cervical-lymph-duct-cannulated-rat-model-for-assessing-lymphatic

Cervical Lymph Duct-Cannulated Rat Model for Assessing Lymphatic Transport from the Head and Brain

Lymph flows from the central nervous system (CNS) via a series of lymphatic vessels (LVs) and lymph nodes that converge at the cervical lymph ducts. In ...

China Pharmaceutical University

Edible lotus ( G.) is widely consumed in Asian countries and treated as a functional food and traditional medicinal herb due to its abundant bioactive compounds. Lotus rhizome peels, rhizome knots, and seed embryos are important byproducts and processing waste of edible lotus ( G.) with commercial significance. Nevertheless, the comprehensive phenolic profiling of different parts of lotus is still scarce. Thus, this study aimed to review the phenolic contents and antioxidant potential in lotus seeds (embryo and cotyledon) and rhizomes (peel, knot, and pulp) grown in Australia. In the phenolic content and antioxidant potential estimation assays by comparing to the corresponding reference standards, the lotus seed embryo exhibited the highest total phenolic content (10.77 ± 0.66 mg GAE/g), total flavonoid content (1.61 ± 0.03 mg QE/g), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (9.66 ± 0.10 mg AAE/g), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging activity (14.35 ± 0.20 mg AAE/g), and total antioxidant capacity (6.46 ± 0.30 mg AAE/g), while the highest value of ferric ion reducing antioxidant power (FRAP) activity and total tannin content was present in the lotus rhizome knot (2.30 ± 0.13 mg AAE/g). A total of 86 phenolic compounds were identified in five parts of lotus by liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS), including phenolic acids (20), flavonoids (51), lignans (3), stilbenes (2), and other polyphenols (10). The most phenolic compounds, reaching up to 68%, were present in the lotus seed embryo (59). Furthermore, the lotus rhizome peel and lotus seed embryo exhibit significantly higher contents of selected polyphenols than other lotus parts according to high-performance liquid chromatography (HPLC) quantification analysis. The results highlighted that byproducts and processing waste of edible lotus are rich sources of phenolic compounds, which may be good candidates for further exploitation and utilization in food, animal feeding, and pharmaceutical industries.

LC-ESI-QTOF-MS/MS Characterization and Estimation of the Antioxidant Potential of Phenolic Compounds from Different Parts of the Lotus () Seed and Rhizome.

Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species.

 L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in  L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a "multi-omics" platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease.

Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.

Spatial Metabolomics Profiling Reveals Curcumin Induces Metabolic Reprogramming in Three-Dimensional Tumor Spheroids.

Colorectal cancer is the second leading cause of cancer-related deaths worldwide, and its development typically involves complex metabolic reprogramming. By mapping the spatial distributions of metabolites and -glycans in heterogeneous colorectal cancer tissues, we can elucidate cancer-associated metabolic and -glycan changes. Herein, we combine mass spectrometry imaging-based metabolomics and -glycomics to characterize the spatially resolved reprogramming of metabolites and -glycans in colorectal cancer tissues. The metabolic characteristics of different regions of colorectal cancer were evaluated through the utilization of orthogonal partial least squares discriminant analysis. In combination with metabolic pathway enrichment analysis, significant alterations were identified in the fatty acid metabolism, arginine and proline metabolism of colorectal cancer. Cancer cell regions exhibited a marked upregulation of saturated fatty acids, monounsaturated fatty acids, polyamines, and histidine. Additionally, we discovered that the high-mannose -glycans were predominantly distributed in tumor tissue regions, whereas complex -glycans were more commonly found in the normal tissue regions adjacent to the tumor. Such findings provide new insights into the spatial signatures of metabolites and -glycans in colorectal cancer, thereby offering a crucial basis for the diagnosis of colorectal cancer and potential vulnerabilities that might be targeted for cancer therapy.

Spatially-resolved characterization of the metabolic and -glycan alterations in colorectal cancer using matrix-assisted laser desorption/ionization mass spectrometry imaging.

