Optimizing Object Detection Algorithms for Congenital Heart Diseases in Echocardiography: Exploring Bounding Box Sizes and Data Augmentation Techniques.

Background: Congenital heart diseases (CHDs), particularly atrial and ventricular septal defects, pose significant health risks and common challenges in detection via echocardiography. Doctors often employ the cardiac structural information during the diagnostic process. However, prior CHD research has not determined the influence of including cardiac structural information during the labeling process and the application of data augmentation techniques. Methods: This study utilizes advanced artificial intelligence (AI)-driven object detection frameworks, specifically You Look Only Once (YOLO)v5, YOLOv7, and YOLOv9, to assess the impact of including cardiac structural information and data augmentation techniques on the identification of septal defects in echocardiographic images. Results: The experimental results reveal that different labeling strategies substantially affect the performance of the detection models. Notably, adjustments in bounding box dimensions and the inclusion of cardiac structural details in the annotations are key factors influencing the accuracy of the model. The application of deep learning techniques in echocardiography enhances the precision of detecting septal heart defects. Conclusions: This study confirms that careful annotation of imaging data is crucial for optimizing the performance of object detection algorithms in medical imaging. These findings suggest potential pathways for refining AI applications in diagnostic cardiology studies.

Single-Atom Catalysts with Isolated Cu1-N4 Sites for Atopic Dermatitis Cascade Catalytic Therapy via Activating PPAR Signaling.

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu1-N4 sites anchored on carbon support (Cu1-N4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu1-N4 ISACs enable the sequential conversion of O2•- to H2O2 and then to harmless H2O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu1-N4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu1-N4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.

Evaluation of an Innovative Postgraduate Medical Education Model Incorporating Social Determinants of Health.

PURPOSE: Incorporating social determinants of health (SDH) into medical education is crucial. However, there are limited data on standard education models and comprehensive SDH curricula in Taiwan are insufficient. This study presents a systematic SDH curriculum instructed primarily by social workers for postgraduate doctors and aims to examine the training outcomes of the innovative curriculum. METHOD: This study assessed training outcomes using Kirkpatrick model levels 1 and 2 regarding trainees' satisfaction and improvement of their knowledge and skills in written and standardized patient (SP) pre- and posttests conducted between 1 August 2021 and 31 July 2022. RESULTS: A total of 28 trainees completed the training. The trainees' overall satisfaction score regarding the curriculum was high (4.6 out of 5). The median pretest scores for the written and SP tests were 66.25 ± 14.38 and 14.50 ± 5.13, respectively, whereas the median posttest scores were 80.00 ± 7.50 and 20.50 ± 6.13, respectively. Both written and SP posttest scores were significantly improved compared to the pretest scores (p < .001). CONCLUSIONS: The presented education model significantly improved postgraduate doctors' SDH knowledge and biopsychosocial assessment skills, and received high satisfaction scores from the trainees. Adopting social workers as primary teachers may enhance interdisciplinary collaboration between social workers and trainee doctors.

Machine Learning-Driven discovery of immunogenic cell Death-Related biomarkers and molecular classification for diabetic ulcers.

In this study, we redefine the diagnostic landscape of diabetic ulcers (DUs), a major diabetes complication. Our research uncovers new biomarkers linked to immunogenic cell death (ICD) in DUs by utilizing RNA-sequencing data of Gene Expression Omnibus (GEO) analysis combined with a comprehensive database interrogation. Employing a random forest algorithm, we have developed a diagnostic model that demonstrates improved accuracy in distinguishing DUs from normal tissue, with satisfactory results from ROC analysis. Beyond mere diagnosis, our model categorizes DUs into novel molecular classifications, which may enhance our comprehension of their underlying pathophysiology. This study bridges the gap between molecular insights and clinical practice. It sets the stage for transformative strategies in DUs management, marking a significant step forward in personalized medicine for diabetic patients.

Unraveling the role of ubiquitin-conjugating enzyme 5 (UBC5) in disease pathogenesis: A comprehensive review.

While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands.

Daytime Dysfunction: Symptoms Associated with Nervous System Disorders Mediated by SIRT1.

