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1.
Pharmaceutics ; 15(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36678807

RESUMO

Gene therapy, as an emerging therapeutic approach, has shown remarkable advantages in the treatment of some major diseases. With the deepening of genomics research, people have gradually realized that the emergence and development of many diseases are related to genetic abnormalities. Therefore, nucleic acid drugs are gradually becoming a new boon in the treatment of diseases (especially tumors and genetic diseases). It is conservatively estimated that the global market of nucleic acid drugs will exceed $20 billion by 2025. They are simple in design, mature in synthesis, and have good biocompatibility. However, the shortcomings of nucleic acid, such as poor stability, low bioavailability, and poor targeting, greatly limit the clinical application of nucleic acid. Liposome nanoparticles can wrap nucleic acid drugs in internal cavities, increase the stability of nucleic acid and prolong blood circulation time, thus improving the transfection efficiency. This review focuses on the recent advances and potential applications of liposome nanoparticles modified with nucleic acid drugs (DNA, RNA, and ASO) and different chemical molecules (peptides, polymers, dendrimers, fluorescent molecules, magnetic nanoparticles, and receptor targeting molecules). The ability of liposome nanoparticles to deliver nucleic acid drugs is also discussed in detail. We hope that this review will help researchers design safer and more efficient liposome nanoparticles, and accelerate the application of nucleic acid drugs in gene therapy.

2.
Signal Transduct Target Ther ; 8(1): 20, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596779

RESUMO

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.


Assuntos
COVID-19 , Vacinas , Adulto , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle
3.
Chemistry ; 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639941

RESUMO

Dual-state emission luminogens (DSEgens) are receiving research interest in the construction of multifunctional materials due to their inherent advantage of high emission efficiency in both the molecularly dispersed solution state and the solid state. However, it remains challenging in synthesizing DSEgens via a delicate manipulation of the molecular structures. This work presents an example of synthesizing bright DSEgens by tuning the molecular electronic structures and conformations. Three coumarin-tetraphenylethylene (TPE) molecules with a donor-acceptor electronic structure and highly twisting conformations have been synthesized. While compound resulting from direct conjugation of coumarin with a TPE unit shows aggregation-induced emission, compound with an N,N-diaminoethyl modification on the 7-position of coumarin and compound with a further phenyl linker between coumarin and TPE units feature strong dual-state emission. Benefiting from their strong solid emission and twisting conformation, these fluorophores display reversible mechanofluorochromism. Finally, applications for rewritable information storage in the solid state and live-cell imaging in the solution state were demonstrated.

4.
Ann Hematol ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633638

RESUMO

Renal impairment (RI) used to exclude multiple myeloma (MM) patients from autologous stem cell transplantation (ASCT) for safety concerns. Here, we retrospectively reviewed 34 consecutively transplanted patients with creatinine clearance < 60 ml/min at ASCT in recent 5 years at our institution. Busulfan/cyclophosphamide and high-dose melphalan were both employed as conditioning regimens. We found 62% grade 1-2 oral mucositis, 12% grade 3 oral mucositis, 48% grade 3 infection, 8% grade ≥ 4 infection, 50% grade 1 transient creatinine increase, 15% cardiac adverse events, and 12% engraftment syndrome. One case of secondary platelet graft failure and 1 case of transplantation-related mortality were observed. Interleukin-6 concentration was elevated among patients with increased body temperature and/or N-terminal pro-brain natriuretic peptide during engraftment, and close monitoring of these markers may help to predict susceptibility to cardiac events and engraftment syndrome. Adverse events occurred frequently, but the majority were manageable in this cohort. ASCT would further deepen the anti-myeloma efficacy and slightly ameliorated renal function. With a median follow-up of 26.2 months post transplantation (range: 1.6-74.8 months), the median progression-free survival (PFS) and overall survival (OS) post-transplantation of patients undergoing first-line transplantation were not reached; the median PFS post-transplantation of patients undergoing rescue transplantation was 19.2 months and the median OS was not reached.

