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The cascade reaction of lipopolysaccharides (LPS), cell-free DNA (cfDNA), and reactive oxygen species (ROS), drives the development of inflammatory bowel disease (IBD). Here, Xu et. al. construct chiral nanomedicines composed of four functional moieties to eliminate LPS, ROS, and cfDNA for targeted treatment of IBD.

Flexible laminated polymer nanocomposites with the polymer layer confined are found to exhibit enhanced thermal stability and improved high-temperature energy storage capabilities.

In this work, we report a strategy with which to realize efficient manipulation of CNT networks by forming double networks with branched polyethylenimine (PEI). The double network was highly viscoelastic and ductile and enabled efficient film stretching or creeping for CNT alignment, which dramatically improved the mechanical strengths of the CNT films. Due to viscous drag from the polymer network, the CNTs showed enhanced movability in reconstructing new networks, which made the film repairable. The repairability resulted from the branched polymeric structure. This double-networking strategy provides a new way to manipulate CNT assemblies for high-performance applications.

Authors obtain high n-type thermoelectric power factor in carbon nanotube films for potential application in automated thermal management of electronic devices. They fabricate a high-power density curl-able thermoelectric generator with carbon nanotubes films.

An amine-support system has been introduced through atom-level design, achieving low regeneration energy, excellent cyclic stability, high capacity, and rapid kinetics, stemming from electron-level interactions preventing carbamate dehydration.

Obesity, a surging global health challenge, needs effective and innovative therapeutic models. Here, the authors show in mice a microneedle drug delivery platform loaded with metal-organic frameworks (MOFs) and CRISPRa-UCP1 system to enable sono-gene therapy for obesity.

MGAT1 is a glycosyltransferase critical for the synthesis and maturation of complex N-glycans. Here, the authors show that MGAT1 modulation of CD73 glycosylation and function regulates tumor immune response in triple-negative breast cancer.

Organic solar modules suffer from poor electrical contacts. Lu et al. embed the silver electrode into a polymer matrix and add chromium to enhance its electrical contact, achieving improved stability and a 14.04% efficiency on flexible modules with an active area of 41 cm².

HPS is a rare autosomal recessive disorder that cause dysfunctions of the lungs, intestine, kidneys, and heart. Here, the authors report the structure of the BLOC complex, BLOC-3 and provides a framework to understand how BLOC-3 cooperates with Rab GTPases (RAB32/38 and RAB9A) to regulate the biogenesis of lysosome-related organelles.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

The authors introduce SelectID, an approach combining CRISPR-guided targeting with methylation-sensitive labeling to identify proteins interacting with methylated repetitive sequences. They suggest that CHD4 directly binds young LINE-1 retrotransposons, suppressing their activity.

This study utilizes Stereo-seq to comprehensively map the geospatial architecture of breast cancer, revealing venular niches that promote immune infiltration and better clinical outcomes, offering new insights into tumor microenvironment regulation.

A next-generation proteolysis-targeting vaccine approach (PROTAR vaccine 2.0) was developed that attenuated influenza viruses by degrading multiple viral proteins and showed promising safety and efficacy in animal models with viral challenge.

Inhaled lipid nanoparticles face several challenges when delivered to the lungs. Here, the authors show “LOOP”-optimized iLNP-HP08^LOOP could withstand shear damage generated during nebulization process and be used to develop mRNA-mediated antibody therapy for treating idiopathic pulmonary fibrosis.

TGFbeta is known to promote cancer metastasis through the promotion of epithelial-mesenchymal transition (EMT). Here, the authors demonstrate that a TGFbeta induced circular RNA (circITGB6) promotes colorectal cancer metastasis via activation of the m6A reader protein, IGF2BP3, resulting in stabilization of an EMT-promoting gene, PDPN.

This protocol leverages tailored adeno-associated virus vectors for effective delivery of pooled CRISPR-based genetic perturbations in live animals combined with single-cell gene expression readout of phenotypic effects.

One advantage of organic solar cells is that they can be fabricated by printing methods, yet the materials must be suitably designed. Now, Jiang et al. devise an alcohol-dispersed formulation of PEDOT with good wettability, solvent orthogonality and low acidity.

Exon–intron-fused RAB22A regulates metastasis of osteosarcoma. Liao et al. show that protein products resulting from chromosomal translocations involving RAB22A mediate release of GTP-bound RhoA, induce its activation and promote lung metastasis of osteosarcoma.

Zhang and Gu used four cohorts to examine associations between skeletal muscle strength (SMS) and chronic kidney disease (CKD) in people with metabolic dysfunction-associated steatotic liver disease (MASLD). Higher handgrip/muscle strength is closely associated with a lower prevalence and incidence of CKD in people with MASLD.

