Browse Articles

Loss of Methyltransferase and Hypomethylated m6A Sarcomere Transcripts Leading to Early-Onset Dilated Cardiomyopathy

Sensitivity of simulations of Plio–Pleistocene climate with the CLIMBER-2 Earth System Model to details of the global carbon cycle

The Earth system model CLIMBER-2 has been used in past work to successfully reproduce the glacial/interglacial cycles of the Plio–Pleistocene and the Mid-Pleistocene Transition (MPT) from predominantly 40 to 100 ky timescale oscillatory behavior as a function of declining volcanic outgassing and regolith removal. In this study, we further examine the sensitivity of this previous work to varying prescribed levels of volcanic outgassing and regolith extent and the long-term dynamics of the global carbon cycle, affecting the exchange and partitioning of carbon between different Earth system reservoirs and therefore global atmospheric CO 2 concentrations. As volcanic outgassing decreases, CO 2 and land carbon storage decrease, while ocean carbon storage, including CaCO 3 sediment, increases. At volcanic outgassing levels below a threshold value of roughly 5.7 Tmol C yr −1 , sea level decreases due to land ice formation, leading to increased carbon accumulation in the ocean and decreased carbon in the CaCO 3 sediment reservoir. Our previous finding of strong hysteresis and path dependence in the glacial/interglacial alternation history [J. Carrillo et al. , Proc. Natl. Acad. Sci. 121, e2322926121 (2024)] appears to be a tenuous climate feature, dependent on the precise representation of carbon cycle processes and, specifically, the numerical precision used in the calculation of certain key state variables in the model’s carbon cycle.

Building a Confluence Charge Transfer Pathway in COFs for Highly Efficient Photosynthesis of Hydrogen Peroxide from Water and Air

Abstract Sunlight‐driven photosynthesis by covalent organic frameworks (COFs) from water and air without using sacrificial reagents is a promising H 2 O 2 fabrication approach but is still restricted by the insufficient charge separation and sluggish 2 e − water oxidation process. Herein, we provide a facile strategy to simultaneously improve charge separation and water oxidation in COFs via confining the charge transfer pathways from two diversion ones to a confluence one through regulating the site of nitrogen in bipyridine. Combining in‐situ characterization with computational calculations, we reveal that compared to COF‐BD1 containing two diversion charge transfer pathways, the charge transfer pathway in COF‐BD2 is confined to a confluence due to the electron‐deficiency effect of nitrogen, which greatly accelerates the intermolecular and out‐of‐plane charge transfer. Via effectively reducing the energy barrier of rate‐determining water oxidation reaction (WOR), the subsequent water oxidation process to produce the key *OH intermediate in COF‐BD2 is also greatly facilitated, boosting the yield of H 2 O 2 (5211 µmol g −1  h −1 ) from water, oxygen, and light without sacrificial agents or additional energy consumption. We further demonstrate that H 2 O 2 can be efficiently produced by COF‐BD2 in a broad pH range, in real water, and in an enlarged reactor using natural sunlight for water decontamination.

Two-Year Outcomes of Transcatheter Edge-to-Edge Repair for Severe Tricuspid Regurgitation: The TRILUMINATE Pivotal Randomized Controlled Trial