5.
J Environ Manage ; 331: 117246, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36642048

RESUMO

Bioaugmentation (BA) and biostimulation (BS) synergistic remediation is an effective remediation strategy for oil-contaminated soil. In this study, the optimal combination system of composite microbial agent TY (Achromobacter: Pseudomona = 2:1) and dehydrocoenzyme activator (NaNO3 (7.0 g/L), (NH4)2HPO4 (1.0 g/L), riboflavin (6.0 mg/L)) was screened. Under the best combination system, the degradation rate of crude oil in oil-contaminated soil reached 79.44% after 60 d, which was 1.74 times and 1.23 times higher than that of compound microbial agent TY treatment and dehydrogenase activator treatment, respectively. In addition, a highly efficient combination system was found to target the degradation of oil C10-C28 fractions by gas chromatography (GC). The increased abundance of dehydrogenase coenzymes such as flavin nucleotides (FAD and FMN), coenzyme I (NAD+, Co I) and coenzyme II (NADP+, Co II) as well as dioxygenases and monooxygenases promote the degradation of crude oil. Furthermore, the dominant genera at the genus level in soil were analyzed by high-throughput sequencing, which were Nocardioides (46.48%-56.07%), Gordonia (11.40%-14.61%), Intrasporangiaceae (5.05%-10.58%), Pseudomonas (1.39%-1.92%) and Dietzia (0.64%-2.77%). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis showed that the abundance of genes associated with crude oil degradation such as ABC transporters (2.89%), fatty acid (1.04%), carbon metabolism (4.5%) and aromatic compound (0.92%) was assigned enhanced after 60 d of remediation. These results indicated that the combination system of the compound bacterium TY and the dehydrocoenzyme activator is a propective option for the bioremediation of oil-contaminated soil.

6.
Compr Psychiatry ; 122: 152370, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36709559

RESUMO

INTRODUCTION: Numerous studies have found an association between autoimmune diseases of the nervous system (ADNS) and schizophrenia (SCZ), but the findings remain controversial. We conducted the first meta-analysis to summarize the current evidence from cohort studies that evaluated the association between ADNS and SCZ. METHODS: PubMed, Web of Science, and Embase were comprehensively searched until May 30, 2022 for articles on the association between ADNS and SCZ. Every included study was reported effect size with 95% CIs for the association between ADNS and SCZ. Meta-regression and subgroup analysis were used to assess the heterogeneity. RESULTS: A total of 8 cohort studies with 12 cohorts were included in the meta-analysis. We observed a significant association between ADNS and SCZ (RR = 1.42; 95%CI, 1.18-1.72). Subgroup analysis showed that the risk of SCZ was significantly increased when ADNS were used as exposure factors (RR = 1.48; 95%CI, 1.15-1.89), whereas with SCZ did not observe an increased risk of subsequent ADNS (RR = 1.33; 95%CI, 0.92-1.92); multiple sclerosis (MS) was positively associated with SCZ (RR = 1.36; 95%CI, 1.12-1.66), but no significant association was found between Guillain-Barre syndrome (GBS) and SCZ (RR = 1.90; 95%CI, 0.87-4.17). Meanwhile, we found location was the source of heterogeneity. LIMITATIONS: High heterogeneity was observed (I2 = 92.0%), and only English literature was included in the meta-analysis. CONCLUSIONS: We found a positive association between ADNS and SCZ, and the association was different across the different types of ADNS. The results of the study are helpful for clinicians to carry out targeted preventive measures for ADNS and SCZ.

7.
Pestic Biochem Physiol ; 189: 105306, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36549813

RESUMO

The immunity of insects plays a vital role in their survival. Our experiments found that lipopolysaccharide (LPS) and glucono-δ-lactone (GDL) could influence the virulence of Serratia marcescens Bizio (SM1) to Odontotermes formosanus (Shiraki) by affecting the immunity. Gram-negative binding proteins (GNBPs) are an important pattern recognition proteins that play a crucial role in the innate immune system. Therefore, two OfGNBPs were cloned in O. formosanus. The expression of OfGNBPs was significantly changed by LPS,SM1 and GDL, not prick. In addition, the immune-related gene expression, the phenoloxidase activity and antibacterial activity of donor termites and recipient termites were significantly induced by SM1. Furthermore, the knockdown of OfGNBP by RNA interference reduced not only individual immunity but also social immunity in O. formosanus, which increased the virulence of SM1 to O. formosanus. Importantly, dsOfGNBP alone also had good control effect on O. formosanus. In summary, we concluded that dsOfGNBPs are important termite immunosuppressants.


