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1.
Sci Total Environ ; 927: 172170, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38575034

RESUMO

Soil heavy metal contamination is an essential challenge in ecological and environmental management, especially for acidic soils. Microbially induced carbonate precipitation (MICP) is an effective and environmentally friendly remediation technology for heavy metal contaminated sites, and one of the key factors for its realization lies in the microorganisms. In this study, Lysinibacillus capsici TSBLM was isolated from heavy metal contaminated soil around a gold mine, and inferred to be a novel ureolytic bacteria after phylogenomic inference and genome characterization. The urease of L. capsici TSBLM was analyzed by genetic analysis and molecular docking, and further applied this bacteria to the remediation of Cu and Pb in solution and acidic soils to investigate its biomineralization mechanism and practical application. The results revealed L. capsici TSBLM possessed a comprehensive urease gene cluster ureABCEFGD, and the encoded urease docked with urea at the lowest binding energy site (ΔG = -3.43 kcal/mol) connected to three amino acids threonine, aspartic, and alanine. The urease of L. capsici TSBLM is synthesized intracellularly but mainly functions extracellularly. L. capsici TSBLM removes Cu/Pb from the solution by generating heavy metal carbonates or co-precipitating with CaCO3 vaterite. For acidic heavy metal-contaminated soil, the carbonate-bound states of Cu and Pb increased significantly from 7 % to 16 % and from 23 % to 35 % after 30 days by L. capsici TSBLM. Soil pH improved additionally. L. capsici TSBLM maintained the dominant status in the remediated soil after 30 days, demonstrating good environmental adaptability and curing persistence. The results provided new strain resources and practical application references for the remediation of acidic heavy metal contaminated soil based on MICP.


Assuntos
Bacillaceae , Biodegradação Ambiental , Metais Pesados , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/metabolismo , Bacillaceae/genética , Bacillaceae/enzimologia , Urease/metabolismo , Solo/química , Recuperação e Remediação Ambiental/métodos , Filogenia , Mineração , Genoma Bacteriano
2.
Pediatr Investig ; 8(1): 66-71, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38516143

RESUMO

The onset of critical rare diseases (RDs) in children is rapid and dangerous, accompanied by a high mortality rate, which brings a heavy burden to both families and society. Multiple malformations, neuromuscular diseases, metabolic diseases, and heart diseases are the most common types of RDs in children of China, often manifesting with multiple organ dysfunction. At present, the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time, a high misdiagnosis rate, limited treatment modalities, and a significant disease burden. However, with the progress in genetic testing technology, the establishment of multidisciplinary diagnosis and treatment platforms, and the implementation of relevant RD policies in China, children with critical RDs will received enhanced medical services, experience improved prognoses, and reintegrate into social life.

3.
PeerJ ; 12: e16921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426148

RESUMO

Objective: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by an unclear pathogenesis. This study aims to screen out key genes related to UC pathogenesis. Methods: Bioinformatics analysis was conducted for screening key genes linked to UC pathogenesis, and the expression of the screened key genes was verified by establishing a UC mouse model. Results: Through bioinformatics analysis, five key genes were obtained. Subsequent infiltration analysis revealed seven significantly different immune cell types between the UC and general samples. Additionally, animal experiment results illustrated markedly decreased body weight, visible colonic shortening and damage, along with a significant increase in the DAI score of the DSS-induced mice in the UC group in comparison with the NC group. In addition, H&E staining results demonstrated histological changes including marked inflammatory cell infiltration, loss of crypts, and epithelial destruction in the colon mucosa epithelium. qRT-PCR analysis indicated a down-regulation of ABCG2 and an up-regulation of IL1RN, REG4, SERPINB5 and TRIM29 in the UC mouse model. Notably, this observed trend showed a significant dependence on the concentration of DSS, with the mouse model of UC induced by 7% DSS demonstrating a more severe disease state compared to that induced by 5% DSS. Conclusion: ABCG2, IL1RN, REG4, SERPINB5 and TRIM29 were screened out as key genes related to UC by bioinformatics analysis. The expression of ABCG2 was down-regulated, and that of IL1RN, REG4, SERPINB5 and TRIM29 were up-regulated in UC mice as revealed by animal experiments.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Regulação para Baixo/genética , Proteínas Associadas a Pancreatite/genética
4.
Eur J Pharmacol ; 968: 176432, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38369275

