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1.
Nutrients ; 16(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38613050

RESUMO

Coenzyme Q10 (CoQ10) is a food active component with blood-pressure-improving properties. However, the association between the variety and quantity of different sources of dietary CoQ10 and new-onset hypertension remains uncertain. We aimed to investigate the associations between the diversity and quantity of CoQ10 intake from eight major food sources and new-onset hypertension risk. A total of 11,489 participants were included. Dietary intake was evaluated via three consecutive 24 h recalls and household food inventory. The diversity score of CoQ10 sources was calculated by the sum of food groups consumed in the ideal range. Cox proportional hazard models were used for evaluating their associations with hypertension. Model performance was assessed by ROC analyses and 200-times ten-fold cross-validation. The relationships between CoQ10 and hypertension were U-shaped for meat, egg, vegetable, and fruit sources, inverse J-shaped for fish, and nut sources, and L-shaped for dairy products sources (all p-values < 0.001). A higher diversity score was associated with lower hypertension risk (HR (95% CI): 0.66 (0.64, 0.69)). The mean areas under the ROC curves for 6, 12 and 18 years were 0.81, 0.80 and 0.78, respectively. There is a negative correlation between the diversity of CoQ10 with moderate intake from different sources and new-onset hypertension. One diversity score based on CoQ10 was developed.


Assuntos
Hipertensão , Ubiquinona/análogos & derivados , Animais , Humanos , Estudos de Coortes , Hipertensão/epidemiologia , Hipertensão/etiologia , Verduras
2.
Water Res ; 256: 121591, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38615606

RESUMO

Risk assessment and adaptation have become key focuses in the examination of urban flooding risk. In recent decades, global climate change has resulted in a high incidence of extreme weather events, notably flooding. This study introduces a spatial multi-indicator model developed for assessing flood risk at the urban agglomeration scale. A crucial addition to the model is the incorporation of an adaptive capacity within the IPCC risk framework. The model systematically considers various flood risk indicators related to the economic, social, and geographic environments of the central and southern Liaoning urban agglomeration (CSLN). It generates a spatial distribution map of integrated flood risk for multiple scenario combinations. Furthermore, the intricate relationship between different risk indicators and flood risk was analyzed using correlation analysis and the Light Gradient Boosting Machine model (Light GBM). The findings reveal notable variations in flood risk under different scenarios. The inclusion of vulnerability indicators increased flood risk by 33 %, while the subsequent inclusion of adaptive indicators decreased flood risk by 45 %. Dense populations and assets contribute to high flood risk, while adaptive capacity significantly mitigates urban flood risk. The framework adopted in this paper can be applied to other areas where urban agglomeration-scale flood risk assessment is needed, and can contribute to advancing scientific research on flood forecasting and mitigation.

