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1.
Sci Transl Med ; 16(748): eadn0223, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38753806

RESUMO

A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01B was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost after eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens.


Assuntos
Vacinas contra a AIDS , Anticorpos Neutralizantes , Anticorpos Anti-HIV , Animais , Humanos , Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Camundongos , Vacinação , Imunização Secundária , HIV-1/imunologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Anticorpos Amplamente Neutralizantes/imunologia
2.
Nat Immunol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816615

RESUMO

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

3.
Sci Immunol ; 9(95): eadn0622, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38753808

RESUMO

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.


Assuntos
Anticorpos Amplamente Neutralizantes , Nanopartículas , RNA Mensageiro , Animais , Camundongos , Humanos , RNA Mensageiro/imunologia , RNA Mensageiro/genética , Nanopartículas/química , Anticorpos Amplamente Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Lipídeos/imunologia , Infecções por HIV/imunologia , Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/imunologia , HIV-1/imunologia , Feminino , Anticorpos Monoclonais , Lipossomos
4.
Materials (Basel) ; 16(20)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37895763

RESUMO

The study aims to enhance the corrosion resistance and bioactivity of Mg alloy substrates through the development of a zinc/hydroxyapatite multi-layer (Zn/HA-ML) coating. The Zn/HA-ML coating was prepared by depositing a cold-sprayed (CS) Zn underlayer and a high-velocity suspension flame sprayed (HVSFS) Zn/HA multi-layer and was compared with the CS Zn coating and the Zn/HA dual-layer (Zn/HA-DL) coating. Phase, microstructure, and bonding strength were examined, respectively, by X-ray diffraction, scanning electron microscopy, and tensile bonding testing. Corrosion behavior and bioactivity were investigated using potentiodynamic polarization, electrochemical impedance spectroscopy, and immersion testing. Results show that the HVSFS Zn/HA composite layers were mainly composed of Zn, HA, and ZnO and were well bonded to the substrate. The HVSFS HA upper layer on the CS Zn underlayer in the Zn/HA-DL coating exhibited microcracks due to their mismatched thermal expansion coefficient (CTE). The Zn/HA-ML coating exhibited good bonding within different layers and showed a higher bonding strength of 27.3 ± 2.3 MPa than the Zn/HA-DL coating of 20.4 ± 2.7 MPa. The CS Zn coating, Zn/HA-DL coating, and Zn/HA-ML coating decreased the corrosion current density of the Mg alloy substrate by around two-fourfold from 3.12 ± 0.75 mA/cm2 to 1.41 ± 0.82mA/cm2, 1.06 ± 0.31 mA/cm2, and 0.88 ± 0.27 mA/cm2, respectively. The Zn/HA-ML coating showed a sixfold decrease in the corrosion current density and more improvements in the corrosion resistance by twofold after an immersion time of 14 days, which was mainly attributed to newly formed apatite and corrosion by-products of Zn particles. The Zn/HA-ML coating effectively combined the advantages of the corrosion resistance of CS Zn underlayer and the bioactivity of HVSFS Zn/HA multi-layers, which proposed a low-temperature strategy for improving corrosion resistance and bioactivity for implant metals.

5.
Medicine (Baltimore) ; 102(35): e34764, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657030

RESUMO

BACKGROUND: Accumulating evidence has indicated a possible connection between post-stroke cognitive impairment (PSCI) and gut microbiota imbalance. To further investigate this association, the present work was designed to systematically assess the dissimilarity of gut microbiota between PSCI and healthy individuals or stroke patients. METHODS: A meta-analysis and systematic review was conducted by searching various databases including PubMed, Web of Science, Embase, VIP, CNKI, and Wangfang for relevant studies. The pooled outcomes were used to estimate the combined dissimilarity of gut microbiota composition between PSCI and healthy individuals or patients with stroke. RESULTS: Nine eligible studies were included in this meta-analysis. The results showed that there were no significant changes in observed richness indexes (Chao1 and ACE) and Shannon index. Notably, a significant decrease in Simpson index was observed in PSCI patients in comparison to the healthy individuals (-0.31, 95% CI: -0.62 to -0.01, P = 0.04). Moreover, the microbiota composition at the phylum level (increased abundance of Proteobacteria), family level (increased abundance of Bacteroidaceae, Lachnospiraceae, and Veillonellaceae; decreased abundance of Enterobacteriaceae), and genus level (increased abundance of Bacteroides, Clostridium XIVa, and Parabacteroides; decreased abundance of Prevotella and Ruminococcus) was found to be significantly different between PSCI and controls. CONCLUSION: This meta-analysis suggests a significant shift of observed species and microbiota composition in PSCI compared to healthy individuals or patients with stroke.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Microbiota , Acidente Vascular Cerebral , Humanos , Bacteroides , Clostridiales , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/complicações
6.
Science ; 378(6623): eadd6502, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36454825

