Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques.

This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (Aß) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting Aß plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.

The association between remnant cholesterol and bone mineral density in US adults: the National Health and Nutrition Examination Survey (NHANES) 2013-2018.

BACKGROUND: Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans. METHODS: This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD. RESULTS: This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (ß= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P < 0.001). Moreover, RC had a stronger effect on total spine BMD than total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). CONCLUSIONS: This study found that serum RC was negatively related to total spine BMD in U.S. adults. These findings emphasized the important role of RC in bone health in American adults.

An Activatable Phototheranostic Nanoplatform for Tumor Specific NIR-II Fluorescence Imaging and Synergistic NIR-II Photothermal-Chemodynamic Therapy.

The phototheranostics in the second near-infrared window (NIR-II) have proven to be promising for the precise cancer theranostics. However, the non-responsive and "always on" imaging mode lacks the selectivity, leading to the poor diagnosis specificity. Herein, a tumor microenvironment (TME) activated NIR-II phototheranostic nanoplatform (Ag2 S-Fe(III)-DBZ Pdots, AFD NPs) is designed based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self-assembly of Ag2 S QDs (NIR-II fluorescence probe) and ultra-small semiconductor polymer dots (DBZ Pdots, NIR-II fluorescence quencher) utilizing Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain in "off" state, due to the FRET between Ag2 S QDs and DBZ Pdots. However, the NIR-II fluorescence signal of AFD NPs can be rapidly "turn on" by the overexpressed GSH in tumor tissues, achieving a superior tumor-to-normal tissue (T/NT) signal ratio. Moreover, the released Pdots and reduced Fe(II) ions provide NIR-II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR-II PTT effect further aggravate CDT mediated oxidative damage toward tumors, achieving the synergistic anti-tumor therapeutic effect. The work provides a promising strategy for the development of TME activated NIR-II phototheranostic nanoprobes.

Site Selectivity of Peptoids as Azobenzene Scaffold for Molecular Solar Thermal Energy Storage.

Storing solar energy is a key challenge in modern science. MOlecular Solar Thermal (MOST) systems, in particular those based on azobenzene switches, have received great interest in the last decades. The energy storage properties of azobenzene (t1/2 <4 days; ΔH~270 kJ/kg) must be improved for future applications. Herein, we introduce peptoids as programmable supramolecular scaffolds to improve the energy storage properties of azobenzene-based MOST systems. We demonstrate with 3-unit peptoids bearing a single azobenzene chromophore that dynamics of the MOST systems can be tuned depending on the anchoring position of the photochromic unit on the macromolecular backbone. We measured a remarkable increase of the half-life of the metastable form up to 14 days at 20 °C for a specific anchoring site, significantly higher than the isolated azobenzene moiety, thus opening new perspectives for MOST development. We also highlight that liquid chromatography coupled to mass spectrometry does not only enable to monitor the different stereoisomers during the photoisomerization process as traditionally done, but also allows to determine the thermal back-isomerization kinetics.

Status and challenges for molecular solar thermal energy storage system based devices.

Molecular solar thermal energy storage systems (MOST) offer emission-free energy storage where solar power is stored via valence isomerization in molecular photoswitches. These photoswitchable molecules can later release the stored energy as heat on-demand. Such systems are emerging in recent years as a vibrant research field that is rapidly transitioning from basic research to applications. Since a major part of the attention is focused on molecular design and engineering, MOST-based device development has not been systematically summarized and introduced to a broad audience. This tutorial review will discuss the most commonly used and developed devices from a chemical engineering point of view. It is expected that future developers of MOST technology could be inspired by the existing devices, keeping in mind the summarized essential practical challenges towards large-scale implementations and more innovative applications.

Mitochondrial Regulation of Ferroptosis in Cancer Therapy.

