Browse Articles

Deciphering the Specificity of Reversible DNA-Phosphate ADP-Ribosylation via the Precise Synthesis and Enzymatic Profiling of Nucleotide-Phospho-ADP-Ribosyl Probes

Abstract ADP-ribosylation (ADPr), long recognized as a canonical protein post-translational modification, has recently expanded to include targeting nucleic acids, uncovering a diverse landscape of noncanonical biological functions. Emerging evidence suggests that ADPr at the 5′-phosphate terminus of DNA is implicated in the DNA damage response, yet understanding its precise molecular function has been hampered by the lack of structurally defined chemical probes. Here, we report the stereoselective synthesis of deoxynucleotide-phospho-ADPr (dN-P-ADPr) probes, representing native fragments of terminal DNA-ADPr. Our strategy leverages a mild, stereocontrolled glycosylation to construct the challenging ribosyl-phosphate linkage, followed by P(III)–P(V) coupling to establish the pyrophosphate bridge. This robust toolkit enabled the systematic biochemical profiling of DNA-ADPr hydrolases across diverse kingdoms of life. Remarkably, using these newly developed probes, we uncover hydrolases across the diversity of life capable of reversing ADPr modifications at phosphorylated DNA ends. We further show that these enzymes exhibit an absolute preference for the native-like α-anomer, independent of the identity of the adjacent DNA nucleobase, suggesting that substrate recognition is governed primarily by the ADPr-phosphate linkages rather than the local nucleobase context. Together, these synthetic probes and biochemical insights provide an essential foundation for deciphering the biological landscape of noncanonical ADPr.

Enhancing gear shaping precision and reducing noise via DRL

Engineering Altermagnetic Transitions in Two-Dimensional Metal–Organic Frameworks via Chemical Symmetry Breaking

Abstract Altermagnets are symmetry-defined magnetic phases that combine momentum-dependent spin splitting with zero net magnetization, offering promising opportunities for spintronics. However, their realization is strongly constrained by rigorous symmetry requirements. Exploiting the shared antiparallel magnetic order and vanishing net magnetization between antiferromagnets and altermagnets, we propose a general chemically driven strategy based on asymmetric ligand modification to transform pristine two-dimensional antiferromagnetic metal–organic frameworks into altermagnetic candidates. Using chromium phthalocyanine (CrPc) as a proof-of-concept model, we show that asymmetric modification lowers the local site symmetry at magnetic Cr centers and generates momentum-dependent spin splitting and anisotropic spin densities, as revealed by first-principles calculations. Oxygen-modified CrPc derivatives further illustrate the chemical tunability of this symmetry-control principle. Our work expands the design space of organic altermagnetic candidates and establishes a chemically grounded route for engineering symmetry-governed magnetic functionality in reticular materials.

Synthesis of a dual-functional hydrazone-based cobalt complex as a catalyst for the cycloaddition of CO2 and radioactive iodine capture

Total Synthesis of Benthol A: The Nominal and the Actual Natural Product

Abstract The total synthesis of the dinoflagellate-derived “super-carbon-chain compound” benthol A rigorously confirmed what the analysis of one of the required building blocks had forecasted, namely that the configuration of the secondary −OH group at C40 had been misassigned by the isolation team as the only one of a total of 35 stereogenic centers decorating the backbone of this polyol/polyether derivative. This conclusion bears implications because the original assignment had been solely based on computational data, which had resulted in a remarkably high score of 99.93% that was ultimately misleading. The multiconvergent blueprint underlying the successful approach accounts for the fact that alongest linear sequence of 32 steps sufficed to reach this intricate marine natural product. The inherent flexibility should also empower future studies aiming at a detailed mapping of the pharmacophore of this compound endowed with significant antiplasmodial activity.

