Browse Articles

IKAROS descent and rise of lenalidomide-associated B-ALL

Dissecting polycomb complexes for enhanced fetal hemoglobin production

Abstract Polycomb repressive complex 1 (PRC1) and PRC2 regulate diverse developmental processes, including the fetal-to-adult switch in hemoglobin (Hb) production, a process whose reversal is a goal for the treatment of sickle cell disease and β-thalassemia. PRC inhibitors show promise for various disorders, but use is limited because of pleiotropic PRC activities. We explored whether fetal Hb (HbF) can be reactivated in adult erythroid cells by selective perturbations of PRC1 or PRC2 components without complete loss of PRC function. A high-density CRISPR–CRISPR-associated protein 9 (Cas9) mutagenesis screen identified a region in EZH2 in which Cas9 induced exon 14 skipping (EZH2Δ14). EZH2Δ14, which lacks a portion of the CXC domain, relieves HbF repression while largely maintaining cellular fitness. EZH2Δ14 retains H3K27 methylation and repression of a PRC target gene subset. Experiments in cells derived from mice bearing human β-globin genes confirm that pathways mediating EZH2 control of HbF expression can function in a mouse model of HBG switching. These findings demonstrate that partial disruption of PRC can yield selective phenotypes, highlighting the therapeutic potential of targeting nonenzymatic domains within chromatin-modifying complexes.

Precision targeting of fetal hemoglobin repressors

How I utilize somatic alterations in the diagnosis, risk stratification, and therapy of hypocellular bone marrow failure

Abstract Hypocellular bone marrow failure (BMF) may be acquired due to immune-mediated disease, the prototype being immune aplastic anemia (IAA), or inherited, due to germ line defects in genes important for hematopoietic stem cell function and maintenance (inherited BMF syndromes [IBMFS]). Proper diagnosis of the underlying etiology of hypocellular BMF, particularly distinguishing IAA, myelodysplastic syndrome (MDS; most relevant in this setting is hypoplastic MDS), and the IBMFS, is important given the differences in clinical management. Clonal hematopoiesis (CH), in this context comprising somatic mutations or chromosomal abnormalities, is incorporated into standard algorithms for classification, risk stratification, and treatment decisions for hematologic malignancies, but the clinical significance in BMF is not well established. Disease-specific clonal signatures have been reported across the BMF spectrum, and here, we present how distinct patterns of CH can aid in distinguishing different etiologies of hypocellular BMF. In addition, detection of somatic alterations in many BMF disorders can estimate risk for secondary myeloid neoplasms, guide surveillance and, in some instances, allow for early therapeutic intervention.

Pound wise, penny foolish: improving value in SCD care

Anti-BCMA/GPRC5D CAR T cells in patients with relapsed or refractory multiple myeloma who have extraosseous extramedullary disease

Abstract Patients with relapsed or refractory multiple myeloma (RRMM) with extraosseous extramedullary disease (EMD) have inferior outcomes and lack effective therapies. We developed anti–B-cell maturation antigen (anti-BCMA)/G protein–coupled receptor, class C group 5 member D (GPRC5D) bispecific chimeric antigen receptors (CARs) to investigate the activity and safety of the CAR T cells in patients with extraosseous EMD. In this single-arm, open-label, phase 2 trial, we enrolled 37 patients with RRMM with extraosseous EMD, and anti-BCMA/GPRC5D bispecific CAR T cells were administered at 2.0 × 106 CAR T cells per kg. At a median follow-up of 10.1 months (interquartile range, 6.4-19.1), 36 of 37 patients (97%) obtained an overall response and measurable residual disease negativity, including 16 (43%) with stringent complete response. The median progression-free survival was 5.8 months (95% confidence interval, 2.2-9.4), and the median overall survival was not reached. The most common grade 3 or worse adverse events were hematologic toxicities (except lymphopenia; 37/37). Twenty-seven patients (73%) experienced cytokine release syndrome, all cases of which were grade 1 or 2. Two patients (5%) had grade 1 or 3 immune effector cell–associated neurotoxicity syndrome. These findings support that anti-BCMA/GPRC5D bispecific CAR T cells induced a high response rate in patients with RRMM with extraosseous EMD, and the safety profile was manageable. This ongoing trial is registered at www.clinicaltrials.gov as NCT05509530.

