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1.
J Agric Food Chem ; 72(15): 8742-8748, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564658

RESUMO

Tyrosinase is capable of oxidizing tyrosine residues in proteins, leading to intermolecular protein cross-linking, which could modify the protein network of food and improve the texture of food. To obtain the recombinant tyrosinase with microbial cell factory instead of isolation tyrosinase from the mushroom Agaricus bisporus, a TYR expression cassette was constructed in this study. The expression cassette was electroporated into Trichoderma reesei Rut-C30 and integrated into its genome, resulting in a recombinant strain C30-TYR. After induction with microcrystalline cellulose for 7 days, recombinant tyrosinase could be successfully expressed and secreted by C30-TYR, corresponding to approximately 2.16 g/L tyrosinase in shake-flask cultures. The recombinant TYR was purified by ammonium sulfate precipitation and gel filtration, and the biological activity of purified TYR was 45.6 U/mL. The purified TYR could catalyze the cross-linking of glycinin, and the emulsion stability index of TYR-treated glycinin emulsion was increased by 30.6% compared with the untreated one. The cross-linking of soy glycinin by TYR resulted in altered properties of oil-in-water emulsions compared to emulsions stabilized by native glycinin. Therefore, cross-linking with this recombinant tyrosinase is a feasible approach to improve the properties of protein-stabilized emulsions and gels.


Assuntos
Reagentes de Ligações Cruzadas , Expressão Gênica , Globulinas , Hypocreales , Monofenol Mono-Oxigenase , Proteínas Recombinantes , Proteínas de Soja , Monofenol Mono-Oxigenase/biossíntese , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/isolamento & purificação , Monofenol Mono-Oxigenase/metabolismo , Reagentes de Ligações Cruzadas/isolamento & purificação , Reagentes de Ligações Cruzadas/metabolismo , Hypocreales/classificação , Hypocreales/genética , Hypocreales/crescimento & desenvolvimento , Hypocreales/metabolismo , Globulinas/química , Globulinas/metabolismo , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Eletroporação , Celulose , Sulfato de Amônio , Cromatografia em Gel , Precipitação Fracionada , Emulsões/química , Emulsões/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Estabilidade Proteica , Retículo Endoplasmático/metabolismo , Sinais Direcionadores de Proteínas , Óleos/química , Água/química
2.
PLoS One ; 19(3): e0300123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547159

RESUMO

The Chinese government aspires for inclusive education to serve as an exemplary model in addressing educational inequity issues and establishing a responsible global image as a major power. Nevertheless, there has been limited focus on China's news media coverage concerning its inclusive education initiatives aimed at international audiences. To bridge this gap, this study employed a corpus-assisted critical discourse analytic approach to examine China's self-image in relation to its inclusive education endeavours. Seventy-three English-language news articles from the official channel were retrieved for meticulous line-by-line concordance analysis. The results indicate that out of the 520 co-occurring instances, they can be broadly categorised into four groups: efforts to develop inclusive education (65.4%); consensus on benefits of inclusive education (24.5%); challenges faced by inclusive education (4.8%); and others (5.4%). This study illuminates the effective utilisation of official media in the image construction of inclusive education in China.


Assuntos
Comunicação , Idioma , China , Problemas Sociais , Meios de Comunicação de Massa
3.
NPJ Vaccines ; 9(1): 22, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310094

RESUMO

Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB.

4.
Hematol Oncol ; 42(1): e3224, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37712442

RESUMO

Myelodysplastic syndromes (MDS) patients often experience CD8+ T lymphocytes exhaustion, which plays a crucial role in the development of MDS. However, the specific role of thymocyte selection-associated high mobility box protein (TOX) in the CD8+ T lymphocytes exhaustion in MDS patients remains unclear. In this study, we investigated the role of TOX in CD8+ T lymphocytes exhaustion in patients with MDS. The expression of TOX, inhibitory receptors (IRs), and functional molecules in peripheral blood T lymphocytes of MDS patients and normal controls were detected using flow cytometry. Lentiviral transduction was used to create stable TOX-knockdown CD8+ T lymphocytes, and small interfering RNA (si-RNA) was used to knock down TOX in Jurkat cells. The expression of TOX was found to be significantly higher in CD8+ T lymphocytes of MDS patients compared to normal controls. This was associated with upregulated IRs and reduced expression of functional molecules such as Granzyme and Perforin. Myelodysplastic syndromes patients with higher TOX expression had poor clinical indicators and shorter survival. Knockdown of TOX using sh-RNA partially reverses the exhausted phenotype and enhances the lethality of CD8+ T lymphocytes. Moreover, the knockdown of TOX using si-RNA in Jurkat cells improved cell proliferation activity, down-regulated IRs and activated PI3K/AKT/mTOR signaling pathway. TOX promotes the exhaustion of CD8+ T lymphocytes by inhibiting PI3K/AKT/mTOR pathway, and targeted inhibition of TOX could partially restore the effector functions and activity of CD8+ T lymphocytes.