Distributed priority-aware multi-objective routing for reliable data delivery in LoRa-enabled UAV networks

Zero Indirect Band Gap and Flat Bands in a Niobium Oxyiodide Cluster Material

Abstract Explorative chemistry in a reaction system composed of NbI4, Li2(CN2), and Li2O has led to the discovery of a number of niobium oxyiodide cluster compounds. During this reaction, the formation of solid phases was detected alongside gaseous phases, resulting in a range of products with cluster cores of varying shapes. After several niobium oxyiodide cluster compounds have already been identified within this reaction system, two additional compounds, Nb6O3I15 and Nb11O6I24, are discovered and structurally characterized by single-crystal X-ray diffraction. Both structures are based on the butterfly-shaped, oxygen-capped niobium cluster [Nb4O], which is extended to larger cluster fragments. The [Nb4O] cluster core in Nb6O3I15 is extended by two [NbO] units to form a three-dimensional framework, and Nb11O6I24 contains two connected [Nb4O] units, which form chiral units within an antiferrochiral hexagonal packing of strings. The striking string-like character of Nb11O6I24 was investigated in terms of its electronic structure and properties. DFT calculations showed Nb11O6I24 to possess a zero indirect band gap, with a pair of 3-dimensional flat bands surrounding the Fermi level. These unusual features of the electronic band structure suggest the presence of strongly correlated intercluster singlet electron states, arising from the helical shape of the clusters, the hexagonal packing of the strings, and the delocalized nature of cluster electron wave functions.

Machine learning-based mechanical prediction and characterization of natural fiber hybrid polyester composites for structural and automotive applications

Influence of Halide Substitution on Local and Average Structure, Lattice Dynamics, and Transport Properties in Cu6PS5X Argyrodites

Abstract Halide-substituted argyrodite materials have attracted increasing attention for energy applications since compositional tuning provides an effective strategy to modulate their structure and transport characteristics. While Li+-based halide argyrodites have been extensively studied, a unified composition-resolved understanding of Cu+-based halide argyrodites that integrates phase evolution, local structure, lattice dynamics, and electronic and ionic transport remain limited. In this work, we investigate Cu6PS5X (X = Cl, Br, I, Cl0.5Br0.5, Cl0.5I0.5, and Br0.5I0.5) within a combined experimental and computational framework. All compositions adopt an average cubic F4̅3m structure at room temperature, while local structural analysis reveals deviations from cubic symmetry consistent with a monoclinic Cc model involving PS43– tetrahedral tilting. 31P MAS NMR spectroscopy corroborates this local symmetry breaking through multiple distinct phosphorus environments arising from relative tetrahedral orientation rather than S2–/X– site disorder. Halide substitution modifies the Cu+ conductivity through changes in the activation energy and the Arrhenius pre-exponential factor, following the Meyer–Neldel behavior, with additional contributions from variations in jump distances and migration pathways. Direction-projected phonon density of states analysis identifies low-frequency Cu+ vibrational components along the crystallographic migration pathways. Analysis of the Meyer–Neldel slope further suggests phonon assisted ion hopping involving multiphonon excitation of low-frequency Cu+ vibrational modes. Together, these findings offer insight into structure–property relationships in Cu6PS5X and suggest that, alongside the migration energy landscape, the vibrational energy scale, thermal population, and directionality of mobile ion modes should be considered when interpreting ion transport, thereby providing a vibrational perspective for the design of solid-state ion conductors.

Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model

Abstract Genetic profiling of a new HPV-negative cervical cancer model identified pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, and DNA damage repair pathways, including homologous recombination, non-homologous end-joining, and mismatch repair. Deficiencies in BRCA 2, RAD51 and MLH1 were among these actionable targets. The newly described cervical cancer model revealed sensitivity towards the PARP inhibitor olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. In contrast, BRCA1/2 -proficient cervical cancer cells exhibited greater resistance to these strategies. This study highlights the potential of in-depth genetic analysis to identify genetic susceptibilities to guide personalized medicine approaches.