Bispecific CAR T for extramedullary myeloma: a minute waltz

Biosimilars approved for hematology use: lessons from comparative efficacy studies and comparative analytical assessments

Abstract Biosimilars used in hematology have been at the forefront of biosimilar development since the first US approval in 2015 of a filgrastim product, with >80 now licensed by the US Food and Drug Administration (FDA). Developers traditionally submitted data from a comparative analytical assessment (CAA) and clinical studies, often including a comparative efficacy study (CES), to support demonstrating their product is “highly similar” to and has “no clinically meaningful differences” from its reference product (RP). However, growing scientific confidence in the analytical comparisons between biosimilars and their RP included in the CAA has prompted the FDA and global regulators to reconsider the utility of CESs. Recently, the FDA published updated recommendations on the need for a CES in biosimilar programs. As approvals for hematologic biosimilars span the entire history of FDA biosimilar development across a breadth of patient ages and diseases, reexamining these programs provides valuable insights into the evolving role of the CES in the past and its role in the future. In this review, we present a historical overview of the development programs for all FDA-approved hematologic biosimilars in the context of an emerging global consensus recognizing that the CAA is more sensitive than the CES for predicting biosimilarity.

ELN-DAVID recommendations for NGS-based <i>FLT3</i> -ITD MRD testing for patients with acute myeloid leukemia

Abstract FLT3-internal tandem duplication measurable residual disease testing for patients in remission from acute myeloid leukemia is now recommended by the recently updated clinical standard-of-care guidelines. This companion technical note provides important laboratory and clinical recommendations regarding such testing.

A Pyridine Mediator Enables High‐Efficiency, Long‐Cycling Anode‐Less/Free Lithium–Sulfur Batteries With Li ₂ S Cathodes

ABSTRACT Lithium sulfide (Li 2 S) is a promising high‐capacity cathode material. Importantly, it can provide lithium source, enabling lithium batteries with an anode‐less/free configuration. However, Li 2 S suffers from poor conductivity, high polarization, low material utilization, as well as the shuttle effect, severely restricting the long cycling performance of batteries. Herein, lithium pyridine‐2‐thiolate (PySLi) is proposed as a multifunctional mediator for Li 2 S‐based anode‐less/free batteries. It is revealed that PySLi can modify the reaction pathway of Li 2 S, comprehensively enhancing its electrochemical redox kinetics and stability. Results show that the energy efficiency of the Li||Li 2 S cell with PySLi stabilizes at ∼80% in the full‐scale range from 0.1 C to 3 C rate, which is much higher than that without PySLi (49% at 0.1 C and 22% at 3 C). The stability of the lithium metal anode is also improved, maintaining a high coulombic efficiency of &gt;98% for 200 cycles and stable lithium stripping/plating behavior for 1000 h. Moreover, an anode‐free battery based on Li 2 S cathode works normally for 150 cycles, and an anode‐less pouch cell retains steady performance for 200 cycles. This multifunctional mediator provides a new strategy for the application of Li 2 S and stable anode‐less/free batteries with high energy density.

Comprehensive Review on Stability of Quasi‐2D Perovskite LEDs: Mechanistic Insights Into Intrinsic/Extrinsic Degradation and Innovative Stabilization Strategies

ABSTRACT Quasi‐two‐dimensional (quasi‐2D) perovskite light‐emitting diodes (PeLEDs) have gained a strong competitive edge in next‐generation display, thanks to their exceptional electronic and optical properties. In recent years, the performance of quasi‐2D PeLEDs has advanced steadily, with their external quantum efficiency (EQE) climbing to approximately 30%, highlighting immense development potential. However, the operational stability of these devices remains a critical bottleneck, severely limiting their commercialization. Consequently, this review focuses on the influencing factors and mechanisms governing the stability of quasi‐2D perovskites. Centering on the stability of quasi‐2D PeLEDs, we first systematically analyze the key stability‐affecting factors from the dual dimensions of intrinsic and extrinsic causes. Subsequently, we summarize strategies for enhancing the stability of quasi‐2D PeLEDs, including component regulation, additive regulation, phase distribution regulation, device structure regulation, process parameter regulation, and so on. Finally, we outline the challenges and opportunities currently faced in achieving stable quasi‐2D PeLEDs, providing a clear direction for the development of high‐performance, long‐lifetime quasi‐2D PeLEDs.

