Browse Articles

A lightweight zero thermal expansion magnesium alloy

Ronceray L, Huibers MHW, Reutter K, et al. High-grade/large B-cell lymphoma-11q has a very good prognosis in children and young people without a predisposition. <i>Blood.</i> 2026;147(2):209-214.

NIH pivots away from agency-directed science

Engineering high environmental robustness in solar evaporation to bridge the lab-to-field performance gap

Beyond ATP: asciminib and the allosteric path in CML

Regulatory grammar in human promoters uncovered by MPRA-based deep learning

Formation of S- and Z-twist supramolecular micro-ropes by peptide stereoisomers

Abstract The intertwined strand arrangement in ropes, from micro- to macro-scale, results in tensile moduli significantly higher than those of single strands. Micro-scale ropes are found in biological systems, most commonly in mechanically-rigid collagen tri-strand arrangements. While human-made macro-ropes possess either left-handed (S) or right-handed (Z) twist, collagen exclusively adopts Z-twist architectures. Despite its natural abundance, the reconstruction and control of these supramolecular ropes in biomimetic systems using minimalist building units remains a fundamental challenge. Here, we demonstrate that cyclo-tryptophan-proline dipeptide stereoisomers self-assemble into complex crystalline supramolecular triple-helical structures. These unique architectures display tunable S- or Z-micro-rope-like twists governed by the configuration of tryptophan residues, as confirmed by co-assembly experiments and molecular dynamics simulations. Tensile testing revealed that these supramolecular micro-ropes exhibit significant moduli. These findings provide a potential platform for designing biomimetic functional helical materials with tunable supramolecular chirality and mechanical strength using minimalist building blocks.

DNA methylation matters: methylation of the γ-globin ( <i>HBG</i> ) gene promoters is required for postnatal silencing of HbF

Abstract Sufficient levels of fetal hemoglobin (HbF) can ameliorate the pathophysiologic basis of sickle cell disease and β-thalassemia postnatally. DNA methylation has long been posited to mediate silencing of HbF expression, but this has been controversial. Recent publications provide definitive evidence for the critical role of HBG gene promoter methylation in silencing and insight into the mechanisms involved. The data support a model in which methylation of CpG sites in the HBG promoters and repressive transcription factors recruit the MBD2-NuRD chromatin remodeling complex, which enforces silencing. These findings have implications for the treatment of β-globin disorders.

Structure-adaptive single-atom nickel catalysts for pure hydrogen peroxide electrosynthesis at industrial current density

Silencing of BCL11A by disrupting enhancer-dependent epigenetic insulation

Abstract The transcription factor BCL11A is a genetically and clinically validated regulator of the fetal-to-adult hemoglobin switch in human erythroid cells. CRISPR editing of an intronic enhancer within the BCL11A gene reactivates fetal hemoglobin (HbF) in adult erythroid cells, serving as the first CRISPR-based therapy for β-hemoglobinopathies. However, the molecular basis for the remarkable efficacy of CRISPR-mediated enhancer ablation remains elusive. Here, we describe a new genome architecture, an enhancer-dependent chromatin rosette, that is essential for epigenetic insulation and the developmentally regulated, hematopoietic lineage–specific expression of BCL11A. CRISPR-mediated disruption of the BCL11A erythroid enhancer impairs transcription of enhancer-driven RNAs and NIPBL-dependent cohesin loading, leading to the destabilization of the rosette structure, loss of chromatin insulation, and epigenetic silencing of BCL11A. Moreover, targeted depletion of enhancer RNAs using antisense oligonucleotides silences BCL11A by disrupting epigenetic insulation, causing HbF reactivation in adult erythroid cells. These findings uncover an essential role for enhancer-driven epigenetic insulation in transcriptional control, presenting a new strategy for the therapeutic targeting of BCL11A.

Mosquito–capsid interactions contribute to flavivirus vector specificity

Mirvetuximab soravtansine plus pembrolizumab in recurrent folate receptor alpha-positive uterine serous carcinoma: a phase II trial

Abstract Immune checkpoint inhibitors (ICI) synergize preclinically with antibody drug conjugates (ADC), harboring anti-tubulin maytansinoid payloads. We conducted an investigator-initiated, single-arm, phase 2 trial of mirvetuximab soravtansine (MIRV), a folate receptor alpha (FOLR1/FRα)-targeting ADC with the maytansinoid payload, DM4, combined with pembrolizumab in female patients with recurrent FOLR1-expressing serous endometrial cancer (EC, NCT03835819). Co-primary objectives include objective response rate (ORR) and rate of progression-free survival at 6 months (PFS6); secondary objectives include PFS, overall survival, duration of response and safety. Exploratory objectives include correlation of tumor genomics and immunoprofiling with clinical activity. Eighteen patients initiated protocol therapy [MIRV 6 mg/kg adjusted ideal body weight IV and pembrolizumab 200 mg IV every 3 weeks]. Confirmed ORR is 28% (1 complete and 4 partial responses, 95% CI:10-53%), Kaplan Meier estimate of PFS6 is 24.4% (95% CI:7.7-46.1%) with 4 patients progression free at 6 months; trial was closed early for feasibility (planned sample size of 35 patients not reached) and hence these results are considered preliminary. G3 treatment-related adverse effects were rare with no grade ≥4 toxicities. We report a population of high FOLR1-expressing tumor-associated macrophages (CD163 + FOLR1 + ), suggesting potential on-target, off-tumor immune editing by MIRV. A composite biomarker score derived in this cohort correlates with objective response to MIRV and pembrolizumab.

