Browse Articles

Evaluation of a proposed link between the SARS-CoV-2 furin cleavage site and mouse-adapted MERS-coronavirus MA30

The origin of the polybasic furin cleavage site (FCS) of SARS-CoV-2 remains a central question in debates on the emergence of COVID-19. One hypothesis proposes a genetic relationship between the SARS-CoV-2 S1/S2 motif RRAR and the RRVR sequence found in the mouse-adapted MERS-CoV strain MERS-MA30. Here, we combined large-scale bioinformatic analysis with experimental virology to evaluate this scenario. Analysis of over 17 million SARS-CoV-2 genomes revealed that the S:684V substitution corresponding to RRVR occurred repeatedly but only sporadically, never became phylogenetically basal, and showed limited geographic and temporal spread. Using reverse genetics, we generated SARS-CoV-2 variants encoding RRVR and demonstrated that S:684V consistently reduced viral entry efficiency and competitive fitness in multiple cell systems, including human respiratory epithelial cultures. RRVR variants did not evolve toward RRAR but instead accumulated alternative substitutions. These findings do not support an evolutionary relationship between MERS-MA30 and the SARS-CoV-2 FCS.

Cryptanalysis and improvement of a distributed zero trust scheme for airborne wireless sensor networks

<i>In situ</i> polymer nanoparticle densitometry via real-time 3D single-particle tracking

Single-particle techniques have the potential to measure the heterogeneous dynamics at the nanoscale within reaction mixtures. However, new tools are needed to gain insight into the molecular structure of evolving chemical systems at the single-particle level. Here, a single-particle method for measuring the density and mass of freely diffusing polymer nanoparticles is introduced and applied to the ring-opening metathesis polymerization of norbornene. Using 3D single-molecule active real-time tracking, growing polymer nanoparticles are tracked in situ, enabling simultaneous real-time measurement of both particle size and particle density. Particle density is extracted from the descent velocity of growing nanoparticles, giving insight into particle composition at the single-particle level. Using this technique, it is found that polynorbornene nanoparticles have a density of 850 ± 30 kg/m3, validated through control measurements on polystyrene beads. Density and size analysis indicate each nanoparticle contains ∼3.5 × 109 densely packed monomers, rather than loosely packed polymer chains. Simulations show that the accuracy of this method depends on particle size, the distance traveled before contact with the coverslip, solvent properties, and the number of trajectories. Overall, this paper presents a technique that enables in situ characterization of the density and mass of individual growing polymer nanoparticles.

Junctophilin-2-orchestrated calcium signalosome regulates brown adipocyte thermogenesis and energy metabolism

Dysfunctional adipocyte calcium handling is implicated in obesity and thermogenesis. Junctophilins (JPs) stabilize calcium microdomain junctions between the plasma membrane and endoplasmic reticulum, but whether JPs are required for adipocyte function is not known. We show that JP2 is enriched in thermogenic brown adipose tissue (BAT) relative to other fat depots and is downregulated under conditions of nutrient overload. Conditional knockdown of JP2 in adipocytes, and more selectively in BAT, exacerbates cold intolerance and susceptibility to diet induced obesity. Mechanistically, JP2-depleted brown adipocytes exhibit calcium handling dysfunction with elevated cytosolic calcium levels at baseline but diminished norepinephrine-induced calcium transients, reduced store-operated calcium entry. Basal cytosolic calcium overload accounts for an increase in calpain activation and ensuing downregulation of STIM1 and hormone-sensitive lipase in JP2-depleted cells. Furthermore, JP2 silencing in brown adipocytes reduced oxygen consumption rates and compromised mitochondrial structure and quality. Together, these findings demonstrate that JP2 is essential for normal calcium homeostasis in brown adipocytes and reveal a critical role for JP2 in thermogenesis and resistance to diet-induced metabolic dysregulation.

