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Abstract Polymeric-based dielectric materials hold great potential as energy storage media in electrostatic capacitors. However, the inferior thermal resistance of polymers leads to severely degraded dielectric energy storage capabilities at elevated temperatures, limiting their applications in harsh environments. Here we present a flexible laminated polymer nanocomposite where the polymer component is confined at the nanoscale, achieving improved thermal-mechanical-electrical stability within the resulting nanocomposite. The nanolaminate, consisting of nanoconfined polyetherimide (PEI) polymer sandwiched between solid Al2O3 layers, exhibits a high energy density of 18.9 J/cm3 with a high energy efficiency of ~ 91% at elevated temperature of 200°C. Our work demonstrates that nanoconfinement of PEI polymer results in reduced diffusion coefficient and constrained thermal dynamics, leading to a remarkable increase of 37°C in glass-transition temperature compared to bulk PEI polymer. The combined effects of nanoconfinement and interfacial trapping within the nanolaminates synergistically contribute to improved electrical breakdown strength and enhanced energy storage performance across temperature range up to 250°C. By utilizing the flexible ultrathin nanolaminate on curved surfaces such as thin metal wires, we introduce an innovative concept that enables the creation of a highly efficient and compact metal-wired capacitor, achieving substantial capacitance despite the minimal device volume.

Abstract Multicolor tuning of persistent luminescence has been extensively studied by deliberately integrating various luminescent units, known as activators or chromophores, into certain host compounds. However, it remains a formidable challenge to fine-tune the persistent luminescence spectra either in organic materials, such as small molecules, polymers, metal-organic complexes and carbon dots, or in doped inorganic crystals. Herein, we present a strategy to delicately control the persistent luminescence wavelength by engineering sub-bandgap donor-acceptor states in a series of single-phase Ca(Sr)ZnOS crystals. The persistent luminescence emission peak can be quasi-linearly tuned across a broad wavelength range (500–630 nm) as a function of Sr/Ca ratio, achieving a precision down to ~5 nm. Theoretical calculations reveal that the persistent luminescence wavelength fine-tuning stems from constantly lowered donor levels accompanying the modified band structure by Sr alloying. Besides, our experimental results show that these crystals exhibit a high initial luminance of 5.36 cd m− 2 at 5 sec after charging and a maximum persistent luminescence duration of 6 h. The superior, color-tunable persistent luminescence enables a rapid, programable patterning technique for high-throughput optical encryption.

Abstract A body area network involving wearable sensors distributed around the human body can continuously monitor physiological signals, finding applications in personal healthcare and athletic evaluation. Existing solutions for near-field body area networks, while facilitating reliable and secure interconnection among battery-free sensors, face challenges including limited spectral stability against external interference. Here we demonstrate a textile metamaterial featuring a coaxially-shielded internal structure designed to mitigate interference from extraneous loadings. The metamaterial can be patterned onto clothing to form a scalable, customizable network, enabling communication between near-field reading devices and battery-free sensing nodes placed within the network. Proof of concept demonstration shows the metamaterial’s robustness against mechanical deformation and exposure to lossy, conductive saline solutions, underscoring its potential applications in wet environments, particularly in athletic activities involving water or significant perspiration, offering insights for the future development of radio frequency components for a robust body area network at a system level.

Abstract α particles must be monitored to be managed as radioactive diagnostic agents or nuclear activity indicators. The new generation of perovskite detectors suffer from limited energy resolution, which affects spectroscopy and imaging applications. Here, we report that the solution-grown CsPbBr3 crystal exhibits a low and stable dark current (34.6 nA·cm−2 at 200 V) by thinning the as-grown crystal to decrease the high concentration CsPb2Br5 phase near the surface. The introduction of the Schottky electrode for the CsPbBr3 detector further reduces the dark current and improves the high-temperature stability. An energy resolution of 6.9% is achieved with the commercial electronic system, while the effects of air scattering and absorption are investigated. Moreover, 1.1% energy resolution is recognized by a full-customized readout application-specific integrated circuit without any additional signal processing, which matches well with the given parameters of the CsPbBr3 detector by reducing the parasitic capacitance and electronic noise.

