Large-scale genome sequencing of giant pandas improves the understanding of population structure and future conservation initiatives.

The extinction risk of the giant panda has been demoted from "endangered" to "vulnerable" on the International Union for Conservation of Nature Red List, but its habitat is more fragmented than ever before, resulting in 33 isolated giant panda populations according to the fourth national survey released by the Chinese government. Further comprehensive investigations of the genetic background and in-depth assessments of the conservation status of wild populations are still necessary and urgently needed. Here, we sequenced the genomes of 612 giant pandas with an average depth of ~26× and generated a high-resolution map of genomic variation with more than 20 million variants covering wild individuals from six mountain ranges and captive representatives in China. We identified distinct genetic clusters within the Minshan population by performing a fine-grained genetic structure. The estimation of inbreeding and genetic load associated with historical population dynamics suggested that future conservation efforts should pay special attention to the Qinling and Liangshan populations. Releasing captive individuals with a genetic background similar to the recipient population appears to be an advantageous genetic rescue strategy for recovering the wild giant panda populations, as this approach introduces fewer deleterious mutations into the wild population than mating with differentiated lineages. These findings emphasize the superiority of large-scale population genomics to provide precise guidelines for future conservation of the giant panda.

Progress of reprogramming astrocytes into neuron.

As the main players in the central nervous system (CNS), neurons dominate most life activities. However, after accidental trauma or neurodegenerative diseases, neurons are unable to regenerate themselves. The loss of this important role can seriously affect the quality of life of patients, ranging from movement disorders to disability and even death. There is no suitable treatment to prevent or reverse this process. Therefore, the regeneration of neurons after loss has been a major clinical problem and the key to treatment. Replacing the lost neurons by transdifferentiation of other cells is the only viable approach. Although much progress has been made in stem cell therapy, ethical issues, immune rejection, and limited cell sources still hinder its clinical application. In recent years, somatic cell reprogramming technology has brought a new dawn. Among them, astrocytes, as endogenously abundant cells homologous to neurons, have good potential and application value for reprogramming into neurons, having been reprogrammed into neurons in vitro and in vivo in a variety of ways.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

Nasal mucosa-derived mesenchymal stem cells prolonged the survival of septic rats by protecting macrophages from pyroptosis.

Sepsis is characterized by an exacerbated inflammatory response, driven by the overproduction of cytokines, a phenomenon known as a cytokine storm. This condition is further compounded by the extensive infiltration of M1 macrophages and the pyroptosis of these cells, leading to immune paralysis. To counteract this, we sought to transition M1 macrophages into the M2 phenotype and safeguard them from pyroptosis. For this purpose, we employed ectodermal mesenchymal stem cells (EMSCs) sourced from the nasal mucosa to examine their impact on both macrophages and septic animal models. The co-culture protocol involving LPS-stimulated rat bone marrow macrophages and EMSCs was employed to examine the paracrine influence of EMSCs on macrophages. The intravenous administration of EMSCs was utilized to observe the enhancement in the survival rate of septic rat models and the protection of associated organs. The findings indicated that EMSCs facilitated M2 polarization of macrophages, which were stimulated by LPS, and significantly diminished levels of pro-inflammatory cytokines and NLRP3. Furthermore, EMSCs notably restored the mitochondrial membrane potential (MMP) of macrophages through paracrine action, eliminated excess reactive oxygen species (ROS), and inhibited macrophage pyroptosis. Additionally, the systemic integration of EMSCs substantially reduced injuries to multiple organs and preserved the fundamental functions of the heart, liver, and kidney in CLP rats, thereby extending their survival.

Reference gene catalog and metagenome-assembled genomes from the gut microbiome reveal the microbial composition, antibiotic resistome, and adaptability of a lignocellulose diet in the giant panda.