Assuntos
Isópteros , Animais , Isópteros/genética , Isópteros/microbiologia , Serratia marcescens/genética , Lipopolissacarídeos/farmacologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-36472734

RESUMO

Little evidence about the effects of cold spells on serum lipid levels is available. The aim of this study was to explore the association between cold spells and serum lipid levels among the elders in Jinan, China. Data of old adults from health check-up program in Shandong Provincial Qianfoshan Hospital was collected for this study. Linear mixed models combined with distributed lag nonlinear models were used to examine the relationship between cold spells and serum lipid levels, considering the confounding effects of age, sex, blood pressure, body mass index, and other meteorological factors. Subgroup analysis by gender and analysis based on different definitions of cold spells were also conducted. Increased TG levels in lag 0-lag 2 days and decreased TG levels in lag 5-lag 8 days after cold spells were observed among the elders. The largest increase was 0.363 mmol/L (95% CI: 0.184 ~ 0.543) in lag 0 day, while the largest decreased TG levels was 0.083 mmol/L (95% CI: 0.147 ~ 0.019) in lag 6 day. Similar results were obtained in the analysis of different sex and based on different definitions of cold spells. However, no significant association was found between cold spells with TC, LDL-C, and HDL-C. This study indicates that cold spells were significantly associated with serum TG levels in the elders. Effective preventive measures should be implemented around the cold spells to reduce the volatility of serum lipid levels and the occurrence of subsequent cardiovascular diseases.

9.
Food Res Int ; 162(Pt A): 111998, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461301

RESUMO

Soybean and derived products are among the most important food for both humans and animals. China is the world's largest importer of soybeans, with more than 100 million tons of annual imports, mainly from the United States of America (US), Brazil, and Argentina. However, there have been limited studies on the microbiota associated with imported soybean grains. Here, we reveal the soybean microbiota using amplicon sequencing based on samples from four countries on three continents of North America (US), South America (Argentina, Brazil), and Asia (China). Our results showed that the soybean-associated microbiota from different continents significantly separated, presenting strong geographic variations. The core microbial taxa and geographically specified taxa were defined, with Alternaria, Enterobacter, Plectosphaerella, Stenotrophomanas, and Xeromyces defined as the core microbiota for soybean from Asia; Amanita, Aspergillus, Fusarium, Nigrospora, Herbiconiux, Pseudomonas, Saccharopolyspora, and Schumannella from North America; and Bradyrhizobium, Colletotrichum, Filobasidium, Phialosimplex, Mycosphaerella, Septoria, Sphingomonas, and Weissalla, from South America. In addition, we build the Random Forest (RF) model to predict the source of imported soybean grains. We could accurately predict the original countries of imported soybean grains within the RF prediction models, with accuracies greater than 95 %. We constructed a database of soybean-related quarantine pathogens using full-length sequences of fungal ITS region and bacterial 16S rDNA region. Two phytopathogenic fungi, Diaporthe caulivora and Cladosporium cucumerinum, listed in the Chinese quarantine catalog, were intercepted through metabarcoding sequencing. The former was further confirmed using an available national standard protocol of qPCR diagnosis. In summary, our NGS-based approach revealed the microbiota associated with soybeans. It could provide comprehensive information and valuable method on the trace the origin of soybean and detection of quarantine pathogens at Customs and departments of inspection and quarantine.


