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1.
Int J Mol Sci ; 25(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38612492

RESUMO

The excavation and utilization of dormancy loci in breeding are effective endeavors for enhancing the resistance to pre-harvest sprouting (PHS) of wheat varieties. CH1539 is a wheat breeding line with high-level seed dormancy. To clarify the dormant loci carried by CH1539 and obtain linked molecular markers, in this study, a recombinant inbred line (RIL) population derived from the cross of weak dormant SY95-71 and strong dormant CH1539 was genotyped using the Wheat17K single-nucleotide polymorphism (SNP) array, and a high-density genetic map covering 21 chromosomes and consisting of 2437 SNP markers was constructed. Then, the germination percentage (GP) and germination index (GI) of the seeds from each RIL were estimated. Two QTLs for GP on chromosomes 5A and 6B, and four QTLs for GI on chromosomes 5A, 6B, 6D and 7A were identified. Among them, the QTL on chromosomes 6B controlling both GP and GI, temporarily named QGp/Gi.sxau-6B, is a major QTL for seed dormancy with the maximum phenotypic variance explained of 17.66~34.11%. One PCR-based diagnostic marker Ger6B-3 for QGp/Gi.sxau-6B was developed, and the genetic effect of QGp/Gi.sxau-6B on the RIL population and a set of wheat germplasm comprising 97 accessions was successfully confirmed. QGp/Gi.sxau-6B located in the 28.7~30.9 Mbp physical position is different from all the known dormancy loci on chromosomes 6B, and within the interval, there are 30 high-confidence annotated genes. Our results revealed a novel QTL QGp/Gi.sxau-6B whose CH1539 allele had a strong and broad effect on seed dormancy, which will be useful in further PHS-resistant wheat breeding.


Assuntos
Dormência de Plantas , Locos de Características Quantitativas , Dormência de Plantas/genética , Triticum/genética , Melhoramento Vegetal , Alelos
2.
ACS Biomater Sci Eng ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639082

RESUMO

Periodontitis is a common condition characterized by a bacterial infection and the disruption of the body's immune-inflammatory response, which causes damage to the teeth and supporting tissues and eventually results in tooth loss. Current therapy involves the systemic and local administration of antibiotics. However, the existing treatments cannot exert effective, sustained release and maintain an effective therapeutic concentration of the drug at the lesion site. Hydrogels are used to treat periodontitis due to their low cytotoxicity, exceptional water retention capability, and controlled drug release profile. Hydrogels can imitate the extracellular matrix of periodontal cells while offering suitable sites to load antibiotics. This article reviews the utilization of hydrogels for periodontitis therapy based on the pathogenesis and clinical manifestations of the disease. Additionally, the latest therapeutic strategies for smart hydrogels and the main techniques for hydrogel preparation have been discussed. The information will aid in designing and preparing future hydrogels for periodontitis treatment.

3.
J Neurosci Res ; 102(4): e25325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38562056

RESUMO

Brain states (wake, sleep, general anesthesia, etc.) are profoundly associated with the spatiotemporal dynamics of brain oscillations. Previous studies showed that the EEG alpha power shifted from the occipital cortex to the frontal cortex (alpha anteriorization) after being induced into a state of general anesthesia via propofol. The sleep research literature suggests that slow waves and sleep spindles are generated locally and propagated gradually to different brain regions. Since sleep and general anesthesia are conceptualized under the same framework of consciousness, the present study examines whether alpha anteriorization similarly occurs during sleep and how the EEG power in other frequency bands changes during different sleep stages. The results from the analysis of three polysomnography datasets of 234 participants show consistent alpha anteriorization during the sleep stages N2 and N3, beta anteriorization during stage REM, and theta posteriorization during stages N2 and N3. Although it is known that the neural circuits responsible for sleep are not exactly the same for general anesthesia, the findings of alpha anteriorization in this study suggest that, at macro level, the circuits for alpha oscillations are organized in the similar cortical areas. The spatial shifts of EEG power in different frequency bands during sleep may offer meaningful neurophysiological markers for the level of consciousness.