Coupling Stress Delocalization With Lithiation Homogenization: Omnidirectional Conformal Interface Integrating Silicon Oxycarbide–Graphite Anode

ABSTRACT Integrating Si‐based anodes with graphite has been widely recognized as an effective strategy for pursuing high‐energy‐density lithium‐ion batteries (LIBs). However, the “stress singularity” effect arising from heterogeneous interfaces gradually leads to interfacial slippage and further triggers electrical isolation, fundamentally resulting in mechanical failure and kinetic heterogeneity within the electrode. Herein, we realize conformal interlocking between silicon oxycarbide (SiOC) and discrete graphite domains in developed omnidirectional conformal interface SiOC–graphite (OSiOCG) electrodes to overcome the “stress singularity” effect. Mechanically, the omnidirectional conformal interface effectively transforms localized piercing force into hydrostatically distributed compressive force, effectively dissipating the “stress singularity” effect. Kinetically, it crosslinks isolated sites of transfer of electron/Li‐ion into 3D‐percolation networks across the entire interface. This mitigates local polarization, regulates the sequence and depth of lithiation for active components, and further dissipates the concentrated stress. The OSiOCG electrodes deliver stabilized cycling for 2000 cycles (average capacity decay &lt; 0.005% per cycle), optimized rate capability (capacity increases of 19.3% at 4C and 12.8% at 10C), and effective practicality validated in pouch cells (88.3% capacity retention at 4C). This work sheds light on interfacial stress delocalization within Si‐based graphite composite electrodes while paving the way for long‐term reliability enhancement of commercialized high‐energy‐density LIBs.

Perception‐Feedback Mapping Strategies for Flexible Human–Machine Interfaces

ABSTRACT The field of flexible human–machine interfaces (HMIs) has been evolving rapidly with progress in materials science, structural design, device fabrication, and system integration. Developments of advanced flexible sensing and feedback devices have remarkably expanded the perceptual modalities, feedback capabilities, and functional scope of these systems. However, the broader deployment of flexible HMIs depends not only on the device performance of sensing/feedback components, but also on the control strategy that translates sensed signals into command outputs for feedback modules. This review highlights recent progress in such perception‐feedback mapping strategies for flexible HMIs. Representative sensing and feedback modules, together with common system‐level physical architectures, are briefly introduced as a basis for analyzing the relationship between sensed inputs and feedback outputs. A systematic framework is then proposed based on the principle of signal flow from the perception to the feedback side, allowing perception‐feedback mapping strategies to be classified into command‐based mapping, continuous mapping, and closed‐loop control. Comprehensive discussions on these three categories of mapping strategies are presented, covering their operating principles, system implementation, and practical applications. Finally, we discuss current challenges and future directions toward more robust, generalizable, and integrated flexible HMI systems.

Pore Engineering of Covalent Organic Frameworks Boosts Chlorine Confinement and Electrochemical Performance in Li─Cl ₂ Batteries

ABSTRACT The development of high‐energy‐density Li─Cl 2 batteries is hindered by insufficient Cl 2 storage in cathodes. Although porous host materials have been preliminarily explored, the effect of pore size on Cl 2 confinement and electrochemical behavior still remains unclear. Herein, two novel covalent organic frameworks (COFs) with distinct pore sizes, namely TH‐COF (mesoporous, 2.7 nm) and HH‐COF (microporous, 0.9 nm), were fabricated by reacting triphenylene‐2,3,6,7,10,11‐hexacarboxylic acid with 3‐ and 6‐connected amines, respectively, to serve as a model system for elucidating the pore‐size effect in Li‐Cl 2 batteries. Owing to its smaller pore size and resultant stronger spatial confinement, the microporous HH‐COF enables superior Cl 2 capture and markedly enhanced battery performance, as exemplified by a high capacity of 4500 mAh g −1 , a high current density of 10 000 mA g −1 , and a Coulombic efficiency (CE) above 94% for each of the 500 cycles, outperforming its mesoporous TH‐COF counterpart and all previously reported electrodes. Density functional theory calculations reveal stronger host‐guest interactions between Cl 2 and the microporous HH‐COF than its mesoporous counterpart TH‐COF. This study not only clarifies the pivotal role of pore‐size engineering in Li‐Cl 2 batteries but also establishes a rational design principle for developing high‐performance Cl 2 host cathodes.