Understanding Electrochemical Alcohol Hydrogenolysis Enabled by Carbonyl Reduction in Lignocellulosic Biomass-Derived Aromatic Oxygenates

Abstract Molecules derived from lignocellulosic biomass are oxygenates with multiple oxygen-containing functional groups, such as hydroxyl and carbonyl groups. Therefore, the ability to selectively reduce a specific oxygenate group is essential for the reductive upgrading of such molecules. Previous studies on electrochemical biomass conversion have shown that alcohol hydrogenolysis, which involves cleavage of the σ(C–Oalcohol) bond, is extremely challenging for furfural and 5-hydroxymethylfurfural (HMF) derivatives, including furfuryl alcohol, 5-methylfurfuryl alcohol (MFA), and 2,5-bis(hydroxymethyl)furan (BHMF). In contrast, HMF itself undergoes alcohol hydrogenolysis relatively easily in acidic aqueous media. Considering that the only structural difference between HMF and BHMF or MFA is the presence of a carbonyl group, this observation raises the question of whether the carbonyl group in HMF facilitates alcohol hydrogenolysis. In this study, we designed systematic experiments to provide a coherent explanation of when and how a carbonyl group enables hydrogenolysis of a copresent alcohol group. Specifically, we show that alcohol hydrogenolysis in HMF proceeds via reduction of the carbonyl group to a ketyl radical, followed by a spin-center shift (SCS) through extended π conjugation. We also elucidate the effect of pH on the selectivity between carbonyl hydrogenation and alcohol hydrogenolysis, both of which share the ketyl radical intermediate. This mechanistic understanding enhances our ability to predict and control alcohol hydrogenolysis in the reductive upgrading of biomass-derived oxygenates.

Mechanical and electrical characteristics and pressure-sensitive response measurements of alkali-activated mortar containing conductive fillers

Facile Fabrication of Redox-Active Covalent Organic Frameworks via Reductive <i>N</i> -methylation

Abstract Redox-active covalent organic frameworks (COFs) are promising materials for electronics, sensing, and catalysis. However, their synthesis is hampered by the scarcity of redox-active monomers and the difficulty of functionalizing as-synthesized frameworks without compromising crystallinity. Here, we introduce a reductive N-methylation strategy that enables the universal and mild conversion of imine-linked COFs into crystalline tertiary amine-linked frameworks (NMe-COFs). The method preserves structural order while imparting strong electron-donating and redox-responsive properties. Among the NMe-COFs, COF-300-NMe exhibits an 11-fold increase in iodine uptake with a distinct gate-opening adsorption profile─a behavior that computational studies attribute to enhanced framework flexibility and raised electronic energy levels. Furthermore, incorporation of the electron acceptor 7,7,8,8-tetracyanoquinodimethane into COF-300-NMe yields a charge-transfer complex exhibiting distinct spin signatures. This work establishes a versatile postsynthetic linkage conversion strategy, paving the way toward stimuli-responsive soft COFs and purely organic spin-active materials.

Semaglutide and COVID-19 mortality risk

Abstract Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used to treat type 2 diabetes and manage weight in individuals with obesity or who are overweight. Semaglutide was found to reduce COVID-19-related mortality risk in a secondary analysis of the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial. We previously demonstrated that diabetes and obesity are associated with higher risks of COVID-19-related mortality in the general population. Using this existing cohort, we found that semaglutide use was associated with a significant 49% reduction in the risk of COVID-19-related death. Diabetes and obesity were linked to higher mortality risk, but an E-value of 3.31 suggests that unmeasured confounders would need to be strong to negate the observed association. These findings suggest that further investigation is warranted into the potential role of semaglutide in reducing risks associated with other causes of death.

In Situ Unveiling of the Coupling Mechanism of Intercalation-Conversion Processes at the Nanoscale in Lithium–Ion/Lithium–Oxygen Hybrid Batteries

Abstract With the rapid growth in energy demand, designing a novel hybrid battery system has become increasingly important. It is critical to reveal the coupling mechanisms of intercalation-conversion hybrid cathodes and provide an in-depth understanding of structure-performance relationships for the electrochemical energy storage devices with high energy density. In this study, a hybrid cathode that combines intercalation-type LiNixCoyMn1-x-yO2 (NCM) with conversion-type oxygen (O2) is proposed. Using in situ electrochemical atomic force microscopy (EC-AFM), we elucidate that the overlithiation of the NCM cathode enhances electronic conductivity and exposes abundant active sites during discharge, thereby inducing the formation of Li2O2. Electrochemical tests demonstrate that the contributions of intercalation and conversion reactions to capacity are rate-dependent, with lower rates favoring the intercalation-dominated electrochemical process. Further scanning transmission electron microscopy characterization indicates that, during prolonged cycling, oxygen vacancies in the NCM intercalation-type cathode serve as preferential sites for the conversion-type Li–O2 intermediates, significantly enhancing the cycling stability of the battery. Ultimately, by optimizing the mass ratio between the intercalation and conversion cathodes, an enhanced cycle stability is achieved. This study offers valuable insights into modulating battery performance through multimechanism reactions in hybrid battery systems.

