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Background Circular RNAs (circRNAs) are well-known regulators of cancer progression and chemoresistance in various types of cancers. This study was performed to investigate the function of hsa_circ_0000277 in esophageal squamous cell carcinoma (ESCC). Methods RNA levels were analyzed via the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8) assay was applied to determine cell proliferation and half maximal inhibitory concentration (IC50) of cisplatin (DDP). Colony formation ability was evaluated by colony formation assay. Cell cycle and apoptosis were measured using flow cytometry. RNA immunoprecipitation (RIP), pull-down assay and dual-luciferase reporter assays were performed for target interaction analysis. The protein levels were determined through western blot. Xenograft models were established for researching hsa_circ_0000277 function in vivo. Results Hsa_circ_0000277 expression was increased in ESCC cells and tissues, and it had important clinical significance. Downregulation of hsa_circ_0000277 repressed ESCC cell proliferation, colony formation, cell cycle, and DDP resistance. Hsa_circ_0000277 acted as a microRNA-873-5p (miR-873-5p) sponge and Sry-related high-mobility group box 4 (SOX4) was validated as a target of miR-873-5p. Moreover, hsa_circ_0000277/miR-873-5p axis and miR-873-5p/SOX4 axis regulated ESCC cell progression and DDP resistance. Hsa_circ_0000277/miR-873-5p axis activated SOX4/Wnt/β-catenin signaling pathway. H sa_circ_0000277 facilitated tumorigenesis and DDP resistance by miR-873-5p/SOX4 axis in vivo. Conclusion These findings unraveled that hsa_circ_0000277 promoted ESCC progression and DDP resistance via miR-873-5p/SOX4/Wnt/β-catenin axis, showing a specific molecular mechanism of carcinogenesis and chemoresistance in ESCC.

It remains a challenge for the effective treatment of neuroinflammatory disease, including multiple sclerosis (MS), stroke, epilepsy, and Alzheimer's and Parkinson's disease. The voltage-gated potassium Kv1.3 channel is of interest, which is considered as a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of T lymphocytes as well as microglial cells. Toxic animals, such as sea anemones, scorpions, spiders, snakes, and cone snails, can produce a variety of toxins that act on the Kv1.3 channel. The K channel blocking toxin (ShK) from the sea anemone is proved as a classical blocker of Kv1.3. One of the synthetic analogs ShK-186, being developed as a therapeutic for autoimmune diseases, has successfully completed first-in-man Phase 1 trials. In addition to addressing the recent progress on the studies underlying the pharmacological characterizations of ShK on MS, the review will also explore the possibility for clinical treatment of ShK-like Kv1.3 blocking polypeptides on other neuroinflammatory diseases.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

The Oriente Basin, as part of the retro-arc foreland basin system, develops tidal-dominated estuary, where the LU layer exhibits complex sedimentary characteristics in lateral that brings great uncertainty to reservoir characterization using only wells. As a result, it is essential to investigate the sedimentary characteristics of the tidal-dominated estuary by incorporating seismic data. First, four electrofacies are established to characterize the logging response of various lithology combinations in an estuary setting. The seismic facies are then studied by establishing the relationship between seismic waveforms and logging response. Finally, a reservoir model of the LU layer is built by quantitatively characterizing the spatial distribution of sedimentary facies based on the electrofacies and seismic facies. Bottom-water reservoirs are reinterpreted as a combination of the upper edge-water reservoir and the lower bottom-water reservoir based on the characterization results, which are verified by the new drilling wells.

