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1.
Small ; 20(9): e2304534, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37849036

RESUMO

The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Camundongos , Nanovacinas , SARS-CoV-2 , Escherichia coli , Lipossomos , COVID-19/prevenção & controle , Lipídeos
2.
BMC Oral Health ; 24(1): 39, 2024 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-38185621

RESUMO

BACKGROUND: Dentigerous cyst are most common odontogenic cyst and they frequently occur at the mandibular third molar. Their asymptomatic long medical history always resulted in severe bone resorption at the distal aspect of the adjacent second molar. BonMaker® ATB demonstrate an excellent autogenous bone graft candidacy. The aim of this study is to share a single team's experience of dentigerous cyst osseous defect repairing by applying autogenous tooth sticky bone graft. METHOD: In total, 18 patients with dentigerous cyst, which was arised from mandibular third molar unilaterally, were enrolled in this study. Enucleation of dentigerous cyst was performed extracting with involving teeth under general anesthesia. Autogenous tooth sticky bone graft was prepared using extracted tooth and autogenous fibrin glue. Subsequently, grafting was performed above covering with concentrate growth factors. Patients were followed up at sixth months. RESULTS: They were eleven male and seven female patients. Their ages ranged from 20 to 40 years, with a mean of 31 years. Primary wound healing of all sites was achieved in all the patients. Sixth months postoperative radiographic assessment show that dentigerous cysts osseous defects of seventeen patients were good bone filling and ossification. One patient occurred slight bone resorption at the distal aspect of the adjacent second molar. CONCLUSION: Within the limitation of sample size and retrospective nature of the present study, autogenous tooth sticky bone graft demonstrates one of the best alternative alveolar bones repairing graft.


Assuntos
Reabsorção Óssea , Cisto Dentígero , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Cisto Dentígero/cirurgia , Dente Serotino/cirurgia , Estudos Retrospectivos , Dente Molar
3.
Sensors (Basel) ; 23(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37299793

RESUMO

The fatigue cracking of orthotropic steel bridge decks (OSDs) is a difficult problem that hinders the development of steel structures. The most important reasons for the occurrence of fatigue cracking are steadily growing traffic loads and unavoidable truck overloading. Stochastic traffic loading leads to the random propagation behavior of fatigue cracks, which increases the difficulty of the fatigue life evaluations of OSDs. This study developed a computational framework for the fatigue crack propagation of OSDs under stochastic traffic loads based on traffic data and finite element methods. Stochastic traffic load models were established based on site-specific, weigh-in-motion measurements to simulate fatigue stress spectra of welded joints. The influence of the transverse loading positions of the wheel tracks on the stress intensity factor of the crack tip was investigated. The random propagation paths of the crack under stochastic traffic loads were evaluated. Both ascending and descending load spectra were considered in the traffic loading pattern. The numerical results indicated that the maximum value of KI was 568.18 (MPa·mm1/2) under the most critical transversal condition of the wheel load. However, the maximum value decreased by 66.4% under the condition of transversal moving by 450 mm. In addition, the propagation angle of the crack tip increased from 0.24° to 0.34°-an increase ratio of 42%. Under the three stochastic load spectra and the simulated wheel loading distributions, the crack propagation range was almost limited to within 10 mm. The migration effect was the most obvious under the descending load spectrum. The research results of this study can provide theoretical and technical support for the fatigue and fatigue reliability evaluation of existing steel bridge decks.


Assuntos
Fadiga , Reprodução , Humanos , Reprodutibilidade dos Testes , Movimento (Física) , Aço
4.
Analyst ; 145(16): 5603-5614, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32776070

