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1.
Pregnancy Hypertens ; 17: 197-202, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31487640

RESUMO

Hyperuricemia (HUA) in women with preeclampsia (PE) not only indicates a reminder of severity but also contributes directly to the pathogenesis of PE. ATP-binding cassette subfamily G member 2 (ABCG2) has a very strong effect on the serum urate concentrations. Our aim was to investigate the association between polymorphisms of ABCG2 with PE in Chinese Han female population. A cohort of 793 preeclamptic women (466 PE with HUA and 327 PE without HUA) and 744 normal pregnant women recruited in this study were genotyped for genetic distribution of Q141K (rs2231142) and Q126X (72552713) in ABCG2 by the TaqMan allelic discrimination real-time PCR. There was no statistically significant difference of genotypic and allelic frequencies between PE and the normal pregnant women in Q141K (Χ2 = 1.11, P = 0.58 by genotype; Χ2 = 0.32, P = 0.57 by allele) and Q126X (P = 0.33 by genotype; P = 0.33 by allele), and no significant difference was found in the genetic distribution of Q141K and Q126X between PE with HUA, PE without HUA and controls. Additionally, this study observed no significant difference in genotypic and allelic distribution between early/late-onset PE with/without HUA or mild/severe PE with/without HUA and control subgroups. Based on our findings, the ABCG2 Q141K and Q126X polymorphisms may not be associated with PE in Chinese Han women.

2.
Curr Opin Genet Dev ; 58-59: 62-69, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31472442

RESUMO

Trans-kingdom RNA plays a key role in host-parasite interactions. Hosts export specific endogenous microRNAs (miRNAs) into pathogens to target pathogen virulence genes and inhibit their invasion. In addition, trans-kingdom sRNAs produced by parasites may function as RNA effectors to suppress host immunity. Here, we summarize recent, important findings regarding trans-kingdom RNA and focus on the roles of trans-kingdom RNA in driving an evolutionary arms race between host and pathogen. We suggest that trans-kingdom RNA is a new platform for such arms races. Furthermore, we conjecture that trans-kingdom RNA contributes to horizontal gene transfer (HGT) involved in host-pathogen interactions. In addition, we propose that trans-kingdom RNA exchange and RNA driven HGT can have a great impact on the evolutionary ecology of interacting species.

3.
J Org Chem ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31496250

RESUMO

The development of novel solid-state fluorescence switches, particularly triggered by visible light, is of increasing interest for the potential application in optical data storage and super-resolution fluorescence microscopies. In this study, two carbazole-dithienylethene-BF2bdk triads CDB1 and CDB2, suspending carbazole and BF2bdk moieties on both sides of dithienylethene unit, have been developed. They exhibit blue-/NIR light-controlled photochromism with solvent-dependent characteristics. Moreover, CDB1 (o) reveals blue-/NIR light induced reversible fluorescent switching behaviors in toluene, chloroform, PMMA film and powder state, while its analogue CDB2 (o) in the powder state exhibits no fluorescence due to a strong intermolecular π-π stacking interaction, and the fluorescent switching performance is observed only in toluene and PMMA film. The DFT calculations further validate the differences in their optical properties in the solution and powder state.

4.
Chem Commun (Camb) ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498358

RESUMO

A luminescent edge-interlocked heteroleptic metallocage based on Cu3(pyrazolate)3 was prepared through a ligand replacement reaction from a homoleptic metallocage and a new ligand. Its structure was confirmed by XRD and MALDI-TOF mass spectrometry. Theoretical calculations revealed the new ligand was evidently responsible for the bathochromic shift of the optimal excitation. This work provides a heteroleptic strategy to regulate the interlocking fashion and photophysical mechanism of metallocages based on Cu3(pyrazolate)3.

