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Abstract The route of oncolytic virotherapy is pivotal for immunotherapeutic efficacy in advanced cancers. In this preclinical study, an oncolytic reovirus (RC402) is orally administered to induce antitumor immunity. Oral reovirus treatment shows no gross toxicities and effectively suppresses multifocal tumor lesions. Orally administered reovirus interacts with the host immune system in the Peyer’s patch of the terminal ileum, increases IgA+ antibody-secreting cells in the lamina propria through MAdCAM-1+ blood vessels, and reshapes the gut microbiome. Oral reovirus promotes antigen presentation, type I/II interferons, and T cell activation within distant tumors, but does not reach or directly infect tumor cells beyond the gastrointestinal tract. In contrast to intratumoral reovirus injection, the presence of the gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells are indispensable for orally administered reovirus-induced antitumor immunity. Oral reovirus treatment is most effective when combined with αPD-1(L1) and/or αCTLA-4, leading to complete colon tumor regression and protective immune memory. Collectively, oral reovirus virotherapy is a feasible and effective immunotherapeutic strategy in preclinical studies.

Abstract Water structures at electrolyte/electrode interfaces play a crucial role in determining the selectivity and kinetics of electrochemical reactions. Despite extensive experimental and theoretical efforts, atomic-level details of ion-specific water structures on metal surfaces remain unclear. Here we show, using scanning tunneling microscopy and noncontact atomic force microscopy, that we can visualize water layers containing alkali metal cations on a charged Au(111) surface with atomic resolution. Our results reveal that Li+ cations are elevated from the surface, facilitating the formation of an ice-like water layer between the Li+ cations and the surface. In contrast, K+ and Cs+ cations are in direct contact with the surface. We observe that the water network structure transitions from a hexagonal arrangement with Li+ to a distorted hydrogen-bonding configuration with Cs+. These observations are consistent with surface-enhanced infrared absorption spectroscopy data and suggest that alkali metal cations significantly impact hydrogen evolution reaction kinetics and efficiency. Our findings provide insights into ion-specific water structures on metal surfaces and underscore the critical role of spectator ions in electrochemical processes.

Abstract The synthesis of sequence-regulated oligosulfates has not yet been established due to the difficulties in precise reactivity control. In this work, we report an example of a multi-directional divergent iterative method to furnish oligosulfates based on a chain homologation approach, in which the fluorosulfate unit is regenerated. The oligosulfate sequences are determined by high resolution mass spectrometry of the hydrolyzed fragments, and polysulfate periodic copolymers are synthesized by using oligomeric bisfluorosulfates in a bi-directional fashion. The synthetic utility of this iterative ligation is demonstrated by preparing crosslinked network polymers as synthetic adhesive materials.

Abstract Surface condensation control strategies are crucial but commonly require relatively tedious, time-consuming, and expensive techniques for surface-chemical and topographical engineering. Here we report a strategy to alter surface condensation behavior without resorting to any molecule-type or topographical transmutations. After ultrafast contact of liquids with and removal from surfaces, the condensation rate and density of water droplets on the surfaces decrease, the extent of which is positively correlated with the polarity of the liquid and the duration of contact. The liquid contact-induced condensation rate/density decrease (LCICD) can be attributed to the decrease of nucleation site density resulted from the liquid contact-induced adaption of surface molecular conformation. Based on this, we find that LCICD is applicable to various surfaces, on condition that there are flexible segments capable of shielding at least part of nucleation sites through changing the conformation under liquid contact induction. Leveraging the LCICD effect, we achieve erasable information storage on diverse substrates. Furthermore, our strategy holds promise for controlling condensation of other substances since LCICD is not specific to the water condensation process.

