Immunoadjuvant-Modified Rhodobacter sphaeroides Potentiate Cancer Photothermal Immunotherapy.

Photothermal immunotherapy has become a promising strategy for tumor treatment. However, the intrinsic drawbacks like light instability, poor immunoadjuvant effect, and poor accumulation of conventional inorganic or organic photothermal agents limit their further applications. Based on the superior carrying capacity and active tumor targeting property of living bacteria, an immunoadjuvant-intensified and engineered tumor-targeting bacterium was constructed to achieve effective photothermal immunotherapy. Specifically, immunoadjuvant imiquimod (R837)-loaded thermosensitive liposomes (R837@TSL) were covalently decorated onto Rhodobacter sphaeroides (R.S) to obtain nanoimmunoadjuvant-armed bacteria (R.S-R837@TSL). The intrinsic photothermal property of R.S combined R837@TSL to achieve in situ near-infrared (NIR) laser-controlled release of R837. Meanwhile, tumor immunogenic cell death (ICD) caused by photothermal effect of R.S-R837@TSL, synergizes with released immunoadjuvants to promote maturation of dendritic cells (DCs), which enhance cytotoxic T lymphocytes (CTLs) infiltration for further tumor eradication. The photosynthetic bacteria armed with immunoadjuvant-loaded liposomes provide a strategy for immunoadjuvant-enhanced cancer photothermal immunotherapy.

Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study.

BACKGROUND: The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation. METHODS: Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro. RESULTS: Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P<0.001), and the increased species of Streptococcus were found to be from the oral site or oral/nasal sites, in which Streptococcus anginosus was identified as the significantly changed species (P<0.004). Microbial source tracker revealed that PPI significantly increased the contribution of oral bacteria to gut microbiota (P=0.026), and no significant difference was found in PM group (P=0.467). Compared to the baseline, there was a 42-fold increase in gut abundance of Streptococcus anginosus in PP group (P=0.002), and the times decreased to 16-fold in PM group (P=0.029). Mouse models showed that combination of PPI and Streptococcus anginosus significantly increased the gut abundance of Streptococcus anginosus compared with using PPI or Streptococcus anginosus only. Furthermore, Streptococcus anginosus cannot survive in vitro at a pH lower than 5. CONCLUSIONS: PPIs altered gut microbiota by promoting oral-originated Streptococcus translocation into gut.

Intracellular Gelation-Mediated Living Bacteria for Advanced Biotherapeutics in Mouse Models.

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.

Toxicological review of micro- and nano-plastics in aquatic environments: Risks to ecosystems, food web dynamics and human health.

The increase of micro- and nano-plastics (MNPs) in aquatic environments has become a significant concern due to their potential toxicological effects on ecosystems, food web dynamics, and human health. These plastic particles emerge from a range of sources, such as the breakdown of larger plastic waste, consumer products, and industrial outputs. This review provides a detailed report of the transmission and dangers of MNPs in aquatic ecosystems, environmental behavior, and interactions within aquatic food webs, emphasizing their toxic impact on marine life. It explores the relationship between particle size and toxicity, their distribution in different tissues, and the process of trophic transfer through the food web. MNPs, once consumed, can be found in various organs, including the digestive system, gills, and liver. Their consumption by lower trophic level organisms facilitates their progression up the food chain, potentially leading to bioaccumulation and biomagnification, thereby posing substantial risks to the health, reproduction, and behavior of aquatic species. This work also explores how MNPs, through their persistence and bioaccumulation, pose risks to aquatic biodiversity and disrupt trophic relationships. The review also addresses the implications of MNPs for human health, particularly through the consumption of contaminated seafood, highlighting the direct and indirect pathways through which humans are exposed to these pollutants. Furthermore, the review highlights the recommendations for future research directions, emphasizing the integration of ecological, toxicological, and human health studies to inform risk assessments and develop mitigation strategies to address the global challenge of plastic pollution in aquatic environments.

Autonomously Assembled Living Capsules by Microbial Coculture for Enhanced Bacteriotherapy of Inflammatory Bowel Disease.

