Has_circ_0002360 Facilitates Immune Evasion by Enhancing Heterogeneous Nuclear Ribonucleoprotein A1 Stability, Thereby Promoting Malignant Progression in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is marked by complex molecular aberrations including differential expression of circular RNAs (circRNAs). hsa_circ_0002360, a circRNA, has been identified as overexpressed in NSCLC. This study aimed to evaluate the expression patterns of hsa_circ_0002360 and its potential role as an oncogenic factor in NSCLC. We analyzed two GEO datasets (GSE112214 and GSE158695) using R software to identify differentially expressed circRNAs. Quantitative reverse transcription PCR (qRT-PCR) assessed the expression of hsa_circ_0002360 in NSCLC tissues and cell lines compared to controls. We used siRNA and overexpression vectors to modulate hsa_circ_0002360 levels in A549 cells, followed by assays to assess proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). Interactions with RNA-binding proteins, specifically HNRNPA1, were investigated using RNA-pull down and RIP assays. In GEO datasets GSE112214 and GSE158695, hsa_circ_0002360 was identified as significantly overexpressed in NSCLC, a finding supported by qRT-PCR analyses showing higher levels in NSCLC tissues and cell lines compared to controls. Functional assays demonstrated that knockdown of hsa_circ_0002360 in A549 cells decreased proliferation, migration, invasion, and altered epithelial-mesenchymal transition marker expression, while inducing apoptosis, suggesting its oncogenic role. Conversely, overexpression promoted tumor characteristics, corroborated by in vivo xenograft models showing increased tumor growth. Hsa_circ_0002360's interaction with HNRNPA1, evidenced through RNA-pull down and RIP assays, implicates it in regulatory pathways that enhance NSCLC progression. This expression was also correlated with advanced TNM stages and metastasis, highlighting its potential as a therapeutic target. hsa_circ_0002360 acts as an oncogene in NSCLC, promoting tumor progression and metastasis through regulation of cell growth, apoptosis, and EMT processes. The interaction between hsa_circ_0002360 and HNRNPA1 suggests a novel mechanism of circRNA-mediated modulation of NSCLC pathology, providing potential targets for therapeutic intervention.

Study on the activity and mechanism of herbal formula anti-infection powder (AIP) against influenza-virus-induced pneumonia through genetic susceptibility genes.

ETHNOPHARMACOLOGICAL RELEVANCE: Anti-infection powder (AIP), a patented Chinese herbal formulation, is used traditionally in the treatment of upper respiratory tract infections. In this study, an ethanol extract of AIP was demonstrated to inhibit influenza A virus (IAV) infection and IAV-induced pneumonia (IVP), both in vitro and in vivo, highlighting its potential mechanism of action. AIM OF THE STUDY: To determine the anti-IAV activity of AIP and to explore the possible mechanisms of inhibiting IAV-induced pneumonia. MATERIALS AND METHODS: An ethanol extract was extracted from AIP and its major ingredients were determined by high-performance liquid chromatography (HPLC). An IAV-infected A549 cell model and an IAV-induced mouse pneumonia model were established to evaluate the therapeutic effects of AIP on IVP in vivo and in vitro. The mice were respectively administered AIP at high- and low-dose in different groups. The anti-IAV activity of AIP was evaluated by detecting viral load, lung lesion, lung index, suvival time, inflammatory cytokines and transcriptomic analysis in the lung tissue. The potential pathways and targets that involved in AIP against IVP were predicted by network pharmacology. Mendelian randomization (MR), colocalization analysis, and molecular docking were employed to identify novel therapeutic targets for IVP. Polymerase chain reaction (PCR) and Western blot (WB) techniques were used to confirm the effect of AIP on the expression of risk target genes in the lungs of IVP mice. RESULTS: In A549 cell line, AIP effectively inhibited IAV infection with IC50 values of 65.49 µg/mL. The anti-IAV activity of AIP was mainly determined by chlorogenic acid, forsythiarin, puerarin, paeoniflorin and prim-o-glucosylcimigin. Moreover, AIP inhibited the neuraminidase activity and the M gene expression in vitro. In vivo, oral administration of AIP significantly reduced viral load and improved lung tissue lesions. AIP decreased the concentration of pro-inflammatory factors such as IL-1ß, TNF-α, and IFN-γ, and significantly increased the concentration of the anti-inflammatory factor IL-4. According to network pharmacology analysis, toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway may be the possible mechanisms by which AIP inhibits IVP and regulates excessive inflammatory response.Two new genes, LRG1 and PSMA4, associated with genetic susceptibility to influenza and pneumonia, predicted as potential IVP drug target genes by MR and colocalization analysis. The antiviral mechanism of AIP may be to inhibit the expression levels of LRG1 and PSMA4 in lungs of mouse IVP. CONCLUSIONS: AIP exhibited anti-IAV activities both in vitro and in vivo. AIP had a protective effect against pneumonia caused by influenza virus and can inhibit the progression of inflammation. This effect may be associated with its ability to inhibit the expression levels of genetic susceptibility genes (LRG1 and PSMA4) in lungs of mouse IVP. The findings of this study enhance our understanding of the role and mechanisms of AIP in the treatment of IVP.