Assuntos
Eletroencefalografia , Sono de Ondas Lentas , Humanos , Eletroencefalografia/métodos , Sono de Ondas Lentas/fisiologia , Sono/fisiologia , Fases do Sono/fisiologia , Polissonografia
4.
Heliyon ; 10(5): e26960, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38444486

RESUMO

Background: Although many circulating miRNAs (c-miRNAs) are associated with coronary artery disease (CAD), they are far from being the biomarker for CAD diagnosis or risk prediction. Therefore, novel c-miRNAs discovery and validation are still required, especially evaluating their prediction capacity. Objectives: Identify novel CAD-related c-miRNAs and evaluate its risk prediction capacity for CAD. Methods: miRNAs associated with CAD were preliminarily investigated in three paired samples representing pre-CAD stage and CAD stage of three female individuals using the Applied Biosystems miRNA TaqMan® Low-Density Array (TLDA). Then, the candidate miRNAs were further verified in an independent case-control study including 129 CAD patients and 76 controls, and their potential practical value in prediction for CAD was evaluated using a machine learning (ML) algorithm. The accuracy of classification and prediction was assessed with the area under the receiver operating characteristic curve (AUC). Results: TLDA analysis shows that miR-140-3p decreased significantly in CAD-stage (FC = -3.01, P = 0.007). Further study shows that miR-140-3p was significantly lower in CAD group [1.26 (0.68, 2.01)] than in control group [2.07 (1.19, 3.21)] (P < 0.001) and independently associated with CAD (P < 0.001). The addition of miR-140-3p to the variables including smoking history, HDL-c, and APOA1 improved the accuracy of classification by logistic regression and of prediction for CAD by ML models. The ML models built with miR-140-3p and HDL-c, respectively, had a similar prediction accuracy. The feature importance of miR-140-3p and HDL-c in the ML models was also similar. Decision curve analysis showed that miR-140-3p and HDL-c had almost identical net benefits. Conclusion: Reduced levels of miR-140-3p is linked to CAD, and it is possible to use the plasma level of miR-140-3p as a means of evaluating the risk of CAD.

5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(1): 37-45, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38475949

RESUMO

OBJECTIVES: This study aimed to investigate the effects of sitagliptin on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in lipopolysaccharide (LPS)-induced inflammatory microenvironment and its molecular mechanism. METHODS: hPDLSCs were cultured in vitro and treated with different concentrations of sitagliptin to detect cell viability and subsequently determine the experimental concentration of sitagliptin. An hPDLSCs inflammation model was established after 24 h of stimulation with 1 µg/mL LPS and divided into blank, control, low-concentration sitagliptin (0.5 µmol/L), medium-concentration sitagliptin (1 µmol/L), and high-concentration sitagliptin (2 µmol/L), high-concentrationsitagliptin+stromal cell derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) pathway inhibitor (AMD3100) (2 µmol/L+10 µg/mL) groups. A cell-counting kit-8 was used to detect the proliferation activity of hPDLSCs after 24, 48, and 72 h culture. The apoptosis of hPDLSCs cultured for 72 h was detected by flow cytometry. After inducing osteogenic differentiation for 21 days, alizarin red staining was used to detect the osteogenic differentiation ability of hPDLSCs. The alkaline phosphatase (ALP) activity in hPDLSCs was determined using a kit. The levels of inflammatory factors [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6] in the supernatant of hPDLSCs culture were detected by enzyme-linked immunosorbent assay. The mRNA expressions of osteogenic differentiation genes [Runt-associated transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN)], SDF-1 and CXCR4 in hPDLSCs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western blot analysis was used to determine SDF-1 and CXCR4 protein expression in hPDLSCs. RESULTS: Compared with the blank group, the proliferative activity, number of mineralized nodules, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in the control group significantly decreased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 significantly increased (P<0.05). Compared with the control group, the proliferative activity, number of mineralized nodule, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in low-, medium-, and high-concentration sitagliptin groups increased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 decreased (P<0.05). AMD3100 partially reversed the effect of high-concentration sitagliptin on LPS-induced hPDLSCs (P<0.05). CONCLUSIONS: Sitagliptin may promote the proliferation and osteogenic differentiation of hPDLSCs in LPS-induced inflammatory microenvironment by activating the SDF-1/CXCR4 signaling pathway. Furthermore, it inhibited the apoptosis and inflammatory response of hPDLSCs.