The giant panda, a strict herbivore that feeds on bamboo, still retains a typical carnivorous digestive system. Reference catalogs of microbial genes and genomes are lacking, largely limiting the antibiotic resistome and functional exploration of the giant panda gut microbiome. Here, we integrated 177 fecal metagenomes of captive and wild giant pandas to construct a giant panda integrated gene catalog (GPIGC) comprised of approximately 4.5 million non-redundant genes and reconstruct 393 metagenome-assembled genomes (MAGs). Taxonomic and functional characterization of genes revealed that the captivity of the giant panda significantly changed the core microbial composition and the distribution of microbial genes. Higher abundance and prevalence of antibiotic resistance genes (ARGs) were detected in the guts of captive giant pandas, and ARG distribution was influenced by geography, for both captive and wild individuals. Escherichia, as the prevalent genus in the guts of captive giant pandas, was the main carrier of ARGs, meaning there is a high risk of ARG transmission by Escherichia. We also found that multiple mcr gene variants, conferring plasmid-mediated mobile colistin resistance, were widespread in the guts of captive and wild giant pandas. There were low proportions of carbohydrate-active enzyme (CAZyme) genes in GPIGC and MAGs compared with several omnivorous and herbivorous mammals. Many members of Clostridium MAGs were significantly enriched in the guts of adult, old and wild giant pandas. The genomes of isolates and MAGs of Clostridiaceae harbored key genes or enzymes in complete pathways for degrading lignocellulose and producing short-chain fatty acids (SCFAs), indicating the potential of these bacteria to utilize the low-nutrient bamboo diet. Overall, our data presented an exhaustive reference gene catalog and MAGs in giant panda gut and provided a comprehensive understanding of the antibiotic resistome and microbial adaptability for a high-lignocellulose diet.

Comparison of Neoatherosclerosis and Neovascularization of Restenosis after Drug-Eluting Stent Implantation: An Optical Coherence Tomography Study.

Background: Neoatherosclerosis (NA) is associated with stent failure. However, systematic studies on the manifestations of NA and neovascularization (NV) at different stages after drug-eluting stent (DES) implantation are lacking. Moreover, the relationship between NA and NV in in-stent restenosis (ISR) has not been reported. This study aimed to characterize NA and NV in patients with ISR at different post-DES stages and compare the association between NA and NV in ISR lesions. Methods: A total of 227 patients with 227 lesions who underwent follow-up optical coherence tomography before percutaneous coronary intervention for DES ISR were enrolled and divided into early (E-ISR: < 1 year), late (L-ISR: 1-5 years), and very-late (VL-ISR: > 5 years) ISR groups. Furthermore, ISR lesions were divided into NV and non-NV groups according to the presence of NV. Results: The prevalence of NA and NV was 52.9% and 41.0%, respectively. The prevalence of lipidic NA (E-ISR, 32.7%; L-ISR, 50.0%; VL-ISR, 58.5%) and intimal NV (E-ISR, 14.5%; L-ISR, 30.8%; VL-ISR, 38.3%) increased with time after stenting. NA was higher in ISR patients with NV lesions than in those without (p < 0.001). Patients with both ISR and NV had a higher incidence of macrophage infiltration, thin-cap fibroatheroma, intimal rupture, and thrombosis (p < 0.01). Conclusions: Progression of lipidic NA was associated with L-ISR and VL-ISR but may not be related to calcified NA. NA was more common in ISR lesions with NV; its formation may substantially promote NA progression and plaque instability.

Effect of Fluoride Atoms on the Electrochemical Performance of Tetracyanoquinodimethane(TCNQ) Electrodes in Zinc-ion Batteries.

Tetracyanoquinodimethane (TCNQ) electrode material has achieved excellent performance in aqueous zinc-ion batteries (AZIBs). However, fundamental understanding about effect of substitutes on electrochemical performance of TCNQ remain unknown. In this work, the effects of fluorine (F) as an electron-absorbing group on the structure, morphology and electrochemical performance of TCNQ and storage mechanism of TCNQ in AZIBs are discussed. Theoretical calculation proves that the introduction of fluorine atoms decreases lowest unoccupied molecular orbital (LUMO) energy of TCNQ thus affect the redox potential. Electrochemical performance of TCNQ/Fluoro-7,7,8,8-tetracyanoquinodimethane (FTCNQ)/2,3,5,6-Tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4 TCNQ) is evaluated from 25 °C to -20 °C in AZIBs. Results tend out that with the increasing substituents of F on TCNQ molecular, their stability in AZIBs decrease. Dipole moment calculation further shows that the introduction of fluorine atoms is inconducive to the stability of the electrode material in aqueous solution. Ex-situ characterization demonstrate that electron withdrawing groups do not change the REDOX center of TCNQ electrode materials. Our work provides a new thought for the selection of the electrode material in AZIBs.

