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Abstract Identifying cell-type-specific 3D chromatin interactions between regulatory elements can help decipher gene regulation and interpret disease-associated non-coding variants. However, achieving this resolution with current 3D genomics technologies is often infeasible given limited input cell numbers. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps, including regulatory interactions, from single-cell ATAC sequencing (scATAC-seq) data alone. ChromaFold uses pseudobulk chromatin accessibility, co-accessibility across metacells, and a CTCF motif track as inputs and employs a lightweight architecture to train on standard GPUs. Trained on paired scATAC-seq and Hi-C data in human samples, ChromaFold accurately predicts the 3D contact map and peak-level interactions across diverse human and mouse test cell types. Compared to leading contact map prediction models that use ATAC-seq and CTCF ChIP-seq, ChromaFold achieves state-of-the-art performance using only scATAC-seq. Finally, fine-tuning ChromaFold on paired scATAC-seq and Hi-C in a complex tissue enables deconvolution of chromatin interactions across cell subpopulations.

Abstract Background Alzheimer's disease (AD) impairs cognitive functions and peripheral systems, including skeletal muscles. The PS19 mouse, expressing the human tau P301S mutation, shows cognitive and muscular pathologies, reflecting the central and peripheral atrophy seen in AD. Methods We analysed skeletal muscle morphology and neuromuscular junction (NMJ) through immunohistochemistry and advanced image quantification. A factorial Analysis of Variance assessed muscle weight, NCAM expression, NMJ, myofibre type distribution, cross‐sectional areas, expression of single or multiple myosin heavy‐chain isoforms, and myofibre grouping in PS19 and wild type (WT) mice over their lifespan (1–12 months). Results Significant weight differences in extensor digitorum longus (EDL) and soleus muscles between WT and PS19 mice were noted by 7–8 months. For EDL muscle in females, WT weighed 0.0113 ± 0.0005 compared with PS19's 0.0071 ± 0.0008 (P

To explore the feasibility of applying nanobodies in colloidal gold immunochromatography assay (GICA) for small-molecule harmful substances, this study systematically investigated the effects of colloidal gold labeling parameters, colloidal gold working buffer and sample pretreatment methods on GICA using the pesticide procymidone as a model. The results showed that the size of colloidal gold particles, labeling pH and the amount of antibody used were the key factors to ensure the stability of the nanobody-gold-labeled probes. Under the optimal conditions, the limit of detection, half-maximal inhibitory concentration (IC50) and visual detection limit of GICA for procymidone were 0.44, 6.29 and 200 μg/L, respectively. The sensitivity was 5.1-fold higher than that of conventional monoclonal antibody-based GICA. The quick, easy, cheap, effective, rugged and safe (QuEChERS) procedure was used for the pretreatment of Chinese leek, cucumber and tomato samples. Based on the excellent organic solvent tolerance of nanobodies, the organic solvent blow-drying procedure was omitted. The average recoveries of the spiked samples ranged from 80.1% to 109.6%, and the results for the actual samples were consistent with those of gas chromatography-mass spectrometry (GC-MS). This study showed that nanobodies are a potential alternative to conventional antibodies for immunoassays for the rapid detection of small molecules. The proposed nanobody-based GICA can be used for the rapid screening of procymidone in vegetables with the advantages of high sensitivity, high accuracy, rapidity and simplicity.

In this study, the Kevin–Voigt viscoelastic constitutive relationship is used to investigate the vibration characteristics and stability of a functionally graded viscoelastic(FGV) fluid-conveying pipe with initial geometric defects under thermal–magnetic coupling fields. First, the nonlinear dimensionless differential equations of motion are derived by applying Timoshenko beam theory. Second, by solving the equilibrium position of the system, the nonlinear term in the differential equations of motion is approximated as the sum of the longitudinal displacement at the current time and longitudinal displacement relative to the position, and the equations are linearized. Third, these equations are discretized using the Galerkin method and are numerically solved under simply supported conditions. Finally, the effects of dimensionless temperature field parameters, dimensionless magnetic field parameters, thermal–magnetic coupling, initial geometric defect types, and the power-law exponent on the complex frequency of the pipe are examined. Results show that increasing the magnetic field intensity enhances the critical velocity of first-order mode instability, whereas a heightened temperature variation reduces the critical velocity of first-order diverge instability. Under thermal–magnetic fields, when the magnetic field intensity and temperature difference are simultaneously increased, their effects on the complex frequency can partially offset each other. Increasing the initial geometric defect amplitude increases the imaginary parts of the complex frequencies; however, for different types of initial geometric defect tubes, it exhibits the most distinct influence only on a certain order.

