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Abstract Molecular recognition of proteins is key to their biological functions and processes such as protein–protein interactions (PPIs). The large binding interface involved and an often relatively flat binding surface make the development of selective protein-binding materials extremely challenging. A general method is reported in this work to construct protein-binding polymeric nanoparticles from cross-linked surfactant micelles. Preparation involves first dynamic covalent chemistry that encodes signature surface lysines on a protein template. A double molecular imprinting procedure fixes the binding groups on the nanoparticle for these lysine groups, meanwhile creating a binding interface complementary to the protein in size, shape, and distribution of acidic groups on the surface. These water-soluble nanoparticles possess excellent specificities for target proteins and sufficient affinities to inhibit natural PPIs such as those between cytochrome c (Cytc) and cytochrome c oxidase (CcO). With the ability to enter cells through a combination of energy-dependent and -independent pathways, they intervene apoptosis by inhibiting the PPI between Cytc and the apoptotic protease activating factor-1 (APAF1). Generality of the preparation and the excellent molecular recognition of the materials have the potential to make them powerful tools to probe protein functions in vitro and in cellulo.

Abstract The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

Abstract The genome’s dynamic nature, exemplified by elements like extrachromosomal circular DNA (eccDNA), is crucial for biodiversity and adaptation. Yet, the role of eccDNA in plants, particularly rice, remains underexplored. Here, we identify 25,598 eccDNAs, unveiling the widespread presence of eccDNA across six rice tissues and revealing its formation as a universal and random process. Interestingly, we discover that direct repeats play a pivotal role in eccDNA formation, pointing to a unique origin mechanism. Despite eccDNA’s prevalence in coding sequences, its impact on gene expression is minimal, implying its roles beyond gene regulation. We also observe the association between eccDNA’s formation and minor chromosomal deletions, providing insights of its possible function in regulating genome stability. Further, we discover eccDNA specifically accumulated in rice leaves, which may be associated with DNA damage caused by environmental stressors like intense light. In summary, our research advances understanding of eccDNA’s role in the genomic architecture and offers valuable insights for rice cultivation and breeding.

Abstract Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning and WGCNA. Aberrations in ‘alanine, aspartate and glutamate metabolism’ proved to be prevalent throughout the ESCC evolution, consistently identified by NMR and MS, and reflected in 16 serum and 10 urine metabolic signatures in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperform clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and are effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613).

Abstract Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.

Abstract Localized interlayer excitons (LIXs) in two-dimensional moiré superlattices exhibit sharp and dense emission peaks, making them promising as highly tunable single-photon sources. However, the fundamental nature of these LIXs is still elusive. Here, we show the donor-acceptor pair (DAP) mechanism as one of the origins of these excitonic peaks. Numerical simulation results of the DAP model agree with the experimental photoluminescence spectra of LIX in the moiré MoSe2/WSe2 heterobilayer. In particular, we find that the emission energy-lifetime correlation and the nonmonotonic power dependence of the lifetime agree well with the DAP IX model. Our results provide insight into the physical mechanism of LIX formation in moiré heterostructures and pave new directions for engineering interlayer exciton properties in moiré superlattices.

Abstract Electrochemical conversion of CO2 to formic acid using Bismuth catalysts is one the most promising pathways for industrialization. However, it is still difficult to achieve high formic acid production at wide voltage intervals and industrial current densities because the Bi catalysts are often poisoned by oxygenated species. Herein, we report a Bi3S2 nanowire-ascorbic acid hybrid catalyst that simultaneously improves formic acid selectivity, activity, and stability at high applied voltages. Specifically, a more than 95% faraday efficiency was achieved for the formate formation over a wide potential range above 1.0 V and at ampere-level current densities. The observed excellent catalytic performance was attributable to a unique reconstruction mechanism to form more defective sites while the ascorbic acid layer further stabilized the defective sites by trapping the poisoning hydroxyl groups. When used in an all-solid-state reactor system, the newly developed catalyst achieved efficient production of pure formic acid over 120 hours at 50 mA cm–2 (200 mA cell current).

Abstract Salt-overly-sensitive 1 (SOS1) is a unique electroneutral Na+/H+ antiporter at the plasma membrane of higher plants and plays a central role in resisting salt stress. SOS1 is kept in a resting state with basal activity and activated upon phosphorylation. Here, we report the structures of SOS1. SOS1 forms a homodimer, with each monomer composed of transmembrane and intracellular domains. We find that SOS1 is locked in an occluded state by shifting of the lateral-gate TM5b toward the dimerization domain, thus shielding the Na+/H+ binding site. We speculate that the dimerization of the intracellular domain is crucial to stabilize the transporter in this specific conformation. Moreover, two discrete fragments and a residue W1013 are important to prevent the transition of SOS1 to an alternative conformational state, as validated by functional complementation assays. Our study enriches understanding of the alternate access model of eukaryotic Na+/H+ exchangers.

