Biochemical characterization of a novel glucose-tolerant GH3 ß-glucosidase (Bgl1973) from Leifsonia sp. ZF2019.

Beta-glucosidase (Bgl) is an enzyme with considerable food, beverage, and biofuel processing potential. However, as many Bgls are inhibited by their reaction end product glucose, their industrial applications are greatly limited. In this study, a novel Bgl gene (Bgl1973) was cloned from Leifsonia sp. ZF2019 and heterologously expressed in E. coli. Sequence analysis and structure modeling revealed that Bgl1973 was 748 aa, giving it a molecular weight of 78 kDa, and it showed high similarity with the glycoside hydrolase 3 (GH3) family Bgls with which its active site residues were conserved. By using pNPGlc (p-nitrophenyl-ß-D-glucopyranoside) as substrate, the optimum temperature and pH of Bgl1973 were shown to be 50 °C and 7.0, respectively. Bgl1973 was insensitive to most metal ions (12.5 mM), 1% urea, and even 0.1% Tween-80. This enzyme maintained 60% of its original activity in the presence of 20% NaCl, demonstrating its excellent salt tolerance. Furthermore, it still had 83% residual activity in 1 M of glucose, displaying its outstanding glucose tolerance. The Km, Vmax, and kcat of Bgl1973 were 0.22 mM, 44.44 µmol/min mg, and 57.78 s-1, respectively. Bgl1973 had a high specific activity for pNPGlc (19.10 ± 0.59 U/mg) and salicin (20.43 ± 0.92 U/mg). Furthermore, molecular docking indicated that the glucose binding location and the narrow and deep active channel geometry might contribute to the glucose tolerance of Bgl1973. Our results lay a foundation for the studying of this glucose-tolerant ß-glucosidase and its applications in many industrial settings. KEY POINTS: • A novel ß-glucosidase from GH3 was obtained from Leifsonia sp. ZF2019. • Bgl1973 demonstrated excellent glucose tolerance. • The glucose tolerance of Bgl1973 was explained using molecular docking analysis.

Lockdown effects on total suspended solids concentrations in the Lower Min River (China) during COVID-19 using time-series remote sensing images.

The COVID-19 pandemic in China in the winter-spring of 2019-2020 has decreased and even stopped many human activities. This study investigates whether there were any changes in the water quality of the Lower Min River (China) during the lockdown period. The time-series remote sensing images from November 2019 to April 2020 was used to examine the dynamics of the river's total suspended solids (TSS) concentrations in the period. A new remote sensing-based prototype was developed to recalibrate an existing algorithm for retrieving TSS concentrations in the river. The Nechad and the Novoa algorithms were used to validate the recalibrated algorithm. The results show that the recalibrated algorithm is highly consistent with the two algorithms. All of the three algorithms indicate significant fluctuation in TSS concentrations in the Lower Min River during the study period. February (COVID-19 lockdown period) has witnessed a 48% fall in TSS concentration. The TSS in March-April showed a progressive and recovery back to normal levels of pre-COVID-19. The spatiotemporal change of TSS has worked as a good indicator of human activities, which revealed that the decline of TSS in the lockdown period was due largely to the substantially-reduced discharges from industrial estates, densely-populated city center, and river's shipping. Remote sensing monitoring of the spatiotemporal changes of TSS helps understand important contributors to the water-quality changes in the river and the impacts of anthropogenic activities on river systems.

Distinct roles of Deinococcus radiodurans RecFOR and RecA in DNA transformation.

RecFOR and RecA are key recombination factors in Deinococcus radiodurans, a bacterium that possesses robust DNA repair capability and is also naturally transformable. While RecFOR functioning as a RecA loader during DNA repair has been established, their relative roles in transformation need further exploration. Here, we constructed recFOR and recA deletion mutants of D. radiodurans, and investigated the effect of these mutations on DNA transformation. recA deletion causes defects in both plasmid and chromosomal transformation. However, it was found that recFOR is not involved in chromosomal transformation, and that only recO and recR mutations compromise plasmid transformation. How recO, recR and recA mutations influence plasmid transformation was further examined by complementation plasmids. Interestingly, the transformation process remains defective in the recA mutant, but gets restored in the recO and recR mutants. This indicates that unlike RecA, RecOR may not be essential for DNA uptake. Therefore, we provide evidence that RecFOR is dispensable for RecA to protect incoming exogenous DNA and to catalyze recombination during transformation. Instead, RecO and RecR are likely to promote later steps in plasmid transformation.

