Browse Articles

Synergy of Oxygen Vacancies and Ni Single Atoms Toward Efficient Urea Photosynthesis from CO ₂ and N ₂

Abstract The direct photochemical synthesis of urea under mild conditions presents considerable promise. Nevertheless, the photocatalytic urea synthesis is severely restricted by the co‐adsorption and activation of inert CO 2 and N 2 molecules. Herein, an ingenious design of a high‐performance Ni 1 /TiO 2‐ X catalyst by strategically coupling Ni single atoms (Ni SAs) and oxygen vacancies (Ov) onto urchin‐like TiO 2 architecture. By virtue of the unique synergistic catalysis between atomically dispersed Ni species and precisely engineered Ov sites, the Ni 1 /TiO 2‐ X catalyst achieves a remarkable urea production rate of 15.73 µmol g cat. −1 h −1 . Further mechanistic studies reveal that the atomically dispersed Ni sites facilitate N 2 adsorption and activation, generating *N 2 species, while the adjacent Ov sites activate CO 2 to form *CO intermediates. More intriguingly, the *CO species can migrate from the Ov site to the nearby Ni active centers, where they spontaneously undergo thermodynamic coupling with *N 2 to form a “tower‐like” urea precursor (*NCON* intermediate), subsequently converting to urea. The present work establishes a dual‐active‐site mechanism, comprising isolated Ni centers and adjacent Ov sites, which synergistically lowers the activation barrier for urea photosynthesis and accelerates reaction kinetics, and pioneers a transition strategy for the environmentally friendly and efficient synthesis of high‐value products.

The Diels–Alder Reaction as a Mechanistic Probe for Vibrational Strong Coupling

Abstract Vibrational Strong Coupling (VSC) has recently been reported to alter reaction kinetics. Hypotheses on how it does this have been proposed, but open questions remain regarding the importance of the polarity of the reaction mechanism and of intramolecular vibrational redistribution (IVR), among other factors. We propose the Diels–Alder (DA) reaction as a probe to study chemistry under VSC, owing to the high diversity of its reaction partners. Herein, fixed‐width cavities and UV–vis spectroscopy were used to determine the rate constants for the reactions of the diene 1,3‐diphenylisobenzofuran (DPIBF) with various dienophiles under different coupling conditions. We investigated the effect of coupling six different solvents and of cooperative coupling of the dienophile through the solvent. Secondly, as the DA reaction can be catalyzed by hydrogen bonding, we investigated how the reaction was influenced by coupling alcohol solvents. Finally, we explored the direct coupling of vibrational modes of the dienophiles, including the stretching mode of the reactive C═C bond. In all cases, no substantial changes to the reaction rate constants were observed among the diverse coupling scenarios explored. This work initiates the use of the DA reaction as a mechanistic platform to understand how VSC changes chemistry and invites further experimental and theoretical studies.

Targeting neutrophils for cancer therapy

Hyaluronidase-enhanced subcutaneous delivery of bNAbs: a phase 1 randomized controlled clinical trial in HIV-uninfected women

Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging

Abstract Inositol hexakisphosphate (IP6) promotes HIV-1 assembly by stabilizing the immature Gag lattice and becomes enriched within virions, where it is required for mature capsid assembly. Previously, we identified Gag mutants that package little IP6 yet assemble particles, though they are non-infectious due to defective capsid formation. Here, we report a compensatory mutation, G225R, in the C-terminus of capsid protein (CA) that restores capsid assembly and infectivity in these IP6-deficient mutants. G225R also enhances in vitro assembly of CA into capsid-like particles at far lower IP6 concentrations than required for wild-type CA. CryoEM structures of G225R CA hexamers and lattices at 2.7 Å resolution reveal that the otherwise disordered C-terminus becomes structured, stabilizing hexamer-hexamer interfaces. Molecular dynamics simulations support this mechanism. These findings uncover how HIV-1 can adapt to IP6 deficiency and highlight a previously unrecognized structural role of the CA C-terminus, while offering tools for capsid-related studies.