Feasibility of a novel wearable magnetic sensor device for swallowing assessment compared with videofluoroscopic swallowing study

Multidomain Relaxation Dispersion NMR Resolves an Intermediate-Gated Binding Pathway for Selective Recognition of Linear Diubiquitin by HOIL-1L

Abstract Molecular recognition is governed not only by the structural complementarity of the final complex, but by the kinetic pathway through which it forms. Polyubiquitin chains, in which sequence-identical domains are covalently linked yet must be discriminated by dedicated receptors to encode distinct cellular signals, exemplify this challenge. For NMR relaxation dispersion studies of such systems, spectral overlap between identical domains prevents conventional uniform isotope labeling from resolving the per-domain exchange contributions. Here we show, using domain-selective 15N labeling combined with R2 relaxation dispersion, that the binding of linear (Met1-linked) diubiquitin to HOIL-1L NZF proceeds through an apparent three-state pathway as detected by relaxation dispersion, in which rapid ligand-dependent pre-equilibration populates a conformationally preorganized intermediate that is selectively captured by NZF in a slower, chain-type-selective step. This kinetic hierarchy offers a mechanistic basis for understanding the discrimination between linear and Lys63-linked ubiquitin chains that static structures alone cannot reveal. This strategy should be broadly applicable to multidomain recognition systems─including epigenetic reader complexes and multivalent signaling adaptors─where the pathway between known structural end points remains hidden.

The prediction of Aedes mosquito abundance using remote sensing and machine learning in Harris County, Texas

Magnetohydrodynamic Williamson fluid flow in ureteral tubes with heat and mass transfer in electromagnetic therapy: numerical and artificial neural network analysis

Arraying Shape-Persistent Molecular Alkynyl Trap into Highly Porous and Robust Zirconium Metal–Organic Framework for Propyne Capture and Propyne/Propylene Separation

Abstract Adsorptive separation of propyne/propylene (C3H4/C3H6) using porous adsorbents offers a promising route toward energy-efficient production of polymer-grade C3H6. Currently, the prevailing adsorbents are ultramicroporous metal–organic frameworks (MOFs) that feature narrow channels and/or consist of inorganic anion pillars, which often lead to limited C3H4 uptake capacity and high isosteric enthalpy of adsorption. We report herein a highly porous and robust zirconium metal–organic framework, termed SJTU-520. This MOF incorporates shape-persistent molecular arrays in three-dimensional space derived from cyclotetrabenzoin, which function as selective sites for the preferential entrapment of C3H4 over C3H6, thus enabling high C3H4 capture capacity, record high C3H4/C3H6 uptake ratio at 1 bar and 298 K, and efficient C3H4/C3H6 separation at ambient conditions. Compared with the cyclotetrabenzoin and tetraacetate cyclotetrabenzoin-based supramolecular organic crystals, SJTU-520 exhibits significantly higher surface area (3650 m2/g versus 42 and 570 m2/g), leading to a C3H4 uptake boost by 6.1-fold and 3.7-fold at 298 K and 1 bar, without any compromise of the C3H4/C3H6 selectivity. The efficient C3H4/C3H6 separation was validated by extensive breakthrough experiments under various conditions with great recyclability and high productivity of polymer-grade C3H6 from a 10/90 C3H4/C3H6 mixture. Computational simulations revealed that the four benzene walls of the cyclotetrabenzoin macrocycle in SJTU-520 formed equidistant π–π interactions with the C≡C triple bond of encapsulated C3H4 molecule. This work illustrates a general and powerful strategy─the reticulation of intrinsically functional organic scaffolds into highly porous frameworks─toward creating bespoke materials with precisely tailored functionalities and enhanced properties.