A New Paradigm for High-dimensional Data: Distance-Based Semiparametric Feature Aggregation Framework via Between-Subject Attributes.

This article proposes a distance-based framework incentivized by the paradigm shift towards feature aggregation for high-dimensional data, which does not rely on the sparse-feature assumption or the permutation-based inference. Focusing on distance-based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high-dimensional variables using pairwise outcomes of between-subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U-statistics-based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root-n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands.

Enhancing tumor endothelial permeability using MUC18-targeted gold nanorods and mild hyperthermia.

The Enhanced Permeability and Retention (EPR) effect, an elevated accumulation of drugs and nanoparticles in tumors versus in normal tissues, is a widely used concept in the field of cancer therapy. It assumes that the vasculature of solid tumors would possess abnormal, leaky endothelial cell barriers, allowing easy access of intravenous-delivered drugs and nanoparticles to tumor regions. However, the EPR effect is not always effective owing to the heterogeneity of tumor endothelium over time, location, and species. Herein, we introduce a unique nanoparticle-based approach, using MUC18-targeted gold nanorods coupled with mild hyperthermia, to specifically enhance tumor endothelial permeability. This improves the efficacy of traditional cancer therapy including photothermal therapy and anticancer drug delivery by increasing the transport of photo-absorbers and drugs across the tumor endothelium. Using single cell imaging tools and classic analytical approaches in molecular biology, we demonstrate that MUC18-targeted gold nanorods and mild hyperthermia enlarge the intercellular gaps of tumor endothelium by inducing circumferential actin remodeling, stress fiber formation, and cell contraction of adjacent endothelial cells. Considering MUC18 is overexpressed on a variety of tumor endothelium and cancer cells, this approach paves a new avenue to improve the efficacy of cancer therapy by actively enhancing the tumor endothelial permeability.

Multispectral Image Stitching via Global-Aware Quadrature Pyramid Regression.

Image stitching is a critical task in panorama perception that involves combining images captured from different viewing positions to reconstruct a wider field-of-view (FOV) image. Existing visible image stitching methods suffer from performance drops under severe conditions since environmental factors can easily impair visible images. In contrast, infrared images possess greater penetrating ability and are less affected by environmental factors. Therefore, we propose an infrared and visible image-based multispectral image stitching method to achieve all-weather, broad FOV scene perception. Specifically, based on two pairs of infrared and visible images, we employ the salient structural information from the infrared images and the textual details from the visible images to infer the correspondences within different modality-specific features. For this purpose, a multiscale progressive mechanism coupled with quadrature correlation is exploited to improve regression in different modalities. Exploiting the complementary properties, accurate and credible homography can be obtained by integrating the deformation parameters of the two modalities to compensate for the missing modality-specific information. A global-aware guided reconstruction module is established to generate an informative and broad scene, wherein the attentive features of different viewpoints are introduced to fuse the source images with a more seamless and comprehensive appearance. We construct a high-quality infrared and visible stitching dataset for evaluation, including real-world and synthetic sets. The qualitative and quantitative results demonstrate that the proposed method outperforms the intuitive cascaded fusion-stitching procedure, achieving more robust and credible panorama generation. Code and dataset are available at https://github.com/Jzy2017/MSGA.

Low-Temperature Plasma-Constructed Ni-Doped W18O49 Nanorod Arrays for Enhanced Electrocatalytic Oxygen Evolution and Urea Oxidation.

