Search

Abstract While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome’s role as biomarkers and potential targets for promoting healthy aging.

Abstract Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis. AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.

Abstract Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.

Abstract Controlling the concentrations of H2O and CO2 at the reaction interface is crucial for achieving efficient electrochemical CO2 reduction. However, precise control of these variables during catalysis remains challenging, and the underlying mechanisms are not fully understood. Herein, guided by a multi-physics model, we demonstrate that tuning the local H2O/CO2 concentrations is achievable by thin polymer coatings on the catalyst surface. Beyond the often-explored hydrophobicity, polymer properties of gas permeability and water-uptake ability are even more critical for this purpose. With these insights, we achieve CO2 reduction on copper with Faradaic efficiency exceeding 87% towards multi-carbon products at a high current density of −2 A cm−2. Encouraging cathodic energy efficiency (>50%) is also observed at this high current density due to the substantially reduced cathodic potential. Additionally, we demonstrate stable CO2 reduction for over 150 h at practically relevant current densities owning to the robust reaction interface. Moreover, this strategy has been extended to membrane electrode assemblies and other catalysts for CO2 reduction. Our findings underscore the significance of fine-tuning the local H2O/CO2 balance for future CO2 reduction applications.

Abstract Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.

Abstract Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V−1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Abstract The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Abstract Native mass spectrometry (MS) is a powerful technique for interrogating membrane protein complexes and their interactions with other molecules. A key aspect of the technique is the ability to preserve native-like structures and noncovalent interactions, which can be challenging depending on the choice of detergent. Different strategies have been employed to reduce charge on protein complexes to minimize activation and preserve non-covalent interactions. Here, we report the synthesis of a class of polyamine detergents tailored for native MS studies of membrane proteins. These detergents, a series of spermine covalently attached to various alkyl tails, are exceptional charge-reducing molecules, exhibiting a ten-fold enhanced potency over spermine. Addition of polyamine detergents to proteins solubilized in maltoside detergents results in improved, charge-reduced native mass spectra and reduced dissociation of subunits. Polyamine detergents open new opportunities to investigate membrane proteins in different detergent environments that have thwarted previous native MS studies.

Abstract Retrosynthesis analysis is an important task in organic chemistry with numerous industrial applications. Previously, machine learning approaches employing natural language processing techniques achieved promising results in this task by first representing reactant molecules as strings and subsequently predicting reactant molecules using text generation or machine translation models. Chemists cannot readily derive useful insights from traditional approaches that rely largely on atom-level decoding in the string representations, because human experts tend to interpret reactions by analyzing substructures that comprise a molecule. It is well-established that some substructures are stable and remain unchanged in reactions. In this paper, we developed a substructure-level decoding model, where commonly preserved portions of product molecules were automatically extracted with a fully data-driven approach. Our model achieves improvement over previously reported models, and we demonstrate that its performance can be boosted further by enhancing the accuracy of these substructures. Analyzing substructures extracted from our machine learning model can provide human experts with additional insights to assist decision-making in retrosynthesis analysis.

ATP13A2 is a lysosomal polyamine transporter, mutated in several diseases including juvenile-onset Parkinson’s disease. Here, the authors report structures of human ATP13A2 in six distinct intermediate states, illustrating most of its conformational cycle.

Nutrient sensing impinges on the autophagosome biogenesis. Here, the authors present evidence that plant energy sensing regulates the autophagosome closure by modulating the phosphorylation status and localization of the ESCRT machinery.

Many transcriptomic pathways in the liver show circadian rhythms, which have been reported to be disrupted in aged mice. Here the authors report that the expression of transcription factor Egr-1 decreases and its rhythm is shifted with age in the liver of male mice, and that deletion of Egr-1 results in increased liver fat accumulation.

Shoot branching is critical in determining soybean yield. Here, the authors report natural variation of Dt2 in controlling soybean branching number and the interaction of Dt2 with GmAgl22 and GmSoc1a to activate transcription of GmAp1a and GmAp1d.

Here the authors show that a RalGAPα1-RalA signal nexus regulates calcium homeostasis in cardiomyocytes via the calcium pump SERCA2a, which plays a protective role to maintain cardiac function under pressure overload conditions.

Insulin promotes hepatic lipogenesis, though underlying regulation remains unclear. Here the authors show that insulin translocates TRIM24 from the nucleus into cytosolic P-bodies to stabilise hepatic Pparγ mRNA, and that inactivation of TRIM24 promotes Pparγ degradation and alleviates hepatosteatosis.

