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1.
Mol Pharm ; 21(5): 2327-2339, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38576375

RESUMO

In the present study, we investigated the role of lipid composition of camptothecin (CPT)-loaded liposomes (CPT-Lips) to adjust their residence time, drug distribution, and therefore the toxicities and antitumor activity. The CPT was loaded into liposomes using a click drug loading method, which utilized liposomes preloaded with GSH and then exposed to CPT-maleimide. The method produced CPT-Lips with a high encapsulation efficiency (>95%) and sustained drug release. It is shown that the residence times of CPT-Lips in the body were highly dependent on lipid compositions with an order of non-PEGylated liposomes of unsaturated lipids < non-PEGylated liposomes of saturated lipids < PEGylated liposomes of saturated lipids. Interestingly, the fast clearance of CPT-Lips resulted in significantly decreased toxicities but did not cause a significant decrease in their in vivo antitumor activity. These results suggested that the lipid composition could effectively adjust the residence time of CPT-Lips in the body and further optimize their therapeutic index, which would guide the development of a liposomal formulation of CPT.


Assuntos
Camptotecina , Lipídeos , Lipossomos , Camptotecina/química , Camptotecina/administração & dosagem , Camptotecina/farmacocinética , Camptotecina/farmacologia , Lipossomos/química , Animais , Camundongos , Lipídeos/química , Humanos , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Feminino , Química Click/métodos , Camundongos Endogâmicos BALB C
2.
J Am Chem Soc ; 144(11): 5023-5028, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35285637

RESUMO

Water, as one of the most important and indispensable small molecules in vivo, plays a crucial role in driving biological self-assembly processes. Real-space detection and identification of water-induced organic structures and further capture of dynamic dehydration processes are important yet challenging, which would help to reveal the cooperation and competition mechanisms among water-involved noncovalent interactions. Herein, introduction of water molecules onto the self-assembled thymine (T) structures under ultrahigh vacuum (UHV) conditions results in the hydration of hydrogen-bonded T dimers forming a well-ordered water-involved T structure. Reversibly, a local dehydration process is achieved by in situ scanning tunneling microscopy (STM) manipulation on single water molecules, where the adjacent T dimers connected with water molecules undergo a local chiral inversion process with the hydrogen-bonding configuration preserved. Such a strategy enables real-space identification and detection of the interactions between water and organic molecules, which may also shed light on the understanding of biologically relevant self-assembly processes driven by water.


Assuntos
Dímeros de Pirimidina , Água , Desidratação , Humanos , Hidrogênio , Ligação de Hidrogênio , Polímeros/química , Água/química
3.
Small ; 18(52): e2205576, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36399632

RESUMO

Facile and controllable synthesis of functional yolk@shell structured nanospheres with a tunable inner core ('yolk') and mesoporous shell is highly desirable, yet it remains a great challenge. Herein, xx developed a strategy based on temperature-regulated swelling and restricted asymmetric shrinkage of polydopamine (PDA) nanospheres, combined with heterogeneous interface self-assembly growth. This method allows a simple and versatile preparation of PDA@mesoporous silica (MS) nanospheres exhibiting tunable yolk@shell architectures and shell pore sizes. Through reaction temperature-regulated swelling degree and confined shrinkage of PDA nanospheres, the volume ratio of the hollow cavity that the PDA core occupies can easily be tuned from ca. 2/3 to ca. 1/2, then to ca. 2/5, finally to ca. 1/3. Owing to the presence of PDA with excellent photothermal conversion capacity, the PDA@MS nanocomposites with asymmetric yolk distributions can become a colloidal nanomotor propelled by near-infrared (NIR) light. Noteworthily, the PDA@MS with half PDA yolk and microcracks in silica shell reaches 2.18 µm2 s-1 of effective diffusion coefficient (De) in the presence of 1.0 W cm-2 NIR light. This temperature-controlled swelling approach may provide new insight into the design and facile preparation of functional PDA-based yolk@shell structured nanocomposites for wide applications in biology and medicine.


