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Lung cancer is the world’s leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n  = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts. Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

Heat stress can hinder the growth of perennial ryegrass (Lolium perenne L.). Methyl jasmonate (MeJA) applied exogenously can increase heat stress tolerance in plants; however, the regulatory mechanisms involved in heat tolerance mediated by MeJA are poorly understood in perennial ryegrass. Here, the microRNA (miRNA) expression profiles of perennial ryegrass were assessed to elucidate the regulatory pathways associated with heat tolerance induced by MeJA. Plants were subjected to four treatments, namely, control (CK), MeJA pre-treatment (T), heat stress treatment (H), and MeJA pre-treatment + heat stress (TH). According to the results, 102 miRNAs were up-regulated in all treatments, with 20, 27, and 33 miRNAs being up-regulated in the T, H, and TH treatment groups, respectively. The co-expression network analysis between the deferentially expressed miRNAs and their corresponding target genes showed that 20 miRNAs modulated 51 potential target genes. Notably, the miRNAs that targeted genes related to with regards to heat tolerance were driven by MeJA, and they were involved in four pathways: novel-m0258-5p mediated signal transduction, novel-m0350-5p mediated protein homeostasis, miR397-z, miR5658-z, and novel-m0008-5p involved in cell wall component, and miR1144-z and miR5185-z dominated chlorophyll degradation. Overall, the findings of this research paved the way for more research into the heat tolerance mechanism in perennial ryegrass and provided a theoretical foundation for developing cultivars with enhanced heat tolerance.

ObjectiveAs the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.DesignPatient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg−/− (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.ResultsSimilar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.ConclusionsOur work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.

Background East Asian dog breeds are one of the most ancient groups of dogs that radiated after the domestication of the dog and represent the most basal lineages of dog evolution. Among these, the Chow Chow is an ancient breed that embodies very distinct morphological and physiological features, such as sturdy build, dense coat, and blue/purple tongue. Results Using a Restricted site Associated DNA (RAD) sequencing approach, we sequenced the genomes of nine Chow Chows from China. Combined with a dataset of 37 canid whole genome sequencing (WGS) from several published works, we found that the Chow Chow is one of the most basal lineages, which originated together with other East Asian breeds, such as the Shar-Pei and Akita. Demographic analysis found that Chow Chows originated from the Chinese indigenous dog about 8300 years ago. The bottleneck leading to Chow Chows was not strong and genetic migration between Chow Chows and other populations is low. Two classes of genes show strong evidence of positive selection along the Chow Chow lineage, namely genes related to metabolism and digestion as well as muscle/heart development and differentiation. Conclusions Dog breeds from East Asia, including the Chow Chow, originated from Chinese indigenous dogs very early in time. The genetic bottleneck leading to Chow Chows and migrations with other populations are found to be quite mild. Our current study represents an early endeavor to characterize the origin of East Asian dog breeds and establishes an important reference point for understanding the origin of ancient breeds in Asia.

Hepatocellular carcinoma (HCC) is one of the deadliest cancer types with diverse etiological factors across the world. Although large scale genomic studies have been conducted in different countries, integrative analysis of HCC genomes and ethnic comparison across cohorts are lacking.Methods: We first integrated genomes of 1,349 HCC patients from five large cohorts across the world and applied multiple statistical methods in identifying driver genes. Subsequently, we systematically compared HCC genomes and transcriptomes between Asians and Europeans using the TCGA cohort.Results: We identified 29 novel candidate driver genes, many of which are infrequent tumor suppressors driving late-stage tumor progression. When we systematically compared ethnic differences in the genomic landscape between Asian and European HCCs using the TCGA cohort (n = 348), we found little differences in driver frequencies. Through multi-modal integrative analysis, we found higher genomic instability in Asians together with a collection of molecular events ranging from tumor mutation burden (TMB), copy number alterations as well as transcriptomic subtypes segregating distinctively between two ethnic backgrounds. Strikingly, we identified an Asian specific transcriptomic subtype with multiple ethnically enriched genomic alterations, in particular chromosome 16 deletion, leading to a clinically aggressive RNA subgroup unique to Asians. Integrating multi-modal information, we found that survival models predict patient prognosis much better in Asians than in Europeans, demonstrating a higher potential for precision medicine applications in Asia.Conclusion: For the first time, we have uncovered an unprecedented amount of genomic differences segregating distinctively across ethnicities in HCC and highlighted the importance of differential disease biology and management in HCC across ethnic backgrounds.

