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Androgenetic alopecia is the most common type of hair loss, but its drivers remain poorly elucidated. Here, the authors show that hyperactive contraction of the follicle connective tissue sheath impairs hair growth by activating mechanosensitive signaling, suggesting a tractable therapeutic target.

Smc5/6 association with DNA junctions can support genomic functions. Here, the authors show that Smc5/6 junction polarity preferences, targeting, and dwell times are determined by its structural modules as well as the RPA and PCNA genomic factors.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

Tissue-specific mRNA or gene editing machinery delivery is achieved with lipid nanoparticles containing peptides with specific sequences, which tune the protein corona of the particles by mechanical optimization of peptide–protein binding affinities.

Neural tissue is a key signalling centre for fundic–antral patterning in development of gastric organoids featuring asymmetric PDX1 patterning.

By reconstituting and visualizing mammalian transcription elongation at the single-molecule level, Wang et al. dissected the effects of individual elongation factors on the speed of RNA polymerase II, which is found to operate as a multi-gear molecular machine.

Chemoresistance limits the success of chemotherapy in patients with cancer. Here, the authors perform 30 genome wide CRISPR knockout screens to identify genes associated to resistance against commonly used chemotherapeutics across multiple cancer types, followed by 26 second round CRISPR screens to identify druggable targets of chemoresistance.

Most eukaryotes do not use a consensus DNA sequence as binding sites for the origin recognition complex (ORC) to initiate DNA replication, however budding yeast do. Here the authors show S. cerevisiae ORC can bind nucleosomes near nucleosome-free regions and recruit replicative helicases to form a pre-replication complex independent of the DNA sequence.

2D semiconductors hold promise for solution-processed circuits requiring low-cost components and manufacturing scalability. Here, the authors investigate the criteria for the electrochemical exfoliation of high aspect-ratio nanosheets from 28 different layered materials, identifying the most promising candidates and key bottlenecks for solution-processed complementary electronics and functional circuits.

Reverse transcriptase is an essential enzyme for HIV replication. Single-molecule studies reveal for the first time the structural dynamics of the reverse transcription initiation complex in real time. Reverse transcriptase can bind its tRNA–vRNA substrate in two opposite orientations and flip between these two states.

A study reveals that most transcripts in Mycobacterium tuberculosis are incomplete, likely because of the tendency of the transcription machinery in this species to pause on genomic DNA.

Here the authors used single-molecule imaging and manipulation to study the mechanical effects of transcription factor Sox2 co-condensation with DNA and chromatin. They found that Sox2 condensates exert a high level of mechanical stress on DNA, but this stress is dramatically attenuated by nucleosomes assembled on the DNA.

Using single-molecule visualization and manipulation, Chang et al. show that the eukaryotic Smc5/6 complex preferentially binds to and stabilizes ssDNA-dsDNA junctions, which could serve as the molecular basis for its diverse roles in genome maintenance.

Efficient and stable catalysts for oxygen reduction reactions are difficult to achieve due to slow kinetics and degradation. Here, the authors use a ‘carbon defect anchoring’ strategy to create Pt₁Ni₁@Pt core-shell nanoparticles with high activity and durability.

Understanding the genetic basis of rubber tree domestication is critical for improving natural rubber production. Here, the authors assemble the genome of the rubber tree clone CATAS8-79 and conduct population and genetic association analyses to reveal the function of phytosulfokine in regulating number of laticifer rings.

An aluminum anode is proposed to achieve high lattice matching between the aluminum anode and the aluminum deposit, allowing the aluminum deposits to maintain preferred crystal face growth on the aluminum anode surface.

Using single-molecule techniques, the authors find that the methyl-CpG-binding protein MeCP2, whose mutations cause Rett syndrome, exhibits distinctive behaviors when bound to nucleosomes versus free DNA, thus directing its multifaceted functions on chromatin.

Proteins continuously undergo non-enzymatic modifications such as glycation, which accumulate under physiological conditions but can be enhanced in disease. Here the authors characterise histone glycation, provide evidence that it affects chromatin, particularly in breast cancer, and identify DJ-1 as a deglycase.

The physical properties of devices made of printed nanosheets and nanowires are determined by their intrinsic nanostructured network morphology. Here, the authors use FIB-SEM nanotomography to quantitatively analyze printed nanostructured networks via 3D reconstructions.

The electrical properties of nanostructured networks are often dominated by junctions between the particles. Here, Gabett et al. develop transport models and utilise impedance spectroscopy to quantify the factors limiting conduction in these systems.

Intravenously injected functionalized carbon quantum dots that bind to the large neutral amino acid transporter 1 and that structurally mimic large amino acids selectively accumulate in human tumours in mice, facilitating targeted theranostics.

T cell development has been a classical model for understanding cell fate regulation by epigenetics. Here the authors show that Cxxc1 controls thymocyte development mainly through regulating several key genes, such as Rorc, Zap70 and Cd8, which requires its H3K4me3 but not DNA methylation function.

Characterization of 22-nucleotide short interfering RNAs in plants finds that they accumulate in response to environmental stress, causing translational repression, inhibition of plant growth and enhanced stress responses.

Biosensors have a wide number of potential applications, but rapidly constructing genetically encoded biosensors remains challenging. Here, authors report a method for rapidly converting ANL superfamily enzymes into biosensors for organic acids, based on their conformational changes upon binding.

Polycomb-group proteins are key regulators of transcriptional programs that maintain cell identity. Here the authors provide evidence that PCGF5, a subunit of Polycomb Repressor Complex 1, is important for the differentiation of mouse embryonic stem cells towards a neural cell fate.

Using single-molecule imaging and manipulation, the authors show linker histone H1 preferentially forms phase-separated droplets with single-stranded nucleic acids over double-stranded DNA and nucleosomes, suggesting a noncanonical nuclear function.

A sequencing method that enables simultaneous determination of both 5′ and 3′ ends of cellular transcripts, SEnd-seq, reveals a more complex picture of transcription in E. coli, including the existence of multiple overlapping bidirectional terminators that regulate the efficiency of transcription termination.

Yijun Ruan and colleagues report the draft genome of the sweet orange, Citrus sinensis. Their data suggests sweet orange originated from a cross between pummelo and mandarin.

Fungal infection induces signaling downstream C-type lectin receptors through the activation of the tyrosine kinase Syk. Xiao and colleagues show that the phosphatase SHP-2 recruits Syk to dectin-1.

A shift in algal species from cold-tolerant to warm-adapted and increased primary productivity in lake Guozha Co, China, suggest rapid ecological changes outpacing climate change in Tibetan glacial lakes, according to combined analysis of lake sedimentary ancient DNA and remote sensing records.

This Primer on optical tweezers describes the instrumentation and experimental designs used in most single-molecule optical tweezers assays and discusses optical tweezers measurements in systems of biophysical interest such as DNA elasticity, protein and RNA folding, and molecular motors.