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Heterogeneous Information Networks (HINs) are information networks with multiple types of nodes and edges. The concept of meta-path, i.e., a sequence of entity types and relation types connecting two entities, is proposed to provide the meta-level explainable semantics for various HIN tasks. Traditionally, meta-paths are primarily used for schema-simple HINs, e.g., bibliographic networks with only a few entity types, where meta-paths are often enumerated with domain knowledge. However, the adoption of meta-paths for schema-complex HINs, such as knowledge bases (KBs) with hundreds of entity and relation types, has been limited due to the computational complexity associated with meta-path enumeration. Additionally, effectively assessing meta-paths requires enumerating relevant path instances, which adds further complexity to the meta-path learning process. To address these challenges, we propose SchemaWalk, an inductive meta-path learning framework for schema-complex HINs. We represent meta-paths with schema-level representations to support the learning of the scores of meta-paths for varying relations, mitigating the need of exhaustive path instance enumeration for each relation. Further, we design a reinforcement-learning based path-finding agent, which directly navigates the network schema (i.e., schema graph) to learn policies for establishing meta-paths with high coverage and confidence for multiple relations. Extensive experiments on real data sets demonstrate the effectiveness of our proposed paradigm.
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The monitoring of hydrological elements in the polar region is the basis for the study of the dynamic environment under the ice. The traditional cross-season subglacial hydrological environment monitoring mainly relies on tether-type vertical profile measurement ice-based buoys, which have the advantages such as high reliability, high measurement accuracy, and real-time communication, while also has disadvantages of high-cost, large volume and weight, high power consumption, and complex layout. Therefore, it is urgent to develop a new type of ice-based profile buoy with low-cost, miniaturization, low power consumption, convenient deployment, and high reliability. In this paper, a novel optical fiber sensing scheme for ice-based buoy monitoring is proposed, which uses arrayed fiber grating to measure seawater temperature and depth profile and uses a dual-conduction mode resonance mechanism to measure seawater salinity. The temperature, depth, and salinity of seawater can be detected by an all-optical fiber technology in real-time. Preliminary experiments show that the temperature accuracy is ±0.1 °C in the range of -5â¼35 °C, the salinity accuracy is ±0.03 in the range of 30â¼40, and the vertical spatial resolution of depth can be adjusted in the range of 0â¼1000 m, which can better meet the requirements of polar hydrological multi-layer profile observation. It can provide an innovative technology and equipment support for studying the spatiotemporal change process of the polar subglacial ocean.
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In high-entropy materials, local chemical fluctuation from multiple elements inhabiting the same crystallographic site plays a crucial role in their unique properties. Using atomic-resolution chemical mapping, we identified the respective contributions of different element characteristics on the local chemical fluctuation of high-entropy structures in thermoelectric materials. Electronegativity and mass had a comparable influence on the fluctuations of constituent elements, while the radius made a slight contribution. The local chemical fluctuation was further tailored by selecting specific elements to induce large lattice distortion and strong strain fluctuation to lower lattice thermal conductivity independent of increased entropy. The chemical bond fluctuation induced by the electronegativity difference had a noticeable contribution to the composition-dependent lattice thermal conductivity in addition to the known fluctuations of mass and strain field. Our findings provide a fundamental principle for tuning local chemical fluctuation and lattice thermal conductivity in high-entropy thermoelectric materials.
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This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 µV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles.