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

Steel slag, a by-product of steelmaking, imposes lots of negative impacts on the environment. For alleviating negative impacts, more and more experiments have been carried out to explore the application possibility of steel slag. The purpose of this study is to explore the feasibility of steel slag being applied in induction healing asphalt concretes to replace coarse and fine aggregate. Surface texture and pore sizes of steel slag were firstly tested, and then steel slag and basalt asphalt mixtures modified with steel fibers were prepared. Moisture susceptibility, dynamic stability, mechanical property, thermal property, induction heating speed, natural cooling speed and healing property of the asphalt mixtures were evaluated. Results showed that steel slags had more obvious holes in the surface while the surface area is much larger than that of basalt. Furthermore, steel fibers and steel slag both have dynamic stability, and steel fibers contribute to increased moisture resistance while steel slag is not. Steel slag asphalt concrete showed better mechanical property and better capacity to store heating. Steel slag asphalt mixtures had a similar heating speed to basalt asphalt mixtures but a significantly slower cooling rate. Finally, the induction healing test and CT scanning test demonstrated that steel slag asphalt mixtures had a similar healing ability to basalt asphalt mixtures. It can be concluded that steel slags have the potential to replace the natural aggregates to be applied in induction heating self-healing asphalt concretes.

We report on a combined experimental and numerical study of convective heat transfer along ratchet surfaces in vertical natural convection (VC). Due to the asymmetry of the convection system caused by the asymmetric ratchet-like wall roughness, two distinct states exist, with markedly different orientations of the large-scale circulation roll (LSCR) and different heat transport efficiencies. Statistical analysis shows that the heat transport efficiency depends on the strength of the LSCR. When a large-scale wind flows along the ratchets in the direction of their smaller slopes, the convection roll is stronger and the heat transport is larger than the case in which the large-scale wind is directed towards the steeper slope side of the ratchets. Further analysis of the time-averaged temperature profiles indicates that the stronger LSCR in the former case triggers the formation of a secondary vortex inside the roughness cavity, which promotes fluid mixing and results in a higher heat transport efficiency. Remarkably, this result differs from classical Rayleigh–Bénard convection (RBC) with asymmetric ratchets (Jiang et al., Phys. Rev. Lett., vol. 120, 2018, 044501), wherein the heat transfer is stronger when the large-scale wind faces the steeper side of the ratchets. We reveal that the reason for the reversed trend for VC as compared to RBC is that the flow is less turbulent in VC at the same $Ra$ . Thus, in VC the heat transport is driven primarily by the coherent LSCR, while in RBC the ejected thermal plumes aided by gravity are the essential carrier of heat. The present work provides opportunities for control of heat transport in engineering and geophysical flows.

Steel slag is the by-product of the steelmaking industry, the negative influences of which prompt more investigation into the recycling methods of steel slag. The purpose of this study is to characterize steel slag filler and study its feasibility of replacing limestone filler in asphalt concrete by evaluating the resistance of asphalt mastic under various aging methods. Firstly, steel slag filler, limestone filler, virgin asphalt, steel slag filler asphalt mastic and limestone filler asphalt mastic were prepared. Subsequently, particle size distribution, surface characterization and pore characterization of the fillers were evaluated. Finally, rheological property, self-healing property and chemical functional groups of the asphalt mastics with various aging methods were tested via dynamic shear rheometer and Fourier transform infrared spectrometer. The results show that there are similar particle size distributions, however, different surface characterization and pore characterization in the fillers. The analysis to asphalt mastics demonstrates how the addition of steel slag filler contributes to the resistance of asphalt mastic under the environment of acid and alkaline but is harmful under UV radiation especially. In addition, the pore structure in steel slag filler should be a potential explanation for the changing resistance of the asphalt mastics. In conclusion, steel slag filler is suggested to replace limestone filler under the environment of acid and alkaline, and environmental factor should be taken into consideration when steel slag filler is applied to replace natural fillers in asphalt mastic.

The design and analysis of an integrated system for residual stress relief and visual detection are presented. The equipment combines a thermal stress relief module with a real-time visual deformation detection system. The visual module uses a high-resolution camera and optical system to monitor deformation during the stress relief process. Experimental results verify the stability and vibration isolation performance of the system, demonstrating effective and high detection sensitivity.