Abstract The Marine Isotope Stage (MIS) 11c interglacial and its preceding glacial termination represent an enigmatically intense climate response to relatively weak insolation forcing. So far, a lack of radiometric age control has confounded a detailed assessment of the insolation-climate relationship during this period. Here, we present 230Th-dated speleothem proxy data from northern Italy and compare them with palaeoclimate records from the North Atlantic region. We find that interglacial conditions started in subtropical to middle latitudes at 423.1 ± 1.3 thousand years (kyr) before present, during a first weak insolation maximum, whereas northern high latitudes remained glaciated (sea level ~ 40 m below present). Some 14.5 ± 2.8 kyr after this early subtropical onset, peak interglacial conditions were reached globally, with sea level 6–13 m above present, despite weak insolation forcing. We attribute this remarkably intense climate response to an exceptionally long (~15 kyr) episode of intense poleward heat flux transport prior to the MIS 11c optimum.

Abstract The current strategies for building 2D organic-inorganic heterojunctions involve mostly wet-chemistry processes or exfoliation and transfer, leading to interface contaminations, poor crystallizing, or limited size. Here we show a bottom-up procedure to fabricate 2D large-scale heterostructure with clean interface and highly-crystalline sheets. As a prototypical example, a well-ordered hydrogen-bonded organic framework is self-assembled on the highly-oriented-pyrolytic-graphite substrate. The organic framework adopts a honeycomb lattice with faulted/unfaulted halves in a unit cell, resemble to molecular “graphene”. Interestingly, the topmost layer of substrate is self-lifted by organic framework via strong interlayer coupling, to form effectively a floating organic framework/graphene heterostructure. The individual layer of heterostructure inherits its intrinsic property, exhibiting distinct Dirac bands of graphene and narrow bands of organic framework. Our results demonstrate a promising approach to fabricate 2D organic-inorganic heterostructure with large-scale uniformity and highly-crystalline via the self-lifting effect, which is generally applicable to most of van der Waals materials.

Abstract Protein ubiquitination regulates a wide range of cellular processes. The degree of protein ubiquitination is determined by the delicate balance between ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase (DUB)-mediated deubiquitination. In comparison to the E3-substrate interactions, the DUB-substrate interactions (DSIs) remain insufficiently investigated. To address this challenge, we introduce a protein sequence-based ab initio method, TransDSI, which transfers proteome-scale evolutionary information to predict unknown DSIs despite inadequate training datasets. An explainable module is integrated to suggest the critical protein regions for DSIs while predicting DSIs. TransDSI outperforms multiple machine learning strategies against both cross-validation and independent test. Two predicted DUBs (USP11 and USP20) for FOXP3 are validated by “wet lab” experiments, along with two predicted substrates (AR and p53) for USP22. TransDSI provides new functional perspective on proteins by identifying regulatory DSIs, and offers clues for potential tumor drug target discovery and precision drug application.

Abstract Creating circularly polarized organic afterglow system with elevated triplet energy levels, suppressed non-radiative transitions, and effective chirality, which are three critical prerequisites for achieving blue circularly polarized afterglow, has posed a formidable challenge. Herein, a straightforward approach is unveiled to attain blue circularly polarized afterglow materials by covalently self-confining isolated chiral chromophore within polymer matrix. The formation of robust hydrogen bonds within the polymer matrix confers a distinctly isolated and stabilized molecular state of chiral chromophores, endowing a blue emission band at 414 nm, lifetime of 3.0 s, and luminescent dissymmetry factor of ~ 10−2. Utilizing the synergistic afterglow and chirality energy transfer, full-color circularly polarized afterglow systems are endowed by doping colorful fluorescent molecules into designed blue polymers, empowering versatile applications. This work paves the way for the streamlined design of blue circularly polarized afterglow materials, expanding the horizons of circularly polarized afterglow materials into various domains.