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BACKGROUND: The influence of the microbiota on hypoglycemic agents is becoming more apparent. The effects of metformin, a primary anti-diabetes drug, on gut microbiota are still not fully understood. RESEARCH DESIGN AND METHODS: This prospective cohort study aims to investigate the longitudinal effects of metformin on the gut microbiota of 25 treatment-naïve diabetes patients, each receiving a daily dose of 1500 mg. Microbiota compositions were analyzed at baseline, and at 1, 3, and 6 months of medication using 16S rRNA gene sequencing. RESULTS: Prior to the 3-month period of metformin treatment, significant improvements were noted in body mass index (BMI) and glycemic-related parameters, such as fasting blood glucose (FPG) and hemoglobin A1c (HbA1c), alongside homeostasis model assessment indices of insulin resistance (HOMA-IR). At the 3-month mark of medication, a significant reduction in the α-diversity of the gut microbiota was noted, while ß-diversity exhibited no marked variances throughout the treatment duration. The Firmicutes to Bacteroidetes ratio. markedly decreased. Metformin treatment consistently increased Escherichia-Shigella and decreased Romboutsia, while Pseudomonas decreased at 3 months. Fuzzy c-means clustering identified three longitudinal trajectory clusters for microbial fluctuations: (i) genera temporarily changing, (ii) genera continuing to decrease (Bacteroides), and (iii) genera continuing to increase(Lachnospiraceae ND3007 group, [Eubacterium] xylanophilum group, Romboutsia, Faecalibacterium and Ruminococcaceae UCG-014). The correlation matrix revealed associations between specific fecal taxa and metformin-related clinical parameters HbA1c, FPG, Uric Acid (UA), high-density lipoproteincholesterol (HDL-C), alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), triglyceride (TG) (P < 0.05). Metacyc database showed that metformin significantly altered 17 functional pathways. Amino acid metabolism pathways such as isoleucine biosynthesis predominated in the post-treatment group. CONCLUSIONS: Metformin's role in glucose metabolism regulation may primarily involve specific alterations in certain gut microbial species rather than an overall increase in microbial species diversity. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hipoglucemiantes , Metformina , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/microbiología , Femenino , Masculino , Persona de Mediana Edad , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Estudios Prospectivos , Anciano , Glucemia/efectos de los fármacos , Adulto , Hemoglobina Glucada/análisisRESUMEN
Purpose: Myofascial trigger points (MTrPs) are the main cause of myofascial pain syndrome (MPS), and patients with MPS also have symptoms of sympathetic abnormalities. Consequently, this study aimed to investigate the potential relationship between MTrPs and sympathetic nerves. Materials and Methods: Twenty-four seven-week-old male rats were randomly divided into four groups (six rats every group). Groups I and II were kept in normal condition (n=12), and groups III and IV underwent MTrPs modelling (n=12). After successful MTrPs modelling, differences in sympathetic outcomes between the MTrPs groups (III and IV) and non-MTrPs groups (I and II) were observed. Sympathetic blockade was then applied to groups III and I (n=12). Data were collected on peak inversion spontaneous potentials (PISPs) and the H-reflex-evoked electromyography during spontaneous discharge at the MTrPs before and after sympathetic blockade. Results: Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were significantly higher in the MTrPs group than in the non-MTrPs group (P<0.05). Compared with group I, group III had the PISPs potential lower wave amplitude, shorter duration and amplitude-to-duration ratio, and lower H latency and latency difference H-M (P<0.05). Compared with group IV, group III had the PISPs potential lower wave amplitude, duration, amplitude-to-duration ratio, M-wave latency, H maximum wave amplitude, and maximal wave amplitude ratio H/M (P<0.05). The changes before and after sympathetic blockade in the MTrPs group were significant, and the amplitude, duration, and amplitude-to-duration ratio of the PISPs potentials were lower after the blockade (P<0.05). Conclusion: MTrPs and sympathetic nerves interact with each other forming a specific relationship. MTrPs sensitize sympathetic nerves, and sympathetic nerve abnormalities affect local muscle myoelectric hyperactivity, leading to MTrPs. This finding is instructive for the clinical management of sympathetic disorders.
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Hormones mediate long-range cell communication and play vital roles in physiology, metabolism, and health. Traditionally, endocrinologists have focused on one hormone or organ system at a time. Yet, hormone signaling by its very nature connects cells of different organs and involves crosstalk of different hormones. Here, we leverage the organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), to systematically map source and target cells for 84 classes of hormones. This work uncovers previously-uncharacterized sites of hormone regulation, and shows that the hormonal signaling network is densely connected, decentralized, and rich in feedback loops. Evolutionary comparisons of hormonal genes and their expression patterns show that mouse lemur better models human hormonal signaling than mouse, at both the genomic and transcriptomic levels, and reveal primate-specific rewiring of hormone-producing/target cells. This work complements the scale and resolution of classical endocrine studies and sheds light on primate hormone regulation.
