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CD8+ T cells are the workhorses executing adaptive anti-tumour response, and targets of various cancer immunotherapies. Latest advances have unearthed the sheer heterogeneity of CD8+ tumour infiltrating lymphocytes, and made it increasingly clear that the bulk of the endogenous and therapeutically induced tumour-suppressive momentum hinges on a particular selection of CD8+ T cells with advantageous attributes, namely the memory and stem-like exhausted subsets. A scrutiny of the contemporary perception of CD8+ T cells in cancer and the subgroups of interest along with the factors arbitrating their infiltration contextures, presented herein, may serve as the groundwork for future endeavours to probe further into the regulatory networks underlying their differentiation and migration, and optimise T cell-based immunotherapies accordingly. [ABSTRACT FROM AUTHOR]

As a subclass of noncoding RNAs, circular RNA play an important role in tumour development. The aim of this study was to investigate the role of circ_0004674 in osteosarcoma glycolysis and the molecular mechanism of its regulation. We examined the expression of circ_0004674, miR‐140‐3p, TCF4 and glycolysis‐related proteins (including HK2, PKM2, GLUT1 and LDHA) in osteosarcoma cells and tissues by quantitative reverse transcription‐polymerase chain reaction and immunoblotting (Western blot analysis). The role of circ_0004674, miR‐140‐3p and TCF4 in the proliferation, apoptosis, migration and invasion of OS cells was examined using CCK8 assay, Apoptosis assay, Wound healing assay, Transwell migration and Matrigel invasion assay. The interaction of circ_0004674/miR‐140‐3p and miR‐1543/TCF4 was also analysed using a dual luciferase reporter assay. Finally, the glycolytic process was assessed by glucose uptake assays and lactate production measurements. The results showed that the expression of circ_0004674 and TCF4 was significantly higher in MG63 and U2OS cells compared to hFOB1.19 cells, while the expression of miR‐140‐3p was downregulated. Silencing of circ_0004674 gene significantly inhibited the proliferation, migration and invasion of cancer cells and promoted apoptosis of cancer cells. Experiments such as dual luciferase reporter analysis showed that circ_0004674 regulates the expression of glycolysis‐related proteins through the miR‐140‐3p/TCF4 pathway, and inhibition of this gene attenuated the depletion of glucose content and the production of lactate in cancer cells. Furthermore, inhibition of miR‐140‐3p or overexpression of TCF could reverse the phenotypic changes in cancer cells induced by circ_0004674 silencing. In summary, this study elucidated the specific function and potential mechanisms of circ_0004674 in osteosarcoma glycolysis. The findings demonstrate that miR‐140‐3p and TCF4 function respectively as a tumor suppressor gene and an oncogene in osteosarcoma. Notably, they influence glycolysis and associated pathways, regulating osteosarcoma proliferation. Therefore, circ_0004674 promotes osteosarcoma glycolysis and proliferation through the miR‐140‐3p/TCF4 pathway, enhancing the malignant behaviour of tumours, and it is expected to be a potential molecular target for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