Deinococcus radiodurans DR1088 is a novel RecF-interacting protein that stimulates single-stranded DNA annealing.

RecF, together with the recombination mediators RecO and RecR, is required in the RecFOR homologous recombination repair pathway in bacteria. In this study, a recF-dr1088 operon, which is highly conserved in the Deinococcus-Thermus phylum, was identified in Deinococcus radiodurans. Interaction between DRRecF and DR1088 was confirmed by yeast two-hybrid and pull-down assays. DR1088 exhibited some RecO-like biochemical properties including single/double-stranded DNA binding activity, ssDNA binding protein (SSB) replacement ability and ssDNA (with or without SSB) annealing activity. However, unlike other recombination proteins, dr1088 is essential for cell viability. These results indicate that DR1088 might play a role in DNA replication and DNA repair processes.

Biochemical and Functional Characterization of the NurA-HerA Complex from Deinococcus radiodurans.

UNLABELLED: In archaea, the NurA nuclease and HerA ATPase/helicase, together with the Mre11-Rad50 complex, function in 3' single-stranded DNA (ssDNA) end processing during homologous recombination (HR). However, bacterial homologs of NurA and HerA have not been characterized. From Deinococcus radiodurans, we identified the manganese-dependent 5'-to-3' ssDNA/double-stranded DNA (dsDNA) exonuclease/endonuclease NurA (DrNurA) and the ATPase HerA (DrHerA). These two proteins stimulated each other's activity through direct protein-protein interactions. The N-terminal HAS domain of DrHerA was the key domain for this interaction. Several critical residues of DrNurA and DrHerA were verified by site-directed mutational analysis. Temperature-dependent activity assays confirmed that the two proteins had mesophilic features, with optimum activity temperatures 10 °C to 15 °C higher than their optimum growth temperatures. Knocking out either nurA or herA affected cell proliferation by shortening the growth phase, especially for growth at a high temperature (37 °C). In addition, both mutant strains displayed almost 10-fold-reduced intermolecular recombination efficiency, indicating that DrNurA and DrHerA might be involved in homologous recombination in vivo. However, single- and double-gene deletions did not show significantly decreased radioresistance. Our results confirmed that the biochemical activities of bacterial NurA and HerA proteins were conserved with archaea. Our phenotypical results suggested that these proteins might have different functions in bacteria. IMPORTANCE: Deinococcus radiodurans NurA (DrNurA) was identified as a manganese-dependent 5'-to-3' ssDNA/dsDNA exonuclease/endonuclease, and Deinococcus radiodurans HerA (DrHerA) was identified as an ATPase. Physical interactions between DrNurA and DrHerA explained mutual stimulation of their activities. The N-terminal HAS domain on DrHerA was identified as the interaction domain. Several essential functional sites on DrNurA and DrHerA were characterized. Both DrHerA and DrNurA showed mesophilic biochemical features, with their optimum activity temperatures 10 °C to 15 °C higher than their optimum growth temperatures in vitro. Knockout of nurA or herA led to abnormal cell proliferation and reduced intermolecular recombination efficiency but no obvious effect on radioresistence.

A newly identified G-quadruplex as a potential target regulating Bcl-2 expression.

BACKGROUND: A new G-quadruplex structure located in the B-cell CLL/lymphoma 2 (Bcl-2) P1 promoter and its physiological function related to Bcl-2 transcription have been studied to find a potential anticancer therapeutic target. METHODS: Absorption, polyacrylamide gel electrophoresis, fluorescence, circular dichroism, and nuclear magnetic resonance spectra have been employed to determine G-quadruplex structure and the interaction between G-quadruplex and phenanthrolin-dicarboxylate. Real time polymerase chain reaction and luciferase assay were done to assess the physiological function of the G-quadruplex structure. RESULTS: The UV-melting and polyacrylamide gel electrophoresis studies show that the p32 DNA sequence forms an intramolecular G-quadruplex structure. Circular dichroism and nuclear magnetic resonance spectra indicate that the G-quadruplex is a hybrid-type structure with four G-tetrads. Fluorescence spectra show that a phenanthroline derivative has a higher binding affinity for p32 G-quadruplex than duplex. Further circular dichroism and nuclear magnetic resonance studies indicate that the phenanthroline derivative can regulate p32 G-quadruplex conformation. Real time polymerase chain reaction and luciferase assays show that the phenanthroline derivative has down-modulated Bcl-2 transcription activity in a concentration-dependent manner. However, no such effect was observed when p32 G-quadruplex was denatured through base mutation. CONCLUSION: The newly identified G-quadruplex located in the P1 promoter of Bcl-2 oncogene is intimately related with Bcl-2 transcription activity, which may be a promising anticancer therapeutic target. GENERAL SIGNIFICANCE: The newly identified G-quadruplex in the Bcl-2 P1 promoter may be a novel anticancer therapeutic target.