RESUMO

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.


Assuntos
Vacinas contra a AIDS , Anticorpos Amplamente Neutralizantes , Células Germinativas , Anticorpos Anti-HIV , Infecções por HIV , Cadeias Pesadas de Imunoglobulinas , Cadeias Leves de Imunoglobulina , Humanos , Adjuvantes Imunológicos , Vacinas contra a AIDS/imunologia , Anticorpos Amplamente Neutralizantes/genética , Anticorpos Amplamente Neutralizantes/imunologia , Infecções por HIV/prevenção & controle , Vacinação , Anticorpos Anti-HIV/genética , Anticorpos Anti-HIV/imunologia , Células Germinativas/imunologia , Linfócitos B/imunologia , Mutação , Cadeias Leves de Imunoglobulina/genética , Cadeias Leves de Imunoglobulina/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Masculino , Feminino , Adulto
7.
Materials (Basel) ; 15(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36234064

RESUMO

The influence of post-process heat treatment on cold-sprayed Zn coatings on the Mg alloy substrate was investigated at different temperatures (150, 250, and 350 °C) and times (2, 8, and 16 h). Phase, microstructure, microhardness, and tensile strength of Zn coatings were analyzed before and after heat treatment. Corrosion properties of Zn coatings after heat treatment were investigated in simulated body fluid by using potentiodynamic polarization and immersion testing. Results show that although the heat treatment presented little effect on phase compositions of Zn coatings, the full width at half maxima of the Zn phase decreased with the heat temperature and time. Zn coatings presented comparable microstructures before and after heat treatment in addition to the inter-diffusion layers, and the inter-diffusion layer was dependent on the heat temperature and time. Both the thickness and the microhardness of inter-diffusion layers were increased with the heat temperature and time, with the largest thickness of 704.1 ± 32.4 µm and the largest microhardness of 323.7 ± 104.1 HV0.025 at 350 °C for 2 h. The microhardness of Zn coating was significantly decreased from 70.8 ± 5.6 HV0.025 to 43.9 ± 12.5 HV0.025, with the heat temperature from the ambient temperature to 350 °C, and was slightly decreased with the heat time at 250 °C. Although the tensile strength of Zn coating was slightly increased by heat treatment, with the highest value of 40.9 ± 3.9 MPa at 150 °C for 2 h, excessive heat temperature and time were detrimental to the tensile strength, with the lowest value of 6.6 ± 1.6 MPa at 350 °C for 2 h. The heat temperature and heat time presented limited effects on the corrosion current and corrosion ratio of the Zn coatings, and Zn coatings before and after heat treatment effectively hindered the simulated body fluid from penetrating into the substrate. The corrosion behavior of Zn coatings was discussed in terms of corrosion products and microstructures after immersion.

8.
Immunity ; 55(11): 2149-2167.e9, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36179689

RESUMO

Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy-chain complementarity-determining region 3 (HCDR3), suggesting that the rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy-chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bound inferred germlines for PCT64 and PG9 and had higher affinities for bnAbs, determined cryo-EM structures of ApexGT trimers complexed with inferred-germline and bnAb forms of PCT64 and PG9, and developed an mRNA-encoded cell-surface ApexGT trimer. These methods and immunogens have promise to assist HIV vaccine development.


