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1.
Front Pharmacol ; 13: 916421, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091794

RESUMO

Background: Due to limited time windows and technical requirements, only a small percentage of patients can receive reperfusion therapy for acute ischemic stroke (AIS). Previous studies have shown that LongShengZhi (LSZ) capsule can improve neurological outcomes in patients after AIS, yet those results have not been finally verified through rigorous randomized controlled trials. Thus, this trial was designed to further clarify the efficacy and safety of LSZ capsule for patients with AIS. Methods: LSZ capsule on Functional Recovery after Acute Ischemic Stroke (LONGAN) trial is a prospective, multicenter, randomized, placebo-controlled, double-blind, parallel-group, superiority trial that enrolls patients from stroke and rehabilitation units in China. We will enroll 1,376 patients aged 18 years or older with AIS within 7 days of symptom onset and a National Institute of Health Stroke Scale (NIHSS) score of 4-15. Eligible patients will be randomized to receive either 2 g LSZ capsules three times a day or placebo LSZ capsules for 90 days. The primary outcome is the proportion of patients with favorable outcomes, as measured by the modified Rankin Scale (mRS) 90 days after randomization. The main safety outcome is the proportion of severe adverse events. Conclusion: This study will be the first randomized, double-blind trial to evaluate the efficacy and safety of LSZ capsule in patients with AIS. In order to improve the transparency and reproducibility of the trial, the data will be analyzed in accordance with this pre-specified plan for statistical analysis to reduce bias due to selective analysis and reporting. This trial aims to provide high-quality evidence for the efficacy and safety of LSZ capsule for AIS.

2.
J Hazard Mater ; 439: 129704, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36104920

RESUMO

The effects of different fertilization on microbial communities and resistome in agricultural soils with a history of fresh manure application remains largely unclear. Here, soil antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and microbial communities were deciphered using metagenomics approach from a long-term field experiment with different fertilizer inputs. A total of 541 ARG subtypes were identified, with Multidrug, Macrolides-Lincosamides-Streptogramins (MLS), and Bacitracin resistance genes as the most universal ARG types. The abundance of ARGs detected in manure (2.52 ARGs/16 S rRNA) treated soils was higher than chemical fertilizer (2.42 ARGs/16 S rRNA) or compost (2.37 ARGs/16 S rRNA) amended soils. The higher abundance of MGEs and the enrichment of Proteobacteria were observed in manure treated soils than in chemical fertilizer or compost amended soils. Proteobacter and Actinobacter were recognized as the main potential hosts of ARGs revealed by network analysis. Further soil pH was identified as the key driver in determining the composition of both microbial community and resistome. The present study investigated the mechanisms driving the microbial community, MGEs and ARG profiles of long-term fertilized soils with ARGs contamination, and our findings could support strategies to manage the dissemination of soil ARGs.


Assuntos
Fertilizantes , Microbiota , Antibacterianos/farmacologia , Fertilizantes/análise , Genes Bacterianos , Esterco/microbiologia , Solo/química , Microbiologia do Solo
3.
Vaccine ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36117002

RESUMO

Persistent infection of high-risk human papillomavirus (HPV) is a leading cause of some cancers, including cervical cancer. However, with over 20 carcinogenic HPV types, it is difficult to design a multivalent vaccine that can offer complete protection. Here, we describe the design and optimization of a HPV51/69/26 triple-type chimeric virus-like particle (VLP) for vaccine development. Using E. coli and a serial N-terminal truncation strategy, we created double- and triple-type chimeric VLPs through loop-swapping at equivalent surface loops. The lead candidate, H69-51BC-26FG, conferred similar particulate properties as that of its parental VLPs and comparable immunogenicity against HPV51, -69 and -26. When produced in a GMP-like facility, these H69-51BC-26FG VLPs were verified to have excellent qualities for the development of a multivalent HPV vaccine. This study showcases an amenable way to create a single VLP using type-specific epitope clustering for the design of a triple-type vaccine.