Assuntos
Síndromes Mielodisplásicas , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Timócitos/metabolismo , Serina-Treonina Quinases TOR , RNA/metabolismo
5.
Inorg Chem ; 63(1): 613-620, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38102774

RESUMO

The self-assembly of the lanthanide metal-organic frameworks presents a formidable challenge but profound significance. Compared with the metal-organic frameworks based on 4f-3d ions, the chemistry of 4f-3p metal-organic frameworks has not been fully explored so far. In this study, two lanthanide-aluminum-based clusters [Ln6Al(IN)10(µ3-OH)5(µ3-O)3(H2O)8]·xH2O (x = 2, Ln = Gd, abbreviated as Gd6Al; x = 2.5, Ln = Eu, abbreviated as Eu6Al; HIN = isonicotinic acid) have been meticulously designed and obtained by hydrothermal reaction at low pH. The crystallographic study revealed that both Gd6Al and Eu6Al clusters exhibit an unprecedented sandwiched metal-organic framework holding a highly ordered honeycomb network. To our knowledge, it is the first case of Ln-Al-based cluster-organic frameworks. Furthermore, magnetic investigation of Gd6Al manifests a decent magnetic entropy change of -ΔSmmax = 28.8 J kg-1 K-1 at 2 K for ΔH = 7.0 T. Significantly, the introduction of AlIII ions into the lanthanide metal-organic frameworks displays excellent solid-state luminescent capability with a lifetime of 371.6 µs and quantum yield of 6.64%. The construction and investigation of these two Ln-Al clusters represent great progress in the 4f-3p metal-organic framework.

6.
Dalton Trans ; 53(3): 1058-1065, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38099604

RESUMO

It is a major challenge to perform one-pot hydroxylation of benzene to phenol under mild conditions, which replaces the environmentally harmful cumene method. Thus, finding highly efficient heterogeneous catalysts that can be recycled is extremely significant. Herein, a (POM)-based hybrid compound {[FeII(pyim)2(C2H5O)][FeII(pyim)2(H2O)][PMoV2MoVI9VIV3O42]}·H2O (pyim = 2-(2-pyridyl)benzimidazole) (Fe2-PMo11V3) was successfully prepared by hydrothermal synthesis using typical Keggin POMs, iron ions and pyim ligands. Single-crystal diffraction shows that the Fe-pyim unit in Fe2-PMo11V3 forms a stable double-supported skeleton by Fe-O bonding to the polyacid anion. Remarkably, due to the introduction of vanadium, Fe2-PMo11V3 forms a divanadium-capped conformation. Benzene oxidation experiments indicated that Fe2-PMo11V3 can catalyze the benzene hydroxylation reaction to phenol in a mixed solution of acetonitrile and acetic acid containing H2O2 at 60 °C, affording a phenol yield of about 16.2% and a selectivity of about 94%.

7.
PLoS One ; 18(11): e0292806, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37943744

RESUMO

Previous studies have examined WATER metaphors in different discourses, yet there has been limited focus on understanding the functions of these metaphors in constructing discourses. To address this research gap, the present paper utilised the metaphor identification procedure developed by the Pragglejaz Group and the Weak Differentiating Model to investigate WATER metaphors in the Coronavirus Corpus. The study reveals that WATER metaphors can be used flexibly for multiple purposes. These include explaining the many pandemic stages, describing the occurrence and performance of the pandemic, explaining how COVID-19 affects human life, rallying the public to take precautions against contagion, and communicating risk. This research highlights the diverse functions that WATER metaphors served in conveying intricate information and influencing public perceptions throughout the COVID-19 pandemic.


