Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

A Systematic Review and Quality Assessment of Cardiovascular Disease-Specific Health Related Quality of Life Instruments: Part II Psychometric Properties.

OBJECTIVES: Health-related Quality of Life (HRQoL) instruments for cardiovascular disease (CVD) have been commonly used to measure important patient-reported outcomes in clinical trials and practices. This study aimed at systematically identifying and evaluating the psychometric properties of CVD-specific HRQoL instruments. METHODS: We searched CINAHL, Embase, and PubMed from inception to January 20, 2022. Studies that reported psychometric properties of CVD-specific instruments were included. Two reviewers independently assessed the methodological quality using the Consensus-based Standards for the Selection of Health Measurement Instruments methods on evaluating measurement properties and quality of evidence. Seven psychometric properties, including structural validity, internal consistency, test-retest reliability, convergent validity, divergent validity, discriminative validity, and responsiveness, were evaluated. RESULTS: We identified 142 studies reporting psychometric properties of 40 instruments. 5 (12.5%) instruments demonstrated measurement properties with "sufficient" or "inconsistent" ratings. 16 (40.0%) instruments did not report any responsiveness evidence. Of the 40 instruments, 15 (37.5%) instruments were rated "sufficient" with high quality of evidence on internal consistency, 4 (10.0%) on structural validity, convergent validity and divergent validity and 3 (7.5%) on discriminative validity. CONCLUSIONS: When measuring patient-reported outcomes in clinical trials or routine practice, it is important to choose instruments with established psychometric properties.

Van der Waals integrated single-junction light-emitting diodes exceeding 10% quantum efficiency at room temperature.

The construction of miniaturized light-emitting diodes (LEDs) with high external quantum efficiency (EQE) at room temperature remains a challenge for on-chip optoelectronics. Here, we demonstrate microsized LEDs fabricated by a dry-transfer van der Waals (vdW) integration method using typical layered Ruddlesden-Popper perovskites (RPPs). A single-crystalline layered RPP nanoflake is used as the active layer and sandwiched between two few-layer graphene contacts, forming van der Waals LEDs (vdWLEDs). Strong electroluminescence (EL) emission with a low turn-on current density of ~20 pA µm-2 and high EQE exceeding 10% is observed at room temperature, which sets the benchmark for the EQE of vdWLEDs ever recorded. Such efficient EL emission is attributed to the inherent multiple quantum well structure and high photoluminescence quantum yield (~35%) of RPPs and a low charge injection barrier of ~0.10 eV facilitated by the Fowler-Nordheim tunneling mechanism. These findings promise a scalable pathway for accessing high-performance miniaturized light sources for on-chip optical optoelectronics.

Entropy in catalyst dynamics under confinement.

Entropy during the dynamic structural evolution of catalysts has a non-trivial influence on chemical reactions. Confinement significantly affects the catalyst dynamics and thus impacts the reactivity. However, a full understanding has not been clearly established. To investigate catalyst dynamics under confinement, we utilize the active learning scheme to effectively train machine learning potentials for computing free energies of catalytic reactions. The scheme enables us to compute the reaction free energies and entropies of O2 dissociation on Pt clusters with different sizes confined inside a carbon nanotube (CNT) at the timescale of tens of nanoseconds while keeping ab initio accuracy. We observe an entropic effect owing to liquid-to-solid phase transitions of clusters at finite temperatures. More importantly, the confinement effect enhances the structural dynamics of the cluster and leads to a lower melting temperature than those of the bare cluster and cluster outside the CNT, consequently facilitating the reaction to occur at lower temperatures and preventing the catalyst from forming unfavorable oxides. Our work reveals the important influence of confinement on structural dynamics, providing useful insight into entropy in dynamic catalysis.

Electrical monitoring of single-event protonation dynamics at the solid-liquid interface and its regulation by external mechanical forces.

