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1.
Proc Natl Acad Sci U S A ; 121(13): e2320386121, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38513101

ABSTRACT

Stimuli-responsive soft robots offer new capabilities for the fields of medical and rehabilitation robotics, artificial intelligence, and soft electronics. Precisely programming the shape morphing and decoupling the multiresponsiveness of such robots is crucial to enable them with ample degrees of freedom and multifunctionality, while ensuring high fabrication accuracy. However, current designs featuring coupled multiresponsiveness or intricate assembly processes face limitations in executing complex transformations and suffer from a lack of precision. Therefore, we propose a one-stepped strategy to program multistep shape-morphing soft millirobots (MSSMs) in response to decoupled environmental stimuli. Our approach involves employing a multilayered elastomer and laser scanning technology to selectively process the structure of MSSMs, achieving a minimum machining precision of 30 µm. The resulting MSSMs are capable of imitating the shape morphing of plants and hand gestures and resemble kirigami, pop-up, and bistable structures. The decoupled multistimuli responsiveness of the MSSMs allows them to conduct shape morphing during locomotion, perform logic circuit control, and remotely repair circuits in response to humidity, temperature, and magnetic field. This strategy presents a paradigm for the effective design and fabrication of untethered soft miniature robots with physical intelligence, advancing the decoupled multiresponsive materials through modular tailoring of robotic body structures and properties to suit specific applications.

2.
Proc Natl Acad Sci U S A ; 120(42): e2308301120, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37792517

ABSTRACT

Artificial cilia integrating both actuation and sensing functions allow simultaneously sensing environmental properties and manipulating fluids in situ, which are promising for environment monitoring and fluidic applications. However, existing artificial cilia have limited ability to sense environmental cues in fluid flows that have versatile information encoded. This limits their potential to work in complex and dynamic fluid-filled environments. Here, we propose a generic actuation-enhanced sensing mechanism to sense complex environmental cues through the active interaction between artificial cilia and the surrounding fluidic environments. The proposed mechanism is based on fluid-cilia interaction by integrating soft robotic artificial cilia with flexible sensors. With a machine learning-based approach, complex environmental cues such as liquid viscosity, environment boundaries, and distributed fluid flows of a wide range of velocities can be sensed, which is beyond the capability of existing artificial cilia. As a proof of concept, we implement this mechanism on magnetically actuated cilia with integrated laser-induced graphene-based sensors and demonstrate sensing fluid apparent viscosity, environment boundaries, and fluid flow speed with a reconfigurable sensitivity and range. The same principle could be potentially applied to other soft robotic systems integrating other actuation and sensing modalities for diverse environmental and fluidic applications.


Subject(s)
Cilia , Magnetics , Physical Phenomena , Hydrodynamics , Magnetic Phenomena
3.
J Am Chem Soc ; 146(8): 5669-5677, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38350029

ABSTRACT

Advanced atomic-level heterointerface engineering provides a promising method for the preparation of next-generation catalysts. Traditional carbon-based heterointerface catalytic performance rely heavily on the undetermined defects in complex and demanding preparation processes, rendering it impossible to control the catalytic performance. Here, we present a general method for the controlled growth of metal atom arrays on graphdiyne (GDY/IrCuOx), and we are surprised to find strong heterointerface strains during the growth. We successfully controlled the thickness of GDY to regulate the heterointerface metal atoms and achieved compressive strain at the interface. Experimental and density functional theory calculation results show that the unique incomplete charge transfer between GDY and metal atoms leads to the formation of strong interactions and significant heterointerface compressive strain between GDY and IrCuOx, which results in high oxidation performances with 1000 mA cm-2 at a low overpotential of 283 mV and long-term stability at large current densities in alkaline simulated seawater. We anticipate that this finding will contribute to construction of high-performance heterogeneous interface structures, leading to the development of new generation of GDY-based heterojunction catalysts in the field of catalysis for future promising performance.

