Current immunotherapies yield remarkable clinical outcomes by boosting the power of host immunity in cancer cell elimination and viral clearance. However, after prolonged antigen exposure, CD8+ T cells differentiate into a special differentiation state known as T-cell exhaustion, which poses one of the major hurdles to antiviral and antitumor immunity during chronic viral infection and tumour development. Growing evidence indicates that exhausted T cells undergo metabolic insufficiency with altered signalling cascades and epigenetic landscapes, which dampen effector immunity and cause poor responsiveness to immune-checkpoint-blockade therapies. How metabolic stress affects T-cell exhaustion remains unclear; therefore, in this Review, we summarize current knowledge of how T-cell exhaustion occurs, and discuss how metabolic insufficiency and prolonged stress responses may affect signalling cascades and epigenetic reprogramming, thus locking T cells into an exhausted state via specialized differentiation programming.Despite the crucial roles of lipids in metabolism, we are still at the early stages of comprehensively annotating lipid species and their genetic basis. Mass spectrometry-based discovery lipidomics offers the potential to globally survey lipids and their relative abundances in various biological samples. To discover the genetics of lipid features obtained through high-resolution liquid chromatography-tandem mass spectrometry, we analysed liver and plasma from 384 diversity outbred mice, and quantified 3,283 molecular features. These features were mapped to 5,622 lipid quantitative trait loci and compiled into a public web resource termed LipidGenie. The data are cross-referenced to the human genome and offer a bridge between genetic associations in humans and mice. https://www.selleckchem.com/products/itacnosertib.html Harnessing this resource, we used genome-lipid association data as an additional aid to identify a number of lipids, for example gangliosides through their association with B4galnt1, and found evidence for a group of sex-specific phosphatidylcholines through their shared locus. Finally, LipidGenie's ability to query either mass or gene-centric terms suggests acyl-chain-specific functions for proteins of the ABHD family.Following activation, conventional T (Tconv) cells undergo an mTOR-driven glycolytic switch. Regulatory T (Treg) cells reportedly repress the mTOR pathway and avoid glycolysis. However, here we demonstrate that human thymus-derived Treg (tTreg) cells can become glycolytic in response to tumour necrosis factor receptor 2 (TNFR2) costimulation. This costimulus increases proliferation and induces a glycolytic switch in CD3-activated tTreg cells, but not in Tconv cells. Glycolysis in CD3-TNFR2-activated tTreg cells is driven by PI3-kinase-mTOR signalling and supports tTreg cell identity and suppressive function. In contrast to glycolytic Tconv cells, glycolytic tTreg cells do not show net lactate secretion and shuttle glucose-derived carbon into the tricarboxylic acid cycle. Ex vivo characterization of blood-derived TNFR2hiCD4+CD25hiCD127lo effector T cells, which were FOXP3+IKZF2+, revealed an increase in glucose consumption and intracellular lactate levels, thus identifying them as glycolytic tTreg cells. Our study links TNFR2 costimulation in human tTreg cells to metabolic remodelling, providing an additional avenue for drug targeting.Digital optical holograms can achieve nanometre-scale resolution as a result of recent advances in metasurface technologies. This has raised hopes for applications in data encryption, data storage, information processing and displays. However, the hologram bandwidth has remained too low for any practical use. To overcome this limitation, information can be stored in the orbital angular momentum of light, as this degree of freedom has an unbounded set of orthogonal helical modes that could function as information channels. Thus far, orbital angular momentum holography has been achieved using phase-only metasurfaces, which, however, are marred by channel crosstalk. As a result, multiplex information from only four channels has been demonstrated. Here, we demonstrate an orbital angular momentum holography technology that is capable of multiplexing up to 200 independent orbital angular momentum channels. This has been achieved by designing a complex-amplitude metasurface in momentum space capable of complete and independent amplitude and phase manipulation. Information was then extracted by Fourier transform using different orbital angular momentum modes of light, allowing lensless reconstruction and holographic videos to be displayed. Our metasurface can be three-dimensionally printed in a polymer matrix on SiO2 for large-area fabrication.Nonlinear optical fibres have been employed for a vast number of applications, including optical frequency conversion, ultrafast laser and optical communication1-4. In current manufacturing technologies, nonlinearity is realized by the injection of nonlinear materials into fibres5-7 or the fabrication of microstructured fibres8-10. Both strategies, however, suffer from either low optical nonlinearity or poor design flexibility. Here, we report the direct growth of MoS2, a highly nonlinear two-dimensional material11, onto the internal walls of a SiO2 optical fibre. This growth is realized via a two-step chemical vapour deposition method, where a solid precursor is pre-deposited to guarantee a homogeneous feedstock before achieving uniform two-dimensional material growth along the entire fibre walls. By using the as-fabricated 25-cm-long fibre, both second- and third-harmonic generation could be enhanced by ~300 times compared with monolayer MoS2/silica. Propagation losses remain at ~0.1 dB cm-1 for a wide frequency range. In addition, we demonstrate an all-fibre mode-locked laser (~6 mW output, ~500 fs pulse width and ~41 MHz repetition rate) by integrating the two-dimensional-material-embedded optical fibre as a saturable absorber. Initial tests show that our fabrication strategy is amenable to other transition metal dichalcogenides, making these embedded fibres versatile for several all-fibre nonlinear optics and optoelectronics applications.