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1.
Int J Biol Macromol ; 266(Pt 1): 131106, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552685

RESUMO

The process of diabetic wound healing was influenced by the excessive proliferation of reactive oxygen species (ROS). Therefore, in the process of healing diabetic wounds, it was crucial to removing ROS. This study designed composited nanoparticles: KBP, consisted by Konjac glucomannan, bovine serum albumin, and Prussian blue. Then they were embedded in Konjac glucomannan and hydroxypropyl trimethylammonium chloride chitosan composite hydrogel (KH), The KBP@KH hydrogel finally achieved excellent efficacy in diabetic wound healing. The in vitro and in vivo experiments demonstrated that KPB nanoparticles exhibited favorable ROS scavenging capability and biosafety. The KBP@KH hydrogel not only effectively eliminated ROS from diabetic wounds, but also exhibited excellent wound adaptability. The KBP@KH hydrogel facilitated angiogenesis and suppressed the production of inflammatory factors. Overall, the KBP@KH hydrogel dressing was characterized by its user-friendly nature, safety, and high efficiency.


Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Ferrocianetos , Hidrogéis , Mananas , Nanocompostos , Espécies Reativas de Oxigênio , Soroalbumina Bovina , Cicatrização , Animais , Bovinos , Humanos , Masculino , Camundongos , Ratos , Antioxidantes/farmacologia , Antioxidantes/química , Bandagens , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Ferrocianetos/química , Ferrocianetos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Hidrogéis/química , Hidrogéis/farmacologia , Mananas/química , Mananas/farmacologia , Nanocompostos/química , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/química , Cicatrização/efeitos dos fármacos
2.
Molecules ; 28(22)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-38005263

RESUMO

Photocatalytic technology for inactivating bacteria in water has received much attention. In this study, we reported a dark-light dual-mode sterilized g-C3N4/chitosan/poly (vinyl alcohol) hydrogel (g-CP) prepared through freeze-thaw cycling and an in situ electron-beam radiation method. The structures and morphologies of g-CP were confirmed using Fourier infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), solid ultraviolet diffuse reflectance spectroscopy (UV-vis DRS), and Brunauer-Emmett-Teller (BET). Photocatalytic degradation experiments demonstrated that 1 wt% g-CP degraded rhodamine B (RhB) up to 65.92% in 60 min. At the same time, g-CP had good antimicrobial abilities for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) within 4 h. The shapes of g-CP were adjustable (such as bar, cylinder, and cube) and had good mechanical properties and biocompatibility. The tensile and compressive modulus of 2 wt% g-CP were 0.093 MPa and 1.61 MPa, respectively. The Cell Counting Kit-8 (CCK-8) test and Hoechst33342/PI double staining were used to prove that g-CP had good biocompatibility. It is expected to be applied to environmental sewage treatment and wound dressing in the future.


Assuntos
Escherichia coli , Staphylococcus aureus , Nanogéis , Elétrons , Microscopia Eletrônica de Varredura
3.
J Org Chem ; 88(24): 16906-16914, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38019102

RESUMO

A stereoselective and environmentally friendly thiolation of terminal alkynes was reported. Thiuram disulfide reagents (tetramethylthiuram disulfide and tetraethylthiuram disulfide) that reacted with alkynes in dimethyl sulfoxide (DMSO)/H2O could give (Z)-vinyl sulfides in good yields (up to 88%). This protocol features broad substrate scope, good stereoselectivity, high atom economy, good yields, and is transition metal-free. Mechanistic studies revealed that water and DMSO served as hydrogen sources, which greatly highlighted the unique reactivity of this special reaction involving two H-atom donors.

4.
Angew Chem Int Ed Engl ; 61(43): e202212253, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36082671

RESUMO

Coordination-driven crosslinking networks with reversible and dynamic characteristics are gaining increasing interest in diverse application fields. Herein, we use a coordination crosslinking approach using metal-organic polyhedra (MOPs) as high-connectivity building blocks to post-assemble a class of coordination hypercrosslinked MOP (CHMOP) polymers. The introduction of 12-connected MOP nodes to the polymeric networks is critical to producing membranes that overcome the trade-off between mechanical properties and dynamic healing, and meanwhile possess multifunctionalities including shape memory, solution processability, and 3D printing. The CHMOPs can also be used for anticorrosion coating and achieve function couplings, e.g., shape memory-assisted self-healing (SMASH), which have not been achieved in the MOP-based hybrid materials yet. This work not only offers a feasible strategy to construct new multifunctional materials but also greatly expands the application scopes of MOPs.

