Spatiotemporal analysis of microstructure, sensory attributes, and full-spectrum metabolomes reveals the relationship between bitterness and nootkatone in Alpinia oxyphylla miquel fruit peel and seeds.

The Alpinia oxyphylla fruit (AOF) is a popular condiment and traditional Chinese medicine in Asia, known for its neuroprotective compound nootkatone. However, there has not been a comprehensive study of its flavor or the relationship between sensory and bioactive compounds. To address this issue, we examined AOF's microstructure, flavor, and metabolomic profiles during fruit maturation. The key markers used to distinguish samples included fruit expansion, testa pigmentation, aril liquefaction, oil cell expansion, peel spiciness, aril sweetness, and seed bitterness. A full-spectrum metabolomic analysis, combining a nontargeted metabolomics approach for volatile compounds and a widely targeted metabolomics approach for nonvolatile compounds, identified 1,448 metabolites, including 1,410 differentially accumulated metabolites (DAMs). Notably, 31 DAMs, including nootkatone, were associated with spicy peel, sweet aril, and bitter seeds. Correlational analysis indicated that bitterness intensity is an easy-to-use biomarker for nootkatone content in seeds. KEGG enrichment analysis linked peel spiciness to phenylpropanoid and capsaicin biosynthesis, seed bitterness to terpenoid (especially nootkatone) biosynthesis, and aril sweetness to starch and sucrose metabolism. This investigation advances the understanding of AOF's complex flavor chemistry and underlying bioactive principle, encapsulating the essence of the adage: "no bitterness, no intelligence" within the realm of phytochemistry.

Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout.

This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.

An origami microfluidic paper device based on core-shell Cu@Cu2S@N-doped carbon hollow nanocubes.

BACKGROUD: The global prevalence of diabetes mellitus, a serious chronic disease with fatal consequences for millions annually, is of utmost concern. The development of efficient and simple devices for monitoring glucose levels is of utmost significance in managing diabetes. The advancement of nanotechnology has resulted in the indispensable utilization of advanced nanomaterials in high-performance glucose sensors. Modulating the morphology and intricate composition of transition metals represents a viable approach to exploit their structure/function correlation, thereby achieving optimal electrocatalytic performance of the synthesized catalysts. RESULTS: Herein, a sensitive and rapid Cu-encapsulated Cu2S@nitrogen-doped carbon (Cu@Cu2S@N-C) hollow nanocubes-functionalized microfluidic paper-based analytical device (µ-PAD) was fabricated. Through a delicate sacrificial template/interface technique and thermal decomposition, inter-connected hollow networks were formed to boost the active sites, and the carbon shell was coated to protect Cu from being oxidation. For application, the constructed µ-PAD is used for glucose sensing utilizing an origami automated sample pretreatment system enabled by a simple application of strong alkaline solution on wax paper. Under optimal circumstances, the Cu@Cu2S@N-C electrochemical biosensor exhibits broad detection range of 2-7500 µM (R2 = 0.996) with low detection limit of 0.16 µM (S/N = 3) and high sensitivity of 1996 µA mM-1 cm-2. Additionally, the constructed µ-PAD also exhibited excellent selectivity, stability, and reproducibility. SIGNIFICANCE: By rationally designing the double-shell hollow nanostructure and introducing Cu-encapsulated inner layer, the synthesized Cu@Cu2S@N-C hollow nanocubes show large specific surface area, short diffusion channels, and high stability. The proposed origami µ-PAD has been successfully applied to serum samples without any additional sample preparation steps for glucose determination, offering a new perspective for early nonenzymatic glucose diagnosis.

Neoadjuvant aumolertinib monotherapy for EGFR-mutant lung squamous cell carcinoma: a case report.