4.
Int J Ophthalmol ; 15(9): 1488-1495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124182

RESUMO

AIM: To perform a quantitative analysis of the peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness changes in patients with early stage of diabetic retinopathy (DR). METHODS: In this case-control study, swept-source optical coherence tomography angiography (SS-OCTA) imaging was used to examine diabetic and age-matched healthy subjects. The optic disc HD 6×6 mm2 blood flow imaging scan mode was selected. Automatic software was used to measure the peripapillary VD, capillary vessel density (CVD), and RNLF in an optic nerve head (ONH) filed based on the Garway-Heath map. In addition, the correlation between peripapillary VD, CVD, and RNFL was further investigated. RESULTS: The cohort consisted of 32 healthy individuals and 72 patients with diabetes (34 eyes with no DR and 38 eyes with mild-moderate NPDR). Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions (P<0.05). Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal (ST) quadrants (P=0.018, P=0.030). In the correlation analysis of each region, the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD (r=0.233, P=0.05; r=0.288, P=0.015). In the TI region, the RNFL thickness was positively correlated with the peripapillary CVD (r=0.237, P=0.047). CONCLUSION: The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR. The peripapillary VD, CVD and RNFL decrease in early DR, and the RNFL thickness altered in association with the CVD or/and VD in some regions.

5.
Brain Res Bull ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126873

RESUMO

BACKGROUND: The gut microbiota is known to be associated with the regulation of many neurological diseases and behaviors, including chronic pain. However, it is unclear whether the gut microbiota is critical to the itch sensation. In this study, we investigated the effects of gut microbiota depletion on acute itch. METHODS: First, an antibiotic cocktail was orally administered to deplete the gut microbiota in male C57BL/6 mice. Then, pruritogens were intradermally injected to induce acute itch behavior. In addition, antibiotic-treated mice received transplantation of fecal microbiota from untreated mice, followed by tests for acute itch. The changes in c-Fos expression in trigeminal ganglia (TG) neurons were also investigated by immunofluorescence staining. RESULTS: Our results indicated that chronic antibiotic treatment significantly reduced the diversity and richness of the gut microbiota of mice. Compared to vehicle-treated mice, antibiotic-treated mice showed reductions in acute itch behavior induced by compound 48/80, chloroquine (CQ), and serotonin (5-HT), respectively. Moreover, repositioning of microbiota reversed the reductions in acute itch behavior in antibiotic-treated mice. In addition, immunofluorescence staining revealed that antibiotic-treated mice displayed decreased c-Fos expression in ipsilateral TG compared to controls. CONCLUSIONS: Our study, for the first time, discovered that antibiotic-induced gut microbiota depletion could reduce acute itch behavior, which may be connected with decreased TG neuronal activity.

6.
Front Pharmacol ; 13: 933140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120362

RESUMO

Background: Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS. Methods: A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075). Results: Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), ginkgo biloba dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for (1) GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MDmRS = -0.42, 95% CI (-0.47, -0.37), five trials, p < 0.00001; GEDM + CM for AIS on NIHSS: MDNIHSS = -1.02, 95% CI (-1.51, -0.52), four trials, p < 0.0001]; (2) GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MDmRS = -0.40, 95% CI (-0.54, -0.26), p < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MDNIHSS = -3.93, 95%CI (-7.72, -0.14), p = 0.04]; (3) GBDP in patients treated with CM; (4) GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and (5) HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs. Conclusions: This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.

7.
Nucleic Acids Res ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36124686

RESUMO

Phase separation (PS) proteins form droplets to regulate myriad membraneless organelles (MLOs) and cellular pathways such as transcription, signaling transduction and protein degeneration. PS droplets are usually liquid-like and can convert to hydrogel/solid-like under certain conditions. The PS behavior of proteins is regulated by co-PS partners and mutations, modifications, oligomerizations, repeat regions and alternative splicing of the proteins. With growing interest in PS condensates and associated proteins, we established PhaSepDB 1.0, which provided experimentally verified PS proteins and MLO-related proteins. The past few years witnessed a surge in PS-related research works; thus, we kept updating PhaSepDB. The current PhaSepDB contains 1419 PS entries, 770 low-throughput MLO-related entries and 7303 high-throughput MLO-related entries. We provided more detailed annotations of PS proteins, including PS verification experiments, regions used in experiments, phase diagrams of different experimental conditions, droplet states, co-PS partners and PS regulatory information. We believe that researchers can go further in studying PS proteins with the updated PhaSepDB (http://db.phasep.pro/).