Abstract The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Abstract Exploring the dynamic structural evolution of electrocatalysts during reactions represents a fundamental objective in the realm of electrocatalytic mechanism research. In pursuit of this objective, we synthesized PhenPtCl2 nanosheets, revealing a N2-Pt-Cl2 coordination structure through various characterization techniques. Remarkably, the electrocatalytic performance of these PhenPtCl2 nanosheets for hydrogen evolution reaction (HER) surpasses that of the commercial Pt/C catalyst across the entire pH range. Furthermore, our discovery of the dynamic coordination changes occurring in the N2-Pt-Cl2 active sites during the electrocatalytic process, as clarified through in situ Raman and X-ray photoelectron spectroscopy, is particularly noteworthy. These changes transition from Phen-Pt-Cl2 to Phen-Pt-Cl and ultimately to Phen-Pt. The Phen-Pt intermediate plays a pivotal role in the electrocatalytic HER, dynamically coordinating with Cl- ions in the electrolyte. Additionally, the unsaturated, two-coordinated Pt within Phen-Pt provides additional space and electrons to enhance both H+ adsorption and H2 evolution. This research illuminates the intricate dynamic coordination evolution and structural adaptability of PhenPtCl2 nanosheets, firmly establishing them as a promising candidate for efficient and tunable electrocatalysts.

Abstract Interferon-gamma (IFN-γ) signaling is necessary for the proinflammatory activation of macrophages but IFN-γ-independent pathways, for which the initiating stimuli and downstream mechanisms are lesser known, also contribute. Here we identify, by high-content screening, SEPTIN2 (SEPT2) as a negative regulation of IFN-γ-independent macrophage autoactivation. Mechanistically, endoplasmic reticulum (ER) stress induces the expression of SEPT2, which balances the competition between acetylation and ubiquitination of heat shock protein 5 at position Lysine 327, thereby alleviating ER stress and constraining M1-like polarization and proinflammatory cytokine release. Disruption of this negative feedback regulation leads to the accumulation of unfolded proteins, resulting in accelerated M1-like polarization, excessive inflammation and tissue damage. Our study thus uncovers an IFN-γ-independent macrophage proinflammatory autoactivation pathway and suggests that SEPT2 may play a role in the prevention or resolution of inflammation during infection.

Abstract Understanding the genetic basis of rubber tree (Hevea brasiliensis) domestication is crucial for further improving natural rubber production to meet its increasing demand worldwide. Here we provide a high-quality H. brasiliensis genome assembly (1.58 Gb, contig N50 of 11.21 megabases), present a map of genome variations by resequencing 335 accessions and reveal domestication-related molecular signals and a major domestication trait, the higher number of laticifer rings. We further show that HbPSK5, encoding the small-peptide hormone phytosulfokine (PSK), is a key domestication gene and closely correlated with the major domestication trait. The transcriptional activation of HbPSK5 by myelocytomatosis (MYC) members links PSK signaling to jasmonates in regulating the laticifer differentiation in rubber tree. Heterologous overexpression of HbPSK5 in Russian dandelion (Taraxacum kok-saghyz) can increase rubber content by promoting laticifer formation. Our results provide an insight into target genes for improving rubber tree and accelerating the domestication of other rubber-producing plants.

Abstract The generation of high-purity localized trions, dynamic exciton–trion interconversion, and their spatial modulation in two-dimensional (2D) semiconductors are building blocks for the realization of trion-based optoelectronic devices. Here, we present a method for the all-optical control of the exciton-to-trion conversion process and its spatial distributions in a MoS2 monolayer. We induce a nanoscale strain gradient in a 2D crystal transferred on a lateral metal–insulator–metal (MIM) waveguide and exploit propagating surface plasmon polaritons (SPPs) to localize hot electrons. These significantly increase the electrons and efficiently funnel excitons in the lateral MIM waveguide, facilitating complete exciton-to-trion conversion even at ambient conditions. Additionally, we modulate the SPP mode using adaptive wavefront shaping, enabling all-optical control of the exciton-to-trion conversion rate and trion distribution in a reversible manner. Our work provides a platform for harnessing excitonic quasiparticles efficiently in the form of trions at ambient conditions, enabling high-efficiency photoconversion.

The difunctionalization of diazo compounds, traditionally with one nucleophile and one electrophile, is a powerful strategy. Here, the authors develop a path of electrochemical oxidative difunctionalization of diazo compounds with two different nucleophiles.

