Search

Dual targeting of BRAF and MAPK signaling in the BRAF v600E mutant colorectal cancer patients has shown limited efficacy in clinical studies. Here, the authors identify PLK1 inhibition as synthetic lethal with dual BRAF and EGFR inhibition due to loss of ferroptosis inhibition via a PLK1-CBX8-GPX4 signaling axis in preclinical models of colorectal cancer.

Hydrogels are essential for stem cell-based tissue regeneration but struggle with hard tissue repair. The authors report a shell-hardened macroporous hydrogel with spatiotemporally programmed mechanics to enhance stem cell-driven bone regeneration.

The proton-sensing GPCRs detect extracellular low pH and regulate diverse physiological responses. Here, the authors report cryo-EM structures of GPR4, which provide insight into the structural features of proton sensing mechanism.

The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.

Pair density modulation, an unusual superconducting state whose superconducting gap is modulated by the wavelength corresponding to the lattice periodicity, is described and observed in exfoliated thin flakes of the iron-based superconductor FeTe_0.55Se_0.45.

In this work, the authors report Cryo-EM structures of the signaling complexes of human GPR21, an orphan GPCR and a potential metabolic disease target, and reveal unique receptor activation conformation when bound to downstream signaling proteins in the absence of any ligand.

Manipulating collective phenomena in solid-state platforms with optical means is an ongoing topic of interest in condensed matter physics. Here, the authors demonstrate all-optical room-temperature manipulation of electronic states in the charge-density-wave material EuTe₄.

It is a challenge to control composition gradient of ferroelectric films. Here, the authors develop a solution epitaxy strategy to produce compositionally-graded ferroelectric films with excellent dielectric stability and high pyroelectric property.

Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.

Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.

Structures of the orphan G-protein-coupled receptor GPR52 in ligand-free, G-protein-coupled and ligand-bound states reveal that extracellular loop 2 occupies the orthosteric binding pocket and functions as a built-in agonist to activate the receptor.

A cryogenic electron microcopy study of structures of a human receptor for bitter taste finds that cholesterol can activate the receptor, while the tastant molecule acts allosterically on the receptor.

How RNA polymerase II transcription of tandemly repetitive satellite DNAs is regulated is poorly understood. Here, the authors identify Topoisomerase I as an evolutionary key regulator for satellite DNA transcription under both normal and DNA double-stranded break conditions.

Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-G_i complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.

Innate immune cells respond to a number of environmental cues including TLR signalling. Here the authors implicate mechanical sensor Piezo1 in the TLR4 mediated host response to bacterial infection and implicate it in the enhancement of macrophage mediated host response.

Combined analysis of Chang’e-3 in situ measurements and Chang’e-5 laboratory samples, with an updated chronology from Chang’e-5 data, reconstructed the relation between age and composition of young lunar mare basalts. Results indicate persistent volcanism 2 Gyr ago, indicative of the presence of a heat source at the time.

In this study, the authors identify and characterize distinct Salmonella Typhimurium rough colony strains, likely originating from Chinese smooth colony strains around 1977 that predominantly belong to sublineage L6.5 and carry a specific csgD promoter mutation.

Jacobsen and colleagues elucidate the nonhierarchical relationship between two types of stem cells: Vwf⁻ hematopoietic stem cells that stably replenish all blood cell lineages without a platelet bias, and Vwf⁺ stem cells that replenish almost exclusively platelets, and demonstrate that the two types utilize cellularly and molecularly distinct progenitor trajectories for replenishment of platelets.

Aqueous sodium-ion batteries show promise for large-scale energy storage, yet face challenges due to water decomposition, limiting their energy density and lifespan. Here, the authors report a cathode surface coating strategy in an alkaline electrolyte to enhance the stability of both electrolyte and battery.

Cancer cells exploit immune checkpoint pathways, such as PD-1/PD-L1, to evade elimination by the immune system. Here, the authors demonstrate that TMUB1 regulates post-translational modifications of PD-L1 and that targeting the TMUB1/PD-L1 interaction promotes anti-tumour T cells responses

Cryo-EM analysis of the human apelin receptor activated by either the endogenous peptide ligand or a potent synthetic small-molecule agonist reveals a mixture of homodimer and monomer organizations shedding light on a versatile regulation mechanism.

