Tumor-derived exosomal hyaluronidase 1 induced M2 macrophage polarization and promoted esophageal cancer progression.

The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.

Cold to Hot: Tumor Immunotherapy by Promoting Vascular Normalization Based on PDGFB Nanocomposites.

Immunotherapy is a promising cancer therapeutic strategy. However, the "cold" tumor immune microenvironment (TIME), characterized by insufficient immune cell infiltration and immunosuppressive status, limits the efficacy of immunotherapy. Tumor vascular abnormalities due to defective pericyte coverage are gradually recognized as a profound determinant in "cold" TIME establishment by hindering immune cell trafficking. Recently, several vascular normalization strategies by improving pericyte coverage have been reported, whereas have unsatisfactory efficacy and high rates of resistance. Herein, a combinatorial strategy to induce tumor vasculature-targeted pericyte recruitment and zinc ion-mediated immune activation with a platelet-derived growth factor B (PDGFB)-loaded, cyclo (Arg-Gly-Asp-D-Phe-Lys)-modified zeolitic imidazolate framework 8 (PDGFB@ZIF8-RGD) nanoplatform is proposed. PDGFB@ZIF8-RGD effectively induced tumor vascular normalization, which facilitated trafficking and infiltration of immune effector cells, including natural killer (NK) cells, M1-like macrophages and CD8+ T cells, into tumor microenvironment. Simultaneously, vascular normalization promoted the accumulation of zinc ions inside tumors to trigger effector cell immune activation and effector molecule production. The synergy between these two effects endowed PDGFB@ZIF8-RGD with superior capabilities in reprogramming the "cold" TIME to a "hot" TIME, thereby initiating robust antitumor immunity and suppressing tumor growth. This combinatorial strategy for improving immune effector cell infiltration and activation is a promising paradigm for solid tumor immunotherapy.

A gene-based score for the risk stratification of stage IA lung adenocarcinoma.

OBJECTIVE: We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. METHODS: Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. RESULTS: Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. CONCLUSIONS: The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.

Circ-HSP90A expedites cell growth, stemness, and immune evasion in non-small cell lung cancer by regulating STAT3 signaling and PD-1/PD-L1 checkpoint.

BACKGROUND: Circular RNAs (circRNAs) are important participators in tumor progression for their stable structure and high tissue-specific expression. The purpose of this research was to clarify the potential and mechanism of a novel circRNA-circ-HSP90A in non-small cell lung cancer (NSCLC). METHODS: Biological potentials of circ-HSP90A in NSCLC were measured by functional assays. Molecular interaction was assessed by bioinformatics analysis and mechanical assays. RESULTS: Results depicted that circ-HSP90A was cyclization from its host gene heat shock protein 90 alpha (HSP90A) and was up-regulated in NSCLC cells. Circ-HSP90A depletion retarded proliferation, migration, invasion, and immune evasion. Mechanistically, circ-HSP90A recruited ubiquitin specific peptidase 30 (USP30) to stabilize HSP90A and then stimulated the signal transducer and activator of transcription 3 (STAT3) signaling. Meanwhile, circ-HSP90A sponged miR-424-5p to programmed cell death ligand 1 (PD-L1). CONCLUSIONS: Our study firstly showed that circ-HSP90A promoted cell growth, stemness, and immune evasion in NSCLC through regulating STAT3 signaling and programmed cell death 1 (PD-1)/PD-L1 checkpoint, mirroring that targeting circ-HSP90A might become a novel target of immunotherapy in NSCLC.

Heterogeneity and Clinical Effect of Epidermal Growth Factor Receptor in Primary Lung and Brain Metastases of Nonsmall Cell Lung Cancer.

