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Free-volume of polymers governs transport of penetrants through polymeric films. Control over free-volume is thus important for the development of better membranes for a wide variety of applications such as gas separations, pharmaceutical purifications and energy storage. To date, methodologies used to create materials with different amounts of free-volume are based primarily on chemical synthesis of new polymers. Here we report a simple methodology for generating free-volume based on the self-assembly of polyethylene-b-polydimethylsiloxane-b-polyethylene triblock copolymers. We have used this method to fabricate a series of membranes with identical compositions but with different amounts of free-volume. We use the term artificial free-volume to refer to the additional free-volume created by self-assembly. The effect of artificial free-volume on selective transport through the membranes was tested using butanol/water and ethanol/water mixtures due to their importance in biofuel production. We found that the introduction of artificial free-volume improves both alcohol permeability and selectivity.

The emergent phenomena such as superconductivity and topological phase transitions can be observed in strict two-dimensional (2D) crystalline matters. Artificial interfaces and one atomic thickness layers are typical 2D materials of this kind. Although having 2D characters, most bulky layered compounds, however, do not possess these striking properties. Here, we report quasi-2D superconductivity in bulky AuTe2Se4/3, where the reduction in dimensionality is achieved through inducing the elongated covalent Te–Te bonds. The atomic-resolution images reveal that the Au, Te, and Se are atomically ordered in a cube, among which are Te–Te bonds of 3.18 and 3.28 Å. The superconductivity at 2.85 K is discovered, which is unraveled to be the quasi-2D nature owing to the Berezinsky–Kosterlitz–Thouless topological transition. The nesting of nearly parallel Fermi sheets could give rise to strong electron–phonon coupling. It is proposed that further depleting the thickness could result in more topologically-related phenomena. [ABSTRACT FROM AUTHOR]

The heat carriers responsible for the unexpectedly large thermal Hall conductivity of the cuprate Mott insulator La2CuO4 were recently shown to be phonons. However, the mechanism by which phonons in cuprates acquire chirality in a magnetic field is still unknown. Here, we report a similar thermal Hall conductivity in two cuprate Mott insulators with significantly different crystal structures and magnetic orders – Nd2CuO4 and Sr2CuO2Cl2 – and show that two potential mechanisms can be excluded – the scattering of phonons by rare-earth impurities and by structural domains. Our comparative study further reveals that orthorhombicity, apical oxygens, the tilting of oxygen octahedra and the canting of spins out of the CuO2 planes are not essential to the mechanism of chirality. Our findings point to a chiral mechanism coming from a coupling of acoustic phonons to the intrinsic excitations of the CuO2 planes. What makes the phonons in cuprates become chiral, as measured by their thermal Hall effect, is an unresolved question. Here, the authors rule out two extrinsic mechanisms and argue that chirality comes from a coupling of acoustic phonons to the intrinsic excitations of the CuO2 planes. [ABSTRACT FROM AUTHOR]

RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box helicase 36 (DHX36) is known to bind and unwind RNA G-quadruplex (rG4) structure but the transcriptome-wide RNA structure remodeling induced by DHX36 binding and the impact on RNA fate remain poorly understood. Here, we investigate the RNA structurome alteration induced by DHX36 depletion. Our findings reveal that DHX36 binding induces structural remodeling not only at the localized binding sites but also on the entire mRNA transcript most pronounced in 3'UTR regions. DHX36 binding increases structural accessibility at 3'UTRs which is correlated with decreased post-transcriptional mRNA abundance. Further analyses and experiments uncover that DHX36 binding sites are enriched for N6-methyladenosine (m 6 A) modification and YTHDF1 binding; and DHX36 induced structural changes may facilitate YTHDF1 binding to m 6 A sites leading to RNA degradation. Altogether, our findings uncover the structural remodeling effect of DHX36 binding and its impact on RNA abundance through regulating m 6 A dependent YTHDF1 binding., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Photon upconversion through lanthanide-doped nanoparticles is of great significance for various applications. However, the current development of upconversion nanoparticles is hindered by the low quantum efficiency and long radiative lifetimes of lanthanide ions, restricting their applications in time-dependent nanophotonics. Herein, we report ultrafast upconversion superfluorescence with a lifetime of sub-2.5 ns in lanthanide-doped nanoparticles at room temperature. Upon excitation with an 800-nm fs-pulsed laser, we achieve a large number (N = 912) of correlated dipoles in Nd 3+ -concentrated nanoparticles, resulting in collective coherent emission with two orders of magnitude amplification in intensity and more than three orders of magnitude improvement in the radiative decay rate. Furthermore, we demonstrate that the control of excitation power and emitting sample length enables the lifetime manipulation of upconversion emission in a wide range from μs to sub-ns, accompanied by the typical superfluorescence signature of Burnham-Chiao ringing. These findings may benefit applications in many advanced technologies such as quantum counting and high-speed super-resolution bioimaging., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Photosynthesis requires chloroplasts, in which most proteins are nucleus-encoded and produced via cytoplasmic translation. The translation initiation factor eIF5B gates the transition from initiation (I) to elongation (E), and the Kozak motif is associated with translation efficiency, but their relationship is previously unknown. Here, with ribosome profiling, we determined the genome-wide I-E transition efficiencies. We discovered that the most prevalent Kozak motif is associated with high I-E transition efficiency in Arabidopsis, rice, and wheat, thus implicating the potential of the Kozak motif in facilitating the I-E transition. Indeed, the effects of Kozak motifs in promoting translation depend on HOT3/eIF5B1 in Arabidopsis. HOT3 preferentially promotes the translation of photosynthesis-associated nuclear genes in a Kozak motif-dependent manner, which explains the chloroplast defects and reduced photosynthesis activity of hot3 mutants. Our study linked the Kozak motif to eIF5B-mediated I-E transition during translation and uncovered the function of HOT3 in the cytoplasmic translational control of chloroplast biogenesis and photosynthesis., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Kagome magnets provide a fascinating platform for the realization of correlated topological quantum phases under various magnetic ground states. However, the effect of the magnetic spin configurations on the characteristic electronic structure of the kagome-lattice layer remains elusive. Here, utilizing angle-resolved photoemission spectroscopy and density functional theory calculations, we report the spectroscopic evidence for the spin-reorientation effect of a kagome ferromagnet Fe 3 Ge, which is composed solely of kagome planes. As the Fe moments cant from the c-axis into the ab plane upon cooling, the two kinds of kagome-derived Dirac fermions respond quite differently. The one with less-dispersive bands (k z   ~  0) containing the 3 d z 2 orbitals evolves from gapped into nearly gapless, while the other with linear dispersions (k z  ~ π) embracing the 3d xz /3d yz components remains intact, suggesting that the effect of spin reorientation on the Dirac fermions has an orbital selectivity. Moreover, we demonstrate that there is no signature of charge order formation in Fe 3 Ge, contrasting with its sibling compound FeGe, a newly established charge-density-wave kagome magnet., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Many plants associate with endophytic microbes that improve root phosphorus (P) uptake. Understanding the interactions between roots and endophytes can enable efforts to improve P utilization. Here, we characterize the interactions between lateral roots of endophytes in a core collection of 50 rapeseed (Brassica napus L.) genotypes with differing sensitivities to low P conditions. With the correlation analysis result between bacterial abundance and plant physiological indices of rapeseeds, and inoculation experiments on plates and soil, we identify one Flavobacterium strain (C2) that significantly alleviates the P deficiency phenotype of rapeseeds. The underlying mechanisms are explored by performing the weighted gene coexpression network analysis (WGCNA), and conducting genome-wide association studies (GWAS) using Flavobacterium abundance as a quantitative trait. Under P-limited conditions, C2 regulates fatty acid and lipid metabolic pathways. For example, C2 improves metabolism of linoleic acid, which mediates root suberin biosynthesis, and enhances P uptake efficiency. In addition, C2 suppresses root jasmonic acid biosynthesis, which depends on α-linolenic acid metabolism, improving C2 colonization and activating P uptake. This study demonstrates that adjusting the endophyte composition can modulate P uptake in B. napus plants, providing a basis for developing agricultural microbial agents., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aryl thianthrenium salts are valuable in photocatalysis but traditionally require external electron donors for activation. This study introduces an energy transfer (EnT) strategy for the activation of aryl thianthrenium salts using 2,3,4,5,6-penta(carbazol-9-yl)benzonitrile (5CzBN) as a metal-free photocatalyst, eliminating the need for external donors. Utilizing this EnT approach, we achieve C-H deuteration of arenes under visible light with CDCl 3 as a deuterium source to synthesize various deuterated aromatic compounds, including important natural products and pharmaceuticals. Additionally, this strategy enables diverse functionalizations including borylation, arylation, cyanation, and selenylation, enhancing the applicability of aryl sulfonium salts in environmentally friendly photocatalysis., (© 2024. The Author(s).)

