Activated Singlet Fission Dictated by Anti-Kasha Property in a Rylene Imide Dye.

A key challenge in the search of new materials capable of singlet fission (SF) arises from the primary energy conservation criterion, i.e., the energy of the triplet exciton has to be half that of the singlet (E(S1) ≥ 2E(T1)), which excludes most photostable organic materials from consideration and confines the design strategy to materials with low energy triplet states. One potential way to overcome this energy requirement and improve the triplet energy is to enable a SF channel from higher energy ("hot") excitonic states (Sn) in a process called activated SF. Herein, we demonstrate that efficient activated SF is achieved in a rylene imide-based derivative acenaphth[l, 2-a]acenaphthylene diimide (AADI). This process is enabled by an increase in the energy gap to greater than 1.0 eV between the S3 and S1 states due to the incorporation of an antiaromatic pentalene unit, which leads to the emergence of anti-Kasha properties in the isolated molecule. Transient spectroscopy studies show that AADI undergoes ultrafast SF from higher singlet excited states in thin film, with excitation wavelength-dependent SF yields. The SF yield of ∼200% is observed upon higher energy excitation, and long-lived free triplets persist on the µs time scale suggesting that AADI can be used in SF-enhanced devices. Our results suggest that enlarging the Sn-S1 energy gap is an effective way to turn on the activated SF channel and shed light on the development of novel, stable SF materials with high triplet energies.

Adversarial dense graph convolutional networks for single-cell classification.

MOTIVATION: In single-cell transcriptomics applications, effective identification of cell types in multicellular organisms and in-depth study of the relationships between genes has become one of the main goals of bioinformatics research. However, data heterogeneity and random noise pose significant difficulties for scRNA-seq data analysis. RESULTS: We have proposed an adversarial dense graph convolutional network architecture for single-cell classification. Specifically, to enhance the representation of higher-order features and the organic combination between features, dense connectivity mechanism and attention-based feature aggregation are introduced for feature learning in convolutional neural networks. To preserve the features of the original data, we use a feature reconstruction module to assist the goal of single-cell classification. In addition, HNNVAT uses virtual adversarial training to improve the generalization and robustness. Experimental results show that our model outperforms the existing classical methods in terms of classification accuracy on benchmark datasets. AVAILABILITY AND IMPLEMENTATION: The source code of HNNVAT is available at https://github.com/DisscLab/HNNVAT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Recent Advance in the Development of Singlet-Fission-Capable Polymeric Materials.

Singlet fission (SF) is a spin-allowed process in which a higher-energy singlet exciton is converted into two lower-energy triplet excitons via a triplet pair intermediate state. Implementing SF in photovoltaic devices holds the potential to exceed the Shockley-Queisser limit of conventional single-junction solar cells. Although great progress has been made in exploiting the underlying mechanism of SF over the past decades, the scope of materials capable of SF, particularly polymeric materials, remains poor. SF-capable polymer is one of the most potential candidates in the implementation of SF into devices due to their distinct superiorities in flexibility, solution processability and self-assembly behavior. Notably, recent advancements have demonstrated high-performance SF in isolated donor-acceptor (D-A) copolymer chains. This review provides an overview of recent progress in the development of SF-capable polymeric materials, with a significant focus on elucidating the mechanisms of SF in polymers and optimizing the design strategies for SF-capable polymers. Additionally, the paper discusses the challenges encountered in this field and presents future perspectives. It is expected that this comprehensive review will offer valuable insights into the design of novel SF-capable polymeric materials, further advancing the potential for SF implementation in photovoltaic devices.

Symmetry-breaking charge separation in a null-excitonic 3-dimensional rigid nonconjugated trimer.

