Epidemiological Trends in Cardiovascular Disease Mortality Attributable to Modifiable Risk Factors and Its Association with Sociodemographic Transitions across BRICS-Plus Countries.

BRICS-Plus countries (Brazil, Russia, India, China, South Africa, and 30 other countries) is a group of 35 countries with emerging economies making up more than half of the world's population. We explored epidemiological trends of cardiovascular disease (CVD) mortality attributable to modifiable risk factors and its association with period and birth cohort effects and sociodemographic index (SDI) across BRICS-Plus countries by using joinpoint regression and age-period-cohort modeling from 1990 to 2019. Between 1990 and 2019, the all-ages CVD deaths increased by 85.2% (6.1 million to 11.3 million) across BRICS-Plus countries. The CVD age-standardized mortality rate attributable to dietary risks and smoking significantly decreased across BRICS-Plus countries, with some exceptions. However, four-fifths of BRICS-Plus countries observed a remarkable increasing trend of high body mass-index (BMI)-related CVD deaths, in particular, among younger adults (25-49 years). Early birth cohorts and individuals aged greater than 50 years showed a higher risk of CVD mortality. Both the China-ASEAN FTA and Mercosur regions stand out for their successful sociodemographic transition, with a significant reduction in CVD mortality over the study period. Singapore and Brazil achieved great progress in CVD mortality reduction and the other BRICS-Plus countries should follow their lead in adopting public health policies and initiatives into practice.

An "AND" Molecular Logic Gate as a Super-Enhancers for De Novo Designing Activatable Probe and Its Application in Atherosclerosis Imaging.

Developing activatable fluorescent probes with superlative fluorescence enhancement factor (F/F0 ) to improve the signal-to-noise (S/N) ratio is still an urgent issue. "AND" molecular logic gates are emerging as a useful tool for enhanced probes selectivity and accuracy. Here, an "AND" logic gate is developed as super-enhancers for designing activatable probes with huge F/F0 and S/N ratio. It utilizes lipid-droplets (LDs) as controllable background input and sets the target analyte as variable input. The fluorescence is tremendously quenching due to double locking, thus an extreme F/F0 ratio of target analyte is obtained. Importantly, this probe can transfer to LDs after a response occurs. The target analyte can be directly visualized through the spatial location without a control group. Accordingly, a peroxynitrite (ONOO- ) activatable probe (CNP2-B) is de novo designed. The F/F0 of CNP2-B achieves 2600 after reacting with ONOO- . Furthermore, CNP2-B can transfer from mitochondria to lipid droplets after being activated. The higher selectivity and S/N ratio of CNP2-B are obtained than commercial probe 3'-(p-hydroxyphenyl) fluorescein (HPFin vitro and in vivo. Therefore, the atherosclerotic plaques at mouse models are delineated clearly after administration with in situ CNP2-B probe gel. Such input controllable "AND" logic gate is envisioned to execute more imaging tasks.

Peroxynitrite/Lipid Droplet Sequence-Activated Dual-Lock Fluorescent Probes Enable Precise Intraoperative Imaging of Atherosclerotic Plaques.

The formation of atherosclerotic plaques is the root cause of various cardiovascular diseases (CVDs). Effective CVD interventions thus call for precise identification of the plaques to aid clinical assessment and treatment of such diseases. In this study, we introduced a dual-analyte sequentially activated logic fluorescence reporting system CNN2-B to precisely identify the atherosclerotic plaques in vivo. This probe was achieved by creating a dual-locked fluorescent sensor that permits highly specific and sensitive detection of peroxynitrite and lipid droplets─the two hallmarks of atherosclerosis (AS). The recognition group of the probe removed after reacting with ONOO- and intramolecular charge rearrangement occurred to generate a coumarin derivative structure. This structure had a strong solvent effect; it could recognize lipid droplets (LDs) in cells, thus exhibiting fluorescence without secondary molecular adjustment. The fluorescence was tremendously quenched by double locking; thus, an extreme fluorescence enhancement factor (F/F0) ratio of 365 for CNN2-B was obtained. Importantly, CNN2-B could move from the mitochondria to lipid droplets after being activated. CNN2-B exhibited higher selectivity and signal-to-noise (S/N) ratio than commercial probe hydroxyphenyl fluorescein (HPF). Therefore, atherosclerotic plaques in mouse models were delineated clearly by fluorescence imaging after in situ administration of CNN2-B.