4.
Small ; : e2401347, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38716685

ABSTRACT

A challenge facing the chlor-alkali process is the lack of electrocatalyst with high activity and selectivity for the efficient industrial production of chlorine. Herein the authors report a new electrocatalyst that can generate multi-interface structure by in situ growth of graphdiyne on the surface of cobalt oxides (GDY/Co3O4), which shows great potential in highly selective and efficient chlorine production. This result is due to the strong electron transfer and high density charge transport between GDY and Co3O4 and the interconversion of the mixed valence states of the Co atoms itself. These intrinsic characteristics efficiently enhance the conductivity of the catalyst, facilitate the reaction kinetics, and improve the overall catalytic selectivity and activity. Besides, the protective effect of the formed GDY layer is remarkable endowing the catalyst with excellent stability. The catalyst can selectively produce chlorine in low-concentration of NaCl aqueous solution at room temperature and pressure with the highest Faraday efficiency of 80.67% and an active chlorine yield rate of 184.40 mg h-1 cm-2, as well as superior long-term stability.

5.
Nat Mater ; 22(10): 1243-1252, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37604911

ABSTRACT

Stimuli-responsive geometric transformations endow metamaterials with dynamic properties and functionalities. However, using existing transformation mechanisms to program a single geometry to transform into diverse final configurations remains challenging, imposing crucial design restrictions on achieving versatile functionalities. Here, we present a programmable strategy for wide-spectrum reconfigurable micro-metastructures using linearly responsive transparent hydrogels as artificial muscles. Actuated by the hydrogel, the transformation of micro-metastructures arises from the collaborative buckling of their building blocks. Rationally designing the three-dimensional printing parameters and geometry features of the metastructures enables their locally isotropic or anisotropic deformation, allowing controllable wide-spectrum pattern transformation with programmable chirality and optical anisotropy. This reconfiguration mechanism can be applied to various materials with a wide range of mechanical properties. Our strategy enables a thermally reconfigurable printed metalattice with pixel-by-pixel mapping of different printing powers and angles for displaying or hiding complex information, providing opportunities for encryption, miniature robotics, photonics and phononics applications.

6.
Cancer Sci ; 114(8): 3396-3410, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37290894

ABSTRACT

Gastric cancer (GC) has high rates of morbidity and mortality, and this phenomenon is particularly evident in coastal regions where local dietary habits favor the consumption of pickled foods such as salted fish and vegetables. In addition, the diagnosis rate of GC remains low due to the lack of diagnostic serum biomarkers. Therefore, in this study, we aimed to identify potential serum GC biomarkers for use in clinical practice. To identify candidate biomarkers of GC, 88 serum samples were first screened using a high-throughput protein microarray to measure the levels of 640 proteins. Then, 333 samples were used to validate the potential biomarkers using a custom antibody chip. ELISA, western blot, and immunohistochemistry were then used to verify the expression of the target proteins. Finally, logistic regression was performed to select serum proteins for the diagnostic model. As a result, five specific differentially expressed proteins, TGFß RIII, LAG-3, carboxypeptidase A2, Decorin and ANGPTL3, were found to have the ability to distinguish GC. Logistic regression analysis showed that the combination of carboxypeptidase A2 and TGFß RIII had superior potential for diagnosing GC (area under the ROC curve [AUC] = 0.801). The results suggested that these five proteins alone and the combination of carboxypeptidase A2 and TGFß RIII may be used as serum markers for the diagnosis of GC.


Subject(s)
Biomarkers, Tumor , Stomach Neoplasms , Humans , Protein Array Analysis , Stomach Neoplasms/diagnosis , Carboxypeptidases A , Early Detection of Cancer , ROC Curve , Angiopoietin-Like Protein 3
7.
BMC Oral Health ; 23(1): 410, 2023 06 21.
Article in English | MEDLINE | ID: mdl-37344826