RESUMO

Dielectrophoresis (DEP) is a powerful technique for label-free cell separation in microfluidics. Easily-fabricated DEP separators with low cost and short turnaround time are in extremely high demand in practical applications, especially clinical usage where disposable devices are needed. DEP separators exploiting microelectrodes made of conducting polydimethylsiloxane (PDMS) composites enable the construction of advantageous 3D volumetric electrodes with a simple soft-lithography process. Yet, existing devices incorporating microelectrodes in conducting PDMS generally have their fluidic sidewalls constructed using a different material, and consequently require extra lithography of a sacrificial layer on the semi-finished master for molding the electrode and fluidic sidewalls in separate steps. Here we demonstrate a novel microfluidic DEP separator with a 3D electrode and fluidic structure entirely integrated within silver-PDMS composites. We develop a further simplified one-step molding process with lower cost using a readily-available and reusable SU8 master, eliminating the need for the additional lithography step in existing techniques. The uniquely designed two-layer electrode exhibits a spatially non-uniform electric field that enables cell migration in the vertical direction. The electrode upper layer then offers a harbor-like region for the trapping of the target cells that have drifted upwards, which shelters them from being dragged away by the main flow streams in the lower layer, and thus allows higher operation flow rate. We also optimize the upper layer thickness as a critical dimension for protecting the trapped cells from high drag and show easy widening of our device by elongation of the digits. We demonstrate that the elongated digits involving more parallel flow paths maintain a high capture efficiency of 95.4% for live cells with 85.6% purity in the separation of live/dead HeLa cells. We also investigate the device feasibility in a viability assay for cells post anti-cancer drug treatment.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Separação Celular , Dimetilpolisiloxanos , Eletroforese , Células HeLa , Humanos , Microeletrodos , Prata
5.
Opt Lett ; 40(23): 5542-5, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26625046

RESUMO

A dual-plane in-line digital holographic imaging method incorporating volume holographic microscopy (VHM) is presented to reconstruct objects in a single shot while eliminating zero-order and twin-image diffracted waves. The proposed imaging method is configured such that information from different axial planes is acquired simultaneously using multiplexed volume holographic imaging gratings, as used in VHM, and recorded as in-line holograms where the corresponding reference beams are generated in the fashion of Gabor's in-line holography. Unlike conventional VHM, which can take axial intensity information only at focal depths, the proposed method digitally reconstructs objects at any axial position. Further, we demonstrate the proposed imaging technique's ability to effectively eliminate zero-order and twin images for single-shot three-dimensional object reconstruction.


Assuntos
Holografia/métodos , Microscopia/métodos , Processamento de Imagem Assistida por Computador , Poliestirenos
6.
J Chromatogr A ; 1726: 464965, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38733925

RESUMO

Aristolochic acids (AAs) naturally occurring in the herbal genus Aristolochia are associated with a high risk of kidney failure, multiple tumors and cancers. However, approaches with high selectivity and rapidity for measuring AAs in biological samples are still inadequate. Inspired by the mechanism of AAs-induced nephrotoxicity, we designed a hybrid magnetic polymer-porous agarose (denoted as MNs@SiO2M@DNV-A), mimicking the effect of basic and aromatic residues of organic anion transporter 1 (OAT1) for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in the plasma. The monomers of vinylbenzyl trimethylammonium chloride (VBTAC), N-vinyl-2-pyrrolidinone (NVP) and divinylbenzene (DVB) were employed to construct the polymer layer, which provided a selective adsorption for AAs by multiple interactions. The porous agarose shell contributed to remove interfering proteins in the plasma samples. A magnetic solid-phase extraction (MSPE) based on the proposed composite enhanced the selectivity toward AA I and AA II in the plasma samples. In combination of HPLC analysis, the proposed method was proved to be applicable to fast and specific quantification of AAs in blood samples, which was characterized by a good linearity, high sensitivity, acceptable recovery, excellent repeatability and satisfactory reusability.


Assuntos
Ácidos Aristolóquicos , Compostos de Amônio Quaternário , Sefarose , Extração em Fase Sólida , Ácidos Aristolóquicos/química , Ácidos Aristolóquicos/isolamento & purificação , Ácidos Aristolóquicos/sangue , Sefarose/química , Extração em Fase Sólida/métodos , Compostos de Amônio Quaternário/química , Cromatografia Líquida de Alta Pressão/métodos , Porosidade , Limite de Detecção , Animais , Humanos , Polímeros/química , Adsorção , Reprodutibilidade dos Testes
7.
J Control Release ; 369: 687-695, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38575073