Abstract Background The discovery of adrenoceptors, which mediate the effects of the sympathetic nervous system neurotransmitter norepinephrine on specific tissues, sparked the development of sympathomimetics that have profound influence on skeletal muscle mass. However, chronic administration has serious side effects that preclude their use for muscle‐wasting conditions such as sarcopenia, the age‐dependent decline in muscle mass, force, and power. Devising interventions that can adjust neurotransmitter release to changing physiological demands will require understanding how the sympathetic nervous system affects muscle motor innervation and muscle mass, which will prevent sarcopenia‐associated impaired mobility, falls, institutionalization, co‐morbidity, and premature death. Here, we tested the hypothesis that prolonged heart and neural crest derivative 2 (Hand2) expression in peripheral sympathetic neurons (SNs) ameliorates sympathetic muscle denervation, motor denervation, and sarcopenia in geriatric mice. Methods We delivered either a viral vector encoding the transcription factor Hand2 or an empty vector (EV) driven to SNs by the PRSx8 promoter by injecting the saphenous vein in 16‐month‐old C57BL/6 mice that were sacrificed 10–11 months later. Studies relied on sympathetic and muscle immunohistochemistry analysed by confocal microscopy, nerve and muscle protein expression assessed by immunoblots, nerve‐evoked and muscle‐evoked maximal muscle contraction force, extensor digitorum longus (EDL) muscle RNA sequencing, SN real‐time PCR, and tests of physical performance using an inverted‐cling grip test and in an open‐arena setting. Results Examining the mice 10–11 months later, we found that inducing Hand2 expression in peripheral SNs preserved (i) the number of neurons (EV: 0.32 ± 0.03/μm2, n = 6; Hand2: 0.92 ± 0.08/μm2, n = 7; P

Abstract Background Sarcopenia, or age‐dependent decline in muscle force and power, impairs mobility, increasing the risk of falls, institutionalization, co‐morbidity, and premature death. The discovery of adrenoceptors, which mediate the effects of the sympathetic nervous system (SNS) neurotransmitter norepinephrine on specific tissues, sparked the development of sympathomimetics that have profound influence on skeletal muscle mass. However, chronic administration has serious side effects that preclude their use for muscle‐wasting conditions. Interventions that can adjust neurotransmitter release to changing physiological demands depend on understanding how the SNS affects neuromuscular transmission, muscle motor innervation, and muscle mass. Methods We examined age‐dependent expression of the heart and neural crest derivative 2 (Hand2), a critical transcription factor for SN maintenance, and we tested the possibility that inducing its expression exclusively in sympathetic neurons (SN) will prevent (i) motor denervation, (ii) impaired neuromuscular junction (NMJ) transmission, and (iii) loss of muscle mass and function in old mice. To test this hypothesis, we delivered a viral vector carrying Hand2 expression or an empty vector exclusively in SNs by vein injection in 16‐month‐old C57BL/6 mice that were sacrificed 6 months later. Techniques include RNA‐sequencing, real‐time PCR, genomic DNA methylation, viral vector construct, tissue immunohistochemistry, immunoblot, confocal microscopy, electrophysiology, and in vivo mouse physical performance. Results Hand2 expression declines throughout life, but inducing its expression increased (i) the number and size of SNs, (ii) muscle sympathetic innervation, (iii) muscle weight and force and whole‐body strength, (iv) myofiber size but not muscle fibre‐type composition, (v) NMJ transmission and nerve‐evoked muscle force, and (vi) motor innervation in old mice. Additionally, the SN controls a set of genes to reduce inflammation and to promote transcription factor activity, cell signalling, and synapse in the skeletal muscle. Hand2 DNA methylation may contribute, at least partially, to gene silencing. Conclusions Selective expression of Hand2 in the mouse SNs from middle age through old age increases muscle mass and force by (i) regulating skeletal muscle sympathetic and motor innervation; (ii) improving acetylcholine receptor stability and NMJ transmission; (iii) preventing inflammation and myofibrillar protein degradation; (iv) increasing autophagy; and (v) probably enhancing protein synthesis.