RESUMO

AIMS: This study aimed to examine the therapeutic effects and response mechanisms of 4-OI in Alzheimer's disease (AD). METHODS: In this study, network pharmacology was employed to analyze potential targets for AD drug therapy. Immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques were utilized to detect inflammatory phenotypes in a 4-OI-resistant mouse microglia cell line (BV2). We conducted four classical behavioral experiments, namely the open field test, new object recognition test, Y maze test, and Morris water maze, to assess the emotional state and cognitive level of APPswe/PS1dE9 (referred to as APP/PS1) mice after 4-OI treatment. Hematoxylin and eosin (HE) staining, along with immunofluorescence staining, were performed to detect amyloid (Aß) deposition in mouse brain tissue. To explore the potential molecular mechanisms regulating the effects of 4-OI treatment, we performed RNA-SEQ and transcription factor prediction analyses. Additionally, mouse BV2 cells underwent Western blotting analysis to elucidate potential molecular mechanisms underlying the observed effects. RESULTS: We discovered that 4-OI exerts an inhibitory effect on neuroinflammation by promoting autophagy. This effect is attributed to the activation of the AMPK/mTOR/ULK1 pathway, achieved through enhanced phosphorylation of AMPK and ULK1, coupled with a reduction in mTOR phosphorylation. Furthermore, 4-OI significantly enhances neuronal recovery in the hippocampus and diminishes Aß plaque deposition in APP/PS1 mice, improved anxiety in mice, and ultimately led to improved cognitive function. CONCLUSIONS: Overall, the results of this study demonstrated that 4-OI improved cognitive deficits in AD mice, confirming the therapeutic effect of 4-OI on AD.


Assuntos
Doença de Alzheimer , Succinatos , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , RNA-Seq , Proteínas Quinases Ativadas por AMP/genética , Serina-Treonina Quinases TOR/genética , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética
5.
Environ Sci Pollut Res Int ; 31(13): 20246-20257, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38372921

RESUMO

An effective way to reduce herbicide quantity is to use adjuvants in order to optimize the amount of herbicide and improve its control efficiency. In order to screen for efficient herbicide tank-mix adjuvants, improve the control of weeds in maize fields, reduce the amount of effective ingredients, and improve the adsorption and digestion behavior of herbicides in soil, this study evaluated the synergistic effects and soil behavior of four types of tank-mix adjuvants combined with herbicides. Different types of adjuvants can enhance herbicide production. Surface tension was significantly reduced by 13% after the pesticide solution was applied with AgroSpred™ Prime. The contact angle with the foliar surface was significantly reduced and solution wettability improved using Atp Lus 245-LQ-(TH). The permeability of topramezone and atrazine in leaves of Amaranthus retroflexus L. and Digitaria sanguinalis (L.) Scop. was increased by 22-96% after adding either tank-mix adjuvant. The solution drying time and maximum retention on leaves were not affected by the tank-mix adjuvants. Ethyl and methylated vegetable oils can reduce the adsorption of topramezone in the soil, thus reducing its half-life in soil. The tank-mix adjuvants had no significant effect on soil dissipation or adsorption of atrazine. AgroSpred™ Prime and Atp Lus 245-LQ-(TH) have the best synergistic effect on topramezone and atrazine in the control of A. retroflexus L. and D. sanguinalis (L.) Scop. in maize fields.