Enzyme Catalysis Biomotor Engineering of Neutrophils for Nanodrug Delivery and Cell-Based Thrombolytic Therapy.

Utilizing neutrophils (NEs) to target and deliver nanodrugs to inflammation sites has received considerable attention. NEs are involved in the formation and development of thrombosis by transforming into neutrophil extracellular traps (NETs); this indicates that NEs may be a natural thrombolytic drug delivery carrier. However, NEs lack an effective power system to overcome blood flow resistance and enhance targeting efficiency. Herein, we report the application of a urease catalysis micromotor powered NEs nanodrug delivery system to promote thrombolysis and suppress rethrombosis. The urease micromotor powered Janus NEs (UM-NEs) were prepared by immobilizing the enzyme asymmetrically onto the surface of natural NEs and then loading urokinase (UK) coupled silver (Ag) nanoparticles (Ag-UK) to obtain the UM-NEs (Ag-UK) system. Urease catalytic endogenous urea is used to generate thrust by producing ammonia and carbon dioxide, which propels NEs actively targeting the thrombus. The UM-NEs (Ag-UK) can be activated by enriched inflammatory cytokines to release NETs at the thrombosis site, resulting in a concomitant release of Ag-UK. Ag-UK induces thrombolysis to restore vascular recanalization. This urease micromotor-driven NEs drug delivery system can significantly reduce the hemorrhagic side effects, promote thrombolysis, and inhibit rethrombosis with high bioavailability and biosafety, which can be used for the treatment of thrombotic diseases.

Lipid-Activatable Fluorescent Probe for Intraoperative Imaging of Atherosclerotic Plaque Using In Situ Patch.

The surgical removal of lesions is among the most common and effective treatments for atherosclerosis. It is often the only curative treatment option, and the ability to visualize the full extent of atherosclerotic plaque during the operation has major implications for the therapeutic outcome. Fluorescence imaging is a promising approach for the inspection of atherosclerotic plaques during surgery. However, there is no systematic strategy for intraoperative fluorescent imaging in atherosclerosis. In this study, the in situ attachment of a lipid-activatable fluorescent probe (CN-N2)-soaked patch to the outer arterial surface is reported for rapid and precise localization of the atherosclerotic plaque in ApoE-deficient mouse during surgery. Stable imaging of the plaque is conducted within 5 min via rapid recognition of abnormally accumulated lipid droplets (LDs) in foam cells. Furthermore, the plaque/normal ratio (P/N) is significantly enhanced to facilitate surgical delineation of carotid atherosclerotic plaques. Visible fluorescence bioimaging using lipid-activatable probes can accurately delineate plaque sizes down to diameters of <0.5 mm, and the images can be swiftly captured within the stable plaque imaging time window. These findings on intraoperative fluorescent imaging of plaques via the in situ attachment of the CN-N2 patch hold promise for effective clinical applications.

Lipid Droplet-Specific Probe for Rapidly Locating Atherosclerotic Plaques and Intraoperative Imaging via In Situ Spraying.

The ability to visualize the full extent of atherosclerotic plaques during surgery has major implications for therapeutic outcomes. Fluorescence imaging is a promising approach for atherosclerotic plaque inspection during surgery. However, a specific strategy for the intraoperative fluorescence imaging of atherosclerosis has not been established. This study presents an in situ spraying aerosol of a lipid droplet-specific probe to rapidly and precisely locate atherosclerotic plaques during surgery. Stable imaging of the plaque was achieved within 5 min by nebulizing the aqueous solution of the lipid droplet-specific probe (CN-PD) into 3 µm droplets and rapidly permeating it in situ. The visible fluorescence bioimaging of CN-PD can accurately delineate the plaque margins and size even with a diameter ≤0.5 mm, which are capable of being swiftly captured during the stable plaque imaging window (>2 h). This strategy combines the consideration of a specific probe design and an efficient in situ delivery, which results in weak interference from the background signals. Therefore, the plaque-to-normal tissue ratio (P/N) is sufficient to facilitate the surgical delineation of carotid atherosclerotic plaques. The originality of the intraoperative fluorescence imaging of the plaques via in situ delivery of the lipid droplet-specific probe holds promise for effective clinical application.