RESUMO

Extracts of the Chilean soapbark tree, Quillaja Saponaria (QS) are the source of potent immune-stimulatory saponin compounds. This study compared the adjuvanticity and toxicity of QS-18 and QS-21, assessing the potential to substitute QS-18 in place of QS-21 for vaccine development. QS-18, the most abundant QS saponin fraction, has been largely overlooked due to safety concerns. We found that QS-18 spontaneously inserted into liposomes, thereby neutralizing hemolytic activity, and following administration did not induce local reactogenicity in a footpad swelling test in mice. With high-dose intramuscular administration, transient weight loss was minor, and QS-18 did not induce significantly more weight loss compared to a liposome vaccine adjuvant system lacking it. Two days after administration, no elevation of inflammatory cytokines was detected in murine serum. In a formulation including cobalt-porphyrin-phospholipid (CoPoP) for short peptide sequestration, QS-18 did not impact the formation of peptide nanoparticles. With immunization, QS-18 peptide particles induced higher levels of cancer neoepitope-specific and tumor-associated antigen-specific CD8+ T cells compared to QS-21 particles, without indication of greater toxicity based on mouse body weight. T cell receptor sequencing of antigen-specific CD8+ T cells showed that QS-18 induced significantly more T cell transcripts. In two murine cancer models, vaccination with QS-18 peptide particles induced a similar therapeutic effect as QS-21 particles, without indication of increased toxicity. Antigen-specific CD8+ T cells in the tumor microenvironment were found to express the exhaustion marker PD-1, pointing to the rationale for exploring combination therapy. Taken together, these data demonstrate that QS-18, when formulated in liposomes, can be a safe and effective adjuvant to induce tumor-inhibiting cellular responses in murine models with potential to facilitate or diminish costs of production for vaccine adjuvant systems. Further studies are warranted to assess liposomal QS-18 immunogic, reactogenic and toxicological profiles in mice and other animal species.


Assuntos
Adjuvantes Imunológicos , Vacinas Anticâncer , Lipossomos , Quillaja , Animais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Quillaja/química , Adjuvantes Imunológicos/administração & dosagem , Feminino , Camundongos Endogâmicos C57BL , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Camundongos , Saponinas de Quilaia , Citocinas , Saponinas/administração & dosagem , Saponinas/farmacologia , Linhagem Celular Tumoral , Vacinas de Subunidades Proteicas
8.
Cell Rep Med ; 5(3): 101433, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38401547

RESUMO

Inclusion of defined quantities of the two major surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA), could benefit seasonal influenza vaccines. Recombinant HA and NA multimeric proteins derived from three influenza serotypes, H1N1, H3N2, and type B, are surface displayed on nanoliposomes co-loaded with immunostimulatory adjuvants, generating "hexaplex" particles that are used to immunize mice. Protective immune responses to hexaplex liposomes involve functional antibody elicitation against each included antigen, comparable to vaccination with monovalent antigen particles. When compared to contemporary recombinant or adjuvanted influenza virus vaccines, hexaplex liposomes perform favorably in many areas, including antibody production, T cell activation, protection from lethal virus challenge, and protection following passive sera transfer. Based on these results, hexaplex liposomes warrant further investigation as an adjuvanted recombinant influenza vaccine formulation.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Camundongos , Animais , Humanos , Hemaglutininas , Neuraminidase/genética , Vírus da Influenza A Subtipo H3N2 , Lipossomos , Adjuvantes Imunológicos , Vacinas Sintéticas
9.
Expert Rev Vaccines ; 22(1): 1022-1040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37878481

RESUMO

INTRODUCTION: Liposomes have been used as carriers for vaccine adjuvants and antigens due to their inherent biocompatibility and versatility as delivery vehicles. Two vial admixture of protein antigens with liposome-formulated immunostimulatory adjuvants has become a broadly used clinical vaccine preparation approach. Compared to freely soluble antigens, liposome-associated forms can enhance antigen delivery to antigen-presenting cells and co-deliver antigens with adjuvants, leading to improved vaccine efficacy. AREAS COVERED: Several antigen-capture strategies for liposomal vaccines have been developed for proteins, peptides, and nucleic acids. Specific antigen delivery methodologies are discussed, including electrostatic adsorption, encapsulation inside the liposome aqueous core, and covalent and non-covalent antigen capture. EXPERT OPINION: Several commercial vaccines include active lipid components, highlighting an increasingly prominent role of liposomes and lipid nanoparticles in vaccine development. Utilizing liposomes to associate antigens offers potential advantages, including antigen and adjuvant dose-sparing, co-delivery of antigen and adjuvant to immune cells, and enhanced immunogenicity. Antigen capture by liposomes has demonstrated feasibility in clinical testing. New antigen-capture techniques have been developed and appear to be of interest for vaccine development.