Ferroptosis, characterized by glutamate overload, glutathione depletion, and cysteine/cystine deprivation during iron- and oxidative-damage-dependent cell death, is a particular mode of regulated cell death. It is expected to effectively treat cancer through its tumor-suppressor function, as mitochondria are the intracellular energy factory and a binding site of reactive oxygen species production, closely related to ferroptosis. This review summarizes relevant research on the mechanisms of ferroptosis, highlights mitochondria's role in it, and collects and classifies the inducers of ferroptosis. A deeper understanding of the relationship between ferroptosis and mitochondrial function may provide new strategies for tumor treatment and drug development based on ferroptosis.

Targeted Degradation of PD-L1 and Activation of the STING Pathway by Carbon-Dot-Based PROTACs for Cancer Immunotherapy.

Proteolysis targeting chimeras (PROTACs) technology is an emerging approach to degrade disease-associated proteins. Here, we report carbon-dot (CD)-based PROTACs (CDTACs) that degrade membrane proteins via the ubiquitin-proteasome system. CDTACs can bind to programmed cell death ligand 1 (PD-L1), recruit cereblon (CRBN) to induce PD-L1 ubiquitination, and degrade them with proteasomes. Fasting-mimicking diet (FMD) is also used to enhance the cellular uptake and proteasome activity. More than 99 % or 90 % of PD-L1 in CT26 or B16-F10 tumor cells can be degraded by CDTACs, respectively. Furthermore, CDTACs can activate the stimulator of interferon genes (STING) pathway to trigger immune responses. Thus, CDTACs with FMD treatment effectively inhibit the growth of CT26 and B16-F10 tumors. Compared with small-molecule-based PROTACs, CDTACs offer several advantages, such as efficient membrane protein degradation, targeted tumor accumulation, immune system activation, and in vivo detection.

Strong coupling between monolayer quantum emitter WS2 and degenerate/non-degenerate surface lattice resonances.

Strong light-matter coupling manifested by Rabi splitting has drawn considerable interest owing to its fundamental significance for impressive interaction enhancement in the fields of ultrafast active plasmonic devices and quantum information. In this paper, we investigate the coherent optical properties of a plasmonic system consisting of periodic metal nanoparticle arrays covered by a WS2 thin film of atomic layer thickness. The coupling factor, energy splitting, and temporal dynamics of this coherent coupling phenomenon are quantitatively revealed by finite-difference time-domain (FDTD) simulation and a full quantum mechanical model proves that the exciton behavior of the fermionic quantum emitter WS2 is carefully modulated by bosonic surface lattice resonances. This work may pave the way for coherent modulation of polariton and plasmon devices and can potentially open up diverse exciting possibilities like nanoscale light sources, single-photon emitters, and all-optical transistors.

Wafer-scale plasmonic metal-dielectric-metal structural color featuring high saturation and low angular dependence.

Structural color has been studied through various methods due to its distinguished features of stability, durability, high information storage density and high integration. However, the artificial structural color samples do not exhibit superior performance in color saturation and low angular dependence. Here, we present an approach to acquire additive reflective color based on a metal-dielectric-metal (MDM) stack. The upper layer composed of Ag particles is perforated in a hexagonal arrangement which profits from the dielectric anodic aluminium oxide (AAO) membrane. The size and shape of the Ag particles are getting inhomogeneous as the deposition thickness of the upper layer increasing, which expands the desired absorption range of surface plasmons. The residual non-anodized Al foil serves as a highly reflective substrate for efficient color presenting through the thin-film interference in this plasmonic MDM system. As a result, the color gamut area of this MDM stack is extended 8 times in CIE chromaticity coordinates. Finally, a wafer-scale (diameter of 83 mm) badge of Harbin Engineering University (HEU) with highly saturated colors and a pattern characterized with low angle-dependent property (up to 60°) are presented, which exhibit promising prospects in commercial coloring and imaging.

Photochemical Phase Transitions Enable Coharvesting of Photon Energy and Ambient Heat for Energetic Molecular Solar Thermal Batteries That Upgrade Thermal Energy.