Assuntos
Atrazina , Herbicidas , Pirazóis , Herbicidas/análise , Adjuvantes Imunológicos , Solo , Zea mays , Trifosfato de Adenosina
6.
Plant Dis ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243183

RESUMO

Alternanthera philoxeroides is a perennial herbaceous plant used as a forage crop (Wang et al. 2005) and is known to have medicinal properties. One of notable active components is flavonoids, which have been found to exhibit anti-Hepatitis B Virus activity (Li et al. 2016). In 2021, a leaf spot on A. philoxeroides was observed in the science and education experimental park of Hebei Agricultural University (38°49'38″ N, 115°26'39″ E). Initial symptoms included leaf tissue water loss, chloro-sis and elliptical lesions scattered across the leaf margin with further development leading to ellipse-shaped disease spots and leaf wilting (Fig. 1A). In the field, 50 plants of A. philoxeroides were randomly selected to investigate and quantify dis-ease. Incidence of leaf disease was approximately 25%, and the infected leaves ex-hibited an average affected area of about 20%. In order to identify the pathogen, three diseased plants were randomly selected from different areas. Stems and leaves of diseased plants were cut into pieces (2 to 3 mm × 5 mm) and disinfested with 1% sodium hypochlorite for 1 minute. After rinsing with sterile water three times, each lesion sample was isolated and purified on PDA at 25°C. Eventually, all samples pro-duced morphologically consistent colonies of pure strains. From the 9 isolates ob-tained, ZLQ-1 was selected as a representative isolate for further study. Colonies were initially white, turning gray from the centre, then gray-brown with cottony aerial hyphae, and finally growing black, stiff, round or irregular sclerotia (0.6 to 4.0 mm × 1.1 to 4.2 mm, n=50) (Fig1. B, C). ZLQ-1 exhibited branched conidia with en-larged apical cells. The conidia of this isolate were unicellular, ovoid or ellipsoid in shape, with dimensions ranging from 5.8 to 16.9 µm × 6.3 to 11.2 µm (n=50) (Fig. 1D). These morphological characteristics were consistent with Botrytis cinerea (Ellis, 1971). The genes of internal transcribed spacer (ITS), heat shock protein (HSP60), DNA-dependent RNA polymerase subunit II (RPB2), and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) were amplified with specific primers ITS1/ITS4, HSP60-F/HSP60-R, RPB2-F/RPB2-R and G3PDH-F/G3PDH-R (Aktaruzzaman et al., 2022). Sequences were deposited into GenBank with accession numbers ON479490 for ITS, ON572246 for G3PDH, ON572248 for HSP60, ON572247 for RPB2. BLASTn analysis showed that the ITS sequence shared 99.62% similarity to B. cinerea (CP009808), and the sequences of the other three nuclear protein-encoding genes (G3PDH, HSP60, and RPB2) showed at least 99.9% identity with the genome of B. ci-nerea (B05.10) (Staats et al. 2005). We have inoculated 10 healthy A. philoxeroides leaves with a suspension of 1x105 spores/mL, and used sterile water treatment as control (Aktaruzzaman et al., 2022). Each leaf was inoculated with 10 µL spore sus-pension. After 7 days in a controlled incubation environment (25℃, 40%RH), the plants inoculated with conidial suspensions displayed lesions covered in a gray-white mycelial layer, resembling those observed in the field (Fig. 1E-G). In con-trast, the plants inoculated with sterile water remained unaffected. Morphological and PCR analysis confirmed that the pathogen responsible for the observed symp-toms was B. cinerea. Koch's postulates were fulfilled as the same pathogen was con-sistently re-isolated from the inoculated leaves and confirmed to be B. cinerea through morphological and molecular methods. This is the first reported case of B. cinerea causing gray mold on A. philoxeroides in China. It is important to monitor and prevent B. cinerea infection during cultivation to ensure the production of healthy Chinese medicine and feed.