Detecting chemical reaction dynamics at solid-liquid interfaces is important for understanding heterogeneous reactions. However, there is a lack of exploration of interface reaction dynamics from the single-molecule perspective, which can reveal the intrinsic reaction mechanism underlying ensemble experiments. Here, single-event protonation reaction dynamics at a solid-liquid interface are studied in-situ using single-molecule junctions. Molecules with amino terminal groups are used to construct single-molecule junctions. An interfacial cationic state present after protonation is discovered. Real-time electrical measurements are used to monitor the reversible reaction between protonated and deprotonated states, thereby revealing the interfacial reaction mechanism through dynamic analysis. The protonation reaction rate constant has a linear positive correlation with proton concentration, whereas the deprotonation reaction rate constant has a linear negative correlation. In addition, external mechanical forces can effectively regulate the protonation reaction process. This work provides a single-molecule perspective for exploring interface science, which will contribute to the development of heterogeneous catalysis and electrochemistry.

Synthesis, characterization, and application of films made from highly substituted N-perfluoroacylated chitosan.

Highly substituted perfluoroacylated chitosan can alter the physicochemical properties of chitosan; however, the currently synthesized perfluoroacylated chitosan has a low degree of substitution. In this study, we present a simple method for the homogeneous preparation of highly substituted N-perfluoroacylated chitosan, conducted at room temperature without requiring strict anhydrous or oxygen-free conditions. Various perfluorocarbon chains were successfully attached to chitosan through a reaction between perfluorinated acid esters and amines, catalyzed by DBU. The synthesized N-perfluoroacylated chitosan, with high degree of substitution, demonstrated excellent solubility in common organic solvents. Comprehensive characterization was performed using elemental analysis, nuclear magnetic resonance (including two-dimensional NMR), gel permeation chromatography, infrared spectroscopy, X-ray diffraction, and thermal analysis. The resulting films exhibited high water contact angles. Notably, as the fluorocarbon chain length increased, tensile strength gradually decreased, while elongation at break improved. Additionally, water uptake, water vapor transmission rate, and oxygen transmission rate all exhibited a declining trend. The films exhibited good biocompatibility, and in the grape preservation experiment, HFBC treatment effectively delayed grape aging and deterioration while enhancing quality preservation. These results suggest that HFBC film holds promising potential for food packaging applications.

Building Confidence in Physiologically Based Pharmacokinetic Modeling of CYP3A Induction Mediated by Rifampin: An Industry Perspective.

Physiologically-based pharmacokinetic (PBPK) modeling offers a viable approach to predict induction drug-drug interactions (DDIs) with the potential to streamline or reduce clinical trial burden if predictions can be made with sufficient confidence. In the current work, the ability to predict the effect of rifampin, a well-characterized strong CYP3A4 inducer, on 20 CYP3A probes with publicly available PBPK models (often developed using a workflow with optimization following a strong inhibitor DDI study to gain confidence in fraction metabolized by CYP3A4, fm,CYP3A4, and fraction available after intestinal metabolism, Fg), was assessed. Substrates with a range of fm,CYP3A4 (0.086-1.0), Fg (0.11-1.0) and hepatic availability (0.09-0.96) were included. Predictions were most often accurate for compounds that are not P-gp substrates or that are P-gp substrates but that have high permeability. Case studies for three challenging DDI predictions (i.e., for eliglustat, tofacitinib, and ribociclib) are presented. Along with parameter sensitivity analysis to understand key parameters impacting DDI simulations, alternative model structures should be considered, for example, a mechanistic absorption model instead of a first-order absorption model might be more appropriate for a P-gp substrate with low permeability. Any mechanisms pertinent to the CYP3A substrate that rifampin might impact (e.g., induction of other enzymes or P-gp) should be considered for inclusion in the model. PBPK modeling was shown to be an effective tool to predict induction DDIs with rifampin for CYP3A substrates with limited mechanistic complications, increasing confidence in the rifampin model. While this analysis focused on rifampin, the learnings may apply to other inducers.

Polyoxometalate Reinforced Perovskite Phase for High-Performance Perovskite Photovoltaics.