8.
Front Microbiol ; 13: 990091, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118193

RESUMO

Antimicrobial resistance (AMR) is a global concern threatening public health. Developing novel antibiotics is one of the effective strategies to tackle AMR. Serine/threonine kinases (STKs) have been recently shown to play critical roles in the physiology and pathogenesis of several important bacterial pathogens which are regarded as a promising antimicrobial drug target. We previously reported the roles of STK in the regulation of bacterial cell division, metabolism, and pathogenesis in Streptococcus suis, an important zoonotic bacterial pathogen. In this study, we firstly identified the Thr167 and Ser175 residues in the activation loop of S. suis STK (ssSTK) as the kinase autophosphorylation sites. Phenotyping results demonstrated that the autophosphorylation deficient strain resembled the stk deletion strain showing essentiality for bacterial growth in minimal medium, abnormal morphology, and decreased virulence when compared with the wild-type S. suis SC19 strain. Based on these findings, we established an ssSTK inhibitor screening approach by measuring the growth of S. suis in a minimal medium and testing the autophosphorylation inhibition by measuring the consumption of ATP in an enzymatic reaction by ssSTK. A series of inhibitors against ssSTK are identified from a commercial kinase inhibitors library, including Staurosporine, K252a, AT9283, and APY29. These inhibitors showed antimicrobial activity in vitro. Moreover, by using Galleria mellonella larvae infection assay, compound APY29 displayed in vivo efficacy against S. suis infection. Additionally, it was predicted by molecular docking that these inhibitors could interact with ssSTK. Collectively, our data illustrated the essential roles of ssSTK autophosphorylation in the physiology and pathogenicity of S. suis and consider these inhibitors as promising antimicrobial lead compounds.

9.
Front Chem ; 10: 987557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105307

RESUMO

Oxathiapiprolin was developed with high antifungal activity and novel target protein and is used in the oomycetes control for crop protection. The structural modifications of oxathiapiprolin are summarized. The achievements and challenges in the structural modification of oxathiapiprolin are also discussed in this mini review. The outlook in this field is perspected according to our own opinion and understanding on the development of oxysterol binding protein inhibition fungicides.

10.
Environ Sci Technol ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36102145

RESUMO

Evolution of gaseous contaminants from biomass pyrolysis has drawn increasing attention. However, the thermal degradation, dynamics, and synergetic evolution mechanisms during real-time biomass pyrolysis remain unclear. Herein, a novel method using thermogravimetry-Fourier transform infrared spectrometry-gas chromatography/mass spectrometry (TG-FTIR-GC/MS) combined with thermal kinetics and two-dimensional correlation spectroscopy was proposed to explore the chemical properties and temperature response mechanisms of gaseous species released during Phragmites communis (PC) and Typha angustifolia (TA) pyrolysis. The thermal degradation mechanisms of PC/TA pyrolysis were mainly associated with the sigmoidal rate and random nucleation mechanisms. The formation intensities of alcohols/ethers, phenols/esters, acids, aldehydes, and ketones were higher during low-temperature TA pyrolysis and high-temperature PC pyrolysis. The average carbon oxidation state (OS¯C) of gaseous species mainly ranged from -1.5 to -0.5, and the OS¯C slope of most gaseous species was greater than -2.0, which was related to the reduction of aldehyde/ketone groups. Two-dimensional (2D)-TG-FTIR-COS analysis revealed that the sequential temperature response of gaseous species followed: acids → phenols, esters → aldehydes → hydrocarbons → alcohols, ethers → aromatics during PC/TA pyrolysis. The establishment of relationships between the sequential response of gases and degraded components provides an important basis for online monitoring/recovery of gaseous contaminants during biomass pyrolysis.

11.
Environ Microbiome ; 17(1): 49, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096891

RESUMO

BACKGROUND: The nitrogenous compound deposited from the atmosphere to the soil is complex, but most field experiments mimic nitrogen deposition with the acid NH4NO3 alone. Thus, whether the acid and non-acid nitrogenous compounds have similar effects on biodiversity and ecosystem functions remains understudied. We mimicked nitrogen deposition with acidic NH4NO3 and (NH4)2SO4, and non-acidic urea, slow-released urea and NH4HCO3 in a temperate steppe, and quantified soil microbial taxonomic and functional gene composition with amplicon sequencing and shotgun metagenomics, respectively. RESULTS: While NH4NO3 and (NH4)2SO4 significantly altered the soil microbial taxonomic and functional composition as well as their carbon decomposition potential, the other three compounds had smaller effects. CONCLUSION: Our results suggested that previous nitrogen deposition experiments mimicked with NH4NO3 or (NH4)2SO4 alone may have overestimated the effect on biodiversity and ecosystem functions in the Eurasian steppe and similar ecosystems affected by mainly nonacidic nitrogen deposition.