7.
Chemosphere ; 352: 141289, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281604

RESUMO

In this study, a sulfate-reducing bacterium, Clostridium thiosulfatireducens (CT) was reported and the performance and removal mechanism of Cr(VI) and Cd(II) removal were investigated. It is noteworthy that the dsrAB gene is absent in this strain, but the strain is capable of producing sulfide. The conversion rate of Cr(VI) by CT was 84.24 % at a concentration of 25 mg/L, and the conversion rate of Cd(II) was 94.19 % at a concentration of 28 mg/L. The complete genome is 6,106,624 bp and the genome consisted of a single chromosome. The GC content of the chromosomes was 29.65 %. The mechanism of heavy metal removal by CT bacteria mainly includes biosorption, electron transfer and redox, with reduction combined with S2- precipitation as the main pathway. The product characterization results showed that the formation of mainly ionic crystals and precipitates (CdS, Cd(OH)2, Cr(OH)3, Cr2O3) after adsorption. Genome-wide techniques have shown that the clearance of Cr(VI) and Cd(II) by CT is largely dependent on sulfate transport, sulfur metabolism, and energy metabolism to some extent. In addition, genes related to ATP binding, electron carrier activity, transporter protein genes, and DNA repair are also important factors to improve the heavy metal resistance and transformation ability of CT strains. Both the Fe-S cycle and the ROS-resistant system can enhance the electron transfer activity and thus slow down the damage of heavy metals to microorganisms. This study fills the gap in the understanding of the basic properties and heavy metal transformation mechanism of CT.


Assuntos
Cádmio , Clostridium , Metais Pesados , Elétrons , Metais Pesados/química , Cromo/química , Genômica , Sulfatos , Enxofre , Adsorção
8.
Rev Sci Instrum ; 95(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38294291

RESUMO

The traditional algorithms for generating 3D human point clouds often face challenges in dealing with issues such as phantom targets and target classification caused by electromagnetic multipath effects, resulting in a lack of accuracy in the generated point clouds and requiring manual labeling of the position of the human body. To address these problems, this paper proposes an adaptive method for generating 3D human point clouds based on 4D millimeter-wave radar (Self-Adaptive mPoint, SA-mPoint). This method estimates the rough human point cloud by considering micro-motion and respiration characteristics while combining the echo dynamic with static information. Furthermore, it enhances the density of point cloud generation. It reduces interference from multipath noise through multi-frame dynamic fusion and an adaptive density-based clustering algorithm based on the center points of humans. The effectiveness of the SA-mPoint algorithm is verified through experiments conducted using the TI Millimeter Wave Cascade Imaging Radar Radio Frequency Evaluation Module 77G 4D cascade radar to collect challenging raw data consisting of single-target and multi-target human poses in an open classroom setting. Experimental results demonstrate that the proposed algorithm achieves an average accuracy rate of 97.94% for generating point clouds. Compared to the popular TI-mPoint algorithm, it generates a higher number of point clouds on average (increased by 87.94%), improves the average accuracy rate for generating point clouds (increased by 78.3%), and reduces the running time on average (reduced by 11.41%). This approach exhibits high practicality and promising application prospects.


Assuntos
Corpo Humano , Radar , Humanos , Algoritmos , Movimento (Física) , Imagens de Fantasmas
9.
Int Immunopharmacol ; 126: 111312, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38043266

RESUMO

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, the activation of glial cells and neuroinflammation, especially the microglia-mediated neuroinflammation, has an essential role in the development and progression of AD. Therefore, the anti-inflammatory treatment is becoming a promising therapeutic strategy. Aucubin (Au) is a natural product derived from many plants with anti-inflammatory and antioxidant activities. Up to now, no research has been conducted to investigate the anti-inflammatory effects of Au and its neuroprotective quality on AD and the potential molecular mechanisms of its medical roles. In our study, the results of network pharmacology revealed the potential therapeutic effect of Au on AD. The results of studies in vivo showed that Au improved the behaviors, counteracted cognitive and memory deficits, and ameliorated AD-like pathological features of the mouse brain, e.g., the deposition of Aß plaques, neuronal damage, and inflammatory responses induced by glial cell overactivation, in APP/PS1 mice. The transcriptome sequencing further confirmed that the pathological symptoms of AD could be reversed by inhibiting the ERK/FOS axis to alleviate the inflammatory response. The in vitro experiments revealed that Au suppressed the BV2 cell activation, inhibited the phosphorylation of ERK1/2 and the expression of c-FOS, and reduced the LPS-induced inflammatory mediator production by BV2 cells and primary astrocytes. Our study suggested that Au exerted its neuroprotective effects by inhibiting the inflammatory responses, which could be a promising treatment of AD.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Doenças Neuroinflamatórias , Camundongos Transgênicos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Microglia
10.
IEEE Trans Biomed Eng ; 71(3): 780-791, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37738180

