereas others only received chemotherapy (37.1%) or supportive care (9.3%). Usage of crizotinib prolonged PFS compared with chemotherapy in ALK-positive patients (median PFS 17.6 m vs. 4.8 m, P < 0.001). ALK-positive NSCLC had more brain metastasis and less pleural effusion than double-negative ones. Crizotinib showed better PFS than chemotherapy in advanced ALK-positive NSCLC at any line. However, half advanced ALK-positive patients never received crizotinib, which was grim and need improving.

Hypoxia upregulates HIG2 expression and contributes to bevacizumab resistance in glioblastoma.

Hypoxia contributes to the maintenance of stem-like cells in glioblastoma (GBM), and activates vascular mimicry and tumor resistance to anti-angiogenesis treatments. The present study examined the expression patterns and biological significance of hypoxia-inducible protein 2 (HIG2, also known as HILPDA) in GBM. HIG2 was highly expressed in gliomas and was correlated with tumor grade, and high HIG2 expression independently predicted poor GBM patient prognosis. HIG2 was upregulated during hypoxia and by hypoxia mimics, and HIG2 knockdown in GBM cells inhibited cell proliferation and invasion. HIF1α bound to the HIG2 promoter and increased its expression in GBM cells, and HIG2 upregulated HIF1α expression. Reconstruction of a HIG2-related molecular network using bioinformatics methods revealed that HIG2 is closely correlated with angiogenesis genes, such as VEGFA, in GBM. HIG2 levels positively correlated with VEGFA in GBM samples. In addition, treatment of transplanted xenograft nude mice with bevacizumab (anti-angiogenesis therapy) resulted in HIG2 upregulation at late stages. We conclude that HIG2 is overexpressed in GBM and upregulated by hypoxia, and is a potential novel therapeutic target. HIG2 overexpression is an independent prognostic indicator and may promote tumor resistance to anti-angiogenesis treatments.