5.
Cells ; 11(15)2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35954164

RESUMO

Axotomy in the CNS activates retrograde signals that can trigger regeneration or cell death. Whether these outcomes use different injury signals is not known. Local protein synthesis in axon tips plays an important role in axon retraction and regeneration. Microarray and RNA-seq studies on cultured mammalian embryonic or early postnatal peripheral neurons showed that axon growth cones contain hundreds to thousands of mRNAs. In the lamprey, identified reticulospinal neurons vary in the probability that their axons will regenerate after axotomy. The bad regenerators undergo early severe axon retraction and very delayed apoptosis. We micro-aspirated axoplasms from 10 growing, 9 static and 5 retracting axon tips of spinal cord transected lampreys and performed single-cell RNA-seq, analyzing the results bioinformatically. Genes were identified that were upregulated selectively in growing (n = 38), static (20) or retracting tips (18). Among them, map3k2, csnk1e and gtf2h were expressed in growing tips, mapk8(1) was expressed in static tips and prkcq was expressed in retracting tips. Venn diagrams revealed more than 40 components of MAPK signaling pathways, including jnk and p38 isoforms, which were differentially distributed in growing, static and/or retracting tips. Real-time q-PCR and immunohistochemistry verified the colocalization of map3k2 and csnk1e in growing axon tips. Thus, differentially regulated MAPK and circadian rhythm signaling pathways may be involved in activating either programs for axon regeneration or axon retraction and apoptosis.


Assuntos
Axônios , Traumatismos da Medula Espinal , Animais , Axônios/metabolismo , Lampreias/genética , Mamíferos , Regeneração Nervosa/genética , RNA-Seq , Transdução de Sinais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Transcriptoma/genética
6.
J Org Chem ; 86(12): 8457-8464, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34100610

RESUMO

A metal-free Cs2CO3-promoted hydrothiolation of alkynes with aryl thioureas for stereoselective synthesis of (Z)-vinyl sulfides has been reported. Vinyl thioethers were obtained without a metal catalyst in good yields via anti-Markovnikov and cis addition. The protocol features a broad substrate scope of the starting materials, high atom economy, good yields, and exclusive stereoselectivity, showing potential synthetic value for the synthesis of a diversity of (Z)-vinyl thioethers.


Assuntos
Alcinos , Tioureia , Catálise , Sulfetos
7.
RSC Adv ; 11(11): 6173-6181, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35423147

RESUMO

A new spherical cellulose-based adsorbent and high phosphate removal rate microcrystalline cellulose-g-acrylamide/ethylenediamine/phthalic anhydride (MCC-g-AM/EDA/PA) loaded Fe(iii) adsorbent was prepared by a pre-radiation grafting and chemical modification method. Fe(iii) was successfully introduced into the modified grafted chains of the MCC-g-AM/EDA/PA resin, and characterized by FTIR, TG, XRD, SEM and XPS. The optimized conditions for the grafting reaction of acrylamide (AM) onto MCC were 20% AM emulsion at an absorbed dose of 30 kGy, and a grafting rate as high as 247%. In addition, the adsorption performance of the adsorbent was tested by static adsorption experiments with phosphate. The adsorbent resin showed excellent adsorption performance under alkaline conditions, contributions to the synergetic effect of precipitation, and inner-sphere surface complex reactions. The adsorption efficiency can reach 89.7% at low concentration. In summary, the neotype spherical cellulose-based adsorbent has the advantages of being separation-free in bulk materials, avoiding secondary pollution, and being easy to recycle, and it could be employed as an environmentally friendly adsorbent for phosphate removal in eutrophic water.

