Browse Articles

Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells

Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.

Publisher's note: “A design technique for transforming statically designed phononic crystals and metamaterials into multifunctional, programmable active acoustic meta-devices” [J. Appl. Phys. 137, 033105 (2025)]

3D ophthalmic ultrasonography at the slit lamp using existing ultrasound systems

Purpose This study aims to explore the feasibility and performance of three-dimensional ultrasound (3DUS) imaging in ophthalmology using commercially available ultrasound probes adapted to a slit lamp. Significance Despite ultrasound’s long-standing application in eye care for visualizing ocular components, the evolution of 3DUS technology has remained inactive, with limited development and commercial availability. This study introduces a novel method that could potentially enhance ophthalmic diagnostics and treatment planning by providing comprehensive 3D views of ocular structures using existing ultrasound probes adapted to the conventional slit lamp. Methods A custom system was designed for mounting a linear actuator to a slit lamp and enabling the horizontal actuation of any ultrasound probe. Ophthalmic and non-ophthalmic ultrasound probes were tested for their ability to reconstruct 3DUS images of the posterior pole. The study involved designing and evaluating three US phantoms ex vivo and performing in vivo imaging on human subjects to assess the system’s applicability. Results The system successfully acquired 3D volume scans of phantoms and live human eyes, demonstrating the system’s potential for detailed ocular imaging. The adaptability of the device allowed for compatibility with various ultrasound probes. In vivo imaging revealed the system’s capability to produce high-resolution 3D reconstructions of ocular structures, including eyes with pathological conditions. Conclusions The introduction of a slit lamp-mounted 3DUS system represents a significant advancement in ophthalmic ultrasonography, offering a practical and accessible solution for comprehensive 3D ocular assessments. The device’s modularity and compatibility with existing ultrasound probes make it a versatile tool for a wide range of ophthalmic applications. Further research and clinical trials are needed to optimize the system’s performance and validate its clinical utility.

Growth and structure of alpha-Ta films for quantum circuit integration

Tantalum films incorporated into superconducting circuits have exhibited low surface losses, resulting in long-lived qubit states. The remaining loss pathways originate in microscopic defects that manifest as two level systems (TLSs) at low temperatures. These defects limit performance, so careful attention to tantalum film structures is critical for optimal use in quantum devices. In this work, we investigate the growth of tantalum using magnetron sputtering on sapphire, Si, and photoresist substrates. In the case of sapphire, we present procedures for the growth of fully-oriented films with α-Ta [1 1 1]//Al2O3 [0 0 0 1] and α-Ta [1 −1 0]//Al2O3 [1 0 −1 0] orientational relationships and having residual resistivity ratio (RRR) ∼ 60 for 220 nm thick films. On Si, we find a complex grain texturing with Ta [1 1 0] normal to the substrate and RRR ∼ 30. We further demonstrate airbridge fabrication using Nb to nucleate α-Ta on photoresist surfaces. For the films on sapphire, resonators show TLS-limited quality factors of 1.3 ± 0.3 × 106 at 10 mK (for a waveguide gap and conductor width of 3 and 6 μm, respectively). Structural characterization using scanning electron microscopy, x-ray diffraction, low temperature transport, secondary ion mass spectrometry, and transmission electron microscopy reveal the dependence of residual impurities and screw dislocation density on processing conditions. The results provide practical insights into the fabrication of advanced superconducting devices including qubit arrays and guide future works on crystallographically deterministic qubit fabrication.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four pathogenic variants of SOX9 identified in a cohort of patients with congenital vertebral malformations. We report a pathogenic missense variant in the transactivation middle (TAM) domain of SOX9 associated with mild skeletal dysplasia and scoliosis. We isolated a Sox9 mutant mouse with an in-frame microdeletion in the TAM domain ( Sox9 Asp272del ), which exhibits skeletal dysplasia including kinked tails, rib cage anomalies, and scoliosis in homozygous mutants. We find that both the human missense and the mouse microdeletion mutations resulted in reduced SOX9 protein stability in cell culture, while Sox9 Asp272del mutant mice show decreased SOX9 expression in the growth plate and annulus fibrosus tissues of the spine. This reduction in SOX9 expression was correlated with the reduction of extracellular matrix components, such as tenascin-X and the Adhesion G-protein coupled receptor ADGRG6. In summary, our work identified and modeled a pathologic variant of SOX9 within the TAM domain and demonstrated its importance for SOX9 protein stability. Our work demonstrates that SOX9 stability is important for the regulation of ADGRG6 expression, which is a known regulator of postnatal spine homeostasis, underscoring the essential role of SOX9 dosage in a spectrum of axial skeleton dysplasia in humans.

