Browse Articles

Near-infrared photon-triggered CH4-to-CH3OH conversion over plasmonic oxyselenides

Immunogenicity and safety of a recombinant gE-Fc fusion protein subunit vaccine for herpes zoster in adults ≥50 years of age: a randomised, active-controlled, non-inferiority trial

Abstract The licensed adjuvanted recombinant glycoprotein E (gE) subunit vaccine (HZ/su) is highly effective against herpes zoster (HZ). This randomised, active-controlled, non-inferiority trial (ChiCTR2300079076) compared the immunogenicity and safety of a novel gE-Fc fusion protein vaccine candidate (LZ901) with HZ/su in 300 healthy adults aged ≥50 years without prior HZ vaccination in Wuxi, China. Participants received either two doses of LZ901 (30-day interval; n = 151) or HZ/su (60-day interval; n = 149). The primary outcomes was the proportion of participants with simultaneous positive responses to two or more cytokines (IFN-γ, IL-2, TNF-α, or CD40L) 30 days after the second dose (referred to as gE-specific CD42+/CD82+ T-cell responses). LZ901 demonstrated non-inferiority to HZ/su (margin > −10%) for both CD4+ and CD8+ T-cell responses. Significantly higher response rates were observed with LZ901 for CD42 + T-cell responses (83.0% [117/141] vs 58.1% [79/136]; p < 0.0001) and CD82 + T-cell responses (46.8% [66/141] vs 8.8% [12/136]; p < 0.0001). Adverse reactions were markedly lower with LZ901 (41.1% [62/151] vs 87.9% [131/149]; p < 0.0001), including grade 3 events (0.7% [1/151] vs 6.0% [9/149]). LZ901 induced superior cellular immunogenicity and exhibited a better safety profile than HZ/su in adults ≥50 years, supporting its potential as a promising HZ prevention candidate vaccine.

Structural basis for substrate recognition mechanism of human SLC26A7

Abstract Solute carrier family 26 (SLC26) mainly mediates transmembrane transport of various anion ions, including chloride and other halide ions, bicarbonate, oxalate, and sulfate. Many severe hereditary human diseases are correlated with SLC26 protein mutations. Here we report cryo-EM structures of human SLC26A7 in apo and iodide binding states. We identify non-canonical binding site for halide ions in SLC26A7. Molecular dynamics simulation and electrophysiological assay confirm the functional importance of key residues involved in iodide and chloride coordination. Together, our discovery marks a step towards an in-depth understanding of SLC26 family protein transport mechanisms.

Widespread ilmenite contributions to the surface water cycle in lunar Procellarum KREEP Terrane

A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers

Abstract The Anaplastic Lymphoma Kinase (ALK) gene is a receptor tyrosine kinase (RTK) with expression restricted to the developing nervous system. Most neuroblastomas express native ALK protein on the cell surface and ALK is uniformly overexpressed in fusion-positive rhabdomyosarcoma and in subsets of metastatic colorectal carcinoma, melanoma, ovarian carcinoma, and breast carcinoma. Here, we first confirm that ALK RNA, protein, and tumor cell surface expression is elevated in multiple pediatric and adult malignancies with minimal expression in childhood normal tissues. We then demonstrate that a humanized ALK-directed antibody conjugated to pyrrolobenzodiazepine (CDX0239-PBD) is internalized in ALK-expressing neuroblastoma cell lines with cell surface expression-dependent cytotoxicity. Finally, we show that CDX0239-PBD exhibits potent antitumor efficacy including maintained complete responses in ALK-expressing patient and cell line-derived neuroblastoma, fusion-positive rhabdomyosarcoma, and colorectal carcinoma xenograft models. These data support the clinical development of a first-in-class ALK-directed antibody-drug conjugate (ADC) for multiple pediatric and adult ALK-expressing malignancies.

Unidirectional electric field enables reversible ferroelectric domain engineering

Design and nonviral delivery of live attenuated vaccine to prevent chronic hepatitis C virus-like infection

Co-translational ribosome pairing enables native assembly of misfolding-prone subunits

Capturing nematic order on tissue surfaces of arbitrary geometry

Microstructural transformation for robust and high-efficiency Zintl thermoelectrics

Flexible Ag2Se-based thin-film thermoelectrics for sustainable energy harvesting and cooling

Abstract The high cost and complexity of fabrication limit the large-scale application of flexible inorganic thermoelectric materials. Currently, Bi2Te3-based materials are the only commercially viable option, but the inclusion of Te significantly increases production costs. This study presents a simple and cost-effective method for fabricating flexible Ag2Se films, employing a combination of solvothermal synthesis, screen printing, and spark plasma sintering. The incorporation of a small amount of Te improves film density and facilitates Te diffusion doping, leading to Ag2Se films with a high power factor of 25.7 μW cm−1 K−2 and a figure of merit (ZT) of 1.06 at 303 K. These films exhibit excellent flexibility, retaining 96% of their performance after 1000 bending cycles at a 5 mm bending radius. Additionally, we design a flexible thermoelectric device featuring a triangular p-n junction structure based on these films. This device achieves a normalized power density of 4.8 μW cm−2 K−2 at a temperature difference of 20 K and a maximum cooling of 29.8 K with an input current of 92.4 mA. These findings highlight the potential of this fabrication method for developing thermoelectric materials and devices for energy harvesting and cooling applications.