Abstract The investigation of chirality at the nanoscale is important to bridge the gap between molecular and macroscopic chirality. Atomically precise metal nanoclusters provide an ideal platform for this research, while their enantiopure preparation poses a challenge. Here, we describe an efficient approach to enantiopure metal nanoclusters via asymmetric transformation, that is, achiral Au23(SC6H11)16 nanoclusters are converted into chiral and enantiopure Au24(L)2(SC6H11)16 nanoclusters by a chiral inducer phosphoramidite (L). Two enantiomers of Au24(L)2(SC6H11)16 are obtained and the crystal structures reveal their hierarchical chirality, which originates from the two introduced chiral L molecules, the transformation-triggered asymmetric rearrangement of the staple motifs on the surface of the gold core, and the helical arrangement of nanocluster molecules. The construction of this type of enantiomerically pure nanoclusters is achieved based on the easy-to-synthesize and modular L. Lastly, the chirality-related chiroptical performance was investigated, revealing a negative nonlinear CD-ee dependence.

Abstract The chiral charge density wave is a many-body collective phenomenon in condensed matter that may play a role in unconventional superconductivity and topological physics. Two-dimensional chiral charge density waves provide the building blocks for the fabrication of various stacking structures and chiral homostructures, in which physical properties such as chiral currents and the anomalous Hall effect may emerge. Here, we demonstrate the phase manipulation of two-dimensional chiral charge density waves and the design of in-plane chiral homostructures in 1T-TaS2. We use chiral Raman spectroscopy to directly monitor the chirality switching of the charge density wave—revealing a temperature-mediated reversible chirality switching. We find that interlayer stacking favours homochirality configurations, which is confirmed by first-principles calculations. By exploiting the interlayer chirality-locking effect, we realise in-plane chiral homostructures in 1T-TaS2. Our results provide a versatile way to manipulate chiral collective phases by interlayer coupling in layered van der Waals semiconductors.

NaV1.6 channel plays a critical role in neuronal excitability. Here, authors present human NaV1.6 structures in apo and 4,9-anhydro-tetrodotoxin bound forms, which reveal molecular mechanisms of NaV1.6 Na+ conductance and inhibition by the blocker.

Most NIR radiation absorbers used in multi jet fusion 3D printing have an intrinsic dark color which prevents printing parts with variable colors. Here, the authors design an activating fusing agent containing a strong NIR absorbing dye that turns colorless after harvesting irradiation energy during the 3D printing process and provide a bright colored part when working with other color agents.

The CaV2.3 channel is involved in synaptic plasticity and neurological disorders. Here, authors resolve the human CaV2.3 structure to explore functional heterogeneity of VSDs and elucidated the closed- and open-state inactivation mechanisms of the channel.

Fluorination of solvents, useful for non-aqueous lithium-based batteries, improves the electrochemical stability but decreases the ionic conductivity. Here, the authors report a targeted functionalization of an ether solvent to balance the electrolyte ionic conductivity and oxidative stability.

Colloidal liquid crystals account for various applications due to the combination of characteristics relevant for liquid crystals and colloids. The authors elaborate the impact of concave geometry on the properties of colloidal liquid crystals for development of functional materials.

A recent synthesis study found 54% of the high-latitude peatlands have been drying and 32% have been wetting over the past centuries, illustrating their complex ecohydrological dynamics and highly uncertain responses to a warming climate.

Hong Kong experienced a severe wave of SARS-CoV-2 in early 2022. Here, the authors use genomic and serosurveillance data and show that this wave was dominated by the Omicron BA.2 sublineage, and that low protective immunity, particularly in older age groups, contributed to its severity.

Excitatory amino acid transporter 2 (EAAT2) mediates glutamate uptake in the synapse. Here, authors report cryo-EM structures of the human EAAT2 in complexes with glutamate or selective inhibitor WAY-213613, revealing important insights into substrate recognition and selective inhibition.

The development of lithium-metal batteries is limited by the low thermodynamic and/or low voltage stability of conventional electrolytes. Here, the authors combined the high voltage stability of fluorinated ethers with high Li+ solvation ability of ethers in a single molecule and realized highly stable lithium-metal batteries.

More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.

T-type calcium channels are implicated in many diseases. Here, multiple structures of CaV3.3 channel elucidate molecular mechanisms of T-type CaV channels activation at low voltage and interaction with different clinically used channel blockers.

NaV1.3 is involved in neuronal development, hormone secretion and pain perception. Here, the authors elucidate the molecular mechanism for modulation of NaV1.3 by a site-2 neurotoxin bulleyaconitine A and a subtype selective antagonist ICA121431.