CH4 oxidation to high value chemicals under mild conditions through photocatalysis confronts critical issues regarding both conversion and selectivity. Here, atomic Pd and oxygen vacancies were integrated on In2O3 nanorods, leading to visible-driven CH4 conversion with a remarkable yield of oxygenates and high selectivity of primary products.

Electrochemical H2O oxidation to H2O2 is challenged by the competitive O2 evolution reaction. Here, the authors report a CO2/carbonate mediation approach to steering the H2O oxidation pathway from O2 evolution to H2O2 generation.

Mitochondrial function is important for muscle maintenance and function, and mitochondrial proteolysis maintains mitochondrial integrity and function. Here the authors report that that loss of LONP1-dependent mitochondrial proteolysis in muscle causes reduced muscle mass and strength via activation of autophagy.

Modifying the interlayer spacing in two-dimensional materials is an effective approach to tune their chemical and physical properties. Here the authors report that intercalation of Pt atoms into cerium-doped MoS2 enables adjusting the interlayer spacing bidirectionally and reversibly.

The preparation of chiral monolayer-protected metal clusters is interesting for their potential applications in a variety of fields, including catalysis. Here, the authors synthesize chiral Ag14 nanoclusters in an all-achiral environment, and decipher the origin of chirality at the molecular level; the solvent choice is key to achieve homochiral crystallization.

Nano-lamellar materials with ultrahigh strengths are highly desirable for technological applications. Here the authors report a nanolamellar architecturing approach by utilizing coherent L12 structures to achieve ultrahigh strength and ductility in Ni-Fe-Co-Cr-Al-Ti multicomponent alloys.

Developing new click chemistry reactions for robust molecular assembly remains challenging. Here the authors report a light-induced primary amines and o-nitrobenzyl alcohols photoclick cyclization for rapid and modular functionalization of small molecules and native biomolecules, in vitro and in living systems.

Here, the authors synthesize a variety of ultra-thin III–V single crystals, ranging from ultra-narrow to wide bandgap semiconductors, through enhancing the interfacial interaction between the III–V crystals and the growth substrates.

Electrochemical CO2 reduction to liquid fuels is limited by low product concentrations and formation of mixtures with traditional liquid electrolytes. Here the authors report an all-solid-state system for a continuous generation of high-purity and high-concentration formic acid vapors and solutions.

The ultrathin oxide nanosheets obtained through previous approaches usually exhibit amorphism or polycrystallinity, which limit their properties towards electronic devices. Here, the authors synthesize ultrathin antimony oxide single crystals with high dielectric constant (~100) and large breakdown voltage (~5.7 GV m−1).

Extracellular vesicles (EVs) containing miRNAs or proteins can coordinate metabolic responses between tissues. Here the authors demonstrate that during lipid overload, the liver secretes miRNA-containing EVs through a Ggpps-Rab27 dependent mechanism, which controls adipose tissue lipid storage capacity.

Forest management may play an important role in climate change mitigation. Here, Tong et al. combine remote sensing and machine learning modelling to map forest cover dynamics in southern China during 2002–2017, showing effects on carbon sequestration that are extensive but of uncertain longevity and possible negative impact on soil water.

Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.

The potential of flexible organic/inorganic hybrids for thermoelectrics is limited by the inability to control their microstructure. Here, the authors demonstrate polymer-nanoparticle hybrids with a monodispersed, periodic nanophase that shows high thermoelectric performance at room temperature.

If decorated with the right surface modifications, nanoparticles can function as Trojan horses, transporting cell death-facilitating compounds to tumor cells. Here, the authors prepare a particle with four enzyme-like activities and show that ferritin can direct nanoparticles to tumor cells.

Precise control of the growth of transition metal dichalcogenides layers in atomically thin van der Waals heterostructures has gained significant attention. Here, the authors report 100% overlapped vertical ReS2/WS2heterostructures by utilizing the twinned growth behaviour of two-dimensional materials.

Cotton plants are characterized by the presence of darkly pigmented glands that accumulate metabolites that contribute to plant defence but limit the use of cottonseed as food. Here, Ma et al. provide evidence that GoPGF, a bHLH transcription factor, is responsible for gland formation.