Liposome-mediated gene editing was used to abolish a mutation in gene Atp2b2 and recover hearing in a mouse model of dominant deafness. Editing was also used to target two mutations to recover hearing. The study detected large deletions due to editing.

Sustainable materials with circularly polarized room-temperature phosphorescence are desirable but challenging to design. Here, the authors report the development of thin films, based on cellulose nanocrystals and lignosulfonate, with circularly polarised room temperature phosphorescence.

Radiomics has been used to discover imaging signatures that predict therapy response and outcomes, but clinical translation has been slow. Using machine learning methods, the authors report tumour subtypes that are applicable across major imaging modalities and three cancer types. The tumour subtypes have distinct radiological and molecular features, as well as survival outcomes after conventional therapies.

An effective expansion system for therapeutic megakaryocyte-biased hematopoietic stem cells has not been developed. Here the authors present a microniche-based system that supports scalable expansion of human Mk-biased HSCs and identify their immune phenotype.

Light-induced azobenzene cis/trans isomerization has been extensively investigated, but the mechanical strength of its cis/trans structure is not well understood. Now it has been shown that cis azobenzene is mechanically less stable than the trans isomer due to its regiochemical structure, as revealed by single-molecule force spectroscopy.

Mutations in mitochondrial DNA (mtDNA) play critical roles in human diseases. Here, the authors describe an integrated Cas12a sensor for sensing mtDNA mutations in vivo, showing potential for diagnostic and therapeutic purposes.

Here, a draft sequence of the giant panda genome is assembled using next-generation sequencing technology alone. Genome analysis reveals a low divergence rate in comparison with dog and human genomes and insights into panda-specific traits; for example, the giant panda's bamboo diet may be more dependent on its gut microbiome than its own genetic composition.

The CA3 region of the hippocampus is involved in spatial working memory. Here, the authors show that neurons in the left CA3 are more active in the choice phase of correct trials of spatial working memory than neurons in the right CA3, revealing lateralization of spatial working memory.

Crystal structures of the human GLP-1 receptor in complex with two negative allosteric modulators reveal a common binding pocket, and, together with mutagenesis and modelling studies, further our understanding of the receptor activation mechanism.Author: Please check the wording of the following statement, which will appear online only.

EGLN2 hydroxylates histone H3 at proline 16, enhancing the binding of KDM5A to H3K4me3. Genome- and transcriptome-wide analyses show that the EGLN2–KDM5A axis regulates target gene expression in mammalian cells.

The development of non-invasive, rapid responsive phosphorescence is highly desirable but has rarely been described. Herein, the authors designed and prepare a series of molecular rotors containing a room temperature phosphorescence active triazine core and three bromobiphenyl units acting as rotors and demonstrate light stimulus triggered phosphorescence.

The crystal structure of the Frizzled 4 receptor transmembrane ___domain is reported to a resolution of 2.4 Å in a ligand-free state.

Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.

Tang et al. present the isolation and characterization of an Mmp1 encapsulin system from Mycobacterium smegmatis, highlighting its structural and functional features. The study reveals the cryo-EM and crystal structures, offering insights into the role of Enc-CD-loaded encapsulin in sulfur storage, stress resistance, and potential therapeutic applications against mycobacterial infections.

The first step in bacterial phospholipid biosynthesis is the acylation of glycerol 3-phosphate to form lysophosphatidic acid. Here, the authors present the high resolution crystal structure of the glycerol 3-phosphate acyltransferase PlsY, a membrane protein and give insights into its catalytical mechanism.

Smoothened receptors (SMO) play a key role in the Hedgehog signalling pathway. Here the authors present the structure of a multi-___domain human SMO with a rationally designed stabilizing ligand bound in the transmembrane ___domain of the receptor, and propose a model for SMO activation.