Impact of exercise with blood flow restriction on muscle hypertrophy and performance outcomes in men and women

Blood flow restriction training (BFRT) has been previously studied as an alternative form of resistance training to gain lean mass and improve performance outcomes. However, in all exercise studies of BFRT, the proportion of female participants represents only 17–29% of all research participants. This highlights a strong underrepresentation of females and the need for more knowledge on the impact of BFRT and sex differences. The primary objective was to compare the impact of 6-week BFRT on lean mass, strength, and performance outcomes between males and females. A total of 38 adults [age, 25.3 ±  3.1 years; female, n = 19 (50%)] performed whole-body resistance training program with blood flow restriction three times per week. Exercises were performed at 30% of 1-repetition maximum (1-RM) and blood flow restriction cuffs were set to 60% of each individual’s limb occlusion pressure. Body composition was assessed via dual-energy x-ray absorptiometry and strength was measured using 1-RM. A significant increase in lean mass was observed in males (p = 0.009) and females (p = 0.023) with no difference in the change between groups (p = 0.279). Both males and females increased 1-RM for upper- and lower-body exercises, with significant interaction effects (time x sex) for chest press (p = 0.003), seated row (p = 0.038), knee flexion (p = 0.043), and knee extension (p = 0.035), suggesting males increased 1-RM more for these exercises. Furthermore, peak power was improved in males (p < 0.001) and females (p = 0.002) during a vertical squat jump, but a significant interaction (time x sex) effect was observed (p = 0.039), suggesting males increased to a greater extent. Males and females significantly increased lean body mass, to a similar degree, following six weeks of resistance training in combination with blood flow restriction. Likewise, both males and females improved muscle strength following 6-week BFRT, however males may improve strength to a greater extent than females.

Exploring magnetic anisotropy in garnet films at low temperatures using ferromagnetic resonance

Ferromagnetic resonance is widely acknowledged as a robust tool for characterizing magnetic materials and studying physical phenomena. Low-temperature magnonics has recently garnered substantial attention; however, it lacks convenient methods for acquiring key magnetic material characteristics. In this study, we introduce a rapid and universal method to determine the temperature dependence of magnetic anisotropy constants of (111)-oriented garnet films using ferromagnetic resonance measurements, demonstrated specifically on the bismuth-substituted iron garnet film grown on a diamagnetic substrate. Our observations reveal a competitive interplay of different anisotropy types as temperature decreases. Notably, the uniaxial magnetic anisotropy constant Ku undergoes a sign change from negative to positive around 120 K, while the anisotropy type remains consistent.

Diffusive topology preserving manifold distances for single-cell data analysis

Manifold learning techniques have emerged as crucial tools for uncovering latent patterns in high-dimensional single-cell data. However, most existing dimensionality reduction methods primarily rely on 2D visualization, which can distort true data relationships and fail to extract reliable biological information. Here, we present DTNE (diffusive topology neighbor embedding), a dimensionality reduction framework that faithfully approximates manifold distance to enhance cellular relationships and dynamics. DTNE constructs a manifold distance matrix using a modified personalized PageRank algorithm, thereby preserving topological structure while enabling diverse single-cell analyses. This approach facilitates distribution-based cellular relationship analysis, pseudotime inference, and clustering within a unified framework. Extensive benchmarking against mainstream algorithms on diverse datasets demonstrates DTNE’s superior performance in maintaining geodesic distances and revealing significant biological patterns. Our results establish DTNE as a powerful tool for high-dimensional data analysis in uncovering meaningful biological insights.