5.
Sensors (Basel) ; 19(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443176

RESUMO

As an important inertial sensor, the gyroscope is mainly used to measure angular velocity in inertial space. However, due to the influence of semiconductor thermal noise and electromagnetic interference, the output of the gyroscope has a certain random noise and drift, which affects the accuracy of the detected angular velocity signal, thus interfering with the accuracy of the stability of the whole system. In order to reduce the noise and compensate for the drift of the MEMS (Micro Electromechanical System) gyroscope during usage, this paper proposes a Kalman filtering method based on information fusion, which uses the MEMS gyroscope and line accelerometer signals to implement the filtering function under the Kalman algorithm. The experimental results show that compared with the commonly used filtering methods, this method allows significant reduction of the noise of the gyroscope signal and accurate estimation of the drift of the gyroscope signal, and thus improves the control performance of the system and the stability accuracy.

6.
Int J Biol Macromol ; 139: 740-751, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377290

RESUMO

Frontal affinity chromatography (FAC) combined with enzyme has been widely used for drug screening. In this paper, the effect of target enzyme activity on screening of bioactive compounds was studied through applying FAC. Trypsin with different degree of inactivation were prepared as target enzyme by thermal denaturation. Their primary structure was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and use Fourier transform infrared (FTIR) and ultraviolet-visible (UV-vis) spectroscopy to detect group structure. Ultimately, it was found that the main structure of enzyme with decreased activity remained unchanged. The oxymatrine and matrine which can interact with trypsin were selected to study their binding to trypsin with different activities in FAC. The results showed that oxymatrine and matrine had a significant difference in the breakthrough volume among seven kinds of columns prepared by trypsins with different activities, at the different concentration. It indicated that trypsins with different activities in FAC could combine with oxymatrine and matrine. The binding constant (Kd) variation between oxymatrine, matrine and trypsin with different activities are 5.520 ±â€¯0.038 and 3.577 ±â€¯0.071, within error range, which indicated that the activity of target enzyme with primary unchanged structure has no effect on screening of bioactive components by FAC.

7.
Oncol Rep ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31436298

RESUMO

Bladder cancer (BC) is a potentially life­threatening malignancy. Due to a high recurrence rate, frequent surveillance strategies and intravesical drug therapies, BC is considered one of the most expensive tumors to treat. As a fundamental evolutionary catabolic process, autophagy plays an important role in the maintenance of cellular environmental homeostasis by degrading and recycling damaged cytoplasmic components, including macromolecules and organelles. Scientific studies in the last two decades have shown that autophagy acts as a double­edged sword with regard to the treatment of cancer. On one hand, autophagy inhibition is able to increase the sensitivity of cancer cells to treatment, a process known as protective autophagy. On the other hand, autophagy overactivation may lead to cell death, referred to as autophagic cell death, similar to apoptosis. Therefore, it is essential to identify the role of autophagy in cancer cells in order to develop novel therapeutic agents. In addition, autophagy may potentially become a novel therapeutic target in human diseases. In this review, the current knowledge on autophagy modulation in BC development and treatment is summarized.

8.
Sheng Li Xue Bao ; 71(4): 637-644, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440761

RESUMO

Mixed linked leukemia 4 (MLL4) is a specific methyltransferase of histone 3 position lysine 4 (H3K4). It is also one of the important members of COMPASS/Set1-like protein complex. Both MLL4 protein itself and its mediated H3K4 methylation modification can cause changes in chromatin structure and function, thus regulating gene transcription and expression. With the studies of MLL4 protein in recent years, the roles of MLL4 gene, MLL4 protein and protein complex in the development of tissues and organs, tumor diseases and other physiological and pathophysiological processes have been gradually revealed. In this paper, the research progress of MLL4 gene, MLL4 protein characteristics, biological function and its effect on disease were reviewed, in order to further understand the effect of histone methyltransferase on gene expression regulation, as well as its non-enzyme dependent function. This paper may provide new ideas for the prevention, diagnosis and treatment of related diseases.