8.
Angew Chem Int Ed Engl ; 60(7): 3647-3653, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33098274

RESUMO

Self-assembly is important for creating photonic structures and structural color is typically tunable by varying the size of building blocks, which are themselves obtained after time-consuming chemical syntheses. The molecular conformation of bottlebrush block copolymers (BBCPs) in solution can be manipulated to create libraries of photonic structures. Amphiphilic BBCPs bearing oxidation-responsive ferrocene groups on the hydrophilic block are used to fabricate porous particles via evaporation-induced self-assembly of water-in-oil-in-water (W/O/W) double emulsions stabilized by the BBCP surfactant. In situ oxidation of the ferrocene groups by hydrogen peroxide at the W/O interface leads to enhanced hydrophilicity, more hydration, and chain extension of the hydrophilic block. Consequently, larger internal water droplets are spontaneously formed, yielding larger pores within the microparticles. The pore diameter is readily tunable from 144 to 301 nm with a single BBCP, thereby generating full-spectrum structural colors. This work provides a straightforward method for fabrication of libraries of photonic pigments in an easy and scalable manner.

9.
Front Immunol ; 11: 574136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162989

RESUMO

Schistosomiasis japonica is an ancient parasitic disease that has severely impacted human health causing a substantial disease burden not only to the Chinese people but also residents of other countries such as the Philippines, Indonesia and, before the 1970s, Japan. Since the founding of the new People's Republic of China (P. R. China), effective control strategies have been implemented with the result that the prevalence of schistosomiasis japonica has decreased markedly in the past 70 years. Historically, the Dongting Lake region in Hunan province is recognised as one of the most highly endemic for schistosomiasis in the P.R. China. The area is characterized by vast marshlands outside the lake embankments and, until recently, the presence of large numbers of domestic animals such as bovines, goats and sheep that can act as reservoir hosts for Schistosoma japonicum. Considerable social, economic and environmental changes have expanded the Oncomelania hupensis hupensis intermediate snail host areas in the Dongting lake region increasing the potential for both the emergence of new hot spots for schistosomiasis transmission, and for its re-emergence in areas where infection is currently under control. In this paper, we review the history, the current endemic status of schistosomiasis and the control strategies in operation in the Dongting Lake region. We also explore epidemiological factors contributing to S. japonicum transmission and highlight key research findings from studies undertaken on schistosomiasis mainly in Hunan but also other endemic Chinese provinces over the past 10 years. We also consider the implications of these research findings on current and future approaches that can lead to the sustainable integrated control and final elimination of schistosomiasis from the P. R. China and other countries in the region where this unyielding disease persists.


Assuntos
Lagos , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/prevenção & controle , Animais , China/epidemiologia , Reservatórios de Doenças/parasitologia , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Lagos/parasitologia , Prevalência , Schistosoma japonicum , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/transmissão , Zoonoses/epidemiologia , Zoonoses/parasitologia , Zoonoses/prevenção & controle , Zoonoses/transmissão
10.
J Org Chem ; 85(2): 493-500, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31845809

RESUMO

A highly efficient synthetic method for the preparation of 2-aminobenzothiazoles starting from arylthioureas has been reported. By using a nickel catalyst, arylthioureas undergo intramolecular oxidative C-H bond functionalization, giving the desired 2-aminobenzothiazoles in good to excellent yields. This protocol features an inexpensive catalyst, low catalyst loading, mild reaction conditions, a short reaction time, and good to excellent yields, and it can be scaled up easily to a gram scale with almost no yields decreasing.