Assuntos
Nanocompostos , Dióxido de Silício , Dióxido de Silício/química , Temperatura , Polímeros/química
4.
Small ; 18(2): e2104477, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34738718

RESUMO

Synthesis of anisotropic carbonaceous nano- and micro-materials with well-ordered mesoporous structures has attracted increasing attention for a broad scope of applications. Although hard-templating method has been widely employed, overcoming the viscous forces to prepare anisotropic mesoporous materials is particularly challenging via the universal soft-templating method, especially from sustainable biomass as a carbon resource. Herein, the synthesis of biomass-derived nanowire-arrays based mesoporous nanorods and teeth-like superstructures is reported, through a simple and straightforward polyelectrolyte assisted soft-templating hydrothermal carbonization (HTC) approach. A surface energy induced interfacial assembly mechanism with the synergetic interactions between micelles, nanowire, nanorods, and polyelectrolyte is proposed. The polyelectrolyte acts not only as a stabilizer to decrease the surface energy of cylindrical micelles, nanowires and nanorods, but also as a structure-directing agent to regulate the oriented attachment and anisotropic assembly of micelles, nanowires, and nanorods. After a calcination treatment, the carbon nanorod and teeth-like superstructure are successfully coupled with Ru to directly produce supported catalysts for the hydrogen evolution reaction, exhibiting much better performance than the isotropic nanospheres based catalyst. This HTC approach will open up new avenues for the synthesis of anisotropic materials with various morphologies and dimensions, expanding the palette of materials selection for many applications.


Assuntos
Nanotubos , Nanofios , Biomassa , Carbono/química , Catálise , Nanotubos/química , Nanofios/química
5.
Biomacromolecules ; 22(5): 2033-2042, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33880924

RESUMO

Efficient enzymatic hydrolysis of cellulose in lignocellulose to glucose is one of the most critical steps for the production of biofuels. The nonproductive adsorption of lignin to expensive cellulase highly impedes the development of biorefinery. Understanding the lignin-cellulase interaction mechanism serves as a vital basis for reducing such nonproductive adsorption in their practical applications. Yet, limited report is available on the direct characterization of the lignin-cellulase interactions. Herein, for the first time, the nanomechanics of the biomacromolecules including lignin, cellulase, and cellulose were systematically investigated by using a surface force apparatus (SFA) at the nanoscale in aqueous solutions. Interestingly, a cation-π interaction was discovered and demonstrated between lignin and cellulase molecules through SFA measurements with the addition of different cations (Na+, K+, etc.). The complementary adsorption tests and theoretical calculations further confirmed the validity of the force measurement results. This finding further inspired the investigation of the interaction between lignin and other noncatalytic-hydrolysis protein (i.e., soy protein). Soy protein was demonstrated as an effective, biocompatible, and inexpensive lignin-blocker based on the molecular force measurements through the combined effects of electrostatic, cation-π, and hydrophobic interactions, which significantly improved the enzymatic hydrolysis efficiencies of cellulose in pretreated lignocellulosic substrates. Our results offer quantitative information on the fundamental understanding of the lignin-cellulase interaction mechanism. Such unraveled nanomechanics provides new insights into the development of advanced biotechnologies for addressing the nonproductive adsorption of lignin to cellulase, with great implications on improving the economics of lignocellulosic biorefinery.


Assuntos
Celulase , Adsorção , Celulose , Hidrólise , Lignina
6.
Int J Mol Sci ; 21(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532004

RESUMO

Molecular imprinting technology is a promising method for detecting chloramphenicol (CAP), a broad-spectrum antibiotic with potential toxicity to humans, in animal-derived foods. This work aimed to investigate the interactions between the CAP as a template and functional monomers required for synthesizing efficient molecularly imprinted polymers for recognition and isolation of CAP based on density functional theory. The most suitable monomer, methacrylic acid (MAA), was determined based on interaction energies and Gibbs free energy changes. Further, the reaction sites of CAP and MAA was predicted through the frontier molecular orbitals and molecular electrostatic potentials. Atoms in molecules topology analysis and non-covalent interactions reduced density gradient were applied to investigate different types of non-covalent and inter-atomic interactions. The simulation results showed that CAP was the main electron donor, while MAA was the main electron acceptor. Moreover, the CAP-MAA complex simultaneously involved N-H···O and C=O···H double hydrogen bonds, where the strength of the latter was greater than that of the former. The existence of hydrogen bonds was also confirmed by theoretical and experimental hydrogen nuclear magnetic resonance and Fourier transform infrared spectroscopic analyses. This research can act as an important reference for intermolecular interactions and provide strong theoretical guidance regarding CAP in the synthesis of molecularly imprinted polymers.


