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1.
Traffic Inj Prev ; : 1-8, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629829

RESUMO

OBJECTIVE: Jaywalking is an important cause of pedestrian-related automobile accidents. Exploring the factors that influence jaywalking behavior and suggesting appropriate improvement measures are critical for reducing automobile accidents involving pedestrians. METHODS: This study divided traffic situations into high-risk and low-risk situations. Each situation contained three visual attention cues: vehicle, traffic light, and group behavior. Based on this, the role of visual cues in guiding pedestrians' attention and influencing their decisions during jaywalking was examined. Sixty participants, with an average age of 19, were recruited. They were shown 84 crosswalk videos randomly while their crossing decisions and eye movement data were recorded. RESULTS: In low-risk situations, pedestrians spent more attention on group behavioral cues when making jaywalking decisions. The rate of jaywalking increased with the number of other jaywalking pedestrians. In high-risk situations, the pedestrians' total fixation duration at vehicle hazard cues was longer when making jaywalking decisions, and the jaywalking rate decreased. CONCLUSIONS: The results indicate that pedestrians' jaywalking decisions were based on other pedestrians' illegal crossing cues and automatic associative processes in low-risk situations. The higher the number of people crossing the street, the higher the number of pedestrians illegally crossing the road. In high-risk situations, pedestrians paid more attention to vehicle hazard cues before making jaywalking decisions, and fewer illegal crossings. The jaywalking decisions were based on a risk assessment, a controlled analytical process. The results verify the effect of visual cues on pedestrians' attentional guidance and decision-making in different traffic situations, as well as the effectiveness of visual attention in predicting decision intention. The findings provide a theoretical basis and data reference for pedestrian safety education and constructing an intelligent driving pedestrian trajectory prediction model.

2.
Bull Entomol Res ; : 1-10, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623047

RESUMO

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.

3.
Mol Cell ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38569554

RESUMO

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

4.
Macromol Rapid Commun ; : e2400151, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635599

RESUMO

The rapid growth of the Internet of Things and wearable sensors has led to advancements in monitoring technology in the field of health. One such advancement is the development of wearable respiratory sensors, which offer a new approach to real-time respiratory monitoring compared to traditional methods. However, the energy consumption of these sensors raises concerns about environmental pollution. To address the issue, this study proposes the use of a triboelectric nanogenerator (TENG) as a sustainable energy source. The electrical conductivity of the TENG is improved by incorporating chitosan and carbon nanotubes (CNTs), with the added benefit of chitosan's biodegradability reducing negative environmental impact. A wireless intelligent respiratory monitoring system (WIRMS) is then introduced, which utilizes a degradable triboelectric nanogenerator for real-time respiratory monitoring, diagnosis and prevention of obstructive respiratory diseases. WIRMS offers stable and highly accurate respiratory information monitoring, while enabling real-time and non-destructive transmission of information. Additionally, machine learning technology is employed for sleep respiration state analysis. The potential applications of WIRMS extend to wearables, medical monitoring and sports monitoring, thereby presenting innovative ideas for modern medical and sports monitoring. This article is protected by copyright. All rights reserved.

5.
Materials (Basel) ; 17(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612053

RESUMO

Diffusion plays a vital role during the fabrication of many materials. It is a well-known fact that stress can influence diffusion behavior. In order to optimize material processing techniques, a quantitative evaluation of the effect of stress on diffusion is essentially required. By analyzing the free energy change in a Ti-O system during diffusion, a phase-field model was developed to address this issue. Using this model, the diffusion of oxygen atoms in pure titanium under different stress states was investigated. It was observed that the true equilibrium concentration of oxygen was proportional to its hydrostatic pressure. Tensile stress can increase the oxygen concentration. This raise in concentration decreased with temperature. However, the promotion of diffusion can be attained in deeper regions at a higher temperature. On the contrary, compressive stress inhibited the diffusion of oxygen in pure titanium. Under a certain compressive stress, the decrease in the oxygen concentration at the surface layer was more significant at a lower temperature, while a decrease could be observed at a deeper distance from the surface at a higher temperature. A thermodynamic explanation of the effect of stress on diffusion was given based on the proposed phase-field model.