A colorimetric and fluorometric dual-modal supramolecular chemosensor and its application for HSA detection.

A colorimetric and fluorometric dual-modal supramolecular chemosensor has been fabricated by using the H- and J-aggregates of a cyanine dye, which has been successfully applied to detect human serum albumin (HSA) in urine with high specificity.

The key residue for SSB-RecO interaction is dispensable for Deinococcus radiodurans DNA repair in vivo.

The RecFOR DNA repair pathway is one of the major RecA-dependent recombinatorial repair pathways in bacteria and plays an important role in double-strand breaks repair. RecO, one of the major recombination mediator proteins in the RecFOR pathway, has been shown to assist RecA loading onto single-stranded binding protein (SSB) coated single-stranded DNA (ssDNA). However, it has not been characterized whether the protein-protein interaction between RecO and SSB contributes to that process in vivo. Here, we identified the residue arginine-121 of Deinococcus radiodurans RecO (drRecO-R121) as the key residue for RecO-SSB interaction. The substitution of drRecO-R121 with alanine greatly abolished the binding of RecO to SSB but not the binding to RecR. Meanwhile, SSB-coated ssDNA annealing activity was also compromised by the mutation of the residue of drRecO. However, the drRecO-R121A strain showed only modest sensitivity to DNA damaging agents. Taking these data together, arginine-121 of drRecO is the key residue for SSB-RecO interaction, which may not play a vital role in the SSB displacement and RecA loading process of RecFOR DNA repair pathway in vivo.

Mesenchymal Stem Cell-Derived Exosomal miR-150-3p Affects Intracerebral Hemorrhage By Regulating TRAF6/NF-κB Axis, Gut Microbiota and Metabolism.

Intracerebral hemorrhage (ICH) is a severe subtype of stroke for which there is no effective treatment. Stem cell and exosome (Exo) therapies have great potential as new approaches for neuroprotection and neurorestoration in treating ICH. We aimed to investigate whether Exo affects ICH by regulating the ecology of gut microbiota and metabolism and the mechanisms involved. First, differential miRNAs in ICH were screened by bioinformatics and verified by qRT-PCR. Then, Exo was extracted from mouse bone marrow mesenchymal stem cells (MSCs) and identified. Dual-luciferase reporter gene assay was utilized to verify the binding relationship between miR-150-3p and TRAF6. A mouse ICH model was constructed and treated with Exo. Next, we knocked down miR-150-3p and performed fecal microbiota transplantation (FMT). Then changes in gut microbiota and differential metabolites were detected by 16S rRNA sequencing and metabolomics analysis. We found that miR-150-3p expression was lowest in the brain tissue of the ICH group compared to the Sham group. Besides, low miR-150-3p level in ICH was encapsulated by MSC-derived Exo. Moreover, miR-150-3p bound to TRAF6 and was negatively correlated. With the addition of ExomiR-150-3p inhibitor, we found that MSC-derived exosomal miR-150-3p may affect ICH injury via TRAF6/NLRP3 axis. MSC-derived exosomal miR-150-3p caused changes in gut microbiota, including Proteobacteria, Muribaculaceae, Lachnospiraceae_NK4A136_group, and Acinetobacter. Moreover, MSC-derived exosomal miR-150-3p caused changes in metabolism. After further FMT, gut microbiota-mediated MSC-derived Exo affected ICH with reduced apoptosis and reduced levels of inflammatory factors. In conclusion, MSC-derived exosomal miR-150-3p affected ICH by regulating TRAF6/NF-κB axis, gut microbiota and metabolism.