Impact of media coverage on the transmission dynamics of TB with vaccines and treatment

Tuberculosis (TB) is one of the deadly infectious diseases affecting millions of individuals throughout the world. The main objective of this study is to investigate the impact of media coverage on the transmission dynamics of TB with vaccine and treatment strategy using mathematical model analysis. In the qualitative analysis of the proposed model we proved the existence, uniqueness, positivity, and boundedness of the model solutions, investigated both the disease-free and endemic equilibrium points, computed the basic and effective reproduction numbers using next generation matrix approach, analyzed the stability analysis of the equilibrium points, the backward bifurcation using the Castillo-Chavez and Song theorem and we re-formulated the corresponding optimal control problem and analyzed by applying the Pontryagin’s Minimum Principle. In the model quantitative (numerical) analysis part, we performed the model parameters sensitivity analysis and carried out numerical simulation to verify the qualitative analysis results. The findings of the study indicate that if the reproduction number is less than one, the solution converges to the disease-free state, signifying the asymptotic stability of the TB-free steady state. Moreover, the existence of a backward bifurcation shows that the disease-free equilibrium coexists with one or more endemic equilibria, even when the basic reproduction number is less than 1. Furthermore, it is found that as media efficacy increases, the disease infection rate decreases, which consequently leads to an increase in prevention and treatment control strategies.

Magnetocaloric effect in La1−<i>z</i>Ce<i>z</i>(Fe0.88−<i>y</i>Mn<i>y</i>Si0.12)13 with tunable, low transition temperature in high magnetic fields

Cryogenic magnetic refrigeration becomes more and more important nowadays, especially for the liquefaction of gases such as hydrogen. In this study, we have synthesized La1−zCez(Fe0.88−yMnySi0.12)13 samples and investigated their magnetic and magnetocaloric properties in order to assess their potential for cryogenic applications. By adjusting the Mn and Ce content and adding excess rare-earth elements, the first-order ferromagnetic transition was lowered from 200 to 40 K and the adiabatic temperature change of the samples was measured directly using pulsed magnetic fields. The sample with the lowest transition temperature still showed a significant adiabatic temperature change in magnetic fields up to 10 T, with an increasingly stronger first-order transition observed in samples with higher Ce substitution. In addition, we synthesized spherical powder with diameters between 20 and 120 μm using ultrasonic atomization while maintaining the magnetic transition, which is a promising starting material for future additive manufacturing of magnetocaloric materials.

Representational geometry explains puzzling error distributions in behavioral tasks

Measuring and interpreting errors in behavioral tasks is critical for understanding cognition. Conventional wisdom assumes that encoding/decoding errors for continuous variables in behavioral tasks should naturally have Gaussian distributions, so that deviations from normality in the empirical data indicate the presence of more complex sources of noise. This line of reasoning has been central for prior research on working memory. Here, we reassess this assumption and find that even in ideal observer models with Gaussian encoding noise, the error distribution is generally non-Gaussian, contrary to the commonly held belief. Critically, we find that the shape of the error distribution is determined by the geometrical structure of the encoding manifold via a simple rule. In the case of a high-dimensional geometry, the error distributions naturally exhibit flat tails. Using this insight, we apply our theory to visual short-term memory tasks, and find that it can account for a large array of experimental data with only two free parameters. Our results challenge the dominant view in the mechanisms and capacity constraints of working memory systems. They instead suggest that the Bayesian framework, which explains various aspects of perceptual behavior, also provides an excellent account of working memory. Overall, our results establish a direct connection between neural manifold geometry and behavior, and call attention to the geometry of the representation as a critically important, yet underappreciated factor in determining the character of errors in human behavior.

The importance of method selection when estimating diet composition with quantitative fatty acid signature analysis

Quantitative fatty acid signature analysis (QFASA) is a common method of estimating the composition of prey species in the diets of consumers from polar and temperate ecosystems in which lipids are an important source of energy. A key characteristic of QFASA is that the large number of fatty acids that typically comprise lipids permits the dietary contributions of a correspondingly large number of prey types to be estimated. Several modifications to the original QFASA methods have been suggested in the literature and a significant extension of the original model published in 2017 allows simultaneous estimation of both diet proportions and calibration coefficients, which are metabolic constants in the model whose values must otherwise be estimated in independent feeding experiments. However, comparisons of diet estimates obtained using different estimation options have been limited. QFASA has been used to estimate the diet composition of several polar bear (Ursus maritimus) subpopulations, including the Southern Beaufort Sea (SBS) subpopulation. Prior QFASA estimates of SBS polar bear diet composition have most often been obtained using variations of the original QFASA model. We investigated the influence of variations in QFASA analytical methods on diet estimates by re-estimating the diet composition of polar bears from the Alaska portion of the SBS using three different methods and found that differences among the three sets of estimates were substantial. Our results illustrate how important the careful and deliberate selection of QFASA methods can be and we provide some guidance on techniques one might use to evaluate options.