The obese heart undergoes metabolic remodeling and exhibits impaired calcium (Ca 2+ ) homeostasis, which are two critical assaults leading to cardiac dysfunction. The molecular mechanisms underlying these alterations in obese heart are not well understood. Here, we show that the Rab-GTPase activating protein AS160 is a lipid-responsive regulator of Ca 2+ homeostasis through governing lysophosphatidylinositol metabolism and signaling. Palmitic acid/high fat diet inhibits AS160 activity through phosphorylation by NEK6, which consequently activates its downstream target Rab8a. Inactivation of AS160 in cardiomyocytes elevates cytosolic Ca 2+ that subsequently impairs cardiac contractility. Mechanistically, Rab8a downstream of AS160 interacts with DDHD1 to increase lysophosphatidylinositol metabolism and signaling that leads to Ca 2+ release from sarcoplasmic reticulum. Inactivation of NEK6 prevents inhibition of AS160 by palmitic acid/high fat diet, and alleviates cardiac dysfunction in high fat diet-fed mice. Together, our findings reveal a regulatory mechanism governing metabolic remodeling and Ca 2+ homeostasis in obese heart, and have therapeutic implications to combat obesity cardiomyopathy., (© 2024. The Author(s).)

High-temperature superconductivity was discovered in the pressurized nickelate La 3 Ni 2 O 7 which has a unique bilayer structure and mixed valence state of nickel. The properties at ambient pressure contain crucial information of the fundamental interactions and bosons mediating superconducting pairing. Here, using X-ray absorption spectroscopy and resonant inelastic X-ray scattering, we identified that Ni 3 d x 2 - y 2 , Ni 3 d z 2 , and ligand oxygen 2p orbitals dominate the low-energy physics with a small charge-transfer energy. Well-defined optical-like magnetic excitations soften into quasi-static spin-density-wave ordering, evidencing the strong electronic correlation and rich magnetic properties. Based on an effective Heisenberg spin model, we extract a much stronger inter-layer effective magnetic superexchange than the intra-layer ones and propose two viable magnetic structures. Our findings emphasize that the Ni 3 d z 2 orbital bonding within the bilayer induces novel electronic and magnetic excitations, setting the stage for further exploration of La 3 Ni 2 O 7 superconductor., (© 2024. The Author(s).)

Efficient heterogeneous catalyst design primarily focuses on engineering the active sites or supports, often neglecting the impact of trace impurities on catalytic performance. Herein, we demonstrate that even trace amounts of sulfate (SO 4 2- ) residuals on Ru/TiO 2 can totally change the CO 2 reduction from methanation to reverse-water gas shift (RWGS) reaction under atmospheric pressure. We reveal that air annealing causes the trace amount of SO 4 2- to migrate from TiO 2 to Ru/TiO 2 interface, leading to the significant changes in product selectivity from CH 4 to CO. Detailed characterizations and DFT calculations show that the sulfate at Ru/TiO 2 interface notably enhances the H transfer from Ru particles to the TiO 2 support, weakening the CO intermediate activation on Ru particles and inhibiting the further hydrogenation of CO to CH 4 . This discovery highlights the vital role of trace impurities in CO 2 hydrogenation reaction, and also provides broad implications for the design and development of more efficient and selective heterogeneous catalysts., (© 2024. The Author(s).)

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a persistent nosocomial pathogen that poses a significant threat to global public health, particularly in intensive care units (ICUs). Here we report a three-month longitudinal genomic surveillance study conducted in a Hangzhou ICU in 2021. This followed a three-month study conducted in the same ICU in 2019, and infection prevention and control (IPC) interventions targeting patients, staff and the ICU environment. Most A. baumannii isolated in this ICU in 2021 were CRAB (80.9%; 419/518) with higher-level resistance to carbapenems. This was accompanied by the proportion of global clone 2 (GC2) isolates falling from 99.5% in 2019 to 50.8% (213/419) in 2021. The phylogenetic diversity of GC2 increased, apparently driven by regular introductions of distinct clusters in association with patients. The remaining CRAB (40.2%; 206/419) were a highly clonal population of ST164. Isolates of ST164 carried bla NDM-1 and bla OXA-23 carbapenemase genes, and exhibited higher carbapenem MIC 50 /MIC 90 values than GC2. Comparative analysis of publicly available genomes from 26 countries (five continents) revealed that ST164 has evolved towards carbapenem resistance on multiple independent occasions. Its success in this ICU and global capacity for acquiring resistance determinants indicate that ST164 CRAB is an emerging high-risk lineage of global concern., (© 2024. The Author(s).)