Effect of Brewster window placement on polarization, beam quality, and output power in a diode-side-pumped ring Nd:YAG/KTP green laser

Influence of guest molecules on shock-induced intrinsic reactivity and reaction pathways of CL-20 based on neuroevolution potential

Incorporating guest molecules into energetic crystal frameworks has proven to be an effective strategy for modulating microstructure and reaction mechanism. In this study, the regulatory mechanisms of guest molecules on the shock-induced intrinsic reactivity and reaction pathways of CL-20 were systematically investigated based on the neuroevolution potential. The results indicate that NCCH3 exhibits the strongest reaction-promoting effect, driving the system into a violent reaction stage rapidly. However, due to its low oxygen balance, both the detonation pressure and velocity are significantly reduced. In contrast, N2O and CO2 behave as weakly reactive, endothermic buffering guests at early stages, which delay the decomposition of CL-20 and enhance its detonation pressure. The temperature rise and detonation performance of CL-20/H2O2 are close to those of α-CL-20, while showing a certain inhibitory effect on the initial temperature increase. Reaction pathway analysis reveals that high pressure can activate additional pathways, including H abstraction, O migration, and NO2 abstraction, thereby promoting parallel reactions and radical capture. H2O and H2O2 promote radical reaction chains through endothermic processes and the release of OH/H radicals, with H2O2 exhibiting faster onset and higher intensity. CO2 and N2O primarily suppress decomposition by diluting active species and through reversible reorganization reactions, with N2O showing a more pronounced retardation effect. NCCH3 strongly promotes early stage decomposition by engaging in multiple reaction pathways, but the overall reaction proceeds incompletely at later stages. The polarity and size of guest molecules can modify the initial crystal structure, while their radical-generating capability and chemical reactivity determine how they participate in reactions, thereby jointly influencing the intrinsic reactivity and decomposition pathways of host-guest crystals.

Nucleotide diversity is a poor predictor of short-term adaptive potential

The capacity to adapt is essential for a population to avoid extinction in a changing world and is recognized as a global conservation priority. Adaptation requires additive (heritable) genetic variation for traits that influence survival and fecundity, but measuring this variation is difficult, particularly in species of conservation concern. Instead, molecular genetic diversity is often used to infer adaptive potential. However, previous research has cast doubt on the suitability of traditional molecular markers (allozymes and microsatellites) for this purpose given their weak relationship with heritability—a common measure of additive genetic variance. Advances in sequencing technology have since shifted focus toward nucleotide diversity and variation in functional regions, but their practicality for predicting adaptive potential remains debated. Furthermore, heritability itself is a poor proxy for adaptive potential because it depends on environmental variance. We collated 2,113 published estimates of evolvability—a measure of additive genetic variance that avoids environmental confounding—across 193 eukaryotic species, and evaluated how well evolvability is predicted by molecular diversity. We find that microsatellite and nucleotide diversity are not significantly correlated to each other, and neither predict evolvability. Nucleotide diversity explains 1.1% of interspecific differences in evolvability and doubling nucleotide diversity only corresponds to a 11.7% increase in evolvability. With theoretical work, we show that such weak associations are expected. Together, our results suggest that simple molecular measures of genetic variation are insufficient for predicting adaptive potential and reliance on these metrics risks misinforming conservation management.

Predicting properties of antifungal drug molecules using neighborhood degree topological indices

Abstract Topological indices are an important part of chemical graph theory as a representation of the molecular structure and a predictor of the physicochemical properties. In this paper, nine neighborhood degree sum based topological indices are use as indicators of predictive potential in a QSPR analysis of twenty antifungal drug molecules. Linear, quadratic, and cubic regression models were used to test the relationships between the structural properties and important physicochemical properties, such as boiling point, density, enthalpy of vaporization, flash point, refractive index, molar refractivity, polarizability, surface tension, and molar volume. The findings also revealed that a cubic regression model provided the most optimal overall performance with the highest level of predictability in the form of molar refractivity and polarizability being the neighborhood inverse product index $$(ND_{4} )$$ ( $$R^{2}$$  = 0.98). These results assert that neighborhood based topological descriptors are effective, especially in modeling the refractivity related and electronic properties of drug molecules.

