In this report, prospects on fragmentation function measurements at the BESIII experiment, including the inclusive production of hadrons and Collins effect measurements, are reported. These ...measurements are important to test the energy evolution effect of the fragmentation functions. Preliminary studies based on Monte Carlo simulations are presented.
Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including ...metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8
T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8
T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.
Flood, drought, hail, low temperature and frost disasters from low temperature and frost (DLTF), and snowstorm are the five main meteorological disasters (MDs) in China. Based on the collection of ...historical documents during 1950–2013 and official records between 2012 and 2013, this paper analyzed the temporal trends of affected area induced by MDs during 1950–2013 and the spatiotemporal characteristics of disaster frequency in recent 2 years in China. Besides, the direct economic losses and deaths caused by MDs were further discussed at a provincial level. Results showed that the affected area of MDs, especially flood, drought and DLTF significantly increased during the past 60 years. Flood was the most frequent disaster in China during 2012 and 2013, followed by hail. Spatial patterns of disaster frequency showed that there were more frequent floods in the middle and lower reaches of the Yellow River and the Yangtze River basin, droughts in central and southwest China, hails in north, northwest and southwest China, DLTFs and snowstorms in north, northwest China and individual areas in south China. However, the economic losses caused by MDs were higher in economically developed provinces, and the deaths were higher in mountain regions. Additionally, flood was the major disasters type that contributing to the most losses in most regions of China. These results play an important theoretical guiding role in meteorological disaster prediction, disaster prevention and reduction in the future.
Soil carbon (SC) is a key component of the carbon cycle and plays an important role in climate change; however, quantitatively assessing SC dynamics at the regional scale remains challenging. Earth ...system model (ESM) that considers multiple environmental factors and spatial heterogeneity has become a powerful tool to explore carbon cycle-climate feedbacks, although the performance of the ESM is diverse and highly uncertain. Thus, identifying reliable ESMs is a prerequisite for better understanding the response of SC dynamics to human activity and climate change. The 16 ESMs that participated in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) were employed to evaluate the skill performance of SC density simulation by comparison with reference data from the International Geosphere-Biosphere Programme Data and Information System (IGBP-DIS). Although ESMs generally reflect spatial patterns with lower SC in northwest China and higher SC in southeast China, 11 of 16 ESMs underestimated the SC in China, and 5 of 16 ESMs overestimated the SC density as most ESMs had large discrepancies in capturing the SC density in the northern high latitudes of China and the Qinghai-Tibet Plateau. According to a series of model performance statistics, SC simulated by Institute Pierre Simon Laplace (IPSL) Coupled Model had a close spatial pattern with IGBP-DIS and showed higher skills for SC predictions in China relative to other CMIP5 ESMs. The multimodel ensemble average obtained by IPSL family ESMs showed that SC density exhibited increasing trends under both the RCP4.5 scenario and RCP8.5 scenario. The SC density increased slowly under RCP8.5 compared with that under RCP4.5 and even displayed a decreasing trend in the late 21st century. The findings of this study can provide a reference for identifying the shortcomings of SC predictions in China and guide SC parameterization improvement in ESMs.
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•We evaluated China's soil carbon density simulated by 16 earth system models.•Most ESMs had a limited ability to capture the soil carbon density in high latitudes of China.•The soil carbon density in China showed an overall increasing trend under both RCP4.5 and RCP8.5.•The Qinghai-Tibet Plateau and southeast China have high potential as soil carbon sinks.
We present the preliminary results of the measurement of the azimuthal asymmetries of two charged pions in the inclusive process
e
+
e
−
→
π
π
X
in the BESIII experiment. These asymmetries are ...attributed to the so-called Collins fragmentation function, which depict the behavior of a hadron produced from a transversely polarized quark. This spin-dependent function is an important input for the global analysis of extracting the transversity inside the nucleon. In addition, by comparison with the measured asymmetries at Belle, this measurement provides the first data to explore the
Q
2
evolution of the spin-dependent fragmentation function. This work is performed based on about 62
pb
−
1
data collected with the BESIII detector at BEPCII at
s
=3.65
GeV.
Long‐term precipitation monitoring plays a vital role in water resource management and disaster prevention and mitigation. This study assesses spatial and temporal trends in seasonal and annual ...precipitation in Pakistan between 1960 and 2016 at an interannual scale. The Mann–Kendall (MK) test, Sen's slope (SS) estimator, and Sequential Mann–Kendall (SQMK) test were employed to assess trends. Cluster analysis and L‐moment approach were used to identify the homogenous precipitation regions. In general, increasing precipitation trends between 1960 and 2016 were evident. Results indicated increasing precipitation in winter, autumn, summer and annual scale at the rates of 0.20, 2.18, 5.16, and 10.89 mm·decade−1, respectively. In spring, the precipitation trend shows a decreasing trend at −0.67 mm·decade−1. Moreover, a significant decreasing trend occurred in winter in southern Pakistan. The overall increasing trends were more noticeable between 1960 and 1988, compared to the declining precipitation during 1989–2016. SQMK analysis indicates a clear downward trend in most regions during 1989–2016, except in autumn. Annual precipitation has increased topographically except at 500 m and 1,500 m during 1960–2016 with a significant increase of 1.37 mm·decade−1 at elevation <250 m. Results indicate a negative correlation in SS test value with seasonal and annual precipitation with elevation and a positive correlation in winter. The seasonal and annual precipitation trends exhibit increasing and decreasing trends before and after 1990, respectively, in most subregions. The notable finding based on the outcomes of this study is that the whole country observed an increasing trend during 1960–1988, followed by a decreasing trend in during 1989–2016. This decreasing tendency is particularly pronounced between 1985 and 1995, except in autumn. Agriculture production is largely reliant on precipitation in many regions. So, a detailed study of the influence of monsoon trends and large‐scale climatic variability controls over Pakistan is vital for improved water resource management in the context of global warming and rising human activity. The results will help policy makers while establishing and updating water‐related initiatives and regulations.