 Ischemic stroke is the second leading cause of death worldwide. Ischemia-reperfusion injury plays a major role in brain function damage and leads to disability. Currently, there are no ideal therapeutic methods for preventing and treating ischemia-reperfusion injury. Extracellular vesicles (EVs) are a promising therapy for cerebral ischemia-reperfusion injury (CIRI). The main purpose of this study was to identify the pivotal miRNAs in EVs that affect functional recovery following CIRI, develop engineered EVs encapsulating key miRNAs, and identify the underlying mechanisms.  Next-generation sequencing was used to identify the crucial differentiating ingredients between EVs from normoxia- and hypoxia-conditioned human neural stem cells (hNSCs). HNSC EVs were electroporated with miR-125a-5p mimics and characterized using nanoparticle tracking analysis and electron microscopy. The role and mechanism by which EV-packaged miR-125a-5p mediates CIRI were investigated  and .  In the present study, miR-125a-5p derived from the EVs of hNSCs was found to signal the crosstalk between different cells, such as microglia and neurons, under ischemic conditions. Furthermore, hNSC-EVs loaded with miR-125a-5p (EVs) promoted the polarization of anti-inflammatory M2 microglia, resulting in altered inflammatory responses and decreased inflammatory cytokine secretion. Additionally, EVs-miR-125a-5p exerts a significant impact on microglia, subsequently translocating to neurons and inhibiting neuronal death. Moreover, increased miR-125a-5p levels in hNSC-EVs effectively inhibited neuronal apoptosis and improved the axonal ultrastructure and neurological function . Mechanistically, EVs regulate the TLR4/NF-κB signaling pathway by targeting  to alleviate neuroinflammation induced by CIRI.  Our findings demonstrate that miR-125a-5p mechanisms contribute to modulating the neuroinflammatory microenvironment and miR-125a-5p-enriched EVs may be a promising therapeutic strategy for CIRI.

MiR-125a-5p in extracellular vesicles of neural stem cells acts as a crosstalk signal modulating neuroinflammatory microenvironment to alleviate cerebral ischemia-reperfusion injury.

Metabolic crosstalk among diverse cellular populations contributes to shaping a competitive and symbiotic tumor microenvironment (TME) to influence cancer progression and immune responses, highlighting vulnerabilities that can be exploited for cancer therapy. Using a spatial multiomics platform to study the cell-specific metabolic spectrum in hepatocellular carcinoma (HCC), we map the metabolic interactions between different cells in the HCC TME and identify a unique tumor-immune-cancer-associated fibroblast (CAF) "interface" zone, where cell-cell interactions are enhanced and accompanied by significant upregulation of lactic acid and long-chain polyunsaturated fatty acids. Further combining single-cell mass spectrometry imaging of patient-derived tumor organoids, cocultured CAFs, and macrophages, we demonstrate that CAFs increase glycolysis and secrete lactic acid to the surrounding microenvironment to drive immunosuppressive macrophage M2 polarization. These findings facilitate the understanding of cancer-associated metabolic interactions in complex TME and provide clues for targeted clinical therapies.

Integrating spatial omics and single-cell mass spectrometry imaging reveals tumor-host metabolic interplay in hepatocellular carcinoma.

Harnessing dandy mechanical property, hydrogels facilitate the construction of wearable fluorescence sensors for minimally-invasive monitoring pesticide residue in living crops, while the interface self-adaptability and detection accuracy remain hugely challenging. Herein, blue-emission aggregation-induced emission nanoparticles (b-TPE NPs) and red-emission Mn-doped ZnS quantum dots (r-Mn@ZnS QDs) are encapsulated inside agarose, borax, and polyvinyl alcohol-co-constituted hydrogel to construct dual-color TPE@Mn@ZnS@AG@PVA as wearable crop sensor. Owing to specific recognition of r-Mn@ZnS QDs by thiophannate-methyl (TM), the customized TPE@Mn@ZnS@AG@PVA shows a gradual color evolution from reddish purple to blue with high resistance to environmental and experimental interferences via quenching r-Mn@ZnS QDs' fluorescence by target-induced aggregation and photo-induced electron transfer while acting negligible disturbance in blue fluorescence of b-TPE NPs, consequently achieving TM dual-color assay with limit of detection at 0.045 µg mL. Additionally, TPE@Mn@ZnS@AG@PVA fascinates smart interface self-adaptability, high adhesion, and outstanding self-repairing function, and then is pasted onto the interfaces of crops to deliver on the sense pesticide residue data in minimally-invasive manner, leading to the monitor of dynamic TM degradation. This study offers an in-depth penetration into dual-color wearable sensor with distinctive features for minimally-invasive monitoring pesticide residue in living crops, advancing the development of wearable crop sensors and precision agriculture.