9.
Soft Matter ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31461108

RESUMO

Effective remote control of mechanical toughening can be achieved by using thermo-responsive grafts such as poly(N-isopropylacrylamide) (PNIPAm) in a hydrophilic covalently cross-linked polymer network. The weight ratio of PNIPAm grafts in the network may impart such a thermo-responsive mechanical reinforcement. Here, we show that the network topology - especially graft length - is likewise crucial. A series of covalently cross-linked poly(N,N-dimethylacrylamide) (PDMA) gels grafted with PNIPAm side-chains of different lengths were designed and studied on both sides of phase separation temperature Tc, at a fixed overall polymer concentration of 16.7 wt% and constant PDMA/PNIPAm weight ratio. Phase-separated PNIPAm organic micro-domains were expected to act as responsive fillers above Tc and to generate a purely organic nanocomposite (NC). In contrast to conventional NC gels where dissipative processes take place at the solid nanoparticle/matrix interface, here dissipation originates from the disruption of the filler itself by the unravelling of the PNIPAm grafts embedded in collapsed domains. Results show that PNIPAm graft length is a key parameter to enhance - reversibly and on-demand - the mechanical response. The longer the graft is, the more effective the mechanical toughening is. Interestingly, for long PNIPAm grafts, above Tc, the hydrogels combine perfect transparency together with both increased stiffness and fracture toughness (up to 150 J m-2) at constant macroscopic volume. As a proof of concept, stimuli-responsive adhesion and shape-memory properties were designed to probe the inter-chain bridging efficiency (in bulk or bridging the interface).

10.
Acta Biomater ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31386929

RESUMO

Magnesium and its alloys were widely investigated in many body fluid microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine microenvironment. In this study, the degradation behaviors of HP-Mg, Mg-1Ca, and Mg-2Zn alloys in simulated uterine fluid (SUF) were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the gluteal muscle of rat was used as the implantation position to study the in vivo biocompatibility as a mimic of the intrauterine device (IUD) fixation part. The 120-day immersion test indicated that the Mg-1Ca alloy had a faster degradation rate than the Mg-2Zn alloy and HP-Mg and dissolved entirely in the SUF. Indirect cytotoxicity assay showed that the extracts of HP-Mg, Mg-1Ca, and Mg-2Zn alloys have positive effects on human uterine smooth muscle cells (HUSMC), human endometrial epithelial cells (HEEC), and human endometrial stromal cells (HESC), especially for the Mg-1Ca alloy group. Furthermore, the in vivo experiment showed that HP-Mg, Mg-1Ca, and Mg-2Zn alloy implants cause a light inflammatory response in the initial 3 days, but they were surrounded mainly by connective tissue, and lymphocytes were rarely observed at 4 weeks. Based on the above facts, we believed that it is feasible for using biomedical Mg alloys in obstetrics and gynecology and proposed three kinds of medical device candidates for future R&D. Statement of Significance Magnesium alloys were widely investigated in various body microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine environment. In this work, the degradation behaviors of Mg alloys in simulated uterine fluid were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the tibialis anterior of a rat model was used as the implantation position to study the in vivo biocompatibility. The comprehensive in vitro and in vivo testing results indicated that biomedical Mg alloys are feasible for use in obstetrics and gynecology. Further, three kinds of medical device candidates were proposed.

11.
Acta Biomater ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394294

RESUMO

Biodegradable magnesium alloys have attracted research interest as matrix materials for next-generation absorbable metallic coronary stents. Subject to cyclic stresses, magnesium alloy stents (MAS) are prone to premature failures caused by corrosion fatigue damage. This work aimed to develop a numerical continuum damage mechanics model, implemented with the finite element method, which can account for the corrosion fatigue of Mg alloys and the applications in coronary stents. The parameters in the resulting phenomenological model were calibrated using our previous experimental data of HP-Mg and WE43 alloy and then applied in assessing the performance of the MAS. The results indicated that it was valid to predict the degradation rate, the damage-induced reduction of the radial stiffness, and the critical location of the MAS. Furthermore, this model and the numerical procedure can be easily adapted for other biodegradable alloy systems, for instance, Fe and Zn, and used to achieve the optimal degradation rate while improving fatigue endurance. STATEMENT OF SIGNIFICANCE: Subject to cyclic stresses, magnesium alloy stents are prone to premature failures caused by corrosion fatigue damage. This work aimed to develop a numerical continuum damage mechanics model, implemented with the finite element method, which can account for the corrosion fatigue of Mg alloys and the applications in coronary stents. The results indicated that it was valid to predict the degradation rate, damage-induced reduction of the radial stiffness, and the critical location of the Mg alloy stent; therefore, these stents can be easily adapted to other biodegradable alloy systems such as Fe and Zn.