RESUMO

OBJECTIVE: The pharmacokinetic (PK) parameters estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide valuable information for clinical research and diagnosis. However, these estimated PK parameters suffer from many sources of variability. Thus, the estimation of the posterior distributions of these PK parameters could provide a way to simultaneously quantify the values and uncertainties of the PK parameters. Our objective is to develop an efficient and flexible method to more closely approximate and estimate the underlying posterior distributions of the PK parameters. METHODS: The normalizing flow model-based parameters distribution estimation neural network (FPDEN) is proposed to adaptively learn and estimate the posterior distributions of the PK parameters. The maximum likelihood estimation (MLE) loss is directly constructed based on the parameter distributions learned by the normalizing flow model, rather than pre-defined distributions. RESULTS: Experimental analysis shows that the proposed method can improve parameter estimation accuracy. Moreover, the uncertainty derived from the parameter distribution constitutes an effective indicator to exclude unreliable parametric results. A successful demonstration is the improved classification performance of the glioma World Health Organization (WHO) grading task, specifically in terms of distinguishing between low and high grades, as well as between Grade III and Grade IV. CONCLUSION: The FPDEN method offers improved accuracy for estimation of PK parameters and boosts the performance of the glioma grading task. SIGNIFICANCE: By enhancing the precision and reliability of DCE-MRI, the proposed method promotes its further applications in clinical practice.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Meios de Contraste , Reprodutibilidade dos Testes , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/patologia
11.
Redox Biol ; 69: 103007, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38150993

RESUMO

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors and the fourth leading cause of cancer-related death globally, which is characterized by complicated pathophysiology, high recurrence rate, and poor prognosis. Our previous study has demonstrated that disulfiram (DSF)/Cu could be repurposed for the treatment of HCC by inducing ferroptosis. However, the effectiveness of DSF/Cu may be compromised by compensatory mechanisms that weaken its sensitivity. The mechanisms underlying these compensatory responses are currently unknown. Herein, we found DSF/Cu induces endoplasmic reticulum stress with disrupted ER structures, increased Ca2+ level and activated expression of ATF4. Further studies verified that DSF/Cu induces both ferroptosis and cuproptosis, accompanied by the depletion of GSH, elevation of lipid peroxides, and compensatory increase of xCT. Comparing ferroptosis and cuproptosis, it is interesting to note that GSH acts at the crossing point of the regulation network and therefore, we hypothesized that compensatory elevation of xCT may be a key aspect of the therapeutic target. Mechanically, knockdown of ATF4 facilitated the DSF/Cu-induced cell death and exacerbated the generation of lipid peroxides under the challenge of DSF/Cu. However, ATF4 knockdown was unable to block the compensatory elevation of xCT and the GSH reduction. Notably, we found that DSF/Cu induced the accumulation of ubiquitinated proteins, promoted the half-life of xCT protein, and dramatically dampened the ubiquitination-proteasome mediated degradation of xCT. Moreover, both pharmacologically and genetically suppressing xCT exacerbated DSF/Cu-induced cell death. In conclusion, the current work provides an in-depth study of the mechanism of DSF/Cu-induced cell death and describes a framework for the further understanding of the crosstalk between ferroptosis and cuproptosis. Inhibiting the compensatory increase of xCT renders HCC cells more susceptible to DSF/Cu, which may provide a promising synergistic strategy to sensitize tumor therapy and overcome drug resistance, as it activates different programmed cell death.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Dissulfiram/farmacologia , Dissulfiram/química , Cobre/química , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Peróxidos Lipídicos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética
12.
Elife ; 122023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38149842