3.
Front Endocrinol (Lausanne) ; 15: 1358311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606083

RESUMO

Background: Increasing evidence indicates that immune response underlies the pathology of type 2 diabetes (T2D). Nevertheless, the specific inflammatory regulators involved in this pathogenesis remain unclear. Methods: We systematically explored circulating inflammatory proteins that are causally associated with T2D via a bidirectional Mendelian randomization (MR) study and further investigated them in prevalent complications of T2D. Genetic instruments for 91 circulating inflammatory proteins were derived from a genome-wide association study (GWAS) that enrolled 14,824 predominantly European participants. Regarding the summary-level GWASs of type 2 diabetes, we adopted the largest meta-analysis of European population (74,124 cases vs. 824,006 controls) and a prospective nested case-cohort study in Europe (9,978 cases vs. 12,348 controls). Summary statistics for five complications of T2D were acquired from the FinnGen R9 repository. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted median and maximum likelihood methods were employed as supplementary analyses. Results from the two T2D studies were combined in a meta-analysis. Sensitivity analyses and phenotype-wide association studies (PheWAS) were performed to detect heterogeneity and potential horizontal pleiotropy in the study. Results: Genetic evidence indicated that elevated levels of TGF-α (OR = 1.16, 95% CI = 1.15-1.17) and CX3CL1 (OR = 1.30, 95% CI = 1.04-1.63) promoted the occurrence of T2D, and increased concentrations of FGF-21 (OR = 0.87, 95% CI = 0.81-0.93) and hGDNF (OR = 0.96, 95% CI = 0.95-0.98) mitigated the risk of developing T2D, while type 2 diabetes did not exert a significant influence on said proteins. Elevated levels of TGF-α were associated with an increased risk of ketoacidosis, neurological complications, and ocular complications in patients with T2D, and increased concentrations of FGF-21 were potentially correlated with a diminished risk of T2D with neurological complications. Higher levels of hGDNF were associated with an increased risk of T2D with peripheral vascular complications, while CX3CL1 did not demonstrate a significant association with T2D complications. Sensitivity analyses and PheWAS further ensure the robustness of our findings. Conclusion: This study determined four circulating inflammatory proteins that affected the occurrence of T2D, providing opportunities for the early prevention and innovative therapy of type 2 diabetes and its complications.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Estudos de Coortes , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Estudos Prospectivos , Fator de Crescimento Transformador alfa
4.
Artigo em Inglês | MEDLINE | ID: mdl-38557611

RESUMO

MiRNA has distinct physiological functions at various cellular locations. However, few effective computational methods for predicting the subcellular location of miRNA exist, thereby leaving considerable room for improvement. Accordingly, our study proposes the MGFmiRNAloc simplified molecular input line entry system (SMILES) format as a new approach for predicting the subcellular localization of miRNA. Additionally, the graphical convolutional network (GCN) technique was employed to extract the atomic nodes and topological structure of a single base, thereby constructing RNA sequence molecular map features. Subsequently, the channel attention and spatial attention mechanisms (CBAM) were designed to mine deeper for more efficient information. Finally, the prediction module was used to detect the subcellular localization of miRNA. The 10-fold cross-validation and independent test set experiments demonstrate that MGFmiRNAloc outperforms the most sophisticated methods. The results indicate that the new atomic level feature representation proposed in this study could overcome the limitations of small samples and short miRNA sequences, accurately predict the subcellular localization of miRNAs, and be extended to the subcellular localization of other sequences.

5.
Food Chem ; 448: 139137, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38569406

RESUMO

This study compared four biocolloids (sanxan, xanthan gum, curdlan, and guar gum) in different concentrations to replace NaCl in improving the recooking quality of salt free frozen cooked noodles (SF-FCNs). Sanxan outperformed NaCl and other biocolloids significantly improving the firmness (21.0%), chewiness (63.5%), and toughness (15.4%) of SF-FCNs after 10 freeze-thaw (FT) cycles. The results of the freezing-thawing curves showed SF-FCNs had prior FT stability when sanxan was added at 1.2%. Subsequently, the result of differential scanning calorimetry and nuclear magnetic resonance revealed sanxan reduced the content and mobility of freezable water while increasing the content of bound water. The scanning electron microscope, mercury intrusion, and optical microscopy analyses indicated that sanxan reduced the size and volume of ice crystals and the structural damage of SF-FCNs by controlling the water. The work contributes to a theoretical framework for enhancing SF-FCNs quality through precise water and ice crystal control.