Assuntos
COVID-19 , Metáfora , Humanos , Pandemias
8.
Curr Microbiol ; 80(12): 367, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37819393

RESUMO

In recent years, pepper wilt has emerged as a pivotal constraint on pepper yield augmentation. Bacillus velezensis S3-1, with a wide array of hosts, can be used as both a biocontrol agent and biofertilizer. Nonetheless, the precise mechanisms underpinning its employment in combating pepper wilt remain cloaked in ambiguity. In our study, we found that B. velezensis S3-1 could significantly inhibit Fusarium sp. F1T that caused pepper wilt. S3-1 could effectively inhibit both the growth and germination of F1T conidia, leading to a reduction in the spore germination percentage from 83.2 to 37.1% in vitro experiments. Additionally, leaf detachment experiments revealed that the volatile compounds produced by S3-1 could inhibit the spread of pepper leaf spot area. Moreover, we observed a significant decrease in the content of malondialdehyde (MDA) in pepper treated with S3-1, along with a significant increase in the content of soluble protein, polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia-lyase (PAL) in pepper. Furthermore, RT-PCR analysis showed that the expression of the defense genes CaPR 1 and CaPIN II in pepper after treatment with S3-1 was significantly upregulated, suggesting that S3-1 had the potential to induce systemic resistance in pepper, thereby enhancing its disease resistance. Hence, our findings suggest that S3-1 can be a promising biocontrol agent for managing pepper wilt in modern agriculture.


Assuntos
Bacillus , Doenças das Plantas , Doenças das Plantas/prevenção & controle , Bacillus/metabolismo , Oxirredutases , Peroxidase/metabolismo
9.
PLoS One ; 18(10): e0292834, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37824546

RESUMO

Many studies have investigated language poverty related to aspects of economic assistance, water scarcity, gender inequality, climate change, etc. However, a focus on language policy discourse has been lacking. Language policy discourse is vital because it can be deemed as preliminary to language poverty alleviation action, influencing the success of its implementation. To fill this gap, this study employed positive discourse analysis to investigate discursive strategies used in the discourse of language poverty alleviation in Chinese language policies. The finding shows that through four main discursive strategies-nomination, argumentation, perspectivisation, and predication-official documents concerning language poverty alleviation constructed motivational discourse and applied campaign-style mobilisation to encourage people to follow the implementation of language poverty alleviation. This study sheds light on the official purpose of using certain discursive strategies in language poverty alleviation discourse and some ideological implications behind it and sets an example of the popularisation of official languages to tackle poverty alleviation from a linguistic perspective for other countries/regions.


Assuntos
Idioma , Pobreza , Humanos , China , Políticas , Linguística
10.
Foods ; 12(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37685203

RESUMO

Packaged foods have significantly expanded their market presence, with the utilization of vice-virtue bundles gaining momentum, particularly in the realm of vice-packaged foods. Consequently, understanding how consumers respond to vice-packaged food with vice-virtue bundles (i.e., vice-packaged food combined with virtue ingredients) becomes crucial. This research investigates this issue through four experiments employing a one-way between-subjects design, incorporating distinct stimuli and measures, and involving samples from diverse sources. In Experiment 1 (n = 172), Experiment 2 (n = 169), and the follow-up experiment (n = 153), variance analysis, chi-square test, and mediating analysis demonstrate that consumers are more inclined to purchase vice-packaged food with vice-virtue bundles owing to the perception of it being healthier than vice packaged food with vice-virtue bundles. Furthermore, Experiment 3 (n = 249) employs moderated mediation analysis, uncovering that both the heightened purchase intention for vice-packaged food with vice-virtue bundles and the mediating effect of perceived healthiness are attenuated among consumers with prevention (vs. promotion) focus. Beyond contributing to theories on packaged food consumption, vice-virtue bundles, and regulatory focus theory, these findings hold practical implications for packaged food marketing, promoting rational food choices, and enhancing healthier diets.

11.
Molecules ; 28(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37513345

RESUMO

A mild, visible-light-induced, regioselective cascade sulfonylation-cyclization of 1,5-dienes with sulfonyl chlorides through the intermolecular radical addition/cyclization of alkenes C(sp2)-H was developed. This procedure proceeds well and affords a mild and efficient route to a range of monosulfonylated pyrrolin-2-ones at room temperatures.

