An effective urobilin clearance strategy based on paramagnetic beads facilitates microscale proteomic analysis of urine.

Urine provides an ideal source for disease biomarker discovery. High-adhesion contaminants such as urobilin, which are difficult to remove from urine, can severely interfere with urinary proteomic analysis. Here, we aimed to establish a strategy based on single-pot, solid-phase-enhanced sample preparation (SP3) technology to prepare samples for urinary proteomics analysis that almost completely eliminates the impact of urobilin. A systematic evaluation of the effects of two urinary protein precipitation methods, two types of protein lysis buffers, and different ratios of magnetic digestion beads on the identification and quantification of the microscale urinary proteome was conducted. Our results indicate that methanol-chloroform precipitation, coupled with efficient lysis facilitated by urea, and subsequent enzymatic digestion using a mix of hydrophilic and hydrophobic magnetic beads offers the best performance. Further applying this strategy to the urine of patients with benign prostatic hyperplasia, prostate cancer and healthy individuals, combined with a narrow window of data-independent acquisition, FGFR4, MYLK, ORM2, GOLM1, SPP1, CD55, CSF1, DLD and TIMP3 were identified as potential biomarkers to discriminate benign prostatic hyperplasia and prostate cancer patients.

Wearable Electrochemical Sensor for Sweat-Based Potassium Ion and Glucose Detection in Exercise Health Monitoring.

The increasing prevalence of wearable devices has sparked a growing interest in real-time health monitoring and physiological parameter tracking. This study focuses on the development of a cost-effective sweat analysis device, utilizing microfluidic technology and selective electrochemical electrodes for non-invasive monitoring of glucose and potassium ions. The device, through real-time monitoring of glucose and potassium ion levels in sweat during physical activity, issues a warning signal when reaching experimentally set thresholds (K+ concentration at 7.5 mM, glucose concentrations at 60 µM and 120 µM). This alerts users to potential dehydration and hypoglycemic conditions. Through the integration of microfluidic devices and precise electrochemical analysis techniques, the device enables accurate and real-time monitoring of glucose and potassium ions in sweat. This advancement in wearable technology holds significant potential for personalized health management and preventive care, promoting overall well-being, and optimizing performance during physical activities.

Adaptive nanotube networks enabling omnidirectionally deformable electro-driven liquid crystal elastomers towards artificial muscles.

Artificial muscles that can convert electrical energy into mechanical energy promise broad scientific and technological applications. However, existing electro-driven artificial muscles have been plagued with problems that hinder their practical applications: large electro-mechanical attenuation during deformation, high-driving voltages, small actuation strain, and low power density. Here, we design and create novel electro-thermal-driven artificial muscles rationally composited by hierarchically structured carbon nanotube (HS-CNT) networks and liquid crystal elastomers (LCEs), which possess adaptive sandwiched nanotube networks with angulated-scissor-like microstructures, thus effectively addressing above problems. These HS-CNT/LCE artificial muscles demonstrate not only large strain (>40%), but also remarkable conductive robustness (R/R0 < 1.03 under actuation), excellent Joule heating efficiency (≈ 233 °C at 4 V), and high load-bearing capacity (R/R0 < 1.15 at 4000 times its weight loaded). In addition, our artificial muscles exhibit real-muscle-like morphing intelligence that enables preventing mechanical damage in response to excessively heavyweight loading. These high-performance artificial muscles uniquely combining omnidirectional stretchability, robust electrothermal actuation, low driving voltage, and powerful mechanical output would exert significant technological impacts on engineering applications such as soft robotics and wearable flexible electronics.

Integrative proteomics and n-glycoproteomics reveal the synergistic anti-tumor effects of aspirin- and gemcitabine-based chemotherapy on pancreatic cancer cells.

OBJECTIVE AND DESIGN: Pancreatic cancer is a highly malignant tumor that is well known for its poor prognosis. Based on glycosylation, we performed integrated quantitative N-glycoproteomics to investigate the synergistic anti-tumor effects of aspirin and gemcitabine on pancreatic cancer cells and explore the potential molecular mechanisms of chemotherapy in pancreatic cancer. METHODS AND RESULTS: Two pancreatic cancer cell lines (PANC-1 and BxPC-3) were treated with gemcitabine, aspirin, and a combination (gemcitabine + aspirin). We found that the addition of aspirin enhanced the inhibitory effect of gemcitabine on the activity of PANC-1 and BxPC-3 cells. Quantitative N-glycoproteome, proteome, phosphorylation, and transcriptome data were obtained from integrated multi-omics analysis to evaluate the anti-tumor effects of aspirin and gemcitabine on pancreatic cancer cells. Mfuzz analysis of intact N-glycopeptide profiles revealed two consistent trends associated with the addition of aspirin, which showed a strong relationship between N-glycosylation and the synergistic effect of aspirin. Further analysis demonstrated that the dynamic regulation of sialylation and high-mannose glycoforms on ECM-related proteins (LAMP1, LAMP2, ITGA3, etc.) was a significant factor for the ability of aspirin to promote the anti-tumor activity of gemcitabine and the drug resistance of pancreatic cancer cells. CONCLUSIONS: In-depth analysis of N-glycosylation-related processes and pathways in pancreatic cancer cells can provide new insight for future studies regarding pancreatic cancer therapeutic targets and drug resistance mechanisms.

Depositional dynamics and vegetation succession in self-organizing processes of deltaic marshes.