BACKGROUND: One-year outcomes of TRILUMINATE Pivotal (Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System Pivotal) found that transcatheter edge-to-edge repair (TEER) for the treatment of severe, symptomatic tricuspid regurgitation improved quality of life compared with medical therapy alone with similar rates of mortality and heart failure hospitalization. However, additional follow-up is necessary to determine the prolonged benefits of tricuspid TEER. METHODS: A total of 572 patients with severe, symptomatic tricuspid regurgitation were randomized to either tricuspid TEER+medical therapy (device group) or medical therapy alone (control). Two-year prespecified end points were recurrent heart failure hospitalization and freedom from all-cause mortality, tricuspid valve surgery, and tricuspid valve intervention after treatment visit, assessed in the intention-to-treat population. RESULTS: The annualized rate of recurrent heart failure hospitalizations through 2 years was significantly lower with tricuspid TEER compared with control (0.19 event per patient-year versus 0.26 event per patient-year; P =0.02; joint frailty model hazard ratio, 0.72; one-sided upper confidence limit, 0.93; P =0.02). Freedom from all-cause mortality, tricuspid valve surgery, and tricuspid valve intervention through 2 years was significantly higher with tricuspid TEER compared with control (77.6% versus 29.3%; P <0.0001), driven by more tricuspid valve intervention in control patients who crossed over to device treatment (3.8% versus 61.5%). Rates of all-cause mortality (17.9% versus 17.1%) and tricuspid valve surgery (2.3% versus 4.3%) were similar between groups. Moderate or less tricuspid regurgitation was present in 84% at 2 years in the device group. CONCLUSIONS: At the 2-year follow-up, tricuspid TEER appeared safe, significantly reduced tricuspid regurgitation severity, and decreased rates of heart failure hospitalization compared with medical therapy alone. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03904147.

Updated fossil analyses reveal critical insights into the origins of monotreme lifestyles

A Capping‐assisted Strategy for Synthesis of Glass‐like Carboxylate‐based Coordination Polymers

Abstract The direct preparation of glass‐like carboxylate‐based coordination polymers (CPs) possessing continuous internal structure and transparency is challenging due to the lack of control on coordination kinetics and subsequently the range of order. Herein, a capping‐assisted strategy was presented to control the molecular assembly during the metal‐ligand coordination in the solution and to inhibit the long‐range of order hence building glass‐like CPs (g‐CPs) mimicking the polymerization process. 1,3,5‐benzene tricarboxylate (BTC) ligand was used to connect the copper cations (Cu 2+ ) into metal‐organic complexes of different Cu: BTC ratios (metal‐organic pool) in presence of an excess of triethyl amine as a capping agent. Concentrating the Cu‐BTC complexes and further drying under mild conditions induced the decapping process which triggered the random crosslinking between the free carboxylate and Cu 2+ to form a boundary‐free continuous internal structure. The as‐prepared Cu‐BTC g‐CP exhibited an approximately similar fine structure like its crystalline counterpart (HKUST‐1), which facilitated solvent and thermal‐induced crystallization. Due to the internal structure continuity, the g‐CP possesses ceramic‐like hardness and wear resistance and plastic‐like resilience. This capping‐assisted strategy has been successfully extended to Ni‐BTC and Fe‐BTC systems under mild conditions and thus presenting a general method for the formation of glass‐like carboxylate‐based CPs.

Reply to Apanovich and Weeks: Exceptions exist, as recognized in the paper, but are too rare to challenge the original findings

Reply to Ogutu et al.: Cattle–wild herbivore interaction studies warrant new lenses from community ecology and environmental justice

Unprecedented “off‐pathway” [2+2] Cycloaddition‐Retroelectrocyclization Reaction Between an Unsymmetric Alkyne and Tetracyanoquinodimethane

Abstract In recent years, the [2+2] cycloaddition‐retroelectrocyclization (CA‐RE) reaction between electron‐rich alkynes and electron‐deficient alkenes has emerged as one of the most effective synthetic routes to prepare a large variety of molecular and polymeric electron donor–acceptor systems. Besides its simplicity, fast rate, and high yield, this reaction may also display complete and predictable regioselectivity, as in the case when tetracyanoquinodimethane (TCNQ) is used in combination with unsymmetric, activated alkynes. Here, we report the first example of a [2+2] CA‐RE reaction between TCNQ and an aniline‐activated alkyne following an “inverted” regiochemistry, thus leading to the exclusive formation of an unexpected regioisomer in contrast to the expected one. A combined experimental and theoretical study helped us to unravel the peculiar reaction mechanism underlying the regioselectivity switching.

