Increased transcriptional elongation and RNA stability of GPCR ligand binding genes unveiled via RNA polymerase II degradation.

RNA polymerase II drives mRNA gene expression, yet our understanding of Pol II degradation is limited. Using auxin-inducible degron, we degraded Pol II's RPB1 subunit, resulting in global repression. Surprisingly, certain genes exhibited increased RNA levels post-degradation. These genes are associated with GPCR ligand binding and are characterized by being less paused and comprising polycomb-bound short genes. RPB1 degradation globally increased KDM6B binding, which was insufficient to explain specific gene activation. In contrast, RPB2 degradation repressed nearly all genes, accompanied by decreased H3K9me3 and SUV39H1 occupancy. We observed a specific increase in serine 2 phosphorylated Pol II and RNA stability for RPB1 degradation-upregulated genes. Additionally, α-amanitin or UV treatment resulted in RPB1 degradation and global gene repression, unveiling subsets of upregulated genes. Our findings highlight the activated transcription elongation and increased RNA stability of signaling genes as potential mechanisms for mammalian cells to counter RPB1 degradation during stress.

Sperm freezing damage: the role of regulated cell death.

Substantial progress in research on sperm cryopreservation has occurred since the twentieth century, especially focusing on improving sperm freezing procedures and optimizing semen extenders. However, the cellular biological mechanisms of sperm freezing damage are still unclear, which greatly restricts the promotion and development of sperm cryopreservation. An essential component of sperm freezing damage is the occurrence of cell death. Considering the existence of multiple types of cell death pathways, this review discusses connections between characteristics of regulated cell death (e.g., apoptosis and ferroptosis), and accidental cell death (e.g., intracellular ice crystals) with sperm freezing damage and explores possible future research directions in this field.

Stable FAPbI3 Perovskite Solar Cells via Alkylammonium Chloride-Mediated Crystallization Control.

α-Phase formamidinium lead iodide (FAPbI3) perovskite solar cells (PSCs) have garnered significant attention, owing to their remarkable efficiency. Methylammonium chloride (MACl), a common additive, is used to control the crystallization of FAPbI3, thereby facilitating the formation of the photoactive α-phase. However, MACl's high volatility raises concerns regarding its stability and potential impact on the stability of the device. In this study, we partially substituted MACl with n-propylammonium chloride (PACl), which has a long alkyl chain, to promote the oriented crystallization of FAPbI3, ultimately forming an δ-phase-free perovskite. The FAPbI3 film containing PACl demonstrates an enhanced photoluminescence intensity and lifetime. Additionally, PACl's presence at grain boundaries acts as a protective layer for the PSCs. Consequently, we achieved a power conversion efficiency (PCE) of 22.4% and exceptional stability. It maintains over 95% of initial PCE for 100 days in an N2 glovebox, over 85% after 100 h of maximum power point tracking, and over 80% after 60 °C thermal aging.

Low-cost dual-energy CBCT by spectral filtration of a dual focal spot X-ray source.

Dual-energy cone beam computed tomography (DE-CBCT) has been shown to provide more information and improve performance compared to a conventional single energy spectrum CBCT. Here we report a low-cost DE-CBCT by spectral filtration of a carbon nanotube x-ray source array. The x-ray photons from two focal spots were filtered respectively by a low and a high energy filter. Projection images were collected by alternatively activating the two beams while the source array and detector rotated around the object, and were processed by a one-step materials decomposition and reconstruction method. The performance of the DE-CBCT scanner was evaluated by imaging a water-equivalent plastic phantom with inserts containing known densities of calcium or iodine and an anthropomorphic head phantom with dental implants. A mean energy separation of 15.5 keV was achieved at acceptable dose rates and imaging time. Accurate materials quantification was obtained by materials decomposition. Metal artifacts were reduced in the virtual monoenergetic images synthesized at high energies. The results demonstrated the feasibility of high quality DE-CBCT imaging by spectral filtration without using either an energy sensitive detector or rapid high voltage switching.