Cryogenic behavior of high-permittivity gate dielectrics: The impact of atomic layer deposition temperature and the lithographic patterning method

Dielectrics featuring a high relative permittivity, i.e., high-k dielectrics, have become the standard insulators in gate architectures, enhancing the electrical performance of both room temperature and cryogenic electronics. This study delves into the cryogenic (3 K) performance of high-k dielectrics commonly used as gate insulators. We fabricated Al2O3 and HfO2 layers via atomic layer deposition (ALD) and extrapolated relative permittivity (k) and dielectric strength (EBD) from AC (100 Hz–100 kHz) and DC measurements on metal–insulator–metal capacitors. Our findings reveal a strong dependence of HfO2 cryogenic performance on ALD growth temperature, while the latter shows a negligible impact on Al2O3. We estimated ∼9% and ∼14% reductions in the relative permittivities of HfO2 and Al2O3, respectively, at temperatures from 300 to 3 K. Additionally, we designed and fabricated Al2O3/HfO2 bilayers and checked their properties at cryogenic temperatures. The study also investigates the impact of the patterning method, namely, UV or electron-beam lithography (acceleration voltage of 10, 20, or 30 kV), on the high-k dielectric properties.

The <i>Pseudomonas</i> ligninolytic catalytic network reveals the importance of auxiliary enzymes in lignin biocatalysts

Lignin degradation by biocatalysts is a key strategy to develop a plant-based sustainable carbon economy and thus alleviate global climate change. This process involves synergy between ligninases and auxiliary enzymes. However, auxiliary enzymes within secretomes, which are composed of thousands of enzymes, remain enigmatic, although several ligninolytic enzymes have been well characterized. Moreover, it is a challenge to understand synergistic lignin degradation via a diverse array of enzymes, especially in bacterial systems. In this study, the coexpression network of the periplasmic proteome uncovers potential accessory enzymes for B-type dye-decolorizing peroxidases (DypBs) in Pseudomonas putida A514. The catalytic network of the DypBs-based multienzyme complex is characterized. DypBs couple with quinone reductases and nitroreductase to participate in quinone redox cycling. They work with superoxide dismutase to induce Fenton reaction for lignin oxidation. A synthetic enzyme cocktail (SEC), recruiting 15 enzymes, was consequently designed with four functions. It overcomes the limitation of lignin repolymerization, exhibiting a capacity comparable to that of the native periplasmic secretome. Importantly, we reveal the synergistic mechanism of a SEC-A514 cell system, which incorporates the advantages of in vitro enzyme catalysis and in vivo microbial catabolism. Chemical analysis shows that this system significantly reduces the molecular weight of lignin, substantially extends the degradation spectra for lignin functional groups, and efficiently metabolizes lignin derivatives. As a result, 25% of lignin is utilized, and its average molecular weight is reduced by 27%. Our study advances the knowledge of bacterial lignin-degrading multienzymes and provides a viable lignin degradation strategy.

Association between chiropractic spinal manipulation for sciatica and opioid-related adverse events: A retrospective cohort study

Background Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM. Methods We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.) of more than 216 million patients, yielding data ranging from 2009 to 2024. We included patients aged ≥18 years with sciatica, excluding those post-spine surgery, prior anesthesia, serious pathology, high risk of ORADEs, and an ORADE ≤ 1-year prior. Patients were divided into two cohorts: (1) CSM and (2) usual medical care. We used propensity score matching to control for confounding variables associated with ORADEs. Comparative outcomes were analyzed by calculating risk ratios (RRs) and 95% confidence intervals (CIs) for the incidence of ORADEs and oral opioid prescription between cohorts. Results 372,471 patients per cohort remained after matching. The incidence of ORADEs over 1-year follow-up was less in the CSM cohort compared to the usual medical care cohort (CSM: 0.09%; usual medical care: 0.30%), yielding an RR of 0.29 (95% CI: 0.25–0.32; P &lt; .00001). CSM patients had a lower risk of receiving an oral opioid prescription (RR of 0.68 [95% CI: 0.68–0.69; P &lt; .00001]). Conclusions This study found that adults with sciatica who initially received CSM had a lower risk of an ORADE compared to matched controls not initially receiving CSM, likely explained by a lower probability of opioid prescription. These findings corroborate existing practice guidelines which recommend adding CSM to the management of sciatica when appropriately indicated.