Optimizing Charge Separated Synergistic Binding Sites in Self‐Healing Crystalline Porous Organic Salts for Benchmark Trace Alkyne/Alkene Separation

Abstract The separation of trace alkyne (C 2 H 2 /C 3 H 4 ) impurities from alkenes (C 2 H 4 /C 3 H 6 ) is a significant but challenging process to produce polymer‐grade C 2 H 4 and C 3 H 6 . Herein, we reported an optimally designed charge‐separated organic framework, crystalline porous organic salt (CPOS‐1), with confined polar channels for highly efficient alkyne/alkene separation. CPOS‐1 exhibits excellent stability, remarkably high C 2 H 2 (18.4 cm 3  g −1 ) and C 3 H 4 (20.9 cm 3  g −1 ) uptakes at 0.01 bar and 298 K, and benchmark C 2 H 2 /C 2 H 4 (25.1) and C 3 H 4 /C 3 H 6 (43.9) separation selectivities for 1/99 alkyne/alkene mixtures. The practical alkyne/alkene separation performance was completely identified by breakthrough‐column experiments under various conditions with excellent cycle stability and high alkene productivities (C 2 H 4 : 216.6 L kg −1 ; C 3 H 6 : 162.4 L kg −1 ). Theoretical calculations indicated that pore aperture in CPOS‐1 acts as a tailored single‐molecule trap, where alkynes are captured by multiple synergistic electropositive and electronegative sites, thus enhancing alkyne recognition. Furthermore, the ease of rehealing facilitates its practical application, transcending the limitations of the metal‐organic frameworks (MOFs) and covalent organic frameworks (COFs).

Correction for Yin et al., Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

Cathodic Hydroxide Ions Induce Tetrose Formation during Glycolaldehyde Electroreduction to Alcohols: A Potential CO ₂ ‐to‐Carbohydrate Pathway

Abstract The electrochemical synthesis of organic compounds from CO 2 can potentially alleviate climate change by hampering the atmospheric accumulation of greenhouse gases. The production of carbohydrates from CO 2 reduction will have promising applications for the manufacturing of valuable, multi‐carbon compounds that are traditionally produced from the petrochemical or agricultural industries. In this work, we analyzed the copper‐catalyzed electrochemical reduction of glycolaldehyde, a commonly observed trace CO 2 RR product that has been previously proposed as an intermediate for alcohol formation. We determine that glycolaldehyde is not the main intermediate on polycrystalline copper‐based electrocatalysts that selectively produce ethanol. In an unbuffered electrolyte, the cathodic hydroxide ions produced induce the coupling of glycolaldehyde to tetroses in the solution phase, yielding a maximum glycolaldehyde‐to‐sugar conversion of 47.2% under ambient conditions. Using in situ infrared spectroscopy coupled with density functional theory (DFT) calculations, we show that glycolaldehyde reduction to alcohols proceeds via adsorption of its enol tautomer, η 2 (C,C)─CHOH═CHOH. Our findings not only shed light on the C 2 alcohol formation pathways during CO 2 RR, but also imply that a CO 2 electrolyzer can potentially produce C 4 carbohydrates via CO 2 reduction to glycolaldehyde followed by C─C coupling in the solution phase, with only a high local pH needed to drive the tetrose formation step.

DNA Nanotubule‐Based Nanodevices with ATP‐Responsive Gating for Direct Cytosolic Delivery of Nucleic Acids and Proteins

Abstract Delivering biomacromolecules to the cytosol remains a formidable challenge, as these molecules are predominantly sequestered within endosomes after endocytosis. The limited efficacy of current delivery systems in promoting reliable endosomal escape underscores the need for innovative strategies. Here, we report a DNA origami nanotubule to construct transmembrane delivery nanodevices with size‐selective gating and ATP‐responsive channel activation. By integrating unilamellar vesicles as large storage compartments, these nanodevices can encapsulate a wide range of macromolecules, including small interfering RNA, messenger RNA, plasmid DNA, and CRISPR‐Cas9 ribonucleoprotein complexes. By bypassing traditional endocytic pathways, the nanotubules enable the delivery of substantial payload quantities directly across the plasma membrane. This approach provides a promising platform for delivering macromolecular therapeutics into the cytosol, advancing gene therapy strategies, and broadening their biomedical applications.