Discovering physicochemical principles for simultaneous harvesting of multiform energy from the environment will advance current sustainable energy technologies. Here we explore photochemical phase transitions-a photochemistry-thermophysics coupled regime-for coharvesting of solar and thermal energy. In particular, we show that photon energy and ambient heat can be stored together and released on demand as high-temperature heat, enabled by room-temperature photochemical crystal↔liquid transitions of engineered molecular photoswitches. Integrating the two forms of energy in single-component molecular materials is capable of providing energy capacity beyond that of traditional solar or thermal energy storage systems based solely on molecular photoisomerization or phase change, respectively. Significantly, the ambient heat that is harvested during photochemical melting into liquid of the low-melting-point, metastable isomer can be released as high-temperature heat by recrystallization of the high-melting-point, parent isomer. This reveals that photon energy drives the upgrading of thermal energy in such a hybrid energy system. Rationally designed small-molecule azo switches achieve high gravimetric energy densities of 0.3-0.4 MJ/kg with long-term storage stability. Rechargeable solar thermal battery devices are fabricated, which upon light triggering provide gravimetric power density of about 2.7 kW/kg and temperature increases of >20 °C in ambient environment. We further show their use as deicing coatings. Our work demonstrates a new concept of energy utilization-combining solar energy and low-grade heat into higher-grade heat-which unlocks the possibility of developing sustainable energy systems powered by a combination of natural sunlight and ambient heat.

Synthesis of Palladium Nanodendrites Using a Mixture of Cationic and Anionic Surfactants.

Surfactants are used widely to control the synthesis of shaped noble-metal nanoparticles. In this work, a mixture of hexadecyltrimethylammonium bromide (CTAB), a cationic surfactant; sodium oleate (NaOL), an anionic surfactant; palladium chloride; and a reducing agent were used in the seed-mediated synthesis of palladium nanoparticles. By controlling the surfactant mixture ratio, we initially discovered that palladium nanodendrites with narrow size distribution were formed instead of the traditional nanocubes, synthesized with only CTAB. In order to investigate the optimal ratio to produce Pd nanodendrites with a high yield and narrow size distribution, samples synthesized with multiple molar ratios of the two surfactants were prepared and studied by transmission electron microscopy, dynamic light scattering, conductance, and ultraviolet-visible spectroscopy. We propose that the addition of NaOL alters the arrangement of surfactants on the Pd seed surface, leading to a new pattern of growth and aggregation. By studying the nanodendrite growth over time, we identified the reduction period of Pd2+ ions and the formation period of the nanodendrites. Our further experiments, including the replacement of CTAB with hexadecyltrimethylammonium chloride (CTAC) and the replacement of NaOL with sodium stearate, showed that CTA+ ions in CTAB and OL- ions in NaOL play the main roles in the formation of nanodendrites. The formation of palladium nanodendrites was robust and achieved with a range of temperatures, pH and mixing speeds.

Donor-Acceptor Substituted Benzo-, Naphtho- and Phenanthro-Fused Norbornadienes.

The photochromic norbornadiene/quadricyclane (NBD/QC) couple has found interest as a molecular solar thermal energy (MOST) system for storage of solar energy. To increase the energy difference between the two isomers, we present here the synthesis of a selection of benzo-fused NBD derivatives that contain an aromatic unit, benzene, naphthalene or phenanthrene, fused to one of the NBD double bonds, while the carbon atoms of the other double bond are functionalized with donor and acceptor groups. The synthesis protocols involve functionalization of benzo-fused NBDs with bromo/chloro substituents followed by a subjection of these intermediates to a cyanation reaction (introducing a cyano acceptor group) followed by a Sonogashira coupling (introducing an arylethynyl donor group, -CCC6H4NMe2 or -CCC6H4OMe). While the derivatives have good absorption properties in the visible region (redshifted relative to parent system) in the context of MOST applications, they lack the ability to undergo NBD-to-QC photoisomerization, even in the presence of a photosensitizer. It seems that loss of aromaticity of the fused aromatics is too significant to allow photoisomerization to occur. The concept of destroying aromaticity of a neighboring moiety as a way to enhance the energy density of the NBD/QC couple thus needs further structural modifications, in the quest for optimum MOST systems.