6.
Environ Int ; 186: 108639, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38603815

RESUMO

Antimicrobial resistance is considered to be one of the biggest public health problems, and airborne transmission is an important but under-appreciated pathway for the spread of antibiotic resistance genes (ARGs) in the environment. Previous research has shown pharmaceutical factories to be a major source of ARGs and antibiotic resistant bacteria (ARB) in the surrounding receiving water and soil environments. Pharmaceutical factories are hotspots of antibiotic resistance, but the atmospheric transmission and its environmental risk remain more concerns. Here, we conducted a metagenomic investigation into the airborne microbiome and resistome in three pharmaceutical factories in China. Soil (average: 38.45%) and wastewater (average: 28.53%) were major contributors of airborne resistome. ARGs (vanR/vanS, blaOXA, and CfxA) conferring resistance to critically important clinically used antibiotics were identified in the air samples. The wastewater treatment area had significantly higher relative abundances of ARGs (average: 0.64 copies/16S rRNA). Approximately 28.2% of the detected airborne ARGs were found to be associated with plasmids, and this increased to about 50% in the wastewater treatment area. We have compiled a list of high-risk airborne ARGs found in pharmaceutical factories. Moreover, A total of 1,043 viral operational taxonomic units were identified and linked to 47 family-group taxa. Different CRISPR-Cas immune systems have been identified in bacterial hosts in response to phage infection. Similarly, higher phage abundance (average: 2451.70 PPM) was found in the air of the wastewater treatment area. Our data provide insights into the antibiotic resistance gene profiles and microbiome (bacterial and non-bacterial) in pharmaceutical factories and reveal the potential role of horizontal transfer in the spread of airborne ARGs, with implications for human and animal health.

7.
Mol Pharm ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606716

RESUMO

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

8.
Chem Commun (Camb) ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38595270

RESUMO

Two typical Cu-based complex catalysts with piperazine (PR) and p-phenylenediamine (pPDA) ligands were designed to elucidate whether the ligands can tailor the reduction behavior of the Cu species and thus modulate their electrochemical CO2 reduction reaction (eCO2RR) activity. Specifically, Cu-PR underwent a significant in situ transformation into Cu nanoparticles enriched with a Cuδ+/Cu0 interface for high eCO2RR activity, compared to Cu-pPDA. This finding reveals the importance of ligand engineering in modulating the eCO2RR performance of Cu-based complexes.

9.
Microb Biotechnol ; 17(4): e14454, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568756

RESUMO

This study investigates the effectiveness of an exopolysaccharide (EPS)-producing strain (Lactiplantibacillus plantarum L75) alone or in combination with Saccharomyces cerevisiae on the fermentation characteristics, antioxidant capacities and microbial community successions of oat silage stored at various temperatures. A rapid decrease in pH and lactic acid accumulation was observed in silages treated with L. plantarum and S. cerevisiae (LS) as early as 3 days of ensiling (p < 0.05). Over the ensiling period of 7-60 days, L. plantarum (L)-inoculated groups showed the lowest pH, lowest ammonia nitrogen and the highest amount of lactic acid regardless of the storage temperatures. When the oat silage was stored at 15°C, LS-inoculated group exhibited a higher superoxide dismutase (SOD) activity than control and L-inoculated group. Furthermore, the proportion of Lactiplantibacillus in the combined inoculation group increased by 65.42% compared to the L-inoculated group (33.26%). Fungal community data revealed abundant Penicillium carneum in the control and L-inoculated groups stored at 15°C. Conclusively, these results showed that combined inoculation of L. plantarum L75 and S. cerevisiae improved the fermentation quality of oat silage at 15°C, thus proposing a technique for enhancing the fermentation quality of silage in regions with low temperatures during harvest season.


Assuntos
Lactobacillus plantarum , Silagem , Silagem/microbiologia , Saccharomyces cerevisiae , Lactobacillus , Avena , Fermentação , Temperatura , Ácido Láctico
10.
Food Microbiol ; 121: 104499, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38637070

RESUMO

In this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.


Assuntos
Monascus , Fermentação , Monascus/genética , Monascus/metabolismo , Pigmentos Biológicos/metabolismo , Consórcios Microbianos , Glicólise
11.
MedComm (2020) ; 5(4): e543, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38585233

RESUMO

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR-1246 levels. Specially, miR-1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR-1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR-1246 in vivo. Collectively, our findings suggest that miR-1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA-targeted gene activation and the potential of miR-1246 for osteosarcoma metastasis therapy.