Photoinduced symmetry-breaking charge separation (SB-CS) has been extensively observed in various oligomers and aggregates, which holds great potential for robust artificial solar energy conversion systems. It attaches great importance to the precise manipulation of interchromophore electronic coupling in realizing efficient SB-CS. The emerging studies on SB-CS suggested that it could be realized in null-excitonic aggregates, and a long-lived SB-CS state was observed, which offers an advanced platform and has gathered immense attention in the SB-CS field. Here, we unveiled the null-exciton coupling induced ultrafast SB-CS in a rigid polycyclic aromatic hydrocarbon framework, triperyleno[3,3,3]propellane triimides (TPPTI), in which three chromophores were attached through a nonconjugated bridge. Through a combination of theoretical calculations and steady-state absorption results, we demonstrated that this nonconjugated TPPTI possesses negligible exciton coupling. Increased solvent polarity was found to significantly enhance state mixing between local excited and charge transfer states. Using transient absorption spectroscopy, ultrafast SB-CS was observed in highly polar dimethylformamide, facilitated by a selective hole-transfer coupling and a favorable charge separation free energy (ΔGCS). Additionally, the rate ratio between SB-CS and charge recombination was at least high to 1800 in dimethylformamide. This investigation provides profound insights into the role of null-exciton coupling in dominating ultrafast SB-CS in multichromophoric systems.

Appending Coronene Diimide with Carbon Nanohoops Allows for Rapid Intersystem Crossing in Neat Film.

The development of innovative triplet materials plays a significant role in various applications. Although effective tuning of triplet formation by intersystem crossing (ISC) has been well established in solution, the modulation of ISC processes in the solid state remains a challenge due to the presence of other exciton decay channels through intermolecular interactions. The cyclic structure of cycloparaphenylenes (CPPs) offers a unique platform to tune the intermolecular packing, which leads to controllable exciton dynamics in the solid state. Herein, by integrating an electron deficient coronene diimide (CDI) unit into the CPP framework, a donor-acceptor type of conjugated macrocycle (CDI-CPP) featuring intramolecular charge-transfer (CT) interaction was designed and synthesized. Effective intermolecular CT interaction resulting from a slipped herringbone packing was confirmed by X-ray crystallography. Transient spectroscopy studies showed that CDI-CPP undergoes ISC in both solution and the film state, with triplet generation time constants of 4.5 ns and 238 ps, respectively. The rapid triplet formation through ISC in the film state can be ascribed to the cooperation between intra- and intermolecular charge-transfer interactions. Our results highlight that intermolecular CT interaction has a pronounced effect on the ISC process in the solid state, and shed light on the use of the characteristic structure of CPPs to manipulate intermolecular CT interactions.

Thermally activated delayed fluorescence (TADF) organic molecules for efficient X-ray scintillation and imaging.

X-ray detection, which plays an important role in medical and industrial fields, usually relies on inorganic scintillators to convert X-rays to visible photons; although several high-quantum-yield fluorescent molecules have been tested as scintillators, they are generally less efficient. High-energy radiation can ionize molecules and create secondary electrons and ions. As a result, a high fraction of triplet states is generated, which act as scintillation loss channels. Here we found that X-ray-induced triplet excitons can be exploited for emission through very rapid, thermally activated up-conversion. We report scintillators based on three thermally activated delayed fluorescence molecules with different emission bands, which showed significantly higher efficiency than conventional anthracene-based scintillators. X-ray imaging with 16.6 line pairs mm-1 resolution was also demonstrated. These results highlight the importance of efficient and prompt harvesting of triplet excitons for efficient X-ray scintillation and radiation detection.

Optimal timing of re-excision in synovial sarcoma patients: Immediate intervention versus waiting for local recurrence.