Assuntos
Fabaceae , Soja , Animais , Humanos , Quarentena , Estruturas Vegetais , Grão Comestível , Brasil
10.
Front Microbiol ; 13: 1049341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452923

RESUMO

Prophage sequences are present in most bacterial genomes and account for up to 20% of its host genome. Integration of temperate phages may have an impact on the expression of host genes, while some prophages could turn into the lytic cycle and affect bacterial host biological characteristics. We investigated the role of spontaneous induction prophages in avian pathogenic Escherichia coli (APEC), which is the causative agent of avian colibacillosis in poultry, and considered a potential zoonotic bacterium related to the fact it serves as an armory of extraintestinal pathogenic E. coli. We found that APEC strain DE458 had a high spontaneous induction rate in vivo and in vitro. The released phage particles, phi458, were isolated, purified, and sequenced, and the deletion mutant, DE458Δphi458, was constructed and characterized. Biofilm formation of DE458Δphi458 was strongly decreased compared to that of the wild-type strain (p < 0.01). In addition, while the addition of DNase (100 µg/ml) did not affect prophage release but could digest eDNA, it significantly reduced the biofilm production of DE458 biofilm to a level close to that of DE458Δphi458. Compared to DE458, the adhesion and invasion abilities of DE458Δphi458 increased by approximately 6-20 times (p < 0.05). The virulence of DE458Δphi458 was enhanced by approximately 10-fold in chickens based on a 50% lethal dose. Furthermore, avian infection assays showed that the bacterial loads of DE458Δphi458 in the lung and liver were increased by 16.5- and 10-fold (p < 0.05), respectively, compared with those of the WT strain. The qRT-PCR revealed that deletion of phi458 led to upregulation of type I fimbriate-related gene fimH and curli-related gene csgC by 3- and 2.8-fold, respectively (p < 0.01). Our study revealed that phi458 promoted biofilm formation by spontaneously inducing and decreasing virulence by repressing virulence genes.

11.
Front Plant Sci ; 13: 1081280, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36570947

RESUMO

The leaf type of a plant determines its photosynthetic efficiency and adaptation to the environment. The normal leaves of modern Ginkgo biloba, which is known as a "living fossil" in gymnosperm, evolved from needle-like to fan-shaped with obvious dichotomous venation. However, a newly discovered Ginkgo variety "SongZhen" have different leaf types on a tree, including needle-, trumpet-, strip-, and deeply split fan-shaped leaves. In order to explore the mechanism in forming these leaf types, the microscopy of different leaf types and transcriptome analysis of apical buds of branches with normal or abnormal leaves were performed. We found that the normal leaf was in an intact and unfolded fan shape, and the abnormal leaf was basically split into two parts from the petiole, and each exhibited different extent of variation. The needle-type leaves were the extreme, having no obvious palisade and spongy tissues, and the phloem cells were scattered and surrounded by xylem cells, while the trumpet-type leaves with normal vascular bundles curled inward to form a loop from the abaxial to adaxial side. The other type of leaves had the characteristics among needle-type, trumpet-type, or normal leaves. The transcriptome analysis and quantitative PCR showed that the genes related to abaxial domain were highly expressed, while the adaxial domain promoting genes were decreasingly expressed in abnormal-type leaf (ANL) buds and abnormal leaves, which might lead to the obvious abaxialized leaves of "SongZhen." In addition, the low expression of genes related to leaf boundary development in ANL buds indicated that single- or double-needle (trumpet) leaves might also be due to the leaf tissue fusion. This study provides an insight into the mechanism of the development of the abnormal leaves in "SongZhen" and lays a foundation for investigating the molecular mechanism of the leaf development in gymnosperms.

12.
Front Public Health ; 10: 1017727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505007

RESUMO

Objective: This study aimed to investigate multi-trajectories of systolic and diastolic hypertension and assess their association with the risk of coronary heart disease (CHD) in middle-aged and older Chinese adults. Methods: The study cohort comprised 4,102 individuals aged 40-75 years with records of at least four systolic blood pressure (SBP) and diastolic blood pressure (DBP). A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic and diastolic hypertension, followed by a logistic model to assess the independent associations between these trajectories and CHD risk. The multinomial logistic model was used to evaluate the impact of baseline covariates on trajectory groups. Results: Six distinct trajectories for systolic and diastolic hypertension were identified which represent distinct stages of hypertension and were characterized as low-stable, low-increasing, medium-decreasing, medium-increasing-decreasing, isolated systolic hypertension phase, and high-decreasing. Compared with the low-stable group, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 2.23 (1.34-3.70) for the medium-increasing-decreasing group and 1.87 (1.12-3.11) for the high-decreasing group after adjustment for baseline covariates. Compared with the low-increasing group, the ORs and 95% CIs were 1.88 (1.06-3.31) for the medium-increasing-decreasing group. Age, gender, drinking, body mass index (BMI), triglyceride (TG), and fasting plasma glucose (FPG) were independent predictors for trajectory groups 4 and 6. Conclusion: Novel, clinically defined multi-trajectories of systolic and diastolic hypertension were identified. Middle-aged and older adults with medium-increasing-decreasing or high-decreasing blood pressure trajectories are potentially critical periods for the development of CHD. Preventing adverse changes in hypertension status and reducing the high risk of CHD is necessary for people in distinct trajectory groups.


