The endosomal sorting complex required for transport (ESCRT) is a multicomplex machinery comprising proteins that are conserved from bacteria to humans and has diverse roles in regulating the dynamics of cellular membranes. ESCRT functions have far-reaching consequences for cell biological processes such as intracellular traffic, membrane repair, cell signalling, metabolic regulation, cell division and genome maintenance. Here we review recent insights that emphasize the pathophysiological consequences of ESCRT dysfunctions, including infections, immune disorders, cancers and neurological diseases. We highlight the possibilities of using our knowledge about ESCRT structures and functions for drug discovery.

Materials emitting circularly polarized light (CPL) are highly sought after for applications ranging from efficient displays to quantum information technologies1-7. However, established methods for time-resolved CPL (TRCPL) characterization have notable limitations8-17, generally requiring a compromise between sensitivity, accessible timescales and spectral information. This has limited the acquisition of in-depth photophysical insight necessary for materials development. Here we demonstrate a high-sensitivity (noise level of the order of 10-4), broadband (about 400-900 nm), transient (nanosecond resolution, millisecond range) full-Stokes (CPL and linear polarizations) spectroscopy setup. The achieved combination of high-sensitivity, broad wavelength response and flexible time ranges represents a substantial advancement over previous TRCPL approaches. As a result, TRCPL measurements are shown to be applicable to hitherto inaccessible material systems and photophysical processes, including systems with low (10-3) dissymmetry factors and luminescence pathways spanning nanosecond to millisecond time ranges. Finally, full-Stokes measurements allow tracking the temporal evolution of linear polarization components, of interest by themselves, but especially relevant in the context of controlling for associated CPL artefacts18,19 in the time domain.

The dendritic cell (DC)-initiated and sustained cancer immunity cycle is indispensable for effective endogenous and therapeutically mobilized antitumour T cell responses1-8. This necessitates the continuous migration of antigen-carrying DCs from the tumour microenvironment (TME) to the tumour draining lymph nodes (tdLNs)7-13. Here, through longitudinal analysis of human and mouse tumours, we observed a progressive decrease in migratory conventional DCs (mig-cDCs) in the tdLNs during tumour progression. This decline compromised tumour-specific T cell priming and subsequent T cell supply to the TME. Using a genome-wide in vivo CRISPR screen, we identified phosphodiesterase 5 (PDE5) and its substrate cyclic guanosine monophosphate (cGMP) as key modulators of DC migration. Advanced tumours disrupted cGMP synthesis in DCs to decrease their motility, while PDE5 perturbation preserved the cGMP pool to restore DC migration. Mechanistically, cGMP enhanced myosin-II activity through Rho-associated factors, extending the paradigm of cGMP-regulated amoeboid migration from Dictyostelium to mammalian immune cells. Pharmacological inhibition of PDE5 using sildenafil restored mig-cDC homing to late-stage tdLNs and sustained antitumour immunity in a DC-dependent manner. Our findings bridge fundamental DC interstitial motility to antitumour immunity, revealing that its disruption in chaotic TME promotes immune evasion, and its enhancement offers a promising direction for DC-centric immunotherapy.

The incorporation of non-canonical amino acids (ncAAs) enables customized chemistry to tailor protein functions1-3. Genetic code expansion offers a general approach for ncAA encoding by reassigning stop codons as the 'blank' codon; however, it is not completely orthogonal to translation termination for cellular transcripts. Here, to generate more bona fide blank codons, we developed an RNA codon-expansion (RCE) strategy that introduces and decodes bioorthogonally assignable pseudouridine (Ψ) codons (ΨGA, ΨAA or ΨAG) on specified mRNA transcripts to incorporate ncAAs in mammalian cells. The RCE strategy comprises a programmable guide RNA4, an engineered decoder tRNA, and aminoacyl-tRNA synthetase. We first developed the RCE(ΨGA) system, which incorporates functional ncAAs into proteins via the ΨGA codon, demonstrating a higher translatome-wide and proteomic specificity compared with the genetic code expansion system. We further expanded our strategy to produce the RCE(ΨAA) and RCE(ΨAG) systems, with all three Ψ codon:(Ψ codon)-tRNAPyl pairs exhibiting mutual orthogonality. Moreover, we demonstrated that the RCE system cooperates compatibly with the genetic code expansion strategy for dual ncAA encoding. In sum, the RCE method utilized Ψ as a post-transcriptional 'letter' to encode and decode RNA codons in specific mRNA transcripts, opening a new route for genetic alphabet expansion and site-specific ncAA incorporation in eukaryotic cells.