ABSTRACT

BACKGROUND: The purpose of this study is to investigate the performance and fracture resistance of different resin-matrix ceramic materials for use in implant-supported single crowns with respect to the abutment design (crown thickness: 1 mm, 2 and 3 mm). METHODS: Forty-eight abutments and crowns were fabricated on implants in the right lower first molar. Two resin-matrix ceramic materials for dental crowns were selected for study: (1) a glass-ceramic in a resin interpenetrating matrix (Vita Enamic, Vita, Germany) and (2) a resin-based composite with nanoparticle ceramic filler (Lava Ultimate, 3 M ESPE, USA). Three types of abutments were designed: 1 mm thick crown + custom titanium abutment, 2 mm thick crown + custom titanium abutment and 3 mm thick crown + prefabricated titanium abutment. The experiment was divided into 6 groups (n = 8) according to the crown materials and abutment designs. After 10,000 thermocycles, fracture resistance was measured using a universal testing machine. The statistical significance of differences between various groups were analysed with ANOVA followed by a post hoc Tukey's honestly significant difference test. The surfaces of the fractured specimens were examined with scanning electron microscopy (SEM). RESULTS: Two-way ANOVA revealed that the abutment design (F = 28.44, P = 1.52 × 10- 8<0.001) and the crown materials (F = 4.37, P = 0.043 < 0.05) had a significant effect on the fracture resistance of implant crown restoration. The Lava Ultimate-2 mm group showed the highest fracture resistance of 2222.74 ± 320.36 N, and the Vita Enamic-3 mm group showed the lowest fracture resistance of 1204.96 ± 130.50 N. Most of the 1 and 2 mm groups had partial crown fractures that could be repaired directly with resin, while the 3 mm group had longitudinal fracture of the crown, and the crowns were detached from the abutments. CONCLUSION: Based on the in vitro data of this study, the fracture resistance of the 2 mm thick resin-matrix ceramic crown design was higher than that of the 1 and 3 mm groups. The 2 mm thick resin-matrix ceramic crown and personalized abutment are an option to replace zirconia for implant crown restoration.


Subject(s)
Dental Implants , Humans , Crowns , Titanium , Ceramics , Dental Porcelain , Materials Testing , Dental Restoration Failure , Dental Stress Analysis , Computer-Aided Design
8.
Int Wound J ; 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37737032

ABSTRACT

Fast track surgery (FTS) is widely used in many procedures and has been shown to reduce complications and accelerate recovery. However, no studies have been conducted to assess their effectiveness in treating wounds after radical prostatectomy (RP). The objective of this study was to evaluate the impact of FTS on RP. We went through 4 major databases. A study was conducted by PubMed, the Cochrane Library, Embase, and the Web of Science to determine the effect of comparison of FTS versus conventional surgery in RP on postoperative wound complications as of 1 July 2023. Based on the review of literature, data extraction and literature quality assessment, we conducted meta-analyses with RevMan 5.3. In the course of the study, the researchers selected 6 of the 404 studies to be analysed according to exclusion criteria. Data analysis showed that the FTS method reduced the postoperative pain associated with VAS and also decreased the rate of postoperative complications in post-surgical patients. However, there was no significant difference between FTS and conventional surgery in terms of blood loss, operation time, and postoperative infection rate. Therefore, generally speaking, FTS has less impact on postoperative complications in patients with minimal invasive prostatic cancer, but it does reduce postoperative pain and total postoperative complications.

9.
Angew Chem Int Ed Engl ; 62(8): e202215968, 2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36593176

ABSTRACT

Rechargeable aqueous zinc ion batteries (AZIBs) promise high energy density, low redox potential, low cost and safety; however, their cycle performances are seriously insufficient to restrict the progress in this field. We propose a new concept of atomic electrode formed on the graphdiyne (GDY). This new idea electrode was synthesized by selectively, uniformly, and stably anchoring Zn atoms on GDY at the beginning of plating. The Zn atoms are induced to grow into larger size Zn clusters, which continue to grow into nanoflat. Finally, a new heterojunction interface is formed on GDY without any Zn dendrites and side reactions, even at high current densities. Such stepwise induction of growth greatly suppresses the formation of Zn dendrites, resulting in high electroplating/stripping reversibility and lifespan of AZIBs.