During 1960–2016, results indicated increasing precipitation in winter, autumn, summer, and annual scale at the rates of 0.20, 2.18, 5.16, and 10.89 mm·decade−1, respectively. Moreover, a significant decreasing trend occurred in winter in southern Pakistan. The overall increasing trends were more noticeable between 1960 and 1988, compared to the declining precipitation during 1989–2016.
Purpose: Exosomes are able to exchange their bioactive RNA cargo to recipient cells. In COPD, exosomes can be controlled and engineered for its use as targeted diagnostic and therapeutic tool. Our ...study explored novel lncRNAs and mRNAs in plasma exosomes that could be involved in the pathogenesis of COPD. Methods: High-throughput sequencing was conducted to detect the alterations in the expression of exosomal lncRNAs and mRNAs. Gene ontology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to determine the significant functions and pathways associated with differentially expressed (DE) lncRNAs. The mRNA expression profile dataset, GSE76925, and microRNA expression profile dataset, GSE70080, were obtained from the GEO database. Venn diagrams were used to find common DE mRNAs between my mRNAs dataset and GSE76925. These common DEGs were subjected to PPI analyses to identify Hub genes. Subsequently, Venn diagrams were used to identify common genes between the target genes of DE-miRNAs and Hub genes as well as DE-miRNAs and my lncRNAs dataset. Finally, a lncRNA-miRNA-mRNA co-expression network was constructed by prediction using proprietary software. The lncRNA and mRNA expressions were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: We identified 1578 differentially regulated lncRNAs and 3071 differentially regulated mRNAs. GO and KEGG pathway analyses suggested that the DE lncRNAs are involved in the pathogenesis of COPD. A lncRNA-miRNA-mRNA meshwork was established to predict the potential interactions among these RNAs. RP3-329A5.8 and MRPS11 expression was then subjected to qRT-PCR for validation. Correlations between MRPS11 and clinic-pathological features were explored. Conclusion: Our study provided a set of lncRNAs and mRNAs that may be involved in the pathogenesis of COPD, thereby highlighting the need for further research on both diagnostic biomarkers and molecular mechanisms. Keywords: stable COPD, plasma, exosomes, lncRNA, mRNA
Up to one third of ovarian cancer patients are intrinsically resistant to platinum-based treatment. However, predictive and therapeutic strategies are lacking due to a poor understanding of the ...underlying molecular mechanisms. This study aimed to identify key molecular characteristics that are associated with primary chemoresistance in epithelial ovarian cancers.
Gene expression profiling was performed on a discovery set of 85 ovarian tumors with clinically well-defined response to chemotherapies as well as on an independent validation dataset containing 138 ovarian patients from the chemotreatment arm of the ICON7 trial.
We identified a distinct "reactive stroma" gene signature that is specifically associated with primary chemoresistant tumors and was further upregulated in posttreatment recurrent tumors. Immunohistochemistry (IHC) and RNA in situ hybridization (RNA ISH) analyses on three of the highest-ranked signature genes (POSTN, LOX, and FAP) confirmed that modulation of the reactive stroma signature genes within the peritumoral stromal compartments was specifically associated with the clinical chemoresistance. Consistent with these findings, chemosensitive ovarian cells grown in the presence of recombinant POSTN promoted resistance to carboplatin and paclitaxel treatment in vitro. Finally, we validated the reactive stroma signature in an independent dataset and demonstrated that a high POSTN expression level predicts shorter progression-free survival following first-line chemotherapy.
Our findings highlight the important interplay between cancer and the tumor microenvironment in ovarian cancer biology and treatment. The identified reactive stromal components in this study provide a molecular basis to the further development of novel diagnostic and therapeutic strategies for overcoming chemoresistance in ovarian cancer.
Lung cancer is one of the leading causes of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Long non-coding RNAs (lncRNAs) ...are promising novel diagnostic and prognostic biomarkers, as well as potential therapeutic targets for lung cancer. Long non-coding RNAs (lncRNAs) have been demonstrated to modulate tumor cells proliferation, cell cycle progression, invasion, and metastasis by regulating gene expression at transcriptional, post-transcriptional, and epigenetic levels. The oncogenic aberrant Wnt/β-catenin signaling is prominent in lung cancer, playing a vital role in tumorigenesis, prognosis, and resistance to therapy. Interestingly, compelling studies have demonstrated that lncRNAs exert either oncogenic or tumor suppressor roles by regulating Wnt/β-catenin signaling. In this review, we aim to present the current accumulated knowledge regarding the roles of Wnt/β-catenin signaling-regulated lncRNAs in the pathogenesis of non-small cell lung cancer (NSCLC). Better understanding of the effects of lncRNAs on Wnt/β-catenin signaling might contribute to the improved understanding of the molecular tumor pathogenesis and to the uncovering of novel therapeutic targets in NSCLC.
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