11.
Front Immunol ; 10: 457, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930899

RESUMO

The Lin28b+Let7- axis in fetal/neonatal development plays a role in promoting CD5+ B1a cell generation as a B-1 B cell developmental outcome. Here we identify the Let7 target, Arid3a, as a crucial molecular effector of the B-1 cell developmental program. Arid3a expression is increased at pro-B cell stage and markedly increased at pre-B and immature B cell stages in the fetal/neonatal liver B-1 development relative to that in the Lin28b-Let7+ adult bone marrow (BM) B-2 cell development. Analysis of B-lineage restricted Lin28b transgenic (Tg) mice, Arid3a knockout and Arid3a Tg mice, confirmed that increased Arid3a allows B cell generation without requiring surrogate light chain (SLC) associated pre-BCR stage, and prevents MHC class II cell expression at the pre-B and newly generated immature B cell stages, distinct from pre-BCR dependent B development with MHC class II in adult BM. Moreover, Arid3a plays a crucial role in supporting B1a cell generation. The increased Arid3a leads higher Myc and Bhlhe41, and lower Siglec-G and CD72 at the pre-B and immature B cell stages than normal adult BM, to allow BCR signaling induced B1a cell generation. Arid3a-deficiency selectively blocks the development of B1a cells, while having no detectable effect on CD5- B1b, MZ B, and FO B cell generation resembling B-2 development outcome. Conversely, enforced expression of Arid3a by transgene is sufficient to promote the development of B1a cells from adult BM. Under the environment change between birth to adult, altered BCR repertoire in increased B1a cells occurred generated from adult BM. However, crossed with B1a-restricted VH/D/J IgH knock-in mice allowed to confirm that SLC-unassociated B1a cell increase and CLL/lymphoma generation can occur in aged from Arid3a increased adult BM. These results confirmed that in fetal/neonatal normal mice, increased Arid3a at the pre-B cell and immature B cell stages is crucial for generating B1a cells together with the environment for self-ligand reactive BCR selection, B1a cell maintenance, and potential for development of CLL/Lymphoma in aged mice.


Assuntos
Subpopulações de Linfócitos B/imunologia , Proteínas de Ligação a DNA/imunologia , Células Precursoras de Linfócitos B/metabolismo , Fatores de Transcrição/imunologia , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Proteínas de Ligação a DNA/genética , Regulação Leucêmica da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Camundongos , Camundongos Knockout , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Fatores de Transcrição/genética
12.
Front Immunol ; 10: 645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001264

RESUMO

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicum infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the S. japonicum, lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) our team developed showed encouraging efficacy against S. japonicum in Chinese water buffaloes. Here we report the results of a double-blind cluster randomized trial aimed at determining the impact of a combination of the SjCTPI bovine vaccine (given as a prime-boost regimen), human mass chemotherapy and snail control on the transmission of S. japonicum in 12 selected administrative villages around the Dongting Lake in Hunan province. The trial confirmed human praziquantel treatment is an effective intervention at the population level. Further, mollusciciding had an indirect ~50% efficacy in reducing human infection rates. Serology showed that the SjCTPI vaccine produced an effective antibody response in vaccinated bovines, resulting in a negative correlation with bovine egg counts observed at all post-vaccination time points. Despite these encouraging outcomes, the effect of the vaccine in preventing human infection was inconclusive. This was likely due to activities undertaken by the China National Schistosomiasis Control Program, notably the treatment, sacrifice or removal of bovines from trial villages, over which we had no control; as a result, the trial design was compromised, reducing power and contaminating outcome measures. This highlights the difficulties in undertaking field trials of this nature and magnitude, particularly over a long period, and emphasizes the importance of mathematical modeling in predicting the potential impact of control intervention measures. A transmission blocking vaccine targeting bovines for the prevention of S. japonicum with the required protective efficacy would be invaluable in tandem with other preventive intervention measures if the goal of eliminating schistosomiasis from China is to become a reality.


Assuntos
Anti-Helmínticos/uso terapêutico , Doenças dos Bovinos/prevenção & controle , Praziquantel/uso terapêutico , Esquistossomose Japônica/prevenção & controle , Vacinação/veterinária , Vacinas/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Búfalos , Bovinos , Criança , Pré-Escolar , China , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Esquistossomose Japônica/transmissão , Esquistossomose Japônica/veterinária , Caramujos , Adulto Jovem
13.
Front Immunol ; 10: 284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30842779

RESUMO

Schistosomiasis remains a serious zoonotic disease in China and the Philippines. Water buffalo and cattle account for the majority of transmission. Vaccination of water buffalo is considered a key strategy to reduce disease prevalence. Previously, we showed that vaccination of water buffalo with SjC23 or SjCTPI plasmid DNA vaccines, induced 50% efficacy to challenge infection. Here, we evaluated several parameters to determine if we can develop a two dose vaccine that maintains the efficacy of the three dose vaccine. We performed four trials evaluating: (1) lab produced vs. GLP grade vaccines, (2) varying the time between prime and boost, (3) the influence of an IL-12 adjuvant, and (4) a two dose heterologous (DNA-protein) prime-boost. We found the source of the DNA vaccines did not matter, nor did increasing the interval between prime and boost. Elimination of the IL-12 plasmid lowered homologous DNA-DNA vaccine efficacy. A major finding was that the heterologous prime boost improved vaccine efficacy, with the prime-boost regimen incorporating both antigens providing a 55% reduction in adult worms and 53% reduction in liver eggs. Vaccinated buffalo produced vaccine-specific antibody responses. These trials suggest that highly effective vaccination against schistosomes can be achieved using a two dose regimen. No adjuvants were used with the protein boost, and the potential that addition of adjuvant to the protein boost to further increase efficacy should be evaluated. These results suggest that use of these two schistosome vaccines can be part of an integrated control strategy to reduce transmission of schistosomiasis in Asia.