12.
BMC Ophthalmol ; 19(1): 167, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370817

RESUMO

BACKGROUND: The aim of this study was to compare the postoperative corneal biomechanical properties between small incision lenticule extraction (SMILE) and other corneal refractive surgeries. METHODS: A systematic review and meta-analysis were conducted. Articles from January 2005, to April 2019, were identified searching PubMed, EMBASE, Web of Science, and International Clinical Trials Registry Platform. Studies that compared SMILE with other corneal refractive surgeries on adult myopia patients and evaluated corneal biomechanics were included. Multiple effect sizes in each study were combined. Random-effects model was conducted in the meta-analysis. RESULTS: Twenty-two studies were included: 5 randomized controlled trials (RCTs), 9 prospective and 6 retrospective cohort studies, and 2 cross-sectional studies. Using the combined effect of corneal hysteresis (CH) and corneal resistance factor (CRF), which were obtained from ocular response analyzer (ORA), the pooled Hedges' g of SMILE versus femtosecond laser-assisted in situ keratomileusis (FS-LASIK) was 0.41 (95% CI, 0.00 to 0.81; p = 0.049; I2 = 78%), versus LASIK was 1.31 (95% CI, 0.54 to 2.08; p < 0.001; I2 = 77%), versus femtosecond lenticule extraction (FLEX) was - 0.01 (95% CI, - 0.31 to 0.30; p = 0.972; I2 = 20%), and versus the group of photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (LASEK) was - 0.26 (95% CI, - 0.67 to 0.16; p = 0.230; I2 = 54%). The summary score of Corvis ST (CST) after SMILE was comparable to FS-LASIK/LASIK with the pooled Hedges' g = - 0.05 (95% CI, - 0.24 to 0.14; p = 0.612, I2 = 55%). CONCLUSIONS: In terms of preserving corneal biomechanical strength after surgeries, SMILE was superior to either FS-LASIK or LASIK, while comparable to FLEX or PRK/LASEK group based on the results from ORA. More studies are needed to apply CST on evaluating corneal biomechanics after refractive surgeries.


Assuntos
Córnea/fisiopatologia , Ceratectomia Subepitelial Assistida por Laser/métodos , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Miopia/cirurgia , Ceratectomia Fotorrefrativa/métodos , Refração Ocular/fisiologia , Acuidade Visual , Fenômenos Biomecânicos , Córnea/cirurgia , Humanos , Miopia/fisiopatologia , Período Pós-Operatório
13.
Molecules ; 24(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31404982

RESUMO

Epigenetic modifications are important mechanisms responsible for cancer progression. Accumulating data suggest that (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, may hamper carcinogenesis by targeting epigenetic alterations. We found that signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor) domain-containing protein 2 (SCUBE2), a tumor suppressor gene, was hypermethylated in breast tumors. However, it is unknown whether EGCG regulates SCUBE2 methylation, and the mechanisms remain undefined. This study was designed to investigate the effect of EGCG on SCUBE2 methylation in breast cancer cells. We reveal that EGCG possesses a significantly inhibitory effect on cell viability in a dose- and time-dependent manner and presents more effects than other catechins. EGCG treatment resulted in enhancement of the SCUBE2 gene, along with elevated E-cadherin and decreased vimentin expression, leading to significant suppression of cell migration and invasion. The inhibitory effect of EGCG on SCUBE2 knock-down cells was remarkably alleviated. Further study demonstrated that EGCG significantly decreased the SCUBE2 methylation status by reducing DNA methyltransferase (DNMT) expression and activity. In summary, this study reported for the first time that SCUBE2 methylation can be reversed by EGCG treatment, finally resulting in the inhibition of breast cancer progression. These results suggest the epigenetic role of EGCG and its potential implication in breast cancer therapy.