Planets are thought to form from dust and gas in protoplanetary disks, with debris disks being the remnants of planet formation. Aged a few million up to a few billion years, debris disks have lost their primordial gas, and their dust is produced by steady-state collisions between larger, rocky bodies1,2. Tens of debris disks, with sizes of tens, sometimes hundreds, of astronomical units have been resolved with high-spatial-resolution, high-contrast imagers at optical and near-infrared or (sub)millimetre interferometers3,4. They commonly show cavities, ring-like structures and gaps, which are often regarded as indirect signatures of the presence of planets that gravitationally interact with unseen planetesimals2,5. However, no planet responsible for these features has been detected yet, probably because of the limited sensitivity (typically 2-10 MJ) of high-contrast imaging instruments (see, for example, refs. 6-9) before the James Webb Space Telescope. Here we have used the unprecedented sensitivity of the James Webb Space Telescope's Mid-Infrared Instrument10,11 in the thermal infrared to search for such planets in the disk of the approximately 6.4-Myr-old star TWA 7. With its pole-on orientation, this three-ring debris disk is indeed ideally suited for such a detection. We unambiguously detected a source 1.5 arcsec from the star, which is best interpreted as a cold, sub-Jupiter-mass planet. Its estimated mass (about 0.3 MJ) and position (about 52 AU, de-projected) can thoroughly account for the main disk structures.

Aharonov-Bohm interference of fractional quasiparticles in the quantum Hall effect generally reveals their elementary charge (e*)1-15. Recently, our interferometry experiments with several 'particle states' reported flux periods of ΔΦ = (e/e*)Φ0 (with Φ0 the flux quantum) at moderate temperatures16. Here we report interference measurements of 'particle-hole conjugated' states at filling factors ν = 2/3, 3/5 and 4/7, which revealed unexpected flux periodicities of ΔΦ = ν-1Φ0. The measured shot-noise Fano factor (F) of the partitioned quasiparticles in each of the quantum point contacts of the interferometer was F = ν (ref. 17) rather than that of the elementary charge F = e*/e (refs. 18,19). These observations indicate that the interference of bunched (clustered) elementary quasiparticles occurred for coherent pairs, triples and quadruplets, respectively. A small metallic gate (top gate), deposited in the centre of the interferometer bulk, formed an antidot (or a dot) when charged, thus introducing local quasiparticles at the perimeter of the (anti)dot. Surprisingly, such charging led to a dissociation of the 'bunched quasiparticles' and, thus, recovered the conventional flux periodicity set by the elementary charge of the quasiparticles. However, the shot-noise Fano factor (of each quantum point contact) consistently remained at F = ν, possibly due to the neutral modes accompanying the conjugated states. The two observations-bunching and debunching (or dissociation)-were not expected by current theories. Similar effects may arise in Jain's 'particle states' (at lower temperatures) and at even denominator fractional quantum Hall states20.

Lanthanides have shown magnetic memory at both the atomic1,2 and molecular3,4 level. The magnetic remanence temperatures of lanthanide single-molecule magnets can surpass d-transition metal examples5,6, and since 2017, energy barriers to magnetic reversal (Ueff) from 1,237(28) cm-1 to 1,631(25) cm-1 and open magnetic hysteresis loops between 40 K and 80 K have typically been achieved with axial dysprosium(III) bis(cyclopentadienyl) complexes7-17. It has been predicted that linear dysprosium(III) compounds could deliver greater mJ (the projection of the total angular momentum, J, on a quantization axis labelled z) state splitting and therefore higher Ueff and hysteresis temperatures18-21, but as lanthanide bonding is predominantly ionic22,23, so far dysprosium bis(amide) complexes have shown highly bent geometries that promote fast magnetic reversal24,25. Here we report a dysprosium bis(amide)-alkene complex, [Dy{N(SiiPr3)[Si(iPr)2C(CH3)=CHCH3]}{N(SiiPr3)(SiiPr2Et)}][Al{OC(CF3)3}4] (1-Dy), that shows Ueff = 1,843(11) cm-1 and slow closing of soft magnetic hysteresis loops up to 100 K. Calculations show that the Ueff value for 1-Dy arises from the charge-dense amide ligands, with a pendant alkene taking a structural role to enforce a large N-Dy-N angle while imposing only a weak equatorial interaction. This leads to molecular spin dynamics up to 100 times slower than the current best single-molecule magnets above 90 K.