Abstract The rational use and conversion of energy are the primary means for achieving the goal of carbon neutrality. MXenes can be used for photothermal conversion, but their opaque appearance limits wider applications. Herein, we successfully develop visible-light transparent and UV-absorbing polymer composite film by solution blending the MXene with polyethylene and then vacuum pressing. The resulting film could be quickly heated to 65 °C under 400 mW cm−2 light irradiation and maintained over 85% visible-light transmittance as well as low haze (

Abstract Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.

Abstract IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1β inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD.

Abstract Some plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). Rice RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here, we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.

Abstract Cobalt oxyhydroxide (CoOOH) is a promising catalytic material for oxygen evolution reaction (OER). In the traditional CoOOH structure, Co3+ exhibits a low-spin state configuration ( $${t}_{2{{{{{\rm{g}}}}}}}^{6}{e}_{{{{{{\rm{g}}}}}}}^{0}$$ t 2 g 6 e g 0 ), with electron transfer occurring in face-to-face $${t}_{2{{{{{\rm{g}}}}}}}^{*}$$ t 2 g * orbitals. In this work, we report the successful synthesis of high-spin state Co3+ CoOOH structure, by introducing coordinatively unsaturated Co atoms. As compared to the low-spin state CoOOH, electron transfer in the high-spin state CoOOH occurs in apex-to-apex $${e}_{{{{{{\rm{g}}}}}}}^{*}$$ e g * orbitals, which exhibits faster electron transfer ability. As a result, the high-spin state CoOOH performs superior OER activity with an overpotential of 226 mV at 10 mA cm−2, which is 148 mV lower than that of the low-spin state CoOOH. This work emphasizes the effect of the spin state of Co3+ on OER activity of CoOOH based electrocatalysts for water splitting, and thus provides a new strategy for designing highly efficient electrocatalysts.

Abstract High performance X-ray detector with ultra-high spatial and temporal resolution are crucial for biomedical imaging. This study reports a dynamic direct-conversion CMOS X-ray detector assembled with screen-printed CsPbBr3, whose mobility-lifetime product is 5.2 × 10−4 cm2 V–1 and X-ray sensitivity is 1.6 × 104 µC Gyair –1 cm–2. Samples larger than 5 cm $$\times$$ × 10 cm can be rapidly imaged by scanning this detector at a speed of 300 frames per second along the vertical and horizontal directions. In comparison to traditional indirect-conversion CMOS X-ray detector, this perovskite CMOS detector offers high spatial resolution (5.0 lp mm−1) X-ray radiographic imaging capability at low radiation dose (260 nGy). Moreover, 3D tomographic images of a biological specimen are also successfully reconstructed. These results highlight the perovskite CMOS detector’s potential in high-resolution, large-area, low-dose dynamic biomedical X-ray and CT imaging, as well as in non-destructive X-ray testing and security scanning.

Abstract Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e−) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.

Abstract The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.

Abstract Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.

Abstract A coupled oxygen evolution mechanism (COM) during oxygen evolution reaction (OER) has been reported in nickel oxyhydroxides (NiOOH)-based materials by realizing e g * band (3d electron states with e g symmetry) broadening and light irradiation. However, the link between the e g * band broadening extent and COM-based OER activities remains unclear. Here, Ni1-xFexOOH (x = 0, 0.05, 0,2) are prepared to investigate the underlying mechanism governing COM-based activities. It is revealed that in low potential region, realizing stronger e g * band broadening could facilitate the *OH deprotonation. Meanwhile, in high potential region where the photon utilization is the rate-determining step, a stronger e g * band broadening would widen the non-overlapping region between d z 2 and a 1g * orbitals, thereby enhancing photon utilization efficiency. Consequently, a stronger e g * band broadening could effectuate more efficient OER activities. Moreover, we demonstrate the universality of this concept by extending it to reconstruction-derived X-NiOOH (X = NiS2, NiSe2, Ni4P5) with varying extent of e g * band broadening. Such an understanding of the COM would provide valuable guidance for the future development of highly efficient OER electrocatalysts.