Assuntos
Lipossomos , Vacinas , Humanos , Antígenos , Adjuvantes Imunológicos , Células Apresentadoras de Antígenos
10.
Mater Horiz ; 10(11): 4724-4745, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37697735

RESUMO

Organs-on-chips are microengineered microfluidic living cell culture devices with continuously perfused chambers penetrating to cells. By mimicking the biological features of the multicellular constructions, interactions among organs, vascular perfusion, physicochemical microenvironments, and so on, these devices are imparted with some key pathophysiological function levels of living organs that are difficult to be achieved in conventional 2D or 3D culture systems. In this technology, biomaterials are extremely important because they affect the microstructures and functionalities of the organ cells and the development of the organs-on-chip functions. Thus, herein, we provide an overview on the advances of biomaterials for the construction of organs-on-chips. After introducing the general components, structures, and fabrication techniques of the biomaterials, we focus on the studies of the functions and applications of these biomaterials in the organs-on-chips systems. Applications of the biomaterial-based organs-on-chips as alternative animal models for pharmaceutical, chemical, and environmental tests are described and highlighted. The prospects for exciting future directions and the challenges of biomaterials for realizing the further functionalization of organs-on-chips are also presented.


Assuntos
Materiais Biocompatíveis , Biomimética , Animais , Materiais Biocompatíveis/uso terapêutico , Técnicas de Cultura de Células , Dispositivos Lab-On-A-Chip , Sistemas Microfisiológicos
11.
Drug Deliv ; 30(1): 2219869, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37309122

RESUMO

Messenger RNA (mRNA) has become one of the most potential drugs in recent years. However, efficient and safe delivery of fragile and easily degradable mRNA is a major challenge. Appropriate delivery system (DS) determines the final effect of mRNA. Cationic lipids play a crucial and decisive role in the entire DS, but also cause huge biosafety problems due to the high toxicity. In this study, a new DS for mRNA delivery that combines negatively charged phospholipids was developed in order to neutralize the positive charge and thus increase the safety. Further, the factors affecting mRNA transfection from cell to animal were investigated. The mRNA DS with optimum condition of lipid composition, proportions, structure, and transfection time was synthesized. Adding an appropriate amount of the anionic lipid to liposomes could increase the safety while maintaining the original transfection efficiency. For transporting mRNA in vivo, requirements regarding the mRNA encapsulation and releasing rate should be further considered to optimize DS design and preparation.


Assuntos
Lipossomos , Fosfolipídeos , Animais , Transfecção , Transporte Biológico , RNA Mensageiro
12.
Huan Jing Ke Xue ; 43(11): 4869-4875, 2022 Nov 08.
Artigo em Zh | MEDLINE | ID: mdl-36437059

RESUMO

Over the recent decades, global plastic production has grown dramatically due to the huge demands of consumption. As a consequence, large amounts of plastic waste have accumulated in the environment and will be cleaved into microplastics. Due to the low bioavailability, the microplastics will exist in the environment persistently and cause massive environmental stress. Plastic pollution is currently one of the biggest environmental concerns. Recent studies have shown the possibility to obtain degrading microorganisms of microplastics from the natural environment. Some microorganisms can break down microplastics into water and carbon dioxide. This paper reviewed the current research on biodegradation of polyethylene (PE), which is the most abundant microplastic type in the environment, and discussed the quantification methods of the degradation effect. Given that current biodegradation efficiency is relatively limited, further research is required.