Astronomical precision spectroscopy underpins searches for life beyond Earth, direct observation of the expanding Universe and constraining the potential variability of physical constants on cosmological scales. Laser frequency combs can provide the required accurate and precise calibration to the astronomical spectrographs. For cosmological studies, extending the calibration with such astrocombs to the ultraviolet spectral range is desirable, however, strong material dispersion and large spectral separation from the established infrared laser oscillators have made this challenging. Here, we demonstrate astronomical spectrograph calibration with an astrocomb in the ultraviolet spectral range below 400 nm. This is accomplished via chip-integrated highly nonlinear photonics in periodically-poled, nano-fabricated lithium niobate waveguides in conjunction with a robust infrared electro-optic comb generator, as well as a chip-integrated microresonator comb. These results demonstrate a viable route towards astronomical precision spectroscopy in the ultraviolet and could contribute to unlock the full potential of next-generation ground-based and future space-based instruments., (© 2024. The Author(s).)

Global warming is increasingly exacerbating biodiversity loss. Populations locally adapted to spatially heterogeneous environments may respond differentially to climate change, but this intraspecific variation has only recently been considered when modelling vulnerability under climate change. Here, we incorporate intraspecific variation in genomic offset and ecological niche modelling to estimate climate change-driven vulnerability in two bird species in the Sino-Himalayan Mountains. We found that the cold-tolerant populations show higher genomic offset but risk less challenge for niche suitability decline under future climate than the warm-tolerant populations. Based on a genome-niche index estimated by combining genomic offset and niche suitability change, we identified the populations with the least genome-niche interruption as potential donors for evolutionary rescue, i.e., the populations tolerant to climate change. We evaluated potential rescue routes via a landscape genetic analysis. Overall, we demonstrate that the integration of genomic offset, niche suitability modelling, and landscape connectivity can improve climate change-driven vulnerability assessments and facilitate effective conservation management., (© 2022. The Author(s).)

Soliton microcombs provide a versatile platform for realizing fundamental studies and technological applications. To be utilized as frequency rulers for precision metrology, soliton microcombs must display broadband phase coherence, a parameter characterized by the optical phase or frequency noise of the comb lines and their corresponding optical linewidths. Here, we analyse the optical phase-noise dynamics in soliton microcombs generated in silicon nitride high-Q microresonators and show that, because of the Raman self-frequency shift or dispersive-wave recoil, the Lorentzian linewidth of some of the comb lines can, surprisingly, be narrower than that of the pump laser. This work elucidates information about the physical limits in phase coherence of soliton microcombs and illustrates a new strategy for the generation of spectrally coherent light on chip., (© 2022. The Author(s).)

Earth system models (ESMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6) experiment exhibit a well-known summertime warm bias in mid-latitude land regions - most notably in the central contiguous United States (CUS). The dominant source of this bias is still under debate. Using validated datasets and both coupled and off-line modeling, we find that the CUS summertime warm bias is driven by the incorrect partitioning of evapotranspiration (ET) into its canopy transpiration and soil evaporation components. Specifically, CMIP6 ESMs do not effectively use available rootzone soil moisture for summertime transpiration and instead rely excessively on shallow soil and canopy-intercepted water storage to supply ET. As such, expected summertime precipitation deficits in CUS induce a negative ET bias into CMIP6 ESMs and a corresponding positive temperature bias via local land-atmosphere coupling. This tendency potentially biases CMIP6 projections of regional water stress and summertime air temperature variability under elevated CO 2 conditions., (© 2022. The Author(s).)

Silk fibre mechanical properties are attributed to the development of a multi-scale hierarchical structure during spinning. By careful ex vivo processing of a B. mori silkworm silk solution we arrest the spinning process, freezing-in mesoscale structures corresponding to three distinctive structure development stages; gelation, fibrilization and the consolidation phase identified in this work, a process highlighted by the emergence and extinction of 'water pockets'. These transient water pockets are a manifestation of the interplay between protein dehydration, phase separation and nanofibril assembly, with their removal due to nanofibril coalescence during consolidation. We modeled and validated how post-draw improves mechanical properties and refines a silk's hierarchical structure as a result of consolidation. These insights enable a better understanding of the sequence of events that occur during spinning, ultimately leading us to propose a robust definition of when a silkworm silk is actually 'spun'.