A carbon nanotube x-ray source array designed for a new multisource cone beam computed tomography scanner.

Cone beam computed tomography (CBCT) is known to suffer from strong scatter and cone beam artifacts. The purpose of this study is to develop and characterize a rapidly scanning carbon nanotube (CNT) field emission x-ray source array to enable a multisource CBCT (ms-CBCT) image acquisition scheme which has been demonstrated to overcome these limitations. A CNT x-ray source array with eight evenly spaced focal spots was designed and fabricated for a medium field of view ms-CBCT for maxillofacial imaging. An external multisource collimator was used to confine the radiation from each focal spot to a narrow cone angle. For ms-CBCT imaging, the array was placed in the axial direction and rapidly scanned while rotating continuously around the object with a flat panel detector. The x-ray beam profile, temporal and spatial resolutions, energy and dose rate were characterized and evaluated for maxillofacial imaging. The CNT x-ray source array achieved a consistent focal spot size of 1.10 ± 0.04 mm × 0.84 ± 0.03 mm and individual beam cone angle of 2.4°±0.08 after collimation. The x-ray beams were rapidly switched with a rising and damping times of 0.21 ms and 0.19 ms, respectively. Under the designed operating condition of 110 kVp and 15 mA, a dose rate of 8245µGy s-1was obtained at the detector surface with the inherent Al filtration and 2312µGy s-1with an additional 0.3 mm Cu filter. There was negligible change of the x-ray dose rate over many operating cycles. A ms-CBCT scan of an adult head phantom was completed in 14.4 s total exposure time for the imaging dose in the range of that of a clinical CBCT scanner. A spatially distributed CNT x-ray source array was designed and fabricated. It has enabled a new multisource CBCT to overcome some of the main inherent limitations of the conventional CBCT.

Predictive Path-Tracking Control of an Autonomous Electric Vehicle with Various Multi-Actuation Topologies.

This paper presents the development of path-tracking control strategies for an over-actuated autonomous electric vehicle. The vehicle platform is equipped with four-wheel steering (4WS) as well as torque vectoring (TV) capabilities, which enable the control of vehicle dynamics to be enhanced. A nonlinear model predictive controller is proposed taking into account the nonlinearities in vehicle dynamics at the limits of handling as well as the crucial actuator constraints. Controllers with different actuation formulations are presented and compared to study the path-tracking performance of the vehicle with different levels of actuation. The controllers are implemented in a high-fidelity simulation environment considering scenarios of vehicle handling limits. According to the simulation results, the vehicle achieves the best overall path-tracking performance with combined 4WS and TV, which illustrates that the over-actuation topology can enhance the path-tracking performance during conditions under the limits of handling. In addition, the performance of the over-actuation controller is further assessed with different sampling times as well as prediction horizons in order to investigate the effect of such parameters on the control performance, and its capability for real-time execution. In the end, the over-actuation control strategy is implemented on a target machine for real-time validation. The control formulation proposed in this paper is proven to be compatible with different levels of actuation, and it is also demonstrated in this work that it is possible to include the particular over-actuation formulation and specific nonlinear vehicle dynamics in real-time operation, with the sampling time and prediction time providing a compromise between path-tracking performance and computational time.

Servo torque fault diagnosis implementation for heavy-legged robots using insufficient information.

The reliability of sensors and servos is paramount in diagnosing the Heavy-Legged Robot (HLR). Servo faults stemming from mechanical wear, environmental disturbances, or electrical issues pose significant challenges to traditional diagnostic methods, which rely heavily on delicate sensors. This study introduces a framework that solely relies on joint position and permanent magnet synchronous motor (PMSM) information to mitigate dependency on fragile sensors for servo-fault diagnosis. An essential contribution involves refining a model that directly connects PMSM currents to HLR motion. Moreover, to address scenarios where actual servo outputs and HLR cylinder velocities are unavailable, an improved sliding mode observer (ISMO) is proposed. Additionally, a Fourier expansion model characterizes the relationship between operation time and fault-free disturbance in the HLR. Subsequently, the dual-line particle filter (DPF) algorithm is employed to predict fault-free disturbance. The outputs of DPF serve as a feedforward to the ISMO, enabling the real-time servo torque fault diagnosis. The accuracy and validity of this technical framework are verified through various simulations in MATLAB/SIMSCAPE and real-world experiments.