Calculation of semiconductor melting temperatures based on Fan-equation approximated by the 37% rule

We present a mathematical model capable of the calculation of semiconductor melting temperatures. Notably, and quite different from previous attempts, the procedure does not require specific knowledge about the thermodynamics of the materials and is based on the Fan equation and the 1/e rule, also known as the 37% rule. Employing this new model, we calculated melting temperatures for 14 semiconductors spanning a wide range of bandgap energies. The results found are in good agreement with previous theoretical and experimental values reported in the literature, establishing the strength of the model in spite of its simplicity. The model also unifies elements and compounds with representative linear trends, showcasing the potential for future expansion.

An analytical model of label-free nanoscale chemical imaging reveals avenues toward improved spatial resolution and sensitivity

Atomic force microscopy–infrared spectroscopy (AFM-IR) is a photothermal scanning probe technique that combines nanoscale spatial resolution with the chemical analysis capability of mid-infrared spectroscopy. Using this hybrid technique, chemical identification down to the single molecule level has been demonstrated. However, the mechanism at the heart of AFM-IR, the transduction of local photothermal heating to cantilever deflection, is still not fully understood. Existing physical models only describe this process in few special cases but not in many of the types of sample geometries encountered in the practical use of AFM-IR. In this work, an analytical expression for modeling the temperature and photothermal expansion process is introduced, verified with finite element simulations, and validated with AFM-IR experiments. This method describes AFM-IR signal amplitudes in vertically and laterally heterogeneous samples and allows studying the effect of position and size of an absorber, pump laser repetition rate and pulse width on AFM-IR signal amplitudes and spatial resolution. The analytical model can be used to identify optimal AFM-IR experimental settings in conventional and advanced AFM-IR modes (e.g., tapping mode, surface-sensitive mode). The model also paves the way for signal inversion based superresolution AFM-IR.

Correction: Intersecting paths: Corporate and green innovation in Chinese firms—A penal cointegration analysis

Optimal power-law fluid flow in tree-like branching networks with self-similar and uniform roughness models

This study presents an analytical model for the flow of a power-law non-Newtonian fluid through a roughened tree-like branching network under volume and surface area constraints. We assume steady-state, axisymmetric, and laminar flow with non-slip boundary conditions along the network walls. We investigate and compare two different roughness models. In the first model, the roughness length scale is self-similar and aligns with the branching network pattern, while in the second model, the surface roughness length scale is uniform. We find that in the case of the self-similar roughness model, the effective conductance remains the same as that of the smooth network. However, in the case of the uniform roughness model, the effective conductance presents an overall decrease. We argue that the uniform roughness model is a more realistic one. Furthermore, the optimal effective conductance, Eopt, and the critical diameter ratio βc, are analyzed as functions of network geometry and fluid rheology. Under both volume and surface area constraints, increasing geometrical parameters such as the number of daughter branches and network generations, generally reduced Eopt, especially for shear-thickening fluids, while shear-thinning fluids were less affected. In macroscopic networks, where roughness is relatively small, the effect of roughness on Eopt is negligible; however, in microscopic networks, where roughness approaches the scale of the diameters of the smallest branches, it leads to pronounced conductance reduction. Furthermore, networks under surface area constraint show significantly lower Eopt values compared to volume-constrained systems. Moreover, we find that the uniform surface roughness model predicts scaling laws for optimal flow (at βc) that vary with all geometrical and rheological parameters. Finally, for macroscopic networks under the uniform roughness assumption, an approximation for βc was derived using linearization with respect to the roughness intensity parameter, and it was found to be in good agreement with the full model equations.

Violence against women and girls research: Leveraging gains across disciplines

Violence against women and girls (VAWG) is a leading cause of mortality and morbidity worldwide, linked to numerous health, economic, and human rights outcomes. Target 5.2 of the Sustainable Development Goals calls for elimination of all forms of VAWG; however, progress toward achieving this goal has been inadequate. A lack of sufficient data and evidence has hindered global efforts to meet this target and hold governments accountable for action. While there have been substantial advancements in VAWG research methodology over the past three decades, researchers from diverse disciplines tend to work in silos, inhibiting progress in VAWG research. To address this challenge, we offer four key recommendations to support researchers in expanding transdisciplinary approaches: 1) leverage insights from a variety of VAWG data sources, 2) improve precision of VAWG definitions and outcomes, 3) create strategies to address underreporting, and 4) advance research ethics and equity. We conclude with a call to action for researchers, institutions, and donors to advance transdisciplinary research and foster collaboration, learning, and cross-fertilization across scientific fields to accelerate VAWG prevention efforts now and for future generations.