Spatial-temporal Bayesian accelerated failure time models for survival endpoints with applications to prostate cancer registry data.

Prostate cancer is the most common cancer after non-melanoma skin cancer and the second leading cause of cancer deaths in US men. Its incidence and mortality rates vary substantially across geographical regions and over time, with large disparities by race, geographic regions (i.e., Appalachia), among others. The widely used Cox proportional hazards model is usually not applicable in such scenarios owing to the violation of the proportional hazards assumption. In this paper, we fit Bayesian accelerated failure time models for the analysis of prostate cancer survival and take dependent spatial structures and temporal information into account by incorporating random effects with multivariate conditional autoregressive priors. In particular, we relax the proportional hazards assumption, consider flexible frailty structures in space and time, and also explore strategies for handling the temporal variable. The parameter estimation and inference are based on a Monte Carlo Markov chain technique under a Bayesian framework. The deviance information criterion is used to check goodness of fit and to select the best candidate model. Extensive simulations are performed to examine and compare the performances of models in different contexts. Finally, we illustrate our approach by using the 2004-2014 Pennsylvania Prostate Cancer Registry data to explore spatial-temporal heterogeneity in overall survival and identify significant risk factors.

Microstructure and Mechanical Properties of IN690 Ni-Based Alloy/316LN Stainless-Steel Dissimilar Ring Joint Welded by Inertia Friction Welding.

Inertia friction welding (IFW) was used to join large-diameter hollow bars made of Inconel 690 and 316LN successfully. The interfacial characteristics, microstructure, mechanical properties and fracture mechanism of welded joints under different process parameters were investigated. The results indicated that a joining mechanism with mechanical interlocking and metallurgical bonding was found in IFW joints. There was a significant mechanical mixing zone at the welding interface. The elemental diffusion layer was found in the "wrinkles" of the mechanical mixing zone. A tiny quantity of C elements accumulated on the friction and secondary friction surfaces. The tensile strength and impact toughness of the joints increased with the total welding energy input. Increasing the friction pressure could make the grain in all parts of the joint uniformly refined, thus enhancing the mechanical properties of welded joints. The maximum tensile strength and impact toughness of the welded joint were 639 MPa and 146 J/cm2, reaching 94% and 68% of that for Inconel 690, respectively, when the flywheel was initially set at 760 rpm, 200 MPa for friction pressure, and 388 kg/m2 for rotary inertia. Due to the Kirkendall effect in the welded joint, superior metallurgical bonding was at the welding interface close to the Inconel 690 side compared to the 316LN side.

Improving the sensing sensitivity of silver nanoparticle-based colorimetric biosensors from the point of salt.

The sensing sensitivity was improved for silver nanoparticles (AgNPs)-based colorimetric biosensors by using the most suitable salt to induce AgNPs aggregation. As for the salt composed of low-affinity anion and monovalent cation, the cation-dependent charge screening effect was the driving force for AgNPs aggregation. Apart from the charge screening effect, both the bridging of multivalent cation to the surface ligand of AgNP and the interaction between anion and Ag contributed to inducing AgNPs aggregation. Considering the higher aggregation efficiency of AgNPs resulted in a narrower sensing range, salt composed of low-affinity anion and monovalent cation was recommended for AgNPs-based colorimetric analysis, which was confirmed by fourfold higher sensitivity of DNA-21 detection using NaF than NaCl. This work inspires further thinking on improving the sensing performance of metal nanomaterials-based sensors from the point of colloidal surface science.

Polycomb protein binding and looping in the ON transcriptional state.

Polycomb group (PcG) proteins mediate epigenetic silencing of important developmental genes by modifying histones and compacting chromatin through two major protein complexes, PRC1 and PRC2. These complexes are recruited to DNA by CpG islands (CGIs) in mammals and Polycomb response elements (PREs) in Drosophila. When PcG target genes are turned OFF, PcG proteins bind to PREs or CGIs, and PREs serve as anchors that loop together and stabilize gene silencing. Here, we address which PcG proteins bind to PREs and whether PREs mediate looping when their targets are in the ON transcriptional state. While the binding of most PcG proteins decreases at PREs in the ON state, one PRC1 component, Ph, remains bound. Further, PREs can loop to each other and with presumptive enhancers in the ON state and, like CGIs, may act as tethering elements between promoters and enhancers. Overall, our data suggest that PREs are important looping elements for developmental loci in both the ON and OFF states.

A uniform step size, low-voltage piezoelectric motor with dual-channel force loop.

