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1.
Neurobiol Dis ; 196: 106505, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38642715

RESUMEN

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.


Asunto(s)
Enfermedad de Alzheimer , Metabolismo de los Lípidos , Enfermedad de Parkinson , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Animales
2.
J Gene Med ; 26(7): e3715, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38962887

RESUMEN

BACKGROUND: The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single-cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue. METHODS: We applied scRNA-sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein-protein interaction networks were constructed to identify crucial genes and pathways. RESULTS: Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level. CONCLUSIONS: Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications.


Asunto(s)
Enfermedad de Crohn , Análisis de la Célula Individual , Ustekinumab , Enfermedad de Crohn/genética , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Ustekinumab/uso terapéutico , Análisis de la Célula Individual/métodos , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de Proteínas , Fibroblastos/metabolismo , Biomarcadores , Femenino , Transcriptoma , Adulto , Masculino , Linfocitos T/metabolismo , Linfocitos T/inmunología , Resultado del Tratamiento , Análisis de Secuencia de ARN/métodos , Redes Reguladoras de Genes
3.
Bioorg Chem ; 142: 106951, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37924755

RESUMEN

Thrombotic diseases, such as myocardial infarction, stroke, and deep vein thrombosis, severely threaten human health, and anticoagulation is an effective way to prevent such illnesses. However, most anticoagulant drugs in the clinic have different bleeding risks. Previous studies have shown that coagulation factor XI is an ideal target for safe anticoagulant drug development. Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively. DX-88mut selectively inhibited FXIa against a panel of serine proteases with an IC50 value of 14.840 ± 0.453 nM, dose-dependently prolonged APTT in mouse, rat and human plasma, and potently inhibited FeCl3-induced carotid artery thrombosis in mice at a dose of 1 µmol/kg. Additionally, DX-88mut did not show a significant bleeding risk at a dose of 5 µmol/kg. Taken together, these results show that DX-88mut is a potential candidate for the development of a novel antithrombotic agent.


Asunto(s)
Factor XIa , Trombosis , Humanos , Ratas , Ratones , Animales , Factor XIa/metabolismo , Factor XIa/farmacología , Coagulación Sanguínea , Anticoagulantes/farmacología , Trombosis/tratamiento farmacológico , Péptidos/farmacología
4.
Sensors (Basel) ; 24(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38894072

RESUMEN

The large amount of sampled data in coherent phase-sensitive optical time-domain reflectometry (Φ-OTDR) brings heavy data transmission, processing, and storage burdens. By using the comparator combined with undersampling, we achieve simultaneous reduction of sampling rate and sampling resolution in hardware, thus greatly decreasing the sampled data volume. But this way will inevitably cause the deterioration of detection signal-to-noise ratio (SNR) due to the quantization noise's dramatic increase. To address this problem, denoising the demodulated phase signals using compressed sensing, which exploits the sparsity of spectrally sparse vibration, is proposed, thereby effectively enhancing the detection SNR. In experiments, the comparator with a sampling parameter of 62.5 MS/s and 1 bit successfully captures the 80 MHz beat signal, where the sampled data volume per second is only 7.45 MB. Then, when the piezoelectric transducer's driving voltage is 1 Vpp, 300 mVpp, and 100 mVpp respectively, the SNRs of the reconstructed 200 Hz sinusoidal signals are respectively enhanced by 23.7 dB, 26.1 dB, and 28.7 dB by using compressed sensing. Moreover, multi-frequency vibrations can also be accurately reconstructed with a high SNR. Therefore, the proposed technique can effectively enhance the system's performance while greatly reducing its hardware burden.

5.
Int J Mol Sci ; 25(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38892266

RESUMEN

Insects have developed sophisticated detoxification systems to protect them from plant secondary metabolites while feeding on plants to obtain necessary nutrients. As an important enzyme in the system, glycosyltransferase 1 (GT1) conjugates toxic compounds to mitigate their harm to insects. However, the evolutionary link between GT1s and insect plant feeding remains elusive. In this study, we explored the evolution of GT1s across different insect orders and feeding niches using publicly available insect genomes. GT1 is widely present in insect species; however, its gene number differs among insect orders. Notably, plant-sap-feeding species have the highest GT1 gene numbers, whereas blood-feeding species display the lowest. GT1s appear to be associated with insect adaptations to different plant substrates in different orders, while the shift to non-plant feeding is related to several losses of GT1s. Most large gene numbers are likely the consequence of tandem duplications showing variations in collinearity among insect orders. These results reveal the potential relationships between the evolution of GT1s and insect adaptation to plant feeding, facilitating our understanding of the molecular mechanisms underlying insect-plant interactions.