Assuntos
Doença das Coronárias , Hipertensão , Pessoa de Meia-Idade , Humanos , Idoso , Doença das Coronárias/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Modelos Logísticos , Triglicerídeos
13.
Adv Mater ; : e2209511, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576022

RESUMO

Sodium (Na) metal anode with high theoretical capacity and low-cost is promising to construct high-energy-density metal battery. However, the unsatisfactory interface between Na and liquid electrolyte induces tardily ion transfer kinetics and dendritic Na growth, especially at ultra-low temperature (-40 °C). Herein, an artificial heterogeneous interphase consisting of disodium selenide (Na2 Se) and metal vanadium (V) is produced on the surface of Na (Na@Na2 Se/V) via an in-situ spontaneous chemical reaction. Such interphase layer possesses high sodiophilicity, excellent ionic conductivity and high Young's modulus, which can promote Na ion adsorption and transport, realizing homogenous Na deposition without dendrites. The symmetric Na@Na2 Se/V cell exhibits outstanding cycling lifespan of over 1790 h (0.5 mA cm-2 /1 mAh cm-2 ) in carbonate-based electrolyte. More remarkably, ab initio molecular dynamics simulations reveal that the artificial Na2 Se/V hybrid interphase can accelerate the desolvation of solvated Na+ at -40 °C. The Na@Na2 Se/V electrode thus exhibits exceptional electrochemical performance in symmetric cell (over 1500 h at 0.5 mA cm-2 /0.5 mAh cm-2 ) and full cell (over 700 cycles at 0.5 C) at -40 °C. This work provides an avenue to design artificial heterogeneous interphase layer for superior high-energy-density metal batteries at ambient and ultra-low temperatures. This article is protected by copyright. All rights reserved.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36538219

RESUMO

The groundwater polluted by an agricultural hormone site was taken as the research object, and a total of 7 groundwater samples were collected at different locations in the plant. The main pollutants in the research area were determined to be extractable petroleum hydrocarbons (C10-C40); 1,2-dichloroethane; 1,1,2-trichloroethane; carbon tetrachloride; vinyl chloride, and chloroform; the maximum content of these pollutants can reach 271 mg/L, 1.68 × 107 µg/L, 1.56 × 104 µg/L, 9.53 × 104 µg/L, 6.58 × 104 µg/L, and 4.81 × 104 µg/L, respectively. Aiming at the problems of groundwater pollution in this area, two sets of oxidation experiments have been carried out. The addition of NaHSO3 modified Fenton oxidation system was used in this contaminated water, which enhanced (2.2 ~ 46.7%) chemical oxygen demand (COD) removal rate. The highest removal rate of extractable petroleum hydrocarbons (C10-C40) can reach 99%. And the degradation rate of chlorinated hydrocarbon pollutants can reach 99% to 100%, which almost achieved the purpose of complete removal. In the NaHSO3 modified Fenton oxidation system, the addition of NaHSO3 accelerates the cycle of Fe3+/Fe2+ and ensures the continuous existence of Fe2+ in the reaction system, thereby producing more ·OH and further oxidizing and degrading organic pollutants. Our work has provided important insights for this economically important treatment of this type water body and laid the foundation for the engineering of this method.