Improving the accuracy of bone mineral density using a multisource CBCT.

Multisource cone beam computed tomography CBCT (ms-CBCT) has been shown to overcome some of the inherent limitations of a conventional CBCT. The purpose of this study was to evaluate the accuracy of ms-CBCT for measuring the bone mineral density (BMD) of mandible and maxilla compared to the conventional CBCT. The values measured from a multi-detector CT (MDCT) were used as substitutes for the ground truth. An anthropomorphic adult skull and tissue equivalent head phantom and a homemade calibration phantom containing inserts with varying densities of calcium hydroxyapatite were imaged using the ms-CBCT, the ms-CBCT operating in the conventional single source CBCT mode, and two clinical CBCT scanners at similar imaging doses; and a clinical MDCT. The images of the anthropomorphic head phantom were reconstructed and registered, and the cortical and cancellous bones of the mandible and the maxilla were segmented. The measured CT Hounsfield Unit (HU) and Greyscale Value (GV) at multiple region-of-interests were converted to the BMD using scanner-specific calibration functions. The results from the various CBCT scanners were compared to that from the MDCT. Statistical analysis showed a significant improvement in the agreement between the ms-CBCT and MDCT compared to that between the CBCT and MDCT.

On-Demand Optimization of Colorimetric Gas Sensors Using a Knowledge-Aware Algorithm-Driven Robotic Experimental Platform.

Synthesizing the best material globally is challenging; it needs to know what and how much the best ingredient composition should be for satisfying multiple figures of merit simultaneously. Traditional one-variable-at-a-time methods are inefficient; the design-build-test-learn (DBTL) method could achieve the optimal composition from only a handful of ingredients. A vast design space needs to be explored to discover the possible global optimal composition for on-demand materials synthesis. This research developed a hypothesis-guided DBTL (H-DBTL) method combined with robots to expand the dimensions of the search space, thereby achieving a better global optimal performance. First, this study engineered the search space with knowledge-aware chemical descriptors and customized multiobjective functions to fulfill on-demand research objectives. To verify this concept, this novel method was used to optimize colorimetric ammonia sensors across a vast design space of as high as 19 variables, achieving two remarkable optimization goals within 1 week: first, a sensing array was developed for ammonia quantification of a wide dynamic range, from 0.5 to 500 ppm; second, a new state-of-the-art detection limit of 50 ppb was reached. This work demonstrates that the H-DBTL approach, combined with a robot, develops a novel paradigm for the on-demand optimization of functional materials.

Sensor Fusion and Advanced Controller for Connected and Automated Vehicles.

Nowadays, intelligent vehicles are equipped with a number of advanced sensors, such as radar and cameras [...].

Electrical stimulation alters DNA methylation and promotes neurite outgrowth.