12.
Heliyon ; 10(6): e28077, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515727

RESUMO

The medicinal plant Spatholobus suberectus Dunn is easily exposed to shade stress during growth, but its shade responses and shade stress resistant mechanisms have not been clarified. In this study, shade treatments including four attenuated sunlight intensities (100%, 60%, 40%, and 10%) and three shade durations (30 d, 45 d, and 60 d) were applied to S. suberectus. The shade-induced morphological indicators, phytohormonal regulations, metabolic flavonoids contents, transcriptomic flavonoid pathway gene expressions, and stress physiological changes of S. suberectus were analyzed. The putative promoter cis-regulatory elements (CREs) of 18 flavonoid biosynthetic pathway genes were identified. Results showed the stem growth indicators of S. suberectus were better at 40% light intensity. Phytohormones were involved in the shade-induced responses. Short-term shade (30 d) increased total flavonoids, gallated catechins and especially epigallocatechin gallate contents and favored for boosting medicinal value. Long-term shade (45 d, 60 d) tended to decrease flavonoids. The shade-induced flavonoids changes were attributed to their corresponding biosynthesizing genes expression variations. The high antioxidant capacity and the presence of phytohormone-, stress-, and development-related CREs provided the basis for stress resistance. In conclusion, the multiple responses under shade and the CREs analysis elucidated S. suberectus' shade tolerance.

13.
Int J Biol Macromol ; 265(Pt 2): 130903, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508549

RESUMO

With the development of gut microbiota-specific interventions for mental disorders, the interactions between plant polysaccharides and microbiota in the intestinal and their consequent effects are becoming increasingly important. In this review, we discussed the role of plant polysaccharides in improving various mental disorders via the microbiota-gut-brain axis. The chemical and structural characteristics and metabolites of these plant polysaccharides were summarised. Plant polysaccharides and their metabolites have great potential for reshaping gut microbiota profiles through gut microbiota-dependent fermentation. Along the microbiota-gut-brain axis, the consequent pharmacological processes that lead to the elimination of the symptoms of mental disorders include 1) regulation of the central monoamine neurotransmitters, amino acid transmitters and cholinergic signalling system; 2) alleviation of central and peripheral inflammation mainly through the NLRP3/NF-κB-related signalling pathway; 3) inhibition of neuronal apoptosis; and 4) enhancement of antioxidant activities. According to this review, monosaccharide glucose and structure -4-α-Glcp-(1→ are the most potent compositions of the most reported plant polysaccharides. However, the causal structure-activity relationship remains to be extensively explored. Moreover, mechanistic elucidation, safety verification, and additional rigorous human studies are expected to advance plant polysaccharide-based product development targeting the microbiota-gut-brain axis for people with mental disorders.


Assuntos
Microbioma Gastrointestinal , Transtornos Mentais , Microbiota , Humanos , Eixo Encéfalo-Intestino , Transtornos Mentais/tratamento farmacológico , Polissacarídeos/farmacologia
14.
Antioxidants (Basel) ; 13(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38539839

RESUMO

Unconventional feed, which is abundant in China, contains anti-nutritional factors and toxins; however, these can be greatly reduced with microbial fermentation, thus improving the nutrient content of the feed, enhancing animal appetites, and ultimately significantly improving the intestinal health and growth performance of animals. When oxidative stress occurs, fermented feed can effectively reduce the damage caused by stress to the gastrointestinal tract, accelerate the removal of gastrointestinal abnormalities, improve the ability to resist intestinal stress, and ensure the efficient production of animals. This review introduces the application of unconventional fermented feed in animal production, and expounds upon the function of unconventional fermented feed in animals with oxidative stress symptoms, so as to provide a theoretical reference for the development and application of unconventional fermented feed in antioxidative stress reduction.