Daytime dysfunction, including symptoms like sleepiness, poor memory, and reduced responsiveness, is not well researched. It is crucial to develop animal models and study the biological mechanisms involved. We simulated sleep disorders through sleep deprivation, and stressful stimuli were used to establish daytime functional animal models. We used tests like the sodium pentobarbital sleep synergy test and the DSI telemetry system to measure sleep duration and structure. We also used tests like the Morris water maze, open field test, grip test, and baton twirling test to assess mental and physical fatigue. To assess the intrinsic biological mechanisms, we measured sleep-wake-related neurotransmitters and related receptor proteins, circadian rhythm-related proteins and cognition-related proteins in hypothalamus tissue, and oxidative stress, inflammatory factors, S100ß, and HPA axis-related indexes in serum. Multi-factor sleep deprivation resulted in the disruption of sleep-wakefulness structure, memory-cognitive function degradation, decreased grip coordination, and other manifestations of decreased energetic and physical strength. The intrinsic biological mechanisms were related to the disturbed expression of sleep-wake, circadian rhythm, memory-cognition-related proteins, as well as the significant elevation of inflammatory factors, oxidative stress, the HPA axis, and other related indicators. Intrinsically related biological mechanisms and reduced sirt1 expression can lead to disruption of circadian rhythms; resulting in disruption of their sleep-wake-related neurotransmitter content and receptor expression. Meanwhile, the reduced expression of sirt1 also resulted in reduced expression of synapse-associated proteins. This study prepared an animal model of daytime dysfunction by means of multi-factor sleep deprivation. With sirt1 as a core target, the relevant biological mechanisms of neurological disorders were modulated.

Ligand-Insertion Strategy for Constructing 2D Conjugated Metal-Organic Framework with Large Pore Size for Electrochemical Analytics.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have shown great promise in various electrochemical applications due to their intrinsic electrical conductivity. A large pore aperture is a favorable feature of this type of material because it facilitates the mass transport of chemical species and electrolytes. In this work, we propose a ligand insertion strategy in which a linear ligand is inserted into the linkage between multitopic ligands, extending the metal ion into a linear unit of -M-ligand-M-, for the construction of 2D c-MOFs with large pore apertures, utilizing only small ligands. As a proof-of-concept trial of this strategy, a 2D c-MOF with mesopores of 3.2 nm was synthesized using commercially available ligands hexahydrotriphenylene and 2,5-dihydroxybenzoquinone. The facilitation of the diffusion of redox species by the large pore size of this MOF was demonstrated through a series of probes. With this feature, it showed superior performance in the electrochemical analysis of a variety of biological species.

Clock protein LHY targets SNAT1 and negatively regulates the biosynthesis of melatonin in Hypericum perforatum.

Hypericum perforatum, also known as "natural fluoxetine," is a commonly used herbal remedy for treating depression. It is unclear whether melatonin in plants regulated by the endogenous circadian clock system is like in vertebrates. In this work, we found that the melatonin signal and melatonin biosynthesis gene, serotonin N-acetyltransferase HpSNAT1, oscillates in a 24-hour cycle in H. perforatum. First, we constructed a yeast complementary DNA library of H. perforatum and found a clock protein HpLHY that can directly bind to the HpSNAT1 promoter. Second, it was confirmed that HpLHY inhibits the expression of HpSNAT1 by targeting the Evening Element. Last, it indicated that HpLHY-overexpressing plants had reduced levels of melatonin in 12-hour light/12-hour dark cycle photoperiod, while loss-of-function mutants exhibited high levels, but this rhythm seems to disappear as well. The results revealed the regulatory role of LHY in melatonin biosynthesis, which may make an important contribution to the field of melatonin synthesis regulation.

Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.

Jumonji domain-containing protein D3 (JMJD3) is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di- and tri-methylated groups from lysine 27 on histone 3 (H3K27me2/3). The erasure of these marks leads to the activation of some associated genes, thereby influencing various biological processes, such as development, differentiation, and immune response. However, comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking. Here, we provide a comprehensive overview of JMJD3, including its structure, functions, and involvement in inflammatory pathways. In addition, we summarize the evidence supporting JMJD3's role in several inflammatory diseases, as well as the potential therapeutic applications of JMJD3 inhibitors. Additionally, we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

In vitro antioxidant and protective effects of the extract of Broussonetia papyrifera leaves on imiquimod-induced skin lesions in psoriasis-like mice.

