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Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900-1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700-900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.

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Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G-Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

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Aim: This study explores Sevoflurane (Sevo)-induced neurotoxicity mechanisms in neonates through transcriptome sequencing and models.Methods: Seven-day-old mice were exposed to 3% Sevo, and hippocampal tissue was collected for analysis of differentially expressed lncRNAs and mRNAs compared with normal mice. MiR-152-3p was selected, and the interaction between H19, USP30, and miR-152-3p was explored in BV2 microglial cells and mouse hippocampal neurons.Results: Sevo disrupts mitochondrial autophagy via USP30 upregulation, exacerbating neurotoxicity and activating NLRP1 inflammasome-mediated inflammation.Conclusion: Sevo neurotoxicity is mediated through the H19/miR-152-3p/USP30 axis, implicating microglial regulation of neuronal pyroptosis.

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[Box: see text].

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The splendid energy storage performances with eminent stability of dielectric ceramics utilized in pulsed power devices have been paid more attention by researchers. This scheme can be basically realized through introducing Li+, Bi(Mg2/3Ta1/3)O3, NaNbO3, and LiF into KNN-based ceramics. Under the breakdown strength (BDS) of 460 kV/cm, an outstanding energy storage density (W) of 6.05 J/cm3 with a high energy efficiency (η) of 85.9% is implemented. Within the broad temperature range from 20 to 140 °C, the numerical fluctuations of energy storage characteristics can be maintained at a relatively stable level (ΔWrec ≈ 3.5%, Δη ≈ 2.8%). As for the charging-discharging performances, this component possesses a fast discharging speed (t0.90 ≈ 51 ns) and remarkable temperature stability (the variations are smaller than 3.5%). Additionally, the internal mechanisms of outstanding energy storage properties can be confirmed via crystal structures and domain structures, the content of oxygen vacancies, dielectric and impedance spectra, and phase simulation. Hence, the combination of outstanding energy storage with remarkable thermal stability can be fulfilled in one ceramic system according to this discovery, providing a research thought of developing the materials for dielectric capacitors.

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Leaf width is a key determinant of planting density and photosynthetic efficiency. In an effort to determine which genes regulate maize plant leaf width, we performed a genome-wide association study (GWAS) of 1.49 × 106 single nucleotide polymorphisms (SNPs) in 80 sequenced backbone inbred maize lines in Jilin Province, China, based upon phenotypic leaf width data from two years. In total, 14 SNPs were identified as being significantly related to leaf width (p < 0.000001), with these SNPs being located on chromosomes 1, 2, 3, 5, 6, 7, 8, and 9. A total of five candidate genes were identified within a mean linkage disequilibrium (LD) distance of 9.7 kb, with a significant SNP being identified within the Zm00001d044327 candidate gene. RNA was then isolated from 12 different inbred maize lines from this GWAS study cohort and was used to conduct qPCR analyses which revealed significant differences in Zm00001d044327 expression among strains exhibiting significant differences in leaf width. Based on an assessment of EMS mutant lines harboring a conserved amino acid stop mutation and two non-synonymous mutations in Zm00001d044327 that exhibited a narrow leaf width, these data suggested that Zm00001d044327 is a key regulator of maize leaf width.

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BACKGROUND: Exposure to indoor air pollution from solid cooking fuel use may increase mental disorders risk through pathways such as oroxidative stress, neuroinflammation, or cerebrovascular damage. However, few studies have explored the underlying mechanism between solid cooking fuel use and psychological distress. The present study aims to investigate the mediating role of sleep quality on the relationship between solid cooking fuel use and psychological distress among older adults in rural Shandong, China. METHODS: This study used the cross-sectional data from the second follow-up survey of the Shandong Rural Elderly Health Cohort (SREHC). A total of 3,240 rural older adults were included in the analysis. Logistic regression and the Karlson, Holm, and Breen (KHB) mediation analyses were performed to investigate the relationship between solid cooking fuel use and psychological distress, as well as the mediating role of sleep quality in this association. RESULTS: This study found that solid cooking fuel use was significantly and positively associated with psychological distress among older adults in rural Shandong, China (OR = 1.38, 95% CI: 1.12,1.70). Mediation analysis revealed that sleep quality mediated the association between solid cooking fuel use and psychological distress among older adults (ß = 0.06, P = 0.011). The mediation effect accounted for 16.18% of the total effect. CONCLUSIONS: Our study showed that solid cooking fuel use was associated with psychological distress among rural older adults, and sleep quality mediated this association. Interventions should focus on addressing cooking fuel types and poor sleep quality to reduce psychological distress. In the future, more aggressive environmental protection policies would be needed to lessen the adverse effects of indoor air pollution on the health of older adults in rural China.