Rotator cuff tendinopathy is the most common tendinopathy type with the worst prognosis. Conventional treatments often elicit heterogeneous drug responses due to the diversity of tendinopathy. Hence, this study attempted a classification of 126 diseased tendons into three distinct subtypes with opposite pathogenic mechanisms based on transcriptomic and clinical features. The hypoxic atrophic subtype with white appearance (Hw) exhibits downregulated neovascularization pathways. The inflammatory proliferative subtype with white appearance (Iw) shows a moderate upregulation of inflammatory characteristics. The inflammatory proliferative subtype with red appearance (Ir) exhibits the highest levels of upregulated neovascularization and inflammatory pathways, along with severe joint dysfunction. We then established research models, including subtype-specific simulations in animal models and clinical data analysis. These revealed that glucocorticoid, a controversial commonly used drug, was only effective in treating the Ir subtype. Hence, the tendinopathy subtypes elucidated in this study have significant implications for developing precision treatment of tendinopathy., (© 2024. The Author(s).)

Lipid droplets (LDs) feature a unique monolayer lipid membrane that has not been extensively studied due to the lack of suitable molecular probes that are able to distinguish this membrane from the LD lipid core. In this work, we present a three-pronged molecular probe design strategy that combines lipophilicity-based organelle targeting with microenvironment-dependent activation and design an LD membrane labeling pro-probe called LDM. Upon activation by the HClO/ClO - microenvironment that surrounds LDs, LDM pro-probe releases LDM-OH probe that binds to LD membrane proteins thus enabling visualization of the ring-like LD membrane. By utilizing LDM, we identify the dynamic mechanism of LD membrane contacts and their protein accumulation parameters. Taken together, LDM represents the first molecular probe for imaging LD membranes in live cells to the best of our knowledge, and represents an attractive tool for further investigations into the specific regulatory mechanisms with LD-related metabolism diseases and drug screening., (© 2024. The Author(s).)

Constructing a LiF-rich solid electrolyte interphase (SEI) is a feasible strategy for inhibiting lithium (Li) dendrites of Li metal anodes (LMAs). However, selecting appropriate F-containing additives with efficient LiF contribution is still under active research. Herein, a series of fluorinated additives with diverse F/C molar ratios are investigated, and we demonstrate that the hexafluoroglutaric anhydride (F 6-0 ) holds the best capability to derive the LiF-rich SEI in regular carbonate electrolytes (RCEs). To ameliorate the decomposition kinetics of the F 6-0 , LiNO 3 (LNO) as an adjuvant is further introduced in the system. As a result, the reduction efficiency of F 6-0 is increased to 91% under the F 6-0 /LNO synergistic effect, enabling the LMA with a uniform LiF-rich SEI in the RCE with merely 4 vol. % F 6-0 /LNO (F6L) addition. The LiNi 0.8 Co 0.1 Mn 0.1 O 2 ||Li-20μm full-cell with the F6L also showcases better cycling and rate performances than the cases with other F-containing additives., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Spatial and genomic heterogeneity of tumors are crucial factors influencing cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on somatic point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their localization in close to single-cell resolution by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors., (© 2024. The Author(s).)

The antiferroelectric-ferroelectric phase transition is a basic principle that holds promise for antiferroelectric ceramics in high capacitance density nonlinear capacitors. So far, the property optimization based on antiferroelectric-ferroelectric transition is solely undertaken by chemical composition tailoring. Alternately, here we propose a phase transition engineering tactic by applying pulsed electric stimulus near the critical electric field, which finally results in ~54.3% enhancement and quick stabilization of capacitance density in Pb 0.97 La 0.02 (Zr 0.35 Sn 0.55 Ti 0.10 )O 3 antiferroelectric ceramics. Ex-situ and in-situ structural characterizations show that electric stimuli can induce the charming successive structural evolution, including domain evolution from multidomain to monodomain state, and modulation period change from 7.49 to 7.73. Structure-property correlation indicates that the antiferroelectric-ferroelectric phase transition engineering mainly stems from the unexpected irreversible recovery of the modulated structures. The present findings would deepen the understanding of the structural phase transition and provoke composition-independent post-treatment property innovation in the incommensurate antiferroelectric materials and devices., (© 2024. The Author(s).)

The Walker circulation is projected to slow down in response to greenhouse gas warming. However, detecting the impact of human activities on changes in the Walker circulation is challenging due to the significant influence of internal variability. Here, based on ensembles of multiple climate models from the Coupled Model Intercomparison Project Phase 6 (CMIP6), we show evidence that the emergence of the human-induced weakening of Walker circulation tends to occur earlier in the middle-upper troposphere than at the surface. This earlier emergence is attributed to a more pronounced initial weakening response of the middle-upper tropospheric Walker circulation to atmospheric CO 2 radiative forcing. We further reveal that the emergence time of a weaker Walker circulation varies across models. This intermodel spread is governed by an ocean thermostat that operates by modulating the zonal sea surface temperature gradient over the tropical Indo-Pacific region. Our findings address the key question of whether and how to detect human-induced large-scale atmospheric circulation changes and provide valuable insights for assessing the associated risks., (© 2024. The Author(s).)