Ternary Heterostructures With Gradient Built‐In Electric Fields Through Stepwise Screening for Highly Reversible Sodium Storage at Low Temperature

ABSTRACT Heterostructure engineering is considered a promising approach to improve sodium storage at low temperatures (LTs). However, the trial‐and‐error fabrication method as well as insufficient interface control dimensions in traditional two‐component heterojunctions result in low efficiency and limited electrochemical performance improvement. Herein, a screening‐driven strategy guided by theoretical descriptors is proposed to identify MoS 2 /MoO 2 as the optimal binary heterostructure for improving sodium storage performance at LTs. Importantly, this result reveals a clear relationship between heterostructure configuration and electrochemical performance, where the work function ( W f ) difference and the resulting charge redistribution regulate Na + storage behavior. Inspired by this understanding, Ti 3 C 2 T x MXene is introduced to construct a multi‐interface system with cascaded W f alignment, establishing a gradient built‐in electric field that overcomes the localized modulation of conventional binary heterostructures. Such heterostructure induces an electron‐enriched region that acts as a Na + reservoir, thereby facilitating efficient Na + storage and transport at LTs. Meanwhile, the multiphase heterointerface optimizes the reaction pathway and mitigates kinetic limitations. Consequently, the MoS 2 /MoO 2 /Ti 3 C 2 T x ternary heterostructure delivers high reversible capacity, excellent rate performance, and robust cycling stability even at −20°C. This work establishes a general and predictive strategy for accelerating the rational design of high‐performance electrodes through the proposed screening framework.

Mechanically, Thermally, and Interfacially Robust Solid Polymer Electrolytes Enabled by an Organic–Inorganic Interwoven Architecture

ABSTRACT Solid polymer electrolytes (SPEs) are promising for use in high‐energy‐density solid‐state Li metal batteries. However, their practical application is hindered by challenges including poor mechanical strength, inadequate thermal stability, electrode‐interface instability, and sluggish ionic transport, which collectively fall short of the required safety and performance standards. Here, we develop an organic–inorganic interwoven architecture using PBO nanofiber and MXene nanosheets as a multifunctional host for SPE. This interwoven framework enhances the mechanical strength and toughness of the solid electrolyte by 12.5‐ and 7‐fold, respectively, and reduces thermal shrinkage below 10% at 200°C. More importantly, we demonstrate that the interwoven structure promotes Li salt dissociation through strong local electric‐field polarization, accelerates Li‐ion transport (0.75 mS cm −1 ), and enhances the stability (8000 h without short‐circuiting) of the Li metal interface during battery operation while suppressing exothermic side reactions under extreme thermal runaway conditions. Using this strategy, solid‐state Li metal pouch cells operate stably under mechanical and thermal abuse conditions, delivering 91.7% capacity retention after 300 cycles at 10C and 90°C. This work effectively addresses the interrelated challenges of mechanical strength, ion transport, and interface/thermal stability of SPE, offering a promising strategy for safe and high‐performance solid‐state Li metal batteries.

Compositional and Structural Engineering of MAX Phases and Their Derivatives for Electrochemical Energy Storage and Conversion

ABSTRACT MAX phases feature exceptional compositional and structural tunability, serving as a versatile materials platform for electrochemical energy storage and conversion, both as direct active materials and as chemical precursors for an array of functional derivatives. However, a unified framework connecting compositional and structural evolution across the MAX‐phase platform materials with electrochemical functionality remains underdeveloped. Here, we review recent advances in MAX phases and their derivatives for electrochemical energy storage and conversion. We focus on compositional design, structural modulation, and derivative engineering and their roles in shaping charge‐storage mechanisms, reaction kinetics, and long‐term stability across secondary batteries, supercapacitors, and electrocatalysis. Finally, we outline future perspectives and design principles based on compositional‐structural‐functional relationships to guide the rational design of MAX‐based materials for electrochemical applications.