Background The associations between APOE genotype and early cognitive impairment and long-term functional prognosis after acute ischemic stroke (AIS) are uncertain. Objective To investigate the associations between APOE genotype and early cognitive impairment and long-term functional prognosis after AIS. Methods Our study was a single-center, prospective cohort study, that included 109 patients with AIS. At baseline, APOE genotype, cognition and white matter hyperintensities (WMH) were assessed within 2 weeks of stroke onset. At 3 months and 18 months, the modified Rankin scale (mRS) was used to assess the functional outcome after stroke. Results ε2 carriers had better cognitive performance than ε2 noncarriers did in the Montreal Cognitive Assessment (MoCA, p  = 0.003) and the Trail Making Test (TMT, p  = 0.038). Multivariate logistic regression analysis revealed that ε2 was an independent protective factor for early post-stroke cognitive impairment (OR 0.213, 95% CI 0.055–0.820), whereas ε4 was not associated with early post-stroke cognitive impairment (OR 2.582, 95% CI 0.314–21.219). ε2 had no significant effect on WMH, whereas ε4 aggravated WMH, especially in the deep white matter (DWM). No significant interaction effect between the Fazekas score and ε2 on early post-stroke cognitive impairment was found. Female sex (OR 7.081, 95% CI 2.531–19.813), admission NIHSS score (OR 1.265, 95% CI 1.062–1.507), and DWM Fazekas score (OR 2.224, 95% CI 1.106–4.469) were independent risk factors for long-term unfavorable prognosis after ischemic stroke. Conclusion ε2 was associated with reduced risk of early post-stroke cognitive impairment, but not with the favorable long-term functional prognosis after stroke.

Introduction Postoperative delirium (POD) is a frequent and serious complication after cardiac surgery. The glucose-to-albumin ratio (GAR) integrates metabolic and nutritional status, but its predictive value for POD in intensive care unit (ICU) patients remains uncertain. Methods We conducted a retrospective cohort study using data from the MIMIC-IV (v3.1) database. A total of 4,307 adult ICU patients admitted within 24 h after cardiac surgery were included. GAR was calculated by dividing serum glucose (mg/dL) by albumin (g/dL). The primary outcome was POD, assessed using the Confusion Assessment Method (CAM). GAR was evaluated as a continuous variable, by quartiles, and by a dichotomized cutoff determined from the receiver operating characteristic (ROC) curve. Logistic regression, restricted cubic splines, and mediation analyses were applied. To reduce confounding, propensity score matching was performed, and the main logistic regression analysis was repeated in the matched cohort. Results Of 4,307 patients, 658 (15.3%) developed POD and 120 (2.8%) died within 90 days. Higher GAR was independently associated with POD (continuous odds ratio [OR] 1.01, 95% confidence interval [CI] 1.00–1.01, p  = 0.027; highest vs. lowest quartile OR 1.54, 95% CI 1.16–2.05, p  = 0.003). The optimal GAR cutoff was 35 (AUROC 0.654). Patients with GAR ≥ 35 had higher delirium risk in both the full cohort (adjusted OR 1.37, 95% CI 1.13–1.67, p  = 0.001) and the matched cohort (OR 1.31, 95% CI 1.06–1.61, p  = 0.012). Mediation analysis suggested that prolonged mechanical ventilation and ICU stay partly explained the GAR–POD relationship. Conclusion GAR is an independent predictor of postoperative delirium in ICU patients undergoing cardiac surgery. It may serve as a practical biomarker for early delirium risk stratification. Prospective studies are warranted to validate these findings and to further establish the clinical utility of GAR in perioperative care.

NKG2A is an inhibitory receptor of both T cells and natural killer (NK) cells. Persistent activation promotes T cells and NK cells to express NKG2A and results in the progression of chronic infection and cancer. However, the characteristics and subsets of NKG2A lymphocytes in human lung cancer are still unclear. Here, we used the Tumor Immune Estimation Resource database and immune profiling of paired biospecimens to uncover the correlation between NKG2A expression and immune infiltration levels in human cancer as well as the characteristics of NKG2A lymphocytes in human lung cancer. We found that KLRC1 expression was especially correlated with CD8 T-cell infiltration levels in 34 types of human cancer through the Tumor Immune Estimation Resource database. Moreover, NKG2A CD8 T cells were the predominant subset of NKG2A lymphocytes in human lung cancer. In contrast, the NKG2A NK cells were decreased in tumors compared with the paired normal lung tissue. Tumor-infiltrating NKG2A CD8 T cells expressed tissue-resident memory T cell (T cell) and exhausted T-cell markers. Cytokines and cytotoxic molecules secreted by tumor-infiltrating NKG2A CD8 T cells were significantly lower than those secreted by NKG2A CD8 T cells . When stimulated with T-cell receptor activator, tumor-infiltrating NKG2A CD8 T cells could secrete large amounts of granzyme B. Our findings demonstrate that tumor-infiltrating NKG2A CD8 T cells form the predominant subset of NKG2A cells in human lung cancer and suggest that targeting NKG2A CD8 T cells is a promising approach for future anti-lung cancer immunotherapy.