6.
iScience ; 27(4): 109615, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38632997

RESUMO

In the smart era, big data analysis based on sensor units is important in intelligent motion. In this study, a dance sports and injury monitoring system (DIMS) based on a recyclable flexible triboelectric nanogenerator (RF-TENG) sensor module, a data processing hardware module, and an upper computer intelligent analysis module are developed to promote intelligent motion. The resultant RF-TENG exhibits an ultra-fast response time of 17 ms, coupled with robust stability demonstrated over 4200 operational cycles, with 6% variation in output voltage. The DIMS enables immersive training by providing visual feedback on sports status and interacting with virtual games. Combined with machine learning (K-nearest neighbor), good classification results are achieved for ground-jumping techniques. In addition, it shows some potential in sports injury prediction (i.e., ankle sprains, knee hyperextension). Overall, the sensing system designed in this study has broad prospects for future applications in intelligent motion and healthcare.

7.
Arch Insect Biochem Physiol ; 115(4): e22114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659314

RESUMO

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.


Assuntos
Blattellidae , Proteínas de Insetos , Oviposição , Pigmentação , Interferência de RNA , Animais , Blattellidae/genética , Blattellidae/fisiologia , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Masculino , Pigmentação/genética , Corte , Melaninas/metabolismo , Comportamento Sexual Animal
8.
J Adv Res ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38609050

RESUMO

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

9.
Saf Health Work ; 15(1): 33-41, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38496280

RESUMO

Background: Dust generated during the processing of building materials enterprises can pose a serious health risk. The study aimed to compare and analyze the results of ART and the Monte Carlo model for the dust exposure assessment in building materials enterprises, to derive the application scope of the two models. Methods: First, ART and the Monte Carlo model were used to assess the exposure to dust in each of the 15 building materials enterprises. Then, a comparative analysis of the exposure assessment results was conducted. Finally, the model factors were analyzed using correlation analysis and the scope of application of the models was determined. Results: The results show that ART is mainly influenced by four factors, namely, localized controls, segregation, dispersion, surface contamination, and fugitive emissions, and applies to scenarios where the workplace information of the building materials enterprises is specific and the average dust concentration is greater than or equal to 1.5 mg/m3. The Monte Carlo model is mainly influenced by the dust concentration in the workplace of building materials enterprises and is suitable for scenarios where the dust concentration in the workplace of the building materials enterprises is relatively uniform and the average dust concentration is less than or equal to 6mg/m3. Conclusion: ART is most accurate when workplace information is specific and average dust concentration is > 1.5 mg/m3; whereas, The Monte Carlo model is the best when dust concentration is homogeneous and average dust concentration is < 6 mg/m3.

10.
Vaccines (Basel) ; 12(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38543885

RESUMO

Vascular cognitive impairment (VCI) encompasses a wide range of cognitive disorders stemming from cerebrovascular issues, such as strokes or small vessel disease. These conditions often pose challenges to traditional diagnostic approaches due to their multifactorial nature and varied clinical presentations. Recently, next-generation sequencing (NGS) technologies have provided detailed analyses of long non-coding RNAs (lncRNAs) in the molecular pathobiology of VCI. These new findings help with molecular-based diagnostics and treatments of VCI. Within this realm, the concept of immune modulation, especially through specific vaccinations, emerges as a promising therapeutic strategy in VCI mitigation. In this review, we comprehensively elucidate the function of lncRNAs in VCI, emphasizing the advanced understanding of VCI's molecular underpinnings made possible through NGS technologies. Significant focus is placed on the immune system's role in VCI, particularly the neuroinflammatory processes which are consequential to cerebrovascular abnormalities. We believe that lncRNAs participate in regulating these immunological pathways, potentially guiding the development of vaccines targeting VCI. In this context, we propose a novel perspective: using knowledge about lncRNA profiles and functions to guide vaccine development, we can potentially exploit the body's immune response to mitigate or prevent VCI. This approach has the potential to revolutionize VCI management by introducing targeted immunization strategies informed by molecular signatures, a concept that remains largely unexplored in current research endeavors. In addition, we summarize current progress and propose future directions, advocating for robust, interdisciplinary studies to validate the potential intersections between lncRNA landscapes, VCI pathology, and immunology. This review aims to spur innovative research and promote the development of lncRNA-informed vaccine strategies as proactive interventions against the cognitive consequences of VCI.