12.
Dalton Trans ; 52(31): 10969-10974, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37491914

RESUMO

The anionic template method is an effective strategy for synthesizing high-nuclearity transition-lanthanide (3d-4f) heterometallic clusters. Herein, two lanthanide clusters with formulas [Gd20Ni21(µ3-OH)21(CO3)6(IDA)21(C2H4NO2)6(C2O4)3(MoO4)1.5(µ2-OH)1.5(H2O)9]Cl10.5·79H2O (1) and [Tb20Ni21(µ3-OH)21(CO3)6(IDA)21(C2H4NO2)6(C2O4)3(MoO4)(µ2-OH)2(H2O)10]Cl11·32H2O (2) were synthesized by introducing MoO42- anions as templates. Structural analysis indicates that compounds 1 and 2 are isomorphic, featuring a fascinating triangular-shaped metal framework. Magnetic property investigations illuminate the fact that compound 1 exhibits a large -ΔSm of 37.83 J kg-1 K-1 at 3 K for ΔH = 7 T. In particular, it is worth mentioning that compound 1 has an excellent low-field magnetic entropy (-ΔSm = 23.85 J kg-1 K-1 at 2 K, 2 T).

13.
Nat Commun ; 14(1): 4048, 2023 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422472

RESUMO

Hypophosphatasia (HPP) is a metabolic bone disease that manifests as developmental abnormalities in bone and dental tissues. HPP patients exhibit hypo-mineralization and osteopenia due to the deficiency or malfunction of tissue non-specific alkaline phosphatase (TNAP), which catalyzes the hydrolysis of phosphate-containing molecules outside the cells, promoting the deposition of hydroxyapatite in the extracellular matrix. Despite the identification of hundreds of pathogenic TNAP mutations, the detailed molecular pathology of HPP remains unclear. Here, to address this issue, we determine the crystal structures of human TNAP at near-atomic resolution and map the major pathogenic mutations onto the structure. Our study reveals an unexpected octameric architecture for TNAP, which is generated by the tetramerization of dimeric TNAPs, potentially stabilizing the TNAPs in the extracellular environments. Moreover, we use cryo-electron microscopy to demonstrate that the TNAP agonist antibody (JTALP001) forms a stable complex with TNAP by binding to the octameric interface. The administration of JTALP001 enhances osteoblast mineralization and promoted recombinant TNAP-rescued mineralization in TNAP knockout osteoblasts. Our findings elucidate the structural pathology of HPP and highlight the therapeutic potential of the TNAP agonist antibody for osteoblast-associated bone disorders.


Assuntos
Fosfatase Alcalina , Hipofosfatasia , Humanos , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Hipofosfatasia/genética , Hipofosfatasia/metabolismo , Hipofosfatasia/patologia , Microscopia Crioeletrônica , Osso e Ossos/metabolismo , Osteoblastos/metabolismo
14.
Medicine (Baltimore) ; 102(22): e33832, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37266652

RESUMO

BACKGROUND: To evaluate the effect of different surgical methods in the treatment of patients with irreparable rotator cuff tears (IRCTs) using a network meta-analysis. METHODS: A search of the PubMed, EMbase, The Cochrane Library, VIP, WanFang Data, and CNKI databases was performed in January 2023 to search for randomized controlled trials and cohort studies of different surgical methods in the treatment of IRCTs. Risk assessment of the included randomized controlled trials was conducted using the risk of bias assessment tool recommended by the Cochrane Manual, and the Newcastle-Ottawa Scale was used for the risk assessment of cohort studies. Data were analyzed and plotted using Stata 15.0 software. RESULTS: A total of 17 studies involving 2123 patients and 10 surgical methods were included in this study. According to the surface under the cumulative ranking curve, the probability ranking in descending order is latissimus dorsi transfer (LDT) + partial repair > LDT > reverse total shoulder arthroplasty > superior capsular reconstruction > patch > partial repair > debridement + tenotomy of the long head of the biceps > debridement > in space subacromial balloon spacer + tenotomy of the long head of the biceps > in space subacromial balloon spacer. CONCLUSION: Among the multiple surgical treatments for patients with IRCTs, LDT + partial repair may have the best effect, and more randomized controlled trials with larger sample sizes are needed for further verification.