Assuntos
Benzilaminas , Ciclamos , Lipopolissacarídeos , Ligamento Periodontal , Humanos , Ligamento Periodontal/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Receptores CXCR4/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Osteogênese , Transdução de Sinais , Inflamação/metabolismo , Células-Tronco , RNA Mensageiro/metabolismo , Apoptose , Proliferação de Células , Células Estromais/metabolismo , Diferenciação Celular , Células Cultivadas
6.
Haematologica ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385270

RESUMO

t(1;19)(q23;p13) is one of the most common translocation genes in childhood acute lymphoblastic leukemia (ALL) and is also present in acute myeloid leukemia (AML) and mixed-phenotype acute leukemia (MPAL). This translocation results in the formation of the oncogenic E2A-PBX1 fusion protein, which contains a trans-activating domain from E2A and a DNA-binding homologous domain from PBX1. Despite its clear oncogenic potential, the pathogenesis of E2A-PBX1 fusion protein is not fully understood (especially in leukemias other than ALL), and effective targeted clinical therapies have not been developed. To address this, we established a stable and heritable zebrafish line expressing human E2A-PBX1 (hE2APBX1) for high-throughput drug screening. Blood phenotype analysis showed that hE2APBX1 expression induced myeloid hyperplasia by increasing myeloid differentiation propensity of hematopoietic stem cells (HSPCs) and myeloid proliferation in larvae, and progressed to AML in adults. Mechanistic studies revealed that hE2A-PBX1 activated the TNF/IL-17/MAPK signaling pathway in blood cells and induced myeloid hyperplasia by upregulating the expression of the runx1. Interestingly, through high-throughput drug screening, three small molecules targeting the TNF/IL-17/MAPK signaling pathway were identified, including OUL35, KJ-Pyr-9, and CID44216842, which not only alleviated the hE2A-PBX1- induced myeloid hyperplasia in zebrafish but also inhibited the growth and oncogenicity of human pre-B ALL cells with E2A-PBX1. Overall, this study provides a novel hE2A-PBX1 transgenic zebrafish leukemia model and identifies potential targeted therapeutic drugs, which may offer new insights into the treatment of E2A-PBX1 leukemia.

7.
Chem Biodivers ; 21(4): e202301993, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342755

RESUMO

A new alkaloids, aplysingoniopora A (1), and new configuration pregnane type steroid compound, 9,17-α-pregn-1,4,20-en-3-one (2), and two known pregnane type steroid compounds (3 and 4) were isolated from hydranth of Goniopora columna corals. The compounds structures and absolute configurations were determined by extensive spectroscopic analysis, MS data, single-crystal X-ray diffraction analysis and quantum chemical calculation. The anticancer effect of the compounds were explored in human non-small-cell lung cancer (NSCLC) A549 cell lines. As the results, the compound 3 and 4 induces toxicity and has proliferation inhibitory effects on A549 cells (IC50=58.99 µM and 58.77 µM, respectively) in vitro.


Assuntos
Alcaloides , Antozoários , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Alcaloides/farmacologia , Alcaloides/química , Esteroides/farmacologia , Esteroides/química , Pregnanos/farmacologia , Estrutura Molecular
8.
3D Print Addit Manuf ; 11(1): 50-59, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38389692

RESUMO

Compared with conventional formwork casting materials, 3D printed concrete (3DPC) is characterized by large amounts of cementitious materials, a low aggregate-binder ratio, and a large water evaporation area, which make the printed materials and structures highly prone to plastic shrinkage and cracking. In this study, cellulose fibers were incorporated into concrete to improve its moisture distribution and increase its early-age strength. The effects of both dry and prewet cellulose fibers on properties of 3DPC were experimentally investigated. To ensure consistency in the amounts of dry fibers used, 0.5-2% dry cellulose fibers and 1-4% prewet cellulose fibers were adopted. The effects of the added cellulose fibers on printability, mechanical strength, shrinkage, and cracking performance of the 3DPC were experimentally studied. Particularly, a constraint method was developed to access the cracking behavior of 3DPC. Favorable shrinkage resistance was achieved, and the 120-day shrinkage decreased by 17.9% and 23.3% by addition of 2% dry fibers and 4% prewet fibers, respectively. Cracking was eliminated with addition of 4% prewet fibers, without influencing the printability and mechanical properties.