Abstract Breakdown of reproductive isolation facilitates flow of useful trait genes into crop plants from their wild relatives. Hybrid sterility, a major form of reproductive isolation exists between cultivated rice (Oryza sativa) and wild rice (O. meridionalis, Mer). Here, we report the cloning of qHMS1, a quantitative trait locus controlling hybrid male sterility between these two species. Like qHMS7, another locus we cloned previously, qHMS1 encodes a toxin-antidote system, but differs in the encoded proteins, their evolutionary origin, and action time point during pollen development. In plants heterozygous at qHMS1, ~ 50% of pollens carrying qHMS1-D (an allele from cultivated rice) are selectively killed. In plants heterozygous at both qHMS1 and qHMS7, ~ 75% pollens without co-presence of qHMS1-Mer and qHMS7-D are selectively killed, indicating that the antidotes function in a toxin-dependent manner. Our results indicate that different toxin-antidote systems provide stacked reproductive isolation for maintaining species identity and shed light on breakdown of hybrid male sterility.

Abstract Polymer nanocomposites with nanoparticles dispersed in polymer matrices have attracted extensive attention due to their significantly improved overall performance, in which the nanoparticle-polymer interface plays a key role. Understanding the structures and properties of the interfacial region, however, remains a major challenge for polymer nanocomposites. Here, we directly observe the presence of two interfacial polymer layers around a nanoparticle in polar polymers, i.e., an inner bound polar layer (~10 nm thick) with aligned dipoles and an outer polar layer (over 100 nm thick) with randomly orientated dipoles. Our results reveal that the impacts of the local nanoparticle surface potential and interparticle distance on molecular dipoles induce interfacial polymer layers with different polar molecular conformations from the bulk polymer. The bilayer interfacial features lead to an exceptional enhancement in polarity-related properties of polymer nanocomposites at ultralow nanoparticle loadings. By maximizing the contribution of inner bound polar layer via a nanolamination design, we achieve an ultrahigh dielectric energy storage density of 86 J/cm3, far superior to state-of-the-art polymers and nanocomposites.

Abstract Melatonin is a functionally conserved broad-spectrum physiological regulator found in most biological organisms in nature. Enrichment of tomato fruit with melatonin not only enhances its agronomic traits but also provides extra health benefits. In this study, we elucidate the full melatonin biosynthesis pathway in tomato fruit by identifying biosynthesis-related genes that encode caffeic acid O-methyltransferase 2 (SlCOMT2) and N-acetyl-5-hydroxytryptamine-methyltransferases 5/7 (SlASMT5/7). We further reveal that red light supplementation significantly enhances the melatonin content in tomato fruit. This induction relies on the “serotonin—N-acetylserotonin—melatonin” biosynthesis route via the SlphyB2-SlPIF4-SlCOMT2 module. Based on the regulatory mechanism, we design a gene-editing strategy to target the binding motif of SlPIF4 in the promoter of SlCOMT2, which significantly enhances the production of melatonin in tomato fruit. Our study provides a good example of how the understanding of plant metabolic pathways responding to environmental factors can guide the engineering of health-promoting foods.

Abstract Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in male mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.