BACKGROUND: To investigate the difference in efficacy of re-excision in synovial sarcoma patients with and without residual tumor following unplanned excision, and to compare the prognostic outcomes of immediate re-excision versus waiting for local recurrence. METHOD: This study included synovial sarcoma patients who underwent re-excision at our center between 2009 and 2019, categorized into groups based on unplanned excision and local recurrence. Analyzed endpoints included overall survival (OS), local recurrence-free survival (LRFS), and distant relapse-free survival (DRFS). Prognostic factors associated with these three different survival outcomes were analyzed through the use of Kaplan-Meier curves and Cox regression approaches. RESULT: In total, this study incorporated 109 synovial sarcoma patients, including 32 (29.4%) with no residual tumor tissue identified after re-excision, 31 (28.4%) with residual tumor tissue after re-excision, and 46 (42.2%) with local recurrence after initial excision. Patients were assessed over a median 52-month follow-up period. The respective 5-year OS, 5-year LRFS, and 5-year DRFS rates were 82.4%, 76.7%, and 74.2% for the nonresidual group, 80.6%, 80.4%, and 77.3% for the residual tumor tissue group, and 63.5%, 50.7%, and 46.3% for the local recurrence group. There was no significant difference in OS of nonresidual group and residual group patients after re-excision (p = 0.471). Concurrent or sequential treatment with chemotherapy and radiotherapy significantly reduced the risk of metastasis and mortality when compared with noncombined chemoradiotherapy, and was more effective in the local recurrence group (p < 0.05). CONCLUSION: Prompt and adequate re-excision is crucial for patients with synovial sarcoma who undergo initial inadequate tumor excision, and their prognosis is significantly better compared with patients who delay re-excision until local recurrence.

MiR-206 may regulate mitochondrial ROS contribute to the progression of Myocardial infarction via TREM1.

Myocardial infarction (MI) is a leading cause of mortality. To better understand its molecular and cellular mechanisms, we used bioinformatic tools and molecular experiments to explore the pathogenesis and prognostic markers. Differential gene expression analysis was conducted using GSE60993 and GSE66360 datasets. Hub genes were identified through pathway enrichment analysis and PPI network construction, and four hub genes (AQP9, MMP9, FPR1, and TREM1) were evaluated for their predictive performance using AUC and qRT-PCR. miR-206 was identified as a potential regulator of TREM1. Finally, miR-206 was found to induce EC senescence and ER stress through upregulating mitochondrial ROS levels via TREM1. These findings may contribute to understanding the pathogenesis of MI and identifying potential prognostic markers.

Recording point spread functions by wavefront modulation for interferenceless coded aperture correlation holography.

Coded aperture correlation holography (COACH) needs the point spread function (PSF) for image reconstruction. Utilizing a pinhole to generate a point light source is the most frequently adopted method for measuring PSF, which, however, has significant issues to resolve. One of the problems is that the resolution of the reconstructed result is limited by the cutoff frequency of the pinhole. The other is that the far-field PSF is undetectable because the amount of light illuminance decreases with the distance. In this work, we present a method for recording the PSF based on wavefront modulation. By modulating a plane wave with both the carrier spherical wave and the coded phase mask, we obtain a virtual point spread function (VPSF) that is used for image reconstruction. It is shown that the resolution of reconstructed results is not limited by the pinhole. We experimentally demonstrate high-resolution reconstruction by the VPSF.

Efficient compressive holographic reconstruction based on hologram segmentation.

Compressive holography can successfully reconstruct a three-dimensional layered object from a two-dimensional hologram. However, the extremely time-consuming reconstruction limits its range of applications. We propose a dimension reduction of measurement matrix (DRMM) method to accelerate compressive holographic reconstruction. The calculation time is substantially reduced while the reconstruction quality is improved by DRMM, which is implemented by a hologram segmentation approach and a parallel computing technique. Holograms of specific target objects are segmented from the hologram of a three-dimensional layered object, and the reconstruction can be implemented in parallel using multicore processors. We present both simulation and experimental results to show the feasibility and effectiveness of the proposed method.

Triplet Acceptors with a D-A Structure and Twisted Conformation for Efficient Organic Solar Cells.