Asunto(s)
Adaptación Fisiológica , Duplicación de Gen , Glicosiltransferasas , Insectos , Animales , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Adaptación Fisiológica/genética , Plantas/genética , Plantas/metabolismo , Evolución Molecular , Filogenia , Herbivoria , Genoma de los Insectos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo
6.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(2): 261-268, 2024 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38413234

RESUMEN

Recent studies have shown that the formation of the primary cilium is associated with a specific cellular organelle known as the midbody remnant (MBR), which is a point-like organelle formed by shedding of the midbody at the end of mitosis. MBRs move along the cell surface close to the center body and regulate it to form primary cilia at the top of the centriole. Primary cilia can act as an organelle to inhibit tumorigenesis, and it is lost in a variety of tumors. Studies have shown that the accumulation of MBRs in tumor cells affects ciliogenesis; in addition, both MBRs and primary cilia are degraded in tumor cells through the autophagy pathway, and MBRs can also transfer tumor signaling pathway factors to primary cilia affecting tumorigenesis. In this article, the basic structure and the formation process of MBR and primary cilia are reviewed and the mechanism of MBRs regulating ciliogenesis is elaborated. The significance of MBR-mediated ciliogenesis in tumorigenesis and its potential as a target for cancer treatment are discussed.


Asunto(s)
Cilios , Neoplasias , Cilios/fisiología , Cilios/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Autofagia/fisiología , Carcinogénesis , Centriolos/metabolismo , Centriolos/fisiología , Transducción de Señal , Orgánulos/metabolismo , Mitosis , Animales
7.
J Transl Med ; 21(1): 15, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627705

RESUMEN

BACKGROUND: The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remains < 50%. Hypoxia patterns are a hallmark of HNSCC that are associated with its occurrence and progression. However, the precise role of hypoxia during HNSCC, such as the relationship between hypoxia, tumor immune landscape and cell communication orchestration remains largely unknown. The current study integrated data from bulk and single-cell RNA sequencing analyses to define the relationship between hypoxia and HNSCC. METHODS: A scoring system named the hypoxia score (HS) was constructed based on hypoxia-related genes (HRGs) expression. The predictive value of HS response for patient outcomes and different treatments was evaluated. Single-cell datasets and cell communication were utilized to rule out cell populations which hypoxia targeted on. RESULTS: The survival outcomes, immune/Estimate scores, responses to targeted inhibitors, and chemotherapeutic, and immunotherapy responses were distinct between a high HS group and a low HS group (all P < 0.05). Single-cell datasets showed different distributions of HS in immune cell populations (P < 0.05). Furthermore, HLA-DPA1/CD4 axis was identified as a unique interaction between CD4 + T Conv and pDC cells. CONCLUSIONS: Altogether, the quantification for hypoxia patterns is a potential biomarker for prognosis, individualized chemotherapeutic and immunotherapy strategies. The portrait of cell communication characteristics over the HNSCC ecosystem enhances the understanding of hypoxia patterns in HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Hipoxia Tumoral , Humanos , Biomarcadores de Tumor/genética , Neoplasias de Cabeza y Cuello/genética , Multiómica , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética
8.
Opt Express ; 31(26): 44054-44075, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38178486

RESUMEN

Sky survey telescopes play a critical role in modern astronomy, but misalignment of their optical elements can introduce significant variations in point spread functions, leading to reduced data quality. To address this, we need a method to obtain misalignment states, aiding in the reconstruction of accurate point spread functions for data processing methods or facilitating adjustments of optical components for improved image quality. Since sky survey telescopes consist of many optical elements, they result in a vast array of potential misalignment states, some of which are intricately coupled, posing detection challenges. However, by continuously adjusting the misalignment states of optical elements, we can disentangle coupled states. Based on this principle, we propose a deep neural network to extract misalignment states from continuously varying point spread functions in different field of views. To ensure sufficient and diverse training data, we recommend employing a digital twin to obtain data for neural network training. Additionally, we introduce the state graph to store misalignment data and explore complex relationships between misalignment states and corresponding point spread functions, guiding the generation of training data from experiments. Once trained, the neural network estimates misalignment states from observation data, regardless of the impacts caused by atmospheric turbulence, noise, and limited spatial sampling rates in the detector. The method proposed in this paper could be used to provide prior information for the active optic system and the optical system alignment.