Electrical stimulation (ES) influences neural regeneration and functionality. We here investigate whether ES regulates DNA demethylation, a critical epigenetic event known to influence nerve regeneration. Retinal ganglion cells (RGCs) have long served as a standard model for central nervous system neurons, whose growth and disease development are reportedly affected by DNA methylation. The current study focuses on the ability of ES to rescue RGCs and preserve vision by modulating DNA demethylation. To evaluate DNA demethylation pattern during development, RGCs from mice at different stages of development, were analyzed using qPCR for ten-eleven translocation (TETs) and immunostained for 5 hydroxymethylcytosine (5hmc) and 5 methylcytosine (5mc). To understand the effect of ES on neurite outgrowth and DNA demethylation, cells were subjected to ES at 75 µAmp biphasic ramp for 20 min and cultured for 5 days. ES increased TETs mediated neurite outgrowth, DNA demethylation, TET1 and growth associated protein 43 levels significantly. Immunostaining of PC12 cells following ES for histone 3 lysine 9 trimethylation showed cells attained an antiheterochromatin configuration. Cultured mouse and human retinal explants stained with ß-III tubulin exhibited increased neurite growth following ES. Finally, mice subjected to optic nerve crush injury followed by ES exhibited improved RGCs function and phenotype as validated using electroretinogram and immunohistochemistry. Our results point to a possible therapeutic regulation of DNA demethylation by ES in neurons.

A simple polarimetric measurement based on a computational algorithm.

A simple and compact polarimeter comprising two electrically controlled liquid-crystal variable retarders (LCVRs) and a linear polarizer is demonstrated, which is enabled by analyzing the intensity variation of the modulated output light based on a computational algorithm. A proof-of-concept prototype is presented, which is mounted onto a power meter or a CMOS camera for the intensity data collection. The polarimetric measurement for the spatial variant polarization states of light is also verified, indicating the possibility of achieving a resolution-lossless polarimeter. Thus, our proposed method shows a cost-effective way to realize a compact polarimeter in polarization optics.

Prediction of intraoperative cerebrospinal fluid leaks in endoscopic endonasal transsphenoidal pituitary surgery based on a deep neural network model trained with MRI images: a pilot study.

Objective: This study aimed to investigate the reliability of a deep neural network (DNN) model trained only on contrast-enhanced T1 (T1CE) images for predicting intraoperative cerebrospinal fluid (ioCSF) leaks in endoscopic transsphenoidal surgery (EETS). Methods: 396 pituitary adenoma (PA) cases were reviewed, only primary PAs with Hardy suprasellar Stages A, B, and C were included in this study. The T1CE images of these patients were collected, and sagittal and coronal T1CE slices were selected for training the DNN model. The model performance was evaluated and tested, and its interpretability was explored. Results: A total of 102 PA cases were enrolled in this study, 51 from the ioCSF leakage group, and 51 from the non-ioCSF leakage group. 306 sagittal and 306 coronal T1CE slices were collected as the original dataset, and data augmentation was applied before model training and testing. In the test dataset, the DNN model provided a single-slice prediction accuracy of 97.29%, a sensitivity of 98.25%, and a specificity of 96.35%. In clinical test, the accuracy of the DNN model in predicting ioCSF leaks in patients reached 84.6%. The feature maps of the model were visualized and the regions of interest for prediction were the tumor roof and suprasellar region. Conclusion: In this study, the DNN model could predict ioCSF leaks based on preoperative T1CE images, especially in PAs in Hardy Stages A, B, and C. The region of interest in the model prediction-making process is similar to that of humans. DNN models trained with preoperative MRI images may provide a novel tool for predicting ioCSF leak risk for PA patients.

Evaluation of the feasibility of a multisource CBCT for maxillofacial imaging.

Objective. The aim of this study was to investigate the feasibility of improving the image quality and accuracy of cone beam computed tomography (CBCT) by replacing the conventional wide cone angle x-ray tube with a distributed x-ray source array positioned in the axial direction.Approach. The multisource CBCT (ms-CBCT) design was experimentally simulated using a benchtop scanner with a carbon nanotube x-ray tube and a flat-panel detector. The source was collimated and translated in the axial direction to simulate a source array with a reduced cone angle for each beam. An adjacent scatter ratio subtraction (ASRS) method was implemented for residual scatter reduction. Several phantoms were imaged using the ms-CBCT and conventional CBCT configurations under otherwise similar conditions. The Requirements of the ms-CBCT design on the x-ray source and detector were evaluated.Main results. Compared to the conventional CBCT, the ms-CBCT design with 8 sources and ASRS significantly improved the image quality and accuracy, including: (1) reducing the cupping artifact from 15% to 3.5%; (2) reducing the spatial nonuniformity of the CT Hounsfield unit values from 38.0 to 9.2; (3) improving the contrast-to-noise ratio of the low contrast objects (acrylic and low density polyethylene inserts) against the water-equivalent background by ∼20% and (4) reducing the root-mean-square error of the HU values by 70%, from 420.1 to 124.4. The imaging dose and scanning time used by the current clinical CBCT for maxillofacial imaging can be achieved by current source and detector technologies.Significance. The ms-CBCT design significantly reduces the scatter and improves the image quality and accuracy compared to the conventional CBCT.

