Background:
A growing amount of evidence has suggested the clinical importance of stromal and immune cells in the gastric cancer microenvironment. However, reliable prognostic signatures based on ...assessments of stromal and immune components have not been well-established. This study aimed to develop a stromal-immune score-based gene signature in gastric cancer.
Methods:
Stromal and immune scores were estimated from transcriptomic profiles of a gastric cancer cohort from TCGA using the ESTIMATE algorithm. A robust partial likelihood-based Cox proportional hazard regression model was applied to select prognostic genes and to construct a stromal-immune score-based gene signature. Two independent datasets from GEO were used for external validation.
Results:
Favorable overall survivals were found in patients with high stromal score (
p
= 0.014) and immune score (
p
= 0.045). Forty-five stromal-immune score-related differentially expressed genes were identified. Using a robust partial likelihood-based Cox proportional hazard regression model, a gene signature containing SOX9, LRRC32, CECR1, and MS4A4A was identified to develop a risk stratification model. Multivariate analysis revealed that the stromal-immune risk score was an independent prognostic factor (
p
= 0.018). Based on the risk stratification model, the cohort was classified into three groups yielding incremental survival outcomes (log-rank test
p
= 0.0004). A nomogram integrating the risk stratification model and clinicopathologic factors was developed. Calibration and decision curves showed a better performance and net benefits for the nomogram. Similar findings were validated in two independent cohorts.
Conclusion:
The stromal-immune score-based gene signature represents a prognosis stratification tool in gastric cancer.
This letter presents a new real‐time and direct measurement method based on energy for piezoelectric resonator. An analytical model considering the stored energy and dissipation energy for quality ...factor measurement is built up. Using this novel direct energy method, the quality factor for piezoelectric resonator can be measured in real time. The finite element method simulations are introduced to verify the analytical model. Experiments results agree well with the theoretical model and show that quality factor can be measured by direct energy method. This work provides a new method for quality factor measurement of piezoelectric resonator.
With the large-scale grid integration of wind power, the inherent space-time characteristics of wind power and the transmission congestion seriously restrict the consumption of wind power and the ...development of demand. In order to improve the wind power accommodation and load acceptance level, the joint planning including the wind power installed capacity and location, the transmission network expansion, and energy storage system locating and sizing is considered. The generation-side operation process and the charging-discharging strategy of energy storage systems are also involved. The source-network-storage joint planning model is established with the goal of minimizing the cost of the transmission network expansion, the construction and operation of energy storage systems, the conventional units' operation, the wind curtailment, and the heavy-load penalty. Furthermore, the energy storage system planning & operation constraints, the heavy-load operation constraints and the quadratic generation cost function are linearized in the MILP model. Through the Wood&Wollenberg 6-bus system, the IEEE RTS-24 test system, and the modified IEEE 118-bus system as the test systems, the joint planning schemes under multiple scenarios are compared and analyzed. The results show that the proposed planning model can effectively improve the load acceptance capability and wind power integration level.
The biological role of miR-500a-5p has not yet been reported in the context of colorectal cancer (CRC). Here, we show that miR-500a-5p expression is decreased in CRC tissues compared with adjacent ...normal tissues. Low miR-500a-5p expression is associated with malignant progression. Moreover, transfection of CRC cells with miR-500a-5p induces G0/G1 cell cycle arrest and inhibits their growth and migration. Mechanistically, miR-500a-5p directly targets HDAC2 and inhibits HDAC2-mediated proliferation in CRC in nude mice. Furthermore, YY1 binds to the promoter of miR-500a-5p and negatively regulates its transcription. Restoration of miR-500a-5p expression is up-regulated via the p300/YY1/HDAC2 complex. Besides, therapeutic delivery of miR-500a-5p significantly suppresses tumour development in a xenograft tumour model and a HDAC2 inhibitor FK228-treated CRC model. Our studies demonstrate that miR-500a-5p functions as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis, which contributes to the development of and provides new potential candidates for CRC therapy.
Remnant cholesterol (RC) represents a low-cost and readily measured lipid index that contributes significantly to residual cardiovascular disease risk. The triglyceride-glucose (TyG) index exhibits a ...significant correlation with cardiovascular disease occurrence. However, RC and the TyG index have rarely been examined for their potentials in predicting coronary artery disease (CAD). Accordingly, the study was designed to validate the correlations of these two biomarkers with CAD and to compare the forecasted values of these two biomarkers for newly diagnosed CAD.
Totally 570 subjects firstly administered coronary angiography were enrolled, including 431 newly diagnosed CAD cases and 139 individuals without CAD. The individuals were classified into two groups according to CAD diagnosis. RC was derived as total cholesterol content (mmol/L) - (high density lipoprotein cholesterol content + low density lipoprotein cholesterol content; both in mmol/L). The TyG index was determined as ln (fasting triglyceride level mg/dL × fasting plasma glucose level mg/dL)/2.
Baseline feature analysis revealed significant differences in RC and the TyG index between the CAD and non-CAD groups (both P < 0.001). RC and the TyG index were independent risk factors for CAD in accordance with logistic regression analysis (both P < 0.05). Moreover, spearman correlation analysis elucidated CAD had a more remarkable correlation with the TyG index compared with RC (both P < 0.001). Furthermore, according to receiver operating characteristic curve analysis, the TyG index was better than RC in predicting CAD.