9.
J Phys Chem Lett ; 15(7): 1818-1827, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38330253

RESUMO

While extensive research has been dedicated to plasmon tuning within non-noble metals, prior investigations primarily concentrated on markedly augmenting the inherently low concentration of free carriers in materials with minimal consideration given to the influence of electron orbitals on surface plasmons. Here, we achieve successful intercalation of Au atoms into the layered structure of Fe3GeTe2 (FGT), thereby exerting control over the orbital electronic states or structure of FGT. This intervention not only amplifies the charge density and electron mobility but also mitigates the loss associated with interband transitions, resulting in increased two-dimensional FGT surface plasmon activity. As a consequence, Au-intercalated FGT detects crystal violet molecules as a surface-enhanced Raman scattering substrate, and the detection lines are 3 orders of magnitude higher than before Au intercalation. Our work provides insight for further studies on plasmon effects and the relation between surface plasmon resonance behavior and electronic structures.

10.
Food Chem ; 445: 138750, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38382258

RESUMO

This paper was dedicated to the study of the effect of sucrose-phosphate on aspects of physicochemical properties, lipid distribution and protein structure during the picklig of reduced-salt salted egg yolk (SEY). This work constructed a reduced-salt pickling system from a new perspective (promoting osmosis) by using a sucrose-phosphate-salt. Results showed that SEY-28d achieved a desirable salt content (1.07 %), hardness (573.46 g) and springiness (0.65 g). The matured SEY was in excellent quality with orange-red color and loose sandy texture. This was because the lipoprotein aggregated with each other through hydrophobic interaction to form a stable network structure. In addition, the hypertonic environment accelerated salt penetration. These also created good condition for lipid spillage. The results of confocal laser scanning microscope also verified this phenomenon. This work provides important guidance for new reduced-salt curing of traditional pickled foods, deep processing of SEY, and industry development in the field of poultry egg.


Assuntos
Gema de Ovo , Fosfatos , Gema de Ovo/química , Fosfatos/farmacologia , Ovos , Cloreto de Sódio/química , Cloreto de Sódio na Dieta/análise , Lipídeos/análise , Osmose
11.
Adv Mater ; 36(13): e2310973, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185875

RESUMO

The conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) offers superior advantages in electronics due to its remarkable combination of high electrical conductivity, excellent biocompatibility, and mechanical flexibility, making it an ideal material among electronic skin, health monitoring, and energy harvesting and storage. Nevertheless, pristine PEDOT:PSS films exhibit limitations in terms of both low conductivity and stretchability; while, conventional processing techniques cannot enhance these properties simultaneously, facing the dilemma that highly conductive interconnected PEDOT:PSS domains are susceptible to tensile strain. Via modifying PEDOT:PSS with ionic liquids (ILs), not only a synergistic enhancement of the electrical and mechanical properties can be achieved but also the requirements for the printable bioelectronic are satisfied. In this comprehensive review, the task of providing a thorough examination of the mechanisms and applications of ILs as modifiers for PEDOT:PSS is undertaken. First, the theoretical mechanisms governing the interactions between ILs and PEDOT:PSS are discussed in detail. Then, the enhanced properties and the elucidation of the underlying mechanisms achieved through the incorporation of ILs are reviewed. Next, specific applications of ILs-modified PEDOT:PSS relevant to bioelectronic devices are presented. Last, there is a concise summary and a discussion regarding the opportunities and challenges in this exciting field.