Global deltaic marshes are currently facing a multitude of pressures, including insufficient sediment supply, rising sea levels, and habitat loss. Consequently, unraveling the internal regulatory mechanisms within deltaic marshes is of paramount importance. Here, we harness years of observational data and high-resolution numerical models to uncover depositional dynamics and vegetation succession in self-organizing processes of deltaic marshes. Our findings indicate that the colonization of salt marsh vegetation triggered a robust phase of growth in the initial stages of river deltas formation. However, as vertical accretion intensifies and inundation decreases, the delta is driven towards a state of critical slowing down due to insufficient sediment supply. We have captured a pivotal turning point in the evolution of deltaic marshes. In accordance with the critical submergence threshold we have established, when the inundation time of deltaic marshes exceeds 0.97 h/d, these salt marsh platforms sustain a higher annual growth rate. Conversely, when the inundation time of deltaic marshes falls below 0.97 h/d, the interannual accretion rate continues to decrease. Our research reveals that, in the absence of human disturbances, the deposition rate in deltaic marshes transitions from growth to decline. During this period, the delta undergoes an interesting succession of pioneer salt marshes (Suaeda salsa) and high-elevation salt marshes (Phragmites australis). Even without reductions in sediment input due to human activities, the vertical deposition rate within deltaic marshes will still shift from acceleration to deceleration under the influence of this internal negative feedback regulation. This adaptive capacity of marshes may foreshadow that when observing a slowdown in vertical accretion on deltaic marsh platforms, it cannot be solely attributed to reductions in sediment input caused by human activities.

Differential analysis of core-fucosylated glycoproteomics enabled by single-step truncation of N-glycans.

Alpha-1,6 fucosylation of N-glycans (core fucosylation, CF) represents a unique form of N-glycans and is widely involved in disease progression. In order to accurately identify CF glycoproteins, several approaches have been developed based on sequential cleavage with different glycosidases to truncate the N-glycans. Since multi-step sample treatments may introduce quantitation bias and affect the practicality of these approaches in large-scale applications. Here, we systematically evaluated the performance of the single-step treatment of intact glycopeptides by endoglycosidase F3 for CF glycoproteome. The single-step truncation (SST) strategy demonstrated higher quantitative stability and higher efficiency compared with previous approaches. The strategy was further practiced on both cell lines and serum samples. The dysregulation of CF glycopeptides between preoperative and postoperative serum from patients with pancreatic ductal adenocarcinoma was revealed, and the CF modifications of BCHE_N369, CDH5_N112 and SERPIND1_N49 were found to be potential prognostic markers. This study thus provides an efficient solution for large-scale quantitative analysis of the CF glycoproteome.

Bioinspired Liquid Crystalline Spinning Enables Scalable Fabrication of High-Performing Fibrous Artificial Muscles.

Leveraging liquid crystal elastomers (LCEs) to realize scalable fabrication of high-performing fibrous artificial muscles is of particular interest because these active soft materials can provide large, reversible, programmable deformations upon environmental stimuli. High-performing fibrous LCEs require the used processing technology to enable shaping LCEs into micro-scale fine fibers as thin as possible while achieving macroscopic LC orientation, which however remains a daunting challenge. Here, a bioinspired spinning technology is reported that allows for continuous, high-speed production (fabrication speed up to 8400 m h-1 ) of thin and aligned LCE microfibers combined with rapid deformation (actuation strain rate up to 810% s-1 ), powerful actuation (actuation stress up to 5.3 MPa), high response frequency (50 Hz), and long cycle life (250 000 cycles without obvious fatigue). Inspired by liquid crystalline spinning of spiders that takes advantage of multiple drawdowns to thin and align their dragline silks, internal drawdown via tapered-wall-induced-shearing and external drawdown via mechanical stretching are employed to shape LCEs into long, thin, aligned microfibers with the desirable actuation performances, which few processing technologies can achieve. This bioinspired processing technology capable of scalable production of high-performing fibrous LCEs would benefit the development of smart fabrics, intelligent wearable devices, humanoid robotics, and other areas.

Reconfigurable Soft Actuators with Multiple-Stimuli Responses.

Multiple-stimuli responsive soft actuators with tunable initial shapes would have substantial potential in broad technological applications, ranging from advanced sensors, smart robots to biomedical devices. However, existing soft actuators are often limited to single initial shape and are unable to reversibly reconfigure into desirable shapes, which severely restricts the multifunctions that can be integrated into one actuator. Here, a novel reconfigurable supramolecular polymer/polyethylene terephthalate (PET) bilayer actuator exhibiting multiple-stimuli responses is presented. In this bilayer actuator, the supramolecular polymer layer constructed of poly(5-Norbornene-2-carboxylic acid-1,3-cyclooctadiene) (PNCCO) and azopyridine derivative (PyAzoPy) via H-bonds provides multiple-stimuli responses: PyAzoPy offers light response and carboxylic groups in PNCCO endow the actuator with humidity response. Meanwhile thermoplastic PET layer enables the bilayer actuators to be reconfigured into various shapes by thermal stimuli. The rationally designed actuators exhibit versatile capabilities to reversibly reconfigure into a set of initial shapes and carry out multiple functions, such as photo-driven "foldback-clip" and Ω-shaped crawling robots. In addition, bio-inspired plants constructed by reconfiguration of such actuators demonstrate reversible multiple-stimuli responses. It is anticipated that these novel actuators with highly tunable geometries and actuation modes would be useful to develop multifunctional devices capable of performing diverse tasks.