Photothermal Therapy Mediated Hybrid Membrane Derived Nano-formulation for Enhanced Cancer Therapy.

Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 µg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section (P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Schematic of EG@EMHM NPs formulation.

Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication.

Formononetin is a flavonoid compound with anti-tumor and anti-inflammatory properties. However, its low solubility limits its clinical use. We employed microfluidic technology to prepare formononetin-loaded PLGA-PEGDA microspheres (Degradable polymer PLGA, Crosslinking agent PEGDA), which can encapsulate and release drugs in a controlled manner. We optimized and characterized the microspheres, and evaluated their antitumor effects. The microspheres had uniform size, high drug loading efficiency, high encapsulation efficiency, and stable release for 35 days. They also inhibited the proliferation, migration, and apoptosis. The antitumor mechanism involved the induction of reactive oxygen species and modulation of Bcl-2 family proteins. These findings suggested that formononetin-loaded PLGA-PEGDA microspheres, created using microfluidic technology, could be a novel drug delivery system that can overcome the limitations of formononetin and enhance its antitumor activity.

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.

Antimicrobial resistance of Escherichia coli, Enterobacter spp., Klebsiella pneumoniae and Enterococcus spp. isolated from the feces of giant panda.

BACKGROUND: Escherichia coli, Enterobacter spp., Klebsiella pneumoniae and Enterococcus spp., common gut bacteria in giant pandas, include opportunistic pathogens. The giant panda is an endangered species, classified as vulnerable by the World Wildlife Foundation. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from giant pandas is vital not only for their protection but also for public health. RESULTS: A total of 166 E. coli, 68 Enterobacter spp., 116 K. pneumoniae and 117 Enterococcus spp. isolates were collected from fecal samples of 166 giant pandas. In the antimicrobial susceptibility tests, 144 E. coli isolates, 66 Enterobacter spp. isolates, 110 K. pneumoniae isolates and 43 Enterococcus spp. isolates were resistant to at least one antimicrobial. The resistant isolates carried antimicrobial resistance genes (ARGs), including sul3, blaTEM, blaSHV and tetA. The differences in the prevalence of the bla types implied that the genetic basis for ß-lactam resistance among the E. coli, Enterobacter spp. and K. pneumoniae isolates was different. The strain K. pneumoniae K85 that was resistant to sixteen antimicrobials was selected for whole genome sequencing. The genome contained Col440I, IncFIBK and IncFIIK plasmids and altogether 258 ARGs were predicted in the genome; 179 of the predicted ARGs were efflux pump genes. The genetic environment of the ß-lactamase genes blaCTX-M-3 and blaTEM-1 in the K. pneumoniae K85 genome was relatively similar to those in other sequenced K. pneumoniae genomes. In comparing the giant panda age groups, the differences in the resistance rates among E. coli, K. pneumoniae and Enterobacter spp. isolates suggested that the infections in giant pandas of different age should be treated differently. CONCLUSIONS: Antimicrobial resistance was prevalent in the bacterial isolates from the giant pandas, implying that the gut bacteria may pose serious health risks for captive giant pandas. The resistance genes in the genome of K. pneumoniae K85 were associated with insertion sequences and integron-integrase genes, implying a potential for the further spread of the antimicrobial resistance.

Comparison of genetic characteristics between captive and wild giant pandas based on 13 mitochondrial coding genes.