12.
Front Biosci (Landmark Ed) ; 29(1): 19, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38287820

RESUMO

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. METHODS: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. RESULTS: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. CONCLUSIONS: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Tiossemicarbazonas , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Simulação de Acoplamento Molecular , Transdução de Sinais/genética , Regulação Neoplásica da Expressão Gênica
13.
Asian J Surg ; 47(1): 477-485, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37438153

RESUMO

BACKGROUND: In the 21st century, 13% of patients undergoing open abdominal surgery, 25% of patients undergoing heart surgery, and 57% of patients admitted to the intensive care unit (ICU) are affected by acute kidney injury (AKI). METHODS: This prospective observational study included patients admitted directly to the ICU between June 2021 and December 2021. RESULTS: A total of 81 patients were enrolled after thoracic and abdominal (non-cardiac) surgery; 36 patients (44.4%) were diagnosed with AKI occurred within 7 days after surgery. Six-hour postoperative central venous pressure(CVP) was a risk factor for AKI in thoracic and abdominal (non-cardiac) postoperative patients (odds ratio [OR], 1.418; 95% confidence intervals [CI], 1.106-1.819; P = 0.006). Six-hour postoperative vein impedance index(VII) and CVP were significantly positively correlated (P = 0.031). The combination of 6-h postoperative VII with CVP (VII ≥0.34, CVP ≥7.5 mmHg) showed an area under the curve (AUC) of 0.787, In the subgroup analysis of patients with 6-h postoperative CVP <7.5 mmHg, there was a significant statistical difference in 6-h postoperative VII between the groups and those without AKI (P = 0.048). At 6-h postoperative CVP <7.5 mmHg, VII of ≥0.44 had a predictive value for AKI after thoracic and abdominal (non-cardiac) surgery, with an AUC of 0.669, a sensitivity of 41.2%, and a specificity of 94.4%. CONCLUSION: Six-hour postoperative CVP combined with VII can better predict the occurrence of AKI occurred within 7 days after thoracic and abdominal (non-cardiac) surgery but cannot predict the severity of AKI.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Humanos , Abdome/cirurgia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pressão Venosa Central , Impedância Elétrica , Estudos Prospectivos
14.
J Dairy Sci ; 107(1): 24-39, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37690710

RESUMO

The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes, whereas it decreased Proteobacteria, Helicobacteraceae, and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis.


Assuntos
Microbioma Gastrointestinal , Leite , Feminino , Gravidez , Ratos , Animais , Camundongos , Dieta Hiperlipídica , Osteopontina/farmacologia , Ácidos e Sais Biliares/farmacologia , Camundongos Endogâmicos C57BL
15.
Gut ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973365

RESUMO

OBJECTIVES: Chronic hepatitis B (CHB) caused by HBV infection greatly increases the risk of liver cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) plays critical roles in the pathogenesis of CHB. HBsAg loss is the key indicator for cure of CHB, but is rarely achieved by current approved anti-HBV drugs. Therefore, novel anti-HBV strategies are urgently needed to achieve sustained HBsAg loss. DESIGN: We developed multiple chimeric antigen receptors (CARs) based on single-chain variable fragments (scFvs, namely MA18/7-scFv and G12-scFv), respectively, targeting HBV large and small envelope proteins. Their impacts on HBsAg secretion and HBV infection, and the underlying mechanisms, were extensively investigated using various cell culture models and HBV mouse models. RESULTS: After secretory signal peptide mediated translocation into endoplasmic reticulum (ER) and secretory pathway, MA18/7-scFv and CARs blocked HBV infection and virion secretion. G12-scFv preferentially inhibited virion secretion, while both its CAR formats and crystallisable fragment (Fc)-attached versions blocked HBsAg secretion. G12-scFv and G12-CAR arrested HBV envelope proteins mainly in ER and potently inhibited HBV budding. Furthermore, G12-scFv-Fc and G12-CAR-Fc strongly suppressed serum HBsAg up to 130-fold in HBV mouse models. The inhibitory effect lasted for at least 8 weeks when delivered by an adeno-associated virus vector. CONCLUSION: CARs possess direct antiviral activity, besides the well-known application in T-cell therapy. Fc attached G12-scFv and G12-CARs could provide a novel approach for reducing circulating HBsAg.