Microbiome data integration via shared dictionary learning

Coagulation factor XII haploinsufficiency is protective against venous thromboembolism in a population-scale multidimensional analysis

CLADES: a hybrid NeuralODE-Gillespie approach for unveiling clonal cell fate and differentiation dynamics

Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation

Abstract CRAF (RAF1) is one of three RAF-family kinases that initiate MAP kinase signaling in response to activated RAS and is essential for oncogenic signaling from mutant KRAS. Like BRAF, CRAF is regulated by 14-3-3 engagement and by intramolecular autoinhibitory interactions of its N-terminal regulatory region. Unlike BRAF, it is thought to require tyrosine phosphorylation in its N-terminal acidic (NtA) motif for full catalytic activation. Here we describe cryo-EM reconstructions of full-length CRAF in complex with MEK1 and a 14-3-3 dimer. These structures reveal a fully autoinhibited conformation analogous to that observed for BRAF and two “open monomer” states in which the inhibitory interactions of the CRD and 14-3-3 dimer are released or rearranged, but the kinase domain remains inactive. Structure-function studies of the NtA motif indicate that phosphorylation or acidic mutations in this segment increase catalytic activity by destabilizing the inactive conformation of the kinase domain. Collectively, these studies provide a structural foundation for understanding the shared and unique regulatory features of CRAF and will inform efforts to selectively block CRAF signaling in cancer.

Inverted temperature gradients in gold–palladium antenna-reactor nanoparticles

Abstract In addition to enhanced fields and possible charge transfer, the concentration of photothermal energy at the nanoscale is a central feature of plasmon-driven photochemistry. It is well known that light energy can be efficiently concentrated in metal nanoparticles to length scales far below the wavelength of light. Here we demonstrate that the energy absorbed by a gold nanoparticle can be further localized within a bimetallic gold-paladium nanoparticle system by the dissipation of energy into the attached palladium satellite nanoparticles. After pulsed excitation of the gold core, the satellites collect nearly all photothermal energy and heat up by 180 K while the light-absorbing gold core remains much colder. By comparing transient absorption dynamics of a series of bimetallic nanoparticles with a three-temperature model, we can precisely assess the temperatures of the electronic and vibrational subsystems. We find a strong inverted temperature gradient that opposes the direction of energy input and concentrates the light energy at the active catalytic nanosite.

Synergistic Self‐Assembled Monolayers Reinforce Buried Interface Anchoring for High‐Efficiency Tandem Perovskite Solar Cells

Abstract Carbazole‐based self‐assembled monolayers (SAMs) have been commonly used as a single‐component hole transport layer (HTL) in inverted perovskite solar cells (PSCs), but suffer from facile π‐π stacking and self‐aggregations in solution and consequently poor anchoring ability with the atop perovskite layer. Herein, we developed a synergistic SAM (syn‐SAM) strategy through blending a non‐planar molecule 3,3‐(4‐amino‐4H‐1,2,4‐triazole‐3,5‐diyl)‐dibenzo acid (ABT) bearing multiple anchoring sites with the commonly used Me‐4PACz SAM. The coexistence of these two components leverages π‐π interactions and hydrogen bonding to mitigate aggregation effects, affording dense and uniform SAM, thereby enhancing anchoring at the perovskite buried interface and alleviating interfacial charge recombination. ABT incorporation further helps to mitigating tensile strain in perovskite film. Additionally, this strategy offers advantages of multi‐device compatibility. The single‐junction champion inverted PSC devices based on syn‐SAM deliver power conversion efficiencies (PCEs) of 25.75% (certified 25.45%) and 22.76% (area: 0.105 cm 2 ) for 1.56  and 1.68 eV bandgap perovskites, respectively. Moreover, this approach is beneficial for the monolithic perovskite/silicon tandem solar cells based on fully textured surfaces of heterojunction (HJT) silicon bottom cells, affording PCEs of 31.56% (area: 1.07 cm 2 ) and 26.57% (area: 20.06 cm 2 ). All devices exhibit excellent long‐term storage and thermal stability even under non‐encapsulated conditions.