Assuntos

Poluição do Ar em Ambientes Fechados , Culinária , População Rural , Qualidade do Sono , Humanos , China/epidemiologia , Masculino , Idoso , Feminino , Estudos Transversais , Poluição do Ar em Ambientes Fechados/efeitos adversos , Angústia Psicológica , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais

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Inflammation involving adipose macrophages is an important inducer of obesity. Regulating macrophages polarization and improving the inflammatory microenvironment of adipose tissue is a new strategy for the treatment of obesity. An amphiphilic chondroitin sulfate phenylborate derivative (CS-PBE) was obtained by modifying the main chain of chondroitin sulfate with the hydrophobic small molecule phenylborate. Using CS-PBE self-assembly, macrophage targeting, reactive oxygen species (ROS) release and celastrol (CLT) encapsulation were achieved. The cytotoxicity, cellular uptake, internalization pathways and transmembrane transport efficiency of CS-PBE micelles were studied in Caco-2 and RAW264.7 cells. Hemolysis and organotoxicity tests were performed to assess the safety of the platform, while its therapeutic efficacy was investigated in high-fat diet-induced obese mice. Multifunctional micelles with macrophage targeting and ROS clearance capabilities were developed to improve the efficacy of CLT in treating obesity.In vitrostudies indicated that CS-PBE micelles had better ability to target M1 macrophages, better protective effects on mitochondrial function, better ability to reduce the number of LPS-stimulated M1 macrophages, better ability to reduce the number of M2 macrophages, and better ability to scavenge ROS in inflammatory macrophages.In vivostudies have shown that CS-PBE micelles improve inflammation and significantly reduce toxicity of CLT in the treatment of obesity. In summary, CS-PBE micelles could significantly improve the ability to target inflammatory macrophages and scavenge ROS in adipose tissue to alleviate inflammation, suggesting that CS-PBE micelles are a highly promising approach for the treatment of obesity.

Assuntos

Macrófagos , Micelas , Mitocôndrias , Obesidade , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células RAW 264.7 , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Células CACO-2 , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Camundongos Endogâmicos C57BL , Masculino , Dieta Hiperlipídica/efeitos adversos , Triterpenos/farmacologia , Triterpenos/química

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Background Ensuring the security of nursing information holds substantial importance. The awareness of information security among nurses in China is generally inadequate, and there is a lack of standardized evaluation tools for nurse information security in nursing practice. The nursing sector necessitates the establishment of a robust culture surrounding information security. Objective The aim of this study was to construct a self-reporting instrument for evaluating nursing information security. Methods The research team utilized literature analysis and group discussions to draft the item pool. After two rounds of Delphi consultation by 15 experts and pilot testing, the initial questionnaire was formed. Item analysis was carried out on the questionnaire, and the validity and reliability of the instrument were statistically tested by computing the Keiser-Meier-Olkin (KMO) and Bartlett tests, an exploratory factor analysis, a confirmatory factor analysis, convergent and discriminative validity, descriptive statistics, Cronbach's α and test-retest reliability. Results A total of 501 nurses participated in the study, supplemented by the inclusion of five experts who were invited to contribute to the assessment of content validity. Four factors were formed using exploratory factor analysis (n=250), and the cumulative variance contribution rate was found to be 60.10%. The confirmatory factor analysis (n=251) showed the model fit was good. The overall Cronbach's α coefficient of the questionnaire was 0.948, and the test-retest reliability was 0.837. Conclusion Finally, the NIS-Q with 38 items and three dimensions of knowledge, attitude and practice were formed. A promising assessment instrument for gauging the degree of nursing information security was introduced. Further, a foundational platform was established for implementing specific enhancement strategies aimed at advancing nursing information security.