Enhanced Adhesion of Carbon Nanotubes by Dopamine Modification.

According to the fact that gecko-inspired vertically aligned carbon nanotubes (VA-CNTs) exhibit ultrastrong adhesion, dopamine is utilized to make a modification to this traditional biomimetic material. The composite material is tested for adhesion performance under different environmental conditions by an atomic force microscope. The adhesion force of the modified VA-CNTs does not show obvious fluctuation during the gradual heating process; however, the material gains improved adhesion when increasing the ambient humidity. In addition, the modified CNTs show a stronger adhesion force than the original CNTs in their performance tests. The dopamine polymer has a good combination with CNTs, which is responsible for the aforementioned excellent performance. Overall, this modification method is simple, convenient, efficient, and environmentally friendly, which all indicates a promising future in its application. The modified CNTs are expected to be used for super-adhesion in harsh environments, as well as in the field of microelectronics.

Developmental trajectory of hope among late-adolescents: Population heterogeneity and the impact of gender and family socioeconomic status.

OBJECTIVE: To study the developmental trajectory of hope among late-adolescents, taking population heterogeneity and the impact of gender and family socioeconomic status (SES) into consideration. METHODS: The study used the Snyder Hope Scale to perform four surveys of a sample of 381 Chinese late-adolescents, both male and female, with a mean age of 17.69 ±â€¯1.12 years, over the course of one year, and employed a growth mixture model to perform data analysis. RESULTS: Although the levels of hope among the respondents who had high and moderate levels of hope at the outset of the study remained relatively stable over the course of the year, those with low levels of hope exhibited a significant decrease over time. CONCLUSIONS: There is significant population heterogeneity in late-adolescents' developmental trajectory of hope. Additionally, gender and family SES have a significant effect on the developmental trajectory of hope, as significantly more female students than male students reported high levels of hope. Furthermore, participants with high family SES outnumbered those with low family SES in the high-hope group, whereas those with low SES outnumbered those with high SES in the low-hope group.

Norbornadiene-Based Photoswitches with Exceptional Combination of Solar Spectrum Match and Long-Term Energy Storage.

Norbornadiene-quadricyclane (NBD-QC) photoswitches are candidates for applications in solar thermal energy storage. Functionally, they rely on an intramolecular [2+2] cycloaddition reaction, which couples the S0 landscape on the NBD side to the S1 landscape on the QC side of the reaction and vice-versa. This commonly results in an unfavourable correlation between the first absorption maximum and the barrier for thermal back-conversion. This work demonstrates that this correlation can be counteracted by using steric repulsion to hamper the rotational motion of the side groups along the back-conversion path. It is shown that this modification reduces the correlation between the effective back-conversion barrier and the first absorption maximum and also increases the back-conversion entropy. The resulting molecules exhibit exceptionally long half-lives for their metastable forms without significantly affecting other properties, most notably solar spectrum match and storage density.

Long non-coding RNA NEAT1 promotes proliferation, migration and invasion of human osteosarcoma cells.

Aim: Long non-coding RNAs (LncRNAs) have been identified to play a crucial role in tumorigenesis and the progression of many types of tumors. However, the clinical significance and biological function of lncRNA nuclear-enriched abundant transcript 1(NEAT1) in human osteosarcoma remains unknown. Here, we investigated the role of NEAT1 in human osteosarcoma cell lines and clinical tumor samples. Methods: In this study, expression of NEAT1 was analyzed in 19 osteosarcoma tissues and paired adjacent non-tumor tissues by using quantitative real-time PCR. Additionally, knockdown of NEAT1 expression using Lentivirus-mediated siRNA was performed in order to explore the biological function of NEAT1 on osteosarcoma cell proliferation and metastasis through MTT, colony formation assay and transwell assay. Results: NEAT1 was over-expressed in osteosarcoma tissues compared with adjacent non-tumor tissues. In addition, knockdown of NEAT1 expression could suppress cell proliferation, migration and invasion in vitro. Conclusion: LncRNA NEAT1 was up-regulated in osteosarcoma tissue, promoting proliferation and metastasis of osteosarcoma cells. These findings indicate the role of this substance, as a growth regulator in osteosarcoma, and thus it may serve as a novel biomarker, and drug target for developing osteosarcoma therapies.

