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1.
J Chromatogr A ; 1633: 461636, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33160254

RESUMO

The traditional preparation of cellulose microspheres always involves tedious synthetic procedures (e.g., dissolution, emulsification and regeneration) and inevitable organic solvents, which undergoes both high production cost and environmental contamination. To overcome these issues, a feasible and green synthesis strategy is proposed to construct porous cellulose microspheres (PCMs) via one-step spontaneous formation relying on sodium periodate oxidation of pure bamboo fibers. By this strategy, a cluster of robust cellulose microspheres grow up on the surface of bamboo fibers in aqueous phase through amorphous oxidized cellulose self-assembly accumulation and then drop out when their sizes increase to about 15 µm. After being immobilized with Cu(II), the prepared cellulose microspheres serve as metal affinity adsorbent for proteins adsorption, showing high adsorption capacity, good selectivity and excellent reusability for bovine hemoglobin (BHb). Together with green and easy synthesis, the novel cellulose microspheres show a promising alternative to commercially available adsorbent support.

2.
Chin J Acad Radiol ; : 1-6, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33225216

RESUMO

The COVID-19 epidemic has swept across China and spread to other countries. The rapid spreading of COVID-19 and panic combined with the lack of a hierarchical medical system in China have resulted in a huge number of hospital visiting which are overwhelming local medical system and increasing the incidence of cross infection. To meliorate this situation, we adopted the management concept of the system of Tiered Diagnosis and Treatment and developed an online tool for self-triage based on the mostly used multi-purpose smartphone app Wechat in China. This online tool helps people perform self-triage so that they can decide whether to quarantine at home or visit hospital. This tool further provides instructions for home quarantine and help patients make an appointment online if hospital visiting suggested. This smartphone application can reduce the burden on hospitals without losing the truly COVID-19 patients and protect people from the danger of cross infection.

4.
Sci Signal ; 13(657)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172955

RESUMO

The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of ß-catenin, a Wnt signaling effector. We investigated how DKK1 expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate DKK1 transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser37, which promoted its nuclear translocation. Also in these cells, EGFR-activated Akt phosphorylated the acetyltransferase p300 at Ser1834 Subsequently, PKM2 and p300 mediated the phosphorylation and acetylation, respectively, of histone H3 at the DKK1 promoter, which synergistically enhanced DKK1 transcription. The mechanism was supported with mutational analyses in cells and in a chemically induced HCC model in rats. The findings suggest that dual inhibition of the MEK and PI3K pathways might suppress the expression of DKK1 and, consequently, tumor metastasis in patients with HCC.

5.
Environ Pollut ; : 115975, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33168374

RESUMO

In this work, the novel technology was used to remove heavy metal from sludge. The coupled with biodegradable ethylenediamine disuccinic acid (EDDS) and approaching anode electrokinetic (AA-EK) technique was used to enhance heavy metal removing from sludge. Electric current, sludge and electrolyte characteristics, heavy metal removal efficiency and residual content distribution, and heavy metal fractions percentage of variation were evaluated during the electrokinetic remediation process. Results demonstrated that the coupled with EDDS and AA-EK technique obtain a predominant heavy metal removal efficiency, and promote electric current increasing during the enhanced electrokinetic remediation process. The catholyte electrical conductivity was higher than the anolyte, and electrical conductivity of near the cathode sludge achieved a higher value than anode sludge during the coupled with EDDS and AA-EK remediation process. AA-EK technique can produce a great number of H+, which caused the sludge acidification and pH decrease. Cu, Zn, Cr, Pb, Ni and Mn obtain the highest extraction efficiency after the coupled with EDDS and AA-EK remediation, which were 52.2 ± 2.57%, 56.8 ± 3.62%, 60.4 ± 3.62%, 47.2 ± 2.35%, 53.0 ± 3.48%, 54.2 ± 3.43%, respectively. Also, heavy metal fractions analysis demonstrated that the oxidizable fraction percentage decreased slowly after the coupled with EDDS and AA-EK remediation.

6.
Cancer Sci ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164305

RESUMO

High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in hepatocellular carcinoma (HCC) cells remains largely unclear. Here, we demonstrated that the expression HMGA2 was upregulated in HCC, and the elevated HMGA2 could promote tumor metastasis. Incubation HCC cells with Epidermal Growth Factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, while a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.