Microorganism-mediated self-assembling of living formulations holds great promise for disease therapy. Here, we constructed a prebiotic-probiotic living capsule (PPLC) by coculturing probiotics (EcN) with Gluconacetobacter xylinus (G. xylinus) in a prebiotic-containing fermentation broth. Through shaking the culture, G. xylinus secretes cellulose fibrils that can spontaneously encapsulate EcN to form microcapsules under shear forces. Additionally, the prebiotic present in the fermentation broth is incorporated into the bacterial cellulose network through van der Waals forces and hydrogen bonding. Afterward, the microcapsules were transferred to a selective LB medium, which facilitated the colonization of dense probiotic colonies within them. The in vivo study demonstrated that PPLC-containing dense colonies of EcN can antagonize intestinal pathogens and restore microbiota homeostasis by showing excellent therapeutic performance in treating enteritis mice. The in situ self-assembly of probiotics and prebiotics-based living materials provides a promising platform for the treatment of inflammatory bowel disease.

Selective separation of monovalent anions by PPy/pTS membrane electrodes in redox transistor electrodialysis.

Selective separation of nitrate over chloride is crucial for eutrophication mitigation and nitrogen resource recovery but remains a challenge due to their similar ionic radius and the same valence. Herein, a polypyrrole membrane electrode (PME) was fabricated by polymerization of pyrrole (Py) and p-toluenesulfonate (pTS), which was used as a working electrode in redox transistor electrodialysis. The anions in the source solution were first incorporated into the PME at reduction potentials and then released to receiving solution at oxidation potentials. Pulse widths and potentials were optimized to maximize the ion separation performance of PME, resulting in the improvement of NO3-/Cl- separation factor up to 6.93. The ion distributions in various depths of PME indicated that both NO3- and Cl- were incorporated into PME at negative potentials. Then, NO3- was preferentially released from PME at positive potentials, but most Cl- was retained. This was ascribed to the high binding energy between Cl- and PPy/pTS structure, which was 51.4% higher than that between NO3- and PPy/pTS structure. Therefore, the higher transport rate of NO3- in comparison with Cl- was achieved, leading to a high NO3- selectivity over Cl-. This work provides a promising avenue for the selective separation of nitrate over chloride, which may contribute to nitrogen resource recycling and reuse.

Degradation of polyethylene by Klebsiella pneumoniae Mk-1 isolated from soil.

The massive accumulation of polyethylene (PE) in the natural environment has caused persecution to the ecological environment. At present, the mechanism of microbial degradation of PE remains unclear, and the related enzymes for degrading PE need to be further explored. In this study, a strain of Klebsiella pneumoniae Mk-1 which can effectively degrade PE was obtained from the soil. The degradation performance of the strains was evaluated by weight loss rate, SEM, ATR/FTIR, WCA, and GPC. The key gene of PE degradation in the strain was further searched, which may be the laccase-like multi-copper oxidase gene. Then, the laccase-like multi-copper oxidase gene (KpMco) was successfully expressed in E.coli and its laccase activity was verified, which reached 85.19 U/L. The optimum temperature and pH of the enzyme are 45 °C and 4.0, respectively; it shows good stability at 30-40 °C and pH 4.5-5.5; Mn2+ and Cu2+ can activate the enzyme effect. After the enzyme was applied to the degradation of PE film, it was found that the laccase-like multi-copper oxidase did have a certain degradation effect on PE film. This study provides new strain and enzyme gene resources for the biodegradation of PE, thereby promoting the process of PE biodegradation.

A Cone Beam Computed Tomography Analysis of Bone Volume Variations of Extra-alveolar Region Based on Sex, Age, Vertical and Sagittal Facial Patterns.