Psoriasis is a chronic inflammatory immune-related skin disease. According to literature reports, the leaves of Broussonetia papyrifera exhibit antioxidant, immune-enhancing and antibacterial effects. These leaves are not only used clinically for the treatment of superficial fungal infections and hepatitis, but also used in the development of health food. However, the treatment of psoriasis with the leaves of B. papyrifera has not been reported yet. The in vitro antioxidant activity of B. papyrifera leaf extract was investigated by DPPH, OH and ABTS assays. Furthermore, IMQ was used to induce a mouse psoriasis-like model and HE staining, enzyme-linked immunosorbent assay and biochemical kits were used to measure relevant pathological indexes. The results showed that the B. papyrifera leaf extract has certain antioxidant capacity in vitro, which was positively correlated with its concentration. In addition, the extract can not only improve IMQ-induced skin damage on the back of mice, inhibit TNF-α and IL-6 factor secretion, but also regulate activity of SOD and the serum levels of MDA. Its mechanism of action related to inhibiting the secretion of inflammatory factors and the regulation of oxidative stress in vivo.

Comprehensive review of the traditional uses and the potential benefits of epimedium folium.

Epimedium Folium has been extensively utilized for medicinal purposes in China for a significant period. This review undertakes a comprehensive examination of literature pertaining to Epimedium and its metabolites over the past decade, drawing from databases such as PubMed. Through meticulous organization and synthesis of pertinent research findings, including disease models, pharmacological effects, and related aspects, this narrative review sheds light on the principal pharmacological activities and associated mechanisms of Epimedium in safeguarding the reproductive system, promoting bone health, mitigating inflammation, and combating tumors and viral infections. Consequently, this review contributes to a more profound comprehension of the recent advances in Epimedium research.

Knockout of the WD40 domain of ATG16L1 enhances foot and mouth disease virus replication.

The WD40 domain is one of the most abundant domains and is among the top interacting domains in eukaryotic genomes. The WD40 domain of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Canonical autophagy was utilized by FMDV, while the relationship between FMDV and non-canonical autophagy is still elusive. In the present study, WD40 knockout (KO) PK15 cells were successfully generated via CRISPR/cas9 technology as a tool for studying the effect of non-canonical autophagy on FMDV replication. The results of growth curve analysis, morphological observation and karyotype analysis showed that the WD40 knockout cell line was stable in terms of growth and morphological characteristics. After infection with FMDV, the expression of viral protein, viral titers, and the number of copies of viral RNA in the WD40-KO cells were significantly greater than those in the wild-type PK15 cells. Moreover, RNA‒seq technology was used to sequence WD40-KO cells and wild-type cells infected or uninfected with FMDV. Differentially expressed factors such as Mx1, RSAD2, IFIT1, IRF9, IFITM3, GBP1, CXCL8, CCL5, TNFRSF17 were significantly enriched in the autophagy, NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and TNF signaling pathway, etc. The expression levels of differentially expressed genes were detected via qRT‒PCR, which was consistent with the RNA‒seq data. Here, we experimentally demonstrate for the first time that knockout of the WD40 domain of ATG16L1 enhances FMDV replication by downregulation innate immune factors. In addition, this result also indicates non-canonical autophagy inhibits FMDV replication. In total, our results play an essential role in regulating the replication level of FMDV and providing new insights into virus-host interactions and potential antiviral strategies.

Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

AQP4 is upregulated in schizophrenia and Its inhibition attenuates MK-801-induced schizophrenia-like behaviors in mice.

BACKGROUND: The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms. METHODS: Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 µM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of AQP4, proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors. RESULTS: Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of AQP4 was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of IL-1ß, IL-6, and TNF-α in MK-801-treated C6 cells and mouse model. CONCLUSIONS: AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.

CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.

Retinal vascular leakage is a major event in several retinal diseases, including diabetic retinopathy (DR). In a previous study, we demonstrated that the aqueous humor concentration of Cystatin C (CST3), a physiological inhibitor of cysteine protease, is negatively correlated with the severity of diabetic macular edema. However, its function in the retina has not been clearly elucidated. In this study, we found a significant decrease in the aqueous humor concentration of CST3 with DR progression. Furthermore, we found that CST3 was expressed in retinal endothelial cells and that its expression was significantly downregulated in high glucose-treated human retinal microvascular endothelial cells (HRMECs) and the retinal vessels of oxygen-induced retinopathy (OIR) mice. Silencing CST3 expression resulted in decreased HRMEC migration and tubule formation ability. Exogenous addition of the CST3 protein significantly improved HRMEC migration and tubular formation. In-vivo experiments demonstrated that CST3 silencing induced retinal vascular leakage in WT mice, while its intravitreal injection significantly reduced retinal leakage in OIR mice. Mechanistically, CST3 promoted the expression of the downstream adhesion molecules, claudin5, VE-cadherin, and ZO-1, in retinal vascular cells by regulating the Rap1 signaling pathway. Therefore, this study revealed a novel mechanism by which CST3 improves retinal vascular function and provided evidence that it is a potential therapeutic target for retinal vascular leakage.