Background: Lung cancer is the malignant tumor with high incidence and mortality in China, and more than 30% of non-small cell lung cancer (NSCLC) patients are in the locally advanced stage at the first-time diagnosis. Currently, neoadjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combined with radical surgery is effective in the treatment of unresectable stage III EGFR-mutated NSCLC (NSCLCm), and related studies are gradually increasing. But the feasibility of neoadjuvant EGFR-TKI combined with radical surgery for unresectable stage III EGFR-mutant lung squamous cell carcinoma (LUSQm) remains controversial. Case Description: This report presented a successful case of neoadjuvant target-therapy with aumolertinib, the third-generation EGFR-TKI, combined with radical surgery for a stage IIIA LUSQm female patient. After four cycles (28 days/cycle) of neoadjuvant target-therapy, the tumor had a partial response on imaging evaluation and pathological evaluation after surgery showed complete tumor response. The neoadjuvant target-therapy was well tolerated. All adverse events (AEs) that occurred during the treatment were grade I, including decreased platelets, impaired liver function, and diarrhea. The patient was instructed to continue taking Aumolertinib for 3 years after surgery. At the cut-off date of April 1, 2024, the patient had no recurrence after 20 months of treatment. Conclusions: The result of patient treatment demonstrated the potential feasibility of neoadjuvant Aumolertinib monotherapy for locally advanced LUSQm. The report provides some support for neoadjuvant target-therapy for LUSQm.

Zinc Doping Engineering in ZnxFe3-xO4 Heterostructures for Enhancing Photodynamic Therapy in the Near-Infrared-II Region.

Currently, photodynamic therapy (PDT) is restricted by the laser penetration depth. Except for PDT at 1064 nm wavelength excitation, the development of other NIR-II-activated nanomaterials with a higher response depth is still hindered and rarely reported in the literature. To overcome these problems, we fabricated a nanoplatform with heterostructures that generate reactive oxygen species (ROS) and ferrite nanoparticles under a high concentration of zinc doping (ZnxFe3-xO4 NPs), which can achieve oxidative damage of tumor cells under near-infrared (NIR) illumination. The recombination of photoelectrons and holes has been markedly inhibited due to the formation of heterostructures in the interfaces, thus greatly enhancing the capability for ROS and oxygen production by modulating the single-component doping content. The efficiency of PDT was verified by in vivo and in vitro assays under NIR light. Our results revealed that NIR-II (1208 nm) light irradiation of ZnxFe3-xO4 NPs exerted a remarkable antitumor activity, superior to NIR-I light (808 nm). More importantly, the reported ZnxFe3-xO4 NPs strategy provides an opportunity for the success of comparison with light in the first and second near-infrared regions.

Dual-ligand lanthanide metal-organic framework based ratiometric fluorescent platform for visual monitoring of aminoglycoside residues in food samples.

Herein, a dual-emission Eu metal-organic framework (Eu-MOF) is prepared and used as the ratiometric fluorescence probe for ultrasensitive detection of aminoglycoside antibiotics (AGs). Due to the strong hydrogen bond interactions between AGs and Eu-MOF, the blue emission is enhanced while the red emission has little fluctuation in Eu-MOF with the addition of AGs, thus a good linear relationship with the logarithm of AGs concentrations from 0.001 to 100 µg/mL can be established for quantitative analysis. Good sensitivity with the detection limit of 0.33 ng/mL for apramycin, 0.32 ng/mL for amikacin and 0.30 ng/mL for kanamycin is achieved. The proposed assay demonstrates good selectivity and applicability for determination of AGs in real milk and honey samples. The Eu-MOF materials are further fabricated as fluorescent test papers for facile visual detection. The as-established ratio fluorescence platform offers a portable and economical way for rapid monitoring AGs residues in complex food samples.

ZnO-CeO2 Hollow Nanospheres for Selective Determination of Dopamine and Uric Acid.

ZnO-CeO2 hollow nanospheres have been successfully synthesized via the hard templating method, in which CeO2 is used as the support skeleton to avoid ZnO agglomeration. The synthesized ZnO-CeO2 hollow nanospheres possess a large electrochemically active area and high electron transfer owing to the high specific surface area and synergistic effect of ZnO and CeO2. Due to the above advantages, the resulting ZnO-CeO2 hollow spheres display high sensitivities of 1122.86 µA mM-1 cm-2 and 908.53 µA mM-1 cm-2 under a neutral environment for the selective detection of dopamine and uric acid. The constructed electrochemical sensor shows excellent selectivity, stability and recovery for the selective analysis of dopamine and uric acid in actual samples. This study provides a valuable strategy for the synthesis of ZnO-CeO2 hollow nanospheres via the hard templating method as electrocatalysts for the selective detection of dopamine and uric acid.