Assuntos
Vacinas contra a AIDS , Infecções por HIV , HIV-1 , Humanos , Anticorpos Amplamente Neutralizantes , Anticorpos Anti-HIV , Produtos do Gene env do Vírus da Imunodeficiência Humana , Anticorpos Neutralizantes , Regiões Determinantes de Complementaridade/genética , Infecções por HIV/prevenção & controle
9.
Clin Appl Thromb Hemost ; 28: 10760296221076152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35287480

RESUMO

OBJECTIVE: To study the efficacy of Yangxin Recipe (YXR) in patients with stable angina pectoris of coronary heart disease and its impacts on coronary CT angiography. METHODS: A total of 78 patients with coronary heart disease and angina pectoris were randomly divided into a control group (n = 39) and a YXR group (n = 39). The control group adopted conventional Western medicine while the YXR group received conventional western medicine + oral administration of YXR. After six months of continuous treatment, the clinical efficacy, traditional Chinese medicine (TCM) syndrome scores, Pittsburgh Sleep Quality Index (PSQI), and the level of coronary CT vascular stenosis were observed. RESULTS: After treatment, the total effective rate of YXR was 92.31%, which was higher than (P < 0.01) that of the western medicine control group. The total score of TCM syndromes in the YXR group was (14.44 ± 9.87), which was significantly lower than (P < 0.001) that in the simple western medicine control group (22.44 ± 13.87). The degree of coronary stenosis in the YXR group decreased to (49.87 ± 7.82) %, which was significantly lower than (P < 0.001) that in the western medicine control group (57.05 ± 9.92) %. CONCLUSION: The efficacy of YXR + conventional western medicine in treating coronary heart disease and angina pectoris is significantly improved compared with the simple conventional western medicine.


Assuntos
Angina Estável , Doença das Coronárias , Medicamentos de Ervas Chinesas , Angina Estável/tratamento farmacológico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Resultado do Tratamento
10.
Cell Rep ; 38(10): 110485, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35263576

RESUMO

Elicitation of HIV broadly neutralizing antibodies (bnAbs) is challenging because unmutated bnAb precursors are rare and seldom bind HIV envelope glycoprotein (Env) trimers. One strategy to initiate bnAb responses is to use germline-targeting (GT) immunogens with high affinity to bnAb-class precursor B cells and then shepherd affinity maturation with booster immunogens that successively look more like native Env. In a mouse model where the frequency of VRC01-precursor (VRC01gHL) B cells mimics that of humans, we show that following a GT HIV Env trimer protein prime, VRC01-class B cells in the germinal center (GC) acquire high-affinity VRC01-class B cell somatic hypermutations (SHMs). Many GC-derived VRC01gHL antibodies robustly bind N276 glycan-deficient Env trimers and neutralize several N276 glycan-deficient tier 2 HIV strains. These results are encouraging for GT Env trimer vaccine designs and demonstrate accumulation of substantial SHMs, including deletions, uncommon point mutations, and functional bnAb features, after a single immunization.


Assuntos
Vacinas contra a AIDS , Infecções por HIV , HIV-1 , Animais , Anticorpos Neutralizantes , Antígenos Virais , Anticorpos Amplamente Neutralizantes , Anticorpos Anti-HIV , Imunização , Camundongos , Polissacarídeos/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana
11.
Food Chem ; 372: 131259, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34627087

RESUMO

A robust data fusion strategy integrating Tri-step infrared spectroscopy (IR) with electronic nose (E-nose) was established for rapid qualitative authentication and quantitative evaluation of red wines using Cabernet Sauvignon as an example. The chemical fingerprints of four types of wines were thoroughly interpreted by Tri-step IR, and the defined spectral fingerprint region of alcohol and sugar was 1200-950 cm-1. The wine types were authenticated by IR-based principal component analysis (PCA). Furthermore, ten quantitative models by partial least squares (PLS) were built to evaluate alcohol and total sugar contents. In particular, the model based on the fusion datasets of spectral fingerprint region and E-nose was superior to the others, in which RMSEP reduced by 47.95% (alcohol) and 79.90% (total sugar), rp increased by 11.95% and 43.47%, and RPD >3.0. The developed methodology would be applicable for mass screening and rapid multi-chemical-component quantification of wines in a more comprehensive and efficient manner.