Recently, a variety of piezoelectric motors with remarkable performance have appeared. However, due to the hysteresis effect of piezoelectrics and stress return errors within the mechanical structures, the existing piezoelectric motors still face some challenges, such as inconsistent step size, high working voltage, and considerable speed variances during upward vs downward movements even under identical driving voltage signals. Here, we introduce a novel low-voltage piezoelectric motor with a dual-channel force loop based on piezoelectric stacks, in which each slider has two force loops connected with other sliders and the internal elastic preload element is installed, which can effectively address these issues. This new type of piezoelectric motor has low working voltage (starting voltage is only 0.8 V, significantly lower than that of conventional piezoelectric motors), large driving force, uniform step size, and excellent linearity.

De Novo Design of Spiro-Type Hole-Transporting Material: Anisotropic Regulation Toward Efficient and Stable Perovskite Solar Cells.

2,2',7,7'-Tetrakis(N,N-di-p-methoxyphenyl)-amine-9,9'-spirobifluorene (Spiro-OMeTAD) represents the state-of-the-art hole-transporting material (HTM) in n-i-p perovskite solar cells (PSCs). However, its susceptibility to stability issues has been a long-standing concern. In this study, we embark on a comprehensive exploration of the untapped potential within the family of spiro-type HTMs using an innovative anisotropic regulation strategy. Diverging from conventional approaches that can only modify spirobifluorene with single functional group, this approach allows us to independently tailor the two orthogonal components of the spiro-skeleton at the molecular level. The newly designed HTM, SF-MPA-MCz, features enhanced thermal stability, precise energy level alignment, superior film morphology, and optimized interfacial properties when compared to Spiro-OMeTAD, which contribute to a remarkable power conversion efficiency (PCE) of 24.53% for PSCs employing SF-MPA-MCz with substantially improved thermal stability and operational stability. Note that the optimal concentration for SF-MPA-MCz solution is only 30 mg/ml, significantly lower than Spiro-OMeTAD (>70 mg/ml), which could remarkably reduce the cost especially for large-area processing in future commercialization. This work presents a promising avenue for the versatile design of multifunctional HTMs, offering a blueprint for achieving efficient and stable PSCs.

Multi-path Fusion in SFCF-Net for Enhanced Multi-frequency Electrical Impedance Tomography.

Multi-frequency electrical impedance tomography (mfEIT) offers a nondestructive imaging technology that reconstructs the distribution of electrical characteristics within a subject based on the impedance spectral differences among biological tissues. However, the technology faces challenges in imaging multi-class lesion targets when the conductivity of background tissues is frequency-dependent. To address these issues, we propose a spatial-frequency cross-fusion network (SFCF-Net) imaging algorithm, built on a multi-path fusion structure. This algorithm uses multi-path structures and hyper-dense connections to capture both spatial and frequency correlations between multi-frequency conductivity images, which achieves differential imaging for lesion targets of multiple categories through cross-fusion of information. According to both simulation and physical experiment results, the proposed SFCF-Net algorithm shows an excellent performance in terms of lesion imaging and category discrimination compared to the weighted frequency-difference, U-Net, and MMV-Net algorithms. The proposed algorithm enhances the ability of mfEIT to simultaneously obtain both structural and spectral information from the tissue being examined and improves the accuracy and reliability of mfEIT, opening new avenues for its application in clinical diagnostics and treatment monitoring.

Exploiting synthetic biology platforms for enhanced biosynthesis of natural products in Yarrowia lipolytica.

With the rapid development of synthetic biology, researchers can design, modify, or even synthesize microorganisms de novo, and microorganisms endowed with unnatural functions can be considered "artificial life" and facilitate the development of functional products. Based on this concept, researchers can solve critical problems related to the insufficient supply of natural products, such as low yields, long production cycles, and cumbersome procedures. Due to its superior performance and unique physiological and biochemical characteristics, Yarrowia lipolytica is a favorable chassis cell used for green biomanufacturing by numerous researchers. This paper mainly reviews the development of synthetic biology techniques for Y. lipolytica and summarizes the recent research progress on the synthesis of natural products in Y. lipolytica. This review will promote the continued innovative development of Y. lipolytica by providing theoretical guidance for research on the biosynthesis of natural products.

Self-Feedback DNAzyme Motor for Cascade-Amplified Imaging of mRNA in Live Cells and In Vivo.