16.
J Neurol ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36396814

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with complex pathophysiology. Therefore, the identification of novel effective fluid biomarkers is essential for Alzheimer's disease diagnosis and drug development. This study aimed to identify potential candidate hub proteins in cerebrospinal fluid for precise Alzheimer's disease diagnosis using bioinformatics methods. METHODS: A total of 29 co-significant differentially expressed proteins were identified by differential protein expression analysis in four different cohorts. Functional enrichment analysis revealed that most of these proteins were enriched in pathways related to glycometabolism. Using the Least Absolute Shrinkage and Selection Operator (LASSO) and random forest feature selection methods, six hub proteins [14-3-3 protein zeta/delta (YWHAZ), SPARC-related modular calcium-binding protein 1 (SMOC1), aldolase A (ALDOA), pyruvate kinase isoenzyme type M2 (PKM), chitinase-3-like protein 1 (CHI3L1), and secreted phosphoprotein 1 (SPP1)] were identified. RESULTS: These six hub proteins were upregulated in the cerebrospinal fluid of patients with Alzheimer's disease compared with cognitively unimpaired control individuals. Meanwhile, SMOC1, ALDOA, and PKM were specifically upregulated in the cerebrospinal fluid of patients with Alzheimer's disease but not in other neurodegenerative diseases. Build AD diagnostic models showed that a single hub protein or six hub proteins combination had an excellent ability to discriminate Alzheimer's disease. CONCLUSIONS: In conclusion, our study suggests that these identified hub proteins, which are related to glycometabolism, may be potential biomarkers for further basic and clinical research in Alzheimer's disease.

17.
Viruses ; 14(11)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36366508

RESUMO

Human parvovirus B19 (HPV B19) is pathogenic to human, which can cause fifth disease, transient aplastic crisis, arthritis, myocarditis, autoimmune disorders, hydrops fetalis, and so on. Currently, no approved vaccines or antiviral drugs are available against HPV B19, and thus the development of effective vaccines is needed. The capsid of HPV B19 is composed of two types of proteins, i.e., the major capsid protein VP2 and the minor protein VP1. Previous experimental studies have shown that the dominant immune responses against HPV B19 are elicited by VP1, especially the unique region on the N-terminus of VP1. It has been found that VP2 alone or VP2 and VP1 together can assemble into virus-like particle (VLP). The VLP structure formed by VP2 has been resolved, however, the location of VP1 in the capsid, especially the location of VP1 unique region with strong immunogenicity, is still not clear. In the present work, using the Hansenula polymorpha expression system developed by our laboratory, two kinds of recombinant HPV B19 VLPs were expressed, i.e., the VLP co-assembled by VP1 and VP2 (VP1/VP2 VLP) and the VLP whose VP1 content was improved (VP1h/VP2 VLP). The expression, purity, and morphology of these two VLPs were characterized, and then their immunogenic properties were investigated and compared with those of the VLP containing VP2 alone (VP2 VLP) previously developed by our group. Furthermore, the location of the VP1 unique region in the VLPs was determined by using the immunogold electron microscopy (IGEM). Our experimental results show that the VP1h/VP2 VLP elicits a stronger neutralization against the HPV B19 than VP2 and VP1/VP2 VLPs, which implies that the increase of VP1 content significantly improves the level of neutralizing antibodies. In addition, the IGEM observations suggest that the unique region of VP1 may be located inside the recombinant VLP. The VLPs recombinantly expressed by our Hansenula polymorpha system may serve as a promising candidate immunogen for HPV B19 vaccine development.


Assuntos
Orthopoxvirus , Infecções por Papillomavirus , Parvovirus B19 Humano , Humanos , Parvovirus B19 Humano/genética , Capsídeo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Anticorpos Antivirais/metabolismo
18.
Allergol Immunopathol (Madr) ; 50(6): 107-114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36335453