With advances in robotic technology, the complexity of control of robot has been increasing owing to fundamental von Neumann bottlenecks. Here, we demonstrate coordinated movement by a fully parallel-processable synaptic array with reduced control complexity.

The adoption of photonic synapses with biosimilarity to realize analog signal transmission is of significance in realizing artificial illuminance modulation responses. Here, the authors report a biomimetic ocular prosthesis system based on quantum dots embedded photonic synapses with improved depression properties through mid-gap trap.

The chromatin accessibility landscape and gene regulatory network of pancreatic cancer has not been fully characterised. Here, the authors perform multi-omics analysis of 84 pancreatic cancer organoid lines and reveal gene regulatory networks and distinct molecular subtypes.

Microporous polymers become increasingly attractive as materials for the fabrication of permeable and selective gas separation membranes but separation performance is often limited by broad pore size distribution. Here, the authors design a porous polymer membrane via multi-crosslinking of miscible blends of microporous polymers enabling simultaneous high permeability and selectivity.

The epitranscriptomic regulation of adenomatous polyposis coli (APC) tumour suppressor gene in cancers is unclear. Here the authors show that N6-methyladenosine methylation writer METTL3 downregulates APC by recruiting YTHDF2 for APC mRNA degradation, and that this promotes glycolysis and tumour growth in oesophageal cancers.

Enzalutamide, an approved drug for prostate cancer, acts on TMPRSS2 expression, a key mediator for SARS-CoV-2 infection. Here, the authors characterize the anti-SARS-CoV-2 effects of Enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and in hACE2-transduced Tmprss2 knockout mice and show lack antiviral action in human lung cells and human lung organoids, likely due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells.

Conjugated microporous polymers (CMPs) have great potential in membrane applications but are often brittle. Here, the authors develop an electropolymerization process to form a skin-core architecture which allows them to overcome mechanical limitations while keeping the excellent separation performance of CMP membranes.

The physiological roles of the Golgi reassembly-stacking protein 55 (GRASP55/GORASP55) remain largely elusive. Here, the authors show that the Golgi-resident protein GRASP55 plays a crucial role in lipid homeostasis by regulating intestinal lipid uptake.

Alloy magic-size clusters (MSCs) are difficult to synthesize, in part because so little is known about how they form. Here, the authors produce single-ensemble alloy CdTeSe MSCs at room temperature by mixing prenucleation-stage solutions of CdTe and CdSe, uncovering a formation pathway that may extend to the synthesis of other alloy MSCs.

High mass loading and fast charge transport are two crucial but often mutually exclusive characteristics of pseudocapacitors. Here, the authors address this challenge by making use of block copolymer phase separation in the synthesis of porous carbon fibres as carbon supports for pseudocapacitors.

There are few available models to study neuroendocrine prostate cancer. Here they develop and characterize patient derived organoids from metastatic lesions, use these models to show the role of EZH2 in driving neuroendocrine phenotype, and perform high throughput organoid screening to identify therapeutic drug combinations.

The stereoselective synthesis of polyesters has been achieved via various methods; however, all routes show limited side-chain group functionality. Here the authors synthesize stereoblock polyesters by photoredox ring-opening polymerization of racemic O-carboxyanhydrides that have abundant side-chain functionality.

Film-thermoelectric cooling devices are expected to provide a promising active thermal management solution with the continues increase of the power density of integrated circuit chips and other electronic devices. However, because the microstructure-related performance of thermoelectric films has not been perfectly matched with the device configuration, the potential of planar devices on chip heat dissipation has still not been fully exploited. Here, by liquid Te assistant growth method, highly (00 l) orientated Bi 2 Te 3 -based films which is comparable to single crystals are obtained in polycrystal films in this work. The high mobility stem from high orientation and low lattice thermal conductivity resulting from excess Te induced staggered stacking faults leads to high in-plane zT values ~1.53 and ~1.10 for P-type Bi 0.4 Sb 1.6 Te 3 and N-type Bi 2 Te 3 films, respectively. The planar devices basing on the geometrically designed high orientation films produce a remarkable temperature reduction of ~8.2 K in the hot spot elimination experiment, demonstrating the great benefit of Te assistant growth method for oriented planar Bi 2 Te 3 films and planar devices devices design, and also bring great enlightenment to the next generation active thermal management for integrated circuits., (© 2024. The Author(s).)