16.
Environ Microbiome ; 18(1): 83, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996910

RESUMO

BACKGROUND: The positive effects of exposing corals to microorganisms have been reported though how the benefits are conferred are poorly understood. Here, we isolated an actinobacterial strain (SCSIO 13291) from Pocillopora damicornis with capabilities to synthesize antioxidants, vitamins, and antibacterial and antiviral compounds supported with phenotypic and/or genomic evidence. Strain SCSIO 13291 was labeled with 5 (and - 6)-carboxytetramethylrhodamine, succinimidyl ester and the labeled cell suspension directly inoculated onto the coral polyp tissues when nubbins were under thermal stress in a mesocosm experiment. We then visualized the labelled bacterial cells and analyzed the coral physiological, transcriptome and microbiome to elucidate the effect this strain conferred on the coral holobiont under thermal stress. RESULTS: Subsequent microscopic observations confirmed the presence of the bacterium attached to the coral polyps. Addition of the SCSIO 13291 strain reduced signs of bleaching in the corals subjected to heat stress. At the same time, alterations in gene expression, which were involved in reactive oxygen species and light damage mitigation, attenuated apoptosis and exocytosis in addition to metabolite utilization, were observed in the coral host and Symbiodiniaceae populations. In addition, the coral associated bacterial community altered with a more stable ecological network for samples inoculated with the bacterial strain. CONCLUSIONS: Our results provide insights into the benefits of a putative actinobacterial probiotic strain that mitigate coral bleaching signs. This study suggests that the inoculation of bacteria can potentially directly benefit the coral holobiont through conferring metabolic activities or through indirect mechanisms of suppling additional nutrient sources.

17.
J Environ Manage ; 348: 119240, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37837767

RESUMO

Methane leakage from deep-sea cold seeps has a major impact on marine ecosystems. Microbes sequester methane in the water column of cold seeps and can be divided into abundant and rare groups. Both abundant and rare groups play an important role in cold seep ecosystems, and the environmental heterogeneity in cold seeps may enhance conversion between taxa with different abundances. Yet, the environmental stratification and assembly mechanisms of these microbial sub-communities remain unclear. We investigated the diversities and assembly mechanisms in microbial sub-communities with distinct abundance in the deep-sea cold seep water column, from 400 m to 1400 m. We found that bacterial ß-diversity, as measured by Sørensen dissimilarities, exhibited a significant species turnover pattern that was influenced by several environmental factors including depth, temperature, SiO32-, and salinity. In contrast, archaeal ß-diversity showed a relatively high percentage of nestedness pattern, which was driven by the levels of soluble reactive phosphate and SiO32-. During the abundance dependency test, abundant taxa of both bacteria and archaea showed a significant species turnover, while the rare taxa possessed a higher percentage of nestedness. Stochastic processes were prominent in shaping the prokaryotic community, but deterministic processes were more pronounced for the abundant taxa than rare ones. Furthermore, the metagenomics results revealed that the abundances of methane oxidation, sulfur oxidation, and nitrogen fixation-related genes and related microbial groups were significantly higher in the bottom water. Our results implied that the carbon, sulfur, and nitrogen cycles were potentially strongly coupled in the bottom water. Overall, the results obtained in this study highlight taxonomic and abundance-dependent microbial community diversity patterns and assembly mechanisms in the water column of cold seeps, which will help understand the impacts of fluid seepage from the sea floor on the microbial community in the water column and further provide guidance for the management of cold seep ecosystem under future environmental pressures.


Assuntos
Ecossistema , Microbiota , Água , Sedimentos Geológicos , Archaea/genética , Bactérias/genética , Metano , Enxofre , Filogenia
18.
Biomimetics (Basel) ; 8(6)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37887587