Abstract Background Hypertriglyceridemia (HTG) is considered an independent risk factor for major adverse cardiovascular events (MACE). Methods This study analyzed the effects of various agents on MACE risk reduction in HTG (serum triglyceride ≥ 150 mg/dl) populations by performing a network meta-analysis. We performed a frequentist network meta-analysis to conduct direct and indirect comparisons of interventions. PubMed, EMBASE, and the Cochrane library were searched for trials until Jul 6, 2020. Randomized controlled trials that reported MACE associated with agents in entire HTG populations or in subgroups were included. The primary outcome was MACE. Results Of the 2005 articles screened, 21 trials including 56,471 patients were included in the analysis. The network meta-analysis results for MACE risk based on frequency data showed that eicosapentaenoic acid (EPA) (OR: 1.32; 95% CI 1.19–1.46), gemfibrozil (OR: 1.53; 95% CI 1.20–1.95), niacin plus clofibrate (OR: 2.00; 95% CI 1.23–3.25), pravastatin (OR: 1.32; 95% CI 1.15–1.52), simvastatin (OR: 2.38; 95% CI 1.55–3.66), and atorvastatin (OR: 0.55; 95% CI 0.37–0.82) significantly reduced the risk of MACE compared to the control conditions. In the subgroup analysis of HTG patients with triglycerides ≥ 200 mg/dL, bezafibrate (OR: 0.56; 95% CI 0.33–0.94), EPA (OR: 0.72; 95% CI 0.62–0.82), and pravastatin (OR: 1.33; 95% CI 1.01–1.75) significantly reduced the MACE risk. Conclusions Simvastatin had a clear advantage in reducing the risk of MACE in the entire HTG population analyzed in this meta-analysis. EPA, but not omega-3 fatty acid, was considered an effective HTG intervention. Among fibrates, gemfibrozil was most effective, though bezafibrate may significantly reduce the risk of MACE in populations with triglyceride levels of 200–300 mg/dL. Trial registration retrospectively registered in PROSPERO (CRD42020213705).

Background Cardiac hypertrophy (CH) is a physiological response that compensates for blood pressure overload. Under pathological conditions, hypertrophy can progress to heart failure as a consequence of the disorganized growth of cardiomyocytes and cardiac tissue. USP10 (ubiquitin‐specific protease 10) is a member of the ubiquitin‐specific protease family of cysteine proteases, which are involved in viral infection, oxidative stress, lipid drop formation, and heat shock. However, the role of USP10 in CH remains largely unclear. Here, we investigated the roles of USP10 in CH. Methods and Results Cardiac‐specific USP10 knockout (USP10‐CKO) mice and USP10‐transgenic (USP10‐TG) mice were used to examined the role of USP10 in CH following aortic banding. The specific functions of USP10 were further examined in isolated cardiomyocytes. USP10 expression was increased in murine hypertrophic hearts following aortic banding and in isolated cardiomyocytes in response to hypertrophic agonist. Mice deficient in USP10 in the heart exhibited exaggerated cardiac hypertrophy and fibrosis following pressure overload stress, which resulted in worsening of cardiac contractile function. In contrast, cardiac overexpression of USP10 protected against pressure overload‐induced maladaptive CH. Mechanistically, we demonstrated that USP10 activation and interaction with Sirt6 in response to angiotensin II led to a marked increase in the ubiquitination of Sirt6 and resulted in Akt signaling downregulation and attenuation of cardiomyocyte hypertrophy. Accordingly, inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6‐induced downstream signaling in cardiomyocytes. Conclusions USP10 functions as a Sirt6 deubiquitinase that induces cardiac myocyte hypertrophy and triggers maladaptive CH.

In recent years, wireless sensor networks have been extensively deployed to collect various data. Due to the effect of harsh environments and the limitation of the computing and communication capabilities of sensor nodes, the quality and reliability of sensor data are affected by outliers. Thus, an effective outlier detection method is essential. The existing outlier detection methods have some drawbacks, such as extra resource consumption introduced by the size growth of a local detector, poor performance of combination methods of local detectors, and the weak adaptability of the dynamic changes of the environment, etc. We propose an isolation-based distributed outlier detection framework using nearest-neighbor ensembles (iNNE) to effectively detect outliers in wireless sensor networks. In our proposed framework, local detectors are constructed in each node by the iNNE algorithm. A new combination method taking advantage of the spatial correlation among sensor nodes for local detectors is presented. The method is based on the weighted voting idea. In addition, we introduce a sliding window to update local detectors, which enables the adaption of dynamic changes in the environment. The extensive experiments are conducted on two classic real sensor datasets. The experimental results show our framework significantly improves the detection accuracy and reduces the false alarm rate compared with other outlier detection frameworks.

High accuracy vehicle localization information is critical for intelligent transportation systems and future autonomous vehicles. It is challenging to achieve the required centimeter-level localization accuracy, especially in urban or global navigation satellite system denied environments. Here we propose a vehicle-to-infrastructure (V2I)-based vehicle localization algorithm. First, it is low-cost and hardware requirements are simplified, the minimum requirement is a single roadside unit and single on-board receiver. Second, it is computationally efficient, the available V2I information is formulated as an over-determined system. Then, the vehicle position is estimated in a closed-form manner via the widely used weighted linear least squares (WLLS) method and meter level accuracy is achievable. Furthermore, the numerical performance of WLLS is consistent with the theoretical results in larger signal-to-noise ratio region.