Abstract Constructing room-temperature phosphorescent materials with multiple emission and special excitation modes is fascinating and challenging for practical applications. Herein, we demonstrate a facile and general strategy to obtain ecofriendly ultralong phosphorescent materials with multi-mode emission, adjustable excitation-dependence, and visible-light excitation using a single organic component, cellulose trimellitate. Based on the regulation of the aggregation state of anionic cellulose trimellitates, such as CBtCOONa, three types of phosphorescent materials with different emission modes are fabricated, including blue, green and color-tunable phosphorescent materials with a strong excitation-dependence. The separated molecularly-dispersed CBtCOONa exhibits blue phosphorescence while the aggregated CBtCOONa emits green phosphorescence; and the CBtCOONa with a coexistence state of single molecular chains and aggregates exhibits color-tunable phosphorescence depending on the excitation wavelength. Moreover, aggregated cellulose trimellitates demonstrate unique visible-light excitation phosphorescence, which emits green or yellow phosphorescence after turning off the visible light. The aggregation-regulated phenomenon provides a simple principle for designing the proof-of-concept and on-demand phosphorescent materials by using a single organic component. Owing to their excellent processability and environmental friendliness, the aforementioned cellulose-based phosphorescent materials are demonstrated as advanced phosphorescence inks to prepare various disposable complex anticounterfeiting patterns and information codes.

Abstract The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury.

Abstract Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.

The development of organic afterglow materials with sufficient color purity and high quantum efficiency for hyperafterglow is a great challenging. Here, the authors demonstrate an efficient strategy to achieve hyperafterglow emission through sensitizing and stabilizing isolated fluorescence chromophores by integrating multiresonance fluorescence chromophores into afterglow host in a singlecomponent copolymer.

The surface localized charges in colloidal quantum dots induce a degradation that limits the electroluminescence performance. Here, Chen et al. propose quantum dots with monmonotonically-graded core/shell/shell structures to boost the device’s performance by reducing the surface-bulk coupling.

This study demonstrates a role of cholesterol metabolism-related gene, Lrp3, in cartilage degeneration and osteoarthritis pathogenesis. LRP3 positively regulates cartilage extracellular matrix metabolism by targeting syndecan-4 via Ras signalling, implicating the cholesterol-LRP3-SDC4 axis in osteoarthritic cartilage degeneration.

By recognizing double-stranded RNA, RIG-I is implicated in anti-viral immune responses, but also in cancer development and intestinal inflammation. Here the authors identify frameshift germline mutations of RIG-I, resulting in the generation of a circular RNA associated with increased susceptibility to colitis-associated colon cancer.

The formation of ternary degrader-protein complexes is a key step in the targeted degradation of proteins of interest. Here, the authors explore the structure and dynamics of such complexes applying high-performance computer simulations augmented with experimental data.

TGF-β has been shown to regulate stem-like CD8 + T cell differentiation into tissue resident memory T cells in chronic infection. Here authors show that in tumour-bearing mice, a similar TGF-βdependent CD8 + T cell differentiation program is carried out in the draining lymph nodes, which impedes generation of anti-tumor migratory effector T cells upon future vaccination.

Wireless delivery of both light and pharmacological agents is important for optogenetic and other mechanistic experiments in the brain. Here the authors present a wireless real-time programmable optofluidic platform that enables optogenetics and photopharmacology experiments that require real-time precise control of light and drug delivery.

Catalytic hydrogenation of available nitroarenes is an environmentally benign and recyclable approach to synthesize value-added amines. Here, the authors design a RuNi single atom alloy with host-dopant synergistic effect, which exhibits outstanding performance toward nitroarenes hydrogenation.

Peroxidase mimics are currently being investigated as catalysts for lignin depolymerisation. In this article, the authors investigate a class of self-assembled and highly stable peptoid/hemin nanomaterials as peroxidase mimics that are highly stable and tuneable for the depolymerisation of a biorefinery lignin.

Aggregation of misfolded proteins underlie dementias. Here, the authors show that stressed cells activate an innate mechanism to resolve aggregates of defective proteins in the endoplasmic reticulum, where a third of cellular proteins are produced.