The Asian monsoon variations under global temperature changes during the Pliocene are still debated. Here we use a sedimentary record of phytoliths (plant silica) from the Weihe Basin, central China, to explore the history of C 4 grasses and quantitatively reconstruct the Asian monsoon climate since the late Miocene. Our results show that C 4 grasses have been a dominant grassland component since ~11.0 Ma. A subsequent marked decrease in warm- and humid-adapted C 4 grasses and an increase in cool- and dry-adapted C 3 grasses occurred in the Pliocene, ~4.0 Ma; the phytolith-based quantitative reconstruction of mean annual precipitation marked a decrease from 800~1673 mm to 443~900 mm, indicating a reduction in Asian monsoon rainfall in the Pliocene. Our newly obtained records conflict with the hypothesis that the growth of the Tibetan Plateau strengthened the Asian monsoon rainfall. Nevertheless, they emphasize the importance of global temperature as a determinant of Pliocene Asian monsoon variations.

Ultrathin metal layers can be highly active carbon dioxide electroreduction catalysts, but may also be prone to oxidation. Here we construct a model of graphene confined ultrathin layers of highly reactive metals, taking the synthetic highly reactive tin quantum sheets confined in graphene as an example. The higher electrochemical active area ensures 9 times larger carbon dioxide adsorption capacity relative to bulk tin, while the highly-conductive graphene favours rate-determining electron transfer from carbon dioxide to its radical anion. The lowered tin-tin coordination numbers, revealed by X-ray absorption fine structure spectroscopy, enable tin quantum sheets confined in graphene to efficiently stabilize the carbon dioxide radical anion, verified by 0.13 volts lowered potential of hydroxyl ion adsorption compared with bulk tin. Hence, the tin quantum sheets confined in graphene show enhanced electrocatalytic activity and stability. This work may provide a promising lead for designing efficient and robust catalysts for electrolytic fuel synthesis.

Influenza A (H7N9) virus has been causing human infections in China since February 2013, raising serious concerns of potential pandemics. Previous studies demonstrate that human infection is directly linked to live animal markets, and that the internal genes of the virus are derived from H9N2 viruses circulating in the Yangtze River Delta area in Eastern China. Here following analysis of 109 viruses, we show a much higher genetic heterogeneity of the H7N9 viruses than previously reported, with a total of 27 newly designated genotypes. Phylogenetic and genealogical inferences reveal that genotypes G0 and G2.6 dominantly co-circulate within poultry, with most human isolates belonging to the genotype G0. G0 viruses are also responsible for the inter- and intra-province transmissions, leading to the genesis of novel genotypes. These observations suggest the province-specific H9N2 virus gene pools increase the genetic diversity of H7N9 via dynamic reassortments and also imply that G0 has not gained overwhelming fitness and the virus continues to undergo reassortment.

The ground tit (Parus humilis) is endemic to the Tibetan plateau. It is a member of family Paridae but it was long thought to be related to the ground jays because of their morphological similarities. Here we present the ground tit's genome and re-sequence two tits and one ground jay, to clarify this controversially taxonomic status and uncover its genetic adaptations to the Tibetan plateau. Our results show that ground tit groups with two tits and it diverges from them between 7.7 and 9.9 Mya. Compared with other avian genomes, ground tit shows expansion in genes linked to energy metabolism and contractions in genes involved in immune and olfactory perception. We also found positively selected and rapidly evolving genes in hypoxia response and skeletal development. These results indicated that ground tit evolves basic strategies and 'tit-to-jay' change for coping with the life in an extreme environment.

Finding ideal material models for studying the role of catalytic active sites remains a great challenge. Here we propose pits confined in an atomically thin sheet as a platform to evaluate carbon monoxide catalytic oxidation at various sites. The artificial three-atomic-layer thin cerium(IV) oxide sheet with approximately 20% pits occupancy possesses abundant pit-surrounding cerium sites having average coordination numbers of 4.6 as revealed by X-ray absorption spectroscopy. Density-functional calculations disclose that the four- and five-fold coordinated pit-surrounding cerium sites assume their respective role in carbon monoxide adsorption and oxygen activation, which lowers the activation barrier and avoids catalytic poisoning. Moreover, the presence of coordination-unsaturated cerium sites increases the carrier density and facilitates carbon monoxide diffusion along the two-dimensional conducting channels of surface pits. The atomically thin sheet with surface-confined pits exhibits lower apparent activation energy than the bulk material (61.7 versus 122.9 kJ mol(-1)), leading to reduced conversion temperature and enhanced carbon monoxide catalytic ability.