Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging.

BACKGROUND: The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS: In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS: We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

Low-Shear Stress Promotes Atherosclerosis via Inducing Endothelial Cell Pyroptosis Mediated by IKKε/STAT1/NLRP3 Pathway.

Atherosclerosis is initiated by vascular endothelial dysfunction, and low-shear stress (LSS) of blood flow is a key factor leading to endothelial dysfunction. Growing evidence suggests that endothelial cell pyroptosis plays an important role in the development of atherosclerosis. Studies have shown that low-shear stress can induce endothelial cell pyroptosis, but the exact mechanism remains unclear. Our experiments demonstrated that low-shear stress induced endothelial cell pyroptosis and the phosphorylation of IκB kinase ε (IKKε). IKKε knockdown not only significantly attenuated atherosclerosis lesions of aortic arch areas in ApoE-/- mice fed with high cholesterol diets, but also markedly reduced endothelial cell pyroptosis and NLRP3 expression triggered by low-shear stress. Further mechanism studies showed that IKKε promoted the expression of NLRP3 via activating signal transducer and activator of transcription 1 (STAT1) and the subsequent binding of STAT1 to NLRP3 promoter region. These results suggest that low-shear stress plays a pro-atherosclerotic role by promoting endothelial cell pyroptosis through the IKKε/STAT1/NLRP3 pathway, which provides new insights into the formation of atherosclerosis.

Effects of novel mRNA-VEGF@USPIO nanoparticles on human brain microvascular endothelial cell injury.

We investigated the effect of mRNA-VEGF@ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles on the repair of human brain microvascular endothelial cell (HBMECs) injury and its related mechanisms. mRNA-VEGF@USPIO nanoparticles were designed, prepared, and characterized using NTA and UV spectrophotometry. Cell viability was determined using the CCK-8. Cells in the control, TNF-α, and mRNA-VEGF@USPIO groups were sequenced and the differentially expressed genes (DEGs) were identified. Finally, a functional analysis of the DEGs was performed. Both NTA and spectrophotometry results indicated that mRNA-VEGF@USPIO was successfully constructed. TNF-α significantly reduced cell viability and promoted apoptosis compared with the control group (p < 0.05), whereas mRNA-VEGF@USPIO nanoparticles reversed the changes caused by TNF-α. Via sequencing, 9063 DEGs were identified between the control and TNF-α groups, 9125 DEGs were identified between the control and mRNA-VEGF@USPIO groups, and 211 DEGs were identified between the TNF-α and mRNA-VEGF@USPIO groups. Additionally, 71 overlapping DEGs were identified in the three groups using Venn diagrams. These overlapping DEGs were mainly enriched in cytokine-cytokine receptor interactions and the TNF signaling pathway, NF-κB signaling pathway, and NOD-like receptor signaling pathway. This study shows that mRNA-VEGF@USPIO nanoparticles can repair HBMECs injury.

Exploring atherosclerosis imaging with contrast-enhanced MRI using PEGylated ultrasmall iron oxide nanoparticles.

Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3 nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72 h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48 h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.

Ultra-compact on-chip spectrometer based on thermally tuned topological miniaturized bound states in the continuum cavity.

On-chip spectrometers are key components in many spectral sensing applications owing to their unique advantages in size and in situ detection. In this work, we propose and demonstrate a class of thermally tunable spectrometers by utilizing topological miniaturized bound states in the continuum (mini-BIC) cavities in a photonic crystal (PhC) slab combined with a metal micro-ring heater. We achieve a resolution of 0.19 nm in a spectral range of ∼6 nm, while the device's footprint is only 42×42µm2. The mini-BIC spectrometer works in nearly vertical incidence and is compatible with array operation. Our work sheds light on the new possibilities of high-performance on-chip spectrometers for applications ranging from bio-sensing to medicine.

Establishment of a Scale for Predicting Early Hematoma Enlargement of Spontaneous Intracerebral Hemorrhage Based on Non-Contrast CT Signs.

