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Abstract Two-thirds of signaling hormones and one-third of approved drugs exert their effects by binding and modulating the G protein-coupled receptors (GPCRs) activation. While the activation mechanism for monomeric GPCRs has been well-established, little is known about GPCRs in dimeric form. Here, by combining transition pathway generation, extensive atomistic simulation-based Markov state models, and experimental signaling assays, we reveal an asymmetric, stepwise millisecond allosteric activation mechanism for the metabotropic glutamate receptor subtype 5 receptor (mGlu5), an obligate dimeric class C GPCR. The dynamic picture is presented that agonist binding induces dimeric ectodomains compaction, amplified by the precise association of the cysteine-rich domains, ultimately loosely bringing the intracellular 7-transmembrane (7TM) domains into proximity and establishing an asymmetric TM6-TM6 interface. The active inter-domain interface enhances their intra-domain flexibility, triggering the activation of micro-switches crucial for downstream signal transduction. Furthermore, we show that the positive allosteric modulator stabilizes both the active inter-domain 7TM interface and an open, extended intra-domain ICL2 conformation. This stabilization leads to the formation of a pseudo-cavity composed of the ICL2, ICL3, TM3, and C-terminus, which facilitates G protein coordination. Our strategy may be generalizable for characterizing millisecond events in other allosteric systems.

Abstract The geodynamic processes that formed Earth’s earliest continents are intensely debated. Particularly, the transformation from ancient crustal nuclei into mature Archaean cratons is unclear, primarily owing to the paucity of well-preserved Eoarchaean–Palaeoarchaean ‘protocrust’. Here, we report a newly identified Palaeoarchaean continental fragment—the Baishanhu nucleus—in northeastern North China Craton. U–Pb geochronology shows that this nucleus preserves five major magmatic events during 3.6–2.5 Ga. Geochemistry and zircon Lu–Hf isotopes reveal ancient 4.2–3.8 Ga mantle extraction ages, as well as later intraplate crustal reworking. Crustal architecture and zircon Hf–O isotopes indicate that proto-North China first formed in a stagnant/squishy lid geodynamic regime characterised by plume-related magmatic underplating. Such cratonic growth and maturation were prerequisites for the emergence of plate tectonics. Finally, these data suggest that North China was part of the Sclavia supercraton and that the Archaean onset of subduction occurred asynchronously worldwide.

Abstract Porous frameworks constructed via noncovalent interactions show wide potential in molecular separation and gas adsorption. However, it remains a major challenge to prepare these materials from low-symmetry molecular building blocks. Herein, we report a facile strategy to fabricate noncovalent porous crystals through modular self-assembly of a low-symmetry helicene racemate. The P and M enantiomers in the racemate first stack into right- and left-handed triangular prisms, respectively, and subsequently the two types of prisms alternatively stack together into a hexagonal network with one-dimensional channels with a diameter of 14.5 Å. Remarkably, the framework reveals high stability upon heating to 275 °C, majorly due to the abundant π-interactions between the complementarily engaged helicene building blocks. Such porous framework can be readily prepared by fast rotary evaporation, and is easy to recycle and repeatedly reform. The refined porous structure and enriched π-conjugation also favor the selective adsorption of a series of small molecules.

Abstract Low-temperature germination (LTG) is an important agronomic trait for rice (Oryza sativa). Japonica rice generally has greater capacity for germination at low temperatures than the indica subpopulation. However, the genetic basis and molecular mechanisms underlying this complex trait are poorly understood. Here, we report that OsUBC12, encoding an E2 ubiquitin-conjugating enzyme, increases low-temperature germinability in japonica, owing to a transposon insertion in its promoter enhancing its expression. Natural variation analysis reveals that transposon insertion in the OsUBC12 promoter mainly occurs in the japonica lineage. The variation detected in eight representative two-line male sterile lines suggests the existence of this allele introgression by indica-japonica hybridization breeding, and varieties carrying the japonica OsUBC12 locus (transposon insertion) have higher low-temperature germinability than varieties without the locus. Further molecular analysis shows that OsUBC12 negatively regulate ABA signaling. OsUBC12-regulated seed germination and ABA signaling mainly depend on a conserved active site required for ubiquitin-conjugating enzyme activity. Furthermore, OsUBC12 directly associates with rice SUCROSE NON-FERMENTING 1-RELATED PROTEIN KINASE 1.1 (OsSnRK1.1), promoting its degradation. OsSnRK1.1 inhibits LTG by enhancing ABA signaling and acts downstream of OsUBC12. These findings shed light on the underlying mechanisms of UBC12 regulating LTG and provide genetic reference points for improving LTG in indica rice.