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Infertility has become one of the most common chronic diseases among reproductive- aged individuals, and male factors account for about 50 %. Zinc is a trace element that is essential for sperm quality and male reproductive system. Although several current studies with small sample sizes have investigated this relationship, the conclusions have been still controversial. Here, using a large population sample involved 25,915 participants from Changzhou Maternity and Child Health Care Hospital, we revealed an inverted "U"-shaped trend between seminal plasma zinc concentrations and sperm motility PR/PR + NP (PR, progressive motility; NP, non-progressive motility). The results showed that the highest values of sperm PR/PR + NP observed in the group with intermediate concentrations of zinc (Group 2, 0.25-2.11 mmol/L). The mean values were 43.17 ± 19.03 % and 56.64 ± 20.28 %, respectively. And the lowest values came out in the highest zinc levels group (Group 4, > 3.04 mmol/L). In vitro cell experiments also showed that zinc caused dose-dependent cytotoxicity for GC-2 cells at a threshold value. Furthermore, RNA-seq analysis demonstrated that high concentrations of zinc exerted toxic effects on GC-2 cells through immune injury. Taken together, our findings suggested that moderate amounts of zinc are crucial for human reproduction and excessive concentrations may have adverse effects on male fertility.

Assuntos

Análise do Sêmen , Sêmen , Motilidade dos Espermatozoides , Zinco , Masculino , Humanos , Zinco/toxicidade , Motilidade dos Espermatozoides/efeitos dos fármacos , Sêmen/efeitos dos fármacos , Adulto , China , Espermatozoides/efeitos dos fármacos

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The excessive consumption of sodium-containing seasonings has led to an increased burden on individuals' cardiovascular system and adversely affected their health. Recently, an innovative salt-reducing strategy utilizing salty peptides has emerged with promising prospects. In this study, Porphyra haitanensis salty peptides (PHSPs) was obtained through hydrolysis and ultrafiltration. The salty taste of 30 mg/mL PHSPs was comparable to that of about 40 mM NaCl. The higher proportion of umami and sweet amino acids in PHSPs was found, which contributed to the salty and umami taste. Factors affecting the flavor of PHSPs were also investigated. CaCl2 exhibited the excellent synergistic enhancement with PHSPs on the salty taste, while the bitter taste of CaCl2 was masked in the presence of PHSPs, which was attributed to the chelation between calcium and peptides. Above all, it is expected that PHSPs can be further developed and support the emerging salt-reducing strategy in food engineering.

Assuntos

Cloreto de Cálcio , Peptídeos , Porphyra , Paladar , Peptídeos/química , Peptídeos/farmacologia , Cloreto de Cálcio/química , Porphyra/química , Humanos , Aromatizantes/química , Cloreto de Sódio/análise , Cloreto de Sódio/farmacologia , Cloreto de Sódio/química

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is a prevalent stress disorder, yet the underlying physiological mechanisms linking stress to appetite and weight loss remain elusive. While most antidepressants are associated with excessive weight and appetite gain, sertraline (SER) exhibits a lower risk of these side effects. Metacinnabar (ß-HgS), the primary component of Tibetan medicine Zuotai, has been shown to enhance mice's resilience against external stress without causing excessive increases in weight or appetite. However, the precise physiological pathway through which ß-HgS restores appetite and weight in stressed mice remains unclear. AIM OF THE STUDY: The objective of this study is to assess the efficacy of ß-HgS in ameliorating weight loss and appetite suppression induced by pressure stimulation in mice, as well as elucidate its potential mechanisms of action. METHODS: The present study employed chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) as experimental models to simulate environmental stress encountered in daily life. Subsequently, a series of experiments were conducted, including behavior tests, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, as well as metabolomics analysis of hippocampal and intestinal contents. RESULT: Dysregulation of glycerophospholipid metabolism may represent the principal pathway underlying reduced appetite, body weight, neurotransmitter and appetite hormone levels, heightened inflammatory response, hippocampal and rectal tissue damage, as well as altered composition of intestinal microbiota in stressed mice. Following intervention with SER and ß-HgS in stressed mice, the deleterious effects induced by stress can be ameliorated, in which the medium-dose ß-HgS exhibited superior performance. CONCLUSION: The aforementioned research findings suggest that the stress-induced decrease in appetite and body weight in mice may be associated with dysregulation in glycerophospholipid metabolism connecting the gut-brain axis. ß-HgS exhibits potential in ameliorating depressive-like symptoms in mice subjected to stress, while concurrently restoring their body weight and appetite without inducing excessive augmentation. Its therapeutic effect may also be attributed to its ability to modulate glycerophospholipid metabolism status and exert influence on the gut-brain axis.