Assuntos
Vinho , Bebidas Alcoólicas , Análise dos Mínimos Quadrados , Análise de Componente Principal , Espectrofotometria Infravermelho , Vinho/análise
12.
Int J Gen Med ; 14: 7557-7566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754228

RESUMO

OBJECTIVE: To investigate the therapeutic effects of Eight Trigrams Boxing combined with a Wenyang Huoxue recipe on the cardiopulmonary motor function and quality of life in patients with coronary heart disease after an interventional operation (percutaneous coronary intervention [PCI]); further, to provide new clinical evidence and ideas for integrated traditional Chinese and Western medicine in cardiac rehabilitation. METHODS: Sixty patients were selected and successfully underwent PCI in designated hospitals after four weeks, from June 2018 to September 2020. The patients were randomly divided into a treatment group and control group, and both groups were given standard pharmaceuticals after PCI and the Wenyang Huoxue recipe. The treatment group was additionally treated with the Eight Trigrams Boxing Method. The control group was provided with aerobic rehabilitation exercise. The maximum oxygen uptake (VO2max), metabolic equivalent (MET), the results of a 6-min walking test, the Seattle Angina Questionnaire (SAQ) score, SF-36 score, and other indicators were evaluated before and after treatment. The therapeutic effect was evaluated by comparison between the groups and within the groups. RESULTS: The VO2max, MET, 6-min walking distance, SAQ score, and SF-36 score in both groups improved after treatment compared with before treatment. There was no difference between the two groups before treatment. However, after treatment, the VO2max, MET, 6 min walking distance, SAQ score, and SF-36 score in the treatment group were higher compared with the control group. CONCLUSION: A traditional Chinese medicine cardiac rehabilitation program of Eight Trigrams Boxing combined with a Wenyang Huoxue recipe can improve the cardiopulmonary function and quality of life of patients. The therapeutic effect was clear and is worthy of further investigation.

13.
Altern Ther Health Med ; 27(2): 58-64, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32412917

RESUMO

CONTEXT: Coronary heart disease (CHD) refers to a disease where coronary atherosclerosis induces stenosis or obstruction of the blood vessels. Endothelial progenitor cells (EPCs) function to protect and repair the vascular endothelium, and their functional activity state reflects the ability of the body to repair vascular damage. In the peripheral blood of patients with CHD, the density of EPCs decreases, and the function of EPCs is low. OBJECTIVE: This study aimed to investigate the effects of a China Food and Drug Administration (CFDA)-approved prescription medicine, Tongxin, on the density and function of endothelial progenitor cells (EPCs) in peripheral blood. DESIGN: In this study, a randomized, single blind, parallel controlled clinical trial was used. The single blind subjects were subjects. SETTING: The study took place in the Cardiology and Emergency Departments at Shanghai Municipal Hospital of Traditional Chinese Medicine in Shanghai, China. PARTICIPANTS: Participants were 48 patients with coronary heart disease at the hospital. INTERVENTION: Participants were randomly divided into 2 groups (n = 24 each): a control group and an intervention group. Both groups received routine drug treatments, such as platelet inhibitors, nitrates, ß-receptor blockers, statins, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), and calcium blockers. The control group was treated with the Shexiang Baoxin Pill, while the intervention group was treated with prescription Tongxin. The course of treatment was 3 months for both groups. OUTCOME MEASURES: Changes in the density and function of EPCs in the peripheral blood of the 2 groups were measured at baseline and postintervention, and the clinical efficacy of the 2 treatments was statistically analyzed. RESULTS: The density of EPCs was significantly higher in both groups after 3 months of treatment, compared to the densities at baseline (P < .05). The change in density between baseline and postintervention was significantly greater for the intervention group than for the control group (P < .05). For the control group, the proliferative vitality [optical density (OD)] value of the EPCs was significantly higher than that at baseline from the fourth day of treatment (P < .05). In the intervention group, the OD value was significantly higher than that at baseline from the first day of treatment (P < .05). Furthermore, the intervention group's cells began to enter the logarithmic growth phase of increase from the fifth day of treatment, and the group's increase as significantly higher than the control group's from the fifth to the seventh dayof treatment (P < .05 for all 3 days). Moreover, the total effective rate was higher in the intervention group than in the control group (P < .05). CONCLUSIONS: Prescription Tongxin can stimulate the release of EPCs from the bone marrow to the peripheral blood of patients with CHD, can significantly increase the proliferation of EPCs in the peripheral blood, and can improve the clinical symptoms of patients. Its curative effect was greater than that of the control treatment.