Physicochemical and digestive properties of corn starch nanoparticles incorporated different polyphenols.

The corn starch nanoparticles were prepared by incorporating three kinds of polyphenols, including quercetin, proanthocyanidins and tannin acid. The physicochemical and digestive properties of corn starch nanoparticles were researched. The quercetin showed a higher complexation index than proanthocyanidins and tannin acid when they complexed with corn starch. The mean size of corn starch quercetin, proanthocyanidins and tannin acid were 168.5 nm, 179.1 nm and 188.6 nm, respectively. XRD results indicated that all the corn starch-polyphenols complex showed V-type crystalline structure, the crystallinity of corn starch-quercetin complex was 19.31 %, which showed more formation of amylose-quercetin single helical formed than the other two starch-polyphenol complexes. In vitro digestion revealed that polyphenols could resist digestion and quercetin increased the content of resistant starch from 23.32 % to 35.24 % and polyphenols can form complexes with starch through hydrophobic interactions or hydrogen bonding. This study indicated the hydrophobic polyphenols had a more significant effect on the digestibility of corn starch. And the cell toxicity assessments demonstrated that all nanoparticles were nontoxic and biocompatible.

A paper-based ratiometric fluorescence sensor based on carbon dots modified with Eu3+ for the selective detection of tetracycline in seafood aquaculture water.

Paper-based ratiometric fluorescence sensors are normally prepared using two or more types of fluorescent materials on a paper chip for simple, low-cost and fast detection. However, the choice of multi-step and one-step modifications on the paper chip affects the analytical performance. Herein, a novel paper-based dual-emission ratiometric fluorescence sensor was designed for the selective detection of tetracycline (TC). Carbon dots (CDs) modified with Eu3+ were combined with a sealed paper-based microfluidic chip by two methods: one-step grafting of CDs-Eu3+ on paper and step-by-step grafting of CDs and Eu3+ on paper. The analytical performance was studied and optimized respectively. The red fluorescence of Eu3+ at 450 nm is enhanced and the blue fluorescence of CDs at 617 nm is quenched by energy transfer in the presence of TC. Under optimal conditions, TC is selectively determined in the linear range from 0.1 µM to 100 µM with a detection limit of 0.03 µM by the step-by-step grafting method. In addition, the sealed paper chip could effectively prevent pollution and volatilization from the reagent. This technique has been used to analyze TC in seafood aquaculture water with satisfactory results.

Metabolomic profiling and antidiabetic activity of Callerya speciosa.

Callerya speciosa is a perennial edible and medicinal plant belonging to the family Fabaceae. This study was to reveal the similarities and differences between phytochemicals in different parts of C. speciosa using a combination of ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). In addition, the anti-diabetic activity of C. speciosa extracts was explored. A total of 141 compounds were identified and 34 robustly known chemical markers were marked. PCA and heat map analyses revealed that the stems, leaves and pods had similar phytochemical compounds, while compounds in roots and flowers differed from each other and from those in the above ground parts. In addition, extracts of C. speciosa roots and flowers exhibited anti-diabetic activity, which can be applied to the development of anti-diabetic drugs.

Preparation of starch-palmitic acid complex nanoparticles and their effect on properties of the starch composite film.