10.
Small ; 18(13): e2107136, 2022 04.
Article in English | MEDLINE | ID: mdl-35119196

ABSTRACT

The intrinsic catalytic activity and active sites of the catalyst originate from the interface efficient charge transfer. A 2D graphdiyne (GDY) layer grown on the surface of zeolitic imidazolate framework nanocubes (ZIFNC@GDY) forms a novel structure of a perfect "donor-bridge-acceptor" interface, in which the ZIFNC and GDY act as electron donor and acceptor, respectively, linked by the sp-C-Co and sp-C-N bonds as bridges. Importantly, the as-prepared catalyst exhibits intrinsically high reactivity for ammonia production through the nitrate reduction reaction (NtRR) in neutral aqueous solutions at ambient pressures and temperatures. The NtRR performance of the as-prepared electrocatalyst is confirmed by the high NH3 yield rate (YNH3 ) of 0.40 ± 0.02 mmol h-1  cm-2 at potential of -0.745V versus RHE and Faradaic efficiency (FE) of 98.51 ± 0.75%, as well as the excellent stability. We show that such unique interfacial structures can accelerate the efficient electron transfers between the zeolitic imidazolate framework nanocubes (ZIFNC) core and GDY shell, enrich the electron density on the GDY surface, and thereby promote fast redox switching, creating more active sites, and improving the catalytic performances.


Subject(s)
Ammonia , Zeolites , Catalysis , Oxidation-Reduction
11.
Luminescence ; 37(12): 2098-2104, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36268695

ABSTRACT

In this paper, the multisignal (different emissions/colours) temperature sensing of NaYF4 :Eu3+ nanoparticles is investigated, which is based on fluorescence intensity ratios (FIRs) between 5 D0 →7 FJ (J=1-4) and 5 D1 →7 FJ' emissions. The 5 D1 →7 FJ' (J'=0-2) emissions can be clearly observed due to the low photon energy of NaYF4 . Based on the FIRs between different 5 D0 →7 FJ and 5 D1 →7 FJ' emissions, higher absolute/relative temperature sensitivities are obtained. Compared with the FIR between whole 5 D0 →7 FJ and 5 D1 →7 FJ' emissions, the maximum value of Sa was improved from 0.27 K-1 to 5.02 K-1 and that of Sr was improved from 0.89%·K-1 to 1.27%·K-1 . Furthermore, the FIRs between different colours of emissions were investigated for the application of wide-range multicolour temperature sensing.


Subject(s)
Nanoparticles , Humans , Photons , Fever
12.
BMC Oral Health ; 22(1): 396, 2022 09 12.
Article in English | MEDLINE | ID: mdl-36096836

ABSTRACT

BACKGROUND: This research aimed to explore feasibility and the time required when erbium-doped yttrium aluminum garnet (Er:YAG) laser as a non-invasive treatment modality to retrieve different thicknesses of zirconia material bonded by two dental cements from titanium implant abutments. METHODS: Prepared 80 titanium blocks (length: 20 mm, width: 10 mm, height: 10 mm) and square zirconia sheets (length: 10 mm) with different thicknesses (1 mm, 2 mm, 3 mm, and 4 mm) were 20 pieces each. Resin modified glass ionomer cement (RelyX Luting 2; RXL) and resin cement (Clearfil SA luting; CSL) were used to bond zirconia sheet and titanium block. Specimens were kept in 100% humidity for 48 h. Er:YAG laser was used to retrieve the zirconia sheet and recorded the time. Universal testing machine was used to measure the residual adhesion of the samples that did not retrieve after 5 min of laser irradiation. Shear bond strength (MPa) and the time data (s) were analyzed using Kruskal-Wallis Test. The bonding surface and the irradiation surface of the zirconia sheet was examined with the scanning electron microscopy (SEM). RESULTS: Within 5 min of laser irradiation, RXL group: 1 mm group all fell off, 2 mm group had 3 specimens did not fall off, there was no statistical difference in the average time between the two groups; CSL group: half of the 1 mm group fell off. Shear bond strength test results: there was no statistical difference between 1 and 2 mm in RXL group and 1 mm in CSL group, there was no statistical difference between 3 mm in RXL group and 2 mm in CSL group, and there were significant differences statistically in comparison between any two groups in the rest. SEM inspection showed that the bonding surface and the irradiation surface of the zirconia sheet had changes. CONCLUSION: In this vitro study, the following could be concluded: it is faster to remove zirconia crowns with thickness less than 2 mm from titanium abutment when luted with RelyX Luting 2 compared to Clearfil SA luting.