Nanostructured alumina supported copper oxide granular sorbents were prepared by the sol-gel method. The properties of the sol-gel derived sorbents were compared with a similar commercial sorbent which has been used in the pilot scale moving-bed copper oxide process for flue gas treatment. The crushing strength of the sol-gel derived sorbents is about 6–7 times that of the commercial samples, while the attrition rate of the former is at least 3 times smaller. At temperatures below 400 °C, SO2 sorption capacity of the sol-gel derived sorbent is about 3 times that of the commercial sorbent with a similar amount of CuO loading (7–9 wt%). The better mechanical properties and higher sulfation capacity of the sol-gel derived alumina supported copper oxide sorbents are due to their unique microstructure and the coating method for CuO.

Transverse vibration and stability of deploying rectangular cross-sectional cantilever beam made of functionally graded material are investigated. The functionally graded material beam is assumed to be constructed with ceramics and metal phases, and the corresponding equivalent parameters of functionally graded material are found to continuously vary across the cross-sectional height with a simple power law. The differential equations of motion of deploying functionally graded material cantilever beam are derived by Hamilton’s principle. Based on the assumed modal method, the beam deflection function is expanded into a series, in which each term is expressed to admissible function multiplied by generalized coordinate. The eigenfunctions of cantilever beam in which the length of the beam is time-dependent are chosen as admissible functions. Galerkin method is employed to discretize the differential equation to a set of time-coordinate-dependent ordinary differential equations, and then the eigenvalue problem depending on time is obtained. The deployment motion of beam is considered as a constant speed in this study, and some numerical results, which are variations of tip deflection response and complex frequencies, are obtained. Finally, the effects of gradient index of functionally graded material, deploying speed, initial length and protruded length, the cross-sectional height on dynamical characteristics, and divergence instability of the deploying functionally graded material beam are discussed.

The thermoelastic coupling vibration characteristics of the axially moving beam with frictional contact are investigated. The piecewise differential equation of motion for the axially moving beam in the thermoelastic coupling case and the continuous conditions at the contact point are established. The eigenequation is derived by the differential quadrature method, and the first order dimensionless complex frequencies of the simply supported axially moving beam under the coupled thermoelastic case are calculated. The effects of the dimensionless thermoelastic coupling factor, the dimensionless moving speed, the spring stiffness, the friction coefficient, and the normal pressure on the thermoelastic coupling vibration characteristics of the axially moving beam with frictional contact are discussed. [DOI: 10.1115/1.4001513] Keywords: thermoelastic coupling, axially moving beam, frictional contact, vibration characteristics, differential quadrature method

Based on the thin plate theory and the two-dimensional viscoelastic differential type constitutive relation, the differential equation of motion of a viscoelastic plate containing an all-over part-through crack and subjected to uniformly distributed tangential follower force is established in Laplace domain. Then, by performing the Laplace inverse transformation, the differential equation of motion of the plate in the time domain is obtained. The expression of the additional rotation induced by the crack is given. The complex eigenvalue equations of the cracked viscoelastic plate subjected to uniformly distributed tangential follower force are obtained by the differential quadrature method, and the [delta] method is adopted at the crack continuity conditions. The general eigenvalue equations of the cracked viscoelastic plate subjected to uniformly distributed tangential follower force under the different boundary conditions are calculated. The transverse vibration characteristics, type of instability, and corresponding critical loads of the cracked viscoelastic plate subjected to uniformly distributed tangential follower force are analyzed. [DOI: 10.1115/1.2936927] Keywords: dynamic stability, follower force, viscoelastic plate, crack, differential quadrature method

NaMgH3 perovskite hydride and NaMgH3–carbon nanomaterials (NH-CM) composites were prepared via the reactive ball-milling method. To investigate the catalytic effect of CM on the dehydriding kinetic properties of NaMgH3 hydride, multiwall carbon nanotubes (MWCNTs) and graphene oxide (GO) were used as catalytic additives. It was found that dehydriding temperatures and activation energies (ΔE1 and ΔE2) for two dehydrogenation steps of NaMgH3 hydride can be greatly reduced with a 5 wt. % CM addition. The NH–2.5M–2.5G composite presents better dehydriding kinetics, a lower dehydriding temperature, and a higher hydrogen-desorbed amount (3.64 wt. %, 638 K). ΔE1 and ΔE2 can be reduced by about 67 kJ/mol and 30 kJ/mol, respectively. The results suggest that the combination of MWCNTs and GO is a better catalyst as compared to MWCNTs or GO alone.