Investigation of isoflavone constituents from tuber of Apios americana Medik and its protective effect against oxidative damage on RIN-m5F cells.

In our previous study, AI-3, a mixture of isoflavones, was obtained from Apios Americana Medik tuber and showed strong protective ability on oxidative damaged RIN-m5F cells. This study aimed to identify the main compounds of AI-3 and elucidate their activities and underlying mechanism. In results, eleven compounds were purified from AI-3. Among them, Compound 8 (2'-Hydroxy, 5-methoxy genistein-7-O-glucoside, HMG) was the most effective compound against H2O2-induced injury in RIN-m5F cells (stronger than positive control α-LA). Further RNA-seq analysis found that compared with H2O2 group, 388 differentially expressed genes (DEGs) were identified in HMG group. The enrichment analyses revealed fluid shear stress and atherosclerosis pathway and hepatocellular carcinoma pathway enriched the most DEGs, in which HOX-1, GST, NQO1, SQSTM, TrxR1 were significantly up-regulated. The finding indicated Keap1-Nrf2-ARE signaling pathway may play essential role in the protective effect of HMG on oxidative damaged RIN-m5F cells.

Determination of oxidative deterioration in edible oils by high-pressure photoionization time-of-flight mass spectrometry.

Since lipid oxidation often causes serious food safety issues worldwide, determination of oil's oxidative deterioration becomes quite significant, which still calls for efficient analytical methods. In this work, high-pressure photoionization time-of-flight mass spectrometry (HPPI-TOFMS) was firstly introduced for rapid detection of oxidative deterioration in edible oils. Through non-targeted qualitative analysis, oxidized oils with various oxidation levels were successfully discriminated for the first time by coupling HPPI-TOFMS with the orthogonal partial least squares discriminant analysis (OPLS-DA). Furthermore, by targeted interpretation of the HPPI-TOFMS mass spectra and the subsequent regression analysis (signal intensities vs TOTOX values), good linear correlations were observed for several predominant VOCs. Those specific VOCs were promising oxidation indicators, which would play important roles as TOTOX to judge the oxidation states of tested samples. The proposed HPPI-TOFMS methodology can be used as an innovative tool for accurate and effective assessment of lipid oxidation in edible oils.

Extreme atmospheric rivers in a warming climate.

Extreme atmospheric rivers (EARs) are responsible for most of the severe precipitation and disastrous flooding along the coastal regions in midlatitudes. However, the current non-eddy-resolving climate models severely underestimate (~50%) EARs, casting significant uncertainties on their future projections. Here, using an unprecedented set of eddy-resolving high-resolution simulations from the Community Earth System Model simulations, we show that the models' ability of simulating EARs is significantly improved (despite a slight overestimate of ~10%) and the EARs are projected to increase almost linearly with temperature warming. Under the Representative Concentration Pathway 8.5 warming scenario, there will be a global doubling or more of the occurrence, integrated water vapor transport and precipitation associated with EARs, and a more concentrated tripling for the landfalling EARs, by the end of the 21st century. We further demonstrate that the coupling relationship between EARs and storms will be reduced in a warming climate, potentially influencing the predictability of future EARs.

Integrative multi-omics analysis depicts the methylome and hydroxymethylome in recurrent bladder cancers and identifies biomarkers for predicting PD-L1 expression.

BACKGROUND: Urinary bladder cancer (UBC) is a common malignancy of the urinary tract; however, the mechanism underlying its high recurrence and responses to immunotherapy remains unclear, making clinical outcome predictions difficult. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly being investigated as biomarkers for diagnostic or prognostic predictions. However, little is known about hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results. METHODS: Tissue samples of bladder cancer patients who underwent laparoscopic radical cystectomy (LRC), partial cystectomy (PC), or transurethral resection of bladder tumor (TURBT) were collected. We utilized a multi-omics approach to analyze both primary and recurrent bladder cancer samples. By integrating various techniques including RNA sequencing, oxidative reduced-representation bisulfite sequencing (oxRRBS), reduced-representation bisulfite sequencing (RRBS), and whole exome sequencing, a comprehensive analysis of the genome, transcriptome, methylome, and hydroxymethylome landscape of these cancers was possible. RESULTS: By whole exome sequencing, we identified driver mutations involved in the development of UBC, including those in FGFR3, KDMTA, and KDMT2C. However, few of these driver mutations were associated with the down-regulation of programmed death-ligand 1 (PD-L1) or recurrence in UBC. By integrating RRBS and oxRRBS data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a series of 5mC hypo differentially methylated regions (DMRs) in the gene body of NFATC1, which is highly involved in T-cell immune responses in bladder cancer samples with high expression of PD-L1. Since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq-based markers that combine the 5mC and 5hmC signals, attenuate cancer-related signals, and therefore, are not optimal as clinical biomarkers. CONCLUSIONS: By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved compared to genetic mutations in the PD-L1 regulation and recurrence of UBC. As proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC levels by the bisulfite-based method compromises the prediction accuracy of epigenetic biomarkers.