Assuntos
Cloranfenicol/química , Metacrilatos/química , Polímeros Molecularmente Impressos/química , Teoria da Densidade Funcional , Espectroscopia de Ressonância Magnética , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
7.
Macromol Rapid Commun ; 40(13): e1900078, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30969012

RESUMO

Polymer brushes exhibit functionalities useful for a large number of applications. Often these functionalities only emerge when the polymer brushes have a desired thickness. Here, a significant breakthrough is achieved in the synthesis of ultra-thick polymer brushes using polymer initiators in the approach of surface-initiated atom transfer radical polymerization, yielding polymer brushes with a controllable thickness up to 15.1 µm. This is reportedly the thickest polymer brush ever synthesized. This approach is applicable for several monomers such as acrylonitrile, methyl acrylate, and styrene, and for other types of polymer substrates such as fibers.


Assuntos
Acrilatos/química , Acrilonitrila/química , Polímeros/química , Estireno/química , Polimerização , Propriedades de Superfície
8.
Ann Hepatol ; 16(6): 888-892, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29055925

RESUMO

PURPOSE: This study aims to investigate the antiviral effect of polyethylene glycol (PEG)-interferon α-2a and PEG-interferon α-2b treatment on hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week of treatment and the 24th and 48th week after withdrawal, in order to provide guidance on the antiviral treatment of HBeAg-positive CHB patients. MATERIAL AND METHODS: Antiviral treatment was performed on 155 HBeAg-positive CHB patients. Among these patients, 66 patients received PEG-interferon α-2a treatment and 89 patients received PEG-interferon α-2b treatment; and these treatments were administered by subcutaneous injection, once per week, which lasted for 48 weeks. Other antiviral and hepatoprotective drugs were not used during the treatment. RESULTS: At the 48th week of treatment, ALT recovery rate, HBsAg seroconversion rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon α-2a group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon α-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg seroconversion rate in these two groups did not change; and HBeAg seroconversion rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The difference between these two groups was not significantly significant. CONCLUSIONS: PEG-interferon α-2a and PEG-interferon α-2b are effective antiviral drugs for the treatment of HbeAgpositive CHB, which has a HBsAg seroconversion rate of more than 5%. Furthermore, this sustained response effect was maintained at the 24th and 48th week of follow-up after withdrawal.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Antivirais/efeitos adversos , Biomarcadores/sangue , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Recidiva , Estudos Retrospectivos , Soroconversão , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto Jovem
9.
Appl Opt ; 53(31): 7369-80, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25402902

RESUMO

A uniform plano-convex spherical microlens array with a long focal length was fabricated by combining the micromilling and injection molding processes in this work. This paper presents a quantitative study of the injection molding process parameters on the uniformity of the height of the microlenses. The variation of the injection process parameters, i.e., barrel temperature, mold temperature, injection speed, and packing pressure, was found to have a significant effect on the uniformity of the height of the microlenses, especially the barrel temperature. The filling-to-packing switchover point is also critical to the uniformity of the height of the microlenses. The optimal uniformity was achieved when the polymer melts completely filled the mold cavity, or even a little excessively filled the cavity, during the filling stage. In addition, due to the filling resistance, the practical filling-to-packing switchover point can vary with the change of the filling processing conditions and lead to a non-negligible effect on the uniformity of the height of the microlenses. Furthermore, the effect of injection speed on the uniformity of the height of the microlenses was analyzed in detail. The results indicated that the effect of injection speed on the uniformity of the height of the microlenses is mainly attributed to the two functions of injection speed: transferring the filling-to-packing switchover point and affecting the distribution of residual flow stress in the polymer melt.


Assuntos
Lentes , Microfluídica/instrumentação , Polimetil Metacrilato/química , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização
10.
Int J Biol Macromol ; 278(Pt 3): 134609, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134197