AIM: To optimize the Spontaneous intracerebral hemorrhage (sICH) early hematoma expansion prediction scoring table to adopt appropriate clinical treatment plans and improve the prognosis of sICH patients. MATERIAL AND METHODS: A total of 150 patients with sICH were enrolled, and 44 had early hematoma expansion. According to the selection and exclusion criteria, the study subjects were screened, their NCCT characteristic signs and clinical data were analyzed statistically. The established prediction score was applied to the follow-up study cohort to conduct a pilot study, and the t-test and ROC curve were used to evaluate its predictive ability. RESULTS: Statistical analysis found that initial hematoma volume, GCS score, and NCCT special signs were independent risk factors for early hematoma expansion after sICH (p < 0.05). Thus, a score table was established. Subjects with ≥10 were divided into high-risk group, 6-8 comprised the medium-risk group, and ≤4 were divided into low-risk group. Among 17 patients with acute sICH, 7 developed early hematoma enlargement. The prediction accuracy was 92.41% in the low-risk group, 98.06% in the medium-risk group, and 84.61% in the high-risk group. CONCLUSION: This optimized prediction score table based on the special signs of NCCT shows the high prediction accuracy of sICH early hematoma.

Cdyl2-60aa encoded by CircCDYL2 accelerates cardiomyocyte death by blocking APAF1 ubiquitination in rats.

The loss of cardiomyocytes (CMs) after myocardial infarction (MI) is widely acknowledged to initiate the development of heart failure (HF). Herein, we found that circCDYL2 (583 nt) derived from chromodomain Y-like 2 (Cdyl2) is significantly upregulated in vitro (oxygen-glucose deprivation (OGD)-treated CMs) and in vivo (failing heart post-MI) and can be translated into a polypeptide termed Cdyl2-60aa (~7 kDa) in the presence of internal ribosomal entry sites (IRES). Downregulation of circCDYL2 significantly decreased the loss of OGD-treated CMs or the infarcted area of the heart post-MI. Additionally, elevated circCDYL2 significantly accelerated CM apoptosis via Cdyl2-60aa. We then discovered that Cdyl2-60aa could stabilize protein apoptotic protease activating factor-1 (APAF1) and promote CM apoptosis; heat shock protein 70 (HSP70) mediated APAF1 degradation in CMs by ubiquitinating APAF1, which Cdyl2-60aa could competitively block. In conclusion, our work substantiated the claim that circCDYL2 could promote CM apoptosis via Cdyl2-60aa, which enhanced APAF1 stability by blocking its ubiquitination by HSP70, suggesting that it is a therapeutic target for HF post-MI in rats.

LILRB2-containing small extracellular vesicles from glioblastoma promote tumor progression by promoting the formation and expansion of myeloid-derived suppressor cells.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) was reported to be an inhibitory molecule with suppressive functions. sEVs mediate communication between cancer cells and other cells. However, the existence of LILRB2 on sEVs in circulation and the function of sEVs-LILRB2 are still unknown. This study aims to investigate the role of LILRB2 in GBM and determine how LILRB2 in sEVs regulates tumor immunity. METHODS: LILRB2 expression in normal brain and GBM tissues was detected by immunohistochemistry, and the effect of LILRB2 on prognosis was evaluated in an orthotopic brain tumor model. Next, a subcutaneous tumor model was constructed to evaluate the function of pirb in vivo. The immune cells in the tumor sites and spleen were detected by immunofluorescence staining and flow cytometry. Then, the presence of pirb in sEVs was confirmed by WB. The percentage of immune cells after incubation with sEVs from GL261 (GL261-sEVs) or sEVs from GL261-pirb+ (GL261-sEVs-pirb) was detected by flow cytometry. Then, the effect of pirb on sEVs was evaluated by a tumor-killing assay and proliferation assay. Finally, subcutaneous tumor models were constructed to evaluate the function of pirb on sEVs. RESULTS: LILRB2 was overexpressed in human GBM tissue and was closely related to an immunosuppressive TME in GBM. Then, a protumor ability of LILRB2 was observed in subcutaneous tumor models, which was related to lower CD8 + T cells and higher MDSCs (myeloid-derived suppressor cells) in the tumor and spleen compared to those of the control group. Next, we found that pirb on sEVs (sEVs-pirb) inhibits the function of CD8 + T cells by promoting the formation and expansion of MDSCs. Furthermore, the protumor function of sEVs-pirb was demonstrated in subcutaneous tumor models. CONCLUSION: We discovered that LILRB2/pirb can be transmitted between GBM cells via sEVs and that pirb on sEVs induces the formation and expansion of MDSCs. The induced MDSCs facilitate the formation of an immunosuppressive TME.