12.
J Agric Food Chem ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106619

RESUMO

Our previous study showed that nuciferine (NF) attenuated non-alcoholic fatty liver disease (NAFLD), which is attributed to a high-fat diet (HFD) through reinforcing intestinal barrier functions, regulating lipid metabolism, and improving inflammation. To clarify whether other mechanisms contribute to the anti-NAFLD efficacy of NF, the present study investigated the influence of NF on bile acid (BA) metabolism and gut microbiota in HFD-fed rats. The data demonstrated that NF changed the composition of colonic BA, particularly elevating conjugated BA and non-12OH BA levels. As shown by downregulated protein levels of FXR, FGF15, FGFR4, and ASBT and upregulated protein levels of CYP7A1 and CYP27A1, NF inhibited ileal FXR signaling, promoted BA synthesis, suppressed BA reabsorption, and facilitated fecal BA excretion. NF might affect hepatic FXR signaling, BA conjugation, and enterohepatic circulation by the changed mRNA levels of Fxr, Shp, Baat, Bacs, Bsep, Ntcp, Ibabp, and Ostα/ß. Meanwhile, NF regulated the gut microbiota, characterized by decreased BSH-producing genus, 7α-dehydroxylation genus, and increased taurine metabolism-related genus. Spearman rank correlation analysis implied that Colidextribacter, Adlercreutzia, Family_XIII_AD3011_group, Lachnospiraceae_UCG-010, Eisenbergiella, and UCG-005 were robustly associated with particular BA monomers. In conclusion, our experiment results suggested that NF could exert a mitigating effect on NAFLD via regulating BA metabolism and modulating the gut microbiota.

13.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077288

RESUMO

Chlorimuron-ethyl is a widely used herbicide in agriculture. However, uncontrolled chlorimuron-ethyl application causes serious environmental problems. Chlorimuron-ethyl can be effectively degraded by microbes, but the underlying molecular mechanisms are not fully understood. In this study, we identified the possible pathways and key genes involved in chlorimuron-ethyl degradation by the Chenggangzhangella methanolivorans strain CHL1, a Methylocystaceae strain with the ability to degrade sulfonylurea herbicides. Using a metabolomics method, eight intermediate degradation products were identified, and three pathways, including a novel pyrimidine-ring-opening pathway, were found to be involved in chlorimuron-ethyl degradation by strain CHL1. Transcriptome sequencing indicated that three genes (atzF, atzD, and cysJ) are involved in chlorimuron-ethyl degradation by strain CHL1. The gene knock-out and complementation techniques allowed for the functions of the three genes to be identified, and the enzymes involved in the different steps of chlorimuron-ethyl degradation pathways were preliminary predicted. The results reveal a previously unreported pathway and the key genes of chlorimuron-ethyl degradation by strain CHL1, which have implications for attempts to enrich the biodegradation mechanism of sulfonylurea herbicides and to construct engineered bacteria in order to remove sulfonylurea herbicide residues from environmental media.


Assuntos
Herbicidas , Methylocystaceae , Poluentes do Solo , Biodegradação Ambiental , Herbicidas/metabolismo , Methylocystaceae/metabolismo , Pirimidinas/metabolismo , Poluentes do Solo/metabolismo , Compostos de Sulfonilureia/metabolismo
14.
Molecules ; 27(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36080439

RESUMO

A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS3) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, v:v) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 µg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS3 method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing-Bablok regression coefficients and Bland-Altman plots showed that the developed LC-MS3 method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS3 method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.