Surface engineering by doping and amorphization is receiving widespread attention from the perspective of the regulation of the electrocatalytic activities of electrocatalysts. However, the effective modulation of active sites on catalysts is still challenging. Herein, a straightforward and efficient method combining hydrothermal treatment with low-temperature plasma processing is presented to synthesize Ni-doped W18O49 nanorod arrays on carbon cloth with abundant oxygen vacancies (CC/WO-Ni-x). Mild plasma doping with Ni modifies the electronic structure of the W18O49 nanorod arrays, resulting in the formation of an amorphous structure that significantly reduces the electron transfer resistance. Additionally, the coupling with high-valent W6+ (derived from W18O49) leads to the partial preoxidation of doped Ni to form active Ni3+ species and oxygen vacancies. These features are collectively responsible for the remarkable oxygen evolution reaction (OER) and urea oxidation reaction (UOR) properties of CC/WO-Ni-4, for example, 10 mA cm-2 current density, an overpotential of 265 mV required for the OER under 1.0 M KOH solution. The addition of 500 mM urea to the 1.0 M KOH solution decreases the overpotential required for the same current density from 265 to 93 mV. This study provides insights into the modification of surface structures and presents an effective strategy to optimize the electrocatalytic active sites and enhance the efficiency of multifunctional electrocatalysts.

Identification and Analysis of Biomarkers Associated with Lipophagy and Therapeutic Agents for COVID-19.

BACKGROUND: Lipids, as a fundamental cell component, play an regulating role in controlling the different cellular biological processes involved in viral infections. A notable feature of coronavirus disease 2019 (COVID-19) is impaired lipid metabolism. The function of lipophagy-related genes in COVID-19 is unknown. The present study aimed to investigate biomarkers and drug targets associated with lipophagy and lipophagy-based therapeutic agents for COVID-19 through bioinformatics analysis. METHODS: Lipophagy-related biomarkers for COVID-19 were identified using machine learning algorithms such as random forest, Support Vector Machine-Recursive Feature Elimination, Generalized Linear Model, and Extreme Gradient Boosting in three COVID-19-associated GEO datasets: scRNA-seq (GSE145926) and bulk RNA-seq (GSE183533 and GSE190496). The cMAP database was searched for potential COVID-19 medications. RESULTS: The lipophagy pathway was downregulated, and the lipid droplet formation pathway was upregulated, resulting in impaired lipid metabolism. Seven lipophagy-related genes, including ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2, were used as biomarkers and drug targets for COVID-19. Moreover, lipophagy may play a role in COVID-19 pathogenesis. As prospective drugs for treating COVID-19, seven potential downregulators (phenoxybenzamine, helveticoside, lanatoside C, geldanamycin, loperamide, pioglitazone, and trichostatin A) were discovered. These medication candidates showed remarkable binding energies against the seven biomarkers. CONCLUSIONS: The lipophagy-related genes ACADVL, HYOU1, DAP, AUP1, PRXAB2, LSS, and PLIN2 can be used as biomarkers and drug targets for COVID-19. Seven potential downregulators of these seven biomarkers may have therapeutic effects for treating COVID-19.

Na-mediated carbon nitride realizing CO2 photoreduction with selectivity modulation.

The depressed directional separation of photogenerated carriers and weak CO2 adsorption/activation activity are the main factors hampering the development of artificial photosynthesis. Herein, Na ions are embedded in graphitic carbon nitride (g-C3N4) to achieve directional migration of the photogenerated electrons to Na sites, while the electron-rich Na sites enhance CO2 adsorption and activation. Na/g-C3N4 (NaCN) shows improved photocatalytic reduction activity of CO2 to CO and CH4, and under simulated sunlight irradiation, the CO yield of NaCN synthesized by embedding Na at 550°C (NaCN-550) is 371.2 µmol g-1 h-1, which is 58.9 times more than that of the monomer g-C3N4. By means of theoretical calculations and experiments including in situ fourier transform infrared spectroscopy, the mechanism is investigated. This strategy which improves carrier separation and reduces the energy barrier at the same time is important to the development of artificial photosynthesis.

A conserved Pol II elongator SPT6L mediates Pol V transcription to regulate RNA-directed DNA methylation in Arabidopsis.