Targeted Degradation of Signal Transduction and Activator of Transcription 3 by Chaperone-Mediated Autophagy Targeting Chimeric Nanoplatform.

Chaperone-mediated autophagy (CMA) is a lysosomal-dependent proteolysis pathway for the degradation of cytosolic proteins. However, exploiting CMA-mediated proteolysis to degrade proteins of interest in cancer therapy has not been widely applied. In this study, we develop a CMA-targeting chimera (CMATAC) to efficiently and specifically degrade signal transduction and activator of transcription 3 (STAT3) in tumor cells. CMATAC consists of STAT3 and heat shock cognate 70 kDa protein (HSC70) targeting peptides connected by a linker. To efficiently deliver CMATACs into tumor cells, lipid nanoparticles (LNPs) are used to encapsulate CMATACs (nCMATACs) and decorated with an insulin-like growth factor 2 receptor (IGF2R) targeting peptide (InCMATACs) to achieve tumor targeting and precise delivery. The CMA pathway is activated in tumor cells by a fasting-mimicking diet (FMD). Furthermore, FMD treatment strongly enhances the cellular uptake and tumor accumulation of InCMATACs by upregulating the IGF2R expression. As a result, InCMATACs efficiently degrade STAT3 protein in both A549 and HCC827 tumor cells and inhibit tumor growths in vivo. This study demonstrates that InCMATACs can be used for selective proteolysis in cancer therapy.

Chaperone-Mediated Autophagy in Brain Injury: A Double-Edged Sword with Therapeutic Potentials.

Autophagy is an intracellular recycling process that maintains cellular homeostasis by degrading excess or defective macromolecules and organelles. Chaperone-mediated autophagy (CMA) is a highly selective form of autophagy in which a substrate containing a KFERQ-like motif is recognized by a chaperone protein, delivered to the lysosomal membrane, and then translocated to the lysosome for degradation with the assistance of lysosomal membrane protein 2A. Normal CMA activity is involved in the regulation of cellular proteostasis, metabolism, differentiation, and survival. CMA dysfunction disturbs cellular homeostasis and directly participates in the pathogenesis of human diseases. Previous investigations on CMA in the central nervous system have primarily focus on neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Recently, mounting evidence suggested that brain injuries involve a wider range of types and severities, making the involvement of CMA in the bidirectional processes of damage and repair even more crucial. In this review, we summarize the basic processes of CMA and its associated regulatory mechanisms and highlight the critical role of CMA in brain injury such as cerebral ischemia, traumatic brain injury, and other specific brain injuries. We also discuss the potential of CMA as a therapeutic target to treat brain injury and provide valuable insights into clinical strategies.

A Mitochondria-Targeted NIR-II Molecule Fluorophore for Precise Cancer Phototheranostics.

Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.

Entanglement generation by strong coupling between surface lattice resonance and exciton in an Al nanoarray-coated WS2 quantum emitter.

Strong light-matter interaction plays a central role in realizing quantum photonic technologies. The entanglement state, which results from the hybridization of excitons and cavity photons, forms the foundation of quantum information science. In this work, an entanglement state is achieved by manipulating the mode coupling between surface lattice resonance and quantum emitter into the strong coupling regime. At the same time, a Rabi splitting of 40 meV is observed. A full quantum model based on the Heisenberg picture is used to describe this unclassical phenomenon, and it perfectly explains the interaction and dissipation process. In addition, the observed concurrency degree of the entanglement state is 0.5, presenting the quantum nonlocality. This work effectively contributes to the understanding of nonclassical quantum effects arising from strong coupling and will intrigue more interesting potential applications in quantum optics.