Browse Articles

Facilitating alkaline hydrogen evolution kinetics via interfacial modulation of hydrogen-bond networks by porous amine cages

Abstract The electrode-electrolyte interface is pivotal in the electrochemical kinetics. However, modulating the electrochemical interface at the atomic or molecular level is challenging due to the lack of efficient interfacial regulators. Here, we employ a porous amine cage as an interfacial modifier to Pt cluster in a confining configuration, largely enhancing alkaline HER kinetics by facilitating charge transfer. In situ electrochemical surface-enhanced Raman spectra, in combination with the ab initio molecular dynamics simulation, elucidates that the interaction between water and the -NH- moiety of cage frame softens the H-bonds net of interfacial water, making it more flexible for charge transfer. Moreover, our investigation pinpointed that the -NH- moiety acted as a pump for charge transfer by Grotthuss mechanism, lowering the kinetic barrier for hydrogen adsorption. Our findings highlight the strategy of establishing a soft-confining interfacial modifier by porous cage, offering opportunities to optimize electrochemical interfaces and promote reaction kinetics in a targeted way.

Striatal dopamine D2/D3 receptor regulation of human reward processing and behaviour

Abstract Signalling at dopamine D2/D3 receptors is thought to underlie motivated behaviour, pleasure experiences and emotional expression based on animal studies, but it is unclear if this is the case in humans or how this relates to neural processing of reward stimuli. Using a randomised, double-blind, placebo-controlled, crossover neuroimaging study, we show in healthy humans that sustained dopamine D2/D3 receptor antagonism for 7 days results in negative symptoms (impairments in motivated behaviour, hedonic experience, verbal and emotional expression) and that this is related to blunted striatal response to reward stimuli. In contrast, 7 days of partial D2/D3 agonism does not disrupt reward signalling, motivated behaviour or hedonic experience. Both D2/D3 antagonism and partial agonism induce motor impairments, which are not related to striatal reward response. These findings identify a central role for D2/D3 signalling and reward processing in the mechanism underlying motivated behaviour and emotional responses in humans, with implications for understanding neuropsychiatric disorders such as schizophrenia and Parkinson’s disease.

Tandem reductive amination and deuteration over a phosphorus-modified iron center

Systematic inference of super-resolution cell spatial profiles from histology images

Increasingly efficient chromatin binding of cohesin and CTCF supports chromatin architecture formation during zebrafish embryogenesis

Abstract The three-dimensional folding of chromosomes is essential for nuclear functions such as DNA replication and gene regulation. The emergence of chromatin architecture is thus an important process during embryogenesis. To shed light on the molecular and kinetic underpinnings of chromatin architecture formation, we characterized biophysical properties of cohesin and CTCF binding to chromatin and their changes upon cofactor depletion using single-molecule imaging in live developing zebrafish embryos. We found that chromatin-bound fractions of both cohesin and CTCF increased significantly between the 1000-cell and shield stages, which we could explain through changes in both their association and dissociation rates. Moreover, increasing binding of cohesin restricted chromatin motion, potentially via loop extrusion, and showed distinct stage-dependent nuclear distribution. Polymer simulations with experimentally derived parameters recapitulated the experimentally observed gradual emergence of chromatin architecture. Our findings reveal molecular kinetics underlying chromatin architecture formation during zebrafish embryogenesis.

Author Correction: Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy

TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts

Abstract TGM6 is a natural antagonist of mammalian TGF-β signaling produced by the murine helminth parasite Heligmosomoides polygyrus. It differs from the previously described agonist, TGM1 (TGF-β Mimic-1), in that it lacks domains 1/2 that bind TGFBR1. It nonetheless retains TGFBR2 binding through domain 3 and potently inhibits TGF-β signaling in fibroblasts and epithelial cells, but does not inhibit TGF-β signaling in T cells, consistent with divergent domains 4/5 and an altered co-receptor binding preference. The crystal structure of TGM6 bound to TGFBR2 reveals an interface remarkably similar to that of TGF-β with TGFBR2. Thus, TGM6 has adapted its structure to mimic TGF-β, while engaging a distinct co-receptor to direct antagonism to fibroblasts and epithelial cells. The co-expression of TGM6, along with immunosuppressive TGMs that activate the TGF-β pathway, may minimize fibrotic damage to the host as the parasite progresses through its life cycle from the intestinal lumen to submucosa and back again. The co-receptor-dependent targeting of TGFBR2 by the parasite provides a template for the development of therapies for targeting the cancer- and fibrosis-promoting activities of the TGF-βs in humans.

Bio-inspired electronics: Soft, biohybrid, and “living” neural interfaces

Abstract Neural interface technologies are increasingly evolving towards bio-inspired approaches to enhance integration and long-term functionality. Recent strategies merge soft materials with tissue engineering to realize biologically-active and/or cell-containing living layers at the tissue-device interface that enable seamless biointegration and novel cell-mediated therapeutic opportunities. This review maps the field of bio-inspired electronics and discusses key recent developments in tissue-like and regenerative bioelectronics, from soft biomaterials and surface-functionalized bioactive coatings to cell-containing ‘biohybrid’ and ‘all-living’ interfaces. We define and contextualize key terminology in this emerging field and highlight how biological and living components can bridge the gap to clinical translation.