Berberine inhibits low shear stress-induced vascular endothelial inflammation via decreasing phosphorylation of Akt and IRF3.

BACKGROUND: Low shear stress (LSS) is closely related to vascular endothelial inflammation and the development of atherosclerosis. Berberine (BBR), a natural compound isolated from Coptis chinensis, has been reported to exert anti-inflammatory and antiatherosclerotic effects. However, the role of berberine in low shear stress-induced endothelial inflammation remains unclear. METHODS: The role of berberine in low shear stress-induced vascular endothelial inflammation was investigated in human umbilical vein endothelial cells (HUVECs) using a plate flow chamber in vitro and in mice with an established LSS model by partial ligation of the carotid artery in vivo. RESULTS: First, in vitro experiments demonstrated that BBR significantly decreased the expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) and the phosphorylation of Akt in HUVECs induced by low shear stress. Moreover, BBR significantly inhibited the low shear stress-mediated phosphorylation of IRF3 and its translocation to the nucleus. Notably, Akt overexpression markedly reversed the inhibitory effects of BBR on LSS-induced IRF3 activation and ICAM-1 expression. Moreover, in vivo experiments showed that BBR markedly decreased intimal ICAM-1 and IRF3 in the LSS areas of partially ligated carotid arteries in mice; however, EC-specific Akt overexpression mediated by adeno-associated viruses abolished the anti-inflammatory effect of BBR. CONCLUSION: Taken together, our findings suggest that BBR treatment attenuates LSS-induced vascular endothelial inflammation by decreasing the activation of the Akt/IRF3 signalling pathway.

High-Density Lipoprotein Is Associated with Leukoaraiosis Severity in Patients with Acute Ischemic Stroke.

Many patients with acute ischemic stroke (AIS) are found to accompany with leukoaraiosis (LA) in brain imaging. The risk factors of LA in patients with AIS were examined in this study. Patients with AIS were recruited and underwent head magnetic resonance imaging. According to Fazekas scores, patients were divided into LA group and non-LA group. We compared demographic and laboratory characteristics in two groups. Multivariate logistic regression analysis demonstrated that high-density lipoprotein (HDL), age, stroke history, admission SBP, and homocysteine were independent risk factors for LA in patients with AIS (P < 0.05). Multinomial logistic regression analysis demonstrated that HDL was an independent risk factor for moderate LA (OR 4.151, 95% CI 1.898-9.078, P < 0.001) and severe LA (OR 3.151, 95% CI 1.350-7.358, P = 0.008). In order to further explore the correlation between HDL level and the severity of LA, HDL was categorized in quartiles and multinomial logistic regression analysis was presented. Regression analysis showed that HDL ≥ 1.34 mmol/L was correlated with moderate and severe LA after adjusting for corresponding confounding factors in different models. After 1-year follow-up, patients were divided into regular statin therapy group and irregular statin therapy group. There was no significant difference in HDL level between two groups; however, the proportion of patients with increased Fazekas scores in regular statin therapy group was significantly less than that in the irregular statin therapy group (P < 0.05). In conclusion, HDL was an independent risk factor for LA and associated with the severity of LA in patients with AIS; regular statin therapy may be negatively related with the progress of LA. These results provide more evidences for controlling risk factors and severity of LA in patient with AIS.

Molecular characteristics of single patient-derived glioma stem-like cells from primary and recurrent glioblastoma.

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro, SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan-Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro, PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.

Neuromedin B receptor stimulation of Cav3.2 T-type Ca2+ channels in primary sensory neurons mediates peripheral pain hypersensitivity.