Assuntos
Células Progenitoras Endoteliais , Adulto , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prescrições , Método Simples-Cego , Estados Unidos
14.
Cancer Manag Res ; 12: 10693-10703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149676

RESUMO

PURPOSE: Long noncoding RNAs (lncRNAs) exert important functions in the progression of cancers. Currently, we aim to investigate the potential roles of lncRNA ADAM Metallopeptidase with Thrombospondin Type 1 Motif 9 Antisense RNA 1 (ADAMTS9-AS1) in breast carcinoma. MATERIALS AND METHODS: The expressions of ADAMTS9-AS1 and miR-513a-5p in breast carcinoma tissues and cell lines were detected using qRT-PCR. Cell Counting Kit-8 (CCK-8) and transwell assays were used to assess the viability and invasive ability of breast cancer cells. The direct interaction between ADAMTS9-AS1 and miR-513a-5p was predicted using bioinformatics tools. The target of miR-513a-5p, ZFP36 Ring Finger Protein (ZFP36) was validated by luciferase assay. The expression of ZFP36 was measured using Western blot assay. Breast cancer MDA-MB-231 cells growth in vivo was evaluated using xenograft tumor assay. RESULTS: ADAMTS9-AS1 was downregulated in breast cancer tissues as well as cell lines. Upregulation of ADAMTS9-AS1 suppressed the growth and invasiveness of breast carcinoma cells in vitro as well as inhibiting cellgrowth in vivo. Furthermore, ZFP36 was manifested as the target gene of miR-513a-5p and negatively modulated by ADAMTS9-AS1. In addition, overexpression of ADAMTS9-AS1 neutralized the promoting impact of miR-513a-5p on the aggressiveness of breast cancer cells. CONCLUSION: In conclusion, lncRNA ADAMTS9-AS1 inhibited the aggressive phenotypes of breast carcinoma cells via sponging miR-513a-5p and regulating ZFP36.

15.
J Nanosci Nanotechnol ; 20(4): 2442-2451, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492260

RESUMO

Two methods of TiO2 addition were applied to prepare hydroxyapatite/TiO2 (HA/TiO2) composite, i.e., in-situ hydrolysis TiO2 in HA powders (N-HA/TiO2) and mixing commercial nano-sized HA and TiO2 powder (C-HA/TiO2). Effects of TiO2 addition methods and sintering temperatures on phase, microstructure and microhardness were investigated for pressureless sintered HA/TiO2 composites, and pure HA was investigated for comparison. Results show that TiO2 from both in-situ hydrolysis and mixing commercial powder presented similar effects on phase structures and composition, and trended to chemically react with HA in the HA/TiO2 composites at high sintering temperature. Weight loss for different composites was investigated by thermal analysis. Sintering behavior for two different composite was also discussed. The TiO2 from in-situ hydrolysis can effectively enhance the TiO2 distribution and densification for the N-HA/TiO2 composites. Both two different composites showed typical grain growth and pore formation with the increase of sintering temperature. The N-HA/TiO2 composite had a lower porosity, higher shrinkage and microhardness than that of C-HA/TiO2 composite at sintering temperature from 700 °C to 1100 °C.

16.
Science ; 366(6470)2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31672916

RESUMO

Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.


Assuntos
Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Evolução Molecular Direcionada/métodos , Anticorpos Anti-HIV/imunologia , Imunogenicidade da Vacina , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Transferência Adotiva , Sequência de Aminoácidos , Animais , Linfócitos B/imunologia , Anticorpos Amplamente Neutralizantes/química , Regiões Determinantes de Complementaridade/imunologia , Modelos Animais de Doenças , Células HEK293 , Anticorpos Anti-HIV/química , Humanos , Camundongos , Camundongos Knockout , Células Precursoras de Linfócitos B/imunologia
17.
Angew Chem Int Ed Engl ; 58(35): 12054-12058, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31197935

RESUMO

Harvesting water from air is a promising strategy for fresh-water production, and it is particularly desirable for areas that lack direct access to clean water. While high-concentration liquid sorbent is well-known for high sorption, it has not been widely used for atmospheric water collection, being primarily limited by the difficulty in desorption. Interfacial solar heating based on a salt-resistant GO-based aerogel is now shown to enable a high-concentration liquid sorbent (CaCl2 50 wt % solution) based atmospheric water generator. Fresh water (2.89 kg m-2 day-1 ) can be produced at about 70 % relative humidity, with only solar energy input and energy efficiency of desorption as high as 66.9 %. This low-cost and effective approach provides an attractive pathway to extract water from air, to relieve the thirst of arid, land-locked, and other areas where fresh water is scarce.