INTRODUCTION: This study aimed to analyze the heterogeneity in epidermal growth factor receptor (EGFR) gene mutation and its impact on clinical outcomes in primary tumor and corresponding brain metastasis (BM) in nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Primary pulmonary tumors and paired BMs of 27 NSCLC patients were surgically removed. All brain lesions were histologically confirmed as metastatic NSCLC. EGFR gene mutation status was detected by using amplification refraction mutation system. McNemar test was performed to compare EGFR mutation status between lung primary tumors and metastatic brain tumors and Kappa test was performed to quantify the agreement between the two. RESULTS: Of the 27 patients, nine cases were found to have EGFR mutations in BMs and 10 had a positive EGFR mutation status in primary lung tumor tissue. The rate of consistency of the matched tumor was 24/27 (88.9%). Among the three cases presenting EGFR mutational heterogeneity, two patients harbored an EGFR mutation in the primary tumor but not in the BMs; meanwhile, the last patient demonstrated the opposite pattern. Compared to patients with consistent EGFR mutations, patients with inconsistent mutations showed better outcomes. Further analysis revealed that the two patients whose EGFR mutant-type primary tumor progressed to wild-type cerebral metastatic tumor had longer overall survival than the patient whose EGFR wild-type primary tumor progressed to mutant-type brain metastatic tumor. CONCLUSIONS: Heterogeneity of EGFR mutation status was observed between primary NSCLC and paired BM. Patients possessing a wild-type EGFR mutation in BM might have better outcomes, especially those with transition from mutant to wild-type.

Patterns and prognostic predictive value of perineural invasion in esophageal squamous cell carcinoma.

BACKGROUND: The pathological phenotype of perineural invasion (PNI) in squamous cell carcinoma (ESCC) is prevalent but highly heterogeneous. METHODS: Postoperative specimens from all patients with ESCC at Shaanxi Provincial People's Hospital were evaluated for PNI using haematoxylin and eosin (H&E) staining and S100 immunohistochemistry (IHC). We determined the correlation between PNI status and clinical outcomes. RESULTS: Among 349 ESCC cases, PNI was identified in 127 patients (36.3%), and four subtypes of PNI were identified in our study. Correlation analysis confirmed that PNI was related to tumour invasion depth (pT stage) and lymph node status (pN stage) (P < 0.05). Multivariate analysis showed that PNI (P = 0.001) was an independent factor affecting disease-free survival (DFS) in ESCC, and a similar result was found for overall survival (OS) (P = 0.017). Further analysis revealed that PNI status was a prognostic factor of DFS (P < 0.001) and OS (P = 0.003) exclusively in pN-negative patients. We also found that patients with the PNI-a subtype had better DFS (P = 0.002) and OS (P = 0.002) than patients with the other three subtypes (PNI-b, c, d). CONCLUSION: The pathological phenotypes of PNI are diverse, and the identification of PNI subtypes has important clinical guiding value.

The role of vascular invasion and lymphatic invasion in predicting recurrent thoracic oesophageal squamous cell carcinoma.

BACKGROUND: Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre. METHODS: This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics. RESULTS: Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P<0.001) and pTNM stage (P<0.001), and similar results were found in VI. Moreover, survival analysis showed that pT stage (P<0.001), pN stage (P=0.001), pTNM stage (p<0.001), VI (P=0.001) and LI (P<0.001) were associated with DFS in ESCC. Furthermore, multivariate analysis suggested that pT stage (RR=1.4, P =0.032), pN stage (RR=1.9, P<0.001) and LI (RR=1.5, P=0.008) were independent predictive factors for DFS. Finally, relapse was observed in 110 patients (lymph node metastasis, 78 and distant, 32) and 147 patients with cancer-related deaths. Subanalysis showed that LI-positive patients had higher lymph node metastasis, although there was no significant difference (32.1% vs. 15.6%, P=0.100). CONCLUSIONS: LI and VI were common in ESCC; they were all survival predictors for patients with ESCC, and LI was independent. Patients with positive LI were more likely to suffer lymph node metastasis.

M2 macrophages-derived exosomal microRNA-501-3p promotes the progression of lung cancer via targeting WD repeat domain 82.

BACKGROUND: Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82). METHODS: Lung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed. RESULTS: TAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p. CONCLUSION: M2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.

The strong interfacial coupling effect of Nafion between LaFeO3/electrolyte for efficient photoelectrochemical water reduction.

Insufficient reduction capability and scanty active substance limit the application of LaFeO3(LFO) in the field of photoelectrochemical (PEC) water splitting. This work demonstrates a judicious combination of LFO/Nafion composite to improve the PEC performance by a unique dip-coating method on the FTO. The photocurrent density of the LFO electrode coated with two layers Nafion increased to -23.9µA cm-2at 0.47 V versus RHE, which is 4.1 times that of the pristine LFO. Based on the experimental data and theoretical analysis, the improvement of the PEC properties is attributed to the construction of organic/inorganic units, which would enable strong electronic coupling and favor interfacial charge transfer, resulting in a 30 mV downward shift of its flat band potential. Thus, the conduction band gets closer to the proton reduction potential of H+to H2after decoration with Nafion, resulting in a stronger photogenerated electron reduction ability. Our study provides insights that organic materials modify semiconductor photoelectrodes for accelerating charge kinetics.

