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Assessing global sustainability performance, imbalance, and coordination over space and time
The problem with career planning in science
Enhancing cap-independent translation of linear mRNA
Abstract While cap-dependent translation remains the primary focus in mRNA-based therapeutics, cap-independent translation holds promise for targeting diseases ranging from cancer to neurodegeneration. However, cap-independently translated mRNAs are unstable, produce less protein than capped mRNAs, and current methods for their improvement are imperfect. Here, we propose the use of in vitro transcription priming with azido-modified dinucleotide primer and post-transcriptional modification utilising click chemistry to improve the properties of cap-independently translated mRNAs. Our results demonstrate a significant enhancement in mRNA stability and protein output without eliciting immunogenicity. Moreover, we show how the mRNA 5′-end modification strategy can be used to investigate transfection and cap-independent translation processes in cells overcoming burdens associated with previous methods. Together, our findings support cap-independent translation as a viable alternative to the established cap-dependent process and provide tools for further exploration and enhancement of this modality.
Long-range optical coupling with epsilon-near-zero materials
Abstract Long-range resonant quantum tunneling of electrons happens across potential barriers when the wavefunction interferes constructively outside the barrier. Here we demonstrate an analogy in optical systems based on epsilon-near-zero materials, achieving phase-modulated, long-range optical interactions between transparent semiconducting oxide layers beyond the evanescent photonic coupling. Distinct from weak thin-film interference, intense electromagnetic fields confined within the epsilon-near-zero thin films show anti-correlated intensity oscillations as a function of interlayer separation up to hundreds of microns. The oscillatory, anti-correlated electromagnetic field intensities were probed by second harmonic generation from wedged indium tin oxide multilayers. Such a system that hosts subwavelength mode footprint and simultaneously long-range radiative coupling offers prospects for long-distance optical communication, large-scale photonic circuits, and hybrid quantum photonic systems.
This gene causes obesity — and shields against heart disease
Cu single-atom embedded g-C3N4 nanosheets rehabilitate multidrug-resistant bacteria infected diabetic wounds via photoswitchable cascade reaction
Abstract To tackle elevated blood glucose, multidrug-resistant (MDR) bacterial infections, and persistent inflammation in diabetic wounds, we present a therapeutic strategy that employs a photoswitch-controlled catalytic cascade reaction, utilizing a photocatalytic material engineered through the synergistic regulation of nitrogen vacancies and single-atom embedding. Under visible light illumination, the N vacancy exist in g-C 3 N 4 (CN) significantly enhances photocatalytic glucose oxidation to regulate the hyperglycemia condition at diabetic wound sites, and the atomically dispersed Cu promotes the generation of •OH and •O 2 – to efficiently eliminate MDR bacteria ( > 99.9%). Under dark conditions, excess ROS are scavenged by Cu/CN, reducing inflammation of wounds and promoting polarization of M2 macrophages. Serum biochemical and vital organs histopathological analyses after 14 days of treatment confirm the biosafety profile of Cu/CN. This photoswitchable cascade reaction effectively treats MDR bacterial-infected diabetic wounds in male mice, highlighting its potential for antibiotic-free therapy with promising clinical translation applications.
Enhanced erosion by continental arc volcanism as a driver of the Cambrian Explosion
How journals can break down barriers for Latin American scientists
Integrated lithium niobate photonics for sub-ångström snapshot spectroscopy
UNESCO stands at a crossroads — researchers must back its new leader
Efficient quantum thermal simulation
Abstract Quantum computers promise to tackle quantum simulation problems that are classically intractable 1 . Although a lot of quantum algorithms 2–4 have been developed for simulating quantum dynamics, a general-purpose method for simulating low-temperature quantum phenomena remains unknown. In classical settings, the analogous task of sampling from thermal distributions has been largely addressed by Markov Chain Monte Carlo (MCMC) methods 5,6 . Here we propose an efficient quantum algorithm for thermal simulation that—akin to MCMC methods—exhibits detailed balance, respects locality and serves as a toy model for thermalization in open quantum systems. The enduring impact of MCMC methods suggests that our new construction may play an equally important part in quantum computing and applications in the physical sciences and beyond.
Aboveground biomass in Australian tropical forests now a net carbon source
In-plane dielectric constant and conductivity of confined water
Abstract Water is essential for almost every aspect of life on our planet and, unsurprisingly, its properties have been studied in great detail1. However, disproportionately little remains known about the electrical properties of interfacial and strongly confined water2,3, in which the structure deviates from that of bulk water, becoming distinctly layered4,5. The structural change is expected to affect the conductivity of water and particularly its polarizability, which in turn modifies intermolecular forces that play a crucial role in many physical and chemical processes6–9. Here we use scanning dielectric microscopy (SDM)10 to probe the in-plane electrical properties of water confined between atomically flat surfaces separated by distances down to 1 nm. For confinement exceeding several nanometres, water exhibits an in-plane dielectric constant close to that of bulk water and its proton conductivity is notably enhanced, gradually increasing with decreasing water thickness. This trend abruptly changes when the confined water becomes only a few molecules thick. Its in-plane dielectric constant reaches large, ferroelectric-like values of about 1,000, whereas the conductivity peaks at several S m−1, close to values characteristic of superionic liquids. We attribute the enhancement to strongly disordered hydrogen bonding induced by the few-layer confinement, which facilitates both easier in-plane polarization of molecular dipoles and faster proton exchange. This insight into the electrical properties of nanoconfined water is important for understanding many phenomena that occur at aqueous interfaces and in nanoscale pores.
Extreme confinement unleashes water’s hidden electrical capabilities
Reprogramming neuroblastoma by diet-enhanced polyamine depletion
Abstract Neuroblastoma is a highly lethal childhood tumour derived from differentiation-arrested neural crest cells1,2. Like all cancers, its growth is fuelled by metabolites obtained from either circulation or local biosynthesis3,4. Neuroblastomas depend on local polyamine biosynthesis, and the inhibitor difluoromethylornithine has shown clinical activity5. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumour differentiation and profound survival gains in the Th-MYCN mouse model. Specifically, an arginine- and proline-free diet decreases the amount of the polyamine precursor ornithine and enhances tumour polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at codons with adenosine in the third position. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by combined dietary and pharmacological intervention, favours a pro-differentiation proteome. These results suggest that the genes of specific cellular programmes have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of paediatric cancers.