In plants, the plant-specific RNA polymerase V (Pol V) transcripts non-coding RNAs and provides a docking platform for the association of accessory proteins in the RNA-directed DNA methylation (RdDM) pathway. Various components have been uncovered that are involved in the process of DNA methylation, but it is still not clear how the transcription of Pol V is regulated. Here, we report that the conserved RNA polymerase II (Pol II) elongator, SPT6L, binds to thousands of intergenic regions in a Pol II-independent manner. The intergenic enrichment of SPT6L, interestingly, co-occupies with the largest subunit of Pol V (NRPE1) and mutation of SPT6L leads to the reduction of DNA methylation but not Pol V enrichment. Furthermore, the association of SPT6L at Pol V loci is dependent on the Pol V associated factor, SPT5L, rather than the presence of Pol V, and the interaction between SPT6L and NRPE1 is compromised in spt5l. Finally, Pol V RIP-seq reveals that SPT6L is required to maintain the amount and length of Pol V transcripts. Our findings thus uncover the critical role of a Pol II conserved elongator in Pol V mediated DNA methylation and transcription, and shed light on the mutual regulation between Pol V and II in plants.

[Short term follow-up of femoral neck dynamic cross screw system and threaded cannulated screw in the treatment of vertically unstable femoral neck fractures].

OBJECTIVE: To analyze and compare the clinical effects of femoral neck dynamic cross screw system (FNS) and cannulated screws(CS) in the treatment of vertically unstable femoral neck fractures. METHODS: The clinical data and short-term follow-up results of 40 patients with vertically unstable femoral neck fractures admitted from July 2020 to August 2021 were retrospectively analyzed. According to different internal fixation methods, 40 patients were divided into two groups, 20 cases in FNS group included 11 males and 9 females with a median of 58.5(50.3, 62.5) years old, and 20 in CS group included 9 males and 11 females with a median of 52.0(40.5, 58.0) years old. The operation time, knife edge length, blood loss and treatment cost of two gruops were observed and compared. The postoperative fracture healing and internal fixation were evaluated with X-ray imaging data, and the femoral neck shortening of the affected side was measured. The incidence of thigh irritation, the time of partial weight bearing and full weight bearing, early necrosis of femoral head, reoperation revision and Harris scores were compared between two groups. RESULTS: FNS group was followed up for 18.0(15.0, 19.0) months, CS group for 17.0(15.0, 18.8) months. There was no significant difference in operation time, incision length and blood loss between two groups(P>0.05). The cost of diagnosis and treatment in FNS group was higher than that in CS group(P<0.001). In FNS group, there was no irritation sign of the affected side thigh, while in CS group, there were 6 cases with discomfort or irritation sign of the lateral thigh(P<0.05). The average time of partial weight bearing activity in CS group was later than that in FNS group(P<0.05); However, there was no significant difference in the activity time of complete weight bearing between two groups(P=0.011>0.05). At the last follow-up, the shortened length of the affected femoral neck in CS group was greater than that in FNS group(P<0.05). There was no early necrosis of femoral head and reoperation in both groups. There was no significant difference in Harris score between two groups 12 months after operation(P>0.05). CONCLUSION: FNS treatment of vertically unstable femoral neck fractures can significantly reduce the incidence of lateral thigh irritation sign, and effectively reduce the postoperative shortening rate of vertically unstable femoral neck fractures, which can provide a relatively stable anti rotation force and anti cutting force, so that patients can go to the ground relatively early, which is conducive to the recovery of the affected hip joint function after surgery. It is a new option for the surgical treatment of vertically unstable femoral neck fractures. However, due to the high cost of treatment, In clinical practice, appropriate surgical treatment is selected according to the actual situation.

Network Structure of Childhood Trauma, Bodily Disturbances, and Schizotypy in Schizophrenia and Nonclinical Controls.