Assuntos
Artroplastia do Ombro , Lesões do Manguito Rotador , Humanos , Lesões do Manguito Rotador/cirurgia , Metanálise em Rede , Artroplastia , Artroplastia do Ombro/métodos , Tenotomia , Resultado do Tratamento , Artroscopia/métodos
15.
Dalton Trans ; 52(27): 9465-9471, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37366139

RESUMO

Two polyoxometalate (POM)-based hybrid compounds have been successfully designed and constructed by the hydrothermal method with molecular formulas [K(H2O)2FeII0.33Co0.67(H2O)2(DAPSC)]2{[FeII0.33Co0.67(H2O)(DAPSC)]2[FeII0.33Co0.67(H2O)4]2[Na2FeIII4P4W32O120]}·21.5H2O (1), and [Na(H2O)2FeII0.33Mn0.67(H2O)2(DAPSC)]2{[FeII0.33Mn0.67(H2O)(DAPSC)]2[FeII0.33Mn0.67(H2O)4]2[Na2FeIII4P4W32O120(H2O)2]}·24H2O (2) (DAPSC = 2,6-diacetylpyridine bis-(semicarbazone)), respectively. Structural analysis revealed that 1 and 2 consisted of metal-organic complexes containing DAPSC ligands with dumbbell-type inorganic clusters, iron-cobalt (iron-manganese) and some other ions. By utilizing a combination of strongly reducing {P2W12} units and bimetal-doped centres the CO2 photoreduction catalytic capacity of 1 and 2 was improved. Notably, the photocatalytic performance of 1 was much better than that of 2. In CO2 photoreduction, 1 exhibited CO selectivity as high as 90.8%. Furthermore, for 1, the CO generation rate reached 6885.1 µmol g-1 h-1 at 8 h with 3 mg, and its better photocatalytic performance was presumably due to the introduction of cobalt and iron elements to give 1 a more appropriate energy band structure. Further recycling experiments indicated that 1 was a highly efficient CO2 photoreduction catalyst, which could still possess catalytic activity after several cycles.

16.
Sci Prog ; 106(2): 368504231172635, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143332

RESUMO

Local corrosion flaws (LCFs) widely exist in large diameter pipelines (LDPs) (e.g. steam, oil/gas pipeline) due to flow-accelerated corrosion, environmental corrosion, and material aging. Frequency-band-selecting eddy current testing (FBS-ECT), as an improved eddy current technique (ECT), has rich harmonic components in exciting signals as a pulsed eddy current technique (PECT), as well as more effective utilization of electromagnetic energy by selecting a frequency band. It is expected that FBS-ECT has promising applications in detecting and evaluating the LCFs in LDP. Therefore, a solution to the magnetic field of FBS-ECT for LCF detection in LDP is of great concern to reveal the features of the FBS-ECT signal and the parameters of the LCF. Extending our previous work, the semi-analytic expression of the magnetic flux density for FBS-ECT in regions 1 and 2 (where the magnetic sensor is located) is deduced according to the superposition principle and TREE, the computation accuracy is validated by numerical simulation; next, a semi-analytic solution to the magnetic field of FBS-ECT for LCF in LDP is proposed; then, the sampling distance in FBS-ECT is optimized by considering the magnitude of △Bz and the sensitivity of △Bz with the LCF depth; finally, a case study is carried out to verify the optimal strategy and find the mapping relationship between the radius/depth and the FBS-ECT signal. The proposed semi-analytic solution for the magnetic field of FBS-ECT is not only helpful to understand the theoretical relationship of the magnetic field and LCFs with higher computation efficiency but also lays a theoretical foundation to promote FBS-ECT to apply in the characterization of other flaws in metal components.

17.
Inorg Chem ; 62(7): 3162-3169, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36734987

RESUMO

The self-assembly of the high-nuclearity Ln-exclusive nanoclusters is challenging but of significance due to its aesthetically pleasing architectures and far-reaching latent applications in magnetic cooling technologies. Herein, two novel high-nuclearity lanthanide nanoclusters were successfully synthesized under solvothermal conditions, formulated as {[Gd18(IN)20(HCOO)8(µ6-O)(µ3-OH)24(H2O)4]·4H2O}n and {[Eu18(IN)16(HCOO)8(CH3COO)4(µ6-O)(µ3-OH)24(H2O)4]·5H2O}n (abbreviated as Gd18 and Eu18, HIN = isonicotinic acid). Both of them possess novel and exquisite windmill-shaped cationic cores in the family of high-nuclearity Ln-exclusive nanoclusters. Remarkably, the adjacent second building units are interconnected into a three-dimensional (3D) metal-organic framework by IN- ligands. As expected, the abundant existence of GdIII ions endows Gd18 with a favorable magnetic entropy change at 2.0 K for ΔH = 7.0 T (-ΔSmmax = 40.0 J kg-1 K-1), and Eu18 displays the typical luminescence of EuIII ions.

