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Spherical geometry, adaptive optics, and highly dense network of neurons bridging the eye with the visual cortex, are the primary features of human eyes which enable wide field-of-view (FoV), low aberration, excellent adaptivity, and preprocessing of perceived visual information. Therefore, fabricating spherical artificial eyes has garnered enormous scientific interest. However, fusing color vision, in-device preprocessing and optical adaptivity into spherical artificial eyes has always been a tremendous challenge. Herein, we demonstrate a bionic eye comprising tunable liquid crystal optics, and a hemispherical neuromorphic retina with filter-free color vision, enabled by wavelength dependent bidirectional synaptic photo-response in a metal-oxide nanotube/perovskite nanowire hybrid structure. Moreover, by tuning the color selectivity with bias, the device can reconstruct full color images. This work demonstrates a unique approach to address the color vision and optical adaptivity issues associated with artificial eyes that can bring them to a new level approaching their biological counterparts.

Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we show that several haloarchaea of the family Halobacteriaceae display a life cycle resembling that of Streptomyces bacteria. Strain YIM 93972 (isolated from a salt marsh) undergoes cellular differentiation into mycelia and spores. Other closely related strains are also able to form mycelia, and comparative genomic analyses point to gene signatures (apparent gain or loss of certain genes) that are shared by members of this clade within the Halobacteriaceae. Genomic, transcriptomic and proteomic analyses of non-differentiating mutants suggest that a Cdc48-family ATPase might be involved in cellular differentiation in strain YIM 93972. Additionally, a gene encoding a putative oligopeptide transporter from YIM 93972 can restore the ability to form hyphae in a Streptomyces coelicolor mutant that carries a deletion in a homologous gene cluster (bldKA-bldKE), suggesting functional equivalence. We propose strain YIM 93972 as representative of a new species in a new genus within the family Halobacteriaceae, for which the name Actinoarchaeum halophilum gen. nov., sp. nov. is herewith proposed. Our demonstration of a complex life cycle in a group of haloarchaea adds a new dimension to our understanding of the biological diversity and environmental adaptation of archaea.

T helper 17 (Th17) cells are a subset of CD4+ T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood. Here, we reveal that deletion of RNA 5-methylcytosine (m5C) methyltransferase Nsun2 in mouse CD4+ T cells specifically inhibits Th17 cell differentiation and alleviates Th17 cell-induced colitis pathogenesis. Mechanistically, RoRγt can recruit Nsun2 to chromatin regions of their targets, including Il17a and Il17f, leading to the transcription-coupled m5C formation and consequently enhanced mRNA stability. Our study demonstrates a m5C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.

Oxide-ion conductors are important in various applications such as solid-oxide fuel cells. Although zirconia-based materials are widely utilized, there remains a strong motivation to discover electrolyte materials with higher conductivity that lowers the working temperature of fuel cells, reducing cost. Oxide-ion conductors with hexagonal perovskite related structures are rare. Herein, we report oxide-ion conductors based on a hexagonal perovskite-related oxide Ba7Nb4MoO20. Ba7Nb3.9Mo1.1O20.05 shows a wide stability range and predominantly oxide-ion conduction in an oxygen partial pressure range from 2 × 10−26 to 1 atm at 600 °C. Surprisingly, bulk conductivity of Ba7Nb3.9Mo1.1O20.05, 5.8 × 10−4 S cm−1, is remarkably high at 310 °C, and higher than Bi2O3- and zirconia-based materials. The high conductivity of Ba7Nb3.9Mo1.1O20.05 is attributable to the interstitial-O5 oxygen site, providing two-dimensional oxide-ion O1−O5 interstitialcy diffusion through lattice-O1 and interstitial-O5 sites in the oxygen-deficient layer, and low activation energy for oxide-ion conductivity. Present findings demonstrate the ability of hexagonal perovskite related oxides as superior oxide-ion conductors.