The corn starch-palmitic acid complex nanoparticles and amylose-palmitic acid complex nanoparticles were prepared through complex and nanoprecipitation. Their mean size values were 138.2 nm and 654.7 nm, respectively, while the two kinds of complex nanoparticles were mainly showed V-type crystalline structure, the crystallinity of these complex nanoparticles was 20.86 % and 46.81 %. Then the starch composite films were prepared using the corn starch-palmitic acid complex nanoparticles and amylose-palmitic acid complex nanoparticles as reinforcement phases. The starch composite film reinforced with amylose-palmitic acid complex nanoparticles had the higher tensile strength and a better wettability with the water contact angle of 86.51°. Though the crystalline properties of starch composite films had no significant difference, the thermal stability improved when the amylose-palmitic acid complex nanoparticles used as reinforcement phase, the maximum thermal degradation temperature was 313 °C. This study provides a new type of reinforcement phase to improve the properties of starch composite films.

Colorimetric and visual sensing of ferrous ion by Fenton reaction-stimulated etching of triangular gold nanoplates.

In this study, a method for ultrasensitive sensing of Fe2+ based on Fenton reaction mediated etching of triangular gold nanoplates (Au NPLs) was developed. In this assay, the etching of Au NPLs by H2O2 was accelerated in the presence of Fe2+ due to the generation of superoxide free radical (O2·-) via Fenton reaction. With the concentration of Fe2+ increased, the shape of Au NPLs changed from triangular to sphere with the blue shifted localized surface plasmon resonance, accompanying a series of consecutive color changes from blue, bluish purple, purple, reddish purple and finally to pink. The rich color variations enable rapid visual quantitative determination of Fe2+ within 10 min. A good linear relationship between the peak shifts and the concentration of Fe2+ was obtained in the range of 0.035 to 1.5 µM (R2 = 0.996). Favorable sensitivity and selectivity in the presence of other tested metal ions were achieved in the proposed colorimetric assay. The detection limits (3Æ¡/k) for Fe2+ was 26 nM by UV-vis spectroscopy, and the clearly discernible concentration of Fe2+ was as low as 0.07 µM by naked eyes. The recoveries of fortified samples in pond water and serum samples ranged from 96% to 106% with interday relative standard deviations <3.6% in all cases, demonstrating the applicability of the assay for measuring Fe2+ in real samples.

A sensitive fluorescence nanoplatform for monitoring benzoyl peroxide in food using carbon dots coupled with glutathione capped gold nanoparticles as FRET probe.

Herein, a sensitive fluorescence nanoplatform for benzoyl peroxide (BPO) detection is constructed from carbon dots (CDs) and glutathione capped gold nanoparticles (GSH-AuNPs). The fluorescence of CDs is first quenched due to the fluorescence resonance energy transfer (FRET) effect in the presence of GSH-AuNPs, and then effectively recovered when adding BPO. The detection mechanism lies in the aggregation of AuNPs in a high salt background due to oxidation of GSH caused by BPO, thus the amount of BPO is reflected by the variations of the recovered signals. The linear range and detection limit in this detection system is found to be 0.05-200 µM (R2 = 0.994) and 0.1 µg g-1 (3σ/K), respectively. Several possible interferents with high concentration show little influence on BPO detection. The proposed assay exhibits good performance for BPO determination in wheat flour and noodles, demonstrating its applicability for facile monitoring BPO additive amount in real foods.

Effectiveness of precise and quantitative rapid pulmonary rehabilitation nursing program for elderly patients with lung cancer during the perioperative period: A randomized controlled trial.

Objective: Preoperative rehabilitation should improve the functional condition of patients. Improvements in metabolism, lung mechanics, cardiovascular function, and muscle-function can be achieved by pulmonary rehabilitation. Hence, we focused on elderly patients with lung cancer undergoing surgery, and assessed the effectiveness of a rapid and precise pulmonary rehabilitation nursing program during the perioperative period. Methods: This randomized controlled trial at the department of thoracic surgery; Shanghai pulmonary hospital, China during 2021 was conducted amongst 218 elderly patients with lung cancer treated by surgical operation into either a precision quantitative nursing model nursing group (experimental group) or a perioperative routine nursing group (control group). After individual planning of the pulmonary rehabilitation nursing outpatient clinic, nurses distributed breathing trainers, instructed the patients in breathing training, and supervised the patients after the operation. For our evaluation we considered pulmonary function tests, postoperative thoracic drainage tube indwelling times, postoperative hospital stays, postoperative complication rates, and postoperative quality of life results. Result: The experimental group showed better pulmonary function, length of hospital stay, and quality of life outcomes than the control group, but the differences were not statistically significant. However, we found a significantly higher postoperative complications rate in the control group (11.9%) than in the experimental group (3.7%; p=0.02). Conclusion: Strengthening pulmonary rehabilitation nursing interventions for elderly patients with lung cancer during the perioperative period can reduce their postoperative complications and promote their rapid recovery. Clinical Trial: Registration Number - ChiCTR2100042916.].