BACKGROUND: Research on genetic diversity based on mitochondrial DNA of giant pandas mainly focused on a single marker or a few genes. OBJECTIVE: To provide a more comprehensive assessment of the genetic diversity on giant pandas based on 13 mitochondrial protein coding genes. METHODS: We assembled 13 protein coding genes in the mitochondrial genome of the giant panda based on the whole genome sequencing data, including ND1, ND2, COX1, COX2, ATP8, ATP6, COX3, ND3, ND4L, ND4, ND5, ND6 and Cyt b. RESULTS: We successfully obtained long sequence of 11,416 base pairs with all 13 genes for 110 giant panda individual, accounting for 67.93% in length of the mitochondrial reference genome. Haplotype diversity was 0.9518 ± 0.009 and nucleotide diversity (π) was 0.00157 ± 0.00014. We detected three new haplotypes, including GPC10 and GPC21 for the CR sequence and GPB12 for the Cyt b gene. CONCLUSION: These multi-gene sequences provided more genetic variable information to compare captive and wild giant panda population.

A polypropylene (PP) supported solid polymer electrolyte enables high-stability organic lithium batteries at low temperature.

We innovatively used a polypropylene (PP) separator as a substrate and PEO-LiTFSI-SN as a paste to coat on both of the PP surfaces, and formed a sandwich-like solid polymer electrolyte (SPE). The SPE shows a conductivity of 4.22 × 10-3 S cm-1 at room temperature and 7.75 × 10-5 S cm-1 at 0 °C. The pyrene-4,5,9,10-tetraone (PTO)||SPE||Li battery shows a maximum discharge specific capacity of 187.8 mA h g-1 at a current density of 20 mA g-1 under 0 °C. After 100 cycles, the capacity could still be obtained at 88.4 mA h g-1, and the coulombic efficiency stayed stable at 98%. This work paved a new way for the development of solid-state organic batteries (SSOBs) at low temperatures.

Metagenomic analysis revealed a wide distribution of antibiotic resistance genes and biosynthesis of antibiotics in the gut of giant pandas.

BACKGROUND: The gut microbiome is essential for the host's health and serves as an essential reservoir of antibiotic resistance genes (ARGs). We investigated the effects of different factors, including the dietary shifts and age, on the functional characteristics of the giant panda's gut microbiome (GPs) through shotgun metagenome sequencing. We explored the association between gut bacterial genera and ARGs within the gut based on network analysis. RESULTS: Fecal samples (n=60) from captive juvenile, adult, and geriatric GPs were processed, and variations were identified in the gut microbiome according to different ages, the abundance of novel ARGs and the biosynthesis of antibiotics. Among 667 ARGs identified, nine from the top ten ARGs had a higher abundance in juveniles. For 102 ARGs against bacteria, a co-occurrence pattern revealed a positive association for predominant ARGs with Streptococcus. A comparative KEGG pathways analysis revealed an abundant biosynthesis of antibiotics among three different groups of GPs, where it was more significantly observed in the juvenile group. A co-occurrence pattern further revealed a positive association for the top ten ARGs, biosynthesis of antibiotics, and metabolic pathways. CONCLUSION: Gut of GPs serve as a reservoir for novel ARGs and biosynthesis of antibiotics. Dietary changes and age may influence the gut microbiome's functional characteristics; however, it needs further studies to ascertain the study outcomes.

The Fecal and Serum Metabolomics of Giant Pandas Based on Untargeted Metabolomics.

Little is comprehensively known or understood about giant panda fecal and serum metabolites, which could serve as important indicators of the physiological metabolism of giant pandas. Therefore, we determined the contents of fecal and serum metabolites of giant pandas based on an untargeted metabolome. Four hundred and 955 metabolites were detected in the feces and serum of giant panda, respectively. Glycerophospholipid and choline metabolism were the main metabolic pathways in feces and serum. A significant correlation between the gut microbiota and fecal metabolites was found (P < 0.01). Fecal metabolites were not greatly affected by the age or gender of giant pandas, but serum metabolites were significantly affected by age and gender. The majority of different metabolites caused by age were higher in serum of younger giant pandas, including fatty acids, lipids, metabolites of bile acids, and intermediate products of vitamin D3. The majority of different metabolites caused by gender included fatty acids, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE). A separate feeding diet should be considered according to different ages and genders of giant panda. Therefore, our results could provide helpful suggestions to further protect captive giant pandas.