Abstract Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here, we discover an aldo-keto reductase termed AKRtyl and present its three-level regulatory mechanism. Specifically, by combining steady-state and transient kinetics, X-ray crystallography and molecular dynamics simulation, we demonstrate that AKRtyl exhibits a positive synergy mediated by an unusual Monod-Wyman-Changeux (MWC) paradigm of allosteric regulation at low concentrations of the cofactor NADPH, but an inhibitory effect at high concentrations is observed. While the substrate tylosin binds at a remote allosteric site with positive cooperativity. We further reveal that these regulatory mechanisms are conserved in AKR12D subfamily, and that substrate cooperativity is common in AKRs across three kingdoms of life. This work provides an intriguing example for understanding complex allosteric regulatory networks.

Abstract The tendency of species to retain ancestral ecological distributions (phylogenetic niche conservatism) is thought to influence which species from a species pool can persist in a particular environment. Thus, investigating the relationships between measures of phylogenetic structure and environmental variables at a global scale can help understand the variation in species richness and phylogenetic structure in biological assemblages across the world. Here, we analyze a comprehensive data set including 341,846 species in 391 angiosperm floras worldwide to explore the relationships between measures of phylogenetic structure and environmental variables for angiosperms in regional floras across the world and for each of individual continental (biogeographic) regions. We find that the global phylogenetic structure of angiosperms shows clear and meaningful relationships with environmental factors. Current climatic variables have the highest predictive power, especially on phylogenetic metrics reflecting recent evolutionary relationships that are also related to current environmental heterogeneity, presumably because this favors plant speciation in various ways. We also find evidence that past climatic conditions, and particularly refugial conditions, play an important role in determining the phylogenetic structure of regional floras. The relationships between environmental conditions and phylogenetic metrics differ between continents, reflecting the different evolutionary histories of their floras.

Abstract The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449–3500, 2278–3257 and 1621–2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.

Abstract Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Abstract Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Abstract Copper-based catalysts serve as the predominant methanol steam reforming material although several fundamental issues remain ambiguous such as the identity of active center and the aspects of reaction mechanism. Herein, we prepare Cu/Cu(Al)O x catalysts with amorphous alumina-stabilized Cu2O adjoining Cu nanoparticle to provide Cu0−Cu+ sites. The optimized catalyst exhibits 99.5% CH3OH conversion with a corresponding H2 production rate of 110.8 μmol s−1 gcat −1 with stability over 300 h at 240 °C. A binary function correlation between the CH3OH reaction rate and surface concentrations of Cu0 and Cu+ is established based on kinetic studies. Intrinsic active sites in the catalyst are investigated with in situ spectroscopy characterization and theoretical calculations. Namely, we find that important oxygen-containing intermediates (CH3O* and HCOO*) adsorb at Cu0−Cu+ sites with a moderate adsorption strength, which promotes electron transfer from the catalyst to surface species and significantly reduces the reaction barrier of the C−H bond cleavage in CH3O* and HCOO* intermediates.

Abstract Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.

Abstract The metal-support interaction (MSI) in heterogeneous catalysts plays a crucial role in reforming reaction to produce renewable hydrogen, but conventional objects are limited to single metal and support. Herein, we report a type of RhNi/TiO2 catalysts with tunable RhNi-TiO2 strong bimetal-support interaction (SBMSI) derived from structure topological transformation of RhNiTi-layered double hydroxides (RhNiTi-LDHs) precursors. The resulting 0.5RhNi/TiO2 catalyst (with 0.5 wt.% Rh) exhibits extraordinary catalytic performance toward ethanol steam reforming (ESR) reaction with a H2 yield of 61.7%, a H2 production rate of 12.2 L h−1 gcat −1 and a high operational stability (300 h), which is preponderant to the state-of-the-art catalysts. By virtue of synergistic catalysis of multifunctional interface structure (Rh-Ni δ−-O v -Ti3+; O v denotes oxygen vacancy), the generation of formate intermediate (the rate-determining step in ESR reaction) from steam reforming of CO and CH x is significantly promoted on 0.5RhNi/TiO2 catalyst, accounting for its ultra-high H2 production.

Abstract Hydroformylation is one of the largest industrially homogeneous processes that strongly relies on catalysts with phosphine ligands such as the Wilkinson’s catalyst (triphenylphosphine coordinated Rh). Heterogeneous catalysts for olefin hydroformylation are highly desired but suffer from poor activity compared with homogeneous catalysts. Herein, we demonstrate that rhodium nanoparticles supported on siliceous MFI zeolite with abundant silanol nests are very active for hydroformylation, giving a turnover frequency as high as ~50,000 h−1 that even outperforms the classical Wilkinson’s catalyst. Mechanism study reveals that the siliceous zeolite with silanol nests could efficiently enrich olefin molecules to adjacent rhodium nanoparticles, enhancing the hydroformylation reaction.

