Browse Articles

Nonlinear electronic streaming instability in lunar plasmas

Combined biosynthesis and site-specific incorporation of phenylalanine derivatives from aryl aldehydes or carboxylic acids

Cryo-EM Structure of the TRPC1/5 Heteromer Enables Design of Antidepressant and Anxiolytic Drug with Reduced Side Effects

Abstract The TRPC1/5 heteromer exhibits electrophysiological and ligand-binding properties distinct from TRPC5 homomers, enabling tissue-specific cellular regulation. Here we present the cryo-EM structure of the TRPC1/5 heterotetramer at 2.8 Å resolution, revealing an asymmetric assembly of three TRPC5 subunits around one TRPC1 subunit. TRPC1 contributes a unique pore-loop configuration and specialized inter-subunit interfaces that sculpt an asymmetrical ion conduction pathway, altering gating and ion selectivity. The heteromer harbors a ligand-binding pocket at the TRPC1-TRPC5 interface absent in homomeric channels. Using this insight, we design JD03-02, a high-affinity antagonist preferentially targeting this pocket with >10,000-fold selectivity for TRPC1/5 over TRPC5 homomers. In mouse models, JD03-02 produces potent anxiolytic and antidepressant effects with reduced off-target activity. These findings elucidate the structural basis of TRPC1/5 function and can guide precision drug design targeting heteromeric ion channels in neuropsychiatric disorders.

Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice

Abstract Spinal muscular atrophy (SMA) results from a deficiency of the survival motor neuron (SMN) protein. Zolgensma, an adeno-associated virus (AAV)-based SMN1 gene-replacement therapy, is approved for SMA, though its long-term efficacy and safety remain uncertain. This study compares a Zolgensma-like benchmark vector with a 2nd-generation vector featuring a codon-optimized SMN1 transgene under the control of an endogenous SMN1 promoter. In SMA mice, intracerebroventricular delivery of the 2nd-generation vector improved survival and phenotypic outcomes compared with the benchmark. However, motor impairment was observed in wild-type mice 20 months post-injection with the 2nd-generation vector. Notably, cardiac thrombosis and hepatocellular carcinoma were associated with the benchmark vector, but not with the 2nd-generation vector. While AAV-related tumorigenesis appears to be species-specific to mice, these findings underscore the need for careful long‑term monitoring in patients treated with Zolgensma.

Human RNA polymerase III termination favors decomposition over facilitated recycling

Astrocyte activation in the ventrolateral medulla modulates breathing and arousal states

Counterfactual evaluation of elementary and secondary school policies in the COVID-19 pandemic

A polymer-coated nanowire sponge–based contact electrocatalytic system for simultaneous disinfection and removal of multiple micropollutants

Trainable neuromorphic spintronic hardware Via analog finite-difference gradient methods

ZNF274 constrains lineage plasticity and drives intrinsic resistance to CDK7 inhibitors in pancreatic cancer

Realization of a chiral photonic-crystal cavity with broken time-reversal symmetry

Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrotic remodeling of the skin and internal organs. Fibrotic tissue changes are considered hardly reversible with current therapies, suggesting that new strategies are required to modulate the disease-associated molecular and cellular phenotype to enable regeneration of affected tissues. Here, analyzing skin biopsy samples from patients with SSc who had received CD19-CAR T cell therapy as part of the CASTLE study or named patient use, we demonstrate structural regeneration of SSc skin structure, as evidenced by recovery of skin papillae. Consistent with these histological changes, cyclic in situ hybridization and imaging mass cytometry analyses suggested that fibroblast populations shifted towards a physiological state, both in terms of composition and function. Moreover, we describe signs of vascular repair and changes in epidermal cell function. These results suggest that B cell depletion using CD19-CAR T cell therapy may lead to skin tissue remodeling in SSc and highlight its potential for tissue regeneration in fibrotic diseases.

RBM20 isoform regulation by independent transcription start sites adapts alternative splicing in development and disease

Abstract RBM20 is a cardiac splicing regulator whose dysfunction causes severe cardiomyopathies. Here, we uncover an unexpected layer of RBM20 regulation through a previously unrecognized transcription start site located between the canonical exon 1 and exon 2. This alternative transcription start site generates a shorter, functional RBM20 isoform translated from an internal ATG in exon 2—identified as the predominant translation start site by ribosome profiling. Despite lacking exon 1, the isoform maintains splicing activity and is conserved across mouse, rat, and human. Strikingly, isoform ratios are tightly controlled during the perinatal period but are selectively altered in disease: in hypertrophic-, unlike in dilated cardiomyopathy, upregulation of RBM20 is driven largely by the alternative isoform. Our findings reveal disease and isoform-specific regulation as a second axis of RBM20 control, operating alongside phosphorylation-dependent nuclear localization, with broad implications for developmental splicing programs, cardiac remodeling, and targeted therapeutic strategies.

