Cellular senescence imaging and senolysis monitoring in cancer therapy based on a ß-galactosidase-activated aggregation-induced emission luminogen.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated ß-galactosidase (SA-ß-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting ß-galactosidase (ß-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with ß-Gal-responsive capabilities. In this study, we introduced a ß-Gal-activated AIEgen named QM-ß-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-ß-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon ß-Gal activation. It showed high specificity towards the activity of ß-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-ß-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the ß-Gal-activated AIEgen, QM-ß-gal, as an in vivo approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. STATEMENT OF SIGNIFICANCE: This work reported a ß-galactosidase-activated AIEgen called QM-ß-gal, which effectively imaged DOX-induced senescent cancer cells both in vitro and in vivo. QM-ß-gal specifically targeted the increased expression and activity of ß-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells in vivo.

Positron Emission Tomography Imaging of Synaptic Dysfunction in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a complex pathogenesis. Aggregations formed by abnormal deposition of alpha-synuclein (αSyn) lead to synapse dysfunction of the dopamine and non-dopamine systems. The loss of dopaminergic neurons and concomitant alterations in non-dopaminergic function in PD constitute its primary pathological manifestation. Positron emission tomography (PET), as a representative molecular imaging technique, enables the non-invasive visualization, characterization, and quantification of biological processes at cellular and molecular levels. Imaging synaptic function with PET would provide insights into the mechanisms underlying PD and facilitate the optimization of clinical management. In this review, we focus on the synaptic dysfunction associated with the αSyn pathology of PD, summarize various related targets and radiopharmaceuticals, and discuss applications and perspectives of PET imaging of synaptic dysfunction in PD.

A Data-Mining Interpretation Method of Pavement Dynamic Response Signal by Combining DBSCAN and Findpeaks Function.

During a heavy traffic flow featuring a substantial number of vehicles, the data reflecting the strain response of asphalt pavement under the vehicle load exhibit notable fluctuations with abnormal values, which can be attributed to the complex operating environment. Thus, there is a need to create a real-time anomalous-data diagnosis system which could effectively extract dynamic strain features, such as peak values and peak separation from the large amount of data. This paper presents a dynamic response signal data analysis method that utilizes the DBSCAN clustering algorithm and the findpeaks function. This method is designed to analyze data collected by sensors installed within the pavement. The first step involves denoising the data using low-pass filters and other techniques. Subsequently, the DBSCAN algorithm, which has been improved using the K-Dist method, is used to diagnose abnormal data after denoising. The refined findpeaks function is further implemented to carry out the adaptive feature extraction of the denoised data which is free from anomalies. The enhanced DBSCAN algorithm is tested via simulation and illustrates its effectiveness while detecting abnormal data in the road dynamic response signal. The findpeaks function enables the relatively accurate identification of peak values, thus leading to the identification of strain signal peaks of complex multi-axle lorries. This study is valuable for efficient data processing and effective information utilization in pavement monitoring.

Nanoscale Insights into the Mechanical Behavior of Interfacial Composite Structures between Calcium Silicate Hydrate/Calcium Hydroxide and Silica.

The failure of the interfacial transition zone has been identified as the primary cause of damage and deterioration in cement-based materials. To further understand the interfacial failure mechanism, interfacial composite structures between the main hydration products of ordinary Portland cement (OPC), calcium silicate hydrate (CSH) and calcium hydroxide (Ca(OH)2), and silica (SiO2) were constructed while considering their anisotropy. Afterwards, uniaxial tensile tests were conducted using molecular dynamics (MD) simulations. Our results showed that the interfacial zones (IZs) of interfacial composite structures tended to have relatively lower densities than those of the bulk, and the anisotropy of the hydration products had almost no effect on the IZ being a low-density zone. Interfacial composite structures with different configurations exhibited diverse nanomechanical behaviors in terms of their ultimate strength, stress-strain relationship and fracture evaluation. A higher strain rate contributed to a higher ultimate strength and a more prolonged decline in the residual strength. In the interfacial composite structures, both CSH and Ca(OH)2 exhibited ruptures of the Ca-O bond as the primary atomic pair during the tensile process. The plastic damage characteristics of the interfacial composite structures during the tensile process were assessed by analyzing the normalized number of broken Ca-O bonds, which also aligned with the atomic chain break characteristics evident in the per-atom stress map.

A chromosome-level genome assembly provides insights into Cornus wilsoniana evolution, oil biosynthesis, and floral bud development.

Cornus wilsoniana W. is a woody oil plant with high oil content and strong hypolipidemic effects, making it a valuable species for medicinal, landscaping, and ecological purposes in China. To advance genetic research on this species, we employed PacBio together with Hi-C data to create a draft genome assembly for C. wilsoniana. Based on an 11-chromosome anchored chromosome-level assembly, the estimated genome size was determined to be 843.51 Mb. The N50 contig size and N50 scaffold size were calculated to be 4.49 and 78.00 Mb, respectively. Furthermore, 30 474 protein-coding genes were annotated. Comparative genomics analysis revealed that C. wilsoniana diverged from its closest species ~12.46 million years ago (Mya). Furthermore, the divergence between Cornaceae and Nyssaceae occurred >62.22 Mya. We also found evidence of whole-genome duplication events and whole-genome triplication γ, occurring at ~44.90 and 115.86 Mya. We further inferred the origins of chromosomes, which sheds light on the complex evolutionary history of the karyotype of C. wilsoniana. Through transcriptional and metabolic analysis, we identified two FAD2 homologous genes that may play a crucial role in controlling the oleic to linoleic acid ratio. We further investigated the correlation between metabolites and genes and identified 33 MADS-TF homologous genes that may affect flower morphology in C. wilsoniana. Overall, this study lays the groundwork for future research aimed at identifying the genetic basis of crucial traits in C. wilsoniana.