Improvements in the polarization of environmentally-friendly perovskite ferroelectrics have proved to be a challenging task in order to replace the toxic Pb-based counterparts. In contrast to common methods by complex chemical composition designs, we have formed Mn-inlaid antiphase boundaries in Mn-doped (K,Na)NbO 3 thin films using pulsed laser deposition method. Here, we observed that mono- or bi-atomic layer of Mn has been identified to inlay along the antiphase boundaries to balance the charges originated from the deficiency of alkali ions and to induce the strain in the KNN films. Thus, rectangular saturated polarization-electric field hysteresis loops have been achieved, with a significantly improved twice remanent polarization of 114 μC/cm 2 with an applied electric field of 606 kV/cm, which can be comparable to that of the typical Pb-based thin films. Moreover, we directly see the Mn occupation at the A-site of KNN perovskite structure using atomic-scale microstructure and composition analysis. The Mn-inlaid antiphase boundary can further enrich the understanding of perovskite crystal structure and give more possibilities for the design and optimization of perovskite materials., (© 2024. The Author(s).)

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)-165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice., (© 2024. The Author(s).)

The ultrahigh flexibility and elasticity achieved in freestanding single-crystalline ferroelectric oxide membranes have attracted much attention recently. However, for antiferroelectric oxides, the flexibility limit and fundamental mechanism in their freestanding membranes are still not explored clearly. Here, we successfully fabricate freestanding single-crystalline PbZrO 3 membranes by a water-soluble sacrificial layer technique. They exhibit good antiferroelectricity and have a commensurate/incommensurate modulated microstructure. Moreover, they also have good shape recoverability when bending with a small radius of curvature (about 2.4 μm for the thickness of 120 nm), corresponding to a bending strain of 2.5%. They could tolerate a maximum bending strain as large as 3.5%, far beyond their bulk counterpart. Our atomistic simulations reveal that this remarkable flexibility originates from the antiferroelectric-ferroelectric phase transition with the aid of polarization rotation. This study not only suggests the mechanism of antiferroelectric oxides to achieve high flexibility but also paves the way for potential applications in flexible electronics., (© 2024. The Author(s).)

Osimertinib (Osi) is a widely used epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). However, the emergence of resistance is inevitable, partly due to the gradual evolution of adaptive resistant cells during initial treatment. Here, we find that Osi treatment rapidly triggers adaptive resistance in tumor cells. Metabolomics analysis reveals a significant enhancement of oxidative phosphorylation (OXPHOS) in Osi adaptive-resistant cells. Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA4-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy., (© 2024. The Author(s).)

Phosphor-glass composites (PGC) are excellent candidates for highly efficient and stable photonic converters; however, their synthesis generally requires harsh procedures and long time, resulting in additional performance loss and energy consumption. Here we develop a rapid synthetic route to PGC within about 10 seconds, which enables uniform dispersion of Y 3 Al 5 O 12 :Ce 3+ (YAG:Ce) phosphor particles through a particle self-stabilization model in molten tellurite glass. Thanks for good wettability between YAG:Ce micro-particles and tellurite glass melt, it creates an energy barrier of 6.94 × 10 5 zJ to prevent atomic-scale contact and sintering of particles in the melt. This in turn allows the generation of YAG:Ce-based PGC as attractive emitters with high quantum efficiency (98.4%) and absorption coefficient (86.8%) that can produce bright white light with luminous flux of 1227 lm and luminous efficiency of 276 lm W -1 under blue laser driving. This work shows a generalizable synthetic strategy for the development of functional glass composites., (© 2024. The Author(s).)