18.
J Fluoresc ; 33(4): 1413-1419, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36719610

RESUMO

As one of the most toxic metals, Mercury ions cause serious environmental pollution and threaten the health of living organisms. Hence, we designed and synthesised a new near-infrared (NIR) ratiometric fluorescent probe toward monitoring of Hg2+ based on quinoline-fused rhodamine dye. Owing to the specific spirolactam ring-opening reaction, the probe exhibits a ratiometric fluorescent change after treatment of Hg2+ with increased emission in NIR and significantly reduced emission in visible region. The specific response mechanism and dual-channel fluorescence change allow the probe to have remarkable detection selectivity, fast response and high detection sensitivity. Moreover, with the properties of excellent cell permeability and low cytotoxicity, probe can be applied as detection tool for mercury ions with dual-channel ratiometric fluorescence imaging in living cell.


Assuntos
Corantes Fluorescentes , Mercúrio , Rodaminas , Microscopia de Fluorescência , Íons
19.
Cell Mol Immunol ; 19(12): 1347-1360, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36369367

RESUMO

Chronic hepatitis B (CHB) infection remains a serious public health problem worldwide; however, the relationship between cholesterol levels and CHB remains unclear. We isolated peripheral blood mononuclear cells from healthy blood donors and CHB patients to analyze free cholesterol levels, lipid raft formation, and cholesterol metabolism-related pathways. Hepatitis B virus (HBV)-carrier mice were generated and used to confirm changes in cholesterol metabolism and cell-surface lipid raft formation in dendritic cells (DCs) in the context of CHB. Additionally, HBV-carrier mice were immunized with a recombinant HBV vaccine (rHBVvac) combined with lipophilic statins and evaluated for vaccine efficacy against HBV. Serum samples were analyzed for HBsAg, anti-HBs, and alanine aminotransferase levels, and liver samples were evaluated for HBV DNA and RNA and HBcAg. CHB reduced free cholesterol levels and suppressed lipid raft formation on DCs in patients with CHB and HBV-carrier mice, whereas administration of lipophilic statins promoted free cholesterol accumulation and restored lipid rafts on DCs accompanied by an enhanced antigen-presentation ability in vitro and in vivo. Cholesterol accumulation on DCs improved the rHBVvac-mediated elimination of serum HBV DNA and intrahepatic HBV DNA, HBV RNA, and HBcAg and promoted the rHBVvac-mediated generation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells, induction of the development of memory responses against HBV reinfection, and seroconversion from HBsAg to anti-HBs. The results demonstrated the important role of cholesterol levels in DC dysfunction during CHB, suggesting that strategies to increase cholesterol accumulation on DCs might enhance therapeutic vaccine efficacy against HBV and support development toward clinical CHB treatment.


Assuntos
Hepatite B Crônica , Hepatite B , Inibidores de Hidroximetilglutaril-CoA Redutases , Vacinas , Camundongos , Animais , Antígenos de Superfície da Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B/uso terapêutico , DNA Viral , Leucócitos Mononucleares , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vírus da Hepatite B , Anticorpos Anti-Hepatite B , Células Dendríticas , Colesterol/uso terapêutico , RNA
20.
Micromachines (Basel) ; 13(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36144023

RESUMO

Global navigation satellite system (GNSS) and inertial navigation system (INS) are indispensable for ground vehicle position and navigation. The Kalman filter (KF) is the first choice to integrate them and output more reliable navigation solutions. However, the GNSS signal is denied in urban areas, i.e., tunnels, and the INS position errors diverge quickly over time. Under normal conditions, the ground vehicle will not slide or jump off the ground; nonholonomic constraints (NHC) and odometers are available to aid the INS and reduce its position errors. Factor graph optimization (FGO) recently attracted attention as an advanced sensor fusion algorithm. This paper implemented the FGO method based on GNSS/INS/NHC/Odometer integration. In the FGO, state transformation, measurement model, the NHC, and the odometer were all regarded as constraints employed to construct a graph; an iterative process was utilized to find the optimal estimation results. Two experiments were carried out: firstly, the FGO-GNSS/INS performance was assessed and compared with the KF-GNSS/INS; secondly, we compared the FGO-GNSS/INS/NHC/Odometer and KF-GNSS/INS/NHC/Odometer under GNSS denied environments. Experimental results supported that the FGO improved the performance.

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