Ionic hybrid perovskites face challenges in maintaining their structural stability against non-equilibrium phase degradation, therefore, it is essential to develop effective ways to reinforce their corner-shared [PbI6]4- octahedral units. To strengthen structural stability, redox-active functional polyoxometalates (POMs) are developed and incorporated into perovskite solar cells (PSCs) to form a robust polyoxometalates/perovskite interlayer for stabilizing the perovskite phase. This approach offers several advantages: 1) promotes the formation of an interfacial connecting layer to passivate interfacial defects in addition to stabilize the [PbI6]4- units through exchanged ammonium cations in POMs with perovskites; 2) facilitates continuous structural repairing of Pb0- and I0-rich defects in the [PbI6]4- unit through redox electron shuttling of the electroactive metal ions in POMs; 3) provides guidance for selecting suitable redox mediators based on the kinetic studies of POM's effectiveness in reacting with targeted defects. The POM-reinforced device maintains 97.2% of its initial PCE after 1500 h of shelf-life test at 65 °C, while also enhancing the long-term operational stability. Additionally, this approach can be generally applicable across scalable sizes and various bandgap perovskites in devices, showing the promise of using functional POMs to enhance perovskite photovoltaic performance.

Anomalous Catalytic Performance on Non-Active-Site Carbon Substrate.

Carbon-based nanomaterials are gaining attention in electrocatalysis. This study investigates the inherent nitrate reduction activity (NO3RR) of commercial carbon paper as a substrate. Results showed that carbon paper, without additional catalysts, achieved approximately 80.42% NH3 Faradaic efficiency (FE) at -2.1 V vs. Hg/HgO in alkaline conditions, 83.51% NH3 FE at -1.9 V vs. Ag/AgCl in neutral conditions, and 14.53% NH3 FE at -1.9 V vs. MSE in acidic conditions. Density Functional Theory (DFT) calculations revealed energy barriers of 2.66 eV, 0.95 eV, and 1.37 eV, respectively. Molecular physisorption on the carbon paper surface generates an induced electric field, promoting charge transfer between the carbon paper and the adsorbed molecules, thus enhancing the activity of the carbon paper. These findings highlight the importance of considering the intrinsic catalytic properties of carbon substrates in catalyst design and evaluation, as overlooking these properties can lead to inaccurate performance assessments. This study emphasizes the need for a comprehensive approach to optimize catalytic systems.

Characterization and Expression Analysis of the C-Type Lectin Ladderlectin in Litopenaeus vannamei Post-WSSV Infection.

C-type lectins are known for agglutination activity and play crucial roles in regulating the prophenoloxidase (proPO) activation system, enhancing phagocytosis and encapsulation, synthesizing antimicrobial peptides, and mediating antiviral immune responses. This work cloned a C-type lectin, ladderlectin (LvLL), from Litopenaeus vannamei. LvLL comprised a 531 bp open reading frame (ORF) that encoded 176 amino acids. The predicted LvLL protein included a signal peptide and a CLECT domain. LvLL was predicted to feature a transmembrane region, suggesting it may be a transmembrane protein. LvLL was predominantly expressed in the shrimp's hepatopancreas. After WSSV infection, LvLL expression in the hepatopancreas increased significantly by 11.35-fold after 228 h, indicating a general upregulation. Knockdown of LvLL resulted in a significant decrease in WSSV viral load and a notable increase in shrimp survival rates. Additionally, knockdown of LvLL led to a significant downregulation of apoptosis-related genes Bcl-2 and caspase 8 and a significant upregulation of p53 and proPO in WSSV-infected shrimp. This study showed that LvLL played a vital role in the interaction between L. vannamei and WSSV.

Integrative Omics Strategies for Understanding and Combating Brown Planthopper Virulence in Rice Production: A Review.