RESUMO

Bacterial infections, excessive reactive oxygen species (ROS) accumulation and a persistent inflammatory response severely impede the wound healing process. In this study, we developed a novel multifunctional hydrogel dressing (LCPN) based on lipoic acid modified chitosan (LAMC), polypyrrole nanoparticles (PPy NPs) and nicotinamide mononucleotide (NMN) for accelerated healing of infected wounds. The synthesized LCPN hydrogel has several properties. Modification of lipoic acid significantly enhances the water solubility of chitosan making it easier to dissolve and absorb wound secretions. Interestingly, owing to the breaking and restructuring of disulfide bonds, LCPN hydrogel can be quickly bonded under UV light without relying on photoinitiators. In addition, the incorporation of PPy NPs not only enhances the electrical conductivity of LCPN hydrogel, but also confers photothermal antimicrobial capability to LCPN hydrogel. More importantly, the sustained release of NMN in LCPN hydrogel can significantly enhance cell proliferation, migration and antioxidant capacity, which is conducive to accelerated wound healing. In vitro and in vivo experiments have shown that LCPN hydrogel has excellent biocompatibility and the ability to promote wound healing. Therefore, the prepared multifunctional hydrogel is expected to be used as a novel dressing to accelerate wound healing.


Assuntos
Bandagens , Quitosana , Hidrogéis , Cicatrização , Quitosana/química , Quitosana/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Nanopartículas/química , Infecção dos Ferimentos/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/química , Luz , Proliferação de Células/efeitos dos fármacos , Polímeros/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química
11.
Colloids Surf B Biointerfaces ; 244: 114183, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39208607

RESUMO

One way to effectively address endophyte infection and loosening is the creation of multifunctional coatings that combine anti-inflammatory, antibacterial, and vascularized osteogenesis. This study started with the preparation of strontium-doped titanium dioxide nanotubes (STN) on the titanium surface. Next, tannic acid (TA), gentamicin sulfate (GS), and pluronic F127 (PF127) were successfully loaded into the STN via layer-by-layer self-assembly, resulting in the STN@TA-GS/PF composite coatings. The findings demonstrated the excellent hydrophilicity and bioactivity of the STN@TA-GS/PF coating. STN@TA-GS/PF inhibited E. coli and S. aureus in vitro to a degree of roughly 80.95 % and 92.45 %, respectively. Cellular investigations revealed that on the STN@TA-GS/PF surface, the immune-system-related RAW264.7, the vasculogenic HUVEC, and the osteogenic MC3T3-E1 showed good adhesion and proliferation activities. STN@TA-GS/PF may influence RAW264.7 polarization toward the M2-type and encourage MC3T3-E1 differentiation toward osteogenesis at the molecular level. Meanwhile, the STN@TA-GS/PF coating achieved effective removal of ROS within HUVEC and significantly promoted angiogenesis. In both infected and non-infected bone defect models, the STN@TA-GS/PF material demonstrated strong anti-inflammatory, antibacterial, and vascularization-promoting osteogenesis properties. In addition, STN@TA-GS/PF had good hemocompatibility and biosafety. The three-step process used in this study to modify the titanium surface for several purposes gave rise to a novel concept for the clinical design of antimicrobial coatings with immunomodulatory properties.


Assuntos
Antibacterianos , Anti-Inflamatórios , Materiais Revestidos Biocompatíveis , Escherichia coli , Nanotubos , Próteses e Implantes , Staphylococcus aureus , Estrôncio , Titânio , Titânio/química , Titânio/farmacologia , Nanotubos/química , Camundongos , Animais , Estrôncio/química , Estrôncio/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Staphylococcus aureus/efeitos dos fármacos , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Células RAW 264.7 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Propriedades de Superfície , Taninos/química , Taninos/farmacologia , Osteogênese/efeitos dos fármacos , Poloxâmero/química , Poloxâmero/farmacologia , Proliferação de Células/efeitos dos fármacos , Gentamicinas/farmacologia , Gentamicinas/química , Tamanho da Partícula
12.
Genomics ; 99(4): 246-55, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22326742

RESUMO

The symbiotic protists in the hindgut of lower termites are critical for lignocellulose decomposition. Due to the unculturability of these protists, information on lignocellulases and their abundance within the gut is unavailable. The advent of high-throughput sequencing technologies enables an investigation of the gene expression profile in this community without culturing these organisms. Here, we carried out 454 pyrosequencing to profile the metatranscriptome of the protistan community in Coptotermes formosanus. In total, 223,477 reads were obtained by sequencing the enriched protistan mRNA. Phagocytosis and cytoskeletal homeostasis pathways were highly represented in the metatranscriptome. Among the metabolic pathways, starch and sucrose metabolism were dominant. A detailed analysis combining Pfam and KEGG annotation identified 118 glycosyl hydrolases belonging to 18 different glycosyl hydrolase families (GHFs). Subsequently, a novel GHF10 endo-1,4-beta-xylanase was functionally characterized to complement our understanding of the protistan hemicellulases.