RESUMO

In this study, we proposed an efficient algorithm (X-LD) for estimating linkage disequilibrium (LD) patterns for a genomic grid, which can be of inter-chromosomal scale or of small segments. Compared with conventional methods, the proposed method was significantly faster, dropped from O(nm2) to O(n2m)-n the sample size and m the number of SNPs, and consequently we were permitted to explore in depth unknown or reveal long-anticipated LD features of the human genome. Having applied the algorithm for 1000 Genome Project (1KG), we found (1) the extended LD, driven by population structure, universally existed, and the strength of inter-chromosomal LD was about 10% of their respective intra-chromosomal LD in relatively homogeneous cohorts, such as FIN, and to nearly 56% in admixed cohort, such as ASW. (2) After splitting each chromosome into upmost of more than a half million grids, we elucidated the LD of the HLA region was nearly 42 folders higher than chromosome 6 in CEU and 11.58 in ASW; on chromosome 11, we observed that the LD of its centromere was nearly 94.05 folders higher than chromosome 11 in YRI and 42.73 in ASW. (3) We uncovered the long-anticipated inversely proportional linear relationship between the length of a chromosome and the strength of chromosomal LD, and their Pearson's correlation was on average over 0.80 for 26 1KG cohorts. However, this linear norm was so far perturbed by chromosome 11 given its more completely sequenced centromere region. Uniquely chromosome 8 of ASW was found most deviated from the linear norm than any other autosomes. The proposed algorithm has been realized in C++ (called X-LD) and is available at https://github.com/gc5k/gear2, and can be applied to explore LD features in any sequenced populations.


Assuntos
Genoma Humano , Polimorfismo de Nucleotídeo Único , Humanos , Desequilíbrio de Ligação , Genômica , Algoritmos
13.
Life Sci ; 335: 122261, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37951537

RESUMO

AIMS: To determine the availability and the potential molecular mechanisms underlying the therapeutic effect of omaveloxolone (RTA408) on Alzheimer's Disease (AD). MATERIALS AND METHODS: This study employed network pharmacology to assess the feasibility of drug treatment of AD. To determine the cognitive status and emotional state of APPswe/PS1dE9 (APP/PS1) mice after the RTA408 treatment, three classical behavioral experiments (water maze, Y-maze, and open field test) were conducted. Immunofluorescence and immunohistochemical staining were utilized to evaluate hippocampal neuronal status and amyloid (Aß) deposition in mice. RNA-seq and transcription factor prediction analyses were performed to explore the potential molecular mechanisms regulating the therapeutic effects of RTA408. Molecular docking was employed to predict the direct drug targets. To validate these molecular mechanisms, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and immunofluorescence analyses were performed in two instrumental cell lines, i.e., mouse hippocampal neuronal cells (HT22) and microglia (BV2). RESULTS: RTA408 was revealed with the capability to reduce Aß plaque deposition and to restore damaged neurons in the hippocampal region of APP/PS1 mice, ultimately leading to an improvement in cognitive function. This beneficial effect was achieved by balancing the STAT3 pathway. Specifically, RTA408 facilitated the activations of both STAT3/OXR1 and NRF2/ARE axes, thereby enhancing the compromised resistance in neurons to oxidative stress. RTA408 inhibited the NFκB/IL6/STAT3 pathway, effectively countering the neuroinflammation triggered by microglial activation. CONCLUSION: RTA408 is revealed with promising potential in the treatment of AD based on preclinical data.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Animais , Camundongos Transgênicos , Simulação de Acoplamento Molecular , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Presenilina-1/genética
14.
Front Mol Neurosci ; 16: 1276726, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965038