Spin–orbit-resolved strong-field ionization from real-time relativistic dynamics

Strong-field ionization exhibits rich ultrafast dynamics arising from intricate electron-field interactions. However, the role of spin–orbit coupling in the strong-field ionization of many-electron systems remains largely unexplored. Here, we develop a fully relativistic framework that combines a complex absorbing potential (CAP) with the exact two-component (X2C) real-time time-dependent density functional theory. We apply this approach to investigate the real-time strong-field dynamics of atomic krypton with a variational treatment of spin–orbit coupling. The CAP-X2C method captures the spin–orbit-resolved ionization-rate trends of the Kr 4p shell. Moreover, we uncover a previously inaccessible coherent population transfer channel between the 4p12 and 4p32 states, opened by spin–orbit coupling, which lifts the nonrelativistic symmetry restriction that forbids their mixing. This work provides a practical framework for exploring strong-field dynamics in systems where spin–orbit coupling plays a significant role.

Correction for Otsuki et al., Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways

Method for AFM investigation of lateral forces required for the surface detachment of neurites

Abstract Resprouting of neurites to establish direct connections between stimulation electrodes and spiral ganglion neurons is of considerable interest in current cochlear implant research. The adhesion strength of neurites to implant surfaces is a critical factor determining whether such connections develop, remain stable or are disrupted shortly after formation. In this study, an in vitro protocol was established to quantify the lateral forces required to detach neurites from the surface of precoated substrates using atomic force microscopy. Spiral ganglion neurons were isolated from mixed primary cell cultures using cytosine β-D-arabinofuranoside hydrochloride as a mitotic inhibitor. After several days of cultivation, the neurites were mechanically hooked with the cantilever tip and laterally dragged across the substrate surface to measure the forces required for detachment. Four different parameters and their influence on the detachment process were evaluated: exposure time to measurement conditions, the distance between growth cone and cantilever, the distance between cantilever and soma, and the total length of the neurite. The mean lateral detachment force was 2.47 ± 0.19 nN, and no significant correlation was observed between the lateral forces and any of the four investigated parameters. Overall, this study provides quantitative information on neurite-surface adhesion behaviour and strength in vitro.

Molecular structure, binding, and disorder in TDBC–Ag plexcitonic assemblies

Plexcitonic assemblies are hybrid materials composed of a plasmonic nanoparticle and molecular or semiconducting emitters whose electronic transitions are strongly coupled to the plasmonic mode. This coupling hybridizes the system modes into upper and lower polariton branches. The interaction strength depends on the number of emitters and on their orientation and spatial arrangement relative to the metallic surface. These structural factors have profound consequences for the ensuing photoexcited dynamics. Despite the extensive spectroscopic work on plexcitonic systems, direct understanding of the molecular geometry at the metal interface remains limited. We present a comprehensive structural characterization of a model plexciton formed by the cyanine dye 5,5′,6,6′-tetrachloro-1,1′-diethyl-3,3′-di(4-sulfobutyl)-benzimidazolocarbocyanine (TDBC) and silver nanodisks using NMR, THz-Raman spectroscopy, and density functional theory calculations. By comparing the signals from the monomeric and aggregated forms of TDBC with those of the plexciton, we identify shared spectral fingerprints that reveal how molecular packing is modified when the aggregate adsorbs on the silver surface. We observe Raman modes specific to plexciton systems and identify NOESY cross-peaks in the aliphatic region that, along with several Raman modes, are sensitive indicators of aggregation geometry and adsorption. We find that TDBC monomers adopt an asymmetric conformation in which both sulfobutyl chains lie on the same side of the chromophore, while J-aggregates adopt a symmetric up–down alternation of the chains from molecule to molecule, which becomes distorted and loses long range periodicity when adsorbed on Ag nanodisks. This work constrains the molecular geometry and interfacial arrangement of a prototypical TDBC–silver plexciton, providing a structural benchmark for understanding geometry-dependent photophysics in exciton–plasmon systems.