OBJECTIVES: The goal of this study is to measure mandibular buccal shelf (MBS) concerning angulation, bone volume, and cortical bone volume as well as bone depth and cortical bone depth of infrazygomatic crest (IZC) via cone beam computed tomography and evaluate the measurements according to sex, age, vertical, and sagittal facial types. MATERIALS AND METHODS: This study collected lateral cephalograms and cone beam computed tomography scans from 100 individuals, which were used to observe angulation, bone and cortical bone volume entailing width and depth of MBS as well as the depth of IZC. FH-MP (mandibular plane angle) and A point-Nasion-B point were adopted to determine vertical and sagittal facial patterns respectively. RESULTS: Bone widths at 6 mm and 11 mm to cementoenamel junction (CEJ) and cortical bone width at 6 mm to CEJ in MBS showed significant sex differences, while bone depths and cortical bone depths in IZC show significant age difference( P <0.05). Bone width and cortical bone width at 6 mm to CEJ at the mesial root and 11 mm to CEJ at both roots as well as angulations of MBS in the mandibular first molar region, bone depth and cortical bone depth at the maxillary first molar distal buccal root, and the proximity region were all correlated to FH-MP ( P <0.05). CONCLUSIONS: Short-faced individuals of Asian ethnicity tend to have greater bone width, greater projection in MBS, and greater bone depth in the posterior region of IZC. The optimal implant sites are 11 mm apical to CEJ at the mandibular second molar distal root and 65° at the maxillary first molar mesial root.

Dual-Principal Component Analysis of the Raman Spectrum Matrix to Automatically Identify and Visualize Microplastics and Nanoplastics.

As emerging contaminants, microplastics are challenging to characterize, particularly when their size is at the nanoscale. While imaging technology has received increasing attention recently, such as Raman imaging, decoding the scanning spectrum matrix can be difficult to achieve result digitally and automatically via software and usually requires the involvement of personal experience and expertise. Herewith, we show a dual-principal component analysis (PCA) approach, where (i) the first round of PCA analysis focuses on the raw spectrum data from the Raman scanning matrix and generates two new matrices, with one containing the spectrum profile to yield the PCA spectrum and the other containing the PCA intensity to be mapped as an image; (ii) the second round of PCA analysis merges the spectrum from the first round of PCA with the standard spectra of eight common plastics, to generate a correlation matrix. From the correlation value, we can digitally assign the principal components from the first round of PCA analysis to the plastics toward imaging, akin to dataset indexing. We also demonstrate the effect of the data pretreatment and the wavenumber variations. Overall, this dual-PCA approach paves the way for machine learning to analyze microplastics and particularly nanoplastics.

In vitro assembly of chimeric virus-like particles composed of a porcine circovirus 2b capsid protein and a B-cell epitope of infectious bursal disease virus.

OBJECTIVES: To develop a method for in vitro assembly of recombinant proteins expressed in E. coli into chimeric virus-like particles (cVLPs). RESULTS: A fusion protein (Bepi-Cap-A) between capsid protein (Cap) of PCV2b and B cell epitope (Bepi) of IBDV was expressed in E. Coli, and purified. For assembling them into cVLPs (Bepi-Cap-VLP), the Bepi-Cap-A was suspended in buffer C [0.03% ("%" stands for "v/v" unless otherwise indicated) polyethylene glycol, 0.4 M Tris, 10 mM ß-mercaptoethanol, 5% glycerol, 0.02% (w/v) gellan gum, 0.1 M glycine, 0.03% Tween 80, 500 mM NaCl], and incubated. After centrifugation, the pellet was resuspended in buffer D [50 mM Na2HPO4, 50 mM NaH2PO4, 0.01% (w/v) gellan gum, 0.05 mM EDTA, 500 mM NaCl, 0.03% Tween 80, pH 6.5], and then dialyzed against dialysis buffer (50 mM Na2HPO4, 50 mM NaH2PO4, 500 mM NaCl, 0.03% Tween 80, pH 6.5). The procedure resulted in typical and immunogenic Bepi-Cap-VLP. CONCLUSIONS: The data provide a method which is feasible for in vitro assembly of recombinant proteins into chimeric virus-like particles.

Engineering Clostridium cellulovorans for highly selective n-butanol production from cellulose in consolidated bioprocessing.