Assuntos
Microplásticos , Polietileno , Polietileno/análise , Plásticos , Monitoramento Ambiental/métodos , Biodegradação Ambiental
13.
Patient Prefer Adherence ; 16: 3045-3058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387048

RESUMO

Background and Purpose: Oral health plays an important role in overall health. But little is known about the problems with oral health behaviors and oral health-related quality of life (OHRQoL) among dental patients in China. This study aimed to investigate oral health behaviors and OHRQoL, as well as to examine the effects of oral health behaviors and associated factors on OHRQoL among dental patients. Methods: This cross-sectional study was conducted from June 2022 to July 2022 in the Department of Stomatology of the First Mobile General Hospital of Armed Police, Hebei, China. The five-item short form of the Oral Health Impact Profile (OHIP-5) was used to evaluate OHRQoL. Oral health behaviors were assessed by a 16-items oral health behavior questionnaire, and socio-demographic data were collected by a socio-demographic questionnaire. The t-test, one-way ANOVA, and multiple linear regression analysis were used to investigate the associations between the study variables. Results: 186 participants were included in the study. The average age of the participants was 24.62 years (SD = 10.67). The mean OHIP-5 score was 4.31 (SD =3.35). Oral health-related quality of life differed significantly by smoking history, history of alcohol consumption, work status, economic pressure, self-rated oral health status, daily brushing frequency, dental caries condition, and whether they take the initiative to learn about oral health. Multivariate analysis found that the self-rated oral health status and work status were significantly associated with the OHIP scores. The retired people and those with poor self-rated oral health displayed poor OHRQoL. Conclusion: In general, dental patients' oral health needs to be improved, the majority of patients reported practicing poor oral health behaviors, among which the retired population and hose with poor self-rated oral health showed poor OHRQoL. OHRQoL in dental patients is a complex issue associated with social and behavioral factors.

14.
Healthcare (Basel) ; 10(6)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35742083

RESUMO

Diabetes and periodontal disease are highly prevalent conditions around the world with a bilateral causative relationship. Research suggests that interprofessional collaboration can improve care delivery and treatment outcomes. However, there continues to be little interprofessional management of these diseases. DiabOH research aims to develop an interprofessional diabetes and oral health care model for primary health care that would be globally applicable. Community medical practitioners (CMPs), community health nurses (CNs), and dentists in Shanghai were recruited to participate in online quantitative surveys. Response data of 76 CMPs, CNs, and dentists was analysed for descriptive statistics and compared with Australian data. Health professionals in China reported that, while screening for diabetes and periodontitis, increasing patient referral and improving interprofessional collaboration would be feasible, these were not within their scope of practice. Oral health screening was rarely conducted by CMPs or CNs, while dentists were not comfortable discussing diabetes with patients. Most participants believed that better collaboration would benefit patients. Chinese professionals concurred that interprofessional collaboration is vital for the improved management of diabetes and periodontitis. These views were similar in Melbourne, except that Shanghai health professionals held increased confidence in managing patients with diabetes and were more welcoming to increased oral health training.

15.
Chemosphere ; 292: 133403, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34968521

RESUMO

Micro- and nano-plastics are common emerging pollutants of great interest. However, the impacts of them on terrestrial plants were still poorly understood. In this study, comparative effects of exposure of polystyrene nanoplastics (PS) and amino-modified polystyrene nanoplastics (PS-NH2) on Chinese cabbage (Brassica rapa L.) plants at different growth stages were investigated. Hydroponically cultured seedlings were exposed to PS and PS-NH2 at 0, 1, 10, and 100 mg/L at skotomorphogenesis stage for 48 h, photomorphogenesis stage for 18 h, and the whole stage, respectively. Results showed that both PS and PS-NH2 had no discernible effect on radicle elongation at the skotomorphogenesis stage whereas significantly (P < 0.05) reduced photosynthetic pigment contents in varying degrees (18.06%-28.52%, 22.46%-36.86%) at the photomorphogenesis stage and the whole stage. Moreover, there was no significant difference between PS treatments and control except the 26.52% decline of chlorophyll a content at 1 mg/L at photomorphogenesis, while PS-NH2 significantly (P < 0.05) decreased photosynthetic pigment contents except the chlorophyll b content at 10 mg/L at photomorphogenesis. The content of chlorophyll a decreased by 26.68% for the PS-NH2-treated group and 22.46% for the PS-treated group at 1 mg/L during the whole stage. Results manifested that less negatively charged PS-NH2 seemed to show more severe phytotoxicity both at the photomorphogenesis stage and the whole stage. Notably, the surface charge of nano-plastics and the integrity of seedling establishment could be the main factors impacting the above difference. These findings are expected to improve our understanding of the effects of PSNPs on crop plants.