Background and Hypothesis: Exposure to childhood trauma has been linked to the development of psychosis and bodily self-disturbances, 2 hallmarks of schizophrenia (SZ). Prior work demonstrated that bodily disturbances serve as a bridge between childhood trauma and SZ symptomatology, but the diagnostic specificity of these connections remains unknown. This study uses network analysis to bridge this gap by comparing the interplays between childhood trauma, bodily self-disturbances, and schizotypy in clinical and general populations. Study Design: Networks were constructed to examine the relationships between schizotypy (Schizotypal Personality Questionnaire; SPQ), bodily self-disturbances (Perceptual Aberration Scale; PAS), and childhood trauma (Childhood Trauma Questionnaire, CTQ) in 152 people with SZ and 162 healthy comparison participants (HC). The Fused Graphical Lasso was used to jointly estimate the networks in the 2 groups and the structure and strength of the networks were compared. Node centrality and shortest paths between CTQ, PAS, and schizotypy were examined. Study Results: When comparing SZ and HC, the network of bodily self-disturbances, childhood trauma, and schizotypy were similarly structured, but the network was significantly stronger in SZ than HC. In both groups, bodily self-disturbances were on one of the shortest paths between childhood trauma to schizotypal experiences. Conclusions: Our findings revealed reliable associations between childhood trauma, bodily self-disturbance, and schizotypy, with bodily disturbances acting as a bridge from childhood trauma to schizotypy. The elevated strength of the SZ network indicates a more highly interconnected, and therefore reactive network in which exposure to childhood trauma can more easily activate bodily disturbances and schizotypy.

Rest-activity rhythm disruption and metabolic health in schizophrenia: a cross-sectional actigraphy study of community-dwelling people living with schizophrenia and nonpsychiatric comparison participants.

STUDY OBJECTIVES: People living with schizophrenia (PLWS) have increased physical comorbidities and premature mortality which may be linked to dysregulated rest-activity rhythms (RARs). This study aimed to compare RARs between PLWS and nonpsychiatric comparison participants (NCs) and to examine the relationships of RARs with age, sleep, metabolic, and physical health outcomes and, among PLWS, relationships of RARs with illness-related factors. METHODS: The study sample included 26 PLWS and 36 NCs, assessed with wrist-worn actigraphy to compute RAR variables and general sleep variables. Participants completed assessments for clinical symptoms, physical health, sleep quality, medication use, and assays for fasting glycosylated hemoglobin (hemoglobin A1c) levels. We examined group differences in RAR and sleep variables, relationships of RAR variables with metabolic and physical health measures, and, among PLWS, relationships between RAR variables and illness-related measures. RESULTS: PLWS had significantly shorter active periods, lower relative amplitude, and lower mean activity during their most active 10 hours compared to the NCs (Cohen's d = 0.79, 0.58, and 0.62, respectively). PLWS had poorer sleep quality, greater mean percent sleep, less wake after sleep onset, and higher total sleep time variability compared to NCs. PLWS had higher rates of antidepressant, anxiolytic, and antipsychotic medication use compared to NCs, which may have impacted sleep quality and objective sleep measures. Across both groups, more fragmented and variable RARs were associated with higher HbA1c levels (ηp2 = .10) and worse physical health (ηp2 = .21). Among PLWS, RARs were correlated with total sleep time (rs = .789, P < .01) and percent sleep (rs = .509, P < .05), but not with age, sleep quality, or other illness-related factors. CONCLUSIONS: RARs provide unique information about sleep and activity for PLWS and have the potential for targeted interventions to improve metabolic health and mortality. CITATION: Mahmood Z, Ramsey A, Kidambi N, et al. Rest-activity rhythm disruption and metabolic health in schizophrenia: a cross-sectional actigraphy study of community-dwelling people living with schizophrenia and nonpsychiatric comparison participants. J Clin Sleep Med. 2024;20(9):1505-1516.

Umbravirus-like RNA viruses are capable of independent systemic plant infection in the absence of encoded movement proteins.