WIP transcriptional regulators modulate developmental progression in both life cycle phases of a moss

The sexual life cycle of bryophytes and vascular plants, the two extant lineages of land plants, is dominated by a gametophytic and a sporophytic phase, respectively. Body plan diversification in these two phases has followed separate evolutionary trajectories in both lineages. However, how evolutionary conserved gene families have accompanied body plan diversification remains poorly understood. WIP transcription factors are conserved in land plants, and their function has been associated with root and flower development in angiosperms. Here, we dissect the function of Pp WIP1 and Pp WIP2 genes in a model bryophyte, the moss Physcomitrium patens . We demonstrate that Pp WIP s are expressed during both phases of the life cycle and regulate specific developmental processes. In the gametophytic phase, Pp WIP s promote the chloronema-to-caulonema transition, but restrict gametophore development. In the sporophytic phase, Pp WIPs prevent polysety, the formation of multiple sporogonia. RNA-seq, DAP-seq, and hormone analysis revealed that both P. patens and A. thaliana proteins act by controlling auxin homeostasis. Interspecies complementation experiments revealed that Pp WIP s are partially able to substitute At WIP molecular function in Arabidopsis root and seeds. Our findings demonstrate that WIPs control developmental progression in both phases of the land plant life cycle through an evolutionarily conserved molecular function.

Isomerization dynamics of dicationic CS2 and OCS driven by electron-impact

The isomerization of dications of CS2 and OCS is investigated using combined experimental and theoretical methods. The dications were generated by a high-energy electron pulse and the fragment ions were detected by a momentum imaging time-of-flight spectrometer. Bond rearrangement reactions leading to C+ + S2+ and C+ + OS+ were identified through coincident measurements. Theoretically, potential energy surfaces along the reaction paths were calculated using high-level quantum chemistry methods. For CS2+, isomerization is initiated by ionization excitation followed by a decay process. In contrast, the isomerization channel for OCS2+ can open on the ground dicationic state through vibrational excitation. The predicted kinetic energy releases agree with the experimental data. This study demonstrates that, as a common process in dissociative ionization, isomerization mechanism may be influenced by molecular symmetry.

Constructing a lower-bound estimate of the global number of insect species on a hyperdiverse empirical foundation

Estimating the number of insect species on Earth is a daunting challenge. The current consensus estimate—about six million species—is likely far too low, as we will show. Our estimate of the global number of insect species rests on a sample of more than 1,600,000 DNA-barcoded insect specimens representing 53,945 species from 15 “core” Malaise traps deployed in dry forest, cloud forest, and rainforest ecosystems of the Área de Conservación Guanacaste (ACG) in Costa Rica. Even this massive sample fails to reveal the full extent of ACG insect species richness. To estimate total ACG insect richness, we adjust the observed count of insect species by an “undersampling ratio,” computed for a hyperdiverse subfamily of parasitoid wasps (Braconidae: Microgastrinae). The ratio compares microgastrine richness from the core Malaise traps to a lower-bound estimate of true microgastrine richness—including undetected species—based on 21,669 specimens from three sources: the 15 core Malaise traps, 15 “peripheral” Malaise traps spanning all three ecosystems, and 11,373 DNA-barcoded specimens reared from some 1,500 species of microgastrine-parasitized caterpillars (Lepidoptera). To estimate global insect richness, we apply Earth/ACG ratios for tree species and several animal taxa to upscale our estimate of ACG insect richness (nearly 333,000 species). Adopting conservative assumptions, we reach an estimate of 14 to 20 million insect species on Earth, depending on the upscaling group—two to three times the current consensus estimates. Upscaling instead from a point estimate of ACG richness with a wide CI, global estimates reach nearly 30 million species.