11.
Front Public Health ; 12: 1352057, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550319

RESUMO

Background: Dry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients' quality of life. The association between air pollution and the risk of dry eye disease remains uncertain. Methods: Data on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution. Results: Among the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 µg/m3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 µm (PM2.5) showed a significant association with DED outpatient visits in males and the 19-59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season. Conclusion: The noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndromes do Olho Seco , Humanos , Masculino , Feminino , Pacientes Ambulatoriais , Qualidade de Vida , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/etiologia , China/epidemiologia
12.
Sci Total Environ ; 926: 171286, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38428617

RESUMO

Vacuolar-type (H+)-ATPase (vATPase) is a conserved multi-subunit eukaryotic enzyme composed of 14 subunits that form a functional complex consisting of an ATP-hydrolytic domain (V1) and a proton-translocation domain (V0). ATP hydrolysis and subsequent H+ translocation rely heavily on a fully assembled V1/V0 complex. Since vATPase is crucial for insect survival, it is a viable molecular target for pest control. However, detailed functional analyses of the 14 subunits and their suitability for pest control have not been fully explored in a single insect species. In this study, we identified 22 vATPase subunit transcripts that correspond to 13 subunits (A1, A2, B, C, D, E, F, G, H, a1, a2, c and d) in the white-backed planthopper (WBPH), Sogatella furcifera, a major hemipteran pest of rice. RNAi screens using microinjection and spray-based methods revealed that the SfVHA-F, SfVHA-a2 and SfVHA-c2 subunits are critical. Furthermore, star polymer (SPc) nanoparticles were utilized to conduct spray-induced and nanoparticle-delivered gene silencing (SI-NDGS) to evaluate the pest control efficacy of RNAi targeting the SfVHA-F, SfVHA-a2 and SfVHA-c2 transcripts. Target mRNA levels and vATPase enzymatic activity were both reduced. Honeydew excreta was likewise reduced in WBPH treated with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. To assess the environmental safety of the nanoparticle-wrapped dsRNAs, Cyrtorhinus lividipennis Reuter, a major natural enemy of planthoppers, was also sprayed with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. Post-spray effects of dsSfVHA-a2 and dsSfVHA-c2 on C. lividipennis were innocuous. This study identifies SfVHA-a2 and SfVHA-c2 as promising targets for biorational control of WBPH and lays the foundation for developing environment-friendly RNAi biopesticides.


Assuntos
Hemípteros , Heterópteros , Oryza , Praguicidas , Animais , Oryza/genética , Interferência de RNA , Medição de Risco , Trifosfato de Adenosina
13.
Colloids Surf B Biointerfaces ; 237: 113835, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479260

RESUMO

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and ß-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO ß-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.


Assuntos
Alho , Hipercolesterolemia , Hiperlipidemias , Óleos Voláteis , beta-Ciclodextrinas , Camundongos , Animais , Lipossomos , Óleos Voláteis/farmacologia , Antioxidantes
14.
bioRxiv ; 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38464138

RESUMO

Mortality rate increases with age and can accelerate upon extrinsic or intrinsic damage to individuals. Identifying factors and mechanisms that curb population mortality rate has wide-ranging implications. Here, we show that targeting the VHL-1 (Von Hippel-Lindau) protein suppresses C. elegans mortality caused by distinct factors, including elevated reactive oxygen species, temperature, and APOE4, the genetic variant that confers high risks of neurodegeneration in Alzheimer's diseases and all-cause mortality in humans. These mortality factors are of different physical-chemical nature, yet result in similar cellular dysfunction and damage that are suppressed by deleting VHL-1. Stabilized HIF-1 (hypoxia inducible factor), a transcription factor normally targeted for degradation by VHL-1, recapitulates the protective effects of deleting VHL-1. HIF-1 orchestrates a genetic program that defends against mitochondrial abnormalities, excess oxidative stress, cellular proteostasis dysregulation, and endo-lysosomal rupture, all events that lead to mortality. Genetic inhibition of Vhl also alleviates cerebral vascular injury and synaptic lesions in APOE4 mice, supporting an evolutionarily conserved mechanism. Collectively, we identify the VHL-HIF axis as a potent modifier of APOE4 and propose that targeting VHL-HIF in non-proliferative animal tissues may suppress tissue injuries and mortality by broadly curbing cellular damage.