The brown planthopper (Nilaparvata lugens, BPH) is a serious insect pest responsible for causing immense economic losses to rice growers around the globe. The development of high-throughput sequencing technologies has significantly improved the research on this pest, and its genome structure, gene expression profiles, and host-plant interactions are being unveiled. The integration of genomic sequencing, transcriptomics, proteomics, and metabolomics has greatly increased our understanding of the biological characteristics of planthoppers, which will benefit the identification of resistant rice varieties and strategies for their control. Strategies like more optimal genome assembly and single-cell RNA-seq help to update our knowledge of gene control structure and cell type-specific usage, shedding light on how planthoppers adjust as well. However, to date, a comprehensive genome-wide investigation of the genetic interactions and population dynamics of BPHs has yet to be exhaustively performed using these next-generation omics technologies. This review summarizes the recent advances and new perspectives regarding the use of omics data for the BPH, with specific emphasis on the integration of both fields to help develop more sustainable pest management strategies. These findings, in combination with those of post-transcriptional and translational modifications involving non-coding RNAs as well as epigenetic variations, further detail intricate host-brown planthopper interaction dynamics, especially regarding resistant rice varieties. Finally, the symbiogenesis of the symbiotic microbial community in a planthopper can be characterized through metagenomic approaches, and its importance in enhancing virulence traits would offer novel opportunities for plant protection by manipulating host-microbe interactions. The concerted diverse omics approaches collectively identified the holistic and complex mechanisms of virulence variation in BPHs, which enables efficient deployment into rice resistance breeding as well as sustainable pest management.

Accurate Calculation of Interatomic Forces with Neural Networks Based on a Generative Transformer Architecture.

Using neural networks to express electronic wave functions represents a new paradigm for solving the Schrödinger equation in quantum chemistry. For practical quantum chemistry simulations, one needs to know not only energies of molecules, but also accurate forces acting on constituent atoms. In this work, we achieve the accurate calculation of interatomic forces on QiankunNet, a platform that combines transformer-based deep neural networks with efficient batched autoregressive sampling. Our approach permits the application of the Hellmann-Feynman theorem to force calculations without introducing corrective Pulay terms. The results show that the calculated interatomic forces are in close agreement with those derived from the full configuration interaction method, irrespective of whether the system is a simple molecule or a strongly correlated electron system like a linear hydrogen chain. Furthermore, the calculated interatomic forces are employed for atomic relaxation in the torsional rotation process of ethylene, and the energy barrier obtained from the scanned potential energy surface is in excellent agreement with the experiment. Our work contributes to the application of artificial intelligence to broader quantum chemistry simulations, such as modeling challenging chemical transformations where electron correlations are difficult to describe.

Diagnostic value of impulse oscillometry in chronic obstructive pulmonary disease: a multicentre, retrospective, observational study.

OBJECTIVES: Diagnosis and assessment of chronic obstructive pulmonary disease (COPD) rely extensively on spirometry, which necessitates patient cooperation. The clinical value of impulse oscillometry (IOS) as a non-volitional method in patients with COPD remains uncertain. DESIGN: This retrospective observational study was conducted using patient data from between January 2014 and December 2015. SETTING: Five public hospitals in China: West China Hospital, Nuclear Industry 416 Hospital, Suining Central Hospital, Affiliated Hospital, Medical College of Chengdu University and 363 Hospital. PARTICIPANTS: The study included 6307 participants aged>40 years, comprising 2109 COPD patients and 4198 general non-COPD individuals, according to the Global Initiative for Obstructive Lung Disease (GOLD) spirometry standard. Participants with lung cancer, pulmonary tuberculosis, pneumonia or those who underwent lung resection were excluded from the study. OUTCOME MEASURES AND ANALYSIS: Demographic data, spirometry results and IOS results were collected. Spearman's correlation analysis was used to examine the correlation between the IOS and spirometry parameters. Receiver operating characteristic curve analysis was used to evaluate the IOS performance in COPD diagnosis and severity staging. RESULTS: Patients with COPD exhibited significant increases in Z5, R5, R20, R5-R20, Fres and Rp, but a decrease in X5 compared with non-COPD subjects (p<0.0001). IOS parameters, including Z5, R5-R20, Fres, Rp and X5, varied with the GOLD stages, with mild-to-moderate correlations with MMEF25%-75%, forced expiratory volume in one second (FEV1)/forced vital capacity and FEV1%, respectively. However, the combination of these five IOS parameters did not exhibit ideal performance in diagnosing COPD (area under the curve (AUC) 0.78; sensitivity 63.68%; specificity 80.09%), differentiating GOLD stage 1 patients from the general non-COPD population (AUC 0.71; sensitivity 54.71%; specificity 77.49%) or identifying GOLD stages 3 and 4 patients among those with COPD (AUC 0.75; sensitivity 69.51%; specificity 70.32%). CONCLUSION: IOS parameters, while showing good correlation with spirometry in patients with COPD, did not perfectly substitute for spirometry in diagnosing COPD, especially in the early and advanced stages of the disease.