Assuntos
Eucariotos/genética , Perfilação da Expressão Gênica/métodos , Isópteros/microbiologia , Lignina/metabolismo , Transcriptoma , Sequência de Aminoácidos , Animais , Endo-1,4-beta-Xilanases/análise , Endo-1,4-beta-Xilanases/metabolismo , Eucariotos/enzimologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Biblioteca Gênica , Metagenoma , Dados de Sequência Molecular , N-Glicosil Hidrolases/análise , N-Glicosil Hidrolases/metabolismo , Filogenia , Alinhamento de Sequência , Análise de Sequência de DNA , Simbiose
13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 30(1): 105-9, 2013 Feb.
Artigo em Zh | MEDLINE | ID: mdl-23488148

RESUMO

To evaluate the biological safety of collagen-based bone repairing material, we implanted the sample or reference substance into rats, and observed relative signs, including the specific inspection targets in animals, blood examination, analysis of immune organ, the pathological examination of organs and tissues, NK cell killing activity assay, lymphocyte group analysis, serum IL-1, IL-6, TNF-alpha detection, detection of immune globulin. Meanwhile, we set control group, sham group, and immunosuppression group. The final results showed that there was no abnormal mental state before and after the experiment. Compared with the control group, the tested group indicated no significant difference in blood test, immune organ analysis, the pathological examination of organs and tissues, NK cell killing activity assay, lymphocyte subset analysis serum IL-1, IL-6, TNF-alphadetection, and detection of immune globulin. Collagen-based bone repairing material produced a slight and transient stimulation on the rats, but created no significant inflammatory responses.


Assuntos
Matriz Óssea/transplante , Substitutos Ósseos , Colágeno/química , Implantes Experimentais , Próteses e Implantes , Implantes Absorvíveis , Animais , Matriz Óssea/fisiologia , Regeneração Óssea , Teste de Materiais , Ratos
14.
Colloids Surf B Biointerfaces ; 224: 113188, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36773409

RESUMO

It is still a big challenge in orthopedics to treat infected bone defects properly using medical metals. The use of three-dimensional (3D) scaffold materials that simultaneously mimic the skeletal hierarchy and induce sustainable osteogenic and antibacterial functions are a promising solution with an increasing appeal. In this study, we first designed a bifunctional fusion peptide (HHC36-RGD, HR) by linking antimicrobial peptide (HHC36) and arginine-glycine-aspartate (RGD) peptide via 6-aminohexanoic acid. Then the 3D scaffold was fabricated by additive manufacturing, and the strontium titanate nanotube structure (3D-STN) was constructed on its surface. Finally, the HR was anchored to the 3D-STN with the aid of polydopamine (PDA, P), forming the 3D-STN-P-HR scaffold. The results showed that the scaffold exhibited an ordered 3D porous structure, and that the surface was covered by a dense HHC36-RGD layer. Expectedly, the adsorption of PDA effectively slowed down the release of HR. Moreover, the functionalized scaffold had a significant inhibitory effect on Staphylococcus aureus and Escherichia coli, and its antibacterial rate could reach more than 95%. The results of in vitro cell culture experiments demonstrated that the 3D-STN-P-HR scaffold possessed excellent cytocompatibility and could promote the transcription of osteogenic differentiation-related genes and the expression of related proteins. In conclusion, the functionally modified 3D porous titanium alloy scaffold (3D-STN-P-HR) has a balanced antibacterial and osteogenic function, which bodes well for future potential in the customized functional reconstruction of complex-shaped infected bone defects.


Assuntos
Nanotubos , Osteogênese , Titânio/farmacologia , Titânio/química , Ligas/farmacologia , Porosidade , Antibacterianos/farmacologia , Antibacterianos/química , Peptídeos/farmacologia , Oligopeptídeos/farmacologia , Nanotubos/química
15.
Front Pharmacol ; 14: 1118584, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937869