Fatigue-free ferroelectricity in Hf0.5Zr0.5O2 ultrathin films via interfacial design

Population structure in a fungal human pathogen is potentially linked to pathogenicity

Gene transcription, neurotransmitter, and neurocognition signatures of brain structural-functional coupling variability

Iron-sulfur clusters in SARS-CoV-2 exoribonuclease and methyltransferase complexes: relevance for viral genome proofreading and capping

Abstract Coronaviruses rely on a multifunctional replication-transcription complex to ensure genome fidelity and support viral propagation. Within this complex, the nsp14-nsp10 heterodimer possesses 3’−5’ exoribonuclease (ExoN) activity, while nsp14 alone functions as an N7-methyltransferase and the nsp16/nsp10 complex completes viral RNA capping via its 2′-O-methyltransferase. Here, we report that nsp14 and nsp10 ligate [Fe4S4] clusters when purified anoxically, in sites previously modeled as zinc centers. Quantum mechanics/molecular mechanics simulations revealed distinct reduction potentials for these iron-sulfur (Fe-S) clusters, and redox titrations demonstrated that changes in oxidation state modulate RNA binding by nsp14 and the nsp10/nsp16 complex. Functionally, Fe-S clusters enhance the methyltransferase activities of nsp14 and nsp10/nsp16, while leaving the ExoN activity unaffected. These findings uncover a redox-regulated role for Fe-S clusters in SARS-CoV-2 RNA processing and suggest that the viral core enzymatic functions may be modulated by the redox state of their Fe-S cofactors.

Organic matter degradation by oceanic fungi differs between polar and non-polar waters

Abstract Recent discoveries have uncovered pelagic fungi as significant contributors to the recycling of organic matter in the ocean. However, their drivers and whether the environmental filtering on the functional role of prokaryotes also applies to pelagic fungi remain unknown. In this study, we employed the metagenomic and metatranscriptomic approaches to explore the fungi mediated organic matter degradation in the sunlit ocean. Samples were collected from the subtropical Atlantic Ocean (non-polar) to the Southern Ocean (polar), and differentiated between small (0.2 − 3 µm, SF) and large ( >3 µm, LF) size fractions, to study niche partitioning in fungal communities and functions. Fungi accounted for 2–5% of eukaryotic genes and transcripts. Fungi contributed over 3% of eukaryotic carbohydrate-active enzymes (CAZymes) transcripts but less than 0.5% of protease transcripts, highlighting their specialized role in carbohydrate degradation. Non-polar and polar regions exhibited distinct fungal community composition and metabolic functions, potentially disrupting the balance of organic matter storage and cycling in these ecologically sensitive regions. Temperature emerged as a key driver of fungal CAZyme activity, revealing sensitivity to ocean warming. Our findings underscore the active role of pelagic fungi in organic matter degradation while revealing the environmental and ecological factors shaping their functional contributions across global oceanic regions.

Lens effect of remnant blocks on deep mantle upwelling causing anomalous subsidence

Bio-inspired multimodal soft actuator with environmental self-adaptation

Abstract Autonomous soft robots with built-in feedback can achieve self-sustained motion under constant, untethered stimuli. However, these systems are constrained to single-mode actuation within a fixed structure under the same type of stimulus and require human intervention to switch modes, lacking the robust and efficient self-adaptation of living organisms in changing environments. Inspired by Gymnura micrura, we developed a light-responsive soft actuator with engineered asymmetry and a dynamic structure, integrating two distinct built-in feedback mechanisms governed by intrinsic bifurcation. Thus, the actuator can seamlessly switch between three different motion modes—tracking, undulation, and oscillation—exhibiting self-adaptation to environmental changes (e.g., light intensity, viscosity, temperatures, and physical contact). Furthermore, this multimodal capability facilitates unique environmental interactions, expanding applications beyond locomotion to include fluid dynamics, electronics, and environmental monitoring. Such an advancement in physical intelligence represents a pivotal step toward next-generation autonomous soft robotic systems, unlocking higher-level autonomy and unprecedented adaptive behaviors.

Functionally deficient UBOX5 variants and primary angle-closure glaucoma

Abstract Primary angle-closure glaucoma is a major cause of irreversible blindness worldwide afflicting >20 million people. Through whole exome sequencing, we analysed the association between gene-based burden of rare, protein-altering genetic variants and disease risk in 4,667 affected individuals and 5,473 unaffected controls. We tested genes surpassing exome-wide significance (P < 2.5 × 10-6) for replication in a further 2,519 cases and 472,189 controls. We observed carriers of rare, protein-altering variants at UBOX5 (observed in 154 out of 7,186 affected individuals [2.1%] and in 3,975 out of 477,197 unaffected controls [0.83%]) to be associated with 2.13-fold increased risk of PACG (95%ci, 1.69 – 2.69; P = 1.25 × 10-10). We performed substrate trapping assays coupled with mass spectrometry and observed Binding Immunoglobulin Protein (BIP) as a key substrate for UBOX5. Biological assays showed UBOX5 acts by ubiquitinating BIP. We evaluated the functional status of 35 UBOX5 variants and observed that functionally deficient variants were enriched in affected individuals compared to controls. We validated this finding in an independent collection where 3 persons carrying functionally deficient variants were observed out of 208 cases (1.4%), whereas none were observed in 600 controls. Our findings suggest the UBOX5—BIP signalling pathway might be involved in biology of primary angle-closure glaucoma.

Compromise-free scaling of qubit speed and coherence