Background: Neuromedin B (Nmb) is implicated in the regulation of nociception of sensory neurons. However, the underlying cellular and molecular mechanisms remain unknown. Methods: Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated shRNA knockdown and animal behaviour tests, we studied the effects of Nmb on the sensory neuronal excitability and peripheral pain sensitivity mediated by Cav3.2 T-type channels. Results: Nmb reversibly and concentration-dependently increased T-type channel currents (IT) in small-sized trigeminal ganglion (TG) neurons through the activation of neuromedin B receptor (NmbR). This NmbR-mediated IT response was Gq protein-coupled, but independent of protein kinase C activity. Either intracellular application of the QEHA peptide or shRNA-mediated knockdown of Gß abolished the NmbR-induced IT response. Inhibition of protein kinase A (PKA) or AMP-activated protein kinase (AMPK) completely abolished the Nmb-induced IT response. Analysis of phospho-AMPK (p-AMPK) revealed that Nmb significantly activated AMPK, while AMPK inhibition prevented the Nmb-induced increase in PKA activity. In a heterologous expression system, activation of NmbR significantly enhanced the Cav3.2 channel currents, while the Cav3.1 and Cav3.3 channel currents remained unaffected. Nmb induced TG neuronal hyperexcitability and concomitantly induced mechanical and thermal hypersensitivity, both of which were attenuated by T-type channel blockade. Moreover, blockade of NmbR signalling prevented mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain, and this effect was attenuated by siRNA knockdown of Cav3.2. Conclusions: Our study reveals a novel mechanism by which NmbR stimulates Cav3.2 channels through a Gßγ-dependent AMPK/PKA pathway. In mouse models, this mechanism appears to drive the hyperexcitability of TG neurons and induce pain hypersensitivity.

MicroRNA-15a-5p plays a role in osteogenic MC3T3-E1 cells differentiation by targeting PDCD4 (programmed cell death 4) via Wnt/ß-catenin dependent signaling pathway.

Osteoporosis is defined as a bone condition characterized by bone mass reduction, bone micro-architectural and quality deterioration, leading to compromised strength and increased chances of fracture. Evidence have shown an essential role of microRNAs (miRNAs) in various osteogenic differentiation processes. However, the function of miR-15a-5p in the differentiation of osteogenic cells and possible mechanisms remains unclear. The present study explored the expression of miR-15a-5p in human osteoporosis specimens and during the osteogenic differentiation of MC3T3-E1 cells. Functions of miR-15a-5p were determined using miR-15a-5p mimics and inhibitors. Luciferase assay was used to verify the binding of miR-15a-5p and PDCD4 3'UTR. Alizarin Red Staining (ARS) and Alkaline phosphatase (ALP) activity were used to determine the miR-15a-5p role in osteogenic differentiation. Finally, Wnt pathway inhibitor was used to determine the miR-15a-5p/PDCD4/Wnt signaling pathway in regulating osteogenic differentiation. We found miR-15a-5p expression was increased in human osteoporosis specimens and during differentiation of MC3T3-E1 cells. PDCD4 was also identified as a target of miR-15a-5p and was found to be involved in osteogenic differentiation. Further, miR-15a-5p mimics attenuated the effects of PDCD4 overexpression. Finally, use of XAV939 (Wnt pathway inhibitor) downregulated osteogenic differentiation in miR-15a5p/PDCD4/Wnt-dependent signaling pathway. In conclusion, miR-15a-5p induced differentiation of osteoblasts and mineralization by modulating osteoblast differentiation factors, mainly OSX, ALP, OCN, and RUNX2, by inhibiting PDCD4 and Wnt signaling pathways. This study provides a modality for the future use of miR-15a-5p in the treatment and prevention of osteoporosis.

METTL3 Promotes the Resistance of Glioma to Temozolomide via Increasing MGMT and ANPG in a m6A Dependent Manner.

Acquired chemoresistance is a major limiting factor in the clinical treatment of glioblastoma (GBM). However, the mechanism by which GBM acquires therapeutic resistance remains unclear. Here, we aimed to investigate whether METTL3-mediated N6-methyladenosine (m6A) modification contributes to the temozolomide (TMZ) resistance in GBM. We demonstrated that METTL3 METTL3-mediated m6A modification were significantly elevated in TMZ-resistant GBM cells. Functionally, METTL3 overexpression impaired the TMZ-sensitivity of GBM cells. In contrast, METTL3 silencing or DAA-mediated total methylation inhibition improved the sensitivity of TMZ-resistant GBM cells to TMZ in vitro and in vivo. Furthermore, we found that two critical DNA repair genes (MGMT and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved TMZ resistance in GBM cells. Collectively, METTL3 acts as a critical promoter of TMZ resistance in glioma and extends the current understanding of m6A related signaling, thereby providing new insights into the field of glioma treatment.

Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3.

Many studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

HOTAIRM1 Promotes Malignant Progression of Transformed Fibroblasts in Glioma Stem-Like Cells Remodeled Microenvironment via Regulating miR-133b-3p/TGFß Axis.