Thermocatalytic alkynol semi-hydrogenation often uses high-pressure H2 and Pd-based catalysts. Here, using a Cu-based electrode, the authors investigate the electrocatalytic alkynol semi-hydrogenation to alkenols with water as the hydrogen source.

Cellular metabolism is important in pluripotency and cell fate regulation. Here, authors observe chromatin remodeling followed by TCA enzyme translocation from the mitochondria to the nucleus, demonstrating pluripotency regulation by mitochondria to nucleus retrograde signaling.

G-protein-signaling modulator 1 (GPSM1), an accessory protein which activates heterotrimeric G-protein signaling, exhibits a genetic association with type 2 diabetes. Here the authors show that myeloid GPSM1 ablation in mice inhibits inflammation and metabolic dysfunction upon high fat diet.

The removal of radioactive elements is important to human health and sustainable development. Here, the authors reveal the synthesis of water-stable Archimedean solids based on the earth-abundant element for the fast removal of trace iodine.

AXL is overexpressed and has been investigated as a therapeutic target in several cancer types, including lung cancer. Here the authors design AXLdirected CAR-T cells and show that their anti-tumor activity can be improved in combination with microwave ablation in preclinical lung cancer models.

METTL3 catalyzes mRNA m6A deposition. The authors identify an acetylation-mediated regulation of METTL3 subcellular localization and compartment-specific functions, a process that is fine-tuned by anti-inflammatory and pro-inflammatory signals, which ultimately determine breast cancer metastasis.

Nonlinear optical properties of metal-organic framework can be tuned for potential optical applications. Here the authors demonstrate an enhancement the nonlinear absorption coefficient of MOF film by applying external electric field.

The selective oxidation of glycerol to glyceric acid is an important value-added cascade catalytic process. Here the authors report a cascade synergistic catalysis strategy by atomic and low-coordinated cluster Pt on well-defined Cu-CuZrOx to simultaneously achieve high activity and selectivity.

The adenomatous polyposis coli (APC)–Asef protein interaction is essential for colorectal cancer metastasis. Here, the authors present the rational design of a sensitivity-enhanced tracer for fluorescence polarization assays, enabling them to discover more efficient APC–Asef interaction inhibitors.

Understanding the mutation landscape of cancer may enable the development of more targeted therapies. Here, the authors sequence a panel of genes in a large Asian cohort and compare to American cohorts and find 64% of the Asian patients have actionable mutations.

Platinum agents, such as carboplatin and cisplatin, have been recommended in combination with gemcitabine for the treatment of metastatic triple negative breast cancer (TNBC). Here the authors report the results of a randomized phase 3 trial to compare the efficacy of first-line nab-paclitaxel/cisplatin to gemcitabine/cisplatin in patients with TNBC.

Potassium channels and membrane potential may influence macrophage function during inflammation. Here the authors show that the Kir2.1 potassium channel affects macrophage metabolism by altering cell surface retention of nutrient transporters and subsequently regulates inflammatory disease responses.

Physically plausible interseismic asperity models determined from GPS velocities suggest that the 2020 Mw 7.8 Simeonof and 2021 Mw 8.2 Chignik earthquakes ruptured distinct persistent asperities on the Alaska-Aleutian subduction zone

Bioinspired architectures are desired to achieve improved mechanical properties, but challenging to achieve in metallic systems. Here the authors fabricate a Mg-Ti interpenetrating phase composite with brick-and-mortar, Bouligand, and crossed-lamellar architectures by pressureless infiltrating method.

Circumsporozoite protein (CSP), the major surface protein of Plasmodium sporozoites, is important for parasite targeting to mosquito salivary glands and the mammalian liver. Here, Zhu et al. show that CSP is required for rodent malaria oocysts to evade mosquito immunity by inducing hemocyte nitration and causing subsequent defects in sporozoite-release from oocysts.

Lignin depolymerization to make heterocyclic aromatic compounds is of great importance to expanding the product portfolio derived from biomass, but it is also particularly challenging. In this work, the authors report pyrimidine synthesis from lignin β-O-4 model compounds via a one-pot multicomponent cascade reaction.