Liquiritin exerts psoriasis therapy and prevention by regulating the YY1/RBP3 axis.

BACKGROUND: Psoriasis (PSO) poses a global health threat. The current research challenge in PSO is relapse. Liquiritin (LIQ), a major active compound from Glycyrrhiza inflata Batalin, has multiple pharmacological properties, including anti-inflammatory and anti-proliferative. Nonetheless, the precise mechanisms underlying LIQ's therapeutic actions in PSO and prevention abilities remain elusive. PURPOSE: The present study aimed to delve into the potential to treat and prevent PSO and the mechanism of LIQ. METHODS: The anti-inflammatory and anti-proliferative effects of LIQ were studied in vitro with the HaCaT cell line. Then, Transcriptional analysis and bioinformatic analysis were used to determine the internal associations of the target set. Subsequently, functional experiment, luciferase report assay, ChIP-PCR, and immunohistochemical validation of clinical samples were performed to investigate the mechanism of LIQ. Finally, the anti-psoriatic effects and prevention abilities of LIQ were verified in vivo with imiquimod (IMQ)-induced PSO-like mouse models. RESULTS: Here, we identified differentially expressed genes in LIQ-stimulated HaCaT cells and Retinol-Binding Protein 3 (RBP3) as the core target, whereas YY1 was a predicted upstream transcription factor of RBP3. The YY1/RBP3 axis was obviously altered after administering LIQ at optimal doses of 20 µM in vitro and 100 µg/ml in vivo. LIQ can significantly inhibit the progression of PSO in vivo. Notably, LIQ also prevented the relapse of psoriatic lesions induced by the second round of low-dose IMQ. Mechanistically, we observed that LIQ could increase the promotion of YY1 for RBP3 by enhancing the binding affinity between them. CONCLUSION: These findings revealed that the YY1/RBP3 axis is a potential psoriatic target, and LIQ is a promising and innovative therapeutic candidate for the treatment and prevention of PSO.

Oxysterole-binding protein targeted by SARS-CoV-2 viral proteins regulates coronavirus replication.

Introduction: Oxysterol-binding protein (OSBP) is known for its crucial role in lipid transport, facilitating cholesterol exchange between the Golgi apparatus and endoplasmic reticulum membranes. Despite its established function in cellular processes, its involvement in coronavirus replication remains unclear. Methods: In this study, we investigated the role of OSBP in coronavirus replication and explored the potential of a novel OSBP-binding compound, ZJ-1, as an antiviral agent against coronaviruses, including SARS-CoV-2. We utilized a combination of biochemical and cellular assays to elucidate the interactions between OSBP and SARS-CoV-2 non-structural proteins (Nsps) and other viral proteins. Results: Our findings demonstrate that OSBP positively regulates coronavirus replication. Moreover, treatment with ZJ-1 resulted in reduced OSBP levels and exhibited potent antiviral effects against multiple coronaviruses. Through our investigation, we identified specific interactions between OSBP and SARS-CoV-2 Nsps, particularly Nsp3, Nsp4, and Nsp6, which are involved in double-membrane vesicle formation-a crucial step in viral replication. Additionally, we observed that Nsp3 a.a.1-1363, Nsp4, and Nsp6 target vesicle-associated membrane protein (VAMP)-associated protein B (VAP-B), which anchors OSBP to the ER membrane. Interestingly, the interaction between OSBP and VAP-B is disrupted by Nsp3 a.a.1-1363 and partially impaired by Nsp6. Furthermore, we identified SARS-CoV-2 orf7a, orf7b, and orf3a as additional OSBP targets, with OSBP contributing to their stabilization. Conclusion: Our study highlights the significance of OSBP in coronavirus replication and identifies it as a promising target for the development of antiviral therapies against SARS-CoV-2 and other coronaviruses. These findings underscore the potential of OSBP-targeted interventions in combating coronavirus infections.

Unveiling the impact of airways: A comparative analysis of oropharyngeal and nasopharyngeal airways in painless fiberoptic bronchoscopy.