DNA motors have attracted extensive interest in biosensing and bioimaging. However, the amplification capacity of the existing DNA motor systems is limited since the products from the walking process are unable to feedback into the original DNA motor systems. As a result, the sensitivities of such systems are limited in the contexts of biosensing and bioimaging. In this study, we report a novel self-feedback DNAzyme motor for the sensitive imaging of tumor-related mRNA in live cells and in vivo with cascade signal amplification capacity. Gold nanoparticles (AuNPs) are modified with hairpin-locked DNAzyme walker and track strands formed by hybridizing Cy5-labeled DNA trigger-incorporated substrate strands with assistant strands. Hybridization of the target mRNA with the hairpin strands activates DNAzyme and promotes the autonomous walking of DNAzyme on AuNPs through DNAzyme-catalyzed substrate cleavage, resulting in the release of many Cy5-labeled substrate segments containing DNA triggers and the generation of an amplified fluorescence signal. Moreover, each released DNA trigger can also bind with the hairpin strand to activate and operate the original motor system, which induces further signal amplification via a feedback mechanism. This motor exhibits a 102-fold improvement in detection sensitivity over conventional DNAzyme motors and high selectivity for target mRNA. It has been successfully applied to distinguish cancer cells from normal cells and diagnose tumors in vivo based on mRNA imaging. The proposed DNAzyme motor provides a promising paradigm for the amplified detection and sensitive imaging of low-abundance biomolecules in vivo.

Bacteria Invade the Brain Following Sterile Intracortical Microelectrode Implantation.

Brain-machine interface performance is largely affected by the neuroinflammatory responses resulting in large part from blood-brain barrier (BBB) damage following intracortical microelectrode implantation. Recent findings strongly suggest that certain gut bacterial constituents penetrate the BBB and are resident in various brain regions of rodents and humans, both in health and disease. Therefore, we hypothesized that damage to the BBB caused by microelectrode implantation could amplify dysregulation of the microbiome-gut-brain axis. Here, we report that bacteria, including those commonly found in the gut, enter the brain following intracortical microelectrode implantation in mice implanted with single-shank silicon microelectrodes. Systemic antibiotic treatment of mice implanted with microelectrodes to suppress bacteria resulted in differential expression of bacteria in the brain tissue and a reduced acute inflammatory response compared to untreated controls, correlating with temporary improvements in microelectrode recording performance. Long-term antibiotic treatment resulted in worsening microelectrode recording performance and dysregulation of neurodegenerative pathways. Fecal microbiome composition was similar between implanted mice and an implanted human, suggesting translational findings. However, a significant portion of invading bacteria was not resident in the brain or gut. Together, the current study established a paradigm-shifting mechanism that may contribute to chronic intracortical microelectrode recording performance and affect overall brain health following intracortical microelectrode implantation.

High-performance terahertz modulators induced by substrate field in Te-based all-2D heterojunctions.

High-performance active terahertz modulators as the indispensable core components are of great importance for the next generation communication technology. However, they currently suffer from the tradeoff between modulation depth and speed. Here, we introduce two-dimensional (2D) tellurium (Te) nanofilms with the unique structure as a new class of optically controlled terahertz modulators and demonstrate their integrated heterojunctions can successfully improve the device performances to the optimal and applicable levels among the existing all-2D broadband modulators. Further photoresponse measurements confirm the significant impact of the stacking order. We first clarify the direction of the substrate-induced electric field through first-principles calculations and uncover the unusual interaction mechanism in the photoexcited carrier dynamics associated with the charge transfer and interlayer exciton recombination. This advances the fundamental and applicative research of Te nanomaterials in high-performance terahertz optoelectronics.

A new method for vascular age estimation based on relative risk difference in vascular aging.

OBJECTIVE: The current models of estimating vascular age (VA) primarily rely on the regression label expressed with chronological age (CA), which does not account individual differences in vascular aging (IDVA) that are difficult to describe by CA. This may lead to inaccuracies in assessing the risk of cardiovascular disease based on VA. To address this limitation, this work aims to develop a new method for estimating VA by considering IDVA. This method will provide a more accurate assessment of cardiovascular disease risk. METHODS: Relative risk difference in vascular aging (RRDVA) is proposed to replace IDVA, which is represented as the numerical difference between individual predicted age (PA) and the corresponding mean PA of healthy population. RRDVA and CA are regard as the influence factors to acquire VA. In order to acquire PA of all samples, this work takes CA as the dependent variable, and mines the two most representative indicators from arteriosclerosis data as the independent variables, to establish a regression model for obtaining PA. RESULTS: The proposed VA based on RRDVA is significantly correlated with 27 indirect indicators for vascular aging evaluation. Moreover, VA is better than CA by comparing the correlation coefficients between VA, CA and 27 indirect indicators, and RRDVA greater than zero presents a higher risk of disease. CONCLUSION: The proposed VA overcomes the limitation of CA in characterizing IDVA, which may help young groups with high disease risk to promote healthy behaviors.

