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Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor ___domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

PandemicLLM adapts the large language model to predict disease trends by converting diverse disease-relevant data into text. It responds to new variants in real time, offering robust, interpretable forecasts for effective public health responses.

The use of Raman spectroscopy in biochemical applications has been hindered by several limitations. Here, the authors present a fiber-array Raman engine, termed FIRE. This tool features a dynamic single-channel photon-counting detector and is used for full Raman spectral imaging in biological samples and whole organisms.

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.

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.

High-throughput immunoassay is crucial for scientific and clinical applications. Here, the authors introduce a multiplex immunoassay platform engineered by modifying a pipette tip with a self-assembled barcoded protein array. It outperforms the gold standard in sensitivity, speed, and sample volume.

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.

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.

CRISPR homing gene drives can suppress pest populations by targeting female fertility genes, converting wild-type alleles into drive alleles in the germline of drive heterozygotes. Here the authors demonstrate a genetic pest suppression system based on dominant female-sterile doublesex alleles and show that releases of transgenic males eliminated Drosophila cage populations, with modelling showing improved performance compared to similar systems.

Gene drive alleles bias their inheritance to spread through populations. Here, we constructed a moderate efficiency 2-gRNA nanos-Cas9 homing suppression drive in the malaria mosquito Anopheles stephensi targeting doublesex. With vasa-Cas9, high efficiency and self-limiting suppression was achieved.

Here the authors demonstrate a temporal Vernier caliper for arbitrary waveform synthesis with a sampling rate over 1 TSa/s. These results, which surpass current electronic systems by an order of magnitude, have potential applications in radar and high-speed communications.

The functional role of the co-presence of aberrant long non-coding RNAs (lncRNAs) and coding genes in cancer remains poorly understood. Here, the transcriptional regulator Prohibitin 2 (PHB2) is shown to co-regulate the transcription of an oncogenic CASC15- New-Isoform 2 (CANT2) lncRNA and the tumour-suppressor gene CCBE1 accelerating tumorigenesis of melanoma.

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.

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.

DNMT3A-nucleosome interaction underpins the genomic DNA methylation landscape. Here, the authors investigate how an N-terminal fragment of DNMT3A recognizes the H2AK119ub1-marked nucleosome, providing insights into the chromatin-targeting mechanism of DNMT3A.

The integration of antibody-guided cell typing and mass spectrometry-based proteomics remains challenging. Here, the authors develop Spatial and Cell-type Proteomics (SCPro), a multimodal spatial proteomics approach for profiling tissue proteome heterogeneity.

Rational regulation of electronic structures to control CO₂ electroreduction pathways is challenging. Here, the authors report modulating the highest occupied orbital of Cu single-sites via electronic metal-support interaction, enabling switchable selectivity between multicarbons and methane.

Hydrogel-based flexible sensors have potential in a number of fields, but mechanical properties can be compromised as a result of water evaporation. Here, the authors report a method for limiting of water loss by addition of a lipid-based coating to the surface of the hydrogel.

The primary risk factor for glaucoma is elevated intraocular pressure. Here, the authors show that AAV-delivered CasRx to reduce the expression of Rock1 and Rock2 as well as Aqp1 and Adrb2 can significantly reduce intraocular pressure, ultimately delaying glaucoma progression in mice.

DNMT3A R882H and R882C are mutation hotspots in acute myeloid leukemia. This study describes the structural and functional consequences of the DNMT3A R882H/R882C mutations which can provide a strategy for therapy of the disease mutations.

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.

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.

Agricultural land-use change affects belowground biodiversity. Here, the authors compare soil microbial communities from natural ecosystems and agricultural systems, finding that agricultural conversion leads to taxonomic and functional homogenisation.

Helium is the second most abundant element in the universe, and at low temperatures it becomes a quantum crystal with exotic physical properties such as second sound, superfluidity, and giant plasticity. Here authors prepare 2D solid helium at room temperature through diamond lattice confinement.

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

This study investigates the regulatory mechanisms of DNA-lncRNA triplexes, specifically their role in gastric cancer through the stable formation and precise oncogenic activity of the SENP5/GAU1 triplex. It shows how PPIA orchestrates the SENP5/GAU1 DNA-lncRNA triplex.

While Zinc anodes are thermodynamically unstable in aqueous solutions, the protons (H+) from the water favor the cathodes of Zinc batteries. Here, the authors address this contradiction by designing an asymmetric electrolyte composed of an inorganic solid-state electrolyte and a hydrogel electrolyte.

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.

Primary biliary cholangitis is a rare, chronic immune-mediated liver disease triggered by environmental exposures in genetically susceptible individuals. Here, the authors investigate the functional mechanism underlying the association of 19p13.3 variants with primary biliary cholangitis.

Hydrogels capable of swift mechanical energy dissipation are desirable for various uses, but traditional energy absorption in hydrogels typically relies on viscoelastic mechanisms and often suffers from slow recovery. Here, the authors report a hydrogel design harnessing molecular friction to achieve efficient energy dissipation and rapid recovery.

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.

In mammals, DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B. Here the authors report the crystal structures of DNMT3B in complex with both CpG and CpA DNA, providing insight into the substrate-recognition mechanism underpinning the divergent genomic methylation activities of DNMT3A and DNMT3B.

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.

MYC2 is a master component of jasmonate signalling, working in concert with MED25, a subunit of the Mediator transcriptional co-activator complex. Here it is shown that MYC2 and MED25 have largely overlapping targets and mediate DNA looping between these enhancer and promoter sequences.

In mammals, de novo DNA methyltransferase DNMT3B is essential for establishing DNA methylation patterns during embryonic development. Here the authors provide a structure-function characterization of homo-oligomeric DNMT3B, revealing the molecular basis for its vulnerability to ICF mutations.

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.

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.

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.

Unconventional superconductivity may emerge from the interplay between strong spin–orbit coupling and magnetism. Here, Chen et al. report an anomalous Fraunhofer pattern in three-dimensional topological insulator Bi₂Se₃ and attribute it as a signature of finite momentum Cooper pairing.