15.
Mar Life Sci Technol ; 6(1): 1-14, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38433969

RESUMO

The electric catfish (Malapterurus electricus), belonging to the family Malapteruridae, order Siluriformes (Actinopterygii: Ostariophysi), is one of the six branches that has independently evolved electrical organs. We assembled a 796.75 Mb M. electricus genome and anchored 88.72% sequences into 28 chromosomes. Gene family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate receptors. Convergent evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like (arhgef4), which is associated with G-protein coupled receptor (GPCR) signaling pathway, underwent adaptive parallel evolution. Gene identification suggests visual degradation in catfishes, and an important role for taste in environmental adaptation. Our findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00197-8.

16.
BMC Cancer ; 24(1): 249, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389042

RESUMO

BACKGROUND: Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). METHODS: A total of 506 patients with ESCC were enrolled in this study. Harrell's concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. RESULTS: Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone. CONCLUSIONS: In conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Hemostáticos , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Prognóstico , Neoplasias Esofágicas/patologia , Fibrinogênio , Linfócitos/patologia , Biomarcadores , Neutrófilos/patologia , Estudos Retrospectivos
17.
Int J Biol Macromol ; 262(Pt 1): 129970, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325689

RESUMO

In humans and animals, the pyruvate dehydrogenase kinase (PDK) family proteins (PDKs 1-4) are excessively activated in metabolic disorders such as obesity, diabetes, and cancer, inhibiting the activity of pyruvate dehydrogenase (PDH) which plays a crucial role in energy and fatty acid metabolism and impairing its function. Intervention and regulation of PDH activity have become important research approaches for the treatment of various metabolic disorders. In this study, a small molecule (g25) targeting PDKs and activating PDH, was identified through multi-level computational screening methods. In vivo and in vitro experiments have shown that g25 activated the activity of PDH and reduced plasma lactate and triglyceride level. Besides, g25 significantly decreased hepatic fat deposition in a diet-induced obesity mouse model. Furthermore, g25 enhanced the tumor-inhibiting activity of cisplatin when used in combination. Molecular dynamics simulations and in vitro kinase assay also revealed the specificity of g25 towards PDK2. Overall, these findings emphasize the importance of targeting the PDK/PDH axis to regulate PDH enzyme activity in the treatment of metabolic disorders, providing directions for future related research. This study provides a possible lead compound for the PDK/PDH axis related diseases and offers insights into the regulatory mechanisms of this pathway in diseases.


Assuntos
Doenças Metabólicas , Neoplasias , Animais , Camundongos , Humanos , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Fosforilação , Doenças Metabólicas/tratamento farmacológico , Obesidade
18.
Biochem Biophys Res Commun ; 701: 149589, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309152

RESUMO

OBJECTIVE: To evaluate the role of PRDX2 in nonalcoholic steatohepatitis (NASH). METHODS: NASH was induced in wild-type (WT) mice and liver-specific PRDX2 knockout (PRDX2 LKO) mice that were fed a methionine-choline deficient diet (MCD) for 5 weeks. Assessments of PRDX2 LKO's impact on the pathogenesis of NASH include histological analyses, quantitative PCR (q-PCR), western blotting (WB), and RNA sequencing (RNA-Seq). RESULTS: PRDX2 LKO mice exhibited a significant increase in hepatic lipid accumulation and inflammation compared to WT mice after MCD feeding. PRDX2 KO markedly elevated circulating levels of aspartate aminotransferase (AST) and the pro-inflammatory signaling pathways within the liver. There was a notable increase in the activities of signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa B (NF-кB). We also found that PRDX2 KO significantly increased the extent of lipid peroxidation in the liver, most likely owing to the impaired peroxidase activity of PRDX2. Of interest, these findings were observed only in MCD-fed female mice, suggesting the sexual dimorphism of PRDX2 KO in MCD-induced NASH. CONCLUSION: PRDX2 deficiency increases MCD-induced NASH in female mice, suggesting a protective role for PRDX2.