The TyG index and RC have significant associations with CAD. Compared with RC, the TyG index possesses a closer correlation with CAD and a higher predictive value for CAD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stone matrix asphalt (SMA) mixture has been widely used in pavement engineering for its preferable in-service performance. However, deterioration of SMA pavement in skid resistance is apparent under ...traffic loading. There remains lacking attention on skid resistance attenuation of SMA pavement, which in turn is important for skid durability design in practice. Hence, this study aims to perform a thorough investigation to reveal the skid resistance attenuation law of SMA pavement. Multiple types of SMA-13 mixtures prepared by different material designs were selected to conduct a kneading test that simulates real surface states of in-service SMA pavement. Pressure-sensitive film and a 3D laser scanner were utilized for evaluating anti-skid performance and skid durability. The finite element (FE) method is introduced to simulate vehicle braking distance for skid-resistance evaluation. The results show that skid resistance attenuation of SMA pavement consists of two stages: In the first stage, the skid resistance of SMA pavement experiences a short enhancement, followed by a long-term weakening stage. Abundant surface texture of SMA helps to mitigate the impact of traffic load on skid resistance. The FE analysis and pressure-sensitive film results demonstrate the potential of skid durability design of SMA pavement based on the skid resistance attenuation law.
The asymptotic formula of the fourth moment of Dirichlet
L
-functions at the central value was predicted in a conjecture by J. B. Conrey, D. W. Farmer, J. P. Keating, M. O. Rubinstein, and N. C. ...Snaith, and the prime moduli case was proved by M. P. Young in 2011. This work establishes this asymptotic formula for general moduli. The work relies on the study of a special divisor sum function, called
D
q
-function, which plays a key role in deducing the main terms. Another key ingredient is an application of new bounds for double sums in Kloosterman sums, applied in the estimate of the error terms.
Pathological brain detection is an automated computer-aided diagnosis for brain images. This study provides a novel method to achieve this goal.We first used synthetic minority oversampling to ...balance the dataset. Then, our system was based on three components: wavelet packet Tsallis entropy, extreme learning machine, and Jaya algorithm. The 10 repetitions of K-fold cross validation showed our method achieved perfect classification on two small datasets, and achieved a sensitivity of 99.64 ± 0.52%, a specificity of 99.14 ± 1.93%, and an accuracy of 99.57 ± 0.57% over a 255-image dataset. Our method performs better than six state-of-the-art approaches. Besides, Jaya algorithm performs better than genetic algorithm, particle swarm optimization, and bat algorithm as ELM training method.
Previous studies have shown an association between coiled-coil domain-containing (CCDC) genes and different cancers. Our previous studies revealed that CCDC43 is highly expressed in colorectal ...cancer, but the expression and molecular mechanisms of CCDC43 in gastric cancer (GC) are yet to be determined. Here, we show that CCDC43 is overexpressed in gastric tissues. CCDC43 expression is closely related to tumor differentiation, lymph-node-metastasis, and prognosis of gastric cancer. Overexpression of CCDC43 promotes the proliferation, invasion, and metastasis of GC cells. CCDC43 may upregulate and stabilize ADRM1, resulting in the construction of the ubiquitin-mediated proteasome. In contrast, inhibition of ADRM1 could reverse the function of CCDC43 in GC both in vitro and in vivo. Our data demonstrate that transcription factor YY1 directly binds to CCDC43 and ADRM1 gene promoters, leading to over-expression of CCDC43 and ADRM1. Furthermore, in vitro experiments demonstrate that knock down of CCDC43 or ADRM1 attenuates the YY1-mediated malignant phenotypes. Finally, the association among YY1, CCDC43 and ADRM1 is validated in clinical samples. Our findings suggest that the CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of GC, and the axis may be a potential therapeutic target for GC.
•CCDC43 is overexpressed in gastric cancer (GC) and associated with prognosis in GC.•CCDC43 promotes GC proliferation, invasion and metastasis.•CCDC43 interaction with ADRM1 promotes proliferation, invasion and metastasis in GC.•CCDC43 and ADRM1 are directly targeted by YY1 in GC cells.
•Ubiquitination-proteasome system modulates tumor microenvironment in gastric cancer.•Ubiquitination-proteasome system of gastric cancer is heterogeneity.•Double times unsupervised consensuses ...identify two distinct molecular subtypes.•Classification of different molecular subtypes helps risk stratification.•Our risk scoring system shows robustness of predicting effect of immunotherapy.
Modulators in ubiquitin-proteasome system (UPS) has been implicated in regulating cancer-related genes, immune responses, and oncogenesis. However, the global UPS expression pattern and its role in gastric cancer (GC) pathology remain elusive. Herein, we integrated the modulators in UPS and dissected their associations with tumor microenvironment (TME), therapeutic response and prognosis in GC. Ten eligible GC cohorts (n = 2161) were collected in this comprehensive analysis. Unsupervised clustering based on expression profile of ubiquitination regulators was performed to identify distinct expression pattern. Then, pathway activation, and TME characteristics and prognosis were explored for patients in each pattern. Finally, a UPS scoring system in GC, termed UPSGC, is developed for individualized quantification of UPS expression pattern. Two prognosis-distinctive UPS expression patterns were identified and validated. Multiple interdependent characteristics were found in each pattern. Patients in the pattern with poor prognosis were found with activation of EMT, TNFα/NF-κB and IL6/JAK/STAT3 signaling, and more infiltration of immunosuppressive M2 macrophages and Th2 cells in TME. And another pattern was characterized by upregulation of angiogenesis, Notch and Wnt-β/catenin signaling, as well as enrichment of microvessels in TME. Based on the UPSGC system, two pattern-related clinical subtypes were identified. Finally, the UPSGC subtypes were validated as robust biomarker to predict patient's therapeutic responses and survival outcomes. In conclusion, this study proposes two previously unexplored UPS expression patterns in GC, in which patients have distinct survival outcomes and molecular characteristics. The findings provide new evidences to support the clinical relevance of ubiquitination with personalized therapy.
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