Oral corticosteroids represents the most prevalent treatment for idiopathic granulomatous mastitis. Ductal lavage with triamcinolone acetonide and antibiotics followed by observation (DL-OBS) has emerged as a novel strategy, but a comparison of them remains lacking. Here in this multicenter, open-label, non-inferiority, randomized trial (ClinicalTrials.gov identifier: NCT03724903), we assigned 140 patients to oral corticosteroids (N = 71) and DL-OBS (N = 69), stratified by baseline M-score. The primary outcome is complete Clinical Response rate at 1 year. The non-inferiority margin is -15%. The primary outcome is 85.5% in DL-OBS and 87.3% in oral corticosteroids (difference: -1.8%; 95%CI, 13.2 to 9.5; P non-inferiority  = .01) in intention-to-treat population, and 92.6% vs 98.2% (difference -5.6%; 95%CI -13.4 to 2.2; P non-inferiority  = .01) in per-protocol population, respectively. The most common (>15%) adverse events were Cushingoid, epigastric pain and arthralgia in oral corticosteroids, and irregular menstruation in DL-OBS, respectively. Here, we report that DL-OBS shows similar efficacy to oral corticosteroids but with better safety profile., (© 2024. The Author(s).)

Neoadjuvant immunochemotherapy (nICT) has dramatically changed the treatment landscape of operable esophageal squamous cell carcinoma (ESCC), but factors influencing tumor response to nICT are not well understood. Here, using single-cell RNA sequencing paired with T cell receptor sequencing, we profile tissues from ESCC patients accepting nICT treatment and characterize the tumor microenvironment context. CXCL13 + CD8 + Tex cells, a subset of exhausted CD8 + T cells, are revealed to highly infiltrate in pre-treatment tumors and show prominent progenitor exhaustion phenotype in post-treatment samples from responders. We validate CXCL13 + CD8 + Tex cells as a predictor of improved response to nICT and reveal CXCL13 to potentiate anti-PD-1 efficacy in vivo. Post-treatment tumors from non-responders are enriched for CXCL13 + CD8 + Tex cells with notably remarkable exhaustion phenotype and TNFRSF4 + CD4 + Tregs with activated immunosuppressive function and a significant clone expansion. Several critical markers for therapeutic resistance are also identified, including LRRC15 + fibroblasts and SPP1 + macrophages, which may recruit Tregs to form an immunosuppressive landscape. Overall, our findings unravel immune features of distinct therapeutic response to nICT treatment, providing a rationale for optimizing individualized neoadjuvant strategy in ESCC., (© 2024. The Author(s).)

Carboxylesterases serve as potent biocatalysts in the enantioselective synthesis of chiral carboxylic acids and esters. However, naturally occurring carboxylesterases exhibit limited enantioselectivity, particularly toward ethyl 3-cyclohexene-1-carboxylate (CHCE, S1), due to its nearly symmetric structure. While machine learning effectively expedites directed evolution, the lack of models for predicting the enantioselectivity for carboxylesterases has hindered progress, primarily due to challenges in obtaining high-quality training datasets. In this study, we devise a high-throughput method by coupling alcohol dehydrogenase to determine the apparent enantioselectivity of the carboxylesterase AcEst1 from Acinetobacter sp. JNU9335, generating a high-quality dataset. Leveraging seven features derived from biochemical considerations, we quantitively describe the steric, hydrophobic, hydrophilic, electrostatic, hydrogen bonding, and π-π interaction effects of residues within AcEst1. A robust gradient boosting regression tree model is trained to facilitate stereodivergent evolution, resulting in the enhanced enantioselectivity of AcEst1 toward S1. Through this approach, we successfully obtain two stereocomplementary variants, DR3 and DS6, demonstrating significantly increased and reversed enantioselectivity. Notably, DR3 and DS6 exhibit utility in the enantioselective hydrolysis of various symmetric esters. Comprehensive kinetic parameter analysis, molecular dynamics simulations, and QM/MM calculations offer insights into the kinetic and thermodynamic features underlying the manipulated enantioselectivity of DR3 and DS6., (© 2024. The Author(s).)