Recent studies have reported that cancer associated fibroblasts (CAFs) and glioma stem-like cells (GSCs) played active roles in glioma progression in tumor microenvironment (TME). Long non-coding RNAs (lncRNAs) have been found to be closely associated with glioma development in recent years, however, their molecular regulatory mechanisms on CAFs in GSCs remodeled TME kept largely unelucidated. Our study found that GSCs could induce malignant transformation of fibroblasts (t-FBs) based on dual-color fluorescence tracing orthotopic model. Associated with poor prognosis, Lnc HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) was highly expressed in high-grade gliomas and t-FBs. Depleting HOTAIRM1 inhibited the proliferation, invasion, migration, and even tumorigenicity of t-FB. Conversely, overexpression of HOTAIRM1 promoted malignancy phenotype of t-FB. Mechanistically, HOTAIRM1 directly bound with miR-133b-3p, and negatively regulated the latter. MiR-133b-3p partly decreased the promotion effect of HOTAIRM1 on t-FBs. Furthermore, transforming growth factor-ß (TGFß) was verified to be a direct target of miR-133b-3p. HOTAIRM1 can modulate TGFß via competing with miR-133b-3p. Collectively, HOTAIRM1/miR-133b-3p/TGFß axis was involved in modulating t-FBs malignancy in TME remodeled by GSCs, which had the potential to serve as a target against gliomas.

SMART transfer method to directly compare the mechanical response of water-supported and free-standing ultrathin polymeric films.

Intrinsic mechanical properties of sub-100 nm thin films are markedly difficult to obtain, yet an ever-growing necessity for emerging fields such as soft organic electronics. To complicate matters, the interfacial contribution plays a major role in such thin films and is often unexplored despite supporting substrates being a main component in current metrologies. Here we present the shear motion assisted robust transfer technique for fabricating free-standing sub-100 nm films and measuring their inherent structural-mechanical properties. We compare these results to water-supported measurements, exploring two phenomena: 1) The influence of confinement on mechanics and 2) the role of water on the mechanical properties of hydrophobic films. Upon confinement, polystyrene films exhibit increased strain at failure, and reduced yield stress, while modulus is reduced only for the thinnest 19 nm film. Water measurements demonstrate subtle differences in mechanics which we elucidate using quartz crystal microbalance and neutron reflectometry.

The coupling and competition of crystallization and phase separation, correlating thermodynamics and kinetics in OPV morphology and performances.

The active layer morphology transition of organic photovoltaics under non-equilibrium conditions are of vital importance in determining the device power conversion efficiency and stability; however, a general and unified picture on this issue has not been well addressed. Using combined in situ and ex situ morphology characterizations, morphological parameters relating to kinetics and thermodynamics of morphology evolution are extracted and studied in model systems under thermal annealing. The coupling and competition of crystallization and demixing are found to be critical in morphology evolution, phase purification and interfacial orientation. A unified model summarizing different phase diagrams and all possible kinetic routes is proposed. The current observations address the fundamental issues underlying the formation of the complex multi-length scale morphology in bulk heterojunction blends and provide useful morphology optimization guidelines for processing devices with higher efficiency and stability.

Absorption Reduction of Large Purcell Enhancement Enabled by Topological State-Led Mode Coupling.

We propose the mechanism of edge state-led mode coupling under topological protection; i.e., localized surface plasmons almost do not have any influence on the edge state, while the edge state greatly changes the local field distribution of surface plasmons. Based on this mechanism, in the well-designed topological photonic structure containing a resonant plasmon nanoantenna, an obvious absorption reduction in the spontaneous emission spectra appears due to the near-field deformation around the antenna induced by the edge state. Because a plasmon antenna with ultrasmall mode volume provides large Purcell enhancement and simultaneously the photonic crystal guides almost all scattering light into its edge state, the rate of nonscattering single photons reaches more than 10^{4}γ_{0}. This topological state-led mode coupling mechanism and induced absorption reduction, which are based on topological protection, will have a profound effect on the study of composite topological photonic structures and related micro- and nanoscale cavity quantum electrodynamics. Also, nonscattering large Purcell enhancement will provide practical use for on-chip quantum light sources, such as single-photon sources and nanolasers.