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Cheirogaleidae , Animales , Cheirogaleidae/genética , Cheirogaleidae/metabolismo , Transcriptoma/genética , Evolución Biológica , Hormonas/metabolismoRESUMEN
OBJECTIVE: The present study aims to evaluate the efficacy and effect of localized delivery of drugs in the treatment of high-grade squamous intraepithelial lesion (HSIL) based on a meta-analysis. STUDY DESIGN: Databases including Cochrane Library, PubMed, Embase, Scopus, CNKI, and Wanfang were searched from their inception till August 2022. Randomized controlled trials (RCTs) that compared the efficacy of drugs and surgery in the treatment of HSIL were collected. A meta-analysis was performed using the software of Review Manager (version 5.4.1). RESULTS: Eight RCTs involving 523 patients were included in the meta-analysis. For HSIL, the rate of cervical lesions histological regression was 69.85 % in the surgery group and 59.88 % in the drug group, there was no significant difference between the two groups [OR = 0.45, 95 % CI (0.07, 3.03), P = 0.41]. The histological regression rate of cervical lesions in the placebo group was 37.76 %, and the difference between the drug group and the placebo group was statistically significant [OR = 4.94, 95 % CI (2.65, 9.20), P < 0.00001]. CONCLUSION: A total of four drugs were involved in the eight RCTS included in this study, which were imiquimod, 5-fluorouracil (5-FU), cidofovir and interferon. The results showed that although drug administration was effective in the histological regression of HSIL, the efficacy was less than about 10% of surgical treatment. Considering the recurrence of the disease after surgery and the problems of abortion, premature delivery and premature rupture of membranes after cervical conization in reproductive women, drug therapy can be used as a supplement to surgery or conservative treatment to promote the histological regression of cervical lesions in patients with HSIL.
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Lesiones Intraepiteliales Escamosas de Cuello Uterino , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Lesiones Intraepiteliales Escamosas de Cuello Uterino/tratamiento farmacológico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/cirugía , Administración Tópica , Ensayos Clínicos Controlados Aleatorios como Asunto , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Displasia del Cuello del Útero/tratamiento farmacológico , Displasia del Cuello del Útero/cirugía , Displasia del Cuello del Útero/patología , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéuticoRESUMEN
Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.
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Hipertensión , Osteoporosis , Adulto , Humanos , Anciano , Densidad Ósea/fisiología , Presión Sanguínea , Encuestas Nutricionales , Estudios Transversales , Osteoporosis/epidemiología , Hipertensión/epidemiologíaRESUMEN
Osteoporosis is a common bone disease characterized by loss of bone mass, reduced bone strength, and deterioration of bone microstructure. ROS-induced oxidative stress plays an important role in osteoporosis. However, the biomarkers and molecular mechanisms of oxidative stress are still unclear. We obtained the datasets from the Gene Expression Omnibus (GEO) database, and performed differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA) analysis out the hub genes. Then, the correlation between inflammatory factors and hub genes was analyzed, and a Mendelian randomization (MR) analysis was performed on cytokines and osteoporosis outcomes. In addition, "CIBERSORT" was used to analyze the infiltration of immune cells and single-cell RNA-seq data was used to analyze the expression distribution of hub genes and cell-cell communications. Finally, we collected human blood samples for RT-qPCR and Elisa experiments, the miRNA-mRNA network was constructed using the miRBase database, the 3D structure was predicted using the RNAfold, Vfold3D database, and the drug sensitivity analysis was performed using the RNAactDrug database. We obtained three differentially expressed genes associated with oxidative stress: DBH, TAF15, and STAT4 by differential, WGCNA clustering, and Venn screening analyses, and further analyzed the correlation of these 3 genes with inflammatory factors and immune cell infiltration and found that STAT4 was significantly and positively correlated with IL-2. Single-cell data analysis showed that the STAT4 gene was highly expressed mainly in dendritic cells and monocytes. In addition, the results of RT-qPCR and Elisa experiments verified that the expression of STAT4 was consistent with the previous analysis, and a significant causal relationship between IL-2 and STAT4 SNPs and osteoporosis was found by Mendelian randomization. Finally, through miRNA-mRNA network and drug sensitivity analysis, we analyzed to get Palbociclib/miR-141-3p/STAT4 axis, which can be used for the prevention and treatment of osteoporosis. In this study, we proposed the Palbociclib/miR-141-3p/STAT4 axis for the first time and provided new insights into the mechanism of oxidative stress in osteoporosis.