Interface-Adaptive Dual-Color Hydrogel with Self-Repairing Function and High Adhesion as Flexible Wearable Sensor for Minimally-Invasive Monitoring Pesticide Residue in Living Crop.

The pharmaceutical industry is undergoing a paradigm shift towards digitalization and smart manufacturing under the Pharma 4.0 framework, with a growing emphasis on integrating Artificial Intelligence (AI) into Quality-by-Design (QbD) principles. This study proposes an AI-powered information management framework to enhance predictive quality control, regulatory compliance, and operational efficiency in pharmaceutical production. The framework consolidates structured process and product datasets with unstructured regulatory documents, enabling comprehensive data integration and decision support. Machine learning and deep learning models were employed to predict critical quality attributes (CQAs) from CPPs, while natural language processing (NLP) was applied to manage regulatory documentation. Explainable AI (XAI) techniques, including SHAP and LIME, were integrated to ensure interpretability and compliance with ICH Q8–Q11 guidelines. Experimental evaluations demonstrated the superior predictive accuracy, robustness, and scalability of deep learning approaches compared to traditional QbD methods such as Design of Experiments (DoE) and regression. Statistical hypothesis testing confirmed that the observed improvements were significant ( < 0.01), while ablation studies highlighted the critical role of NLP, dimensionality reduction, and XAI modules in ensuring compliance and efficiency. Benchmarking results further established that the proposed framework outperforms conventional approaches in adaptability to high-dimensional, large-scale datasets, with deep learning models demonstrating resilience under noise, missing data, and process variability. The findings underscore the transformative potential of AI-powered QbD frameworks for advancing smart pharmaceutical production. By integrating predictive analytics, explainability, and regulatory alignment, the proposed approach provides a scalable and compliant pathway toward Pharma 4.0, enabling continuous improvement and patient-centric outcomes.

Article	Year
LC-ESI-QTOF-MS/MS Characterization and Estimation of the Antioxidant Potential of Phenolic Compounds from Different Parts of the Lotus () Seed and Rhizome. ACS omega\| PubMed ID: 35557671	2022
Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species. Discover nano\| PubMed ID: 37581715	2023
Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease. Journal of pharmaceutical analysis\| PubMed ID: 38655398	2024
Spatial Metabolomics Profiling Reveals Curcumin Induces Metabolic Reprogramming in Three-Dimensional Tumor Spheroids. Metabolites\| PubMed ID: 39330489	2024
Spatially-resolved characterization of the metabolic and -glycan alterations in colorectal cancer using matrix-assisted laser desorption/ionization mass spectrometry imaging. RSC advances\| PubMed ID: 39839237	2025
MiR-125a-5p in extracellular vesicles of neural stem cells acts as a crosstalk signal modulating neuroinflammatory microenvironment to alleviate cerebral ischemia-reperfusion injury. Theranostics\| PubMed ID: 40585973	2025
Integrating spatial omics and single-cell mass spectrometry imaging reveals tumor-host metabolic interplay in hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 40729385	2025
Interface-Adaptive Dual-Color Hydrogel with Self-Repairing Function and High Adhesion as Flexible Wearable Sensor for Minimally-Invasive Monitoring Pesticide Residue in Living Crop. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 41082387	2026
Intelligent information management enables quality-by-design in pharmaceutical production. Scientific reports\| PubMed ID: 41419511	2025

Zihan Zhu

Biography

JoVE Journal Publications

Other Publications