The signature feature of all plant viruses is the encoding of movement proteins (MPs) that supports the movement of the viral genome into adjacent cells and through the vascular system. The recent discovery of umbravirus-like viruses (ULVs), some of which only encode replication-associated proteins, suggested that they, as with umbraviruses that lack encoded capsid proteins (CPs) and silencing suppressors, would require association with a helper virus to complete an infection cycle. We examined the infection properties of 2 ULVs: citrus yellow vein associated virus 1 (CY1), which only encodes replication proteins, and closely related CY2 from hemp, which encodes an additional protein (ORF5CY2) that was assumed to be an MP. We report that both CY1 and CY2 can independently infect the model plant Nicotiana benthamiana in a phloem-limited fashion when delivered by agroinfiltration. Unlike encoded MPs, ORF5CY2 was dispensable for infection of CY2, but was associated with faster symptom development. Examination of ORF5CY2 revealed features more similar to luteoviruses/poleroviruses/sobemovirus CPs than to 30K class MPs, which all share a similar single jelly-roll domain. In addition, only CY2-infected plants contained virus-like particles (VLPs) associated with CY2 RNA and ORF5CY2. CY1 RNA and a defective (D)-RNA that arises during infection interacted with host protein phloem protein 2 (PP2) in vitro and in vivo, and formed a high molecular weight complex with sap proteins in vitro that was partially resistant to RNase treatment. When CY1 was used as a virus-induced gene silencing (VIGS) vector to target PP2 transcripts, CY1 accumulation was reduced in systemic leaves, supporting the usage of PP2 for systemic movement. ULVs are therefore the first plant viruses encoding replication and CPs but no MPs, and whose systemic movement relies on a host MP. This explains the lack of discernable helper viruses in many ULV-infected plants and evokes comparisons with the initial viruses transferred into plants that must have similarly required host proteins for movement.

Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear. AIM OF THE STUDY: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs). MATERIALS AND METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking. RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/ß-catenin signaling pathway. Further, ß-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs. CONCLUSION: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/ß-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.

Monophenyl luminescent material with dual-state emission and pH sensitivity for cell imaging.

Dual-state emission (DSE) luminescent materials are a newly discovered category of luminescent materials that exhibit efficient light emission in multiple states, including dilute solutions, highly concentrated solutions, aggregated states and solid states. These materials effectively address the aggregation-caused quenching (ACQ) observed in traditional organic luminescent materials with large conjugated planes, as well as the limitations of aggregation-induced emission (AIE) materials, which typically do not emit light in dilute solutions. The design and development of DSE luminescent materials for organelle imaging applications has attracted considerable interest. In this context, this study presents the design and synthesis of a novel luminescent compound, DMSS-AM, characterised by intramolecular hydrogen bonding and a D-π-A structure. As a monophenyl luminescent material, DMSS-AM exhibits DSE properties with fluorescence quantum yields of 22.1% in solution and 14.0% in the solid state. In particular, it exhibits unique pH-responsive properties, facilitating the targeted detection of lysosomal pH changes. Confocal laser scanning microscopy imaging of cells demonstrated that DSE emitters at both low and high concentrations do not affect image quality for bio-imaging applications. This advance is expected to significantly broaden the applicability of DSE luminescent materials in future applications.

A Task-Guided, Implicitly-Searched and Meta-Initialized Deep Model for Image Fusion.

Image fusion plays a key role in a variety of multi-sensor-based vision systems, especially for enhancing visual quality and/or extracting aggregated features for perception. However, most existing methods just consider image fusion as an individual task, thus ignoring its underlying relationship with these downstream vision problems. Furthermore, designing proper fusion architectures often requires huge engineering labor. It also lacks mechanisms to improve the flexibility and generalization ability of current fusion approaches. To mitigate these issues, we establish a Task-guided, Implicit-searched and Meta-initialized (TIM) deep model to address the image fusion problem in a challenging real-world scenario. Specifically, we first propose a constrained strategy to incorporate information from downstream tasks to guide the unsupervised learning process of image fusion. Within this framework, we then design an implicit search scheme to automatically discover compact architectures for our fusion model with high efficiency. In addition, a pretext meta initialization technique is introduced to leverage divergence fusion data to support fast adaptation for different kinds of image fusion tasks. Qualitative and quantitative experimental results on different categories of image fusion problems and related downstream tasks (e.g., visual enhancement and semantic understanding) substantiate the flexibility and effectiveness of our TIM.

Ethanol extract of Eclipta prostrata induces multiple myeloma ferroptosis via Keap1/Nrf2/HO-1 axis.