15.
BMC Bioinformatics ; 25(1): 108, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475723

RESUMO

RNA-protein interaction (RPI) is crucial to the life processes of diverse organisms. Various researchers have identified RPI through long-term and high-cost biological experiments. Although numerous machine learning and deep learning-based methods for predicting RPI currently exist, their robustness and generalizability have significant room for improvement. This study proposes LPI-MFF, an RPI prediction model based on multi-source information fusion, to address these issues. The LPI-MFF employed protein-protein interactions features, sequence features, secondary structure features, and physical and chemical properties as the information sources with the corresponding coding scheme, followed by the random forest algorithm for feature screening. Finally, all information was combined and a classification method based on convolutional neural networks is used. The experimental results of fivefold cross-validation demonstrated that the accuracy of LPI-MFF on RPI1807 and NPInter was 97.60% and 97.67%, respectively. In addition, the accuracy rate on the independent test set RPI1168 was 84.9%, and the accuracy rate on the Mus musculus dataset was 90.91%. Accordingly, LPI-MFF demonstrated greater robustness and generalization than other prevalent RPI prediction methods.


Assuntos
Aprendizado Profundo , RNA Longo não Codificante , Animais , Camundongos , RNA Longo não Codificante/química , Algoritmo Florestas Aleatórias , Redes Neurais de Computação , Aprendizado de Máquina , Biologia Computacional/métodos
16.
Huan Jing Ke Xue ; 45(2): 1004-1014, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471938

RESUMO

To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plants, samples of the surface soil, soil column, wastewater treatment process water, ground water, and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samples, and the maximum concentrations at each sampling point in the surface soil, soil column, residue dregs, wastewater treatment process water, and groundwater were 420 ng·g-1, 595 ng·g-1, 139 ng·g-1, 1 151 ng·L-1, and 6.65 ng·L-1, respectively. Most of the antibiotics were found in the surface soil, showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazine, sulfaquinoxaline, tetracycline, chlorotetracycline, and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.


Assuntos
Antibacterianos , Poluentes Químicos da Água , Antibacterianos/análise , Poluentes Químicos da Água/análise , Águas Residuárias , Água/análise , China , Solo , Preparações Farmacêuticas
18.
Small ; : e2311782, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497813

RESUMO

With the development of electric vehicles, exploiting anode materials with high capacity and fast charging capability is an urgent requirement for lithium-ion batteries (LIBs). Borophene, with the merits of high capacity, high electronic conductivity and fast diffusion kinetics, holds great potential as anode for LIBs. However, it is difficult to fabricate for the intrinsic electron-deficiency of boron atom. Herein, heterogeneous-structured MoB2 (h-MoB2 ) with amorphous shell and crystalline core, is prepared by solid phase molten salt method. As demonstrated, crystalline core can encapsulate the honeycomb borophene within two adjacent Mo atoms, and amorphous shell can accommodate more lithium ions to strengthen the lithium storage capacity and diffusion kinetics. According to theoretical calculations, the lithium adsorption energy in MoB2 is about -2.7 eV, and the lithium diffusion energy barrier in MoB2 is calculated to be 0.199 eV, guaranteeing the enhanced adsorption capability and fast diffusion kinetic behavior of Li+ ions. As a result, h-MoB2 anode presents high capacity of 798 mAh g-1 at 0.1 A g-1 , excellent rate performance of 183 mAh g-1 at 5 A g-1 and long-term cyclic stability for 1200 cycles. This work may inspire ideas for the fabrication of borophene analogs and two-dimensional metal borides.