Brain tissue development of neonates with Congenital Septal Defect: Study on MRI Image Evaluation of Deep Learning Algorithm.

OBJECTIVES: This article is based on deep learning algorithms and uses MRI to study the development of congenital heart septal defects in neonatal brain tissue. METHODS: From January 2018 to December 2019, 150 cases of congenital cardiac paper septal defect were retrospectively analyzed on 50 cases of normal newborns and neonates. The four index parametersbrain MR imaging, lateral ventricle pre-angle measurement index (F/F'), body index (D/ D'), caudal nucleus index (C/C') were analyzed. The independent sample t test is performed to compare the difference parameters between groups. RESULTS: F congenital heart disease group and control group/F 'values were 0.301 ± 0.035 and 0.296 ± 0.031; Evans index was 0.239 ± 0.052 and 0.233 ± 0.025; 2 sets of D/D' values were 0.261 ± 0.039 and 0.234 ± 0.032; C/C 'value was 0.138 ± 0.018 and 0.124 ± 0.015 respectively. The congenital heart disease group D/D ', and the value of C/C' obtained under the ROC curve area value, respectively 0.698 and 0.750, Youden index corresponding to the maximum D/D ', and the value of C/C' values were 0.28 and 0.12. CONCLUSION: Lateral ventricle D/D 'and C/C' is more sensitive indicator which can be evaluated with the difference between the volume of congenital heart septal defects in newborn normal neonatal brain; when the D/D 'value> 0.28, C/C' value> 0.12. For the diagnosis and evaluation of congenital heart septal defect neonatal brain volume abnormalities have a certain reference value.

Risk factors for predicting cement leakage following percutaneous vertebroplasty for osteoporotic vertebral compression fractures.

PURPOSE: The purpose of the present study is to identify independent risk factors for the occurrence of cement leakage (CL) during percutaneous vertebroplasty (PVP) for four different leakage types in treating osteoporotic vertebral compression fractures (OVCFs). METHODS: We retrospectively reviewed 292 patients who underwent PVP for single-level OVCF from January 2009 to March 2011. The influences of several potential risk factors that might affect the occurrence of CL were assessed using univariate and multivariate analyses. Cement leakage was evaluated by computed tomography and classified into four different types: through the basivertebral vein (B-type), the segmental vein (S-type), a cortical defect (C-type), and intradiscal leakage (D-type). RESULTS: Cement leakage was found in 227 of the 292 treated vertebrae. None of the parameters showed a statistically significant effect by univariate analysis. However, multivariate analysis showed that cement viscosity was an independent risk factor in B-type CL, fracture severity and fracture type were in S-type CL, fracture severity and presence of cleft on MRI were in C-type CL, and fracture severity, cortical disruption on MRI, presence of cleft on MRI and cement viscosity were in D-type CL. CONCLUSION: Each different vertebral fracture pattern has its own risk factors for CL. Identification of the above predicting factors for CL preoperatively might be helpful for more rigorous and strict patient selection criteria for the appropriate candidates for PVP.

MiR-429 Induces Gastric Carcinoma Cell Apoptosis Through Bcl-2.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of gastric carcinoma (GC). MiR-429 has been recently reported to inhibit GC growth, but the underlying mechanisms are not clear. METHODS: Here, we studied the levels of miR-429 and anti-apoptotic protein Bcl-2 in GC specimens. We performed bioinformatics analyses and used luciferase-reporter assay to analyze the relationship between miR-429 and Bcl-2 in GC cells. Cell survival upon Fluorouracil treatment was analyzed in a CCK assay. Cell apoptosis was measured by flow cytometry based FITC Annexin V apoptosis detection assay. RESULTS: MiR-429 levels were significantly decreased and Bcl-2 levels were significantly increased in GC specimens, compared to the paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-429 and Bcl-2 inversely correlated in GC specimens. MiR-429-low subjects had an overall inferior survival, compared to miR-429-high subjects. Bioinformatics analyses showed that miR-429 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-429 inhibited Bcl-2-mediated cell survival against apoptosis induced by Fluorouracil, while depletion of miR-429 augmented it. CONCLUSION: Our data suggest that miR-429 suppression in GC promotes Bcl-2-mediated cancer cell survival against chemotherapy-induced cell death. Re-expression of miR-429 levels in GC cells may enhance cancer apoptosis during chemotherapy.