NLRP3 inflammasome blockade treats intestinal inflammation associated with chronic granulomatous disease

Abstract Chronic granulomatous disease (CGD) is an inborn error of immunity associated with a 50% prevalence of inflammatory bowel disease (IBD) for which current treatments are suboptimal due to the increased risk of infections in this population. CGD results from defects in the nicotinamide adenine dinucleotide phosphate oxidase 2 complex, leading to minimal or absent phagocyte-derived reactive oxygen species production. Patients with CGD present with recurrent infections and severe inflammatory complications, especially in the gut. These inflammatory complications have been associated with the increased systemic activation of the nucleotide-binding domain and leucine-rich-repeat–containing protein 3 (NLRP3) inflammasome and dysregulation of the T-cell compartment. However, the role of the NLRP3 inflammasome at the intestinal barrier and whether it can be targeted to treat CGD-associated IBD (CGD-IBD) remain unclear. β-Hydroxybutyrate (βHB), a ketone body produced during fasting or adherence to a ketogenic diet, can inhibit the NLRP3 inflammasome and restore T-cell balance. In this preclinical study, we demonstrated that a ketogenic diet significantly improves colitis in CGD mice, to a greater extent than in wild-type mice, by reducing NLRP3 inflammasome activity, altering the microbiota, and inducing tolerogenic immune populations at the intestinal mucosal barrier. We also showed that βHB supplementation could significantly improve colitis in CGD mice and decrease systemic inflammation. We further confirmed that, in the blood cells of humans with CGD, βHB effectively reduces the levels of cytokines associated with inflammasome activation. In conclusion, our study identified that NLRP3 inflammasome blockade using a ketogenic diet or βHB supplementation is a potential novel and safer treatment for CGD-IBD.

Single droplet displacement infrared action spectroscopy

Uncovering the genomic complexity of <i>PAX5</i> intragenic tandem multiplication via long-read and short-read sequencing

Abstract By integrating short-read whole-genome sequencing and RNA sequencing (RNA-seq) data with long-read RNA-seq, we dissect the complex genomic architecture of PAX5 intragenic tandem multiplication, revealing that these complex rearrangements result in in-frame transcripts that likely encode proteins with altered domains.

Parkinson’s disease as a somato-cognitive action network disorder

Tropical precipitation response to anthropogenic climate change in recent decades

Abstract Tropical rainfall plays a central role in the climate system, shaping ecosystems and societies. Here we show that recent tropical rainfall changes are primarily driven by spatial shifts in atmospheric circulation rather than thermodynamic processes, and cannot be explained by the “Wet Get Wetter” or “Warm Get Wetter” paradigms. Observations reveal a northward shift in precipitation with wetting in the western and northern equatorial Pacific, northern Indian region, and drying south of the equator in the Pacific and South America. These trends coincide with a La Niña-like sea surface temperature pattern, strengthened Walker circulation, Southern Ocean cooling, enhanced land-sea and inter-hemispheric thermal gradients, and intensification of the Indo-Pacific warm pool. Climate models largely miss the first three features, projecting instead a reduced equatorial Pacific sea surface temperature gradient, but capture large-scale thermal gradients and Indo-Pacific warm pool changes. We show that amplified land-sea thermal contrast and Indo-Pacific warm pool intensification reproduce the observed circulation and rainfall changes. Coupled sensitivity experiments further confirm that land warming and ongoing desertification in the Northern Hemisphere act as active drivers of current tropical hydroclimate changes, challenging ocean-centric assumptions in current climate models.

Targeting enhancer RNAs to silence transcription

Attentional semantic attack for enhancing adversarial samples transferability

Analysis of medieval burials from Ibiza reveals genetic and pathogenic diversity during the Islamic period

Abstract Ibiza, an island in present-day Spain, was conquered in 902 CE by the Umayyad Emirate of Córdoba. The island remained under Islamic rule until 1235. Here, we analyse the genetic and metagenomic profiles of 13 individuals from an Islamic cemetery in Ibiza, dated to 950–1150 CE. Genome-wide analyses reveal heterogeneity, with ancestry components from Europe, North Africa, and Sub-Saharan Africa. Our analyses estimate that North African gene flow occurred two to seven generations before these individuals lived, suggesting admixture following the Islamic conquest of Iberia and potentially on Ibiza itself. Notably, two individuals trace their Sub-Saharan origins to distinct regions, Senegambia and present-day southern Chad, providing direct evidence of trans-Saharan connections via military and slave networks documented in contemporary Arabic sources. Metagenomic analyses detect several pathogens in this community, with one individual carrying Mycobacterium leprae , offering insight into the presence of leprosy in Ibiza. Our findings align with the historically documented two-pulse demographic model, indicating an initial settlement following the early tenth-century conquest and a second influx associated with Almoravid movements in the twelfth century. These securely dated genomes offer insights into medieval population dynamics and health in the Balearics.