Anti-cancer adjuvant drug screening via epithelial-mesenchymal transition-related aptamer probe.

Epithelial-mesenchymal transition (EMT) is implicated in the pathological processes of cancer metastasis and drug resistance. Anti-cancer drugs may also potentially lead to EMT, resulting in their reduced therapeutic effect. Therefore, the combination of these anti-cancer drugs with anti-EMT agents has been promoted in clinic. Screening anti-EMT drugs and evaluation of EMT process are highly dependent on EMT biomarkers on cell membrane. At present, the detection of EMT biomarker is mainly by Western blot method, which is time-consuming and complicated. In this work, for effectively screening anti-EMT drugs by evaluation of the EMT process, a type of aptamer probe based on aggregation-induced emission (AIE) was designed. The aptamer SYL3C was employed to target the EMT biomarker EpCAM on cell membrane. Two fluorophores, FAM and tetraphenylethene (TPE, an AIE dye), were modified at the two ends of SYL3C, respectively. This aptamer probe (TPE-SYL3C-FAM) can monitor the EpCAM expression, which can be recovered by anti-EMT drugs. By observation of the change in TPE emission intensity, the anti-EMT effect of drugs can be evaluated. The FAM emission was used as internal reference to reduce environmental interferences. This probe can be potentially used to screen anti-EMT agents as anti-cancer adjuvant drugs with high throughput.

Controlled "off-on" fluorescent probe for the specific detection of hyperhomocysteinemia.

Hyperhomocysteinemia is an established risk factor for atherosclerosis and vascular disease. Therefore, designing a hyperhomocysteinemia specific probe is of great significance for the early warning of cardiovascular diseases. However, developing probes that can efficiently and specifically recognize homocysteine (Hcy) remains a tremendous challenge. Therefore, we designed an Hcy-specific fluorescent probe (HSFP) with excellent selectivity and anti-interference capability. Interestingly, this probe can automatically "off-on" in water solution, but the fluorescence of HSFP remains "off" when Hcy is present in the solution. The spectroscopic data demonstrated that the fluorescence of HSFP attenuated 13.8 folds toward Hcy in water without interference from other biothiols and amino acids. Furthermore, HSFP can sensitively reflect the change of Hcy content in cells. Therefore, HSFP was further applied to detect hyperhomocysteinemia in vivo with high efficiency. In summary, we have developed an Hcy-specific fluorescent probe to efficiently detect Hcy in vivo and in vitro, which may contribute to basic or clinical research.

A Bioresponsive Near-Infrared Fluorescent Probe for Facile and Persistent Live-Cell Tracking.

Molecular imaging significantly transforms the field of biomedical science and facilitates the visualization, characterization, and quantification of biologic processes. However, it is still challenging to monitor cell localization in vivo, which is essential to the study of tumor metastasis and in the development of cell-based therapies. While most conventional small-molecule fluorescent probes cannot afford durable cell labeling, transfection of cells with fluorescent proteins is limited by their fixed fluorescence, poor tissue penetration, and interference of autofluorescence background. Here, a bioresponsive near-infrared fluorescent probe is reported as facile and reliable tool for real-time cell tracking in vivo. The design of this probe relies on a new phenomenon observed upon fluorobenzene-conjugated fluorescent dyes, which can form complexes with cytosolic glutathione and actively translocates to lysosomes, exhibiting enhanced and stable cell labeling. Fluorobenzene-coupled hemicyanine, a near-infrared fluorophore manifests to efficiently staining tumor cells without affecting their invasive property and enables persistent monitoring of cell migration in metastatic tumor murine models at high resolution for one week. The method of fluorobenzene functionalization also provides a simple and universal "add-on" strategy to render ordinary fluorescent probes suitable for long-term live-cell tracking, for which currently there is a deficit of suitable molecular tools.

CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer.

Gambogic acid (GA) is a natural anti-tumor drug whose application is restricted by its poor aqueous solubility and inefficient bioavailability. Developing nanomaterials with excellent biocompatibility can amplify the therapeutic effects of GA. In this study, a tumor-targeted redox controllable self-assembled nano-system with magnetic enhanced EPR effects (mPEG-HA/CSO-SS-Hex/SPION/GA) was developed to improve the anticancer efficacy of GA. The nano-system is constituted by three layers: the outer layer is mono-aminated poly(ethylene glycol) grafted hyaluronic acid (mPEG-HA), which can target the CD44 receptor in breast cancer cells; the middle layer consists of disulfide linked hexadecanol (Hex) and chitosan oligosaccharide (CSO) to control the drug release by reduction response; the core layer is superparamagnetic iron oxide nanoparticles (SPION), which can enhance the EPR effect by magnetic guidance and contribute to GA entrapment. Different experiments were performed to characterize the complex self-assembly, and the cytotoxicity, pharmacokinetics, and in vivo antitumor activity of the self-assembly were investigated to evaluate its anti-tumor effects. The results revealed that mPEG-HA/CSO-SS-Hex/SPION/GA is an excellent nanosystem with appropriate size and sensitive responsiveness; it can accumulate in tumor sites and achieve excellent therapeutic effects on triple-negative breast cancer (TNBC). In summary, a CD44-targeted redox-triggered self-assembly nanosystem with magnetic enhanced EPR effects was developed for effective amplification of GA; it has potential to act as an effective carrier in drug delivery for chemotherapy of TNBC.

Mitochondrial membrane anchored photosensitive nano-device for lipid hydroperoxides burst and inducing ferroptosis to surmount therapy-resistant cancer.

Rationale: Ferroptosis is a regulated process of cell death caused by iron-dependent accumulation of lipid hydroperoxides (LPO). It is sensitive to epithelial-to-mesenchymal transition (EMT) cells, a well-known therapy-resistant state of cancer. Previous studies on nanomaterials did not investigate the immense value of ferroptosis therapy (FT) in epithelial cell carcinoma during EMT. Herein, we describe an EMT-specific nanodevice for a comprehensive FT strategy involving LPO burst. Methods: Mitochondrial membrane anchored oxidation/reduction response and Fenton-Reaction-Accelerable magnetic nanophotosensitizer complex self-assemblies loading sorafenib (CSO-SS-Cy7-Hex/SPION/Srfn) were constructed in this study for LPO produced to overcome the therapy-resistant state of cancer. Both in vitro and in vivo experiments were performed using breast cancer cells to investigate the anti-tumor efficacy of the complex self-assemblies. Results: The nano-device enriched the tumor sites by magnetic targeting of enhanced permeability and retention effects (EPR), which were disassembled by the redox response under high levels of ROS and GSH in FT cells. Superparamagnetic iron oxide nanoparticles (SPION) released Fe2+ and Fe3+ in the acidic environment of lysosomes, and the NIR photosensitizer Cy7-Hex anchored to the mitochondrial membrane, combined sorafenib (Srfn) leading to LPO burst, which was accumulated ~18-fold of treatment group in breast cancer cells. In vivo pharmacodynamic test results showed that this nanodevice with small particle size and high cytotoxicity increased Srfn circulation and shortened the period of epithelial cancer treatment. Conclusion: Ferroptosis therapy had a successful effect on EMT cells. These findings have great potential in the treatment of therapy-resistant epithelial cell carcinomas.

BHQ-Cyanine-Based "Off-On" Long-Circulating Assembly as a Ferroptosis Amplifier for Cancer Treatment: A Lipid-Peroxidation Burst Device.