9.
Cell Commun Signal ; 21(1): 233, 2023 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-37723552

RESUMEN

Cancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αß T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1-/-) mice bearing subcutaneous tumor and Apc Min/+;LFA-1-/- mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth. Furthermore, it also demonstrated that the numbers of regulatory T cells (Treg cells) in the spleen, blood, mesenteric lymph nodes were decreased in LFA-1-/- mice, and the numbers of Treg cells in mesenteric lymph nodes were also decreased in Apc Min/+;LFA-1-/- mice compared with Apc Min/+ mice. LFA-1 inhibitor (BIRT377) was administered to subcutaneous tumor-bearing LFA-1+/+ mice, and the results showed that the tumor growth was inhibited and the number of Treg cells was reduced. The analysis of TIMER tumor database indicated that LFA-1 expression is positively associated with Treg cells and TNM stage. Conclusively, this suggests that LFA-1 knockout would inhibit tumor growth and is correlated with Treg cells. LFA-1 may be one potential target for cancer immunotherapy. Video Abstract.


Asunto(s)
Antígeno-1 Asociado a Función de Linfocito , Neoplasias , Animales , Ratones , Linfocitos T Reguladores , Bazo , Bases de Datos Factuales
10.
Environ Res ; 216(Pt 2): 114589, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36244442

RESUMEN

This study investigated the culture and characteristics of quinoline-degraded aerobic granular sludge (AGS) under 8-h and 12-h cycle duration. According to results, the cultivation of an 8-h cycle duration enhanced the growth of quinoline-degraded AGS, as well as the settleability of sludge and the retention of biomass. Quinoline can be removed from mature AGS at a rate of more than 90%, but it is removed at a rate slightly higher when the AGS are cultured for 12-h. Compared to 12-h cycle duration, 8-h cycle duration result in a greater increase in the production of extracellular polymeric substances, particularly extracellular proteins. In these two systems, Acidovorax and Paracoccus dominated the quinoline degrading bacteria. In addition, analysis by non-metric multidimensional scaling (based on Bray-curtis distance) showed significant differences of community structure between the two reactors. Clostridia and Acidaminobacter are different bacteria with an 8-h cycle duration compared to 12 h. Relative abundance of nitrogen metabolism genes based on PICRUSt2 prediction, which explain the better total nitrogen removal for an 8-h cycle duration compared to a 12-h cycle duration. Finally, the KEGG pathway was analyzed in order to confirm the results of the microbial analysis.


Asunto(s)
Microbiota , Quinolinas , Aguas del Alcantarillado/microbiología , Matriz Extracelular de Sustancias Poliméricas , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos , Aerobiosis , Nitrógeno , Bacterias/genética
11.
Public Health Nutr ; 26(1): 190-198, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35581171

RESUMEN

OBJECTIVE: To determine if limb lengths, as markers of early life environment, are associated with the risk of diabetes in China. DESIGN: We performed a cohort analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), and multivariable-adjusted Cox proportional hazard regression models were used to examine the associations between baseline limb lengths and subsequent risk of diabetes. SETTING: The CHARLS, 2011-2018. PARTICIPANTS: The study confined the eligible subject to 10 711 adults aged over 45 years from the CHARLS. RESULTS: During a mean follow-up period of 6·13 years, 1358 cases of incident diabetes were detected. When controlling for potential covariates, upper arm length was inversely related to diabetes (hazard ratio (HR) 0·95, 95 % CI (0·91, 0·99), P = 0·028), and for every 1-cm difference in knee height, the risk of diabetes decreased by about 4 % (HR 0·96, 95 % CI (0·93, 0·99), P = 0·023). The association between upper arm length and diabetes was only significant among females while the association between knee height and diabetes was only significant among males. In analyses stratified by BMI, significant associations between upper arm length/knee height and diabetes only existed among those who were underweight (HR 0·91, 95 % CI (0·83, 1·00), P = 0·049, HR 0·92, 95 % CI (0·86, 0·99), P = 0·031). CONCLUSIONS: Inverse associations were observed between upper arm length, knee height and the risk for diabetes development in a large Asian population, suggesting early life environment, especially infant nutritional status, may play an important role in the determination of future diabetes risk.