Assembly and Disassembly of Nanoparticles for Antitumor Applications: Mechanisms, Strategies, and Functions

ABSTRACT Nanoparticles (NPs) demonstrate tremendous potential in tumor therapy, diagnostic imaging, and precision medicine. Their performance is regulated by their assembly and disassembly, which influence drug delivery, therapeutic efficacy, and biosafety. However, existing reviews are confined to single therapeutic modalities, specific assembly strategies, or isolated functional optimization approaches, and do not systematically examine of NP assembly‐disassembly processes and their biological functions. Accordingly, this review first discusses the driving forces behind NP assembly and disassembly, including hydrophobic, electrostatic, hydrogen bonding, and π–π interactions. Subsequently, the NP assembly strategies, covering ex situ and in situ self‐assembly, are summarized, and the applications by which assembled NP extend blood circulation residence time, enhance tumor accumulation, protect therapeutic cargo, and potentiate therapeutic efficacy are examined. The major NP disassembly pathways, including bond cleavage, carrier degradation, coordination dissociation, supramolecular dissociation, and phase transition, are subsequently discussed, highlighting their involvement in drug release, intracellular trafficking, and molecular imaging. Finally, a trade‐off‐based assembly and disassembly discussion outlines the key challenges for clinical translation, aiming to guide the development of more effective NP‐based therapeutic systems.

Cryogenic Thermoelectric Enhancement by Nonparabolic Band‐Edge Transport in Bi ₂ Te ₃

ABSTRACT Selective scattering of electrons near the Fermi level is the kinetic origin of the thermoelectric effect. Pronounced band nonparabolicity near the band edge is expected to promote the decoupling of a high Seebeck coefficient from high electrical conductivity; however, accessing this band‐edge transport regime at low temperatures remains challenging, as defect‐dominated scattering often masks the intrinsic band‐structure effects. Here, we experimentally show that single‐crystalline Bi 2 Te 3 can access a reduced‐scattering band‐edge transport regime in which the transport distribution becomes strongly energy dependent, enabling simultaneously a sizable thermopower and a high carrier mobility at cryogenic temperatures. This approach yields a record thermoelectric power factor of three times as high as that of conventional parabolic band‐dominated Bi 2 Te 3 . Quantum oscillation measurements reveal multiband transport components consistent with the band‐structure complexity of Bi 2 Te 3 , and magneto‐thermal conductivity measurements indicate a reduced Lorenz factor and suppressed electronic thermal conductivity in the same regime. The resultant over 600% thermoelectric enhancement in conventional Bi 2 Te 3 demonstrates a practical strategy of advancement by engineering band‐edge transport in strong spin–orbit coupled materials.

Confinement‐Induced Donnan Potential Enables Sealed Hydrovoltaic Power From Microliter Water

ABSTRACT Hydrovoltaic power generation offers a promising route for sustainable energy generation, yet existing systems typically rely on evaporation‐driven flow or environmental moisture gradients, limiting device encapsulation and compact integration. Here, we introduce a confinement‐induced ion‐selective mechanism that enables sealed hydrovoltaic power generation from minimal water input. By engineering asymmetric nanochannel confinement in MXene/cellulose nanofiber (CNF) composites, localized hydration generates spatially distinct cation selectivity, establishing a persistent ion gradient and a confinement‐dependent Donnan potential that drives capacitive charge accumulation. The harvested energy derives from substantial interfacial free energy released upon hydration of nanochannels with a high surface‐to‐volume ratio. Slow capillary migration then delays relaxation of the ion gradient, sustaining this charging and prolonging the resulting direct current (DC) output, without reliance on evaporation‐driven flow or ambient humidity. Consequently, a single 3 µL water droplet enables stable DC output for up to 45 h. The device operates robustly under airflow (5–20 L min −1 ), relative humidity (17%–90%), and various electrolytes (tap water, seawater, and sweat), demonstrating humidity‐insensitive, sealed operation. This confinement‐governed hydrovoltaic framework expands the mechanistic understanding of water‐enabled energy generation and provides a scalable platform for wearable and distributed electronics.