Ferroptosis is an iron-dependent cell death caused by accumulation of lipid peroxidation (LPO), which is a new strategy for cancer treatment. Th current ferroptosis therapy nanodevices have low efficiency and side effects generally. Hence, we developed a Black Hole Quencher (BHQ)-based fluorescence "off-on" nanophotosensitizer complex assembly (CSO-BHQ-IR780-Hex/MIONPs/Sor). CSO-connected BHQ-IR780-Hex and -loaded magnetic iron oxide nanoparticles (MIONPs) and sorafenib (Sor) formed a very concise functionalized delivery system. CSO-BHQ-IR780-Hex disassembled by GSH attack and released IR780-Hex, MIONPs, and sorafenib. IR780-Hex anchored to the mitochondrial membrane, which would contribute to amplifying the efficiency of the photosensitizer. When NIR irradiation was given to CSO-BHQ-IR780-Hex/MIONPs/Sor-treated cells, iron supply increased, the xCT/GSH/GPX-4 system was triggered, and a lot of LPO burst. A malondialdehyde test showed that LPO in complex assembly-treated cells was explosive and increased about 18-fold compared to the control. The accumulation process of particles was monitored by an IR780-Hex photosensitizer, which showed an excellent tumor target ability by magnetic of nanodevice in vivo. Interestingly, the half-life of sorafenib in a nanodevice was increased about 26-fold compared to the control group. Importantly, the complex assembly effectively inhibits tumor growth in the breast tumor mouse model. This work would provide ideas in designing nanomedicines for the ferroptosis treatment of cancer.

Enhanced identification of the in vivo metabolites of Ecliptae Herba in rat plasma by integrating untargeted data-dependent MS2 and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan.

Detection and identification of the in vivo metabolites of traditional Chinese medicine by untargeted profiling strategies are often confronted with severe interference from complex endogenous substances. Here we developed an integral approach, by combining untargeted data-dependent MS2 (dd-MS2) of Q-Orbitrap mass spectrometry and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan (pMRM-IDA-EPI) of triple quadrupole-linear ion trap (QTRAP) mass spectrometry, aiming to detect and identify more extensive metabolites in bio-samples. Ecliptae Herba (EH) is a widely consumed medicinal herb with the effects of nourishing liver/kidney, but its metabolites in vivo have not been fully elucidated. Firstly, after UHPLC separation on an HSS T3 column, chemical fingerprinting of 70% ethanolic extract of EH was performed by untargeted dd-MS2 in negative ion mode. We could characterize 41 compounds from EH, and 24 were detectable in the plasma of rats (prototypes) after oral administration of EH extract (1 g/kg). Secondly, using echinocystic acid (triterpene), wedelolactone (coumarin), and apigenin (flavonoid) as the different parent templates, an MRM list containing 150 predicted ion-pairs was established to enhance MS2 scan by pMRM-IDA-EPI, which enabled the primary identification of up to 200 metabolites. The biotransformations mainly involve oxidation, hydrogenation, methylation, glucuronidation, sulfonation etc. Thirdly, the rat plasma samples obtained after oral administration of three pure compounds (echinocystic acid, wedelolactone and apigenin) were analyzed to verify the reliability of metabolites identification, and 11, 4, and 10 metabolites were found individually. This is the first comprehensive research on the metabolism of EH in vivo.

Improved druggability of gambogic acid using core-shell nanoparticles.

Gambogic acid (GA) is a natural antitumor drug candidate with advantages of broad-spectrum activity, low toxicity and multiple mechanisms. Its clinical application is hindered, however, by low aqueous solubility, instability and poor pharmacokinetic properties. In this research, core-shell hybrid nanoparticles have been developed to improve the druggability of GA. The nanoparticles are composed of a benzylamidated poly(γ-glutamic acid) (BzPGA) derivative as a core material and an amphiphilic hyaluronic acid derivative grafted with all-trans retinoic acid (HA-C6-ATRA) as a shell material. Through π-π stacking interactions, GA is encapsulated into BzPGA to form the "core" of the hybrid nanoparticle and the "shell" is formed by HA-C6-ATRA with a π-π stacking mediated "molecular fence". The nanovehicle, with sub 100 nm size, provides almost 100% encapsulation efficiency, a good protective effect and a sustained release profile for GA. A series of evaluations suggest that the core-shell nanoparticles provide a stable aqueous injection formulation (I), improved stability (II), prolonged circulation time and conferred tumor targeting properties (III) for GA. As a result, the anti-tumor activity of GA is significantly enhanced without causing higher toxicity, indicating that the designed nanoplatform dramatically improves the druggability of GA. This study may also provide inspiration for drug development research.

