Four Bases of Xi Jinping's Thoughts on the Government of China

Since the 18th CPC National Congress, the CPC Central Committee, led by General Secretary Xi Jinping, has unswervingly adhered to the continuing development of socialism with Chinese characteristics. Through courageous practice and excellent innovation, the CPC Central Committee has shaped a series of new ideas, thoughts and strategies of state governing, which serve as scientific guidelines for the actions and theories on further deepening the Reform and Opening-up and accelerating the modernization of socialism in China. Compared with “new ideas and new strategies,” the “new thoughts” are more extensive, inclusive and thorough. In fact, “new thoughts” include “new ideas” and “new strategies” and are demonstrated by the latter two. Presenting the new CPC Central Committee’s achievements in both practical and theoretical innovations with Xi Jinping’s governing thought as the guide can further promote and deepen the essence of General Secretary Xi Jinping’s series of key speeches. Xi Jinping’s governing thought has its historical basis, realistic basis, theoretical basis and political basis

Niclosamide Induces Cell Cycle Arrest in G1 Phase in Head and Neck Squamous Cell Carcinoma Through Let-7d/CDC34 Axis

Niclosamide is a traditional anti-tapeworm drug that exhibits potent anti-cancer activity. Our previous study showed that niclosamide induces cell cycle arrest in G1 phase. Nevertheless, the underlying mechanism remains unknown. The following study investigated the molecular mechanism through which niclosamide induced G1 arrest in head and neck squamous cell carcinoma (HNSCC) cell lines. The effect of niclosamide on human HNSCC cell line WSU-HN6 and CNE-2Z were analyzed using IncuCyte ZOOMTM assay, flow cytometry (FCM), real-time PCR and western blot. Luciferase assay was conducted to demonstrate the interaction between let-7d (a let-7 family member which functions as a tumor suppressor by regulating cell cycle) and 3′UTR of CDC34 mRNA. Xenografts tumor model was established to evaluate the niclosamide treatment efficacy in vivo. Briefly, an exposure to niclosamide treatment led to an increased let-7d expression and a decreased expression of cell cycle regulator CDC34, finally leading to G1 phase arrest. Moreover, an overexpression of let-7d induced G1 phase arrest and downregulated CDC34, while the knockdown of let-7d partially rescued the niclosamide-induced G1 phase arrest. Luciferase assay confirmed the direct inhibition of CDC34 through the targeting of let-7d. Furthermore, niclosamide markedly inhibited the xenografts growth through up-regulation of let-7d and down-regulation of CDC34. To sum up, our findings suggest that niclosamide induces cell cycle arrest in G1 phase in HNSCC through let-7d/CDC34 axis, which enriches the anti-cancer mechanism of niclosamide

日本におけるハマダイコンの葉毛密度の地理的変異

Understanding the geographic variation of leaf trichome in wild radish accessions would help to elucidate how morphological variation can be molded by natural selection. Here, we investigated the geographic variation of leaf trichomes in wild radish populations across Japan covering Ryukyu Islands and mainland. And we also sought the possible selection pressures involved in the evolution and maintenance of leaf trichome polymorphism. Results showed leaf trichome density in wild radish was highly variable across the Japanese archipelago, with plants from southern insular populations tending to exhibit glabrous leaves, while those of northern mainland Japan were completely covered by dense trichomes. This trichome variation in Japanese populations of wild radish was probably attributing to external stress involving in protecting against frost damage and resistance to herbivores. This study will be helpful to understand the morphological variation under divergent selections in wild radish and contribute to the areas of breeding and evolutionary studies in radish.ハマダイコンは日本においては西表島から北海道までの幅広い緯度の海岸に生育する。著者らの従来の観察では，琉球列島では葉や茎が無毛である傾向があり，反対に本州北部では粗長毛が密に生える傾向が見られた。そこで本研究では曖昧な印象であった毛の密度について調べるために，日本列島内の緯度に沿った11集団に由来する個体の，葉の向軸側の毛の密度を実体顕微鏡で計測した。その結果，琉球列島だけにおいて無毛の個体が存在するとともに，少数ながら粗長毛が密に生える個体も共存した。その一方で，北緯33度以上の本州の集団ではすべての個体で葉に粗長毛が密に生えていた。近年のアブラナ科植物での研究では，毛が草食性昆虫などの食害を防ぐなどの役割があると報告されており，今後には，なぜ南西諸島の集団で無毛の個体が共存できるのかという検討が必要である

Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis

BackgroundTo identify differentially expressed lipid metabolism-related genes (DE-LMRGs) responsible for immune dysfunction in sepsis.MethodsThe lipid metabolism-related hub genes were screened using machine learning algorithms, and the immune cell infiltration of these hub genes were assessed by CIBERSORT and Single-sample GSEA. Next, the immune function of these hub genes at the single-cell level were validated by comparing multiregional immune landscapes between septic patients (SP) and healthy control (HC). Then, the support vector machine-recursive feature elimination (SVM-RFE) algorithm was conducted to compare the significantly altered metabolites critical to hub genes between SP and HC. Furthermore, the role of the key hub gene was verified in sepsis rats and LPS-induced cardiomyocytes, respectively.ResultsA total of 508 DE-LMRGs were identified between SP and HC, and 5 hub genes relevant to lipid metabolism (MAPK14, EPHX2, BMX, FCER1A, and PAFAH2) were screened. Then, we found an immunosuppressive microenvironment in sepsis. The role of hub genes in immune cells was further confirmed by the single-cell RNA landscape. Moreover, significantly altered metabolites were mainly enriched in lipid metabolism-related signaling pathways and were associated with MAPK14. Finally, inhibiting MAPK14 decreased the levels of inflammatory cytokines and improved the survival and myocardial injury of sepsis.ConclusionThe lipid metabolism-related hub genes may have great potential in prognosis prediction and precise treatment for sepsis patients

遺伝子流動存在下で自然選択によって維持されている日本のハマダイコンの系統隔離

京都大学0048新制・課程博士博士(人間・環境学)甲第20459号人博第809号新制||人||194(附属図書館)28||人博||809(吉田南総合図書館)京都大学大学院人間・環境学研究科相関環境学専攻(主査)教授 瀬戸口 浩彰, 教授 加藤 眞, 教授 市岡 孝朗学位規則第4条第1項該当Doctor of Human and Environmental StudiesKyoto UniversityDGA

Lineage isolation in the face of active gene flow in the coastal plant wild radish is reinforced by differentiated vernalisation responses

Background: The respective role and relative importance of natural selection and gene flow in the process of population divergence has been a central theme in the speciation literature. A previous study presented conclusive evidence that wild radish on Japanese islands comprises two genetically isolated lineages: the southern and northern groups. However, a general understanding of the lineage isolation with frequent seed flow of the coastal plant species is still unclear. We surveyed nucleotide polymorphisms over 14 nuclear loci in 72 individuals across the Japan-Ryukyu Islands Arc to address the demographic history of wild radish utilising the isolation-with-migration (IM) model. In addition, we investigated the flowering times of individuals in different wild radish lineages, with and without cold exposure, to assess their respective vernalisation responses. Results: Coalescent simulations suggested that divergence between the southern and northern lineages of wild radish began ∼18, 000 years ago, initially during the Last Glacial Maximum (LGM) period. The gene flow from the southern to northern groups was considerably higher than that in the opposite direction, indicating effective dispersal of viable seeds via the northward Kuroshio Current. Our greenhouse experiments indicated that cold exposure was not required for flowering in the southern group, but could advance the date of flowering, suggesting that vernalisation would be facultative in the southern group. In contrast, the northern group was either unable to flower or flowered later without prior cold exposure, and thus had an obligate requirement for cold treatment. Conclusions: The south-north lineage divergence in wild radish could be triggered by a directional change in the sea current during the ice age, despite gene flow due to the high dispersability and longevity of seeds. We also found that temperature profoundly affected the vernalisation responses of wild radish, which may repress reproductive success and ultimately drive and reinforce intra-specific differentiation between the two lineages of wild radish. This study provides new insights into the maintenance of lineage differentiation with on-going gene flow in coastal plants

Distinct Phylogeographic Structures of Wild Radish (Raphanus sativus L. var. raphanistroides Makino) in Japan.

Coastal plants with simple linear distribution ranges along coastlines provide a suitable system for improving our understanding of patterns of intra-specific distributional history and genetic variation. Due to the combination of high seed longevity and high dispersibility of seeds via seawater, we hypothesized that wild radish would poorly represent phylogeographic structure at the local scale. On the other hand, we also hypothesized that wild radish populations might be geographically differentiated, as has been exhibited by their considerable phenotypic variations along the islands of Japan. We conducted nuclear DNA microsatellite loci and chloroplast DNA haplotype analyses for 486 samples and 144 samples, respectively, from 18 populations to investigate the phylogeographic structure of wild radish in Japan. Cluster analysis supported the existence of differential genetic structures between the Ryukyu Islands and mainland Japan populations. A significant strong pattern of isolation by distance and significant evidence of a recent bottleneck were detected. The chloroplast marker analysis resulted in the generation of eight haplotypes, of which two haplotypes (A and B) were broadly distributed in most wild radish populations. High levels of variation in microsatellite loci were identified, whereas cpDNA displayed low levels of genetic diversity within populations. Our results indicate that the Kuroshio Current would have contributed to the sculpting of the phylogeographic structure by shaping genetic gaps between isolated populations. In addition, the Tokara Strait would have created a geographic barrier between the Ryukyu Islands and mainland Japan. Finally, extant habitat disturbances (coastal erosion), migration patterns (linear expansion), and geographic characteristics (small islands and sea currents) have influenced the expansion and historical population dynamics of wild radish. Our study is the first to record the robust phylogeographic structure in wild radish between the Ryukyu Islands and mainland Japan, and might provide new insight into the genetic differentiation of coastal plants across islands