Finding an effective way to greatly tune spin Hall angle in a low power manner is of fundamental importance for tunable and energy-efficient spintronic devices. Recently, topological insulator of Bi 2 Se 3 , having a large intrinsic spin Hall angle, show great capability to generate strong current-induced spin-orbit torques. Here we demonstrate that the spin Hall angle in Bi 2 Se 3 can be effectively tuned asymmetrically and even enhanced about 600% reversibly by applying a bipolar electric field across the piezoelectric substrate. We reveal that the enhancement of spin Hall angle originates from both the charge doping and piezoelectric strain effet on the spin Berry curvature near Fermi level in Bi 2 Se 3 . Our findings provide a platform for achieving low power consumption and tunable spintronic devices., (© 2022. The Author(s).)

Developing low-cost and highly efficient catalysts toward the efficient oxygen evolution reaction (OER) is highly desirable for photoelectrochemical (PEC) water splitting. Herein, we demonstrated that N-incorporation could efficiently activate NiFeO x catalysts for significantly enhancing the oxygen evolution activity and stability of BiVO 4 photoanodes, and the photocurrent density has been achieved up to 6.4 mA cm -2 at 1.23 V (vs. reversible hydrogen electrode (RHE), AM 1.5 G). Systematic studies indicate that the partial substitution of O sites in NiFeO x catalysts by low electronegative N atoms enriched the electron densities in both Fe and Ni sites. The electron-enriched Ni sites conversely donated electrons to V sites of BiVO 4 for restraining V 5+ dissolution and improving the PEC stability, while the enhanced hole-attracting ability of Fe sites significantly promotes the oxygen-evolution activity. This work provides a promising strategy for optimizing OER catalysts to construct highly efficient and stable PEC water splitting devices., (© 2021. The Author(s).)

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.

The Asian monsoon (AM) played an important role in the dynastic history of China, yet it remains unknown whether AM-mediated shifts in Chinese societies affect earth surface processes to the point of exceeding natural variability. Here, we present a dust storm intensity record dating back to the first unified dynasty of China (the Qin Dynasty, 221-207 B.C.E.). Marked increases in dust storm activity coincided with unified dynasties with large populations during strong AM periods. By contrast, reduced dust storm activity corresponded to decreased population sizes and periods of civil unrest, which was co-eval with a weakened AM. The strengthened AM may have facilitated the development of Chinese civilizations, destabilizing the topsoil and thereby increasing the dust storm frequency. Beginning at least 2000 years ago, human activities might have started to overtake natural climatic variability as the dominant controls of dust storm activity in eastern China.

The indica and japonica rice (Oryza sativa) subspecies differ in nitrate (NO 3 - ) assimilation capacity and nitrogen (N) use efficiency (NUE). Here, we show that a major component of this difference is conferred by allelic variation at OsNR2, a gene encoding a NADH/NADPH-dependent NO 3 - reductase (NR). Selection-driven allelic divergence has resulted in variant indica and japonica OsNR2 alleles encoding structurally distinct OsNR2 proteins, with indica OsNR2 exhibiting greater NR activity. Indica OsNR2 also promotes NO 3 - uptake via feed-forward interaction with OsNRT1.1B, a gene encoding a NO 3 - uptake transporter. These properties enable indica OsNR2 to confer increased effective tiller number, grain yield and NUE on japonica rice, effects enhanced by interaction with an additionally introgressed indica OsNRT1.1B allele. In consequence, indica OsNR2 provides an important breeding resource for the sustainable increases in japonica rice yields necessary for future global food security.

Poly-substituted aromatic sulfur compounds are widely found in pharmaceuticals, agrochemicals and organic materials. However, the position that a sulfur moiety can be introduced to is largely restricted to a pre-functionalized site; otherwise, use of electronically biased substrates or auxiliary groups that direct catalysis is required. Here we report a general ortho thiolation of common aryl and heteroaryl iodides via palladium-norbornene cooperative catalysis. Using this approach, an aryl or alky sulfur moiety can be site-selectively introduced at the arene ortho position without using sterically or electronically biased substrates. The arene ipso functionalization is simultaneously achieved through Heck, Suzuki or Sonogashira termination. The reaction is enabled by a unique class of electrophiles in palladium-norbornene cooperative catalysis, which are sulfenamides derived from seven-membered lactams. The broad substrates scope and high chemoselectivity could make this method attractive for synthesis of complex sulfur-containing aromatic compounds.