7.
Theranostics ; 10(26): 12263-12278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204341

RESUMO

Emerging evidence is revealing that microRNAs (miRNAs) play essential roles in mechanosensing for regulating osteogenesis. However, no mechanoresponsive miRNAs have been identified in human bone specimens. Methods: Bedridden and aged patients, hindlimb unloaded and aged mice, and Random Positioning Machine and primary aged osteoblasts were adopted to simulate mechanical unloading conditions at the human, animal and cellular levels, respectively. Treadmill exercise and Flexcell cyclic mechanical stretching were used to simulate mechanical loading in vivo and in vitro, respectively. Results: Here, we found increased miR-138-5p levels with a lower degree of bone formation in bone specimens from bedridden and aged patients. Loss- and gain-of-function studies showed that miR-138-5p directly targeted microtubule actin crosslinking factor 1 (MACF1) to inhibit osteoblast differentiation under different mechanical conditions. Regarding translational medicine, bone-targeted inhibition of miR-138-5p attenuated the decrease in the mechanical bone anabolic response in hindlimb unloaded mice. Moreover, bone-targeted inhibition of miR-138-5p sensitized the bone anabolic response to mechanical loading in both miR-138-5p transgenic mice and aged mice to promote bone formation. Conclusion: These data suggest that miR-138-5p as a mechanoresponsive miRNA accounts for the mechanosensitivity of the bone anabolic response and that inhibition of miR-138-5p in osteoblasts may be a novel bone anabolic sensitization strategy for ameliorating disuse or senile osteoporosis.

9.
Oral Dis ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078488

RESUMO

OBJECTIVE: To determine whether risk factors other than hyperglycemia lead to failed osseointegration in patients with type 2 diabetes mellitus (T2DM) during the healing period. MATERIALS AND METHODS: We compared the success rates between patients with and without T2DM during the healing period at our center. Bone marrow mesenchymal stem cells (BMSCs) were cultured from subjects. Proteomics was used to detect differentially expressed proteins (DEPs) among the DM failure (DM-F), DM success (DM-S), and control (Con) groups. The correlation between the expression levels of nine target DEPs and medium glucose concentrations was investigated. RESULTS: Higher failure rates were observed in the T2DM patients. Fifty-two DEPs were found between the DM-F and DM-S groups. Seventy-three DEPs were found between the DM-F and Con groups. Forty-three DEPs were found between the DM-S and Con groups. Five target DEPs were expressed at the same levels in the medium with different glucose concentrations. Gene ontology annotation and functional enrichment analysis suggest that the DEPs detected in the DM-F group may affect the biological function and regulatory potential of BMSCs. CONCLUSIONS: The DEPs detected in the DM-F group can be intervention targets for to prevent implant failure in T2DM patients. Risk factors besides hyperglycemia may affect osseointegration during healing period.

10.
Nat Commun ; 11(1): 5367, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097735

RESUMO

Alkali metals are widely studied in various fields such as medicine and battery. However, limited by the chemical reactivity and electron/ion beam sensitivity, the intrinsic atomic structure of alkali metals and its fundamental properties are difficult to be revealed. Here, a simple and versatile method is proposed to form the alkali metals in situ inside the transmission electron microscope. Taking alkali salts as the starting materials and electron beam as the trigger, alkali metals can be obtained directly. With this method, atomic resolution imaging of lithium and sodium metal is achieved at room temperature, and the growth of alkali metals is visualized at atomic-scale with millisecond temporal resolution. Furthermore, our observations unravel the ambiguities in lithium metal growth on garnet-type solid electrolytes for lithium-metal batteries. Finally, our method enables a direct study of physical contact property of lithium metal as well as its surface passivation oxide layer, which may contribute to better understanding of lithium dendrite and solid electrolyte interphase issues in lithium ion batteries.

11.
J Ethnopharmacol ; 266: 113446, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031902

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is an aggressive malignancy with increasing mortality in China. Screening and identifying effective anticancer compounds from active traditional Chinese herbs for HCC are in demand. Akebia trifoliata (Thunb) Koidz, with pharmacological anti-HCC activities in clinical, has been shown in previous research. In the present research, we elucidated a potential anticancer effect of Akebia saponin E (ASE), which is isolated from the immature seeds of Akebia trifoliata (Thunb.) Koidz, and revealed that ASE could induce severe expanded vacuoles in HCC cells. But the potential mechanism of vacuole-formation and the anti-HCC effects by ASE remain uncover. AIM OF THIS STUDY: To elucidate the potential mechanism of vacuole-formation and the proliferation inhibition effects by ASE in HCC cell lines. MATERIALS AND METHODS: MTT assay, colony formation assay and flow cytometry were performed to detect cell viability. Immunofluorescence analysis was used to examine the biomarkers of endomembrane. Cells were infected with tandem mRFP-GFP-LC3 lentivirus to assess autophagy flux. RNA-seq was conducted to analyze the genome-wide transcriptional between treatment cell groups. In vitro PIKfyve kinase assay is detected by the ADP-GloTM Kinase Assay Kit. RESULTS: ASE could inhibit the proliferation of HCC with severe expanded vacuoles in vitro, and could significantly reduce the size and weight of xenograft tumor in vivo. Further, the vacuoles induced by ASE were aberrant enlarged lysosomes instead of autophagosome or autolysosomes. With cytoplasmic vacuolation, ASE induced a mTOR-independent TFEB activation for lysosomal biogenesis and a decrement of cholesterol levels in HCC cells. Furthermore, ASE could reduce the activity of PIKfyve (phosphoinositide kinase containing a FYVE-type finger), causing aberrant lysosomal biogenesis and cholesterol dyshomeostasis which triggered the expanded vacuole formation. CONCLUSION: ASE can prospectively inhibit the kinase activity of PIKfyve to induce lysosome-associated cytoplasmic vacuolation, and may be utilized as an alternative candidate to treat human HCC.