Assuntos
Búfalos/imunologia , Proteínas de Helminto/imunologia , Schistosoma/imunologia , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos de Helmintos/imunologia , Búfalos/parasitologia , China , Imunização Secundária/métodos , Interleucina-12/imunologia , Vacinação/métodos , Zoonoses/imunologia , Zoonoses/parasitologia , Zoonoses/prevenção & controle
14.
Infect Dis Poverty ; 8(1): 23, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922403

RESUMO

BACKGROUND: With the closure of the Three Gorges Dam in 2003 the hydrology of Poyang Lake was altered dramatically leading to significant changes in the environment. In order to assess the impact on schistosomiasis this study assessed the spatial and temporal patterns of the snail intermediate host, Oncomelania hupensis in the Poyang Lake tributaries. The results of the study have important implications for future snail control strategies leading to disease elimination. METHODS: The marshland area surrounding Poyang Lake was divided randomly into 200 × 200 m vector grids using ArcGIS software, and the surveyed grids were randomly selected by the software. The snail survey was conducted in each selected grid using a survey frame of 50 × 50 m with one sideline of each grid serving as the starting line. No less than ten frames were used in each surveyed grid with Global Positioning System (GPS) recordings for each. All snails in each frame were collected to determine infection status by microscopy. Altitude data for all frames were extracted from a lake bottom topographic map in order to analyze the average altitude. All snail survey data were collected and statistically analyzed with SPSS 20.0 software in order to determine the difference of the percentage of frames with living snails and mean density of living snails in different regions of Poyang Lake. The altitude of the snail-infested marshlands and snail dens were subsequently identified. RESULTS: A total of 1159 potential snail sampling grids were surveyed, of which 15 231 frames (0.1 m2/frame) were investigated. 1241 frames had live Oncomelania snails corresponding to 8.15% of the total number of frames. The mean density of living snails was 0.463/0.1 m2 with a maximum of 57 snails per frame. The percent of frames with snails in the southern sector (8.13%) of Poyang Lake did not differ statistically from the north (8.21%). However, the mean density of live snails in the northern sector (0.164/0.1 m2) of the lake was statistically higher (F = 6.727; P = 0.010) than the south (0.141/0.1 m2). In the south of the lake, the elevation of snail-inhabited marshland ranged between 11 - 16 m, and could be further subdivided into two snail-concentrated belts at 12-13 m of elevation and 15-16 m of elevation respectively. In the north of the lake, the elevation of snail-inhabited marshland ranged between 9- 16 m with the elevation of 12-14 m being the snail-concentrated zone. CONCLUSIONS: The elevation of snail-infested marshlands in the Poyang Lake region ranged from 9 to 16 m. The snail distribution and habitat has moved north of the lake and to a lower altitude due to changes in the water level post dam closure. Based on the current geological features of the snail habitant focused mollusciciding should occur in snail dense northern regions with frequent bovine and human traffic. Targeting these identified 'hotspots' of transmission will assist in elimination efforts.


Assuntos
Lagos/parasitologia , Esquistossomose Japônica/transmissão , Caramujos/parasitologia , Animais , China , Vetores de Doenças , Sistemas de Informação Geográfica , Geografia , Humanos , Esquistossomose Japônica/prevenção & controle
15.
Angew Chem Int Ed Engl ; 57(51): 16888-16892, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30417592

RESUMO

A one-step procedure for the self-switchable block copolymerization of monomer mixtures of epoxides, cyclic anhydrides, and lactide (LA) was developed by using simple organocatalysts without an external stimulus. This multicomponent polymerization bridges two catalytic cycles involving ring-opening alternating copolymerization of epoxides with anhydrides and ring-opening polymerization (ROP) of LA, in which the presence/absence of anhydrides in mixed feedstocks switched the ROP of LA off/on. The self-switchable terpolymerization showed distinct noncoordinating and living nature, as well as perfect chemoselectivity. Different combinations of epoxides, anhydrides, and initiators enabled the generation of a variety of new block polyester polyols.