Mn3O4/NiO Nanoparticles Decorated on Carbon Nanofibers as an Enzyme-Free Electrochemical Sensor for Glucose Detection.

Transition metal oxides have garnered a lot of attention in the field of electrocatalysis along with their unique crystal structure and excellent catalytic properties. In this study, carbon nanofibers (CNFs) decorated with Mn3O4/NiO nanoparticles were made using electrospinning and calcination. The conductive network constructed by CNFs not only facilitates electron transport, but also provides landing sites for nanoparticles, thus reducing nanoparticle aggregation and exposing more active sites. Additionally, the synergistic interaction between Mn3O4 and NiO improved electrocatalytic capacity for glucose oxidation. The Mn3O4/NiO/CNFs modified glassy carbon electrode shows satisfactory results in terms of linear range and anti-interference capability for glucose detection, suggesting that the constructed enzyme-free sensor has a promising application in clinical diagnosis.

Coaxial electrospinning synthesis of size-tunable CuO/NiO hollow heterostructured nanofibers: Towards detection of glucose level in human serum.

Nanofibers (NFs) have found wide applications by virtue of their particular morphology and high specific surface area. In this study, size-tunable hollow CuO/NiO NFs were synthesized by coaxial electrospinning and subsequent calcination. The synthesized hollow CuO/NiO NFs owned large specific surface area for catalytic active sites. In addition, the formation of heterostructure interface between CuO and NiO was beneficial to improve the electrocatalytic performance. As non-enzymatic electrode material, the synthesized CuO/NiO NFs exhibited superior electrocatalytic capability for glucose oxidation. When the molar ratio of CuO to NiO is 0.4, the composite NFs achieved the optimal electrocatalytic ability for glucose oxidation, performing high sensitivity of 1324.17 µA mM-1 cm-2 and wide liner range from 1 to 10,000 µM. The constructed electrode has been utilized to detect glucose concentration in real serum with excellent recovery, indicating that CuO/NiO hollow heterostructured NFs are promising materials for biomedical applications.

A sandwich-type electrochemical immunosensor based on spherical nucleic acids-templated Ag nanoclusters for ultrasensitive detection of tumor biomarker.

The accurate determination of tumor biomarkers in blood is of vital significance in the diagnosis and therapy of tumor disease. In this research, an innovative sandwich-type electrochemical immunosensor is designed for the ultrasensitive determination of tumor biomarker AFP using spherical nucleic acids-templated silver nanoclusters (AgNCs) sensing platform. For this purpose, on one hand, DNA functionalized gold nanoparticles (AuNPs@DNA) is selected not only as the cross-linker to immobilize the primary antibody (anti-AFP antibody 1, Ab1) to obtain AuNPs@DNA-Ab1, but also as the template for synthesizing AgNCs on AuNPs to form AuNPs@DNA-AgNCs. On the other hand, p-sulfonated calix[4]arene (pSC4) modified Au is chosen to immobilize the secondary antibody (anti-AFP antibody 2, Ab2) through host-guest recognition between Ab2 and pSC4. When AFP is encountered, the immunoreaction signal can be significantly amplified by the electrochemical reduction of AgNCs. Under optimal circumstances, the sandwich-type electrochemical immunosensor exhibits broad limit of linearity from 0.001 to 100 ng mL-1 (R2 = 0.997) and low detection limit of 7.74 fg mL-1 (S/N = 3). The immunosensor possesses excellent repeatability and selectivity, offering a novel method for sensitive clinical diagnosis of tumor markers in human hepatocellular carcinoma.