RESUMO

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by enterovirus (EV) infection. EV71 is one of the major pathogens causing hand, foot, and mouth disease and is more likely to cause exacerbation and death than other enteroviruses. Although a monovalent vaccine for EV71 has been developed, there are no clinically available anti-EV71 specific drugs. Here, we performed virtual screening and biological experiments based on the traditional Chinese medicine monomer library. We identified a traditional Chinese medicine monomer, Salvianolic acid A (SA), a polyphenolic compound isolated from Salvia miltiorrhiza. Salvianolic acid A inhibits EV71 virus infection in a concentration-dependent manner, and its antiviral activity is higher than that of other reported natural polyphenols and has a high biosafety. Furthermore, molecular dynamics simulations showed that salvianolic acid A can anchor to E71, a member of the enzyme catalytic triad, and cause H40 to move away from the catalytic center. Meanwhile, molecular mechanics generalized born surface area (MMGBSA) and steered molecular dynamics (SMD) results showed that the P1 group of SA was most easily unbound to the S1 pocket of 3Cpro, which provided theoretical support to further improve the affinity of salvianolic acid A with 3Cpro. These findings suggest that salvianolic acid A is a novel EV71 3Cpro inhibitor with excellent antiviral activity and is a promising candidate for clinical studies.

16.
Pathol Int ; 62(8): 565-70, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22827767

RESUMO

A 15-month boy with fatal hand, foot, and mouth disease (HFMD) exhibited atypical symptoms and progressed rapidly to death. An autopsy was performed the next day and tissue sections were stained for histopathological examination. His intestinal samples were tested for enterovirus 71 (EV71), and the whole-genome sequence of EV71 was analyzed. An autopsy revealed that the central nervous system, lungs, and gut displayed severe meningitis and brainstem encephalitis, remarkable pulmonary congestion, edema, moderate inflammatory infiltration, and hemorrhage as well as intestinal mucosal congestion, epithelial necrosis, thinning intestinal wall, and submucosal lymphoid follicular hyperplasia. The heart showed myocardial interstitial congestion, myocardial edema, and some inflammatory infiltrates. There were no significant alterations in the architecture of other organs. EV71 antigen and apoptotic cells were detected in brain, lung and intestine by immunohistochemical staining and TUNEL (TdT-mediated dUTP nick-end labeling) respectively. Intestinal contents and intestinal autopsy samples of this case were positive for EV71, and the EV71 strain was classified as subgenogroup C4. In China, the severe forms of HFMD were mostly caused by EV71 subgenogroup C4 infection. Severe intestinal damages may relate to EV71 subgenogroup C4 infection. Thus, children with severe EV71 HFMD may have serious pathological changes in their central nervous system, lungs, and gut. Physicians should pay special attention to infants with atypical symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.


Assuntos
Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/patologia , Doença de Mão, Pé e Boca/patologia , China/epidemiologia , Enterovirus Humano D/genética , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Evolução Fatal , Genes Virais , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Masculino , RNA Viral , Análise de Sequência de DNA
17.
PLoS One ; 17(7): e0272136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35895725

RESUMO

Nowadays there are many types of glass fiber reinforced polymer(GFRP) composite beam and column joints, such as standard connection, bolted through connection, angle steel connection, tube connection and so on, most of which connected by high-strength bolts with round holes. In this paper, monotonic loading tests on GFRPcomposite beam and column joints connected by slotted-hole bolts were conducted. To compare the performance of different joints, two groups of specimens were used in this study; one of group was the beam-column joints connected by the angle steel, and other group was connected by the tube connection. Specimens with different bolt holes, side plate reinforcement condition, and different bolt pre-tightening forces were studied. Failure modes, bending moment curves, plastic rotation, and yield stiffness of the two groups of joints were compared. Results showed thatthe ultimate bending moment bearing capacity of specimens with side plates could be increased by 30%. Under the same conditions, the bearing capacity of the tube joints was about 10% larger than that of the angle steel joints. Although the bearing capacity of joints was not increased by using slotted holes, plastic rotation capacity and yield stiffness of joints with slotted-hole bolts were 1.1 times than that of the ordinary round-hole bolts joints.