Triplet acceptors have been developed to construct high-performance organic solar cells (OSCs) as the long lifetime and diffusion range of triplet excitons may dissociate into free charges instead of net recombination when the energy levels of the lowest triplet state (T1 ) are close to those of charge-transfer states (3 CT). The current triplet acceptors were designed by introducing heavy atoms to enhance the intersystem crossing, limiting their applications. Herein, two twisted acceptors without heavy atoms, analogues of Y6, constructed with large π-conjugated core and D-A structure, were confirmed to be triplet materials, leading to high-performance OSCs. The mechanism of triplet excitons were investigated to show that the twisted and D-A structures result in large spin-orbit coupling (SOC) and small energy gap between the singlet and triplet states, and thus efficient intersystem crossing. Moreover, the energy level of T1 is close to 3 CT, facilitating the split of triplet exciton to free charges.

Differential Proteomic Analysis of Gender-dependent Hepatic Tumorigenesis in Hras12V Transgenic Mice.

Male prevalence is an outstanding characteristic of hepatocellular carcinoma (HCC), and the underlying mechanisms for this have remained largely unknown. In the present study, Hras12V transgenic mice, in which hepatocyte-specific expression of the ras oncogene induces male-biased hepatic tumorigenesis, were studied, and altered proteins were detected by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Protein samples from hepatic tumor tissues (T) and peritumor tissues (P) of transgenic males and females and the corresponding normal liver tissues (Wt) of nontransgenic males and females were subjected to pairwise comparisons based on proteomic analysis. Among 2381 autodetected protein spots, more than 1600 were differentially expressed based on a pairwise comparison (|ratio| > = 1.5, p < = 0.05). Of these, 180 spots were randomly selected for matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) identification; finally, 89 distinct proteins were obtained. Among these 89 proteins, 7 and 50 proteins were further validated by Western blotting and literature investigation, respectively. Intriguingly, compared with Wt, the altered proteins were relatively concentrated in T in transgenic females but in P in transgenic males. Consistently, the levels of p-ERK and p-mTOR were significantly higher in the T of females compared with that of males. The pathway enrichment assay showed that 5 pathways in males but only 1 in females were significantly altered in terms of the upregulated proteins in T compared with Wt. These data indicate that female hepatocytes are disturbed by oncogenes with great difficulty, whereas male hepatocytes readily do so. In addition, 33 proteins were gender-dependently altered in hepatic tumorigenesis. Moreover, 4% DNA packaging and 4% homeostasis-related functional proteins were found in females but not in males, and more nucleus proteins were found in females (8%) than in males (3%). In conclusion, the proteomic data and comparative analysis presented here offer crucial clues for elucidating the mechanisms that underlie the male prevalence in HCC.

B lymphocytes repress hepatic tumorigenesis but not development in Hras12V transgenic mice.

Increasing reports show noninflammation underlying HCC, challenging our understanding of the roles of the immune system in hepatocarcinogenesis. By exploring a mouse model of hepatic tumor induced by hepatocyte-specific expression of the Hras12V oncogene without obvious inflammation, we found that the proportion of B cells, but not T cells, progressively and significantly decreased in 3, 5-month-old transgenic mice (Tg) compared with non-transgenic mice. Notably, the proportions of total and activated B and T cells all significantly decreased in 9-month-old Tg with multiple massive hepatic tumors. Together with the decreased B cell proportion, serum IgG1/2 also significantly decreased in 5, 9-month-old Tg. Interestingly, homozygous Tg showed significantly higher B cell proportion and IgG2 levels, accompanied by significantly lower incidences of liver nodules but not adenomas and carcinomas compared with heterozygous Tg. Treatment of Tg with PCI-32765, a potent Bruton's tyrosine kinase (BTK) inhibitor for suppressing B cell proliferation and activation, significantly decreased the B cell proportion and IgG2 levels, accompanied by a significantly higher incidence of liver nodules, but had no effects on adenoma and carcinoma. Treatment of Tg with insulin-like growth factor 1 (IGF-1) significantly increased the B cell proportion and IgG2 levels, accompanied by a significantly lower incidence of liver nodules and carcinoma, but had no effects on adenoma. Conclusively, B cells and IgG2 may play important roles in suppressing hepatic tumorigenesis, but not development. In addition, hepatocyte-specific expression of the ras oncogene may play roles in suppressing B cells, while developed hepatic tumors suppress both B and T cells.