16.
J Exp Med ; 214(10): 3067-3083, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-28878001

RESUMO

Although B cell development requires expression of the B cell antigen receptor (BCR), it remains unclear whether engagement of self-antigen provides a positive impact for most B cells. Here, we show that BCR engagement by self-ligand during development in vivo results in up-regulation of the Nod-like receptor member Nod1, which recognizes the products of intestinal commensal bacteria. In anti-thymocyte/Thy-1 autoreactive BCR knock-in mice lacking self-Thy-1 ligand, immunoglobulin light chain editing occurred, generating B cells with up-regulated Nod1, including follicular and marginal zone B cells with natural autoreactivity. This BCR editing with increased Nod1 resulted in preferential survival. In normal adult mice, most mature B cells are enriched for Nod1 up-regulated cells, and signaling through Nod1 promotes competitive survival of mature B cells. These findings demonstrate a role for microbial products in promoting survival of mature B cells through up-regulated Nod1, providing a positive effect of BCR engagement on development of most B cells.


Assuntos
Linfócitos B/fisiologia , Proteínas NLR/fisiologia , Proteína Adaptadora de Sinalização NOD1/fisiologia , Receptores de Antígenos de Linfócitos B/fisiologia , Envelhecimento/fisiologia , Animais , Linfócitos B/metabolismo , Técnicas de Introdução de Genes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais/fisiologia , Regulação para Cima
17.
J Immunol ; 199(5): 1706-1715, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28739882

RESUMO

CD79a and CD79b proteins associate with Ig receptors as integral signaling components of the B cell Ag receptor complex. To study B cell development in zebrafish, we isolated orthologs of these genes and performed in situ hybridization, finding that their expression colocalized with IgH-µ in the kidney, which is the site of B cell development. CD79 transgenic lines were made by linking the promoter and upstream regulatory segments of CD79a and CD79b to enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-µ expression in sorted cells. We crossed these CD79-GFP lines to a recombination activating gene (Rag)2:mCherry transgenic line to identify B cell development stages in kidney marrow. Initiation of CD79:GFP expression in Rag2:mCherry+ cells and the timing of Ig H and L chain expression revealed simultaneous expression of both IgH-µ- and IgL-κ-chains, without progressing through the stage of IgH-µ-chain alone. Rag2:mCherry+ cells without CD79:GFP showed the highest Rag1 and Rag2 mRNAs compared with CD79a and CD79b:GFP+ B cells, which showed strongly reduced Rag mRNAs. Thus, B cell development in zebrafish does not go through a Raghi CD79+IgH-µ+ pre-B cell stage, different from mammals. After the generation of CD79:GFP+ B cells, decreased CD79 expression occurred upon differentiation to Ig secretion, as detected by alteration from membrane to secreted IgH-µ exon usage, similar to in mammals. This confirmed a conserved role for CD79 in B cell development and differentiation, without the requirement of a pre-B cell stage in zebrafish.


Assuntos
Linfócitos B/fisiologia , Antígenos CD79/metabolismo , Proteínas de Peixes/metabolismo , Rim/fisiologia , Células Precursoras de Linfócitos B/fisiologia , Peixe-Zebra/imunologia , Animais , Animais Geneticamente Modificados , Antígenos CD79/genética , Diferenciação Celular , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Proteínas de Peixes/genética , Genes Reporter/genética , Proteínas de Fluorescência Verde/genética , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Cadeias Leves de Imunoglobulina/genética , Cadeias Leves de Imunoglobulina/metabolismo , Ativação Linfocitária , Transgenes/genética , Proteínas de Peixe-Zebra/genética
18.
J Inherit Metab Dis ; 40(1): 113-120, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27444757