Recognize three different human telomeric G-quadruplex conformations by quinacrine.

Recognition of different human telomeric G-quadruplex structures has been a very important task for developing anti-cancer drug design. However, it also is a very challenging question since multiple conformational isomers of telomeric G-quadruplexes coexist under some conditions. Here, three different conformations including parallel, antiparallel, and mixed-type telomeric G-quadruplex structures have been well recognized by quinacrine (QNA) through monitoring its absorption, fluorescence, and fluorescence lifetime spectra. The multiple structures of H22 G-quadruplexes under physiological K(+) conditions could also be easily determined to coexist as mixed-type and antiparallel G-quadruplexes. The recognition mechanism based on the different binding affinity and binding sites has been further elucidated by association with the nuclear magnetic resonance (NMR) results.

Visual detection of potassium by a cyanine dye supramolecular aggregate responsive to G-quadruplex motif transition.

A supramolecular probe is designed for visual detection of potassium based on a novel cyanine dye aggregate recognizing the motif transition of telomeric G-quadruplexes under the Na(+) background. The practical application for colorimetric measurement of urine potassium has been tested.

Verification of specific G-quadruplex structure by using a novel cyanine dye supramolecular assembly: II. The binding characterization with specific intramolecular G-quadruplex and the recognizing mechanism.

The supramolecular assembly of a novel cyanine dye, 3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-ethyl-thiacarbocyanine triethylammonium salt (ETC) was designed to verify specific intramolecular G-quadruplexes from duplex and single-strand DNAs. Spectral results have shown that ETC presented two major distinct signatures with specific intramolecular G-quadruplexes in vitro: (i) dramatic changes in the absorption spectra (including disappearance of absorption peak around 660 nm and appearance of independent new peak around 584 nm); (ii) approximately 70 times enhancement of fluorescence signal at 600 nm. Furthermore, based on (1)H-nuclear magnetic resonance and circular dichroism results, the preferring binding of ETC to specific intramolecular G-quadruplexes probably result from end-stacking, and the loop structure nearby also plays an important role.

Seasonal variations of the antioxidant composition in ground bamboo Sasa argenteastriatus leaves.

Sasa argenteastriatus, with abundant active compounds and high antioxidant activity in leaves, is a new leafy bamboo grove suitable for exploitation. To utilize it more effectively and scientifically, we investigate the seasonal variations of antioxidant composition in its leaves and antioxidant activity. The leaves of Sasa argenteastriatus were collected on the 5th day of each month in three same-sized sample plots from May 2009 to May 2011. The total flavonoids (TF): phenolics (TP) and triterpenoid (TT) of bamboo leaves were extracted and the contents analyzed by UV-spectrophotometer. Our data showed that all exhibited variations with the changing seasons, with the highest levels appearing in November to March. Antioxidant activity was measured using DPPH and FRAP methods. The highest antioxidant activity appeared in December with the lowest in May. Correlation analyses demonstrated that TP and TF exhibited high correlation with bamboo antioxidant activity. Eight bamboo characteristic compounds (orientin, isoorientin, vitexin, homovitexin and p-coumaric acid, chlorogenic acid, caffeic acid, ferulic acid) were determined by RP-HPLC synchronously. We found that chlorogenic acid, isoorientin and vitexin are the main compounds in Sasa argenteastriatus leaves and the content of isovitexin and chlorogenic acid showed a similar seasonal variation with the TF, TP and TT. Our results suggested that the optimum season for harvesting Sasa argenteastriatus leaves is between autumn and winter.

Acute myocardial infarction due to Kounis syndrome: A case report.