Optical molecular imaging and theranostics in neurological diseases based on aggregation-induced emission luminogens.

Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further applied for molecular imaging and image-guided theranostics in neurological diseases such as cerebrovascular disease, neurodegenerative disease, and brain tumor, which help us understand more about the pathophysiological state of brain through noninvasive optical imaging approaches. Herein, we focus on representative AIEgens investigated on brain vasculature imaging and theranostics in neurological diseases including cerebrovascular disease, neurodegenerative disease, and brain tumor. Considering different imaging modalities and various therapeutic functions, AIEgens have great potential to broaden neurological research and meet urgent needs in clinical practice. It will be inspiring to develop more practical and versatile AIEgens as molecular imaging agents for preclinical and clinical use on neurological diseases.

Visualization of Mitochondria During Embryogenesis in Zebrafish by Aggregation-Induced Emission Molecules.

PURPOSE: Aggregation-induced emission (AIE) molecules have been widely utilized for fluorescence imaging in many biomedical applications, benefited from large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. And visualization of mitochondria is almost investigated in vitro and ex vivo, but in vivo study of mitochondria is more essential for systematic biological research, especially during embryogenesis. Therefore, suitable and time-saving alternatives with simple operation based on AIE molecules are urgently needed compared with traditional transgenic approach. PROCEDURES: Five tetraphenylethylene isoquinolinium (TPE-IQ)-based molecules with AIE characteristics and their ability of mitochondrial visualization in vitro and in vivo and mitochondrial tracking during embryogenesis on zebrafish model were investigated. The biosafety of these AIE molecules was also evaluated systematically in vitro and in vivo. RESULTS: All these five AIE molecules could image mitochondria in vitro with good biocompatibility. In them, TPE-IQ1 exhibited excellent imaging quality for in vivo visualization and tracking of mitochondria during the 4-day embryogenesis in zebrafish, in comparison with the conventional transgenic fluorescent protein. Furthermore, TPE-IQ1 could visualize mitochondrial damage induced by chemicals in real time on 24-h post fertilization (hpf) embryos. CONCLUSIONS: This study indicated TPE-IQ-based AIE molecules had the potential for mitochondrial imaging and tracking during embryogenesis and mitochondrial damage visualization in vivo.

Positron emission tomography molecular imaging-based cancer phenotyping.

During the past several decades, numerous studies have provided insights into biological characteristics of cancer cells and identified various hallmarks of cancer acquired in the tumorigenic processes. However, it is still challenging to image these distinctive traits of cancer to facilitate the management of patients in clinical settings. The rapidly evolving field of positron emission tomography (PET) imaging has provided opportunities to investigate cancer's biological characteristics in vivo. This article reviews the current status of PET imaging on characterizing hallmarks of cancer and discusses the future directions of PET imaging strategies facilitating in vivo cancer phenotyping.

Phosphorus Substitution Preference in Ye'elimite: Experiments and Density Functional Theory Simulations.

Density functional theory (DFT) simulation has been recently introduced to understand the doping behavior of impurities in clinker phases. P-doped ye'elimite, a typical doping clinker phase, tends to form when phosphogypsum is used to manufacture calcium sulfoaluminate cement (CSA) clinkers. However, the substitution mechanism of P has not been uncovered yet. In this study, the influence of different doping amounts of P on the crystalline and electronic structure of ye'elimite was investigated using backscattered scanning electron microscopy-energy X-ray dispersive spectroscopy, X-ray diffraction tests, Rietveld quantitative phase analysis, and DFT simulations. Furthermore, the substitution preference of P in ye'elimite was revealed. Our results showed that increasing the doping amount of P increased the impurity contents in CSA clinkers, transforming the ye'elimite crystal system from the orthorhombic to the cubic system and decreasing the interplanar spacing of ye'elimite. Based on the calculation results of the defect formation energies, additional energies were required for P atoms to substitute Ca/Al atoms compared with those required for P atoms to substitute S atoms in both orthorhombic and cubic systems of ye'elimite. Combined calculation results of the bond length-bond order and partial density of states showed that the doped P atoms preferably substituted S atoms; the second possible substituted atoms were Al atoms, while there was only a slight possibility for substitution of Ca atoms. The substitution of P atoms for S atoms can be verified based on the elemental distribution in P-doped ye'elimite and the increasing residual CaSO4 contents. The transition of the crystal system and a decrease in the interplanar spacing for ye'elimite can also prove that the substitution of P atoms for Al atoms occurred substantially.