Tumor-specific activated photodynamic therapy with an oxidation-regulated strategy for enhancing anti-tumor efficacy.

Photodynamic therapy relies on photosensitizers to generate cytotoxic reactive oxygen species (ROS) resulting in the apoptois of tumor cells. However, there is an antioxidant system that impedes the elevation of oxidation levels in tumor cells. Thus, photodynamic therapy may exhibit insufficient curative effects due to ungenerous reactive oxygen species levels. Herein, we describe tumor-specific activated photodynamic therapy using an oxidation-regulating strategy. Methods: We first synthesised a reactive oxygen species-sensitive amphipathic prodrug of gambogic acid-grafted hyaluronic acid (HA-GA). The hydrophobic photosensitizer chlorin e6 (Ce6) was then loaded into HA-GA by hydrophobic interactions between GA and Ce6, forming amphipathic nanomicelles (HA-GA@Ce6). The ROS-responsive behavior, cytotoxicity, cell uptake, tumor cell killing, in vivo biodistribution and in vivo anti-tumor efficacy of HA-GA@Ce6 were investigated. The in vitro and in vivo experiments were performed on 4T1 murine breast cancer cells and 4T1 tumor model. Results: We validated that the micelles of HA-GA@Ce6 showed stronger cell uptake in 4T1 tumor cells and lower cytotoxicity in normal cells compared with free Ce6 and GA, which exhibited the benefits of nanomicelles on enhancing the tumor cell acumulation and reducing the side effects on normal cells synchronously. Additionally, the cytotoxic free radicals of photodynamic therapy were generated after irradiation and the high oxidation levels activated the ROS-sensitive GA prodrug efficiently, which killed the tumor cells and depleted intracellular glutathione (GSH), thereby impairing antioxidant levels and enhancing photodynamic therapy. Conclusion: With the successfully eradicated tumor growth in vivo. Our work represents a new photodynamic therapy concept, achieving superior anti-tumor efficacy by reducing intracellular antioxidant levels.

Reticuloendothelial System Pre-Block Strategy to Improve Tumor Targeting Efficacy for Hyaluronic Acid Related Drug Delivery System.

Hyaluronic acid (HA) is widely used in many tumor targeting drug delivery systems (TDDS) due to its biocompatibility and modifiability. Moreover, HA receptors are over-expressed on many tumor cells. However, the clearance of the HA-related TDDS by the reticuloendothelial system (RES) need urgent consideration on account of the high affinity between HA and related receptors in RES. A pre-block strategy before TDDS administration had been designed to overcome RES clearance. In order to avoid the rapid RES clearance and further improve tumor targeting efficiency for HA-related TDDS, we designed a novel strategy of selectively pre-blocking HA receptors in RES by injecting HA-coated blank liposome (pre-block formulation) prior to dosing of HA-related TDDS. The molecule weight and surface density of HA in pre-block formulation as well as TDDS, the time interval between dosing, and the concentration of pre-block formulation, were optimized by a series of in vitro cellular uptake studies in macrophages and 4T1 tumor cell lines, which was further confirmed by in vivo studies. The result shows that that the optimized pre-block formulation can saturate the RES, by which the RES clearance is weakened and the tumor targeting efficiency for HA-related TDDS is finally improved.

Multifunctional Hyaluronic Acid-Decorated Redox-Responsive Magnetic Complex Micelle for Targeted Drug Delivery with Enhanced Antitumor Efficiency and Anti-Cell-Migration Activity.