Given that ischemic stroke ranks as one of the most fatal diseases globally, it is imperative to develop clinically effective neuroprotective agents for stroke. Microglia serve as innate immune cells for maintaining brain homeostasis, and upon activation, they are well-known to be able to transform into two functional phenotypes, namely, the M1 and M2 types, which can convert each other and exert opposing effects on neurotoxicity and neuroprotection, respectively. Traditional Chinese medicine possesses a deep-rooted and profound history with rich theory in treating cerebrovascular disorders, and its natural compounds have been considered as promising adjunctive therapies. Recently, researchers have been devoting attention to the inflammation-suppressive properties of the compounds from Chinese herbs. These compounds are gradually emerging as adoptable therapeutic agents with wide application prospect for improving stroke outcomes, through regulating microglial polarization to attenuate neuroinflammation. Thereby, we reviewed the functions of microglial cells in inflammation and neuroprotection and explored the regulation of microglial activity by natural compounds to alleviate neuroinflammation and protect neural function after ischemic stroke. Collectively, using natural compounds to suppress the microglia-mediated detrimental inflammatory response, meanwhile enhancing their anti-inflammatory abilities to accelerate neuronal recovery, will be promising therapeutic approaches for ischemic stroke.

[This corrects the article DOI: 10.3389/fnins.2019.01393.].

Shales represent strongly intrinsic vertical transverse isotropy (VTI) property or polar anisotropy. The presence of vertically aligned fractures makes shale exhibit orthogonal anisotropy and the seismic responses have azimuthal variation. Conventional linearized PP-wave reflectivity expression for orthorhombic (ORT) media includes at least 8 parameters to be inverted, and the amplitude inversion based on such equations can be highly ill-posed. In this paper, we derive a modified PP-wave approximation of reflection coefficients in ORT media and propose a two-step strategy based on the Bayesian-framework inversion method. The new equation represents the seismic response of polar anisotropy and azimuthal anisotropy separately, and it consists of only 5 model parameters to be inverted. Three of these model parameters are azimuthal independent: A—acoustic impedance, B—anisotropic shear modulus and C—horizontal P-wave phase velocity (along the fracture strike), and two of them are azimuthal dependent: D—azimuthal anisotropic gradient and E—horizontal P-wave anisotropy parameter. Accuracy analysis demonstrates that the derived approximation has similar accuracy to the existing approximation. A stepwise inversion strategy is proposed to invert azimuthal-independent parameters and azimuthal-dependent parameters separately. Synthetic tests show that the proposed strategy is more stable and better conditioned than the existing multi-parameter simultaneous inversion. Field seismic data set of a fractured shale-gas reservoir is also used to demonstrate the stability and accuracy of the proposed inversion method.Article HighlightsPP-wave reflection coefficient is derived in terms of only 5 model parameters for orthorhombic media. Three of them are azimuthal independent: A—acoustic impedance, B—anisotropic shear modulus, C—horizontal P-wave phase velocity (along the fracture strike), and the others are azimuthal dependent: D—azimuthal anisotropic gradient, and E—horizontal P-wave anisotropy parameterA stepwise inversion strategy for inverting azimuthal-independent parameters and azimuthal-dependent parameters is proposedTests on synthetic and field seismic datasets imply that the proposed inversion method has the potential to generate reliable results of the model parameters for reservoir characterization