Cellulosic n-butanol from renewable lignocellulosic biomass has gained increased interest. Previously, we have engineered Clostridium cellulovorans, a cellulolytic acidogen, to overexpress the bifunctional butyraldehyde/butanol dehydrogenase gene adhE2 from C. acetobutylicum for n-butanol production from crystalline cellulose. However, butanol production by this engineered strain had a relatively low yield of approximately 0.22 g/g cellulose due to the coproduction of ethanol and acids. We hypothesized that strengthening the carbon flux through the central butyryl-CoA biosynthesis pathway and increasing intracellular NADH availability in C. cellulovorans adhE2 would enhance n-butanol production. In this study, thiolase (thlACA ) from C. acetobutylicum and 3-hydroxybutyryl-CoA dehydrogenase (hbdCT ) from C. tyrobutyricum were overexpressed in C. cellulovorans adhE2 to increase the flux from acetyl-CoA to butyryl-CoA. In addition, ferredoxin-NAD(P)+ oxidoreductase (fnr), which can regenerate the intracellular NAD(P)H and thus increase butanol biosynthesis, was also overexpressed. Metabolic flux analyses showed that mutants overexpressing these genes had a significantly increased carbon flux toward butyryl-CoA, which resulted in increased production of butyrate and butanol. The addition of methyl viologen as an electron carrier in batch fermentation further directed more carbon flux towards n-butanol biosynthesis due to increased reducing equivalent or NADH. The engineered strain C. cellulovorans adhE2-fnrCA -thlACA -hbdCT produced n-butanol from cellulose at a 50% higher yield (0.34 g/g), the highest ever obtained in batch fermentation by any known bacterial strain. The engineered C. cellulovorans is thus a promising host for n-butanol production from cellulosic biomass in consolidated bioprocessing.

Epigenetics-Based Tumor Cells Pyroptosis for Enhancing the Immunological Effect of Chemotherapeutic Nanocarriers.

Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.

Multifunctional oligomer immobilized on quartz crystal microbalance: a facile and stabilized molecular imprinting strategy for glycoprotein detection.

Glycoprotein detection holds great potential for early diagnosis of diverse diseases. For this purpose, the combination of quartz crystal microbalance (QCM) sensor and molecular imprinting has attracted increasing attention. Nonetheless, the recently common imprinted films fabricated on QCM electrode are thick and rigid, lacking flexibility in aqueous phase. Alternatively, small molecules immobilized on the electrode to construct molecular scale film could address this problem, while stabilization of the imprinted sites remains challenging. Herein, a co-assembly complex was obtained by the mixture of template and multifunctional oligomer, which was then immobilized on the amino-modified transducer surface through epoxy-amino reaction to form a protein-imprinted film. Afterward, the remaining epoxy groups in oligomer chains were cross-linked to conserve and stabilize the orientation of imprinted sites after template elution. Template rebinding tests show that cross-linked film has much higher imprinting factors than that of the non-cross-linked counterpart. Furthermore, control proteins that are distinct in properties and structures were employed to demonstrate the selectivity of this approach, and the imprinted assay reveals high affinity and specificity towards template protein. Graphical Abstract.

PD-1 Blockade for Improving the Antitumor Efficiency of Polymer-Doxorubicin Nanoprodrug.

Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs-mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD-1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA-Psi-DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme-activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP-2. It is found that HA-Psi-DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon-γ. This cytokine promotes the expression of programmed cell death protein-ligand 1 (PD-L1) on tumor cells, which will cause immunosuppression after interacting with PD-1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA-Psi-DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti-PD-1 antibody (α-PD1) due to the neutralization of immunosuppression by blocking the interaction between PD-L1 and PD-1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy.

The enhanced effect of activated sludge attached to the roots of Pistia stratiotes on nutrient removal for secondary effluent.

Aquatic plants are widely used for treating wastewater treatment plant secondary effluent. During this process, some residual activated sludge in the secondary effluent is intercepted and attaches to the plant roots. However, the effect of the attached activated sludge on nutrient removal in secondary effluent has up to now been unknown. Aiming at this problem, this investigation was conducted to compare the nutrient removal rates in secondary effluent by washed Pistia stratiotes (washed batch) and Pistia stratiotes with activated sludge attached to the roots (study batch). Extracellular polymeric substances (EPS) from the activated sludge attached to the roots were extracted and characterized by three-dimensional excitation emission matrix (3D-EEM) fluorescence spectroscopy. The results showed that the nutrient removal rates in the study batch were better than that in the washed batch. The 3D-EEM results showed that the protein content of EPS increased during the experiment, indicating the growth of microorganisms in the attached activated sludge. Our work demonstrated the enhanced effect of activated sludge attached to the roots of Pistia stratiotes on the removal of pollutants in secondary effluent, which is useful to guide the practical engineering of secondary effluent treatment.