The Bohai Bay Basin, located in the eastern North China Block, is an important sedimentary basin for studying the Quaternary climate and environment of northern China. Although sporo-pollen analyses have been used to study the paleoclimate, quantitative research via geochemistry had not been conducted. The sedimentary sequence, geochemistry, and mineralogy of Quaternary sediments from core GJ01 in the Yongding River fluvial plain, northern Bohai Bay Basin, were studied to determine their provenance and investigate climate change during the Quaternary. The stratigraphic sequence of the Quaternary was mainly formed by fluviation by a meandering river, showing a typical dual structure. The sediments have relatively high Si[O.sub.2] and CaO concentrations, and low [Al.sub.2][O.sub.3], [Na.sub.2]O, and [Fe.sub.2][O.sub.3.sup.T] concentrations. In terms of trace elements, most large ion lithophile elements are slightly enriched, and Rb and K concentrations are close to those of post-Archean Australian shale (PAAS); most high field strength elements are slightly to moderately depleted. Rare earth elements (REEs) vary significantly, with light rare earth elements (LREEs) obviously enriched relative to heavy rare earth elements (HREEs). A slightly negative Eu anomaly is present, with nearly no Ce anomaly. Mineralogical analysis shows that the main minerals in the fine-grained sediments are quartz, plagioclase, and K-feldspar. The geochemistry and mineralogy of the sediments indicate that the main provenances were recycled sedimentary rocks and felsic igneous rocks. The sediments have low chemical index of alteration (CIA) values, demonstrating that the source rocks underwent slight weathering. The mean annual precipitation and temperature of the studied area during the Quaternary varied from 531 to 875 mm and from 4.1 to 11.8 [degrees]C, respectively. Key words: geochemistry, Quaternary, Bohai Bay Basin, North China. Le bassin de la baie de Bohai, situé dans la partie orientale du bloc de Chine septentrionale, est un important bassin sédimentaire pour la recherche sur le climat et l'environnement dans le nord de la Chine durant le Quaternaire. Si des analyses de spores et pollens ont été utilisées pour étudier le paléoclimat, des travaux quantitatifs de géochimie n'ont pas encore été effectués. La séquence sédimentaire, la géochimie et la minéralogie de sédiments quaternaires de la carotte GJ01 provenant de la plaine fluviale de la rivière Yongding, dans le nord du bassin de la baie de Bohai, sont étudiées afin d'examiner la provenance de ces sédiments et les changements climatiques durant le Quaternaire. La séquence stratigraphique quaternaire est principalement le résultat de processus fluviaux d'une rivière méandrique présentant une structure bimodale typique. Les sédiments ont des concentrations relativement élevées de Si[O.sub.2] et CaO et faibles de [Al.sub.2][O.sub.3], [Na.sub.2]O et [Fe.sub.2][O.sub.3.sup.T]. Pour ce qui est des éléments en traces, la plupart des éléments lithophiles à grand rayon ionique sont légèrement enrichis, et les concentrations de Rb et K s'approchent de celles du schiste post-archéen moyen (PAAS); la plupart des éléments à forte liaison atomique sont légèrement à modérément appauvris. Les éléments de terres rares (ÉTR) varient significativement, les ÉTR légers étant nettement enrichis par rapport aux ÉTR lourds. Une anomalie légèrement négative d'Eu est présente, le Ce ne présentant quasiment aucune anomalie. L'analyse minéralogique montre que les principaux minéraux dans les sédiments fins sont le quartz, le plagioclase et le feldspath potassique. La géochimie et la minéralogie des sédiments démontrent qu'ils proviennent principalement de roches sédimentaires recyclées et de roches ignées felsiques. Les sédiments ont des indices chimiques d'altération (CIA) faibles, indiquant une faible météorisation des roches mères. La pluviométrie et les températures annuelles moyennes dans la région à l'étude durant le Quaternaire allaient de 531 mm à 875 mm et de 4,1 [degré]C à 11,8 [degré]C, respectivement. [Traduit par la Rédaction] Mots-clés : géochimie, Quaternaire, bassin de la baie de Bohai, Chine septentrionale., Introduction The North China Block is located in eastern China (Fig. 1a) and has undergone huge tectonic transformation since the late Mesozoic (Ren et al. 2002; Qi and Yang 2010; [...]

An ideal DNA‐encoded library (DEL) selection requires the library to consist of diverse core skeletons and cover chemical space as much as possible. However, the lack of efficient on‐DNA synthetic approaches toward core skeletons has greatly restricted the diversity of DEL. To mitigate this issue, this work disclosed a "Mask & Release" strategy to streamline the challenging on‐DNA core skeleton synthesis. N‐phenoxyacetamide is used as a masked phenol and versatile directing group to mediate diversified DNA‐compatible C‐H functionalization, introducing the 1st‐dimensional diversity at a defined site, and simultaneously releasing the phenol functionality, which can facilitate the introduction of the 2nd diversity. This work not only provides a set of efficient syntheses toward DNA‐conjugated drug‐like core skeletons such as ortho‐alkenyl/sulfiliminyl/cyclopropyl phenol, benzofuran, dihydrobenzofuran but also provides a paradigm for on‐DNA core skeleton synthetic method development. [ABSTRACT FROM AUTHOR]