A novel multifunctional hyaluronic acid-decorated redox-responsive magnetic complex micelle (HA/CSO-SS-Hex/Fe3O4/PTX) based on a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and loaded with paclitaxel (PTX) Fe3O4 nanoparticles is developed. HA is coated onto the surface of micelles via electrostatic absorption and acts as a targeting ligand for CD44 over expression in many tumor cells. A CSO-SS-Hex polymer micelle was used for PTX incorporation and GSH-triggered intracellular release. The PTX in micelles was used to provide chemotherapy. Fe3O4 nanoparticles were used for magnetic targeting. The complex micelle showed enhanced antitumor efficiency and anti-cell-migration activity. The HA/CSO-SS-Hex/Fe3O4/PTX micelle was stable under physiological conditions, while it was sensitive to release the loaded drug in the presence of 10 mM glutathione (GSH). The complex micelle showed enhanced cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated internalization and redox-response drug release in tumor cells. Cell viability tests revealed that HA/CSO-SS-Hex/Fe3O4/PTX micelle displayed enhanced cytotoxicity against A549, B16F10 and HepG2 cell lines compared to non-targeted formulations of PTX. An anti-cell migration assay was also performed. The result showed that although there was no significant difference in the anti-cell migration activities between the HA/CSO-SS-Hex/Fe3O4/PTX micelle and free PTX, the activities of HA/CSO-SS-Hex/Fe3O4/PTX were stronger than non-targeted CSO-SS-Hex/Fe3O4/PTX micelles. Thus, the novel HA/CSO-SS-Hex/Fe3O4/PTX micelle is highly effective for targeted drug delivery and might have potential implications for the chemotherapy of primary tumors and their metastases.

Modeling and optimizing inhibitory activities of Nelumbinis folium extract on xanthine oxidase using response surface methodology.

Xanthine oxidase (XOD), which could oxidize hypoxanthine to xanthine and then to uric acid, is a key enzyme in the pathogenesis of hyperuricemia and also a well-known target for the drug development to treat gout. In our study, the total alkaloids of Nelumbinis folium markedly inhibited XOD activity, with IC50 value being 3.313µg/mL. UHPLC-Q-TOF-MS and 3D docking analysis indicated that roemerine was a potential active ingredient. A response surface methodology combined with central composite design experiment was further developed and validated for the optimization of the reaction conditions between the total alkaloids of Nelumbinis folium and XOD, which could be considered as a meaningful research for the development of XOD inhibitor rapidly and sensitively.

Rapid profiling and pharmacokinetic studies of major compounds in crude extract from Polygonum multiflorum by UHPLC-Q-TOF-MS and UPLC-MS/MS.

A reliable, rapid analytical method was established for characterization of constituents in the ethanol extract of Polygonum multiflorum by combining an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). 131 constituents which including phenolic acids, stilbenes, flavones, anthraquinones, naphthalenes and their derivatives were identified or tentatively identified by using characteristic diagnostic fragment ions and references. The established method was further applied to analyze blood samples, and successfully identified 41 compounds which were absorbed through the gastrointestine in rats after administration the extract of P. multiflorum. Moreover, the pharmacokinetic studies of some major compounds in blood were investigated by using ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method. This study showed a comprehensive research of P. multiflorum, which could provide a meaningful basis for further quality control, pharmacological as well as toxicological researches.

Analysis of the Constituents in "Zhu She Yong Xue Shuan Tong" by Ultra High Performance Liquid Chromatography with Quadrupole Time-of-Flight Mass Spectrometry Combined with Preparative High Performance Liquid Chromatography.

"Zhu She Yong Xue Shuan Tong" lyophilized powder (ZSYXST), consists of a series of saponins extracted from Panax notoginseng, which has been widely used in China for the treatment of strokes. In this study, an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) combined with preparative high performance liquid chromatography (PHPLC) method was developed to rapidly identify both major and minor saponins in ZSYXST. Some high content components were removed through PHPLC in order to increase the sensitivity of the trace saponins. Then, specific characteristic fragment ions in both positive and negative mode were utilized to determine the types of aglycone, saccharide, as well as the saccharide chain linkages. As a result, 94 saponins, including 20 pairs of isomers and ten new compounds, which could represent higher than 98% components in ZSYXST, were identified or tentatively identified in commercial ZSYXST samples.