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MicroARNs , Osteoporosis , Humanos , Interleucina-2 , Osteoporosis/genética , Biología Computacional , MicroARNs/genética , ARN Mensajero , Factor de Transcripción STAT4RESUMEN
Background: China has experienced one of the fastest increases in the incidence of acute lymphoid leukemia (ALL). The aim of this study was to assess the long-term trends of the incidence and mortality of ALL in mainland China between 1990 and 2019 and to project these trends through 2028. Methods: Data on ALL were extracted from the Global Burden of Disease Study 2019; population data were extracted from World Population Prospects 2019. An age-period-cohort framework was used in the analysis. Results: The net drift for the incidence of ALL was 7.5% (95% confidence interval [CI]: 7.1%, 7.8%) per year in women and 7.1% (95% CI: 6.7%, 7.6%) in men, and local drift was found to be higher than 0 in every studied age group (p<0.05). The net drift for mortality was 1.2% (95% CI: 1.0%, 1.5%) in women and 2.0% (95% CI: 1.7%, 2.3%) in men. Local drift was lower than 0 in boys aged 0-4 years and girls aged 0-9 years and higher than 0 in men aged 10-84 years and women aged 15-84 years. The estimated period relative risks (RRs) for both incidence and mortality showed increasing trends in the recent period. The cohort RRs for incidence showed increasing trends in both sexes; however, the cohort RR for mortality was decreased in the recent birth cohort (women born after 1988-1992 and men born after 2003-2007). Compared with that in 2019, the incidence of ALL in 2028 is projected to increase by 64.1% in men and 75.0% in women, and the mortality is predicted to decrease by 11.1% in men and 14.3% in women. The proportion of older adult/adults individuals with incident ALL and ALL-related death was projected to increase. Conclusions: Over the last three decades, the incidence and mortality rates of ALL have generally increased. It is projected that the incidence rate of ALL in mainland China will continue to increase in the future, but the associated mortality rate will decline. The proportion of older adult/adults individuals with incident ALL and ALL-related death was projected to increase gradually among both sexes. More efforts are needed, especially for older adult/adults individuals.
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The main cause of groundwater nitrate contamination is the continual downward migration of dissolved nitrogen (N) in vadose zone with leachate. In recent years it has been found that dissolved organic N (DON) rise to forefront due to its great migration capacity and environmental effects. However, it remains unknown how the transformation behaviors of DONs with different properties in vadose zone profile may impact N forms distribution and groundwater nitrate contamination. To address the issue, we conducted a series of 60-day microcosm incubation experiments to investigate the effects of various DONs transformation behaviors on the distribution of N forms, microbial communities, and functional genes. The results revealed that urea and amino acids mineralized immediately after substrates addition. By contrast, amino sugars and proteins caused less dissolved N throughout entire incubation period. The transformation behaviors could substantially alter the microbial communities. Moreover, we discovered that amino sugars remarkably increased the absolute abundances of denitrification function genes. These results delineated that DONs with unique characteristics (such as amino sugar) promoted different N geochemical processes in distinct ways: different contributions to nitrification and denitrification. This can provide new insights for nitrate non-point source pollution control in groundwater.
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Agua Subterránea , Nitratos , Nitrificación , Desnitrificación , Amino AzúcaresRESUMEN
Under the policy background of "joint prevention and control" of global greenhouse gas emission reduction and regional air pollutants, the power industry, as an important target industry of energy conservation and emission reduction policies, has become an effective choice to release dual pressures. In this paper, the "bottom-up" emission factor method was used to measure the emission of CO2 and NOX from 2011 to 2019. Then, the contributions of six factors to NOX emission reduction in China's power industry were identified using the Kaya identity and logarithmic mean divisia index (LMDI) decomposition methods. The research results show that (1) there is a significant synergistic emission reduction effect between CO2 emission reduction and NOX emission reduction; (2) the factor that inhibits the growth of NOX emissions reduction in the power industry is economic development factor; and (3) the main factors that promote the reduction of NOX emission from the power industry are synergy effect, energy intensity, power generation intensity, and power production structure factors. Several suggestions are proposed, which are the power industry should adjust its structure, improve energy intensity, focus on applying low-nitrogen combustion technology, and improve the air pollutant emission information disclosure system to reduce NOX emissions.
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Contaminantes Atmosféricos , Gases de Efecto Invernadero , Dióxido de Carbono/análisis , Industrias , Contaminantes Atmosféricos/análisis , Desarrollo Económico , China , Carbono/análisisRESUMEN
Missense vitamin K epoxide reductase (VKOR) mutations in patients cause resistance to warfarin treatment but not abnormal bleeding due to defective VKOR activity. The underlying mechanism of these phenotypes remains unknown. Here we show that the redox state of these mutants is essential to their activity and warfarin resistance. Using a mass spectrometry-based footprinting method, we found that severe warfarin-resistant mutations change the VKOR active site to an aberrantly reduced state in cells. Molecular dynamics simulation based on our recent crystal structures of VKOR reveals that these mutations induce an artificial opening of the protein conformation that increases access of small molecules, enabling them to reduce the active site and generating constitutive activity uninhibited by warfarin. Increased activity also compensates for the weakened substrate binding caused by these mutations, thereby maintaining normal VKOR function. The uninhibited nature of severe resistance mutations suggests that patients showing signs of such mutations should be treated by alternative anticoagulation strategies.