Correction for Guo et al., Targeting amyloid-β in glaucoma treatment

Beyond Structure: Methylation Fine‐Tunes Stability and Folding Kinetics of bcl2Mid G‐Quadruplex

Abstract Cytosine methylation, a key epigenetic modification in the regulation of gene expression, raises intriguing questions about its role in the formation and thermodynamic stability of G‐quadruplex (G4) structures. We investigated the impact of the 5‐methylcytosine residue (C m ) on the well‐characterized bcl2Mid G4 structure that forms in a GC‐rich region of the B‐cell lymphoma 2 (BCL2) gene promoter, which influences its expression. Using solution‐state NMR and biophysical techniques, we discovered an unexpected sequence‐specific effect of C m on the folding kinetics of bcl2Mid G4. Specifically, substituting cytosine at position C6 with C6 m   slows down G4 folding kinetics and influences the equilibrium between major and minor structures in the presence of K + ions. Notably, the increased population of the minor structure enabled the characterization of its previously unidentified topology. Additionally, the presence of a single C m residue induces local structural rearrangements in the major G4 structure and decreases its thermodynamic stability. Furthermore, we found that the zinc finger 3 motif of the Sp1 transcription factor preferentially binds to the minor G4 structure. These results suggest that C m not only influences G4 polymorphism but may also regulate interactions with transcription factors, potentially affecting the regulation of gene expression.

Structurally Engineering Multi‐Shell Hollow Zeolite Single Crystals via Defect‐Directed Oriented‐Kinetics Transformation and Their Heterostructures for Hydrodeoxygenation Reaction

Abstract Single‐crystalline multi‐shell hollow porous materials with high compartment capacity, large active surface area, and superior structural stability are expected to unlock tremendous potential across diverse critical applications. However, their synthetic methodology has not yet been well established. Here, we develop a defect‐directed oriented‐kinetics transformation approach to prepare multi‐shell hollow aluminosilicate ZSM‐5 zeolite ( MFI ) crystals with single‐crystalline feature, hierarchical macro‐/mesoporosity, controllable shell number, and high structural stability. The methodology lies in the creation of zeolite precursors consisting of multiple inhomogeneous layers with gradient‐distributed defects along the [100] and [010] directions and irregularly discrete defects‐rich regions along the [001] direction via continuous epitaxial growth. Subsequently, the locations with more defects could be preferentially etched to form voids or mesopores, meanwhile oriented recrystallization interconnects the nanoshells into a unified architecture along the [001] direction. Benefiting from the easily accessible bifunctional metal/acid sites and the capability for reactant accumulation, the resultant multi‐shell hollow Ni‐loaded zeolite catalysts show significantly enhanced catalytic activity in the hydrodeoxygenation of stearic acid into liquid fuels. The insight gained from this systematic study will facilitate the rational design and synthesis of diverse multi‐shell hollow structured single‐crystalline porous materials for a broad range of potential applications.

Tetranuclear Titanium Nitride Cluster: Dinitrogen Cleavage Under Mild Conditions and Its Reactivity

Abstract Heating the readily available trinuclear Ti dinitrogen complex [{TiCp*( µ ‐Cl)} 3 ( µ 3 ‐ η 1 :  η 2 :  η 2 ‐N 2 )] 1 (Cp* = η 5 ‐C 5 Me 5 ), originally reported by C. Yélamos and J. Jover, in benzene at 80 °C leads to the cleavage of N≡N bond, forming a tetranuclear titanium nitride cluster [{TiCp*} 4 Cl( µ ‐Cl) 3 ( µ 3 ‐N) 2 ] 2 . The structure of 2 was confirmed by single‐crystal X‐ray diffraction analysis. Kinetics study and density functional theory (DFT) calculations indicate that the energy barrier for the NN bond cleavage in the transformation from 1 to 2 is about 26 kcal mol −1 . Complex 2 exhibits reactivity toward various electrophiles, producing a range of nitrogen‐containing compounds in the presence of air, while concurrently regenerating Ti(IV) salts. Furthermore, complex 2 reacts with pinacolborane, leading to the formation of N‐B bond derivatives [{TiCp*( µ ‐NBPin)Cl} 2 ] 3 . When complex 2 – 15 N is treated with pyridine or 4‐dimethylaminopyridine (DMAP), it dissociates to form a bent trinuclear Ti nitrido complex [{TiCp*} 3 Cl 3 (L) 2 ( µ ‐ 15 N) 2 ] 4‐L (L = py or DMAP).