The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration

Near-global spawning strategies of large pelagic fish

Photonic terahertz phased array via selective excitation of nonlinear Pancharatnam-Berry elements

Abstract Phased arrays are crucial in various technologies, such as radar and wireless communications, due to their ability to precisely control and steer electromagnetic waves. This precise control improves signal processing and enhances imaging performance. However, extending phased arrays to the terahertz (THz) frequency range has proven challenging, especially for high-frequency operation, broadband performance, two-dimensional (2D) phase control with large antenna arrays, and flexible phase modulation. Here, we introduce a photonic platform to realize a THz phased array that bypasses the above challenges. Our method employs 2D phase coding with 2-bit across a broad THz frequency range from 0.8 to 1.4 THz. The core of our design is a pixelated nonlinear Pancharatnam-Berry (PB) metasurface driven by a spatially modulated femtosecond laser for selective excitation of the desired PB elements, allowing precise phase and wavefront control of the emitted THz signals. We showcase the effectiveness of our method through four proof-of-concept applications: single beamforming, dual beamforming, imaging, and vortex beam generation. The realized photonic platform provides a promising pathway for developing broadband phased arrays in the THz regime.

Metalloenzyme‐Catalyzed Asymmetric Transfer Hydrogenation for the Synthesis of Chiral Amines

Abstract Chiral amines are prevalent in natural products, pharmaceuticals, and organic catalysts. Their increasing demand has driven the advancement of synthetic methods. In this study, we developed a metalloenzyme‐catalyzed asymmetric transfer hydrogenation method for the synthesis of chiral amines. Given the challenges of traditional chemical synthesis, which relies on precious metals and complex synthetic ligands, our approach utilizes base metals derived from natural metalloenzymes for transfer hydrogenation and employs protein scaffolds to achieve stereochemical control. Furthermore, in contrast to natural NAD(P)H‐dependent C═N bond reductases, this strategy utilizes silanes as reducing agents and is entirely orthogonal to conventional NAD(P)H‐dependent cellular functions. This reactivity highlights the potential to develop new‐to‐nature enzymatic functions capable of addressing challenges in both organic synthesis and biosynthesis.

Mature and migratory dendritic cells promote immune infiltration and response to anti-PD-1 checkpoint blockade in metastatic melanoma

Abstract Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells. Importantly, mregDC abundance predicts progression-free survival (PFS) with ICIs and other therapies, especially when combined with the TCF7 + /– CD8 T cell ratio. Analysis of an independent cohort (n = 318) validates mregDC as a predictive biomarker for anti-CTLA-4 plus anti-PD-1 therapies. Further characterization of mregDCs versus conventional dendritic cells (cDC1/cDC2) highlights their unique transcriptional, epigenetic (single-nucleus ATAC-seq data for cDCs from 14 matched samples), and interaction profiles, offering new insights for improving immunotherapy response and guiding future combination treatments.

A C‐to‐B Atom Swap on Coumarins and Dibenzolactones

Abstract We report a carbon‐to‐boron “C‐to‐B” atom swap reaction to transform readily available coumarins into their isosteric benzoxaborins via a net replacement of the C═O group with a B─OH moiety. These conditions were applied to coumarin natural products and other 6–7‐membered lactones (25 examples, 29%–93%). We leverage this methodology to transform a flat polyaromatic hydrocarbon into three‐dimensional tribenzo[b.d.f]oxepines through a series of atom‐swapping reactions followed by ring expansion via the oxaborin intermediate.

Application of new approach methodologies for nonclinical safety assessment of drug candidates

Aerosol iodide accelerates reactive nitrogen cycling in the marine atmosphere

The Overlooked Dual Phosphorescence of Lappert's Diamino Stannylene Sn[N(SiMe ₃ ) ₂ ] ₂

Abstract The first stable heavy carbene homologues, the heavy tetrylenes, were reported in 1973 by Lappert and coworkers. These tetrylenes were extensively investigated with respect to ground state reactivity, such as small molecule activation, insertion into σ‐bonds, coordination chemistry, materials chemistry, or catalysis. Their photophysical properties remained essentially unexplored. We report that the bright yellow‐colored diamino stannylene Sn[N(SiMe 3 ) 2 ] 2 shows thermally activated dual orange/green phosphorescence with microsecond lifetime in fluid solution at room temperature, which has been overlooked for more than 50 years. These unique electronic and photophysical properties are studied in detail by temperature‐dependent time‐resolved emission and absorption spectroscopy and are corroborated by (time‐dependent) density functional theory (DFT) calculations. The mechanism of photochemical radical formation has been disclosed, involving unprecedented stannylene excimers with second‐order Jahn–Teller distorted structures. The present study provides new insights toward a rational design of tetrel(II) complexes with long‐lived emissive excited states, with Sn[N(SiMe 3 ) 2 ] 2 being the prototype.