Silicon doping assisted phase transition of <i>h</i> -BN to <i>c</i> -BN via thermal annealing

Heteroatom doping in hexagonal boron nitride (h-BN) films has been regarded as an effective solution to adjust their electrical and optical properties for realizing applications in various technologies. A high-temperature annealing process is routinely utilized to enhance the doping efficiency following film growth, which is, however, accompanied by other unexpected effects. Thus, understanding the dopant behavior induced by temperature is crucial for unlocking unprecedented development of h-BN. Here, we report the thermally induced mutual diffusion in Si-doped h-BN films grown on sapphire substrates, which can facilitate the transition from the hexagonal to the cubic phase. Spectral analysis indicates that as the annealing temperature increases, the doped films undergo a phase transition from hexagonal to cubic BN phases via an intermediate of explosive BN. Combined x-ray photoelectron spectroscopy and secondary ion mass spectrometry reveal that the thermal annealing above 1000 °C induces the interdiffusion of Si and Al through the interface, where the latter originates from the decomposition of the sapphire substrate. First-principles calculations reveal that the substitution of Si within BN reduces the energy barrier from sp2 to sp3 phase transformation by supplying electrons to adjacent N atoms. This work provides novel insights into understanding the doping behavior in h-BN films and the development of h-BN based devices.

Reply to Wang: Policy failure can be assessed from observed outcomes

Coupled internal energy modes in DSMC

The Landau–Teller model for vibrational energy relaxation of gases toward equilibrium is a first-order kinetic model where the rate of relaxation is proportional to the current defect between the energy in that mode and the equilibrium amount of energy in the mode. In Direct Simulation Monte Carlo (DSMC), collisions are first resolved using a total collision cross section; then, if a collision occurs, the internal energy modes of the colliding particles are tested for relaxation. To reproduce the Landau–Teller model in gases with multiple internal modes, the relaxation of multiple internal modes in a single DSMC collision must be prohibited. This work provides analytical comparison of model-form differences between four models: (1) Landau–Teller theory, (2) the vibrational master equation for a mixture of harmonic oscillators, and DSMC when (3) allowing or (4) prohibiting multiple relaxation in a single collision. This is followed by a rigorous examination of the quantitative effect of the algorithmic choice of allowing or prohibiting multiple relaxation in DSMC. The deviation from the Landau–Teller model caused by allowing multiple relaxations in DSMC is minimal compared to the statistical noise in most cases. However, DSMC practitioners are advised to carefully consider the importance of direct coupling between internal modes, as neglecting these can lead to significant errors.

Beyond unit cells: Programmable morphogenetic design of irregular architected materials

Architected materials derive functionality from geometry, yet conventional unit cell–based design limits functional heterogeneity, geometric adaptability, and robustness to defects. Inspired by natural morphogenesis, we introduce RDGenCAD, a morphogenetic design framework that translates programmable growth rules into reaction–diffusion dynamics to generate self-organized, CAD-ready architectures. A database of 120,000 morphogenetic structures reveals statistically deterministic and continuous tunability of elastic properties across auxetic and conventional regimes, despite pronounced geometric irregularity. These architectures further exhibit emergent flaw insensitivity and crack deflection through stress compartmentalization, leading to synergistic gains in strength and toughness relative to regular lattices. By shifting architected material design from unit-cell tessellation to programmable morphogenetic growth, this work establishes self-organization as a generative principle for designing materials that are irregular yet predictable, heterogeneous yet “coherent,” and directly manufacturable.

A density-based continuous local symmetry measure

Although continuous symmetry theory has attracted increasing attention in modern chemistry, local symmetry remains under-investigated. As a consequence, the relationship between symmetry and chemical behavior is often obscured, limiting the practical use of fuzzy symmetry measures. In this study, we introduce a novel framework for evaluating local symmetry based on electron density localization and present continuous symmetry representations for several representative molecules. Our approach not only quantitatively captures global symmetry but also reveals distinctive features of symmetry in a local chemical environment. The related concept, local chirality or chirotopicity, is also discussed. Overall, the proposed local symmetry and chirality measures provide valuable insights into molecular structure and structure–property relationships.