RESUMO

Cystathionine ß-synthase (CBS) deficiency is a recessive inborn error of metabolism in which patients have extremely elevated plasma total homocysteine and have clinical manifestations in the vascular, visual, skeletal, and nervous systems. Homocysteine is an intermediary metabolite produced from the hydrolysis of S-adenosylhomocysteine (SAH), which is a by-product of methylation reactions involving the methyl-donor S-adenosylmethionine (SAM). Here, we have measured SAM, SAH, DNA and histone methylation status in an inducible mouse model of CBS deficiency to test the hypothesis that homocysteine-related phenotypes are caused by inhibition of methylation due to elevated SAH and reduced SAM/SAH ratio. We found that mice lacking CBS have elevated cellular SAH and reduced SAM/SAH ratios in both liver and kidney, but this was not associated with alterations in the level of 5-methylcytosine or various histone modifications. Using methylated DNA immunoprecipitation in combination with microarray, we found that of the 241 most differentially methylated promoter probes, 89 % were actually hypermethylated in CBS deficient mice. In addition, we did not find that changes in DNA methylation correlated well with changes in RNA expression in the livers of induced and uninduced CBS mice. Our data indicates that reduction in the SAM/SAH ratio, due to loss of CBS activity, does not result in overall hypomethylation of either DNA or histones.


Assuntos
Cistationina beta-Sintase/genética , Metilação de DNA/genética , Epigênese Genética/genética , Homocistinúria/genética , Animais , Cistationina beta-Sintase/metabolismo , DNA/genética , Modelos Animais de Doenças , Epigenômica/métodos , Homocisteína/genética , Homocisteína/metabolismo , Homocistinúria/metabolismo , Rim/metabolismo , Fígado/metabolismo , Camundongos , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo
19.
Dalton Trans ; 45(25): 10308-18, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27241779

RESUMO

Novel Zr(iv) and Hf(iv) complexes bearing two constrained bulky ß-enaminoketonato ligands {[ArN[double bond, length as m-dash]CH-C8H3(CH2)n(R)O]2MBn2, M = Zr or Hf; n = 1, 2 or 3; R = H or C6H5; Ar = C6H5 or C6F5} were synthesized and clearly characterized. X-ray crystal structure analysis reveals that these complexes adopt a distorted octahedral geometry. Compared with non-constrained analogues, the Zr(iv) complexes with a cyclic skeleton exhibited high catalytic activities (up to 16.4 kgPE mmolZr(-1) h(-1)) toward ethylene polymerization at ambient pressure and elevated temperatures. Moreover, the catalytic properties of these complexes could be governed exquisitely by appropriate variation of the N-aryl substituents and the size of the benzocyclane. The Zr(iv) complexes bearing a non-fluorinated N-aryl group yielded oligomers, while the fluorinated analogues bearing a five-membered or six-membered cyclane group produced high molecular weight polyethylenes (33.4-306 kg mol(-1)) under similar conditions on account of the suppression effects on ß-H elimination. The Zr(iv) complexes are more active toward ethylene polymerization than the Hf(iv) analogues, and the resulting polymers exhibited higher molecular weight and narrower molecular weight distribution.

20.
ACS Appl Mater Interfaces ; 8(19): 12445-55, 2016 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-27136676

RESUMO

We report here a series of novel spontaneously healable thermoplastic elastomers (TPEs) with a combination of improved mechanical and good autonomic self-healing performances. Hard-soft diblock and hard-soft-hard triblock copolymers with poly[exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-benzeno-l,4-methanoanthracene] (PHBM) as the hard block and secondary amide group containing norbornene derivative polymer as the soft block were synthesized via living ring-opening metathesis copolymerization by use of Grubbs third-generation catalyst through sequential monomer addition. The microstructure, mechanical, self-healing, and surface morphologies of the block copolymers were thoroughly studied. Both excellent mechanical performance and self-healing capability were achieved for the block copolymers because of the interplayed physical cross-link of hard block and dynamic interaction formed by soft block in the self-assembled network. Under an optimized hard block (PHBM) weight ratio of 5%, a significant recovery of tensile strength (up to 100%) and strain at break (ca. 85%) was achieved at ambient temperature without any treatment even after complete rupture. Moreover, the simple reaction operations and well-designed monomers offer versatility in tuning the architectures and properties of the resulting block copolymers.

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