Deconvolution-Based Pharmacokinetic Analysis to Improve the Prediction of Pathological Information of Breast Cancer.

Pharmacokinetic (PK) parameters, revealing changes in the tumor microenvironment, are related to the pathological information of breast cancer. Tracer kinetic models (e.g., Tofts-Kety model) with a nonlinear least square solver are commonly used to estimate PK parameters. However, the method is sensitive to noise in images. To relieve the effects of noise, a deconvolution (DEC) method, which was validated on synthetic concentration-time series, was proposed to accurately calculate PK parameters from breast dynamic contrast-enhanced magnetic resonance imaging. A time-to-peak-based tumor partitioning method was used to divide the whole tumor into three tumor subregions with different kinetic patterns. Radiomic features were calculated from the tumor subregion and whole tumor-based PK parameter maps. The optimal features determined by the fivefold cross-validation method were used to build random forest classifiers to predict molecular subtypes, Ki-67, and tumor grade. The diagnostic performance evaluated by the area under the receiver operating characteristic curve (AUC) was compared between the subregion and whole tumor-based PK parameters. The results showed that the DEC method obtained more accurate PK parameters than the Tofts method. Moreover, the results showed that the subregion-based Ktrans (best AUCs = 0.8319, 0.7032, 0.7132, 0.7490, 0.8074, and 0.6950) achieved a better diagnostic performance than the whole tumor-based Ktrans (AUCs = 0.8222, 0.6970, 0.6511, 0.7109, 0.7620, and 0.5894) for molecular subtypes, Ki-67, and tumor grade. These findings indicate that DEC-based Ktrans in the subregion has the potential to accurately predict molecular subtypes, Ki-67, and tumor grade.

magpie: A power evaluation method for differential RNA methylation analysis in N6-methyladenosine sequencing.

Recently, novel biotechnologies to quantify RNA modifications became an increasingly popular choice for researchers who study epitranscriptome. When studying RNA methylations such as N6-methyladenosine (m6A), researchers need to make several decisions in its experimental design, especially the sample size and a proper statistical power. Due to the complexity and high-throughput nature of m6A sequencing measurements, methods for power calculation and study design are still currently unavailable. In this work, we propose a statistical power assessment tool, magpie, for power calculation and experimental design for epitranscriptome studies using m6A sequencing data. Our simulation-based power assessment tool will borrow information from real pilot data, and inspect various influential factors including sample size, sequencing depth, effect size, and basal expression ranges. We integrate two modules in magpie: (i) a flexible and realistic simulator module to synthesize m6A sequencing data based on real data; and (ii) a power assessment module to examine a set of comprehensive evaluation metrics.

Lead remediation by geological fluorapatite combined with Penicillium Oxalicum and Red yeast.

Phosphate solubilizing fungi Penicillium oxalicum (POX) and Red yeast Rhodotorula mucilaginosa (Rho) have been applied in Pb remediation with the combination of fluorapatite (FAp), respectively. The secretion of oxalic acid by POX and the production of extracellular polymers (EPS) by Rho dominate the Pb remediation. In this study, the potential of Pb remediation by the fungal combined system (POX and Rho) with FAp was investigated. After six days of incubation, the combination of POX and Rho showed the highest Pb remove ratio (99.7%) and the lowest TCLP-Pb concentration (2.9 mg/L). The EPS combined with POX also enhanced Pb remediation, which has a 99.3% Pb removal ratio and 5.5 mg/L TCLP-Pb concentration. Meanwhile, Rho and EPS can also stimulate POX to secrete more oxalic acid, which reached 1510.1 and 1450.6 mg/L in six days, respectively. The secreted oxalic acid can promote FAp dissolution and the formation of lead oxalate and pyromorphite. Meanwhile, the EPS produced by Rho can combine with Pb to form EPS-Pb. In the combined system of POX + Rho and POX + EPS, all of the lead oxalate, pyromorphite, and EPS-Pb were observed. Our findings suggest that the combined application of POX and Rho with FAp is an effective approach for enhancing Pb remediation.

Ultrafast Response Organic Photoswitch Materials and Their Application in Volumetric 3D Display.