Prevailing frameworks to address planetary environmental challenges tend to focus on setting goals, targets, or boundaries to limit human harm to ecosystems or species. Here we propose an aspirational approach aimed at empowering people to shape a better future for all of life on Earth. We do this by building on the human development approach and its supporting metrics, especially the Human Development Index (HDI), a broadly influential framework that has contributed to decades of human progress by measuring and promoting people's capabilities to lead the lives that they value. Rather than assessing the state or dynamics of the biosphere, we propose the Nature Relationship Index (NRI), which would focus on measuring the progress of nations towards delivering mutually beneficial relationships among people and the rest of the living world in terms that people widely understand and value. Through an open-ended process informed by expert consultation, international concept testing and indicator development, the NRI could help to incentivize progress towards a world in which humanity thrives together with the rest of life on Earth. We explore the challenges and opportunities of developing a robust NRI and invite broader participation to facilitate this development in collaboration with the United Nations Development Programme Human Development Report.

A key virtue of spin qubits is their sub-micron footprint, enabling a single silicon chip to host the millions of qubits required to execute useful quantum algorithms with error correction1-3. However, with each physical qubit needing multiple control lines, a fundamental barrier to scale is the extreme density of connections that bridge quantum devices to their external control and readout hardware4-6. A promising solution is to co-locate the control system proximal to the qubit platform at milli-kelvin temperatures, wired up by miniaturized interconnects7-10. Even so, heat and crosstalk from closely integrated control have the potential to degrade qubit performance, particularly for two-qubit entangling gates based on exchange coupling that are sensitive to electrical noise11,12. Here we benchmark silicon metal-oxide-semiconductor (MOS)-style electron spin qubits controlled by heterogeneously integrated cryo-complementary metal-oxide-semiconductor (cryo-CMOS) circuits with a power density sufficiently low to enable scale-up. Demonstrating that cryo-CMOS can efficiently perform universal logic operations for spin qubits, we go on to show that milli-kelvin control has little impact on the performance of single- and two-qubit gates. Given the complexity of our sub-kelvin CMOS platform, with about 100,000 transistors, these results open the prospect of scalable control based on the tight packaging of spin qubits with a 'chiplet-style' control architecture.

Emergence of universal collective behaviour from interactions within a sufficiently large group of elementary constituents is a fundamental scientific concept1. In physics, correlations in fluctuating microscopic observables can provide key information about collective states of matter, such as deconfined quark-gluon plasma in heavy-ion collisions2 or expanding quantum degenerate gases3,4. Mesoscopic colliders, through shot-noise measurements, have provided smoking-gun evidence on the nature of exotic electronic excitations such as fractional charges5,6, levitons7 and anyon statistics8. Yet, bridging the gap between two-particle collisions and the emergence of collectivity9 as the number of interacting particles increases10 remains a challenging task at the microscopic level. Here we demonstrate all-body correlations in the partitioning of electron droplets containing up to N = 5 electrons, driven by a moving potential well through a Y-junction in a semiconductor device. Analysing the partitioning data using high-order multivariate cumulants and finite-size scaling towards the thermodynamic limit reveals distinctive fingerprints of a strongly correlated Coulomb liquid. These fingerprints agree well with a universal limit at which the partitioning of a droplet is predicted by a single collective variable. Our electron-droplet scattering experiments illustrate how coordinated behaviour emerges through interactions of only a few elementary constituents. Studying similar signatures in other physical platforms such as cold-atom simulators4,11 or collections of anyonic excitations8,12 may help identify emergence of exotic phases and, more broadly, advance understanding of matter engineering.