There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSNs) functionalized with EGFR-targeting aptamers (MSN-AP) specifically recognize and bind blood-borne negatively charged oncogenic exosomes (A-Exo), and tow A-Exo across hepatobiliary layers and Oddi’s sphincter into the small intestine. MSN-AP specifically distinguish and bind A-Exo from interfering exosomes in cell culture and rat and patient blood to form MSN-AP and A-Exo conjugates (MSN-Exo) that transverse hepatocytes, cholangiocytes, and endothelial monolayers via endocytosis and exocytosis mechanisms, although Kupffer cells have been shown to engulf some MSN-Exo. Blood MSN-AP significantly decreased circulating A-Exo levels, sequentially increased intestinal A-Exo and attenuated A-Exo-induced lung metastasis in mice. This study opens an innovative avenue to relocate blood-borne life-threatening biohazards to the intestine., Oncogenic exosomes can circulate in the blood, but their selective removal has not been possible. Here the authors show that aptamer-functionalised mesoporous silica nanoparticles can find to a specific population of circulating exosomes and eliminate them via the hepatobiliary route.

Nonpolar alkyl moieties, especially methyl group, are frequently used to modify bioactive molecules during lead optimization in medicinal chemistry. Thus transition-metal catalyzed alkylative cross-coupling reactions by using readily available and environmentally benign C–O electrophiles have been established as powerful tools to install alkyl groups, however, the C(sp3)–C(sp2) cross-coupling via asymmetric activation of aromatic C–O bond for the synthesis of alkylated chiral compounds remains elusive. Here, we unlock a C(sp3)–C(sp2) cross-coupling via enantioselective activation of aromatic C–O bond for the efficient synthesis of versatile axially chiral 2-alkyl-2’-hydroxyl-biaryl compounds. By employing a unique chiral N-heterocyclic carbene ligand, this transformation is accomplished via nickel catalysis with good enantiocontrol. Mechanistic studies indicate that bis-ligated nickel complexes might be formed as catalytically active species in the enantioselective alkylative cross-coupling. Moreover, further derivation experiments suggest this developed methodology holds great promise for complex molecule synthesis and asymmetric catalysis.

Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention., Abnormal placentation is associated with recurrent spontaneous abortion (RSA) risk. Here the authors report that low embryonic villous succinate level associates with risk of RSA in patients, and increasing succinate levels is sufficient to reduce the incidence rate in a mouse model of spontaneous abortion.

Cotton is an important natural fiber crop, however, its comprehensive and high-resolution gene map is lacking. Here we integrate four complementary high-throughput techniques, including Pacbio long read Iso-seq, strand-specific RNA-seq, CAGE-seq, and PolyA-seq, to systematically explore the transcription landscape across 16 tissues or different organ types in Gossypium arboreum. We devise a computational pipeline, named IGIA, to reconstruct accurate gene structures from the integrated data. Our results reveal a dynamic and diverse transcriptional map in cotton: tissue-specific gene expression, alternative usage of TSSs and polyadenylation sites, hotspot of alternative splicing, and transcriptional read-through. These regulated events affect many genes in various aspects such as gain or loss of functional RNA motifs and protein domains, fine-tuning of DNA binding activity, and co-regulation for genes in the same complex or pathway. The methods and findings provide valuable resources for further functional genomic studies such as understanding natural SNP variations for plant community., In-depth functional characterization of genomes relies on comprehensive transcriptome data. Here, the authors employ four complementary RNA sequencing technologies to explore the transcription landscape across 16 tissues or different organ types in diploid A genome cotton using a newly developed computational pipeline.

The electron-phonon coupling (EPC) in a material is at the frontier of the fundamental research, underlying many quantum behaviors. van der Waals heterostructures (vdWHs) provide an ideal platform to reveal the intrinsic interaction between their electrons and phonons. In particular, the flexible van der Waals stacking of different atomic crystals leads to multiple opportunities to engineer the interlayer phonon modes for EPC. Here, in hBN/WS2 vdWH, we report the strong cross-dimensional coupling between the layer-breathing phonons well extended over tens to hundreds of layer thick vdWH and the electrons localized within the few-layer WS2 constituent. The strength of such cross-dimensional EPC can be well reproduced by a microscopic picture through the mediation by the interfacial coupling and also the interlayer bond polarizability model in vdWHs. The study on cross-dimensional EPC paves the way to manipulate the interaction between electrons and phonons in various vdWHs by interfacial engineering for possible interesting physical phenomena., The strength of electron-phonon coupling can be directly probed by Raman spectroscopy. Here, the authors use low-frequency Raman spectroscopy to unveil the existence of a strong cross-dimensional coupling between the bulk-like layer-breathing phonons in an hBN/WS2 heterostructure and the electrons localized within its few-layer WS2 constituent.