Fatty acid synthesis promoted by PA1895-1897 operon delays quorum sensing activation in Pseudomonas aeruginosa.

PA1895-1897 is a quorum sensing (QS) operon regulated by the anti-activator LuxR homologue QscR in Pseudomonas aeruginosa. We aimed to investigate its impact on bacterial metabolism, and whether it contributes to the delayed QS activation. We performed liquid chromatograph-mass spectrometer-based metabolomics using wildtype PAO1, PA1895-1897-knockout mutant, and mutant with pJN105.PA1895-1897 overexpression vector. The impact of metabolites on QS signaling molecule (3OC12-HSL and C4-HSL) concentrations, pyocyanin production, and QS gene (lasR, lasI, rhlR, and rhlI) expression was examined. Metabolomics analysis found that fatty acid biosynthesis had the highest fold enrichment among all metabolic pathways in PA1895-1897-overexpressed mutants. Among these enriched fatty acids, palmitoleic acid and acetic acid were the predominantly abundant ones that significantly affected by PA1895-1897 operon. When different doses of exogenous palmitoleic acid or acetic acid were added to the cultures of PA1895-1897 knockout mutants, their levels of 3OC12-HSL, C4-HSL, and pyocyanin were decreased in a dose-dependent manner. High doses of palmitoleic acid and acetic acid suppressed the mRNA expression of lasR, rhlR, and rhlI. Inhibition of fatty acid biosynthesis increased the production of 3OC12-HSL, C4-HSL, and pyocyanin in PA1895-1897-overexpressed cultures. Our data suggest that fatty acid synthesis is promoted by PA1895-1897 operon, and contributes the delayed expression of QS phenotypes, furthering the understanding about the regulation of bacterial QS activation.

Scaffold-based tissue engineering strategies for urethral repair and reconstruction.

Urethral strictures are common in urology; however, the reconstruction of long urethral strictures remains challenging. There are still unavoidable limitations in the clinical application of grafts for urethral injuries, which has facilitated the advancement of urethral tissue engineering. Tissue-engineered urethral scaffolds that combine cells or bioactive factors with a biomaterial to mimic the native microenvironment of the urethra, offer a promising approach to urethral reconstruction. Despite the recent rapid development of tissue engineering materials and techniques, a consensus on the optimal strategy for urethral repair and reconstruction is still lacking. This review aims to collect the achievements of urethral tissue engineering in recent years and to categorize and summarize them to shed new light on their design. Finally, we visualize several important future directions for urethral repair and reconstruction.

Severe multiple injuries in a 15-year-old boy with pelvic fracture complete anterior dislocation of the sacroiliac joint and rupture of the internal and external iliac arteries: A case report of a rare injury.