RESUMO

Cyclists are vulnerable road users and often suffer head-neck injuries in car-cyclist accidents. Wearing a helmet is currently the most prevalent protection method against such injuries. Today, there is an ongoing debate about the ability of helmets to protect the cyclists' head-neck from injury. In the current study, we numerically reconstructed five real-world car-cyclist impact accidents, incorporating previously developed finite element models of four cyclist helmets to evaluate their protective performances. We made comparative head-neck injury predictions for unhelmeted and helmeted cyclists. The results show that helmets could clearly lower the risk of severe (AIS 4+) brain injury and skull fracture, as assessed by the predicted head injury criterion (HIC), while a relatively limited decrease in AIS 4+ brain injury risk can be achieved in terms of the analysis of CSDM0.25. Assessment using the maximum principal strain (MPS0.98) and head impact power (HIP) criteria suggests that helmets could lower the risk of diffuse axonal injury and subdural hematoma of the cyclist. The helmet efficacy in neck protection depends on the impact scenario. Therefore, wearing a helmet does not seem to cause a significant neck injury risk level increase to the cyclist. Our work presents important insights into the helmet's efficacy in protecting the head-neck of cyclists and motivates further optimization of protective equipment.

19.
Emerg Med Int ; 2023: 6694313, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720549

RESUMO

Background: The extensive burns devastate trauma. The research was designed to analyse the predictive value of early platelet (PLT) indices on the development of acute kidney injury (AKI) after severe burns. Methods and Results: 186 patients with extensive burns (burn area ≥30%) were eventually involved. Multivariate analyses pointed out that platelet distribution width (PDW) in the first 24 h after admission was an independent risk factor for AKI, severe AKI, and RRT requirement in patients with severe burns, and AKI risk showed an increase of 30.9% per increase of 1% in PDW (OR = 1.309, CI, 1.075-1.594, and P = 0.007). It was found that the area under the ROC curve (AUC) of PDW predicting AKI was 0.735 and that the AUC value was 0.81 for AKI after combining PDW and blood urea nitrogen (BUN). Based on the cut-off value PDW = 17.7%, patients were divided into high- (PDW ≥17.7%) and low-risk (PDW <17.7%) groups. In the KM analysis, there was a higher cumulative incidence of AKI if patients were in a high-risk group (in 30 days); and the stages of AKI showed a linear upward trend (chi-square test for linear trend P < 0.001) as there was an increase in the risk level. Conclusion: The PDW level in the early stage serves as an important risk factor for AKI, severe AKI, and RRT requirement in extensive burns. When PDW >17.7%, burn patients are not only at a higher risk for AKI but may also have higher AKI severity. Due to low cost and wide availability, PDW has the potential to be the tool that can predict AKI in extensive burn patients.

20.
J Environ Manage ; 347: 119148, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37776790

RESUMO

Vegetation restoration is vital for soil ecological restoration in post-mining areas, but a global-scale quantitative assessment of its effects on soil metal elements is lacking. Here, we conducted a meta-analysis with 2308 paired observations collected from 137 publications to evaluate vegetation restoration effects on the concentrations of 17 metal elements, namely K, AK (available K), Ca, Na, Mg, Fe, Mn, Zn, Cu, Al, Cr, Co, Ni, Cd, Sb, Hg, and Pb in post-mining soils. We found that (1) vegetation restoration significantly increased the concentrations of K, AK, Ca, Mg and Co by 43.2, 42.5, 53.4, 53.7, and 137.2%, respectively, but did not affect the concentrations of Na, Fe, Mn, Zn, Cu, Al, Cr, Ni, Cd, Sb, Hg, and Pb; (2) the effects of vegetation restoration on soil metal concentration were seldom impacted by vegetation type, while soil depth only affected the responses of AK, Cd, and Pb concentrations to vegetation restoration, and leaf type only impacted the responses of Ca and Ni concentrations to vegetation restoration; (3) latitude, elevation, restoration year, climate, and initial soil properties were also important moderator variables of vegetation restoration effects, but their impacts varied among different metals. Overall, our results clearly showed that vegetation restoration in posting-mining areas generally have a positive effect on the concentrations of nutrient elements but did not influence that of toxic elements, which provides useful information for the restoration and reconstruction of soil ecosystem in post-mining areas.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Solo , Metais Pesados/análise , Ecossistema , Cádmio , Chumbo , Monitoramento Ambiental/métodos , Mercúrio/análise , Poluentes do Solo/análise , Medição de Risco , China
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