Experimental Demonstration of Laser Guiding and Wakefield Acceleration in a Curved Plasma Channel.

Curved plasma channels have been proposed to guide intense lasers for various applications, such as x-ray laser emission, compact synchrotron radiation, and multistage laser wakefield acceleration [e.g. J. Luo et al., Phys. Rev. Lett. 120, 154801 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.154801]. Here, a carefully designed experiment shows evidences of intense laser guidance and wakefield acceleration in a centimeter-scale curved plasma channel. Both experiments and simulations indicate that when the channel curvature radius is gradually increased and the laser incidence offset is optimized, the transverse oscillation of the laser beam can be mitigated, and the stably guided laser pulse excites wakefields and accelerates electrons along the curved plasma channel to a maximum energy of 0.7 GeV. Our results also show that such a channel exhibits good potential for seamless multistage laser wakefield acceleration.

Preparation and characterization of antibacterial, antioxidant, and biocompatible p-coumaric acid modified quaternized chitosan nanoparticles.

To fabricate multifunctional nanoparticles (NPs) based on chitosan (CS) derivative, we first prepared quaternized CS (2-hydroxypropyltrimethyl ammonium chloride CS, HTCC) via a one-step approach, then synthesized p-coumaric acid (p-CA) modified HTCC (HTCC-CA) for the first time through amide reaction, and finally fabricated a series of NPs (HTCC-CA NPs) using HTCC-CAs with different substitution degrees and sodium tripolyphosphate (TPP) by ionic gelation. Newly-prepared HTCC and HTCC-CAs were characterized by FT-IR, 1H NMR, elemental analysis (EA), full-wavelength UV scanning, silver nitrate titration, and Folin-Ciocalteu methods. DLS and TEM results demonstrated that three selected HTCC-CA NPs had moderate size (< 350 nm), good dispersion (PDI < 0.4), and positive zeta potential (11-20 mV). The HTCC-CA NPs had high antibacterial activity against six bacterial strains, and the minimum inhibitory concentration (MIC) values were almost the same as the minimum bactericidal concentration (MBC) values (250-1000 µg/mL). Also, the HTCC-CA NPs had good antioxidation (radical scavenging ratio > 65 %) and low cytotoxicity (relative cell viability >80 %) to the tested cells. Totally, HTCC-CA NPs with high antibacterial activity, great antioxidation, and low cytotoxicity might serve as new biomedical materials for promoting skin wound healing.

4D Printing of Butterfly Scale-Inspired Structures for Wide-Angle Directional Liquid Transport.

Unidirectional liquid transport has been extensively explored for water/fog harvesting, electrochemical sensing, and desalination. However, current research mainly focuses on linear liquid transport (transport angle α = 0°), which exhibits hindered lateral liquid spreading and low unidirectional transport efficiency. Inspired by the wide-angle (0° < α < 180°) liquid transport on butterfly wings, this work successfully achieves linear (α = 0°), wide-angle, and even ultra-wide-angle (α = 180°) liquid transport by four-dimensional (4D) printing of butterfly scale-inspired re-entrant structures. These asymmetric re-entrant structures can achieve unidirectional liquid transport, and their layout can control the Laplace pressure in the forward (structure-tilting) and lateral directions to adjust the transport angle. Specifically, high transport efficiency and programmable forward/lateral transport paths are simultaneously achieved by the ultra-wide-angle transport, where liquid fills the lateral path before being transported forward. Moreover, the ultra-wide-angle transport is also validated in 3D space, which provides an innovative platform for advanced biochemical microreaction, large-area evaporation, and self-propelled oil-water separation.