Assuntos
Monitoramento de Medicamentos , Epilepsia , Carbamazepina/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Epilepsia/tratamento farmacológico , Humanos , Oxcarbazepina , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
15.
Nat Commun ; 13(1): 5182, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056024

RESUMO

Influenza A viruses pose a significant threat globally each year, underscoring the need for a vaccine- or antiviral-based broad-protection strategy. Here, we describe a chimeric monoclonal antibody, C12H5, that offers neutralization against seasonal and pandemic H1N1 viruses, and cross-protection against some H5N1 viruses. Notably, C12H5 mAb offers broad neutralizing activity against H1N1 and H5N1 viruses by controlling virus entry and egress, and offers protection against H1N1 and H5N1 viral challenge in vivo. Through structural analyses, we show that C12H5 engages hemagglutinin (HA), the major surface glycoprotein on influenza, at a distinct epitope overlapping the receptor binding site and covering the 140-loop. We identified eight highly conserved (~90%) residues that are essential for broad H1N1 recognition, with evidence of tolerance for Asp or Glu at position 190; this site is a molecular determinant for human or avian host-specific recognition and this tolerance endows C12H5 with cross-neutralization potential. Our results could benefit the development of antiviral drugs and the design of broad-protection influenza vaccines.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Sítios de Ligação , Anticorpos Amplamente Neutralizantes , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Humanos
16.
J Environ Manage ; 320: 115867, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36056488

RESUMO

Black-odorous water, which exists widely in rural areas of China, affects the living environments of residents and causes a loss of ecosystem functions, and improper treatment may even cause secondary pollution. Moreover, the transformation relationships among the components of humus in the sediments of black-odorous water are largely unknown. Therefore, it is necessary to select appropriate methods for treating black-odorous water in rural areas and to understand the characteristics of humus in sediment during the treatment process. In this study, the use of aeration in treating black-odorous water and interstitial water in rural areas was studied and the effects of different treatment methods on the contents and spectral characteristics of humus components in sediments were explored. It was found that the quality of the treated water improved from severe black-odorous to nonblack-odorous, the colour of the sediment changed from black to greyish-brown to turquoise, and the odour changed from strong to weak. The removal rates of ammonia nitrogen, total nitrogen, total phosphorus, and chemical oxygen demand in the sediment aeration group reached more than 50% in the upper water, and more than 70% in the interstitial water. After treatment, the content of fulvic acid, the main black substance in sediment, decreased by 0.36-1.58 g/kg, and the molecular structure of the humus was simplified.


Assuntos
Sedimentos Geológicos , Poluentes Químicos da Água , China , Ecossistema , Sedimentos Geológicos/química , Nitrogênio/análise , Odorantes , Fósforo/análise , Solo , Poluentes Químicos da Água/análise , Qualidade da Água
17.
Adv Healthc Mater ; : e2201615, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100559

RESUMO

The combination of photothermal therapy (PTT) and chemotherapy is considered a promising tumor treatment modality, nevertheless, cellular resistance induced by heat shock proteins (HSPs) overexpressed in tumor cells will restrict the therapeutic effect. Herein, a multifunctional nanobeacon DOX/HCuS@PDA-MB (D/CP-MB) with a scout function for HSP90 mRNA fluorescence detection and near-infrared (NIR) triggered drug release for sensitizing chemo-photothermal therapy, is proposed. In the theranostic nanobeacons, HSP90MBs not only enable fluorescence detection of intracellular HSP90 mRNAs, but also downregulate the expression of HSP90 to reduce cell resistance. With the assistance of NIR and guidance of fluorescence imaging, spatiotemporal doxorubicin release can be achieved by the trigger of the photothermal effect, allowing for combined chemotherapy and photothermal treatment. Furthermore, the dual photothermal effect of hollow mesoporous CuS (HCuS) and polydopamine will lead to a better photothermal effect. Moreover, compared with other control groups, D/CP-MB nanobeacons exhibit effective boost therapeutic efficacy by inducing significant suppression of tumor proliferation and enhancement of apoptosis both in vitro and in vivo. In summary, this work provides novel theranostic nanobeacons that integrate imaging and therapy in a single nanoparticle, this strategy of imaging-guided therapy can enable precise tumor treatment and effectively improve tumor treatment efficacy.