One-dimensional CsPbBr3 superlattices with polarized and amplified spontaneous circularly polarized emissions

Abstract Nanocrystal superlattices typically occur in two- or three-dimensional configurations, constrained to the micrometer scale and with limited size tunability. Here, we report one-dimensional superlattices prepared by self-assembly of CsPbBr 3 nanorods and nanoplatelets. These exhibit a hierarchical structure, evolving from ribbons (µm) of nanorods or nanoplatelets to assemblies of ribbons (mm). These superlattices have a diameter of 0.8–1 µm and length in the range of 13–1500 µm, and their aspect ratio can be tuned from 14 to 1200 by adjusting the shape of the nanorods and nanoplatelets. Thanks to their anisotropic structure, the superlattices show strong polarized emission with a near-unity degree of polarization, ≈4 times larger than that of randomly assembled film. These superlattices also exhibit chiral optical response (circular dichroism and circularly polarized emission). Since no chiral ligands are used in the synthesis, the chiral signal (negative or positive) from the superlattices is random. However, the signal can be controlled after the addition of chiral ligands. The maximum dissymmetry factor of the luminescence ( g lum ) is −0.11, and can be further amplified to −0.32 in the amplified spontaneous emission of the superlattices.

PD-1 regulates latent effector differentiation of thymic cytotoxic CD8+ T cells

Abstract Durable T cell immunity against cancer depends on the continual replenishment of effector CD8⁺ T cells. Thymic output has been associated with favorable prognosis in cancer patients across a range of ages, suggesting that the thymus is an important source for replenishing T cells capable of controlling cancer progression. However, whether CD8⁺ T cells acquire effector potential within the thymus, and how thymic output of effector CD8⁺ T cells contribute to peripheral tumor immunity, remain unclear. In this study, we discover that thymic single-positive (SP) CD8⁺ T cells undergo latent effector differentiation following thymic selection, but this process is subject to PD-1 regulation. We further demonstrate that PD-1 limits the contribution of thymic output of CD8⁺ T cells in shaping the TCR repertoire within the tumor tissues for tumor immunosurveillance. Although PD-1 inhibition facilitates the expansion of effector CD8⁺ T cells in the periphery, these cells gradually lose antitumor activity within tumors due to accelerated exhaustion in the absence of PD-1. Thus, while latent effector differentiation of thymic CD8⁺ T cells enables a rapid response to malignant cells in the periphery, PD-1 restrains this process to prevent overt or terminal effector differentiation, which may compromise balanced and durable peripheral immunity.

Emergent Spin Supersolids in Frustrated Quantum Materials

ABSTRACT Recent years have witnessed the emergence of spin supersolids in frustrated quantum magnets, establishing a material‐based platform for supersolidity beyond its original context in solid helium. A spin supersolid is characterized by the coexistence of longitudinal spin order that breaks lattice translational symmetry and transverse spin order associated with the spontaneous breaking of the spin U(1) symmetry. Extensive experimental investigations, together with advanced numerical studies, have now revealed a coherent and internally consistent picture of these phases, substantially deepening our understanding of supersolidity in quantum magnetic materials. Beyond their fundamental interest as exotic quantum states, potential applications in highly efficient demagnetization cooling have been supported by a giant magnetocaloric effect observed in candidate materials. Moreover, the possible dissipationless spin supercurrents could open promising perspectives for spin transport and spintronic applications. This review summarizes recent progress on emergent spin supersolids in frustrated triangular‐lattice quantum antiferromagnets, surveys experimental evidence from thermodynamic and spectroscopic measurements, and compares these results with theoretical studies of minimal models addressing global phase diagrams, ground state properties, and collective excitations. In addition, this review discusses characteristic spin‐transport phenomena and outlines future directions for exploring spin supersolids as functional quantum materials.

Lead Halide Perovskite Photoelectrocatalysis

ABSTRACT Lead halide perovskites have emerged as an outstanding class of light harvesting materials. While much progress has been made in solar cell efficiency, the materials also proved potential for light‐driven conversion of water, CO 2 or organic waste streams into solar fuels and value‐added chemicals. This case study highlights advances made in the rational photoelectrode design to improve solar‐to‐chemical conversion efficiency, product scope, and scalability. To this end, we will explore the interplay between device architecture and performance, strategies to suppress moisture degradation pathways, as well as fundamental mechanisms to steer selectivity of CO 2 reduction products. These insights are generalizable to a wide scope of thin‐film buried‐junction photoelectrodes, highlighting the unique applicability of this technology to real‐world scenarios.

Computational design, synthesis and biological evaluation of novel pyridinone derivatives as NNRTIs

Multifaceted gold vanoparticles by bark extract of Sweetinia mahagoni and their potential antimicrobial, antioxidant, anticancer and antiviral applications

Integrated deep learning model for multi-label retinal disease diagnosis