Assuntos

Apetite , Microbioma Gastrointestinal , Estresse Psicológico , Animais , Masculino , Estresse Psicológico/tratamento farmacológico , Camundongos , Apetite/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Depressão/tratamento farmacológico , Antidepressivos/farmacologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Comportamento Animal/efeitos dos fármacos

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Background: Atherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic's anti-atherosclerotic effects remain unclear. Aims: This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis. Methods: The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets. Results: The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis. Conclusion: Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

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With the growing interest to harness cancer metabolism and energy reprogramming, this mini review aimed to explain the metabolic programming revealing the mechanisms regarding the treatment resistance. This mini review summarized the prominent cancer metabolic reprogramming on macromolecules. In addition, metabolic reprogramming explaining immune response and treatment resistance as well as energy reprogramming mechanisms are briefly discussed. Finally, some prospects in MR for reversing cancer drug resistance are highlighted.

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bZIP transcription factors play important roles in regulating plant development and stress responses. Although bZIPs have been identified in many plant species, there is little information on the bZIPs in Chrysanthemum. In this study, bZIP TFs were identified from the leaf transcriptome of C. mongolicum, a plant naturally tolerant to drought. A total of 28 full-length bZIP family members were identified from the leaf transcriptome of C. mongolicum and were divided into five subfamilies based on their phylogenetic relationships with the bZIPs from Arabidopsis. Ten conserved motifs were detected among the bZIP proteins of C. mongolicum. Subcellular localization assays revealed that most of the CmbZIPs were predicted to be localized in the nucleus. A novel bZIP gene, designated as CmbZIP9, was cloned based on a sequence of the data of the C. mongolicum transcriptome and was overexpressed in tobacco. The results indicated that the overexpression of CmbZIP9 reduced the malondialdehyde (MDA) content and increased the peroxidase (POD) and superoxide dismutase (SOD) activities as well as the expression levels of stress-related genes under drought stress, thus enhancing the drought tolerance of transgenic tobacco lines. These results provide a theoretical basis for further exploring the functions of the bZIP family genes and lay a foundation for stress resistance improvement in chrysanthemums in the future.

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PURPOSE: Asthma, an airway inflammatory disease, involves multiple tumor necrosis factors (TNF). TNF ligand superfamily member 11 (TNFSF11) and its known receptor, TNF receptor superfamily 11A (TNFRSF11A), has been implicated in asthma; however, the related mechanisms remain unknown. METHODS: The serum and bronchial airway of patients with asthma and healthy subjects were examined. The air-liquid interface of primary human bronchial epithelial (HBE) cells, and Tnfsf11+/- mouse, Tnfrsf11a+/- mouse, and a humanized HSC-NOG-EXL mouse model were established. This study constructed short hairpin RNA (shRNA) of TNFSF11, TNFRSF11A, transforming growth factor ß1 (TGFß1), and transforming growth factor ß receptor type 1 (TGFßR1) using lentivirus to further examine the ability of TNFSF11 protein. RESULTS: This study was the first to uncover TNFSF11 overexpression in the airway and serum of asthmatic human subjects, and the TNFSF11 in serum was closely correlated with lung function. The TNFSF11/TNFRSF11A axis deficiency in Tnfsf11+/- or Tnfrsf11a+/- mice remarkably attenuated the house dust mite (HDM)-induced signal transducer and activator of transcription 3 (STAT3) action and remodeling protein expression. Similarly, the HDM-induced STAT3 action and remodeling protein expression in HBE cells decreased after pretreatment with TNFSF11 or TNFRSF11A shRNA. Meanwhile, the expression of the remodeling proteins induced by TNFSF11 significantly decreased after pretreatment with-stattic (inhibitor of STAT3 phosphorylation) in HBE cells. The STAT3 phosphorylation and remodeling protein expression induced by TNFSF11 obviously decreased after pretreatment with TGFß1 or TGFßR1 shRNA in HBE cells. The above results also verified that blocking TNFSF11 with denosumab alleviated airway remodeling via the TGFß1/STAT3 signaling in the humanized HSC-NOG-EXL mice with HDM-induced asthma. CONCLUSIONS: TGFß1/STAT3 action was closely correlated with TNFSF11/TNFRSF11A axis-mediated airway remodeling. This study presented a novel strategy that blocks the TNFSF11/TNFRSF11A axis to exert a protective effect against asthma.