14.
J Org Chem ; 84(17): 10805-10813, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31418570

RESUMO

In this work, selectivity-controllable base-promoted transition-metal-free borylation and dehalogenation of aryl halides are described. Under the conditions of borylation, the dehalogenation which emerges as a competitive side reaction has been well-controlled by carefully controlling the borylation conditions. On the other hand, the dehalogenation using benzaldehyde as a hydrogen source has also been accomplished. The applications of direct radical borylation and dehalogenation of aryl halides demonstrate their synthetic practicability in pharmaceutical-oriented organic synthesis. Based on the experimental evidences, the tBuOK/1,10-Phen-triggered radical nature of both competitive reactions has been revealed.

15.
Sheng Wu Gong Cheng Xue Bao ; 35(8): 1463-1468, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31441617

RESUMO

We studied the construction of fusion protein TAT-RIG-I-GFP prokaryotic expression vector and verified the function of TAT in transmembrane delivery. First, four pairs of specific primers were designed, and the RIG-I gene of Mallard Duck (Anas platyrhynchos) was cloned. Then, the pET-TAT-RIG-I-GFP and pET-RIG-I-GFP prokaryotic expression vectors were constructed. Meanwhile, they were converted to E. coli BL21 (DE3), which were induced to be expressed after culture. After the purification of His-60 nickel affinity chromatography column and the identification of SDS-PAGE, the purified TAT-RIG-I-GFP and RIG-I-GFP proteins were incubated to DF-1 cells. Finally, fluorescence microscopy was used to observe whether the corresponding fluorescence was produced in DF-1 cells. The results showed that pET-TAT-RIG-I-GFP fusion with TAT showed obvious green fluorescence in DF-1 cells. However, the pET-RIG-I-GFP without TAT cannot display green fluorescence. This shows that TAT-fused protein have successfully delivered DF-1 cells and play a key role in transmembrane delivery. In conclusion, these results provide a solid material basis for further study of antiviral drugs in poultry.


Assuntos
Produtos do Gene tat , Membrana Celular , Primers do DNA , Escherichia coli , Expressão Gênica , Vetores Genéticos , Proteínas Recombinantes de Fusão
16.
FEBS Lett ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365127

RESUMO

Bromhexine was reported to relieve the symptoms of Sjogren Syndrome at an early stage. However, the underlying mechanism remains unclear. Here, we administered bromhexine at low doses in human primary conjunctival fornix epithelial cells, and found it stimulated MUC5AC secretion and lipid droplet production. Expression of the metabolism-related gene CHML was also upregulated by bromhexine treatment, and REP2, the protein produced by the CHML gene, was induced. These results suggest that bromhexine is a potential candidate eye drop drug for the treatment of multiple types of dry eye disease, not only limited to the treatment of dry eyes in Sjogren Syndrome.

17.
Analyst ; 144(18): 5324-5352, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31348475

RESUMO

Medicinal plants with complex matrices are endowed with a wide scope of biological activities. The separation, quantification, characterization and purification of bioactive components from herbal medicine extracts have always challenged analysts. Fortunately, the advancement of various emerging techniques has provided potent support for improving the method selectivity, sensitivity and run speeds in medicinal plant analyses. In recent years, the advent of new-generation supercritical fluid chromatography (SFC) instruments and a wide diversity of column chemistries, coupled with the intrinsic technical features of SFC, have made it an alternative and prominent analytical platform in the medicinal plant research area. This work aims to give a comprehensive overview of the fundamentals, technical advancement and investigating parameters of SFC in combination with three prevalent detectors. Moreover, the latest research progress of SFC applications in medicinal plant analyses is illuminated, with focus on herbal medicine-related SFC papers on the analytical and preparative scale that were published during the period of 2012 to December 2018. The most relevant applications were classified based on the constituents to be analysed. As for the respective research cases, analytical protocols and data processing strategies were provided, along with the indicated restrictions or superiority of the method; thus, the current status of SFC in medicinal plant analysis was presented.