Assuntos
Deficiência de Colina , Hepatopatia Gordurosa não Alcoólica , Camundongos , Feminino , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Colina/metabolismo , Metionina/metabolismo , Deficiência de Colina/metabolismo , Fígado/metabolismo , Racemetionina/metabolismo , Dieta , Camundongos Knockout , Camundongos Endogâmicos C57BL
19.
Front Immunol ; 15: 1327565, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357546

RESUMO

Background: Globally, gastric cancer (GC) is a category of prevalent malignant tumors. Its high occurrence and fatality rates represent a severe threat to public health. According to recent research, lipid metabolism (LM) reprogramming impacts immune cells' ordinary function and is critical for the onset and development of cancer. Consequently, the article conducted a sophisticated bioinformatics analysis to explore the potential connection between LM and GC. Methods: We first undertook a differential analysis of the TCGA queue to recognize lipid metabolism-related genes (LRGs) that are differentially expressed. Subsequently, we utilized the LASSO and Cox regression analyses to create a predictive signature and validated it with the GSE15459 cohort. Furthermore, we examined somatic mutations, immune checkpoints, tumor immune dysfunction and exclusion (TIDE), and drug sensitivity analyses to forecast the signature's immunotherapy responses. Results: Kaplan-Meier (K-M) curves exhibited considerably longer OS and PFS (p<0.001) of the low-risk (LR) group. PCA analysis and ROC curves evaluated the model's predictive efficacy. Additionally, GSEA analysis demonstrated that a multitude of carcinogenic and matrix-related pathways were much in the high-risk (HR) group. We then developed a nomogram to enhance its clinical practicality, and we quantitatively analyzed tumor-infiltrating immune cells (TIICs) using the CIBERSORT and ssGSEA algorithms. The low-risk group has a lower likelihood of immune escape and more effective in chemotherapy and immunotherapy. Eventually, we selected BCHE as a potential biomarker for further research and validated its expression. Next, we conducted a series of cell experiments (including CCK-8 assay, Colony formation assay, wound healing assay and Transwell assays) to prove the impact of BCHE on gastric cancer biological behavior. Discussion: Our research illustrated the possible consequences of lipid metabolism in GC, and we identified BCHE as a potential therapeutic target for GC. The LRG-based signature could independently forecast the outcome of GC patients and guide personalized therapy.


Assuntos
Neoplasias Gástricas , Humanos , Algoritmos , Bioensaio , Biomarcadores , Progressão da Doença , Metabolismo dos Lipídeos , Neoplasias Gástricas/genética
20.
Geriatr Nurs ; 56: 7-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38185005

RESUMO

An effective screening tool is essential to elder abuse research. Although several instruments have been developed in China to measure elder abuse, they present several limitations. The instrument development involved three components: (1) generating questionnaire items; (2) questionnaire testing and data collection in older adults; and (3) psychometric evaluation of the Domestic Elder Abuse Scale (DEAS). We collected questionnaire responses from 3725 community-dwelling Chinese older adults. The 26-item DEAS showed good reliability and validity across five dimensions: physical abuse, psychological abuse, financial exploitation, neglect, and abandonment. These five factors accounted for 78.432 % of the total variance, and model fitting results were acceptable. The Cronbach's alpha coefficient of the scale was 0.975, and the test-retest intraclass correlation coefficient (ICC) was 0.934 after 2 weeks. This study developed a five-dimension instrument to measure elder abuse, with good psychometric properties, which can play an essential role in community-based studies in China.


Assuntos
Abuso de Idosos , Humanos , Idoso , Psicometria/métodos , Abuso de Idosos/diagnóstico , Reprodutibilidade dos Testes , Inquéritos e Questionários , China
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