Glass-to-glass transitions can help understanding the glass nature, but it remains difficult to tune metallic glasses into significantly different glass states. Here the authors demonstrate the high-entropy effects in glass-to-glass transitions of high-entropy metallic glasses.

Organic room-temperature phosphorescence (RTP) materials often suffer from poor processability because of their crystalline or cross-linked nature. Here, the authors demonstrate phosphorescence in a processable cellulose derivative by introducing cationic groups such as imidazolium cations which are able to promote intersystem crossing and to form hydrogen bonds, inhibiting non-radiative transitions.

Defects in BRCA1, a gene involved in homologous recombination DNA repair, are common in triple negative breast cancer. Here the authors show that Brca1 deficiency in preclinical breast cancer models is associated with the accumulation of myeloid derived suppressive cells and resistance to immune checkpoint blockade, that could be overcome by targeting S100A9 and CXCL12.

MAPK cascades play an important role in innate immunity. Here, the authors show that that beet black scorch virus activates MAPK signaling in Nicotiana benthamiana and the viral coat protein counteracts MAPK-mediated defence by competitively binding to a MAPKKKα interactor.

Hole-spin qubits in germanium are promising candidates for rapid, all-electrical qubit control. Here the authors report Rabi oscillations with the record frequency of 540 MHz in a hole-based double quantum dot in a germanium hut wire, which is attributed to strong spin-orbit interaction of heavy holes.

The glucagon-like peptide-1 receptor (GLP-1R) can be targeted in the treatment of diabetes, obesity and other metabolic disorders. Here, the authors assess the molecular mechanisms of peptide agonists binding to GLP-1R and the responses elucidated by these ligands, including distinct kinetics of G protein activation.

Immune responses to pancreatic ductal adenocarcinoma can be inhibited by cancer cells. Here the authors show that high levels of progranulin in PDAC inhibits immune responses by reducing MHC class I antigen presentation through enhanced degradation of MHC class I via autophagy.

Metabolic conditions associated with alterations of the gut microbiome, such as obesity and diabetes, predispose to gallstone disease. Here the authors demonstrate that the gut microbiome, in particular the genus Desulfovibrionale, contribute to gallstone formation in mice.

Regulatory T (Treg) cells are important modulators of the tumor microenvironment. Here the authors perform transcriptome profiling of immune cells from patients with renal clear cell carcinoma to find a Treg signature that correlates with poorer prognosis, with CD177 being implicated as the main mediator for related alterations in Treg activity and tumor outcome.

Aggregation-induced emission (AIE) fluorescence probes are indispensable for biomedical imaging, however, interference with tissue autofluorescence results in low signal-to-noise ratio limiting the development of bioimaging with AIE materials. Here the authors develop AIEgen room-temperature phosphors with long emission lifetimes efficiently eliminating intereference with the background signal in imaging.

PTENα is an N-terminally extended isoform of PTEN, a gene frequently mutated in human cancers. Here the authors show that PTENα remains active in PTEN-mutant cancers and is associated with tumor immune escape by promoting tumor cell resistance to T cell cytotoxicity.

There is a need to optimise cryo-EM data acquisition approaches to improve the resolution of GPCR cryo-EM structures to better than 2.5 Å, in order to use them for structure-based drug design purposes. Here, the authors present a systematic analysis of the main cryo-EM experimental parameters using three GPCRs as test cases, which is also of interest for the cryo-EM structure determination of other small membrane proteins.

Colloidal quantum dots are promising for next-generation displays, yet the technology to realise high-resolution and uniform patterning is still scarce. Here, the authors report full-colour QD large area patterning by combining photolithography and selective electrophoretic deposition technique.

Different cells of the tumour microenvironment in HBV-associated human hepatocellular carcinoma (HCC) interact to promote tumour immunity. Here the authors use single cell RNA sequencing to identify TIGIT-NECTIN2 as a pathway by which tumour-associated macrophages reduce intratumour T cell activation.