RESUMO

Introduction: Traumatic brain injury (TBI) is a major health concern worldwide. D-dimer levels, commonly used in the diagnosis and treatment of neurological diseases, may be associated with adverse events in patients with TBI. However, the relationship between D-dimer levels, TBI-related in-hospital complications, and long-term mortality in patients with TBI has not been investigated. Here, examined whether elevated D-dimer levels facilitate the prediction of in-hospital complications and mortality in patients with TBI. Methods: Overall, 1,338 patients with TBI admitted to our institute between January 2016 and June 2022 were retrospectively examined. D-dimer levels were assessed within 24 h of admission, and propensity score matching was used to adjust for baseline characteristics. Results: Among the in-hospital complications, high D-dimer levels were associated with electrolyte metabolism disorders, pulmonary infections, and intensive care unit admission (p < 0.05). Compared with patients with low (0.00-1.54 mg/L) D-dimer levels, the odds of long-term mortality were significantly higher in all other patients, including those with D-dimer levels between 1.55 mg/L and 6.35 mg/L (adjusted hazard ratio [aHR] 1.655, 95% CI 0.9632.843), 6.36 mg/L and 19.99 mg/L (aHR 2.38, 95% CI 1.416-4.000), and >20 mg/L (aHR 3.635, 95% CI 2.195-6.018; p < 0.001). D-dimer levels were positively correlated with the risk of death when the D-dimer level reached 6.82 mg/L. Conclusion: Overall, elevated D-dimer levels at admission were associated with adverse outcomes and may predict poor prognosis in patients with TBI. Our findings will aid in the acute diagnosis, classification, and management of TBI.

15.
BMC Anesthesiol ; 23(1): 393, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036983

RESUMO

BACKGROUND: We aimed to develop a nomogram that can be combined with point-of-care gastric ultrasound and utilised to predict postoperative nausea and vomiting (PONV) in adult patients after emergency surgery. METHODS: Imaging and clinical data of 236 adult patients undergoing emergency surgery in a university hospital between April 2022 and February 2023 were prospectively collected. Patients were divided into a training cohort (n = 177) and a verification cohort (n = 59) in a ratio of 3:1, according to a random number table. After univariate analysis and multivariate logistic regression analysis of the training cohort, independent risk factors for PONV were screened to develop the nomogram model. The receiver operating characteristic curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the prediction efficiency, accuracy, and clinical practicability of the model. RESULTS: Univariate analysis and multivariate logistic regression analysis showed that female sex, history of PONV, history of migraine and gastric cross-sectional area were independent risk factors for PONV. These four independent risk factors were utilised to construct the nomogram model, which achieved significant concordance indices of 0.832 (95% confidence interval [CI], 0.771-0.893) and 0.827 (95% CI, 0.722-0.932) for predicting PONV in the training and validation cohorts, respectively. The nomogram also had well-fitted calibration curves. DCA and CIC indicated that the nomogram had great clinical practicability. CONCLUSIONS: This study demonstrated the prediction efficacy, differentiation, and clinical practicability of a nomogram for predicting PONV. This nomogram may serve as an intuitive and visual guide for rapid risk assessment in patients with PONV before emergency surgery.


Assuntos
Nomogramas , Náusea e Vômito Pós-Operatórios , Adulto , Humanos , Feminino , Náusea e Vômito Pós-Operatórios/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Estômago
16.
J Agric Food Chem ; 71(49): 19324-19332, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38019973

RESUMO

The absorption, transport, and subcellular distribution of strobilurin fungicides (azoxystrobin, pyraclostrobin, and trifloxystrobin) have been studied in cucumbers. Under hydroponic laboratory conditions, pyraclostrobin and trifloxystrobin mainly accumulated in cucumber roots whereas azoxystrobin accumulated in cucumber leaves. In the subcellular distribution experiment, azoxystrobin mainly accumulated as a soluble component. Pyraclostrobin and trifloxystrobin accumulated more in the organelles and cell walls. Azoxystrobin and pyraclostrobin enter the root primarily through the apoplast pathway, whereas trifloxystrobin enters the root through the symplastic pathway. Azoxystrobin can be transported in cucumber through anion and cation channels, whereas pyraclostrobin and trifloxystrobin can be transported only through anion channels. This study has great significance in evaluating environmental risks and food safety.