BACKGROUND: Acute myocardial infarction (AMI) can be induced by several factors. However, AMI induced by Kounis syndrome (an allergic reaction) is extremely rare and is highly susceptible to misdiagnosis. CASE SUMMARY: A 70-year-old man presented after suffering an allergic reaction that caused chest pain triggered upon eating ice cream. Troponin I was found to be elevated, and an electrocardiogram showed ST-segment elevation. The diagnosis was AMI. He underwent two coronary angiographies, with one intravascular ultrasound during hospitalization showing no evidence of atherosclerotic coronary artery disease. The final diagnosis was vasospastic myocardial infarction due to Kounis syndrome. The patient was then treated with hydrocortisone and intravenous antihistamines, and his chest pain symptoms resolved. CONCLUSION: Allergic reactions (such as Kounis syndrome) can cause serious damage to the heart. Physicians should be alert to the consequences and avoid misdiagnosis.

Biochemical and Structural Study of RuvC and YqgF from Deinococcus radiodurans.

Deinococcus radiodurans possesses robust DNA damage response and repair abilities, and this is mainly due to its efficient homologous recombination repair system, which incorporates an uncharacterized Holliday junction (HJ) resolution process. D. radiodurans encodes two putative HJ resolvase (HJR) homologs: RuvC (DrRuvC) and YqgF (DrYqgF). Here, both DrRuvC and DrYqgF were identified as essential proteins for the survival of D. radiodurans. The crystal structures and the biochemical properties of DrRuvC and DrYqgF were also studied. DrRuvC crystallized as a homodimer, while DrYqgF crystallized as a monomer. DrRuvC could preferentially cleave HJ at the consensus 5'-(G/C)TC↓(G/C)-3' sequence and could prefer using Mn2+ for catalysis in vitro, which would be different from the preferences of the other previously characterized RuvCs. On the other hand, DrYqgF was identified as a Mn2+-dependent RNA 5'-3' exo/endonuclease with a sequence preference for poly(A) and without any HJR activity. IMPORTANCE Deinococcus radiodurans is one of the most radioresistant bacteria in the world due to its robust DNA damage response and repair abilities, which are contributed by its efficient homologous recombination repair system. However, the late steps of homologous recombination, especially the Holliday junction (HJ) resolution process, have not yet been well-studied in D. radiodurans. We characterized the structural and biochemical features of the two putative HJ resolvases, DrRuvC and DrYqgF, in D. radiodurans. It was identified that DrRuvC and DrYqgF exhibit HJ resolvase (HJR) activity and RNA exo/endonuclease activity, respectively. Furthermore, both DrRuvC and DrYqgF digest substrates in a sequence-specific manner with a preferred sequence that is different from those of the other characterized RuvCs or YqgFs. Our findings provide new insights into the HJ resolution process and reveal a novel RNase involved in RNA metabolism in D. radiodurans.

Microemulsion Delivery System Improves Cellular Uptake of Genipin and Its Protective Effect against Aß1-42-Induced PC12 Cell Cytotoxicity.

Genipin has attracted much attention for its hepatoprotective, anti-inflammatory, and neuroprotection activities. However, poor water solubility and active chemical properties limit its application in food and pharmaceutical industries. This article aimed to develop a lipid-based microemulsion delivery system to improve the stability and bioavailability of genipin. The excipients for a genipin microemulsion (GME) preparation were screened and a pseudo-ternary phase diagram was established. The droplet size (DS), zeta potential (ZP), polydispersity index (PDI), physical and simulated gastrointestinal digestion stability, and in vitro drug release properties were characterized. Finally, the effect of the microemulsion on its cellular uptake by Caco-2 cells and the protective effect on PC12 cells were investigated. The prepared GME had a transparent appearance with a DS of 16.17 ± 0.27 nm, ZP of -8.11 ± 0.77 mV, and PDI of 0.183 ± 0.013. It exhibited good temperature, pH, ionic strength, and simulated gastrointestinal digestion stability. The in vitro release and cellular uptake data showed that the GME had a lower release rate and better bioavailability compared with that of free genipin. Interestingly, the GME showed a significantly better protective effect against amyloid-ß (Aß1-42)-induced PC12 cell cytotoxicity than that of the unencapsulated genipin. These findings suggest that the lipid-based microemulsion delivery system could serve as a promising approach to improve the application of genipin.