N-doping is an effective way to increase the electron conductivity of organic semiconductors and achieve ohmic cathode contacts in organic electronics. To avoid the use of difficult-to-handle highly reactive n-dopants, air-stable precursors are widely used nowadays, which could decompose to release reactive species in a subtractive way though always with unwanted and even harmful byproducts during processing. Here, we show that air-stable metals, such as copper, silver and gold, could release free electrons readily in the presence of chelating ligands, as the irreversible coordination reaction between metal ions and the ligands would push the equilibrium between metals and metal ions to the forward direction. By using a well-designed multi-functional electron transport material with a strong nucleophilic quality, 4,7-dimethoxy-1,10-phenanthroline (p-MeO-Phen), silver could function as an n-dopant stronger than cesium and could be used to fabricate organic light-emitting diodes with higher performance than the cesium-doped control device.

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generate the first single cell integrated map of chromatin accessibility and transcriptome in early embryos and demonstrate the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states. The ability to obtain these two layers of omics data will help provide more accurate definitions of "single cell state" and enable the deconvolution of regulatory heterogeneity from complex cell populations.

The mid-Pleistocene transition (MPT) is widely recognized as a shift in paleoclimatic periodicity from 41- to 100-kyr cycles, which largely reflects integrated changes in global ice volume, sea level, and ocean temperature from the marine realm. However, much less is known about monsoon-induced terrestrial vegetation change across the MPT. Here, on the basis of a 1.7-million-year δ 13 C record of loess carbonates from the Chinese Loess Plateau, we document a unique MPT reflecting terrestrial vegetation changes from a dominant 23-kyr periodicity before 1.2 Ma to combined 100, 41, and 23-kyr cycles after 0.7 Ma, very different from the conventional MPT characteristics. Model simulations further reveal that the MPT transition likely reflects decreased sensitivity of monsoonal hydroclimate to insolation forcing as the Northern Hemisphere became increasingly glaciated through the MPT. Our proxy-model comparison suggests varied responses of temperature and precipitation to astronomical forcing under different ice/CO 2 boundary conditions, which greatly improves our understanding of monsoon variability and dynamics from the natural past to the anthropogenic future.

Most tumor cells take up more glucose than normal cells. Splicing dysregulation is one of the molecular hallmarks of cancer. However, the role of splicing factor in glucose metabolism and tumor development remains poorly defined. Here, we show that upon glucose intake, the splicing factor SRSF5 is specifically induced through Tip60-mediated acetylation on K125, which antagonizes Smurf1-mediated ubiquitylation. SRSF5 promotes the alternative splicing of CCAR1 to produce CCAR1S proteins, which promote tumor growth by enhancing glucose consumption and acetyl-CoA production. Conversely, upon glucose starvation, SRSF5 is deacetylated by HDAC1, and ubiquitylated by Smurf1 on the same lysine, resulting in proteasomal degradation of SRSF5. The CCAR1L proteins accumulate to promote apoptosis. Importantly, SRSF5 is hyperacetylated and upregulated in human lung cancers, which correlates with increased CCAR1S expression and tumor progression. Thus, SRSF5 responds to high glucose to promote cancer development, and SRSF5-CCAR1 axis may be valuable targets for cancer therapeutics.

Despite the great promise of armchair graphene nanoribbons (aGNRs) as high-performance semiconductors, practical band-gap engineering of aGNRs remains an unmet challenge. Given that width and edge structures are the two key factors for modulating band-gaps of aGNRs, a reliable synthetic method that allows control of both factors would be highly desirable. Here we report a simple modular strategy for efficient preparation of N = 6 aGNR, the narrowest member in the N = 3p (p: natural number) aGNR family, and two unsymmetrically edge-functionalized GNRs that contain benzothiadiazole and benzotriazole moieties. The trend of band-gap transitions among these GNRs parallels those in donor-acceptor alternating conjugated polymers. In addition, post-functionalization of the unsymmetrical heterocyclic edge via C-H borylation permits further band-gap tuning. Therefore, this method opens the door for convenient band-gap engineering of aGNRs through modifying the heteroarenes on the edge.