Linking chromatin acylation mark-defined proteome and genome in living cells.

A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and ß-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr's gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the "metabolites-modification-regulation" axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.

Metabolomic analysis of seminal plasma to identify goat semen freezability markers.

Factors affecting sperm freezability in goat seminal plasma were investigated. Based on the total motility of thawed sperm, goats were divided into a high-freezability (HF) group with >60% total motility (n = 8) and a low-freezability (LF) group with <45% total motility (n = 8). Sperm and seminal plasma from the HF and LF groups were separated, HF seminal plasma was mixed with LF spermatozoa, LF seminal plasma was mixed with HF sperm, and the products were subjected to a freeze-thaw procedure. Semen from individual goats exhibited differences in freezability. HF semen had higher sperm motility parameters and plasma membrane and acrosome integrity after thawing; this difference could be related to the composition of seminal plasma. Seminal plasma from the HF and LF groups was evaluated using metabolomic analysis, and multivariate statistical analysis revealed a clear separation of metabolic patterns in the seminal plasma of goats with different freezability classifications. Forty-one differential metabolites were identified using the following screening conditions: variable importance in the projection > 1 and 0.05 < P-value < 0.1. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significant enrichment of central carbon metabolism in cancer, protein digestion and absorption, aminoacyl-tRNA, and other pathways and significant differences in the abundance of seven differential metabolites, including L-glutamine, L-aspartate, L-arginine, phenylpyruvate, benzoic acid, ketoisocaproic acid, and choline between seminal plasma from the HF and LF groups (P-value < 0.05). These significantly differentially-expressed metabolites may be potential biomarkers for sperm freezability. L-glutamine, L-aspartate, and L-arginine may directly affect sperm freezability. Benzoic acid, ketoisocaproic acid, and choline may regulate sperm freezability by participating in anabolic processes involving phenylalanine, leucine, and phosphatidylcholine in sperm.

Achieving Ultrahigh Energy Storage Density of La and Ta Codoped AgNbO3 Ceramics by Optimizing the Field-Induced Phase Transitions.

Energy storage capacitors are extensively used in pulsed power devices because of fast charge/discharge rates and high power density. However, the low energy storage density and efficiency of dielectric capacitors limit their further commercialization in modern energy storage applications. Lead-free AgNbO3-based antiferroelectric (AFE) ceramics are considered to be one of the most promising environmentally friendly materials for dielectric capacitors because of their characteristic double polarization-electric field hysteresis loops with small remanent polarization and large maximum polarization. An enhancement of these characteristics allows achieving a synergistic improvement of both the energy storage density and efficiency of the antiferroelectric materials. This work reports on a feasible codoping strategy enabling the preparation of AgNbO3-based ceramics with high energy storage performance. An introduction of La3+ and Ta5+ ions into the AgNbO3 perovskite lattice was found to increase the structural stability of the antiferroelectric phase at the expense of a reduction of local polar regions, resulting in the shifting of the electric field-induced antiferroelectric-ferroelectric phase transition toward higher fields. An ultrahigh recoverable energy storage density of 6.73 J/cm3 and high energy storage efficiency of 74.1% are obtained for the Ag0.94La0.02Nb0.8Ta0.2O3 ceramic subjected to a unipolar electric field of 540 kV/cm. These values represent the best energy performance in reported lead-free ceramics so far. Hence, the La3+/Ta5+ codoping has been shown to be a good route to improve the energy storage properties of AgNbO3 ceramics.