RATIONALE: Anterior dislocation of the sacroiliac joint combined with pelvic fractures is relatively rare in clinical practice. It is often associated with hemodynamic instability and severe injuries to other regions, resulting in a complex condition, prolonged treatment duration, and high rates of mortality and disability. However, there are few reports in the literature describing the diagnosis and treatment of anterior dislocation of the sacroiliac joint. In this case, the patient sustained a pelvic fracture with anterior sacroiliac joint dislocation and rupture of both the internal and external iliac arteries following a motor vehicle accident, making it an even rarer and more challenging case to treat. Reporting such cases can enhance the understanding of the diagnosis and treatment of anterior sacroiliac joint dislocation with rupture of the iliac arteries and provide valuable references for similar cases. PATIENT CONCERNS: The patient was riding an electric bicycle and was hit by a small truck, resulting in a pelvic fracture, anterior dislocation of the sacroiliac joint, and rupture of the internal and external iliac arteries. DIAGNOSIS: The patient was diagnosed with open pelvic fracture (type C1.2), left complete anterior dislocation of the sacroiliac joint, left acetabular fracture, left internal and external iliac arteriovenous rupture. INTERVENTIONS: emergency room resuscitation, intensive care unit resuscitation, 6 surgeries and perioperative management. RESULTS: He has been discharged from the hospital for more than 1 year and was rechecked every month after discharge, the fracture has healed, there is no obvious pain and discomfort in and around the wound, he has been fitted with a prosthesis, and he is doing the walking function exercise. LESSONS: Pelvic fracture with anterior sacroiliac dislocation is clinically rare and critical, and is associated with large vessel rupture, severe organ damage, and high mortality and disability rates. Rapid restoration of pelvic stability and hemodynamic stability is the key to treatment. Rapid transfer to a tertiary trauma center, rapid examination through the green channel to clarify the diagnosis, close intensive care, and reasonable multidisciplinary teamwork for surgical intervention are all valuable experiences that we have concluded.

Depicting Primate-Like Granular Dorsolateral Prefrontal Cortex in the Chinese Tree Shrew.

It remains unknown whether the Chinese tree shrew, regarded as the closest sister of primate, has evolved a dorsolateral prefrontal cortex (dlPFC) comparable with primates that is characterized by a fourth layer (L4) enriched with granular cells and reciprocal connections with the mediodorsal nucleus (MD). Here, we reported that following AAV-hSyn-EGFP expression in the MD neurons, the fluorescence micro-optical sectioning tomography revealed their projection trajectories and targeted brain areas, such as the hippocampus, the corpus striatum, and the dlPFC. Cre-dependent transsynaptic viral tracing identified the MD projection terminals that targeted the L4 of the dlPFC, in which the presence of granular cells was confirmed via cytoarchitectural studies by using the Nissl, Golgi, and vGlut2 stainings. Additionally, the L5/6 of the dlPFC projected back to the MD. These results suggest that the tree shrew has evolved a primate-like dlPFC which can serve as an alternative for studying cognition-related functions of the dlPFC.

Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity.

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

General Approach to Hydrolysis Resistive Aluminum Nitride and Its High-Performance Thermal Interface Materials.

Aluminum nitride (AlN), noted for its excellent thermal conductivity and exceptional electrical insulation, presents a promising alternative to traditional ceramic particles in thermal interface materials (TIMs). However, its broader adoption in practical applications is limited by performance degradation due to the vulnerability of its crystal structure to ubiquitous moisture. This study introduces a dual solution, utilizing a mechanochemical method to design a dense outer layer of Galinstan liquid metal (LM) that simultaneously enhances AlN's resistance to hydrolysis and improves its thermal performance in TIM applications. The high surface free energy of the LM layer imparts hydrophobic properties to the AlN surface and, combined with outer metal oxides, forms a dual-layer protective barrier that prevents water penetration, significantly enhancing the TIM's long-term stability in high-humidity conditions. Additionally, the LM layer at the interface improves the thixotropic properties of the TIM and enhances interfacial heat transport through the bridging effect of the LM, resulting in improved rheological mobility and thermal conductivity of the composite material. This win-win surface modification strategy opens opportunities for the practical and durable application of AlN in widespread electronic thermal management.