SNIP1 methylation initiates its oncogenic functions. Here, the authors show that SNIP1 is methylated by KMT5A and this leads to downstream signalling that activates the YAP pathway, resulting in tumorigenesis and metastasis.

Electrocatalytic recycling of waste nitrate to NH3 under ambient conditions maybe an appealing alternative to the Haber−Bosch process. Here the authors report a tandem catalyst system involving cooperative adsorption of reaction intermediate on different transition metal active sites for nitrate electroreduction with high efficiency.

This study explores N–heterocyclic carbene copper complexes toward selective electrocatalytic reduction of acetylene to ethylene. The electron–rich copper sites were found to facilitate acetylene adsorption and ethylene desorption and achieved high activity and selectivity for ethylene production.

Constructing strong metal-support interactions (SMSI) is an effective means of regulating the interfacial properties of noble metal-based supported catalysts. Here, the authors propose a strategy of ultrafast laser-induced SMSI that can be constructed on a CeO2-supported Pt system by confining electric field in localized interface.

Rational design and synthesis of superior electrocatalysts for ethanol oxidation is crucial to practical applications of direct ethanol fuel cells. Here, authors report the construction of Pd-Zn dual sites with well exposure and uniformity can improve the efficiency of ethanol electro-oxidation.

G protein-coupled receptors (GPCRs) are a critical target in modern drug development across a wide range of indications. Here the authors provide a comprehensive characterization of a typical GPCR, the angiotensin II (AngII) type 1 receptor (AT1R), and provide insight into its activation mechanism that suggest avenues for the design of allosteric GPCR modulators.

It is of great significance to exert the synergistic effect between single atom and support. Here, the authors prepare polyoxometalates-stabilized single-atom site catalysts in confined space with enhanced activity for alkynes diboration.

The use of room temperature exciton–polariton Bose–Einstein condensation is limited by the need for external high-finesse microcavities. The authors generate room temperature EPs with single-crystal microribbons as waveguide Fabry–Pérot microcavities, and demonstrate controllable output of coherent light.

Dysfunctional and disfiguring scars can result from aberrant wound repair. Here, the authors develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for scarless wound repair.

Cyclic polymers have a number of unique physical properties compared to their linear counterparts but their synthesis is very limited. Here, the authors show a method to form a wide variety of multicyclic polymers by a rhodanine˗based Knoevenagel reaction and ring-opening polymerization.

The crystal phase-based heterostructures of noble metal nanomaterials are of interest for various applications. Here, the authors report the wet-chemical synthesis of gold nanorods with a well-defined fcc-2H-fcc heterophase, which possess unique optical and catalytic properties.

The controllable synthesis of organometallic polymers that can be used in ultrahigh information storage and anti-counterfeiting security has been an unsolved challenge. Here, the authors show sequence-controlled electrosynthesis of organometallic polymers with exquisite insertion of multiple and distinct monomers.

Interest in rechargeable Zn-air batteries has been renewed in recent years, however, their oxygen electrocatalysts remain not fully understood. Here the authors reveal the presence of a current-driven oxyhydroxide shell in a so-called dynamic eletrocatalyst that enables optimized battery performance.

Effective electrocatalyst is crucial in promoting CO2 reduction to address current energy/environmental issue. Here, the authors develop bimetallic layered two-dimensional conjugated metal-organic framework to synergistically and efficiently electro-catalyze CO2 to CO toward syngas synthesis.

Identifying distinct cyclometallation pathways is essential to new types of C-H activation and functionalization in organic synthesis. Here, the authors show the activation of an olefinic C-H bond geminal to the directing group via four- to eight-membered exo-palladacycles with broad substrate scope.

Noble metals play a momentous role in heterogeneous catalysis but still face a huge challenge in selectivity control. Herein, the authors demonstrate that isolating contiguous Pt atoms and forming Pt-Zn intermetallic nanoparticles is an effective strategy to optimize the selectivity of Pt catalysts.

Nanofluidic channels can capture osmotic energy from salinity gradients, but output power densities should be improved for practical applications. Here the authors report high-strength nanosheet/nanofiber composite membranes for harvesting osmotic energy from natural water with high output power.

The efficiency and selectivity of the transformation process for an aqueous solution of mixed oxygenates produced by biomass fermentation remains a challenge. Here, the authors report a simple reaction for the conversion of aqueous biomass fermentation broth to a water-immiscible product efficiently and selectively.

Developing high-performance potassium-ion batteries remains a challenge. Here, the authors show that few-layered Sb2S3/carbon composite anode synthesized via simple exfoliation minimizes the volume changes during (de)intercalation of K+ ions with boosted rate performance and cyclability.