18.
Front Public Health ; 10: 1007130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148343

RESUMO

Enterocytozoon bieneusi is a zoonotic pathogen commonly found in humans and animals all over the world. Here, we investigated the occurrence and genotype constitute of E. bieneusi among the individuals from Haikou city of Hainan, China. A total of 1,264 fecal samples of humans were collected, including 628 samples from patients with diarrhea (325 adults and 303 children) and 636 samples from the asymptomatic population (383 college students and 253 kindergarten children). E. bieneusi was detected using nested polymerase chain reaction (PCR) amplification of the internal transcribed spacer (ITS) region. A phylogenetic tree was constructed using a neighbor-joining tree construction method. The overall prevalence of E. bieneusi was 3.7% (47/1,264), while it was 5.6% in the patients with diarrhea (5.8% in adults and 5.3% in children) and 1.9% in the asymptomatic population (2.9% in college students and 0.4% in kindergarten children). The prevalence of E. bieneusi in humans with diarrhea was significantly higher than that in the asymptomatic population (χ2 = 36.9; P < 0.05). A total of 28 genotypes were identified, including ten known genotypes: CHG2 (n = 3), CHG3 (n = 5), CHG5 (n = 10), CM21 (n = 1), EbpA (n = 1), EbpC (n = 1), PigEBITS4 (n = 1), PigEBITS7 (n = 1), SHR1 (n = 4), Type IV (n = 2), and 18 novel genotypes (HNH-1 to HNH-18; one each). All these genotypes were categorized into three groups, including group 1 (n = 6), group 2 (n = 14), and group 13 (n = 8). This was the first study on the identification of E. bieneusi among humans in Hainan, China. The correlation between E. bieneusi infection and diarrhea was observed. The high diversity and distinctive distribution of E. bieneusi genotypes found in this study reflected the unique epidemic genetic characteristics of E. bieneusi in humans living in Hainan.

19.
J Med Virol ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36059257

RESUMO

In 2019, a serious dengue virus (DENV) infection broke out in the Xishuangbanna Dai Autonomous Prefecture, China. Therefore, we conducted a molecular epidemiological analysis in people that contracted DENV serotype 1 (DENV-1) during this year. We analyzed the molecular epidemiology of six DENV-1 epidemic strains in 2019 by full-length genome sequencing, amino acid mutation site analysis, evolutionary tree analysis, and recombination site comparison analysis. Through the analysis of amino acid mutation sites, it was found that DENV-1 strain (MW386867) was different from the other five epidemic DENV-1 strains in Xishuangbanna in 2019. MW386867 had unique mutation sites at six loci. The six epidemic DENV-1 strains in Xishuangbanna in 2019 were divided into two clusters. MW386867 was highly similar to the MG679800 (Myanmar 2017), MG679801 (Myanmar 2017), and KC172834 (Laos 2008), and the other five strains were highly similar to JQ045660 (Vietnam 2011), FJ176780 (GuangDong 2006). Genetic recombination analysis revealed that there was no recombination signal in the six epidemic DENV-1 strains in Xishuangbanna in 2019. We speculate that the DENV-1 epidemic in 2019 has a co-epidemic of local strains and cross-border strains.

20.
BMC Plant Biol ; 22(1): 454, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131236

RESUMO

BACKGROUND: A gene family comprises a group of genes with similar functional domains that play various roles in plant growth, development, and responses to environmental stimuli. Barley (Hordeum vulgare L.) is the fourth most cultivated cereal crop worldwide, and it is an important model species for genetic studies. Systematic identification and annotation of gene families are key for studies of molecular function and evolutionary history. RESULTS: We constructed a multi-omics database containing 5593 genes of 77 gene families called the Barley Gene Family Database (BGFD: http://barleygfdb.com ). BGFD is a free, user-friendly, and web-accessible platform that provides data on barley family genes. BGFD provides intuitive visual displays to facilitate studies of the physicochemical properties, gene structure, phylogenetic relationships, and motif organization of genes. Massive multi-omics datasets have been acquired and processed to generate an atlas of expression pattern profiles and genetic variation in BGFD. The platform offers several practical toolkits to conduct searches, browse, and employ BLAST functions, and the data are downloadable. CONCLUSIONS: BGFD will aid research on the domestication and adaptive evolution of barley; it will also facilitate the screening of candidate genes and exploration of important agronomic traits in barley.


Assuntos
Hordeum , Hordeum/genética , Filogenia
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