19.
JHEP Rep ; 6(4): 101019, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38455470

RESUMO

Background & Aims: Recent studies have implicated platelets, particularly α-granules, in the development of non-alcoholic steatohepatitis (NASH). However, the specific mechanisms involved have yet to be determined. Notably, thrombospondin 1 (TSP1) is a major component of the platelet α-granules released during platelet activation. Hence, we aimed to determine the role of platelet-derived TSP1 in NASH. Methods: Platelet-specific Tsp1 knockout mice (TSP1Δpf4) and their wild-type littermates (TSP1F/F) were used. NASH was induced by feeding the mice with a diet enriched in fat, sucrose, fructose, and cholesterol (AMLN diet). A human liver NASH organoid model was also employed. Results: Although TSP1 deletion in platelets did not affect diet-induced steatosis, TSP1Δpf4 mice exhibited attenuated NASH and liver fibrosis, accompanied by improvements in plasma glucose and lipid homeostasis. Furthermore, TSP1Δpf4 mice showed reduced intrahepatic platelet accumulation, activation, and chemokine production, correlating with decreased immune cell infiltration into the liver. Consequently, this diminished proinflammatory signaling in the liver, thereby mitigating the progression of NAFLD. Moreover, in vitro data revealed that co-culturing TSP1-deficient platelets in a human liver NASH organoid model attenuated hepatic stellate cell activation and NASH progression. Additionally, TSP1-deficient platelets play a role in regulating brown fat endocrine function, specifically affecting Nrg4 (neuregulin 4) production. Crosstalk between brown fat and the liver may also influence the progression of NAFLD. Conclusions: These data suggest that platelet α-granule-derived TSP1 is a significant contributor to diet-induced NASH and fibrosis, potentially serving as a new therapeutic target for this severe liver disease. Impact and implications: Recent studies have implicated platelets, specifically α-granules, in the development of non-alcoholic steatohepatitis, yet the precise mechanisms remain unknown. In this study, through the utilization of a tissue-specific knockout mouse model and human 3D liver organoid, we demonstrated that platelet α-granule-derived TSP1 significantly contributes to diet-induced non-alcoholic steatohepatitis and fibrosis. This contribution is, in part, attributed to the regulation of intrahepatic immune cell infiltration and potential crosstalk between fat and the liver. These findings suggest that platelet-derived TSP1 may represent a novel therapeutic target in non-alcoholic fatty liver disease.

20.
BMC Med Educ ; 24(1): 305, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504238

RESUMO

BACKGROUND: Laboratory biosafety should be a priority in all healthcare institutions. In traditional laboratory safety teaching students typically receive knowledge passively from their teachers without active involvement. The combination of experiential learning and mobile learning may provide students with greater engagement, retention, and application of knowledge. To address this issue, we developed and conducted a convergent mixed methods study to assess the feasibility and usability of a WeChat mini program (WMP) named WeMed for laboratory biosafety education for medical laboratory students at Guangzhou Medical University (GMU). METHODS: The study was conducted between November 2022 and October 2023 among second-year undergraduate students at GMU. It involved the concurrent collection, analysis, and interpretation of both qualitative and quantitative data to assess feasibility and usability. In the quantitative strand, two evaluations were conducted via online surveys from students (n = 67) after a four-week study period. The System Usability Scale (SUS) was used to evaluate usability, while self-developed questions were used to assess feasibility. Additionally, a knowledge test was administered 6 months after the program completion. In the qualitative strand, fourteen semi-structured interviews were conducted, whereby a reflexive thematic analysis was utilized to analyze the interview data. RESULTS: The overall SUS score is adequate (M = 68.17, SD = 14.39). The acceptability of the WeMed program is in the marginal high range. Most students agreed that WeMed was useful for learning biosafety knowledge and skills (13/14, 93%), while 79% (11/14) agreed it was easy to use and they intended to continue using it. After 6 months, a significant difference in the knowledge test scores was observed between the WeMed group (n = 67; 2nd year students) and the traditional training group (n = 90; 3rd year students). However, the results should be interpreted cautiously due to the absence of a pretest. CONCLUSION: The combination of experiential learning and mobile learning with WMP is a feasible tool for providing laboratory biosafety knowledge and skills. Ongoing improvements should be made in order to increase long-term acceptance.


Assuntos
Estudantes de Medicina , Humanos , Contenção de Riscos Biológicos , Estudos de Viabilidade , Universidades , Aprendizagem
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