Dual-Stage Light Amplified Photodynamic Therapy against Hypoxic Tumor Based on an O2 Self-Sufficient Nanoplatform.

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome-based nanoparticle (designated as LipoMB/CaO2 ) with O2 self-sufficient property for dual-stage light-driven PDT is demonstrated to address this problem. Through a short time irradiation, 1 O2 activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO2 with H2 O, resulting in accelerated O2 production. Accelerated O2 level further regulates hypoxic tumor microenvironment and in turn improves 1 O2 generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO2 to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side-effect. The O2 self-sufficient LipoMB/CaO2 nanoplatform with dual-stage light manipulation is a successful attempt for PDT against hypoxic tumor.

Advances in Peptide Functionalization on Mesoporous Silica Nanoparticles for Controlled Drug Release.

During the last decade, using versatile, promising, and fascinating mesoporous silica nanoparticles (MSNs) as site-specific and stimuli-responsive drug delivery systems (DDSs) has received concentrated research interest. As one of the most attractive surface modification units, peptides have inherent bioactivity, biodegradability and biocompatibility. Recent progresses in the utilization of versatile peptides for surface functionalization of MSNs to achieve cell-specific targeting, fluorescence imaging, and intracellular diagnosis and treatment of tumors are summarized in this review. The various functional peptides decorated on the MSNs are introduced and classified into three types, including targeting peptides, stimuli-responsive peptides and multifunctional chimeric peptides. The limitations and challenges of peptide modified MSNs and their potential applications are further discussed.

Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation.

BACKGROUND: Corynebacterium crenatum SYPA 5 is the industrial strain for L-arginine production. Poly-ß-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and L-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the L-arginine biosynthesis in C. crenatum SYPA 5. RESULTS: C. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of L-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L L-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key L-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9-3.0 times compared with the parent strain. CONCLUSIONS: Accumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time L-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular L-arginine and intracellular PHB simultaneously. All of these have a potential biotechnological application as a strategy for high-yield L-arginine.

Human Basic Fibroblast Growth Factor Inhibits Tau Phosphorylation via the PI3K/Akt-GSK3ß Signaling Pathway in a 6-Hydroxydopamine-Induced Model of Parkinson's Disease.

BACKGROUND: Basic fibroblast growth factor (bFGF) has been increasingly investigated due to its neuroprotection in neurodegenerative disorders. Because there are still no cures for any of these disorders, it is crucial to identify new therapeutic targets and screen potential drugs. The increased phosphorylation of tau at Ser396 leads to intracellular tau accumulation, which forms neurofibrillary tangles in Parkinson's disease (PD). In this study, neuroprotection by bFGF was observed, and the mechanisms related to its regulation of phosphorylated tau were investigated. METHODS: bFGF-loaded liposome carriers were intranasally administered to rats. The neuroprotective effects of bFGF were assessed in a PD model induced by 6-hydroxydopamine (6-OHDA) in vivo and in vitro. The phosphorylation of tau was measured, and the PI3K/Akt-GSK3ß signaling pathway was investigated. RESULTS: Our study demonstrated that liposomes markedly assisted in the delivery of bFGF to the striatum and substantia nigra of rats and enhanced the neuroprotective effects of bFGF on dopaminergic neurons. bFGF treatment significantly ameliorated the behavioral deficits induced by 6-OHDA, rescued the loss of tyrosine hydroxylase-positive neurons and increased the number of Nissl bodies. bFGF reduced the phosphorylation of tau and GSK3ß and increased the phosphorylation of PI3K/Akt. CONCLUSION: Liposomes markedly assisted in the delivery of bFGF to the brain and enhanced the neuroprotective effects of bFGF by inhibiting the phosphorylation of tau. bFGF down-regulated the phosphorylation of tau by increasing the phosphorylation of GSK3ß via the PI3K/Akt signaling pathway. These findings provide a new vision of bFGF as a potential therapy for PD.