The low cultivability of environmental bacteria has been widely acknowledged, but most previous estimates focused on the proportion of cultivable cells rather than cultivable taxa. Here, we estimate the proportions of cultivable cells and cultivable taxa for two sample types (soil and activated sludge) using cell counting, 16S rRNA gene amplicon sequencing, metagenomics, and cultivation on agar plates under various conditions. We find that the proportion of cultivable taxa exceeds that of cultivable cells at the sample level. A large proportion of cultivable taxa are taxonomically novel but tend to be present at very low abundance on agar plates, forming microcolonies, and some of them cease to grow during subculture. Compared with uncultivable taxa (under the conditions used in our study), cultivatable taxa tend to display higher metabolic activity as inferred by measuring rRNA copies per cell. Finally, we use the generated taxonomic and genomic information as a guide to isolate a strain representing a yet-uncultured class within the Bacteroidota and to enhance the cultivable diversity of Burkholderiales from activated sludge., (© 2024. The Author(s).)

Iron is an essential biomineral in the human body. Here, we describe a subset of iron-loaded cancer-associated fibroblasts, termed as FerroCAFs, that utilize iron to induce immunosuppression in prostate cancer and predict an unfavorable clinical outcome. FerroCAFs secrete myeloid cell-associated proteins, including CCL2, CSF1 and CXCL1, to recruit immunosuppressive myeloid cells. We report the presence of FerroCAFs in prostate cancer from both mice and human, as well as in human lung and ovarian cancers, and identify a conserved cell surface marker, the poliovirus receptor. Mechanistically, the accumulated iron in FerroCAFs is caused by Hmox1-mediated iron release from heme degradation. The intracellular iron activates the Kdm6b, an iron-dependent epigenetic enzyme, to induce an accessible chromatin state and transcription of myeloid cell-associated protein genes. Targeting the FerroCAFs by inhibiting the Hmox1/iron/Kdm6b signaling axis incurs anti-tumor immunity and tumor suppression. Collectively, we report an iron-loaded FerroCAF cluster that drives immunosuppression through an iron-dependent epigenetic reprogramming mechanism and reveal promising therapeutic targets to boost anti-tumor immunity., (© 2024. The Author(s).)

Transposable elements are ubiquitous mobile DNA sequences generating insertion polymorphisms, contributing to genomic diversity. We present GraffiTE, a flexible pipeline to analyze polymorphic mobile elements insertions. By integrating state-of-the-art structural variant detection algorithms and graph genomes, GraffiTE identifies polymorphic mobile elements from genomic assemblies or long-read sequencing data, and genotypes these variants using short or long read sets. Benchmarking on simulated and real datasets reports high precision and recall rates. GraffiTE is designed to allow non-expert users to perform comprehensive analyses, including in models with limited transposable element knowledge and is compatible with various sequencing technologies. Here, we demonstrate the versatility of GraffiTE by analyzing human, Drosophila melanogaster, maize, and Cannabis sativa pangenome data. These analyses reveal the landscapes of polymorphic mobile elements and their frequency variations across individuals, strains, and cultivars., (© 2024. The Author(s).)

Electrons and holes, fundamental charge carriers in semiconductors, dominate optical transitions and detection processes. Twisted van der Waals (vdW) heterostructures offer an effective approach to manipulate radiation, separation, and collection processes of electron-hole pairs by creating an atomically sharp interface. Here, we demonstrate that twisted interfaces in vdW layered black phosphorus (BP), an infrared semiconductor with highly anisotropic crystalline structure and properties, can significantly alter both recombination and separation processes of electron-hole pairs. On the one hand, the twisted interface breaks the symmetry of optical transition states resulting in infrared light emission of originally symmetry-forbidden optical states along the zigzag direction. On the other hand, spontaneous electronic polarization/bulk photovoltaic effect is generated at the twisted interface enabling effective separation of electron-hole pairs without external voltage bias. This is supported by first-principles calculations and repeated experiments at various twisted angles from 0 to 90°. Importantly, these phenomena can be observed in twisted heterostructures with thickness beyond two-dimensional. Our results suggest that the engineering of vdW twisted interfaces is an effective strategy for manipulating the optoelectronic properties of materials and constructing functional devices., (© 2024. The Author(s).)

The Four Core Genotypes (FCG) is a mouse model system used to disentangle the function of sex chromosomes and hormones. We report that a copy of a 3.2 MB region of the X chromosome has translocated to the Y Sry- chromosome and thus increased the expression of X-linked genes including the single-stranded RNA sensor and autoimmune disease mediator Tlr7. This previously-unreported X-Y translocation complicates the interpretation of studies reliant on C57BL/6J FCG mice., (© 2024. The Author(s).)