To overcome the fundamental challenge of the weak natural response of antiferromagnetic materials under a magnetic field, voltage manipulation of antiferromagnetic interaction is developed to realize ultrafast, high-density, and power efficient antiferromagnetic spintronics. Here, we report a low voltage modulation of Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction via ionic liquid gating in synthetic antiferromagnetic multilayers of FeCoB/Ru/FeCoB and (Pt/Co) 2 /Ru/(Co/Pt) 2 . At room temperature, the distinct voltage control of transition between antiferromagnetic and ferromagnetic ordering is realized and up to 80% of perpendicular magnetic moments manage to switch with a small-applied voltage bias of 2.5 V. We related this ionic liquid gating-induced RKKY interaction modification to the disturbance of itinerant electrons inside synthetic antiferromagnetic heterostructure and the corresponding change of its Fermi level. Voltage tuning of RKKY interaction may enable the next generation of switchable spintronics between antiferromagnetic and ferromagnetic modes with both fundamental and practical perspectives.

In crops, nitrogen directly determines productivity and biomass. However, the improvement of nitrogen utilization efficiency (NUE) is still a major challenge in modern agriculture. Here, we report the characterization of are1, a genetic suppressor of a rice fd-gogat mutant defective in nitrogen assimilation. ARE1 is a highly conserved gene, encoding a chloroplast-localized protein. Loss-of-function mutations in ARE1 cause delayed senescence and result in 10-20% grain yield increases, hence enhance NUE under nitrogen-limiting conditions. Analysis of a panel of 2155 rice varieties reveals that 18% indica and 48% aus accessions carry small insertions in the ARE1 promoter, which result in a reduction in ARE1 expression and an increase in grain yield under nitrogen-limiting conditions. We propose that ARE1 is a key mediator of NUE and represents a promising target for breeding high-yield cultivars under nitrogen-limiting condition.

The soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) constitute the core machinery for membrane fusion during eukaryotic cell vesicular trafficking. However, how the assembly of the SNARE complex is initiated is unknown. Here we report that Sec3, a component of the exocyst complex that mediates vesicle tethering during exocytosis, directly interacts with the t-SNARE protein Sso2. This interaction promotes the formation of an Sso2-Sec9 'binary' t-SNARE complex, the early rate-limiting step in SNARE complex assembly, and stimulates membrane fusion. The crystal structure of the Sec3-Sso2 complex suggests that Sec3 binding induces conformational changes of Sso2 that are crucial for the relief of its auto-inhibition. Interestingly, specific disruption of the Sec3-Sso2 interaction in cells blocks exocytosis without affecting the function of Sec3 in vesicle tethering. Our study reveals an activation mechanism for SNARE complex assembly, and uncovers a role of the exocyst in promoting membrane fusion in addition to vesicle tethering.

In plants, auxin signalling is initiated by the auxin-promoted interaction between the auxin receptor TIR1, an E3 ubiquitin ligase, and the Aux/IAA transcriptional repressors, which are subsequently degraded by the proteasome. Gain-of-function mutations in the highly conserved domain II of Aux/IAAs abolish the TIR1-Aux/IAA interaction and thus cause an auxin-resistant phenotype. Here we show that peptidyl-prolyl isomerization of rice OsIAA11 catalysed by LATERAL ROOTLESS2 (LRT2), a cyclophilin-type peptidyl-prolyl cis/trans isomerase, directly regulates the stability of OsIAA11. NMR spectroscopy reveals that LRT2 efficiently catalyses the cis/trans isomerization of OsIAA11. The lrt2 mutation reduces OsTIR1-OsIAA11 interaction and consequently causes the accumulation of a higher level of OsIAA11 protein. Moreover, knockdown of the OsIAA11 expression partially rescues the lrt2 mutant phenotype in lateral root development. Together, these results illustrate cyclophilin-catalysed peptidyl-prolyl isomerization promotes Aux/IAA degradation, as a mechanism regulating auxin signalling.