Metabotropic glutamate (mGlu) receptors form both homo- and heterodimers that respond to ligands differently. Here, the authors elucidate the mechanism of activation and differential pharmacology in mGlu_2/4 heteromers, which may guide targeted therapy.

Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases, but its relationship with MAFLD remains unclear. Here, the authors show that SR-A3 is an important modulator of hepatic energy metabolism and is a potential therapeutic target against MAFLD.

In this study, the authors perform an interactome study of Zika virus (ZIKV) 5’UTR stem-loop B region and identify two host factors, interleukin enhancer binding factor 3 (ILF3) and DEAH-box helicase 9 (DHX9), that positively regulate antiviral RNAi to inhibit virus replication and ZIKV-induced microcephaly in vivo.

The induction of long-term systemic immunosurveillance can protect against post-surgery tumor recurrence. Here the authors describe the design of optogenetic-controlled cytokine secreting (IFN-β, TNF-α, and IL-12) engineered mesenchymal stem cells loaded into a hydrogel scaffold, eliciting long-term immune memory and preventing post-operative recurrence in preclinical cancer models.

Early life experience modulates stress resilience in later life. Here the authors show that maternal care triggers microglia-derived IGF-1 levels, which suppresses the neuronal C/EBPβ-DRP1 axis, promoting stress resilience in adolescent mice.

Cryo-EM structures reveal the molecular mechanism of ligands and G protein selectivity for prostaglandin F_2α receptor, providing guidance for development of better postpartum hemorrhage drugs.

The B-cell receptor of primary mouse B cells can be engineered to affinity mature an HIV-1-entry inhibitor in vivo.

The mitochondrial unfolded protein response is shown to inhibit pluripotency during somatic cell reprogramming and to inhibit the mesenchymal-to-epithelial transition through c-Jun-mediated histone acetylation.

Mitochondrial dysfunction in cardiomyocytes contributes to the pathogenesis during heart failure. Here the authors report that the transcriptional repressor HEY2 regulates mitochondrial metabolism and cardiac function in adult mouse and zebrafish hearts.

Here, authors present cryo-EM structures and simulations of urea transporter members in resting-, transport-, or inactive-states bound with synthetic competitive, uncompetitive or noncompetitive inhibitor.

The nanoparticle-polymer interface plays a key role in nanoparticle-polymer composites but understanding the structures and properties of the interfacial region remains challenging. Here, the authors directly observe the presence of two interfacial polymer layers around a nanoparticle in polar polymers with different polar molecular conformations from the bulk polymer leading to an enhancement in polarity-related properties of polymer nanocomposites

The therapeutic approaches directly targeting activated β-catenin in liver cancers are restricted by toxicities. Here the authors identify that the solute carrier transporter SLC13A3 is upregulated by activation of β-catenin and silencing of SLC13A3 induces ferroptosis, which could be exploited as a therapeutic opportunity in β-catenin-driven liver cancers.

Here the authors identify SUZ12 as a cellular substate of casein kinase 2 (CK2), and show this phosphorylation changes the active site structure of Polycomb repressive complex 2 (PRC2) and promotes PRC2 function in cell identity maintenance during stem cell differentiation.

Long-term control of therapeutic transgene expression is needed. Here the authors report a muscone-induced transgene system packaged into AAVs based on a G protein-coupled murine olfactory receptor and a synthetic cAMP-responsive promoter: they show dose- and exposure-time-dependent gene expression control in mice.

Methods for catalytically constructing of N–N axially chiral scaffolds have garnered significant attention. Here, the authors report a highly diastereoselective and enantioselective organocatalyzed [4 + 1] annulation method for synthesizing diverse valuable isoindolinones that possessing N–N axial and central chiralities.

A controllable protease-based protein secretion platform was developed for the rapid delivery of user-defined therapeutic protein secretion in response to FDA-approved drugs, tumor antigen and light, enabling cell-based precision therapies.

The identification of cryptic allosteric sites presents a formidable challenge. Here, the authors develop a residue-intuitive hybrid ML model coupled with MD simulation to successfully identify a novel allosteric site of β2AR and a negative allosteric modulator.

Heterocycles containing difluoromethyl groups are molecules with potential application in pharmaceutical, agricultural and materials science. Here, the authors show an organophotocatalytic difluoromethylation of heterocycles using O₂ as green oxidant and preliminarily study the products’ bioactivity.

Limited whole genome sequencing (WGS) of Asian populations results in a lack of representative reference panels, hindering imputation of Asian ancestry-specific genetic variants. Here the authors use WGS data from 11,067 individuals across 17 Asian countries to create a new reference panel which shows improved imputation accuracy for South Asian populations.

Chemokine receptors are G protein-coupled receptors (GPCRs) involved in immune responses and characterized by ligand promiscuity Here, the authors characterize signaling through chemokine receptors CXCR4 and CXCR7, with insights into intrinsic-bias encoded in the CXCR4-CXCR7 system.