Assuntos
Brassica rapa , Poliestirenos , China , Clorofila A , Microplásticos , Plântula
16.
Chemosphere ; 288(Pt 2): 132516, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34648785

RESUMO

Nanoplastics and carbon nanotubes (CNTs) is one of the emerging environmental contaminants and a widely used engineering nanomaterial, and their biological toxicity has been frequently studied. However, there has been no research on the combined exposure of these two totally different shape nanoparticles. To explore their potential threat to freshwater ecosystems, Microcystis aeruginosa (M. aeruginosa) was exposed to concentration gradients of polystyrene nanoplastics (Nano-PS) and multi-walled carbon nanotubes (MWCNTs). The physiological analysis and whole-transcriptome sequencing were integrated to certify the cytotoxicity. As the physiological results showed, the low concentration (5 mg/L) of these two nanoparticles showed a stimulation on the growth (6.49%-12.2%) and photosynthesis (0-7.6%), and the coexposure was slightly higher than individuals. However, other concentrations showed inhibitory effect, especially at high concentration (50 mg/L), and all physical signs and electron microscope images showed obvious cytotoxicity. Compared with the individuals, the coexposure showed an antagonistic effect induced by the heterogeneous agglomeration which decreased the surface toxicity and the contact with algae of nanomaterials. Transcriptome results showed that coexposure treatment had the fewest differential genes, and the primary effects embodied in the disturbances of cellular and metabolic processes which were superior to the individuals. In the 50 mg/L Nano-PS, the translation process was significantly disordered, and MWCNTs could disrupted the photosynthesis, multiple metabolism processes, membrane transport, and translation. These findings demonstrated the aquatic toxic mechanism from cellular and metabolic processes of Nano-PS and MWCNTs for M. aeruginosa and provided valuable data for environmental risk assessment of them.


Assuntos
Microcystis , Nanotubos de Carbono , Ecossistema , Humanos , Microplásticos , Nanotubos de Carbono/toxicidade
17.
J Drug Target ; 30(2): 219-231, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34319831

RESUMO

Nanoparticles (NPs) with 'stealth' properties have been designed to decrease the phagocytosis of such particles by mononuclear phagocytes and to protect them from enzymatic degradation, thus improving circulation time and bioavailability after intravenous administration. Brain-targeting modifications endow NPs with the capacity to cross the blood-brain barrier, facilitating chemotherapy for brain diseases such as glioma. In this study, newly designed alkoxy cyanoacrylate (CA)-based NPs with stealth and brain-targeting properties were synthesised and evaluated. The monomers for NP core polymerisation were chemically modified to hydrophilic short alkoxy structure for stealth purposes and coated with polysorbate-80 for brain targeting. Two monomers (2-methoxyethyl CA and 2-(2-methoxyethyl)ethyl CA) were used to create NP2 and NP3, respectively. Both NPs were successfully loaded with anti-sense oligonucleotide (ASON) of transforming growth factor beta 2. Compared to traditional n-butyl CA-based ASON-NP1, ASON-NP3 was found to decrease phagocytosis by mononuclear macrophages (RAW264.7) and to increase cellular uptake by cancer cells. ASON-NP3 showed definite brain targeting and anti-cancer effects. This work provides a potential new strategy for preparing stealth NPs core, providing a new NP vehicle for clinical drug delivery that may be targeted to the brain and circulates in the blood for an extended period of time.