RESUMO

OBJECTIVE: To assess the effects of anethole on monosodium urate (MSU)-induced inflammatory response, investigate its role in acute gouty arthritis (AGA), and verify its molecular mechanism. METHODS: Hematoxylin and eosin staining assay and time-dependent detection of degree of ankle swelling were performed to assess the effects of anethole on joint injury in MSU-induced AGA mice. Enzyme-linked-immunosorbent serologic assay was performed to demonstrate the production levels of inflammatory factors (interleukin 1ß [IL-1ß], interleukin 6 [IL-6], interleukin 8 [IL-8], tumor necrosis factor α [TNF-α], and monocyte chemo-attractant protein-1 [MCP-1]) in MSU-induced AGA mice. Western blot assays were used to confirm the effects of anethole on oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity and the activation of toll-like receptors (TLRs)-myeloid differentiation factor 88 (MyD88) pathway in MSU-induced AGA mice. RESULTS: We observed that a significant joint injury occurred in MSU-induced AGA mice. Anethole could alleviate the pathological injury of the synovium in MSU-induced AGA mice and suppressed ankle swelling. In addition, we observed that anethole could inhibit MSU-induced inflammatory response and inflammasome activation in MSU-induced AGA mice. Moreover, we discovered that anethole enabled to inhibit the activation of TLRs/MyD88 pathway in MSU-induced AGA mice. Our findings further confirmed that anethole contributed to the inhibitory effects on progression in MSU-induced AGA mice. CONCLUSION: It confirmed that anethole ameliorated the MSU-induced inflammatory response in AGA mice in vivo via inhibiting TLRs-MyD88 pathway.


Assuntos
Artrite Gotosa , Camundongos , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Ácido Úrico/efeitos adversos , Fator 88 de Diferenciação Mieloide/metabolismo , Inflamassomos/efeitos adversos , Inflamassomos/metabolismo , Inflamação/patologia , Interleucina-1beta/efeitos adversos , Interleucina-1beta/metabolismo
19.
Medicine (Baltimore) ; 101(43): e31552, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316834

RESUMO

The aim of our study was to determine the prevalence, distribution, and risk factors for constipation in peritoneal dialysis (PD) and hemodialysis (HD) patients in our center. In this cross-sectional study, 858 dialysis patients over 18 years of age (681 HD cases and 177 PD cases from our hospital) were enrolled. A constipation assessment scale (CAS) questionnaire was used to evaluate constipation status. Logistic regression analysis was performed to define independent risk factors for CAS scores. The prevalence of constipation in HD and PD patients was 52.7% and 77.4%, respectively. The mean CAS score in HD and PD patients was 1.73 ± 2.31 and 2.42 ± 2.34, respectively. Age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors associated with constipation in the HD population (OR = 1.67, 95% CI: 1.15-2.90, P = .019; OR = 3.31, 95% CI: 1.65-6.11, P < .001, respectively). In the PD population, only serum prealbumin was independently associated with constipation (OR = 0.88, 95% CI: 0.79-0.96, P = .007). The multivariable logistic regression analysis demonstrated that PD modality, age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors for constipation (OR = 2.15, 95% CI: 1.41-3.32, P < .001; OR = 1.65, 95% CI: 1.13-2.33, P = .003; OR = 3.19, 95% CI: 1.76-5.093, P < .001, respectively). The prevalence of constipation in PD patients was higher than that in HD patients in our center. PD modality for renal replacement therapy, age ≥ 65 and diabetic kidney disease for renal failure were closely associated with constipation in dialysis patients.


Assuntos
Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Adolescente , Adulto , Diálise Renal/efeitos adversos , Estudos Transversais , Prevalência , Nefropatias Diabéticas/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Constipação Intestinal/etiologia , Constipação Intestinal/complicações
20.
Artigo em Inglês | MEDLINE | ID: mdl-36441889

RESUMO

In this study, a 0.8-V- Vin 200-mA- Io capless low-dropout voltage regulator (LDO) is developed for a wireless respiration monitoring system. The biaxially driven power transistor (BDP) technique is proposed in the LDO, with a current driven stimulation on the bulk and a voltage on the gate terminal. With the BDP technique, an adaptively biased current-driven loop (ABCL) is designed which can reduce the high threshold voltage of power transistor, thus presenting lower input voltage and reduced power consumption. Moreover, this loop can provide an improved dynamic response due to its increased discharging current. Based on an error amplifier with enhanced DC gain and gain bandwidth, the capless LDO achieves superior power supply rejection (PSR) and stability without a complex frequency compensation mechanism. The proposed LDO is fabricated in the SMIC 180 nm process with a chip area of 0.046 mm 2. Measurement results indicate that this LDO can obtain a 200-mA load current range and greater than -66 dB PSR up to 1 kHz at a supply voltage as low as 0.8 V.

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