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Errores Innatos del Metabolismo , Warfarina , Humanos , Warfarina/farmacología , Vitamina K Epóxido Reductasas/química , Anticoagulantes/farmacologíaRESUMEN
With the increase of nitrogen (N) input in vadose zones-groundwater systems, N contamination in groundwater has become a global environmental and geological issue that has a profound impact on the ecological environment and human health. N migration in the vadose zone is the most significant means of contaminating the groundwater aquifer. However, the current research on the control of groundwater N contamination focuses solely on the content change of certain indicators and is unable to comprehend the cause and subsequent development of groundwater N contamination. These factors pose significant environmental management challenges in areas where groundwater is contaminated with nitrate. In recent years, research on the migration and transformation behavior of various N forms in vadose zones-groundwater systems has yielded some breakthroughs but also encountered some roadblocks. The biogeochemical behavior of nitrogen consists of a series of intricate chain reaction cycles (called N-cycle). The crucial role of microorganisms in the N biogeochemical process has attracted the interest of soil carbon- and N-cycle researchers and become a hot topic of study. Nonetheless, the role of microbial regulation in groundwater systems has been largely neglected and needs to be summarized immediately. Consequently, this review summarizes recent advancements, mechanisms, and challenges, and proposes a dynamic perspective on microbial regulation. On the basis of these findings, we propose a dynamic and comprehensive groundwater N system centered on microbial regulation. In addition, we critically summarized the migration and transformation behavior of the most recent N indicators, the impact of global environmental change on each N component, and the non-negligible effects of these factors on the control of groundwater N contamination. Future research must focus on the migration and transformation behavior of nitrogen in the deep vadose zone, based on the dynamic regulation of microorganisms, and complete the missing pieces of the developed N-cycle index system. These are essential for providing scientific guidance for global N management and effectively mitigating N contamination in groundwater.
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Agua Subterránea , Contaminantes Químicos del Agua , Humanos , Nitrógeno/análisis , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Suelo , Agua Subterránea/química , Nitratos/análisisRESUMEN
In many domains of empirical sciences, discovering the causal structure within variables remains an indispensable task. Recently, to tackle unoriented edges or latent assumptions violation suffered by conventional methods, researchers formulated a reinforcement learning (RL) procedure for causal discovery and equipped a REINFORCE algorithm to search for the best rewarded directed acyclic graph. The two keys to the overall performance of the procedure are the robustness of RL methods and the efficient encoding of variables. However, on the one hand, REINFORCE is prone to local convergence and unstable performance during training. Neither trust region policy optimization, being computationally expensive, nor proximal policy optimization (PPO), suffering from aggregate constraint deviation, is a decent alternative for combinatory optimization problems with considerable individual subactions. We propose a trust region-navigated clipping policy optimization method for causal discovery that guarantees both better search efficiency and steadiness in policy optimization, in comparison with REINFORCE, PPO, and our prioritized sampling-guided REINFORCE implementation. On the other hand, to boost the efficient encoding of variables, we propose a refined graph attention encoder called SDGAT that can grasp more feature information without priori neighborhood information. With these improvements, the proposed method outperforms the former RL method in both synthetic and benchmark datasets in terms of output results and optimization robustness.
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BACKGROUND: Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics. METHODS: This was a caseâcontrol study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software. RESULTS: The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway. CONCLUSIONS: Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.
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Hiperlipidemias , Hiperuricemia , Enfermedades Metabólicas , Humanos , Triptófano/metabolismo , Ácido Aspártico/metabolismo , Estudios de Casos y Controles , Hiperlipidemias/complicaciones , Ácido Linoleico , Espectrometría de Masas , Redes y Vías Metabólicas , Tirosina/metabolismo , Fenilalanina/metabolismo , Treonina/metabolismo , Alanina/metabolismo , Glicina/metabolismo , Serina/metabolismo , Biomarcadores/metabolismoRESUMEN
The human body is programmed with definite quantities, magnitudes, and proportions. At the microscopic level, such definite sizes manifest in individual cells - different cell types are characterized by distinct cell sizes whereas cells of the same type are highly uniform in size. How do cells in a population maintain uniformity in cell size, and how are changes in target size programmed? A convergence of recent and historical studies suggest - just as a thermostat maintains room temperature - the size of proliferating animal cells is similarly maintained by homeostatic mechanisms. In this review, we first summarize old and new literature on the existence of cell size checkpoints, then discuss additional advances in the study of size homeostasis that involve feedback regulation of cellular growth rate. We further discuss recent progress on the molecules that underlie cell size checkpoints and mechanisms that specify target size setpoints. Lastly, we discuss a less-well explored teleological question: why does cell size matter and what is the functional importance of cell size control?