MyD88-silenced dendritic cells induce T-cell hyporesponsiveness and promote Th2 polarization in vivo.

BACKGROUND AIMS: Previous studies have determined that the absence of MyD88 enhances the tolerogenicity of dendritic cells (DCs), suggesting that inhibiting innate immunity may be a potential strategy to facilitate the induction of transplant tolerance by DCs. However, the underlying mechanism remains unclear. METHODS: Recipient rats were preconditioned with MyD88 gene-silenced DCs. In vivo distribution of infused MyD88 gene-silenced DCs in lymphatic organs was also analyzed. The response ability of recipient spleen T cells was determined by cell proliferation assay. The concentrations of interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-5 and IL-10 in cell culture supernates were measured with sandwich enzyme-linked immunosorbent assay. Flow cytometry was used to detect the transfection efficiency and CD4(+)CD25(+)FoxP3(+) T cell assay. RESULTS: After being infused into allogenic recipient rats, both MyD88-or control-silenced DCs were efficiently trafficked to the lymphatic organs and liver. The ex vivo analysis of proliferative responses revealed the donor-specific inhibition of alloimmune reactivity by MyD88-silenced DCs. This effect was associated with the marked inhibition of Th1-type cytokine production (IFN-γ and IL-2) but with significant promotion of Th2 type cytokine secretion (IL-4 and IL-5). CONCLUSIONS: It was demonstrated that T cells from recipients pretreated with MyD88-silenced DCs exhibited significantly reduced secretion of IFN-γ and IL-2 but markedly enhanced production of IL-4 and IL-5.

Pd(II)-catalyzed C(sp(3))-H arylation of amino acid derivatives with click-triazoles as removable directing groups.

By using click-triazoles as conveniently approachable and removable directing groups, the direct palladium-catalyzed C(sp(3))-H arylation of amino acid derivatives with various aryl iodides bearing different electronic properties has been achieved. Notably, the desired amino acid molecule can be obtained by the cleavage of the tethered click-triazoles after the catalytic reaction, which aims to provide a practical protocol for the accessibility of both natural and synthetic amino acids.

A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer.

We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003-2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases.

High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

Effect of vanillin-conjugated chitosan-stabilized emulsions on dough and bread characteristics.

In this study, the effect of chitosan-vanillin Schiff base emulsions (CSVAEs) on dough and bread characteristics was investigated. The results revealed that CSVAEs were embedded in the gluten and that the viscoelasticity and mechanical strength of the dough gradually increased with increasing CSVAEs concentration, α-helical and ß-fold content, and elastic structure in the dough increased with the same patterns. The basic properties of bread were measured, and it was found that low concentrations of CSVAEs were effective in improving the quality of bread and slowing the staling rate. As the storage time increased, CSVAEs had less effect on the rate of moisture loss, hardness and springiness of the bread and more effect on the inhibition of the acidity of the bread. The addition of CSVAEs slowed the increase in bacteria and molds and extended the shelf life of the bread.

An Adaptively Weighted Averaging Method for Regional Time Series Extraction of fMRI-based Brain Decoding.

Brain decoding that classifies cognitive states using the functional fluctuations of the brain can provide insightful information for understanding the brain mechanisms of cognitive functions. Among the common procedures of decoding the brain cognitive states with functional magnetic resonance imaging (fMRI), extracting the time series of each brain region after brain parcellation traditionally averages across the voxels within a brain region. This neglects the spatial information among the voxels and the requirement of extracting information for the downstream tasks. In this study, we propose to use a fully connected neural network that is jointly trained with the brain decoder to perform an adaptively weighted average across the voxels within each brain region. We perform extensive evaluations by cognitive state decoding, manifold learning, and interpretability analysis on the Human Connectome Project (HCP) dataset. The performance comparison of the cognitive state decoding presents an accuracy increase of up to 5% and stable accuracy improvement under different time window sizes, resampling sizes, and training data sizes. The results of manifold learning show that our method presents a considerable separability among cognitive states and basically excludes subject-specific information. The interpretability analysis shows that our method can identify reasonable brain regions corresponding to each cognitive state. Our study would aid the improvement of the basic pipeline of fMRI processing.