Assuntos
Placas Ósseas , Aço , Plásticos , Polímeros
18.
Mater Horiz ; 9(7): 1969-1977, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35583553

RESUMO

The development of liposome-based drugs was severely limited due to inefficient loading strategies. Herein, we developed a click reaction-mediated loading procedure by designing an enzyme-sensitive maleimide (MAL) tag for ferrying chemotherapeutics into preformed liposomes containing glutathione (GSH). Based on this strategy, various hydrophobic drugs could be encapsulated into liposomes within 5-30 min with encapsulation efficiency >95% and loading capacity of 10-30% (w/w). The entrapped cargo could be slowly released from the liposomes, followed by rapid enzyme-mediated conversion into active drugs to exert antitumor activity under physiological conditions. The resulting drug-loaded liposomes significantly prolonged the blood circulation of cargos and displayed more potent in vivo antitumor efficacy than free drugs at the equitoxic dose. More importantly, this method is a remote drug loading strategy in nature, which is suitable for industrial production. This is the first demonstration of active loading of MAL-tagged chemotherapeutics in liposomes for improved antitumor efficacies, which has the potential to serve as a universal drug loading strategy for the development of liposomal formulations of chemotherapeutics.


Assuntos
Lipossomos , Composição de Medicamentos , Lipossomos/química
19.
Appl Environ Microbiol ; 77(1): 48-56, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21057022

RESUMO

Fungus-growing termites play an important role in lignocellulose degradation and carbon mineralization in tropical and subtropical regions, but the degradation potentiality of their gut microbiota has long been neglected. The high quality and quantity of intestinal microbial DNA are indispensable for exploring new cellulose genes from termites by function-based screening. Here, using a refined intestinal microbial DNA extraction method followed by multiple-displacement amplification (MDA), a fosmid library was constructed from the total microbial DNA isolated from the gut of a termite growing in fungi. Functional screening for endoglucanase, cellobiohydrolase, ß-glucosidase, and xylanase resulted in 12 ß-glucosidase-positive clones and one xylanase-positive clone. The sequencing result of the xylanase-positive clone revealed an 1,818-bp open reading frame (ORF) encoding a 64.5-kDa multidomain endo-1,4-ß-xylanase, designated Xyl6E7, which consisted of an N-terminal GH11 family catalytic domain, a CBM_4_9 domain, and a Listeria-Bacteroides repeat domain. Xyl6E7 was a highly active, substrate-specific, and endo-acting alkaline xylanase with considerably wide pH tolerance and stability but extremely low thermostability.


Assuntos
Celulases/genética , Isópteros/microbiologia , Metagenoma , Animais , Biblioteca Gênica , Lignina/metabolismo , Dados de Sequência Molecular , Análise de Sequência de DNA , Homologia de Sequência
20.
Shanghai Kou Qiang Yi Xue ; 30(2): 162-166, 2021 Apr.
Artigo em Zh | MEDLINE | ID: mdl-34109355

RESUMO

PURPOSE: To investigate the effect of root development on root and periodontal tissues of maxillary impacted anterior teeth after orthodontic traction based on cone-beam CT (CBCT). METHODS: Thirty-four patients (34 teeth) requiring orthodontic traction for maxillary impacted anterior teeth in Southwest Medical University Affiliated Stomatological Hospital from July 2018 to March 2019 were selected. The patients were divided into incomplete development group and complete development group according to root development, each with 17 cases. All patients received orthodontic traction treatment. Root length, thickness of root canal wall, pulp vitality, width of the attachment ridge, bone mineral density around root and orthodontic traction time were compared between the two groups. Statistic analysis was completed by SPSS 20.0 software package. RESULTS: Root length of complete development group was significantly longer than that of incomplete development group before treatment(P<0.05). After treatment, the root length of incomplete development group was significantly longer than that of the complete development group(P<0.05). The thickness of root canal wall was significantly greater in complete development group than in incomplete development group before treatment (P<0.05), which had no significant difference between groups after treatment(P>0.05). The pulp vitality and width of the attachment ridge had no significant difference between two groups after treatment(P>0.05). Bone mineral density around root was significantly decreased in both groups after treatment(P<0.05), and was lower in complete development group than in incomplete development group(P<0.05). The orthodontic traction time in the complete development group was significantly longer than that in incomplete development group(P<0.05). CONCLUSIONS: In orthodontic traction treatment, the impacted anterior teeth with undeveloped roots have advantages of mild root absorption, rapid periodontal tissue reconstruction, short orthodontic traction time with the root, thickness of root canal wall and pulp vitality in the normal range.


Assuntos
Dente Impactado , Tração , Tomografia Computadorizada de Feixe Cônico , Humanos , Incisivo , Maxila/diagnóstico por imagem , Raiz Dentária/diagnóstico por imagem , Dente Impactado/diagnóstico por imagem
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