Abnormal levels of intracellular hydrogen sulphide (H2S) have been associated with different pathological conditions, including cancer. Here the authors report the design of a H2S-responsive and -depleting nanoplatform that, combined with NIR-II photodynamic properties, can be used for H2S imaging and cancer therapy.

Though stretchable semiconducting polymers are advantageous for electronic applications requiring low cost, the low performance of patterned microstructures remains a challenge. Here, the authors realize high mobility, stretchable polymer microstructures via a capillary-gradient assembly method.

Novel dry electrodes with enhanced mechano-electrical stability and conformability are attractive for long-time electrophysiological signal monitoring. Here, the authors report polymer-covered CVD-grown graphene with enhanced optoelectronic performance for biopotential monitoring.

Sodium/proton exchanger 1 (NHE1) and its obligate binding partner Calcineurin B-homologous protein 1 (CHP1) regulate intracellular pH and volume homeostasis. Structures of the human NHE1-CHP1 complex offer insight into the regulation of NHE1 pH-sensitivity by CHP1 and into the interactions with NHE1 inhibitors.

The genomic organization and origin of the avenacin biosynthetic gene cluster remain unknown. Here, the authors assemble the genome of diploid oat Avena strigosa, reveal the structure and organization of the consecutive genes, characterize the last two missing pathway steps, and investigate the origin of the pathway in cereals.

The genus Miscanthus has great potential for bio-energy production due to its high biomass yield and strong stress resistance. Here, the authors report the genome assembly of the diploid M. lutarioriparius, showing it has an allotetraploid origin and an expanded number of genes in families related to stress resistance.

The ability to control magnetic coupling in graphene nanomaterials remains elusive. Here, the authors report an approach of engineering magnetic ground states in open-shell bipartite/nonbipartite nanographenes where the magnetic coupling sign between two spins are controlled via breaking bipartite lattice symmetry.

Metal single-atom catalysts offer great potential in bridging the gap between heterogeneous and homogeneous catalysis. Here the authors demonstrate a multilayer stabilization strategy for fabricating high-loading single-atom catalysts including non-precious and noble metals.

Though DNA framework-based scaffolds for biomolecular assembly are attractive for bioimaging applications, realizing super-multiplex fluorescent amplifiers remains a challenge. Here, the authors report a topological engineering approach to designing fractal DNA frameworks for multiplexed amplifiers.

Typically, the performance of the state-of-the-art laser sensors is insufficient for many high precision applications. Here, the authors report mode-phase-difference photothermal spectroscopy with a dual-mode anti-resonant hollow-core optical fiber and demonstrate acetylene detection with ultra-high sensitivity.

Maize rough dwarf disease threatens its production. Here, the authors show that a helitron transposon insertion in the Rab GDP dissociation inhibitor alpha leads to recessive viral resistance by affecting its interaction with viral P7-1 protein and that all naturally occurring alleles come from a single mutation event after domestication.

Developing hybrid rice cultivars requires time consuming random crossing. Here, the authors develop a new next generation sequencing-based quantitative trait locus mapping method to dissect heterotic gene OsMADS1 and demonstrate the feasibility of pyramiding two genes to achieve large heterotic effect.

Anti-counterfeiting technologies should ideally be unclonable, yet simple to fabricate and decode. Here, the authors develop an inkjet-printable and unclonable security label based on random patterning of quantum dot inks, and accompany it with an artificial intelligence decoding mechanism capable of authenticating the patterns.

The basic mechanisms behind the East Asian Summer Monsoon remain poorly understood. Using proxy-based reconstructions and simulations, here the authors show that changes in the orientation and position of the westerly jet stream resulted in regionally asynchronous Holocene precipitation maxima.

Lithium metal batteries suffer from the dendrite growth upon electrochemical cycling. Here the authors introduce a lithiophilic-lithiophobic gradient interfacial ZnO/CNT layer, which facilitates the formation of a stable solid electrolyte interphase, and suppresses the growth of lithium dendrite.

Abstract The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.

Breviscapine is the flavonoid extract from medical plant Erigeron breviscapus for the treatment of cardio- and cerebrovascular disease. Here, the authors identify the key enzymes of the biosynthetic pathway from the plant genome and engineer yeast to produce breviscapine from glucose.

Chromosomal abnormalities such as 11q deletion are associated with poor prognosis in neuroblastoma. Here, the authors perform a genome-wide association study and identify an association between a variant within a Matrix metalloproteinase (MMP) gene member, MMP20, and 11q-deletion subtype neuroblastoma.

Bacterial lipoproteins have important biological functions, and the lipoprotien biogenesis enzyme Lgt is essential in most gram-negative bacteria. Here, the authors use structural and biochemical techniques to shed light on the function of Lgt in post-translational transacylation modification.

The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”. Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.” This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.