12.
Phys Rev Lett ; 125(12): 123901, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33016716

RESUMO

Optical nonreciprocity is an essential property for a wide range of applications, such as building nonreciprocal optical devices that include isolators and circulators. The realization of optical nonreciprocity relies on breaking the symmetry associated with Lorentz reciprocity, which typically requires stringent conditions such as introducing a strong magnetic field or a high-finesse cavity with nonreciprocal coupling geometry. Here we discover that the collision effect of thermal atoms, which is undesirable for most studies, can induce broadband optical nonreciprocity. By exploiting the thermal atomic collision, we experimentally observe magnet-free and cavity-free optical nonreciprocity, which possesses a high isolation ratio, ultrabroad bandwidth, and low insertion loss simultaneously. The maximum isolation ratio is close to 40 dB, while the insertion loss is less than 1 dB. The bandwidth for an isolation ratio exceeding 20 dB is over 1.2 GHz, which is 2 orders of magnitude broader than typical resonance-enhanced optical isolators. Our work paves the way for the realization of high-performance optical nonreciprocal devices and provides opportunities for applications in integrated optics and quantum networks.

13.
Anal Bioanal Chem ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064163

RESUMO

Ochratoxin A (OTA) is a toxic metabolite produced mainly by Aspergillus and Penicillium species. A quantitative method was developed for the rapid, simple, and sensitive detection of OTA in corn by quantum dots-based fluorescent immunochromatographic assay (QDs-ICA). The CdSe/ZnS QDs-labelled anti-OTA monoclonal antibody (mAb) conjugates were designed as the fluorescent signal probe. The QDs-ICA included the designation of test line (T line) and control line (C line), which were sprayed with optimal concentrations of the OTA-OVA and staphylococcal protein-A (SPA), respectively. Under the optimal experimental conditions, the QDs-ICA exhibited excellent specificity and good accuracy and precision. For qualitative detection, the cut-off value for the T line of the visual detection method was 2.5 ng/mL. For quantitative detection, the linear regression equation of the standard curve was y = 0.366x + 0.514 with a reliable correlation coefficient (R2 = 0.992). Moreover, the 50% inhibition value (IC50) of the QDs-ICA was 0.91 ng/mL, the limit of detection (LOD) was 0.07 ng/mL, and the detection range was 0.05 to 10 ng/mL. In addition, the recovery rates ranged from 91.82 to 100.35% with a coefficient of variation (CV) below 3% for intra-assay, whereas the recovery rates for inter-assay changed from 94.29 to 104.62% with a CV below 10%. These results indicate that the QDs-ICA can serve as a potential large-scale preliminary device for rapid determination of OTA. Using CdSe/ZnS QDs as the fluorescent signal for quantum dots-based fluorescent immunochromatographic assay, the QDs-ICA provided a novel method for the rapid simultaneous qualitative and quantitative determination of OTA.

14.
Chin Med J (Engl) ; 133(22): 2731-2742, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32889913

RESUMO

BACKGROUND: Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. METHODS: The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. RESULTS: A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34). CONCLUSIONS: In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.

15.
Financ Res Lett ; : 101749, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32908465

RESUMO

The main purpose of this paper is to investigate whether the Infectious Disease EMV tracker (IDEMV) proposed by Baker et al. (2020) has additional predictive ability for European stock market volatility during the COVID-19 pandemic. The three European stock markets we consider are France, UK and Germany. Our investigation is based on the HAR and its augmented models. We find that the IDEMV has stronger predictive power for the France and UK stock markets volatilities during the global pandemic, and the VIX has also superior predictive ability for the three European stock markets during this period.