18.
Sci Rep ; 9(1): 8256, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164667

RESUMO

Mid-infrared (MIR) and near-infrared (NIR) spectroscopy combined with chemometrics were explored to classify Cabernet Sauvignon wines from different countries (Australia, Chile and China). Commercial wines (n = 540) were scanned in transmission mode using MIR and NIR, and their characteristic fingerprint bands were extracted at 1750-1000 cm-1 and 4555-4353 cm-1. Through the identification system of Tri-step infrared spectroscopy, the correlation between macroscopic chemical fingerprints and geographical regions was explored more deeply. Furthermore, Principal component analysis (PCA), soft independent modelling of class analogy (SIMCA) and discriminant analysis (DA) based on MIR and NIR spectra were used to visualize or discriminate differences between samples and to realize geographical origin traceability of Cabernet Sauvignon wines. Through "external test set (n = 157)" validation, SIMCA models correctly classified 97%, 97% and 92% of Australian, Chilean and Chinese Cabernet Sauvignon wines, while the DA models correctly classified 86%, 85% and 77%, respectively. Based on unique digital fingerprints of spectroscopy (FT-MIR and FT-NIR) associated with chemometrics, geographical origin traceability was achieved in a more comprehensive, effective and rapid manner. The developed database models based on IR fingerprint spectroscopy with chemometrics could provide scientific basis and reference for geographical origin traceability of Cabernet Sauvignon wines (Australia, Chile and China).

19.
Environ Sci Pollut Res Int ; 26(16): 16085-16096, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968293

RESUMO

A reliable system simulation of the reciprocal mechanism between water resource utilization and dualistic water cycle is essential to the basin water resource sustainability management. In this study, a system dynamic model was built to simulate the water cycle change and lake water environmental pressure under the influence of water resources utilization, and the procedure of a progressive operational scenario analysis of how to relieve water environment pressure was illustrated. Dianchi Lake, which is the sixth largest and the most severely polluted freshwater lake in China, was employed as a case study to demonstrate the applicability of the model. The change of runoff components and pollution load of total nitrogen from 2000 to 2030 were discussed. Also, the sustainable water resource management was ultimately realized in the planning period through three progressive levels of water resource regulation scenarios. Compared with business-as-usual scenario, the TN pollution load into lake and total water demand decrease by 27.1 and 27.3%, and the domestic water use, industry water use, tertiary industry water use, and irrigation decrease 9.0, 16.8, 29.5, and 30% in the scenario 3.


Assuntos
Conservação dos Recursos Hídricos/métodos , Modelos Teóricos , Ciclo Hidrológico , China , Lagos , Nitrogênio/análise , Desenvolvimento Sustentável , Poluição Química da Água/análise , Poluição Química da Água/prevenção & controle , Recursos Hídricos
20.
Langmuir ; 35(2): 428-434, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30540194

RESUMO

Asphaltenes in crude oil play a pivotal role in reservoir oil production because they control rock-surface wettability. Upon crude oil invasion into a brine-filled reservoir trap, rock adherence of sticky asphaltene agglomerates formed at the crude oil/brine interface can change the initially water-wet porous medium into mixed-oil wetting. If thick, stable water films coat the rock surfaces, however, asphaltenic-oil adhesion is thought to be prevented. We investigate whether water films influence the uptake of asphaltenes in crude oil onto silica surfaces. Water films of known thickness are formed at a silica surface in a quartz crystal microbalance with dissipation and contacted by toluene-solubilized asphaltene. We confirm that thick water films prevent asphaltene molecular contact with the silica surface blocking asphaltene adhesion. The thicker the water film, the smaller is the amount of asphaltene deposited. Film thickness necessary for complete blockage onto silica is greater than about 500 nm, well beyond the range of molecular-chain contact. Water films of thickness less than 500 nm, sandwiched between toluene and solid silica, apparently rupture into thick water pockets and interposed molecularly thin water layers that permit asphaltene adherence.

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