The Innovative Development Concept of Socialism With Chinese Characteristics for a New Era

This paper has illustrated the connotation of innovative development concept from four dimensions of theoretical innovation, institutional innovation, technological innovation and cultural innovation, and proposed the innovative development concept is the dynamic guarantee for adapting and guiding the Chinese economy for a new ear, strategic support for improving the China’s national strength, and an important magic weapon for promoting the rejuvenation of the Chinese nation. By comparing and analyzing the innovative ideas in the Marxist Political Economics, this paper proposes that innovative development concept is the inheritance and development of Marxist Political Economics, and it is also the new achievement in the study of the political economy of socialism with Chinese characteristics

Identification of tumor mutation burden-associated molecular and clinical features in cancer by analyzing multi-omics data

BackgroundTumor mutation burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in cancer. Systematic identification of molecular features correlated with TMB is significant, although such investigation remains insufficient.MethodsWe analyzed associations of somatic mutations, pathways, protein expression, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), competing endogenous RNA (ceRNA) antitumor immune signatures, and clinical features with TMB in various cancers using multi-omics datasets from The Cancer Genome Atlas (TCGA) program and datasets for cancer cohorts receiving the immune checkpoint blockade therapy.ResultsAmong the 32 TCGA cancer types, melanoma harbored the highest percentage of high-TMB (≥ 10/Mb) cancers (49.4%), followed by lung adenocarcinoma (36.9%) and lung squamous cell carcinoma (28.1%). Three hundred seventy-six genes had significant correlations of their mutations with increased TMB in various cancers, including 11 genes (ARID1A, ARID1B, BRIP1, NOTCH2, NOTCH4, EPHA5, ROS1, FAT1, SPEN, NSD1,and PTPRT) with the characteristic of their mutations associated with a favorable response to immunotherapy. Based on the mutation profiles in three genes (ROS1, SPEN, and PTPRT), we defined the TMB prognostic score that could predict cancer survival prognosis in the immunotherapy setting but not in the non-immunotherapy setting. It suggests that the TMB prognostic score’s ability to predict cancer prognosis is associated with the positive correlation between immunotherapy response and TMB. Nine cancer-associated pathways correlated positively with TMB in various cancers, including nucleotide excision repair, DNA replication, homologous recombination, base excision repair, mismatch repair, cell cycle, spliceosome, proteasome, and RNA degradation. In contrast, seven pathways correlated inversely with TMB in multiple cancers, including Wnt, Hedgehog, PI3K-AKT, MAPK, neurotrophin, axon guidance, and pathways in cancer. High-TMB cancers displayed higher levels of antitumor immune signatures and PD-L1 expression than low-TMB cancers in diverse cancers. The association between TMB and survival prognosis was positive in bladder, gastric, and endometrial cancers and negative in liver and head and neck cancers. TMB also showed significant associations with age, gender, height, weight, smoking, and race in certain cohorts.ConclusionsThe molecular and clinical features significantly associated with TMB could be valuable predictors for TMB and immunotherapy response and therefore have potential clinical values for cancer management

A sensitive and rapid HPLC-DAD method for the determination of 3-hydroxy-1,2-dimethyl-4-pyridone and its distribution in rats

Purpose: To establish a sensitive and rapid method for the determination of the tissue distribution of 3-hydroxy-1,2-dimethyl-4-pyridone (L1) in vivo, and its plasma protein binding capacity.Methods: This study optimized a reverse-phase HPLC method for specific and sensitive determination of L1 as well as its plasma and tissue  distributions. The optimized method was used to determine the plasma protein-binding capacity of L1 in Wistar rats.Results: A rapid, sensitive and simple HPLC-DAD method was established for studying the plasma and tissue distribution of L1. Following TI  administration, its liver concentrations peaked at 60 min and 360min, followed 360 min later with peak level in the kidney (second highest). The L1 concentration was significantly lower after 360 min than after 60 min, and values of its mean binding to plasma proteins was 5.2 % at different L1 concentrations.Conclusion: These results indicate that L1 is a drug with rapid-absorption and rapid-elimination thath is distributed widely in vivo in rats. Moreover, the drug has a weak plasma protein-binding capacity. Keywords: 3-Hydroxy-1,2-dimethyl-4-pyridone, Distribution, Alzheimer’s disease, Therap