16.
Talanta ; 219: 121363, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887085

RESUMO

In this work, the correlations between retention behavior and lipophilicity of a large set of hydrophilic neutral and ionic analytes were studied based on three hydrophilic interaction liquid chromatography (HILIC) stationary phases, including zwitterionic, crosslinked diol and triazole stationary phases. It was found that HILIC, due to the diversity of retention mechanism, is a more complex chromatography separation mode than reversed-phase liquid chromatography (RPLC) which has been widely accepted for lipophilicity assessment. Because electrostatic interactions contributed to the overall retention of the charged solutes on all three stationary phases, ion-strength of the mobile phase kept the same during the whole experiment. After the correlations between retention factor log k and water volume fraction Φ were investigated, the mixed retention model was revealed to be more suitable for HILIC retention behavior than other single models including partitioning and adsorption model. Moreover, in order to bridge the relationship between HILIC log k and lipophilicity parameter log D, net charge ne and Abraham solvation parameter were introduced in the quantitative structure-retention relationship (QSRR) model. Although the correlation coefficients between log D and log k were still moderate, the significant improvement in correlation has made HILIC a potential choice as the complement of RPLC for log D measurement.

17.
Theranostics ; 10(21): 9663-9673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863952

RESUMO

Introduction: To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality. Methods: We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis. Results: In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions, P for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72), P=0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91), P=0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality. Conclusions: In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19.


Assuntos
Cardiomiopatias/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Troponina I/sangue , Idoso , Cardiomiopatias/sangue , China , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
18.
Mater Sci Eng C Mater Biol Appl ; 114: 111047, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32994009

RESUMO

This study presents a state-of-the-art soft and biocompatible transducer capable of detecting vessel inner-wall pressure for biomedical applications. The device includes a 3D electroactive polymer core element encapsulated by polydimethylsiloxane with an ellipsoidal structure. The device produces a voltage output when its sensing mechanism experiences different pressures, resulting in deformation at different orientations. Thus, it can be employed to detect the pressure exerted by inner vessel walls of different stiffness values. The output voltage is induced by the strain experienced by the sensing mechanism of the device without the need for any external electrical power source. The core element, which is made of an ionic polymer-metal composite, possesses a unique hollow design; this allows a catheter to pass through, and the core element can be anchored at an arbitrary position on the catheter. We also demonstrate that the fabricated device can be integrated with a medically used percutaneous transluminal angioplasty balloon catheter to form a smart sensing module. This module can detect different levels of fat accumulation around the inner wall of a blood vessel phantom. Evaluating vessel blockage and stiffness using the signals acquired from the developed device is discussed.

19.
Int J Prosthodont ; 33(5): 565-571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956438

RESUMO

This case history report describes a comprehensive digital workflow for implant treatment and occlusal reconstruction to provide a systematic protocol for implant-supported restorations in edentulous patients. In this case, a restoration-oriented surgical protocol was created using an oral implant planning and design software. The implant surgery was completed under the guidance of a fully guided surgical template. This is the first report of the combined application of computer-aided diagnosis axiograph and neuromuscular evaluation systems in implant-supported occlusal reconstruction. Digital technologies can increase the accuracy, efficiency, and comfort of implant treatment and achieve satisfactory occlusal reconstruction outcomes in edentulous patients.


Assuntos
Implantes Dentários , Arcada Edêntula/cirurgia , Cirurgia Assistida por Computador , Desenho Assistido por Computador , Implantação Dentária Endo-Óssea , Prótese Dentária Fixada por Implante , Humanos , Mandíbula , Fluxo de Trabalho
20.
Exp Neurol ; 334: 113482, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979370

RESUMO

Wnt5b, a member of Wnt family, plays multiple roles in tumor progression and metastasis. However, whether Wnt5b contributes to the sensitization of dorsal root ganglia (DRG) neurons and pathogenesis of bone cancer pain still remains unclear. Here, we found that the protein expression of Wnt5b and its atypical tyrosine protein kinase receptor Ryk was upregulated in ipsilateral DRGs in tumor-bearing mice. Application of Wnt5b evoked an increased discharge frequency in isolated DRG neurons and pain hypersensitivity in naïve mice which were almost completely prevented by anti-Ryk antibody. Moreover, intrathecal injection of anti-Ryk antibody to tumor-bearing mice significantly inhibited bone cancer-induced mechanic allodynia and thermal hyperalgesia. Subsequently, we also demonstrated that application of Wnt5b to cultured DRG neurons could enhance membrane P2X3 receptors and α,ß-meATP-induced currents. Intrathecal injection of calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 or P2X3 receptors antagonist A317491 almost completely abolished Wnt5b-induced mechanical allodynia and thermal hyperalgesia in mice. Meanwhile, pretreatment with anti-Ryk antibody or CaMKII inhibitor KN93 can attenuate bone-cancer induced the upregulation of P2X3 membrane protein as well as pain hypersensitivity. These findings suggested that Wnt5b/Ryk promoted the trafficking of P2X3 receptors to the membrane via the activation of CaMKII in primary sensory neurons, resulting in peripheral sensitization and bone cancer-induced pain. Our results may offer a potential therapeutic strategy for bone cancer pain.

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