Diversity and Composition of Gut Bacterial Community in Giant Panda with Anorexia.

The giant panda (GP) is the most precious animal in China. Gastrointestinal tract disease, especially associated with dysbiosis of gut microbiota, is the leading cause of death in GPs. Here, we performed 16S rRNA high-throughput sequencing to investigate the gut microbiota of GPs having symptoms of anorexia. Results showed that gut microbiota of GP with anorexia had lower richness (Chao1 index) than the healthy GP. However, no significant differences in alpha diversity were observed. There is a significance in the microbial structure between anorexia and healthy GPs. The abundance of phylum Firmicutes (99.23% ± 7.1%), unidentified genus Clostridiales (24.75% ± 2.5%), was significantly higher in the subadult anorexia group (P < 0.01), and that of the unidentified genus Clostridiales (4.53% ± 1.2%) was also significantly higher in the adult anorexia group (P < 0.01). Weissella and Streptococcus were found to be decreased in both anorexia groups. The decreased abundance of Weissella (0.02% ± 0.0%, 0.08% ± 0.0%) and Streptococcus (73.89% ± 4.3%, 91.15% ± 7.6%) and increase in Clostridium may cause symptoms of anorexia in giant pandas. The correlation analysis indicated that there is a symbiotic relationship among Streptococcus, Leuconostoc, Weissella, and Bacillus which are classified as probiotics (r > 0.6, P < 0.05). Importantly, a negative correlation has been found between Streptococcus and unidentified_Clostridium in two groups (r > 0.6, P < 0.05). Our results suggested that Streptococcus might be used as probiotics to control the growth of Clostridium causing the anorexia.

Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System.

This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50 mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12 nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged Tmax, t1/2, and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.

A Tetrakis(terpyridine) Ligand-Based Cobalt(II) Complex Nanosheet as a Stable Dual-Ion Battery Cathode Material.

Inspired by the flexibility of the bottom-up approach in terms of selecting molecular components and thus tailoring functionalities, a terpyridine derivative (1,2,4,5-tetrakis(4-(2,2':6',2″-terpyridyl)phenyl)benzene) (Tetra-tpy) is synthesized and coordinated with Co(II) ion to self-assemble into a nanosheet Co-sheet by a facile interface-assisted synthesis. The bis(terpyridine)-Co(II) complex nanosheet formed not only shows good stability, but also features the layered structure and rich electrochemical activity inherited from the embedded Co(terpyridine)2 motif. Thus, Co-sheet can serve as a cathode material for a dual-ion battery prototype, which exhibits a high utilization of redox-active sites, good cycling stability, and rate capability, thus expanding the potential application of this kind of easily prepared metal-complex nanosheets in the field of energy storage.

Enhanced oral bioavailability of self-assembling curcumin-vitamin E prodrug-nanoparticles by co-nanoprecipitation with vitamin E TPGS.

Curcumin (CUR), a nontoxic natural compound with potent antitumor activity, was limited in clinical application due to its insolubility and exceedingly low bioavailability. In this study, a novel prodrug-nanoparticle (CSSV/TPGS-NPs) self-assembled by co-nanoprecipitation of CUR-s-s-vitamin E conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was prepared in attempt to solve aforementioned obstacles. CSSV/TPGS-NPs showed smaller sizes and better stability compared with that of CUR-s-s-vitamin E conjugate prodrug-nanoparticles (CSSV-NPs). Significantly, the absorption constant and effective permeability of CSSV/TPGS-NPs in different intestinal tracts increased 1.31-2.78 times and 1.81-6.95 times than that of CUR suspension, respectively. Pharmacokinetic study in Sprague-Dawley (SD) rats demonstrated that orally administered CSSV/TPGS-NPs displayed a prolonged plasma circulation with 8.06-fold increase in relative bioavailability compared to that of the CUR suspension. Altogether, conjugation of hydrophobic native CUR with vitamin E to form CSSV/TPGS-NPs is a promising technology for sustained and controlled drug delivery of CUR with improved oral bioavailability in vivo.