Towards High‐Performance Aqueous Zn‐Organic Batteries via Using I ⁻ ‐Based Active Electrolyte

Abstract Organic cathodes possess inherent structural diversity and fast redox kinetics, showing great application prospects in aqueous Zn batteries. Nevertheless, most of the reported organic cathodes display low average working voltage resulting in poor energy density. Herein, diquinoxalino [2,3‐a:2′,3′‐c] phenazine (HATN)@CMK‐3 composite is utilized as cathode for aqueous zinc battery, which combines the Zn 2+ and H + co‐storage and I − /I 0 conversion by introducing I − ‐based active additive into 0.5 M Zn(OTf) 2 electrolyte. The in situ/ex situ analyses and computational studies disclose that HATN@CMK‐3 with C═N groups not only stores Zn 2+ and H + ions at low potential but also acts as a substrate to promote the conversion reaction of I − /I 0 at high potential. Accordingly, the Zn//HATN@CMK‐3 cell delivers a high average voltage of 0.75 V, prominent long‐life (10 000 cycles) and, high energy density (198 Wh kg −1 ). Remarkably, under high mass loading (10 mg cm −2 ) or low‐temperature conditions, the cell still achieves decent capacity and cycle stability.

Theory‐Guided Design of Surface‐Enhanced Ni–Mn Diatomic Site Catalysts for Efficient Seawater Electrolysis via the Degradation of High Ionization Potential Organic Pollutants

Abstract In response to energy shortages and hard‐to‐degrade chemical pollution, especially high ionization potential (IP) organic pollutants, this study developed a novel photoelectrocatalyst, Ni‐Mn@OBN, for degrading IP pollutants in seawater and generating hydrogen. Incorporating Ni–Mn dual atoms into an O‐doped boron nitride (OBN) framework, Ni‐Mn@OBN, shows excellent stability and HER performance. Density functional theory (DFT) analysis revealed its low Gibbs free energy change (Δ G H* = 0.03 eV) for HER, outperforming Pt (111). Achieving an ultralow overpotential of 43.8 mV at 500 mA cm⁻ 2 under AM 1.5G, simulated light surpasses commercial Pt/C catalysts. High IP pollutants enhance hydrogen evolution rates, indicating a synergistic effect. Theoretical calculations elucidated the interplay between seawater electrolytes and high IP values on the photoelectrocatalytic performance. Ni‐Mn@OBN demonstrated excellent stability and a solar‐to‐hydrogen (STH) efficiency of 3.72%, offering a sustainable solution for marine pollution control and clean energy production.

Octalenobisterphenylene and Its Diradical Dianionic Cyclodimer: Synthesis, Structural Analysis, and Properties

Abstract Octalenobisterphenylene 1 (also known as terphenylene dimer) was synthesized from 3,3′,5,5′‐tetraaryl‐substituted biaryl by tert ‐butyllithium‐mediated cyclization followed by oxidative coupling. This one‐pot two‐step protocol facilitated the successive formation of four four‐membered and two eight‐membered rings. Treatment of 1 with sodium metal, followed by crystallization from THF, yielded the remarkable diradical dianion [( 1 •– ) 2 ] 2− , where the two molecular halves are connected by four σ bonds. The cyclodimerization is driven by the pronounced reactivity and strain of the central six‐membered ring within the [3]phenylene subunit. The structure and diradical nature of [(Na + ) 2 ( 1 •– ) 2 ] were confirmed through X‐ray crystallography, DFT computations, and 1 H NMR and ESR spectra. These investigations revealed that the two spins, one on each molecular half, exhibit minimal mutual interaction.