Subject(s)
Dental Bonding , Dental Implants , Lasers, Solid-State , Crowns , Humans , Lasers, Solid-State/therapeutic use , Titanium , Zirconium
13.
J Pak Med Assoc ; 72(6): 1201-1204, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35751336

ABSTRACT

The aim of this study was to investigate the relationship between apoA-I, chemerin, and Procalcitonin (PCT) and the severity of hyperlipidaemia-induced acute pancreatitis (HLAP), as well as the importance of their application in the diagnosis of severe HLAP. This study was conducted at the 363 Hospital, Chengdu City, China, from January 2016 to August 2020. There were significant differences in the levels of serum apoA-I, chemerin, and PCT among the three-mild, moderate and severe-groups (all p <0.001). Serum apoA-I was negatively correlated with chemerin and PCT levels in the severe group (p=0.006, p=0.011, respectively). Serum chemerin and PCT levels in the severe group was a positive correlation (p=0.032). Receiver Operating Characteristic (ROC) curve area of serum apoA-I in the diagnosis of severe HLAP was 0.808 (95% CI:0.727-0.888, p value <0.001), which was higher than that in serum chemerin and PCT, and its sensitivity and specificity were 0.628 and 0.814, respectively. Hence, in patients with HLAP, serum apoA-I, chemerin, and PCT are closely correlated. The efficacy of serum apoA-I in the diagnosis of severe HLAP is higher than that of serum chemerin and PCT.


Subject(s)
Hyperlipidemias , Pancreatitis , Acute Disease , Apolipoprotein A-I , Biomarkers , Humans , Hyperlipidemias/complications , Pancreatitis/diagnosis , Procalcitonin , Prognosis , ROC Curve
14.
BMC Vet Res ; 17(1): 266, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34362358

ABSTRACT

BACKGROUND: Humoral immunity plays an important role in the prevention of canine distemper. Anti-CD virus (CDV) antibody has strong antiviral activity and is widely used in the treatment of CD. However, with the increase of CD cases, the availability of therapeutic CD antibody fell short of the clinical needs. RESULTS: The high-titer antiserum with the high-titer neutralizing activity against CDV was obtained from the donkeys (Dezhou Donkey) immunized with the inactivated CDV vaccine. The donkey anti-CDV IgG was purified from the donkey serum, which was identified to significantly inhibit the CDV replication in the cultured Vero cells and effectively reduce the clinical symptoms and increase the survival rates (75%) of CDV-infected dogs (Shih-tzu Dog), similar to that treated with the dog-derived anti-CDV IgG. These results indicate that donkey-derived IgG is a potential substitute for dog-derived IgG to treat the CD in clinic. CONCLUSIONS: Administration of donkey-derived anti-CDV IgG can ameliorate clinical symptoms and inhibit virus replication, thereby increasing the survival of CDV-infected dogs. This study opens up a new source of therapeutic antibody for CD treatment.


Subject(s)
Antibodies, Viral/therapeutic use , Distemper Virus, Canine/immunology , Distemper/therapy , Immune Sera/immunology , Immunization, Passive/veterinary , Immunoglobulin G/therapeutic use , Animals , Antibodies, Viral/blood , Dogs , Equidae , Immunoglobulin G/blood , Survival Rate , Virus Replication
15.
BMC Oral Health ; 21(1): 335, 2021 07 07.
Article in English | MEDLINE | ID: mdl-34233683

ABSTRACT

BACKGROUND: Conventional static computer-assisted implant surgery (s-CAIS) requires special equipment, such as 3D printers or computer numerical control (CNC) lathes. We present a low-cost workflow for manufacturing dental implant guides based on tetrahedron positioning technology (TPT). The aim of this case report was to use a surgical guide technique for dental implant placement using tetrahedron positioning technology. CASE PRESENTATION: A 28-year-old man consulted for the treatment of a missing right first mandibular molar by implant placement. The cone-beam computed tomography (CBCT) data were imported into medical image processing software for analysis, and the implant design was simulated. The implant design on CBCT was transferred to the mandibular model using TPT, and the implant surgical guide was made to guide the dental implant operation. CBCT was performed postoperatively and compared with the preoperative design to check the accuracy. The central deviation of the implant head was 0.31 mm, the central deviation of the implant apex was 0.93 mm, and the implant angular deviation was 2.45°. CONCLUSION: The use of tetrahedral positioning technology based on CBCT data is a new method for making implant guides. It is a promising technique offering a highly predictable outcome and lower risk of iatrogenic damage. However, these results should be interpreted with care since they are based on limited evidence from a case report. Larger population studies with longer follow-up periods and standardized experimental studies are required.