18.
Mol Immunol ; 114: 72-80, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31344551

RESUMO

Scleroderma is an inflammatory autoimmune disease characterized by extensive tissue fibrosis. The imbalance of effector T (Teff) and regulatory T (Treg) cells and the production of autoantibodies contribute to the pathogenesis of this disease. Metformin (MET) has anti-inflammatory and anti-fibrotic effects, but its effect on the in vivo pathogenesis of scleroderma remains unknown. Therefore, we investigated the potential therapeutic effects of MET treatment of mice with bleomycin (BLM)-induced scleroderma. Scleroderma was induced in female C57BL mice by daily subcutaneous injections of BLM for 28 days. After each 2 h BLM injection, mice received MET (200, 100 or 50 mg/kg) or saline (control) by intraperitoneal injection. At the end of the fourth week, spleen mononuclear cells were collected for flow cytometry analysis. Skin samples were harvested for immunohistochemistry and quantification of other biological parameters.Our results showed that BLM increased dermal thickness, collagen deposition, and hydroxyproline level, and MET markedly mitigated these effects. MET also restored the Treg/Teff cell balance. Accordingly, the level of IL-17A and RORγt (related to Th17 cells) decreased, but Foxp3 (related to Treg function) increased in a dose-dependent manner. In addition, MET treatment inhibited spleen germinal center formation. These results indicate that the immunomodulatory and anti-fibrosis effects of MET on BLM-induced scleroderma are mediated by the upregulation of Treg cell differentiation, inhibition of Teff cell differentiation, and suppression of spleen germinal center formation. These results suggest that MET may be a potential therapeutic for scleroderma.

19.
Int J Biol Macromol ; 138: 321-333, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295499

RESUMO

The aim of this study was to develop an effective wound dressing using a temperature-responsive hydroxybutyl chitosan (HBC) based hydrogel. The HBC - chitosan (CS) - dopamine (HCS-DOPA) composite hydrogels were prepared by the dopamine self-polymerization at different concentrations (0, 0.5, 1.0 and 2.0 mg/mL), termed as HCS, HCS-DOPA-0.5, HCS-DOPA-1 and HCS-DOPA-2, respectively. The gelling characteristic of HBC hydrogel was not influenced by composite CS and DOPA. The HCS-DOPA composite hydrogels were non-cytotoxic to mouse fibroblast cells (L929), and induced under 5.0% hemolysis rate. In vitro antibacterial studies, composite HCS-DOPA-2 hydrogels exhibited lasting inhibition to S. aureus >8 h. The whole blood test in vitro demonstrated that blood clotting time treated with HCS-DOPA-2 composite hydrogels was shortened to 95.6 s compared with that of HCS in vitro hemostasis. The results suggested that HCS-DOPA-2 composite hydrogels could be applied as a promising wound dressing for hemostasis in vitro.

20.
Int J Cancer ; 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31310010

RESUMO

Using a method optimized in hepatocellular carcinoma (HCC), we established patient-derived xenograft (PDX) models with an increased take rate (42.2%) and demonstrated that FBS +10% dimethyl sulfoxide exhibited the highest tumor take rate efficacy. Among 254 HCC patients, 103 stably transplantable xenograft lines that could be serially passaged, cryopreserved and revived were established. These lines maintained the diversity of HCC and the essential features of the original specimens at the histological, transcriptome, proteomic and genomic levels. Tumor engraftment was associated with lack of encapsulation, poor tumor differentiation, large size and overexpression of cancer stem cell biomarkers, and was an independent predictor for overall survival and tumor recurrence after resection. To confirm the preclinical value of the PDX model in HCC treatment, several antitumor agents were tested in 16 selected PDX models. The results revealed a high degree of pharmacologic heterogeneity in the cohort, as well as heterogeneity to different agents in the same individual. The sorafenib responses observed between HCC patients and the corresponding PDXs were also consistent. After molecular characterization of the PDX models, we explored the predictive markers for sorafenib response and found that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) might play an important role in sorafenib resistance and sorafenib response is impaired in patients with MAP3K1 downexpression. Our results indicated that PDX models could accurately reproduce patient tumors biology and could aid in the discovery of new treatments to advance in precision medicine.

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