Biocatalysis is an attractive approach for the synthesis of chiral pharmaceuticals and fine chemicals, but assessing and/or improving the enantioselectivity of biocatalyst towards target substrates is often time and resource intensive. Although machine learning has been used to reveal the underlying relationship between protein sequences and biocatalytic enantioselectivity, the establishment of substrate fitness space is usually disregarded by chemists and is still a challenge. Using 240 datasets collected in our previous works, we adopt chemistry and geometry descriptors and build random forest classification models for predicting the enantioselectivity of amidase towards new substrates. We further propose a heuristic strategy based on these models, by which the rational protein engineering can be efficiently performed to synthesize chiral compounds with higher ee values, and the optimized variant results in a 53-fold higher E-value comparing to the wild-type amidase. This data-driven methodology is expected to broaden the application of machine learning in biocatalysis research., (© 2024. The Author(s).)

Questions of unfairness and inequity pose critical challenges to the successful deployment of artificial intelligence (AI) in healthcare settings. In AI models, unequal performance across protected groups may be partially attributable to the learning of spurious or otherwise undesirable correlations between sensitive attributes and disease-related information. Here, we introduce the Attribute Neutral Framework, designed to disentangle biased attributes from disease-relevant information and subsequently neutralize them to improve representation across diverse subgroups. Within the framework, we develop the Attribute Neutralizer (AttrNzr) to generate neutralized data, for which protected attributes can no longer be easily predicted by humans or by machine learning classifiers. We then utilize these data to train the disease diagnosis model (DDM). Comparative analysis with other unfairness mitigation algorithms demonstrates that AttrNzr outperforms in reducing the unfairness of the DDM while maintaining DDM's overall disease diagnosis performance. Furthermore, AttrNzr supports the simultaneous neutralization of multiple attributes and demonstrates utility even when applied solely during the training phase, without being used in the test phase. Moreover, instead of introducing additional constraints to the DDM, the AttrNzr directly addresses a root cause of unfairness, providing a model-independent solution. Our results with AttrNzr highlight the potential of data-centered and model-independent solutions for fairness challenges in AI-enabled medical systems., (© 2024. The Author(s).)

Targeted protein degradation has emerged as a novel therapeutic modality to treat human diseases by utilizing the cell's own disposal systems to remove protein target. Significant clinical benefits have been observed for degrading many intracellular proteins. Recently, the degradation of extracellular proteins in the lysosome has been developed. However, there have been limited successes in selectively degrading protein targets in disease-relevant cells or tissues, which would greatly enhance the development of precision medicine. Additionally, most degraders are not readily available due to their complexity. We report a class of easily accessible Folate Receptor TArgeting Chimeras (FRTACs) to recruit the folate receptor, primarily expressed on malignant cells, to degrade extracellular soluble and membrane cancer-related proteins in vitro and in vivo. Our results indicate that FRTAC is a general platform for developing more precise and effective chemical probes and therapeutics for the study and treatment of cancers., (© 2024. The Author(s).)

Forests harbor extensive biodiversity and act as a strong global carbon and nitrogen sink. Although enhancing tree diversity has been shown to mitigate climate change by sequestering more carbon and nitrogen in biomass and soils in manipulative experiments, it is still unknown how varying environmental gradients, such as gradients in resource availability, mediate the effects of tree diversity on carbon and nitrogen accrual in natural forests. Here, we use Canada's National Forest Inventory data to explore how the relationships between tree diversity and the accumulation of carbon and nitrogen in tree biomass and soils vary with resource availability and environmental stressors in natural forests. We find that the positive relationship between tree functional diversity (rather than species richness) and the accumulation of carbon in tree biomass strengthens with increasing light and soil nutrient availability. Moreover, the positive relationship between tree functional diversity and the accumulation of carbon and nitrogen in both organic and mineral soil horizons is more pronounced at sites with greater water and nutrient availabilities. Our results highlight that conserving and promoting functionally diverse forests in resource-rich environments could play a greater role than in resource-poor environments in enhancing carbon and nitrogen sequestration in Canada's forests., (© 2024. The Author(s).)

The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis. After the addition of ligand cyclic arginine-glycine-aspartic acid (cRGD) and mannose, the mixed nanocarrier with immune adjuvant resiquimod encapsulation can target B16F10 cells for in situ tumor vaccination and TAMs for M1 phenotype polarization. In vivo studies indicate that the mixed targeting nanoplatform elicits tumor ICD, dendritic cell maturation, TAM polarization, and cytotoxic T lymphocyte infiltration and inhibits melanoma volume growth. In combination with immune checkpoint blockade, the survival time of mice is markedly prolonged. This study provides a strategy for utilizing immunoactive materials in the innate and adaptive immune responses to augment cancer therapy., (© 2024. The Author(s).)

CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with "one to more" aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics., (© 2024. The Author(s).)

Polymers capable of depolymerizing back to their own monomers offer a promising solution to address the challenges in polymer sustainability. Despite significant progress has been achieved in plastics circularity, chemical recycling of thermoplastic elastomers is relatively less concerned, largely because of their intrinsic complex multicomponents. This work creates a homopolymer-based platform towards chemically recyclable but tough thermoplastic elastomers. It is enabled by a semicrystalline polymer with high molecular weight but low crystallinity, which is prepared through ring-opening metathesis polymerization of a fully biobased cyclic olefin. By shifting the ring-chain equilibrium, quantitative conversions were achieved for both forward polymerization and reverse depolymerization. This simple circular, high-performance thermoplastic elastomer platform based on biomass highlights the importance of monomer design in addressing three challenges in sustainable polymers: the feedstock renewability, depolymerization selectivity, and performance trade-offs., (© 2024. The Author(s).)

Glycolytic metabolic reprogramming in cancer is regulated by both cancer intrinsic variations like isocitrate dehydrogenase 1 (IDH1) status and non-cancerous microenvironment components like tumor associated macrophages (TAMs). However, the detailed mechanism remains elusive. Here, we identify hexosaminidase B (HEXB) as a key regulator for glycolysis in glioblastoma (GBM). HEXB intercellularly manipulates TAMs to promote glycolysis in GBM cells, while intrinsically enhancing cancer cell glycolysis. Mechanistically, HEXB elevation augments tumor HIF1α protein stability through activating ITGB1/ILK/YAP1; Subsequently, HIF1α promotes HEXB and multiple glycolytic gene transcription in GBM cells. Genetic ablation and pharmacological inhibition of HEXB elicits substantial therapeutic effects in preclinical GBM models, while targeting HEXB doesn't induce significant reduction in IDH1 mutant glioma and inhibiting IDH1 mutation-derived 2-hydroxyglutaric acid (2-HG) significantly restores HEXB expression in glioma cells. Our work highlights a HEXB driven TAMs-associated glycolysis-promoting network in GBM and provides clues for developing more effective therapies against it., (© 2024. The Author(s).)

Spermiogenesis, the complex transformation of haploid spermatids into mature spermatozoa, relies on precise spatiotemporal regulation of gene expression at the post-transcriptional level. The mechanisms underlying this critical process remain incompletely understood. Here, we identify centrosomal protein 112 (CEP112) as an essential regulator of mRNA translation during this critical developmental process. Mutations in CEP112 are discovered in oligoasthenoteratospermic patients, and Cep112-deficient male mice recapitulate key phenotypes of human asthenoteratozoospermia. CEP112 localizes to the neck and atypical centrioles of mature sperm and forms RNA granules during spermiogenesis, enriching target mRNAs such as Fsip2, Cfap61, and Cfap74. Through multi-omics analyses and the TRICK reporter assay, we demonstrate that CEP112 orchestrates the translation of target mRNAs. Co-immunoprecipitation and mass spectrometry identify CEP112's interactions with translation-related proteins, including hnRNPA2B1, EEF1A1, and EIF4A1. In vitro, CEP112 undergoes liquid-liquid phase separation, forming condensates that recruit essential proteins and mRNAs. Moreover, variants in patient-derived CEP112 disrupt phase separation and impair translation efficiency. Our results suggest that CEP112 mediates the assembly of RNA granules through liquid-liquid phase separation to control the post-transcriptional expression of fertility-related genes. This study not only clarifies CEP112's role in spermatogenesis but also highlights the role of phase separation in translational regulation, providing insights into male infertility and suggesting potential therapeutic targets., (© 2024. The Author(s).)

Human economic activities drive the production and consumption of goods and services, contribute to the achievement of the United Nations Sustainable Development Goals (SDGs). However, the extent of economic growth's influence on the SDGs remains unclear. To fill this knowledge gap, here, we quantified the environmental effects of economic activities and explored correlations between environmental effect and achieving SDGs. We developed six Environmental Footprint Indices, with a higher score indicating better efficiency or lower burden. Here we show that the various Environmental Footprint Indices had synergistic and trade-off effects on most SDG targets indices, but the synergistic effects prevailed. As income increased, the correlation between Environmental Footprint Indices and SDG target indices gradually strengthened. improved production efficiency and consumption changes notably advance SDGs, especially in low-income group countries. Our work provides scientific insights into the impact and prospects of environmental regulation required for achieving the SDGs by 2030., (© 2024. The Author(s).)