Subject(s)
Dental Implants , Adult , Computer-Aided Design , Cone-Beam Computed Tomography , Dental Implantation, Endosseous , Humans , Imaging, Three-Dimensional , Male , Technology
16.
Mol Cell Probes ; 49: 101493, 2020 02.
Article in English | MEDLINE | ID: mdl-31816413

ABSTRACT

Autophagy plays a crucial role in eliminating protein aggregates, damaged organelles and invading pathogens. Genetically engineered cell line stably expressing green fluorescent protein (GFP)-tagged microtubule-associated protein light chain 3 (LC3) is extensively used to test autophagy through observing GFP puncta formation in the cells by fluorescence imaging. However, canine LC3 (cLC3) gene has not been cloned, therefore, GFP-tagged canine LC3 (GFP-cLC3) detection system has not been established. To generate GFP-cLC3 stably expressing canine-derived macrophages, the cLC3 cDNA was first amplified by RT-PCR and inserted into pEGFP-C1 plasmid to create GFP-cLC3 gene fusion. This genetic element was then transducted into canine macrophages mediated by lentivirus vector to generate the canine macrophages stably expressing fusion protein. Results showed that the sequence of cLC3 cloned in this study is highly homologous with other animals (80-95% homology). Phenotypic and functional analysis of these engineered cells revealed that GFP-cLC3 was indeed stably expressed and rapamycin or starvation can effectively induce GFP puncta formation in the cells, indicative of autophagosome formation. These GFP-cLC3-expressing cells may thus be useful to study autophagy in canine.


Subject(s)
Autophagy , Dogs/metabolism , Green Fluorescent Proteins/metabolism , Macrophages/cytology , Macrophages/metabolism , Microtubule-Associated Proteins/metabolism , Amino Acid Sequence , Animals , Autophagy/drug effects , Base Sequence , DNA, Complementary/genetics , Eukaryotic Cells/drug effects , Eukaryotic Cells/metabolism , Gene Amplification , Genetic Vectors/metabolism , Genome , Lentivirus/genetics , Macrophages/drug effects , Madin Darby Canine Kidney Cells , Microtubule-Associated Proteins/chemistry , Microtubule-Associated Proteins/genetics , Recombinant Fusion Proteins/metabolism , Recombination, Genetic/genetics , Sirolimus/pharmacology
17.
Macromol Rapid Commun ; 41(2): e1900450, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31778252

ABSTRACT

The latest generation of wearable devices features materials that are flexible, conductive, and stretchable, thus meeting the requirements of stability and reliability. However, the metal conductors that are currently used in various equipments cannot achieve these high performance expectations. Hence, a mussel-inspired conductive hydrogel (HAC-B-PAM) is prepared with a facile approach by employing polyacrylamide (PAM), dopamine-functionalized hyaluronic acid (HAC), borax as a dynamic cross-linker agent, and Li+ and Na+ as conductive ions. HAC-B-PAM hydrogels demonstrate an excellent stretchability (up to 2800%), high tensile toughness (42.4 kPa), self-adhesive properties (adhesion strength to porcine skin of 49.6 kPa), and good self-healing properties without any stimuli at room temperature. Furthermore, the fabricated hydrogel-based strain sensor is sensitive to deformation and can detect human body motion. Multifunctional hydrogels can be assembled into flexible wearable devices with potential applications in the field of electronic skin and soft robotics.


Subject(s)
Adhesives/chemistry , Bivalvia/chemistry , Hydrogels/chemistry , Wearable Electronic Devices , Acrylic Resins/chemistry , Animals , Biosensing Techniques , Borates/chemistry , Dopamine/chemistry , Elasticity , Electric Conductivity , Humans , Hyaluronic Acid/chemistry , Ions/chemistry , Motion , Shear Strength
18.
Mol Ther ; 27(5): 1039-1050, 2019 05 08.
Article in English | MEDLINE | ID: mdl-30852137