Lanthanum ions assisted non-enzymatic ratiometric fluorescence probe for monitoring fenthion residues in agro-product samples.

In this work, a La3+ assisted glutathione-capped gold nanoclusters and carbon dots (GSH-Au NCs/CDs) nanoplatform for sensitive detection of fenthion (FEN) is fabricated. The fluorescence response of GSH-Au NCs significantly increases due to aggregation-induced emission enhancement (AIEE) effect induced by La3+, which is further enhanced with adding FEN due to the coordination between La3+ and FEN. Taking the fluorescence intensity of CDs as the signal background, the ratiometric fluorescence of GSH-Au NCs and CDs has a good linear relationship with the FEN concentration from 0.01 to 1.10 µg mL-1, and detecting FEN exhibits a good sensitivity at a low detection limit of 6.74 ng g-1. The La3+ assisted GSH-Au NCs/CDs nanoplatform demonstrates desirable selectivity and applicability for monitoring trace level of FEN in fruit and vegetable samples. The non-enzymatic strategy by taking advantage of successive AIEE of GSH-Au NCs has a great potential for facile screening organophosphate pesticides in agro-products.

Characterization and antibacterial activity study of α-Lactalbumin-carvacrol complex.

Food contamination and poisoning caused by bacteria will endanger human health, and the development of natural antibacterial agents is a pressing issue. We prepared ALA-Car complex and demonstrated its formation by multi-spectroscopy techniques and localized surface plasmon resonance experiments. Computer simulations have shown that van der Waals forces dominate the interaction between ALA and Car. The minimum inhibitory concentration (MIC) of Car toward Gram-negative Escherichia coli was decreased from 336 µg/mL to 224 µg/mL after binding to ALA. It had little effect on the MIC of Gram-positive Staphylococcus aureus (224 µg/mL), but further proved Car had a weaker antibacterial activity than the ALA-Car complex by the spread plate method. Overall, this work demonstrated that the ALA-Car complex had significantly higher antibacterial activities than Car, further advancing the development of natural antibacterial agents.

Novel triterpenoids from Alisma plantago-aquatica with influence on LDL uptake in HepG2 cells by inhibiting PCSK9.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been regarded as an effective and exciting target in the treatment of atherosclerotic cardiovascular disease since 2003. Only two monoclonal antibodies have been approved in the market which, however, were also criticized for their high cost to $9000 per dose and delivery route. Exploration of natural new effective and cheaper small molecule alternatives with effective PCSK9 inhibition is feasible and desired. PURPOSE: The aim of the study was to explore natural small molecules with anti-hyperlipidemia activity through PCSK9 from Alisma plantago-aquatica. METHOD: A targeted isolation of triterpenoids from A. plantago-aquatica by LC-Orbitrap-QDa was conducted. The isolates were evaluated for their DiI-LDL uptake promoting activity with fluorescence intensity assayed in High-content Imaging System and PCSK9 inhibitory activity by Human PCSK9 Kit or western blot. The LDL uptake and PCSK9 level of target component in different concentrations and their mRNA level were further verified by corresponding kit, qPCR and western blot. RESULTS: Six novel triterpenoids, including three unusual nor-triterpenoids (1-3) and three protostane-type triterpenoids (4-6), along with thirty-four known ones, were isolated from A. plantago-aquatica. Compound 2 had the lowest number of carbon atoms than previous reported nor-PTs in this plant. The 17 triterpenoids showed relatively remarkable activities in promoting LDL uptake with relevant structure-activity relationships. And 6 triterpenoids may improve LDL uptake in HepG2 cells by inhibiting PCSK9, especially for alisol G (28) with PCSK9 inhibition reaching to 55.6%, which demonstrated to increase LDLR mRNA or protein, and simultaneously reduce PCSK9 mRNA or protein significantly. CONCLUSION: The protostane triterpenoids may serve as a new source for PCSK9 inhibitors.