Kinetic cation effect in alkaline hydrogen electrocatalysis and double layer proton transfer

Tightly bonded excitons in chiral metal clusters for luminescent brilliance

Fabrication of atomically dispersed barium hydride catalysts for the synthesis of deuterated alkylarenes

Molecularly engineered supramolecular fluorescent chemodosimeter for measuring epinephrine dynamics

Abstract Accurately visualizing epinephrine (EP) activity is essential for understanding its physiological functions and pathological processes in brain. However, to the best of our knowledge, reliable, rapid, and specifical measurement of EP dynamics at cellular and in vivo level hasn’t been previously reported. Herein, we report the probe for EP imaging and biosensing in neurons and living brain of freely behaving animals, based on creating a series of supramolecular fluorescent chemodosimeters through host-guest interaction. The optimized chemodosimeter enables real-time imaging and quantifying of EP with high specificity, sensitivity, signal-to-noise ratio, and rapid kinetics (~240 ms) in neurons, brain tissues and zebrafish. More significantly, we demonstrate real-time monitoring of EP in 26 regions within deep brain of freely behaving male mice, unraveling an augmented EP concentration in the amygdala, thalamus, hypothalamus, hippocampus and striatum under fear-induced stress. These findings highlight our chemodosimeter as a powerful tool for precise measurements of EP dynamics in diverse model organisms.

Cerebellar output neurons can impair non-motor behaviors by altering development of extracerebellar connectivity

Vacancies in sulfides facilitate fluid-induced solid-state diffusion and critical metals accumulation

Engineering anisotropic electrodynamics at the graphene/CrSBr interface

Abstract Graphene is a privileged 2D platform for hosting confined light-matter excitations known as surface plasmon polaritons (SPPs), as it possesses low intrinsic losses and a high degree of optical confinement. However, the isotropic nature of graphene limits its ability to guide and focus SPPs, making it less suitable than anisotropic elliptical and hyperbolic materials for polaritonic lensing and canalization. Here, we present graphene/CrSBr as an engineered 2D interface that hosts highly anisotropic SPP propagation across mid-infrared and terahertz energies. Using scanning tunneling microscopy, scattering-type scanning near-field optical microscopy, and first-principles calculations, we demonstrate mutual doping in excess of 1013 cm–2 holes/electrons between the interfacial layers of graphene/CrSBr. SPPs in graphene activated by charge transfer interact with charge-induced electronic anisotropy in the interfacial doped CrSBr, leading to preferential SPP propagation along the quasi-1D chains that compose each CrSBr layer. This multifaceted proximity effect both creates SPPs and endows them with anisotropic propagation lengths that differ by an order-of-magnitude between the in-plane crystallographic axes of CrSBr.

Forcing mechanisms of the half-precession cycle in the western equatorial Pacific temperature

Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial

Exploring the principles behind antibiotics with limited resistance

Abstract Antibiotics that target multiple cellular functions are anticipated to be less prone to bacterial resistance. Here we hypothesize that while dual targeting is crucial, it is not sufficient in preventing resistance. Only those antibiotics that simultaneously target membrane integrity and block another cellular pathway display reduced resistance development. To test the hypothesis, we focus on three antibiotic candidates, POL7306, Tridecaptin M152-P3 and SCH79797, all of which fulfill the above criteria. Here we show that resistance evolution against these antibiotics is limited in ESKAPE pathogens, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, while dual-target topoisomerase antibiotics are prone to resistance. We discover several mechanisms restricting resistance. First, de novo mutations result in only a limited elevation in resistance, including those affecting the molecular targets and efflux pumps. Second, resistance is inaccessible through gene amplification. Third, functional metagenomics reveal that mobile resistance genes are rare in human gut, soil and clinical microbiomes. Finally, we detect rapid eradication of bacterial populations upon toxic exposure to membrane targeting antibiotics. We conclude that resistance mechanisms commonly found in natural bacterial pathogens provide only limited protection to these antibiotics. Our work provides guidelines for the future development of antibiotics.

Ab initio quantum many-body description of superconducting trends in the cuprates

Sub-femtomolar drug monitoring via co-calibration mechanism with nanoconfined DNA probes

Abstract Synthetic drugs fundamentally reshape the illicit drug market due to their low cost, ease of production, and rapid manufacturing processes. However, current drug detection methods, which rely on complex instruments, have limited applicability and often neglect the influence of pH fluctuations, leading to potential bias and unreliable results. Herein, we propose co-calibration DNA probes on a nanoconfined biosensor (N C B S ), covering the range of sweat pH 3–8 to achieve significantly enhanced target signal recognition. The N C B S exhibits a linear response range of 10 3 -10 8 fM with a low limit of detection (LOD) of 3.58 fM in artificial sweat. Compared to the single-aptamer N C B S , the dual-aptamer N C B S offers a broader linear response range, primarily due to the synergistic effects of changes in surface wettability and the capture of hydrion, which together reduce signal interference in proton transport. The linear response range doubles, and its detection sensitivity improves by 4–5 orders of magnitude compared to existing drug detection methods. This sensing strategy expands the application scope of aptamer-based composite probes, offering an approach for ultra-sensitive drug detection and demonstrating significant potential in sweat sensing and drug monitoring fields.