ABSTRACT

Histone deacetylase inhibitors (HDACis) are the recommended treatment for many solid tumors; however, resistance is a major clinical obstacle for their efficacy. High levels of the transcription factor nuclear factor erythroid 2 like-2 (Nrf2) in cancer cells suggest a vital role in chemoresistance, and regulation of autophagy is one mechanism by which Nrf2 mediates chemoresistance. Although the molecular mechanisms underlying this activity are unclear, understanding them may ultimately improve therapeutic outcomes following HDACi treatment. In this study, we found that HDACi treatment increased Nrf2 mRNA and protein levels and enhanced Nrf2 transcriptional activity. Conversely, Nrf2 knockdown or inhibition blocked HDACi-induced autophagy. In addition, a microRNA (miRNA) array identified upregulation of miR-129-3p in response to Nrf2 overexpression. Chromatin immunoprecipitation assays confirmed miR-129-3p to be a direct Nrf2 target. RepTar and RNAhybrid databases indicated mammalian target of rapamycin (mTOR) as a potential miR-129-3p target, which we experimentally confirmed. Finally, Nrf2 inhibition or miR-129-3p in combination with HDACis increased cell death in vitro and in vivo. Collectively, these results demonstrated that Nrf2 regulates mTOR during HDACi-induced autophagy through miRNA-129-3p and inhibition of this pathway could enhance HDACi-mediated cell death.


Subject(s)
MicroRNAs/genetics , NF-E2-Related Factor 2/genetics , Neoplasms/drug therapy , TOR Serine-Threonine Kinases/genetics , Animals , Autophagy/drug effects , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Gene Regulatory Networks/genetics , Heterografts , Histone Deacetylase Inhibitors/pharmacology , Humans , Mice , NF-E2-Related Factor 2/antagonists & inhibitors , Neoplasms/genetics , Neoplasms/pathology
19.
Gen Comp Endocrinol ; 298: 113554, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32687932

ABSTRACT

Estrogens play important regulatory roles in the pituitary of vertebrates. Two forms of estrogen receptor 2 (Esr2), namely Esr2a and Esr2b, are identified in teleosts, but their differential roles remain to be fully elucidated. In the present study, expression and potential functional roles of Esr2a and Esr2b were characterized in ricefield eels. esr2a and esr2b mRNA were broadly distributed in tissues, with high levels observed in the brain, pituitary, and gonads. In order to examine the cellular localization of Esr2a and Esr2b in the pituitary, specific antisera against ricefield eel Esr2a and Esr2b were generated, respectively. Interestingly, immunohistochemistry and Western blot analysis revealed that Esr2a and Esr2b were differentially distributed in the pituitary, with the former localized to the adenohypophysis while the latter to the neurohypophysis. Dual fluorescent immunostaining showed that immunoreactive Esr2a was present in Gh and Prl cells, but not in Lh and Fsh cells. Estradiol (E2) stimulated lhb and prl gene expression in dispersed pituitary cells of intersexual ricefield eels, but had no effects on gh, fshb, and gnrhr2 gene expression and Gh release. Results of the present study are helpful for further understanding the roles and mechanisms of estrogen signals in the pituitary.


Subject(s)
Eels/metabolism , Estrogen Receptor beta/metabolism , Pituitary Gland/metabolism , Animals , Antibody Specificity/immunology , Estradiol/pharmacology , Estrogen Receptor beta/genetics , Female , Gene Expression Regulation/drug effects , Immune Sera/metabolism , Pituitary Gland/drug effects , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , Pituitary Gland, Posterior/drug effects , Pituitary Gland, Posterior/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tissue Distribution/drug effects
20.
Euro Surveill ; 25(28)2020 07.
Article in English | MEDLINE | ID: mdl-32700671

ABSTRACT

BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Severe Acute Respiratory Syndrome/immunology , Severe acute respiratory syndrome-related coronavirus/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/genetics , Blotting, Western , COS Cells , COVID-19 , Chlorocebus aethiops , Conserved Sequence , Coronavirus Infections/genetics , Coronavirus Infections/virology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay/methods , Fluorescent Antibody Technique/methods , Genome, Viral , Mice , Pandemics , Peptidyl-Dipeptidase A/immunology , Plasmids , Pneumonia, Viral/genetics , Recombinant Proteins/immunology , Severe acute respiratory syndrome-related coronavirus/genetics , SARS-CoV-2 , Sequence Alignment , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/genetics , Transfection , Vero Cells , Virus Integration
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