LMGATCDA: Graph Neural Network With Labeling Trick for Predicting circRNA-Disease Associations.

Previous studies have proven that circular RNAs (circRNAs) are inextricably connected to the etiology and pathophysiology of complicated diseases. Since conventional biological research are frequently small-scale, expensive, and time-consuming, it is essential to establish an efficient and reasonable computation-based method to identify disease-related circRNAs. In this article, we proposed a novel ensemble model for predicting probable circRNA-disease associations based on multi-source similarity information(LMGATCDA). In particular, LMGATCDA first incorporates information on circRNA functional similarity, disease semantic similarity, and the Gaussian interaction profile (GIP) kernel similarity as explicit features, along with node-labeling of the three-hop subgraphs extracted from each linked target node as graph structural features. After that, the fused features are used as input, and further implied features are extracted by graph sampling aggregation (GraphSAGE) and multi-hop attention graph neural network (MAGNA). Finally, the prediction scores are obtained through a fully connected layer. With five-fold cross-validation, LMGATCDA demonstrated excellent competitiveness against gold standard data, reaching 95.37% accuracy and 91.31% recall with an AUC of 94.25% on the circR2Disease benchmark dataset. Collectively, the noteworthy findings from these case studies support our conclusion that the LMGATCDA model can provide reliable circRNA-disease associations for clinical research while helping to mitigate experimental uncertainties in wet-lab investigations.

Efficient Intersystem Crossing in Extended Helical Perylene Diimide Dimers with Chalcogen-Annulation.

The properties and formation mechanisms of the triplet state have been widely investigated since they are crucial intermediates in photo functional devices. Specifically, helical PDI dimers, horizontal expanded π-conjugated derivatives of PDI, have shown outstanding performance as electron acceptors in enhancing the performance of photovoltaics. Therefore, the exploration of triplet generation in helical PDI dimers plays a crucial role in understanding the mechanisms and excavating their further application. We make use of Se-annulation to induce intersystem crossing (ISC) in helical PDI dimers and further explore the triplet evolution process systematically as the number of Se atoms increases by transient absorption spectroscopy and the hole-electron analysis method. It shows that the twisted molecular conformation has paved the way for potential ISC in a parent molecule PDI2. The incorporation of Se atoms can result in evident promotion in the efficiency of ISC (ϕTPDI2-2Se = 96.9%) compared to the parent molecule PDI2 (ϕTPDI2 = 26.5%), indicating that chalcogen-annulation is also an efficient strategy in a π-extended system. Our results provide useful insights for understanding the triplet evolution process, which can help broaden the application of the π-extended PDI system into high-performance photovoltaics.

KLF4 inhibited the senescence-associated secretory phenotype in ox-LDL-treated endothelial cells via PDGFRA/NAMPT/mitochondrial ROS.