Identification and location of ship pipeline leakage based on VMD

Pipeline plays an important role in various systems of the ship. However, due to the harsh environment, leakage often occurs in ship pipeline. This paper proposes a method to identity and locate the pipeline leakage. Using the variational mode decomposition (VMD) algorithm, the vibration signal is decomposed into band-limited intrinsic mode functions (BIMFs). The effective BIMFs are then selected by the correlation coefficient. Center frequency and energy value of the effective BIMFs are extracted as feature vector. Radial Basis Function (RBF) neural network is then used as a tool to identify and locate the leakage. The proposed method is finally verified by experiments

miR-181a Post-Transcriptionally Downregulates Oncogenic RalA and Contributes to Growth Inhibition and Apoptosis in Chronic Myelogenous Leukemia (CML)

MicroRNAs (miRNAs) are a class of short RNAs that regulate gene expression through either translational repression or mRNA cleavage. miRNA-181a (miR-181a), one of the many miRNAs conserved among vertebrates, is differentially expressed in a variety of leukemia. However, its function in leukemia, particularly chronic myelogenous leukemia (CML), is poorly understood. Here we have reported the identification of miR-181a targets by combining TargetScan software prediction and expression profiling through overexpression of miR-181a mimic in leukemic K562 cells. Four overlapping genes were found to be the likely targets of miR-181a. Among the four genes, RalA is a downstream molecule of bcr-abl fusion protein in ras signaling pathway. However, its role in CML remains elusive. Luciferase reporter and Western blot assays confirmed that RalA is a direct target of miR-181a. overexpression of miR-181a effectively suppresses cell growth and induces G2-phase arrest and apoptosis partially by targeting RalA in leukemic K562 cells. Using the KEGG database combined with recent publications, downstream signaling pathway of RalA was graphed by cytoscape software. Therefore, our study is the first to report that RalA is directly regulated by miR-181a and plays an important role in CML. The approach of computational prediction combined with expression profiling might be valuable for the identification of miRNA targets in animal

Phosphorylation of TGB1 by protein kinase CK2 promotes barley stripe mosaic virus movement in monocots and dicots.

The barley stripe mosaic virus (BSMV) triple gene block 1 (TGB1) protein is required for virus cell-to-cell movement. However, little information is available about how these activities are regulated by post-translational modifications. In this study, we showed that the BSMV Xinjiang strain TGB1 (XJTGB1) is phosphorylated in vivo and in vitro by protein kinase CK2 from barley and Nicotiana benthamiana. Liquid chromatography tandem mass spectrometry analysis and in vitro phosphorylation assays demonstrated that Thr-401 is the major phosphorylation site of the XJTGB1 protein, and suggested that a Thr-395 kinase docking site supports Thr-401 phosphorylation. Substitution of Thr-395 with alanine (T395A) only moderately impaired virus cell-to-cell movement and systemic infection. In contrast, the Thr-401 alanine (T401A) virus mutant was unable to systemically infect N. benthamiana but had only minor effects in monocot hosts. Substitution of Thr-395 or Thr-401 with aspartic acid interfered with monocot and dicot cell-to-cell movement and the plants failed to develop systemic infections. However, virus derivatives with single glutamic acid substitutions at Thr-395 and Thr-401 developed nearly normal systemic infections in the monocot hosts but were unable to infect N. benthamiana systemically, and none of the double mutants was able to infect dicot and monocot hosts. The mutant XJTGB1T395A/T401A weakened in vitro interactions between XJTGB1 and XJTGB3 proteins but had little effect on XJTGB1 RNA-binding ability. Taken together, our results support a critical role of CK2 phosphorylation in the movement of BSMV in monocots and dicots, and provide new insights into the roles of phosphorylation in TGB protein functions

Critical charge and spin instabilities in superconducting La3_3Ni2_2O7_7

Motivated by the recent discovery of superconductivity in La$_3$Ni$_2$O$_7$ under high pressure, we explore its potential charge and spin instabilities through combined model analysis and first-principles calculations. Taking into account the negative charge-transfer nature of high valence nickel, a fully correlated two-cluster model identifies a lattice-coupled rocksalt-type charge instability characterized by substantial fluctuations of oxygen holes. This instability is corroborated by density-functional-theory plus $U$ calculations that also reveal a strong tendency towards concurrent antiferromagnetic ordering. The charge, spin, and associated lattice instabilities are significantly suppressed with increasing external pressure, contributing to the emergence of superconductivity in pressurized La$_3$Ni$_2$O$_7$. Carrier doping is found to effectively suppress these instabilities, suggesting a viable strategy to stabilize a superconducting phase under ambient pressure