Protein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates translational control at the ISR core. To provide insight into the mechanism of translational control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms bound with its nucleotide exchange factor eIF2B by electron cryomicroscopy. The structures reveal that eIF2 undergoes large rearrangements to promote binding of eIF2α to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2αP binding to eIF2B, suggesting that the higher affinity of eIF2αP for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex., During the integrated stress response, translation is modulated through the phosphorylation of translation initiation factor eIF2 and the formation of a complex with eIF2B. Here the authors present structures of the eIF2:eIF2B complex with and without phosphorylation, shedding light on how eIF2 phosphorylation regulates translation.

Metastasis is the leading cause of cancer-related death. Despite the recent advancements in cancer treatment, there is currently no approved therapy for metastasis. The present study reveals a potent and selective activity of PRAK in the regulation of tumor metastasis. While showing no apparent effect on the growth of primary breast cancers or subcutaneously inoculated tumor lines, Prak deficiency abrogates lung metastases in PyMT mice or mice receiving intravenous injection of tumor cells. Consistently, PRAK expression is closely associated with metastatic risk in human cancers. Further analysis indicates that loss of function of PRAK leads to a pronounced inhibition of HIF-1α protein synthesis, possibly due to reduced mTORC1 activities. Notably, pharmacological inactivation of PRAK with a clinically relevant inhibitor recapitulates the anti-metastatic effect of Prak depletion, highlighting the therapeutic potential of targeting PRAK in the control of metastasis., Metastasis is one of the leading causes of cancer-related death. Here, the authors report a pro-metastatic role of PRAK in breast cancer lung metastasis via a mechanism involving enhanced HIF-1α translation, and propose PRAK targeting as a strategy to treat metastasis.

Qubit initialization is a critical task in quantum computation and communication. Extensive efforts have been made to achieve this with high speed, efficiency and scalability. However, previous approaches have either been measurement-based and required fast feedback, suffered from crosstalk or required sophisticated calibration. Here, we report a fast and high-fidelity reset scheme, avoiding the issues above without any additional chip architecture. By modulating the flux through a transmon qubit, we realize a swap between the qubit and its readout resonator that suppresses the excited state population to 0.08% $\pm$ 0.08% within 34 ns (284 ns if photon depletion of the resonator is required). Furthermore, our approach (i) can achieve effective second excited state depletion, (ii) has negligible effects on neighbouring qubits, and (iii) offers a way to entangle the qubit with an itinerant single photon, useful in quantum communication applications., Comment: 38 pages, 15 figures

There are no non-hormonal male contraceptives currently on the market despite decades of efforts toward the development of “male pills”. Here, we report that triptonide, a natural compound purified from the Chinese herb Tripterygium Wilfordii Hook F displays reversible male contraceptive effects in both mice and monkeys. Single daily oral doses of triptonide induces deformed sperm with minimal or no forward motility (close to 100% penetrance) and consequently male infertility in 3–4 and 5–6 weeks in mice and cynomolgus monkeys, respectively. Male fertility is regained in ~4–6 weeks after cessation of triptonide intake in both species. Either short- or long-term triptonide treatment causes no discernable systematic toxic side effects based on histological examination of vital organs in mice and hematological and serum biochemical analyses in monkeys. Triptonide appears to target junction plakoglobin and disrupts its interactions with SPEM1 during spermiogenesis. Our data further prove that targeting late spermiogenesis represents an effective strategy for developing non-hormonal male contraceptives., No male contraceptive pills are currently available. Here, the authors use triptonide, a compound derived from a Chinese plant, to deform sperm so that they cannot move properly, thereby causing reversible infertility in male mice and monkeys.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen–antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections., Here, the authors identify and characterize two mouse-derived monoclonal antibodies against SARS-CoV-2 spike protein that target different epitopes in RBD and block the interaction S/ACE2 and show that a formulated humanized version cocktail exhibits prophylaxis and therapeutic antiviral effects in an hACE2-adenovector expressed mouse model.