BACKGROUND: Inflammation is one of the significant consequences of ox-LDL-induced endothelial cell (EC) dysfunction. The senescence-associated secretory phenotype (SASP) is a critical source of inflammation factors. However, the molecular mechanism by which the SASP is regulated in ECs under ox-LDL conditions remains unknown. RESULTS: The level of SASP was increased in ox-LDL-treated ECs, which could be augmented by KLF4 knockdown whereas restored by KLF4 knock-in. Furthermore, we found that KLF4 directly promoted PDGFRA transcription and confirmed the central role of the NAPMT/mitochondrial ROS pathway in KLF4/PDGFRA-mediated inhibition of SASP. Animal experiments showed a higher SASP HFD-fed mice, compared with normal feed (ND)-fed mice, and the endothelium of EC-specific KLF4-/- mice exhibited a higher proportion of SA-ß-gal-positive cells and lower PDGFRA/NAMPT expression. CONCLUSIONS: Our results revealed that KLF4 inhibits the SASP of endothelial cells under ox-LDL conditions through the PDGFRA/NAMPT/mitochondrial ROS. METHODS: Ox-LDL-treated ECs and HFD-fed mice were used as endothelial senescence models in vitro and in vivo. SA-ß-gal stain, detection of SAHF and the expression of inflammatory factors determined SASP and senescence of ECs. The direct interaction of KLF4 and PDGFRA promotor was analyzed by EMSA and fluorescent dual luciferase reporting analysis.

Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R.

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

FOXD3 suppresses the Proliferation of CRC Bone Metastatic Cells via the Ras/Raf/MEK/ERK Signaling Pathway.

BACKGROUND: The improvements in the treatment of colorectal cancer (CRC) and prolongation of survival time have improved the incidence of bone metastasis. Forkhead box D3 (FOXD3) is involved in the development of CRC. However, the role and mechanism of FOXD3 in CRC bone metastases development are unknown. OBJECTIVE: Using the combined bioinformatics and cytology experimental analyses, this study aimed to explore the mechanistic role of FOXD3 in the bone metastasis of colon cancer, thereby aiding in the treatment of colon cancer bone metastasis and identification of drug-targeting markers. METHODS: First, the changes in the expression levels of the FOXD3 gene and differentially expressed genes (DEGs) between the colon cancer samples and colon cancer metastases were obtained from The Cancer Genome Atlas (TCGA) database. Then, the correlations of the FOXD3 gene with the DEGs were identified. Next, the effects of the FOXD3 on the proliferation and invasion abilities of colon cancer bone metastatic cells were identified using Cell Counting Kit-8 (CCK8) and Transwell cell migration assays, respectively. In addition, Western blot analysis was used to identify the expression levels of the proteins related to the EGFR/Ras/Raf/MEK/ERK(EGFR/ERK) signaling pathway and epithelial-to-mesenchymal transition (EMT). RESULTS: FOXD3 was downregulated in colon cancer and could interact with multiple DEGs in colon cancer bone metastases. FOXD3 gene knockdown could increase the proliferation of human colon cancer bone metastatic cells and their invasive ability. FOXD3 gene knockdown could activate the expression of EGFR/ERK signaling pathway-related proteins and inhibit/promote the expression of EMT-related proteins, which in turn promoted the proliferation and metastasis of LoVo cells from colon cancer bone metastases. CONCLUSION: Overall, this study demonstrated that the downregulation of the FOXD3 gene might promote the proliferation of colon cancer bone metastatic cell lines through the EGFR/ERK pathway and promote their migration through EMT, thereby serving as a promising therapeutic target.

Fabrication of near infrared light responsive photoelectrochemical immunosensor for in vivo detection of melanoma cells.

Effective and convenient detection of melanoma cells with high sensitivity is essential to identify malignant melanoma in its early stage. However, the existing detection methods, such as immunohistochemical analysis, are too complicated and time-consuming to realize the convenient in vivo and in situ detection. Herein, a near infrared responsive photoelectrochemical (PEC) immunosensor is proposed with plasmonic Au nanoparticles-photonic TiO2 nanocaves (Au/TiO2 NCs) as photon harvest and conversion transducer and antibody as cell recognition unit. The micro-antibody/Au/TiO2 NCs photoelectrode can easily in vivo distinguish melanoma cells and can realize sensitive detection of melanoma cells in short time of 1 min with a lowest limit of detection of 2 cell mL-1. The PEC immunosensor strategy not only allows us to pioneeringly implement sensitive in vivo bio-detection, but also opens up a new avenue for rational design of cell recognition units and micro-electrode for universal and reliable bio-detections.