Assuntos
Cucumis sativus , Fungicidas Industriais , Estrobilurinas , Fungicidas Industriais/farmacologia , Ânions
17.
iScience ; 26(11): 108041, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37876818

RESUMO

Accurate pathological classification and grading of gliomas is crucial in clinical diagnosis and treatment. The application of deep learning techniques holds promise for automated histological pathology diagnosis. In this study, we collected 733 whole slide images from four medical centers, of which 456 were used for model training, 150 for internal validation, and 127 for multi-center testing. The study includes 5 types of common gliomas. A subtask-guided multi-instance learning image-to-label training pipeline was employed. The pipeline leveraged "patch prompting" for the model to converge with reasonable computational cost. Experiments showed that an overall accuracy of 0.79 in the internal validation dataset. The performance on the multi-center testing dataset showed an overall accuracy to 0.73. The findings suggest a minor yet acceptable performance decrease in multi-center data, demonstrating the model's strong generalizability and establishing a robust foundation for future clinical applications.

18.
Anal Chem ; 95(40): 14842-14852, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37779463

RESUMO

Liquid chromatography-mass spectrometry (LC-MS) is widely used in the detection of pesticide residues. However, the detection sensitivity of low-polarity pesticides by commonly used electrospray ionization may be severely suppressed, which greatly affects the limit of detection and repeatability. Herein, a plasma-excited nebulizer gas-assisted electrospray ionization (PENG-ESI) device has been developed. By introducing the discharge plasma formed by Tesla coil into the electrospray nebulizer gas channel, the sensitivity of low-polarity pesticides was significantly increased while maintaining sensitivity to polar pesticides. Under the optimized conditions, the limit of detection for S-bioallethrin was achieved at the level of 100 pg/g with good linearity (R2 > 0.99) and precision (RSD ≤ 4.61%). The matrix effect of a series of spiked matrix samples is less than 13.1%. Finally, different pyrethroid pesticide residues were successfully analyzed without separation, highlighting that the technology has potential application prospects in food quality control, environmental monitoring, and other fields.

19.
Materials (Basel) ; 16(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37687496

RESUMO

In this paper, a dual-core photonic crystal fiber (DC-PCF) sensitivity sensor filled with magnetic liquid is introduced and investigated with the finite element method (FEM). To regulate the energy coupling involving the two cores, the magnetic fluid is filled into the pore between the two cores. To adjust the coupling between the supermodes in the DC-PCF, the refractive index (RI) of the air hole filled magnetic fluid may change due to the external magnetic field. This specifically created a magnetic fluid-filled DC-PCF; the magnetic fluid-filled hole is not used as the core for energy transmission, thus avoiding transmission loss. The dip wavelength and the magnetic field displayed an excellent linear connection between 80 and 260 Oe, depending on the numerical data. The detection sensitivity of the magnetic field reached 515.75 pm/Oe at a short fiber length of 482 µm. The designed magnetic fluid-filled DC-PCF has high sensitivity and small volume and has great application prospects in magnetic field detection in the medical and industrial fields.

20.
Chem Soc Rev ; 52(20): 7197-7261, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37743716

RESUMO

In the realm of biological research, the invention of super-resolution microscopy (SRM) has enabled the visualization of ultrafine sub-cellular structures and their functions in live cells at the nano-scale level, beyond the diffraction limit, which has opened up a new window for advanced biomedical studies to unravel the complex unknown details of physiological disorders at the sub-cellular level with unprecedented resolution and clarity. However, most of the SRM techniques are highly reliant on the personalized special photophysical features of the fluorophores. In recent times, there has been an unprecedented surge in the development of robust new fluorophore systems with personalized features for various super-resolution imaging techniques. To date, xanthene, cyanine, oxazine and BODIPY cores have been authoritatively utilized as the basic fluorophore units in most of the small-molecule-based organic fluorescent probe designing strategies for SRM owing to their excellent photophysical characteristics and easy synthetic acquiescence. Since the future of next-generation SRM studies will be decided by the availability of advanced fluorescent probes and these four fluorescent building blocks will play an important role in progressive new fluorophore design, there is an urgent need to review the recent advancements in designing fluorophores for different SRM methods based on these fluorescent dye cores. This review article not only includes a comprehensive discussion about the recent developments in designing fluorescent probes for various SRM techniques based on these four important fluorophore building blocks with special emphasis on their effective integration into live cell super-resolution bio-imaging applications but also critically evaluates the background of each of the fluorescent dye cores to highlight their merits and demerits towards developing newer fluorescent probes for SRM.

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