Volumetric three-dimensional (3D) display technology based on static screens is a crucial branch of 3D displays. The essential component in volumetric 3D displays is selectively excitable display media that can generate voxels at any position. Here, we synthesized a series of organic photoswitch materials to meet the specific requirements of 3D display mediums. In these photoswitch solutions, voxels are activated ultrafast within tens of picoseconds at the intersection of two control lasers and faded rapidly within tens of milliseconds when switching light is turned off. An experimental volumetric 3D display system utilizing an organic photoswitch solution as a screen is demonstrated. The system not only achieves a dynamic 3D display but also enables 360° viewing. The volumetric 3D display system can display true 3D images without auxiliary glasses and is expected to be applicable in fields as diverse as virtual reality, medical imaging, architectural design, and military visualization.

Hormetic effect of a short-chain PFBS on Microcystis aeruginosa and its molecular mechanism.

Short-chain Perfluorinated compounds (PFCs), used as substitutes for highly toxic long-chain PFCs, are increasingly entering the aquatic environment. However, the toxicity of short-chain PFCs in the environment is still controversial. This study investigated the effects of short-chain perfluorobutanesulfonic acid (PFBS) at different concentrations (2.5, 6, 14.4, 36, and 90 mg/L) on M. aeruginosa growth under 12-day exposure and explored the molecular mechanism of toxicity using transcriptomics. The results showed that M. aeruginosa exhibited hormetic effects after exposure to PFBS. Low PFBS concentrations stimulated algal growth, whereas high PFBS concentrations inhibited it, and this inhibitory effect became progressively more pronounced with increasing PFBS exposure concentrations. Transcriptomics showed that PFBS promoted the pathways of photosynthesis, glycolysis, energy metabolism and peptidoglycan synthesis, providing the energy required for cell growth and maintaining cellular morphology. PFBS, on the other hand, caused growth inhibition in algae mainly through oxidative stress, streptomycin synthesis, and genetic damage. Our findings provide new insights into the toxicity and underlying mechanism of short-chain PFCs on algae and inform the understanding of the hormetic effect of short-chain PFCs, which are crucial for assessing their ecological risks in aquatic environments.

Bioactive chitosan-citral Schiff base zinc complex: A pH-responsive platform for potential therapeutic applications.

The application of CO2 supercritical fluid (SCF) technology has developed rapidly because of its non-toxic, environmentally friendly, mild reaction conditions and safety. The SCF technology can effectively speed up the reaction process of nano-material synthesis, and maintains a high degree of controllability and repeatability. This study mainly included carboxymethyl chitosan sodium salt (CCS), citral (CT), p-coumaric acid (CA), and ZnSO4 as raw materials to prepare CCS-CT-CA-Zn complex as a pH-responsive agent and was investigated using supercritical fluid technique. The coordination structure of Bridge-CCS-CT-CH3COO-CA-Zn-Schiff base/OH and the morphology of the complex agents were verified. The prepared CCS-CT-CA-Zn complex showed good dispersion and uniformity (mean size: 852 ± 202 nm, PdI: 0.301, and mean zeta potential: -31 ± 6 mV). Also, it has a good pH responsive release in an acid environment. Besides, both of CCS-CT-CA-Zn complex (DS-B) and its decomposed mixture in acid (DS-A) demonstrated significant antioxidant and anti-vibrio activity. Moreover, both DS-B complex and DS-A mixture inhibited biofilm formation, swimming, and swarming motilities of V. parahaemolyticus in a dose-dependent manner. This work will provide a scientific basis for the further design and development of natural products derived antibacterial-antioxidant complex agents, food additives and feed additives.

Characterizations of Water-Soluble Chitosan/Curdlan Edible Coatings and the Inhibitory Effect on Postharvest Pathogenic Fungi.

This study focused on developing a composite coating comprising water-soluble chitosan (CTS) and curdlan (CUR). Cherry tomatoes served as the test material for assessing the preservative efficacy of these coatings. The incorporation of CUR markedly enhanced the coating's surface properties, refined its molecular structure, and improved its tensile strength and elongation at break. Additionally, the coating demonstrated enhanced permeability to water vapor, oxygen, and carbon dioxide and improved light transmission. The storage experiment, conducted at 25 ± 1 °C with a relative humidity of approximately 92% over 10 days, revealed that the CTS/CUR composite coating at a 1:1 ratio significantly outperformed the individual CTS or CUR coating and uncoated samples in maintaining the quality of postharvest cherry tomatoes. The 1:1 CTS/CUR composite coating demonstrated superior preservative effects. This study suggested that water-soluble chitosan/curdlan composite coatings have considerable potential for use in the preservation of postharvest fruits and vegetables.