Background: This study compared the efficacy of oropharyngeal airways (OA) and nasopharyngeal airways (NA) in maintaining oxygenation during painless fiberoptic bronchoscopy (PFB) in patients sedated with remimazolam besylate. Methods: Two hundred and fifty-two patients were randomized to the OA or NA group. Remimazolam besylate was used for anesthesia induction and maintenance in both groups. We measured and recorded several physiological parameters, including mean arterial pressure, heart rate and oxygen saturation (SpO2), at various time points: before anesthesia (T1), after anesthesia induction (T2), immediately after the bronchoscope reached the trachea (T3), during the procedure (T4), and 5 min after transfer to the post-anesthesia care unit (T5). The incidence and frequency of hypoxemia, minimum SpO2 during the procedure and patient awakening time after flumazenil administration were also recorded. Additionally, the relationship between minimum SpO2 and body mass index (BMI) was investigated. Results: Patients in the NA group experienced a higher incidence of hypoxemia compared to the OA group. Patients in the OA group maintained higher SpO2 levels at T3 and had a higher minimum SpO2 during the procedure than the NA group. Furthermore, a significant negative correlation was observed between minimum SpO2 and BMI. Following flumazenil anesthesia reversal, nearly 97 % of patients awakened within 1 min. Conclusions: This study suggests that OA may provide a better safety profile than NA by preserving respiratory function during PFB.

Supramolecular Nano-Tracker for Real-Time Tracking of Drug Release and Efficient Combination Therapy.

Real-time tracking of drug release from nanomedicine in vivo is crucial for optimizing its therapeutic efficacy in clinical settings, particularly in dosage control and determining the optimal therapeutic window. However, most current real-time tracking systems require a tedious synthesis and purification process. Herein, a supramolecular nano-tracker (SNT) capable of real-time tracking of drug release in vivo based on non-covalent host-guest interactions is presented. By integrating multiple cavities into a single nanoparticle, SNT achieves co-loading of drugs and probes while efficiently quenching the photophysical properties of the probe through host-guest complexation. Moreover, SNT is readily degraded under hypoxic tumor tissues, leading to the simultaneous release of drugs and probes and the fluorescence recovery of probes. With this spatial and temporal consistency in drug loading and fluorescence quenching, as well as drug release and fluorescence recovery, SNT successfully achieves real-time tracking of drug release in vivo (Pearson r = 0.9166, R2 = 0.8247). Furthermore, the released drugs can synergize effectively with fluorescent probes upon light irradiation, achieving potent chemo-photodynamic combination therapy in 4T1-bearing mice with a significantly improved survival rate (33%), providing a potential platform to significantly advance the development of nanomedicine and achieve optimal therapeutic effects in the clinic.

Effect and mechanism of Jinkui Shenqi Pill on preventing neural tube defects in mice based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: jinkui Shenqi Pill (JSP) is a classic traditional Chinese medicine used to treat "Kidney Yang Deficiency" disease. Previous studies indicate a protective effect of JSP on apoptosis in mouse neurons. AIM OF THE STUDY: This research, combining network pharmacology with in vivo experiments, explores the mechanism of JSP in preventing neural tube defects (NTDs) in mice. MATERIALS AND METHODS: Network pharmacology analyzed JSP components and targets, identifying common genes with NTDs and exploring potential pathways. Molecular docking assessed interactions between key JSP components and pathway proteins. In an all-trans retinoic acid (atRA)-induced NTDs mouse model, histopathological changes were observed using HE staining, neuronal apoptosis was detected using TUNEL, and Western Blot assessed changes in the PI3K/AKT signaling pathway and apoptosis-related proteins. RESULTS: Different concentrations of JSP led to varying degrees of reduction in the occurrence of neural tube defects in mouse embryos, with the highest dose showing the most significant decrease. Furthermore, it showed a better reduction in NTDs rates compared to folic acid (FA). Network pharmacology constructed a Drug-Active Ingredient-Gene Target network, suggesting key active ingredients such as Quercetin, Wogonin, Beta-Sitosterol, Kaempferol, and Stigmasterol, possibly acting on the PI3K/Akt signaling pathway. Molecular docking confirmed stable binding structures. Western Blot analysis demonstrated increased expression of p-PI3K, p-Akt, p-Akt1, p-Akt2, p-Akt3, downregulation of cleaved caspase-3 and Bax, and upregulation of Bcl-2, indicating prevention of NTDs through anti-apoptotic effects. CONCLUSION: We have identified an effective dosage of JSP for preventing NTDs, revealing its potential by activating the PI3K/Akt signaling pathway and inhibiting cell apoptosis in atRA-induced mouse embryonic NTDs.