Assuntos
Nanopartículas , Álcoois , Encéfalo , Cianoacrilatos , Sistemas de Liberação de Medicamentos , Nanopartículas/química
18.
J Am Med Inform Assoc ; 29(9): 1449-1460, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35799370

RESUMO

OBJECTIVES: To develop and validate a standards-based phenotyping tool to author electronic health record (EHR)-based phenotype definitions and demonstrate execution of the definitions against heterogeneous clinical research data platforms. MATERIALS AND METHODS: We developed an open-source, standards-compliant phenotyping tool known as the PhEMA Workbench that enables a phenotype representation using the Fast Healthcare Interoperability Resources (FHIR) and Clinical Quality Language (CQL) standards. We then demonstrated how this tool can be used to conduct EHR-based phenotyping, including phenotype authoring, execution, and validation. We validated the performance of the tool by executing a thrombotic event phenotype definition at 3 sites, Mayo Clinic (MC), Northwestern Medicine (NM), and Weill Cornell Medicine (WCM), and used manual review to determine precision and recall. RESULTS: An initial version of the PhEMA Workbench has been released, which supports phenotype authoring, execution, and publishing to a shared phenotype definition repository. The resulting thrombotic event phenotype definition consisted of 11 CQL statements, and 24 value sets containing a total of 834 codes. Technical validation showed satisfactory performance (both NM and MC had 100% precision and recall and WCM had a precision of 95% and a recall of 84%). CONCLUSIONS: We demonstrate that the PhEMA Workbench can facilitate EHR-driven phenotype definition, execution, and phenotype sharing in heterogeneous clinical research data environments. A phenotype definition that integrates with existing standards-compliant systems, and the use of a formal representation facilitates automation and can decrease potential for human error.


Assuntos
Registros Eletrônicos de Saúde , Poli-Hidroxietil Metacrilato , Humanos , Idioma , Fenótipo
19.
Int J Biol Macromol ; 168: 526-536, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33310104

RESUMO

Phototherapy holds promise in cancer treatment for its prominent antitumor efficacy and low systematic toxicity compared with traditional chemotherapy. However, the higher risk of tumor metastasis caused by the severe hypoxic state during phototherapy is a threat in practical use. Here, in order to tackle this challenge, we developed a delivery system via loading the photosensitizer indocyanine green (ICG) into the low molecular weight heparin (LMWH) modified liposomes (LMWH-ICG-Lip) to realize the synergistic effects between photosensitizer and drug vehicle, achieving better phototherapeutic efficacy and meanwhile alleviating the potential risk of tumor metastasis caused by phototherapy. In this system, besides elongating the photosensitizers' circulation time and enhancing their accumulating efficacy to tumor tissues, LMWH itself also exhibited anti-metastasis efficacy via inhibiting adhesion of platelets to tumor cells and decreasing migration and invasion capability of tumor cells. In vivo efficacy evaluation was conducted on orthotopic 4T1 breast cancer model, and the system of LMWH-ICG-Lip could alleviate metastasis potential of residual tumor cells after irradiation, and elicit optimistic antitumor and anti-metastasis efficacy for phototherapy.


Assuntos
Neoplasias da Mama/terapia , Heparina de Baixo Peso Molecular/química , Verde de Indocianina/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Lipossomos , Camundongos , Metástase Neoplásica , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Int Med Res ; 49(11): 3000605211060175, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34851774

RESUMO

OBJECTIVE: Caries risk assessment tools are essential for identifying and providing treatment for individuals at high risk of developing caries. We aimed to develop a nomogram for the assessment and evaluation of caries risk among Chinese children. METHODS: We enrolled schoolchildren age 7 years from a primary school in Shanghai. Baseline information of participants was collected using a questionnaire completed by children's caregivers. A nomogram of a novel prediction scoring model was established based on predictors detected in univariate and multivariate analyses. Predictive accuracy and discriminative ability of the nomogram were calculated using the concordance index (C index). The bootstrap method (1000 samples) was used to decrease overfitting. The net benefit of the model was validated using decision curve analysis. RESULTS: Overall, 406 children with complete information and two completed dental examinations were included in the final analysis. The nomogram based on logistic regression model coefficients demonstrated a C index of 0.766 (95% confidence interval: 0.761-0.771) for caries risk. The net benefit of the decision curve analysis was 38.6% at 55% threshold probability. CONCLUSION: This nomogram model, derived using dietary habits, oral hygiene status, and caries experience, showed promising predictive ability to assess the caries risk among Chinese children.


Assuntos
Cárie Dentária , Nomogramas , Criança , China/epidemiologia , Estudos de Coortes , Cárie Dentária/diagnóstico , Cárie Dentária/epidemiologia , Suscetibilidade à Cárie Dentária , Humanos , Modelos Logísticos
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