BACKGROUND: Multiple myeloma (MM) is an incurable hematological malignancy with limited therapeutic efficacy. Eclipta prostrata is a traditional Chinese medicinal plant reported to possess antitumor properties. However, the effects of E. prostrata in MM have not been explored. PURPOSE: The aim of this study was to define the mechanism of the ethanol extract of E. prostrata (EEEP) in treating MM and identify its major components. METHODS: The pro-ferroptotic effects of EEEP on cell death, cell proliferation, iron accumulation, lipid peroxidation, and mitochondrial morphology were determined in RPMI-8226 and U266 cells. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and 4-hydroxynonenal (4HNE) were detected using western blotting during EEEP-mediated ferroptosis regulation. The RPMI-8226 and U266 xenograft mouse models were used to explore the in vivo anticancer effects of EEEP. Finally, high performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry system (UPLC-Q/TOF-MS) were used to identify the major constituents of EEEP. RESULTS: EEEP inhibited MM cell growth and induced cell death in vitro and in vivo. By promoting malondialdehyde and Fe2+ accumulation, lipid peroxidation, and GSH suppression, EEEP triggers ferroptosis in MM. Mechanistically, EEEP regulates the Keap1/Nrf2/HO-1 axis and stimulates ferroptosis. EEEP-induced lipid peroxidation and malondialdehyde accumulation were blocked by the Nrf2 activator NK-252. In addition, HPLC and UPLC-Q/TOF-MS analysis elucidated the main components of EEEP, including demethylwedelolactone, wedelolactone, chlorogenic acid and apigenin, which may play important roles in the anti-tumor function of EEEP. CONCLUSION: In summary, EEEP exerts its anti-MM function by inducing MM cell death and inhibiting tumor growth in mice. We also showed that EEEP can induce lipid peroxidation and accumulation of ferrous irons in MM cells both in vivo and in vitro, leading to ferroptosis. In addition, this anti-tumor function may be achieved by the EEEP activation of Keap1/Nrf2/HO-1 axis. This is the first study to reveal that EEEP exerts anti-MM activity through the Keap1/Nrf2/HO-1-dependent ferroptosis regulatory axis, making it a promising candidate for MM treatment.

N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial-Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer.

Endothelial-mesenchymal transition (EndoMT) of vascular endothelial cells has recently been considered as a key player in the early progression of a variety of vascular and nonvascular diseases, including atherosclerosis, cancer, and organ fibrosis. However, current strategies attempting to identify pharmacological inhibitors to block the regulatory pathways of EndoMT suffer from poor selectivity, unwanted side effects, and a heterogeneous response from endothelial cells with different origins. Furthermore, EndoMT inhibitors focus on preventing EndoMT, leaving the endothelial cells that have already undergone EndoMT unresolved. Here, we report the design of a simple but powerful nanoparticle system (i.e., N-cadherin targeted melanin nanoparticles) to convert cytokine-activated, mesenchymal-like endothelial cells back to their original endothelial phenotype. We term this process "Reversed EndoMT" (R-EndoMT). R-EndoMT allows the impaired endothelial barriers to recover their quiescence and intactness, with significantly reduced leukocyte and cancer cell adhesion and transmigration, which could potentially stop atheromatous plaque formation and cancer metastasis in the early stages. R-EndoMT is achieved on different endothelial cell types originating from arteries, veins, and capillaries, independent of activating cytokines. We reveal that N-cadherin targeted melanin nanoparticles reverse EndoMT by downregulating an N-cadherin dependent RhoA activation pathway. Overall, this approach offers a different prospect to treat multiple EndoMT-associated diseases by designing nanoparticles to reverse the phenotypical transition of endothelial cells.

Co single atom coupled oxygen vacancy on W18O49 nanowires surface to construct asymmetric active site enhanced peroxymonosulfate activation.

Enhancing the activation of peroxymonosulfate (PMS) is essential for generating more reactive oxygen species in advanced oxidation process (AOPs). Nevertheless, improving PMS adsorption and expediting interfacial electron transfer to enhance reaction kinetics pose significant challenges. Herein, we construct confined W18O49 nanowires with asymmetric active centers containing Co-Vo-W (Vo: oxygen vacancy). The design incorporates surface-rich Vo and single-atom Co, and the resulting material is employed for PMS activation in water purification. By coupling unsaturated coordinated electrons in Vo with low-valence Co single atoms to construct an the "electron fountainhead", the adsorption and activation of PMS are enhanced. This results in the generation of more active free radicals (SO4•-, •OH, •O2-) and non-free radicals (1O2) for the decomposition of micropollutants. Thereinto, the degradation rate of bisphenol A (BPA) by Co-W18O49 is 32.6 times faster that of W18O49 monomer, which is also much higher than those of other transition-metal-doped W18O49 composites. This work is expected to help to elucidate the rational design and efficient PMS activation of catalysts with asymmetric active centers.