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Hepatocellular carcinoma (HCC) is a major fatal cancer that is known for its high recurrence and metastasis. An increasing number of studies have shown that the tumor microenvironment is closely related to the metastasis and invasion of HCC. The HCC microenvironment is a complex integrated system composed of cellular components, the extracellular matrix (ECM), and signaling molecules such as chemokines, growth factors, and cytokines, which are generally regarded as crucial molecules that regulate a series of important processes, such as the migration and invasion of HCC cells. Considering the crucial role of signaling molecules, this review aims to elucidate the regulatory effects of chemokines, growth factors, and cytokines on HCC cells in their microenvironment to provide important references for clarifying the development of HCC and exploring effective therapeutic targets.

Assuntos

Carcinoma Hepatocelular , Neoplasias Hepáticas , Transdução de Sinais , Microambiente Tumoral , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Citocinas/metabolismo , Quimiocinas/metabolismo , Matriz Extracelular/metabolismo , Animais

RESUMO

The manipulation of the energy or source of food for cancer cells has attracted significant attention in oncology research. Metabolic reprogramming of the immune system allows for a deeper understanding of cancer cell mechanisms, thereby impeding their progression. A more targeted approach is the restriction of cancer cells through dietary restriction (CR), which deprives cancer cells of the preferred energy sources within the tumor microenvironment, thereby enhancing immune cell efficacy. Although there is a plethora of CR strategies that can be employed to impede cancer progression, there is currently no comprehensive review that delineates the specific dietary restrictions that target the diverse metabolic pathways of cancer cells. This mini-review introduces amino acids as anti-cancer agents and discusses the role of dietary interventions in cancer prevention and treatment. It highlights the potential of a ketogenic diet as a therapeutic approach for cancer, elucidating its distinct mechanisms of action in tumor progression. Additionally, the potential of plant-based diets as anti-cancer agents and the role of polyphenols and vitamins in anti-cancer therapy were also discussed, along with some prospective interventions for CR as anti-tumor progression.

Assuntos

Dieta Cetogênica , Metabolismo Energético , Neoplasias , Humanos , Neoplasias/dietoterapia , Neoplasias/metabolismo , Metabolismo Energético/fisiologia , Restrição Calórica , Microambiente Tumoral , Animais , Aminoácidos/metabolismo

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Complex systems with many interacting nodes are inherently stochastic and best described by stochastic differential equations. Despite increasing observation data, inferring these equations from empirical data remains challenging. Here, we propose the Langevin graph network approach to learn the hidden stochastic differential equations of complex networked systems, outperforming five state-of-the-art methods. We apply our approach to two real systems: bird flock movement and tau pathology diffusion in brains. The inferred equation for bird flocks closely resembles the second-order Vicsek model, providing unprecedented evidence that the Vicsek model captures genuine flocking dynamics. Moreover, our approach uncovers the governing equation for the spread of abnormal tau proteins in mouse brains, enabling early prediction of tau occupation in each brain region and revealing distinct pathology dynamics in mutant mice. By learning interpretable stochastic dynamics of complex systems, our findings open new avenues for downstream applications such as control.

Assuntos

Encéfalo , Processos Estocásticos , Animais , Camundongos , Encéfalo/metabolismo , Proteínas tau/metabolismo , Proteínas tau/genética , Aves , Algoritmos

RESUMO

Background: Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks. Methods: In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology. Results: (1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets. Conclusion: This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

Assuntos

Ácidos e Sais Biliares , Doenças das Artérias Carótidas , Metabolômica , Farmacologia em Rede , Humanos , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/sangue , Masculino , Feminino , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/sangue , Pessoa de Meia-Idade , Metabolômica/métodos , Idoso , Estudos de Casos e Controles , Biomarcadores/sangue , Receptores Acoplados a Proteínas G/metabolismo , Espectrometria de Massas em Tandem

RESUMO

OBJECTIVE: Employing network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression. METHODS: The main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database. RESULTS: Integration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism. CONCLUSION: This study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.