Asunto(s)
Diabetes Mellitus , Jubilación , Anciano , Adulto , Masculino , Persona de Mediana Edad , Femenino , Humanos , Estudios Longitudinales , Brazo , Diabetes Mellitus/epidemiología , China/epidemiología , Factores de Riesgo
12.
Sensors (Basel) ; 23(20)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37896707

RESUMEN

In the domain of optical fiber distributed acoustic sensing, the persistent challenge of extending sensing distances while concurrently improving spatial resolution and frequency response range has been a complex endeavor. The amalgamation of pulse compression and frequency division multiplexing methodologies has provided certain advantages. Nevertheless, this approach is accompanied by the drawback of significant bandwidth utilization and amplified hardware investments. This study introduces an innovative distributed optical fiber acoustic sensing system aimed at optimizing the efficient utilization of spectral resources by combining compressed pulses and frequency division multiplexing. The system continuously injects non-linear frequency modulation detection pulses spanning various frequency ranges. The incorporation of non-uniform frequency division multiplexing augments the vibration frequency response spectrum. Additionally, nonlinear frequency modulation adeptly reduces crosstalk and enhances sidelobe suppression, all while maintaining a favorable signal-to-noise ratio. Consequently, this methodology substantially advances the spatial resolution of the sensing system. Experimental validation encompassed the multiplexing of eight frequencies within a 120 MHz bandwidth. The results illustrate a spatial resolution of approximately 5 m and an expanded frequency response range extending from 1 to 20 kHz across a 16.3 km optical fiber. This achievement not only enhances spectral resource utilization but also reduces hardware costs, making the system even more suitable for practical engineering applications.

13.
Entropy (Basel) ; 25(5)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37238566

RESUMEN

Blockchain technology affords data integrity protection and building trust mechanisms in transactions for distributed networks, and, therefore, is seen as a promising revolutionary information technology. At the same time, the ongoing breakthrough in quantum computation technology contributes toward large-scale quantum computers, which might attack classic cryptography, seriously threatening the classic cryptography security currently employed in the blockchain. As a better alternative, a quantum blockchain has high expectations of being immune to quantum computing attacks perpetrated by quantum adversaries. Although several works have been presented, the problems of impracticality and inefficiency in quantum blockchain systems remain prominent and need to be addressed. First, this paper develops a quantum-secure blockchain (QSB) scheme by introducing a consensus mechanism-quantum proof of authority (QPoA) and an identity-based quantum signature (IQS)-wherein QPoA is used for new block generation and IQS is used for transaction signing and verification. Second, QPoA is developed by adopting a quantum voting protocol to achieve secure and efficient decentralization for the blockchain system, and a quantum random number generator (QRNG) is deployed for randomized leader node election to protect the blockchain system from centralized attacks like distributed denial of service (DDoS). Compared to previous work, our scheme is more practical and efficient without sacrificing security, greatly contributing to better addressing the challenges in the quantum era. Extensive security analysis demonstrates that our scheme provides better protection against quantum computing attacks than classic blockchains. Overall, our scheme presents a feasible solution for blockchain systems against quantum computing attacks through a quantum strategy, contributing toward quantum-secured blockchain in the quantum era.

14.
Appl Opt ; 61(3): 844-850, 2022 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-35200793

RESUMEN

The discovery of monolayer graphene allows the unprecedented chance for exploring its Goos-Hänchen (GH) shift. However, most of the pronounced GH shifts are achieved in various structures with two-dimensional continuous monolayer graphene. Here, we report on the giant GH shift of reflected wave in monolayer graphene strips by constructing the multilayer dielectric grating structure under them. The observed GH shift here is as high as 7000 times that of the incident wave at the near-infrared frequency region, whose magnification is significantly larger than that of the monolayer graphene ribbon array. We further elucidate that the enhanced GH shift originates from the guided mode resonance of the dielectric grating structure and its magnitude and sign can be manipulated by chemical potential of the monolayer graphene strip. Our work enables a promising route for enhancing and controlling the GH shifts of reflected wave in monolayer graphene strips, which might contribute to their applications in biosensors and detectors.

15.
J Environ Manage ; 316: 115198, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35537270

RESUMEN

With rapid urbanization and industrialization, environmental pollution caused by such activities has drawn much attention due to its adverse impacts on environmental quality and public health. Therefore, under the current background of China's ecological civilization construction, promoting the precise and scientific treatment of environmental pollution holds great significance. This paper proposes an improved perpetual inventory method to systematically measure the capital stock of urban and industrial pollution control. The efficiency of urban and industrial pollution control is measured by adopting the global data envelopment analysis (DEA) model. Then, the influencing factors of pollution control efficiency are empirically analyzed by using the spatial Tobit regression model. The results reveal that, first, the growth rate of the capital input scale of urban pollution control is greater than that of industrial pollution control, and the spatial distribution of capital input is unbalanced. Second, the efficiency of urban and industrial pollution control from 1991 to 2019 was generally low. The current efficiency values of urban and industrial pollution control are less than 0.2 and 0.5, respectively, indicating that urban and industrial pollution control are far from efficient. Third, the efficiency of urban and industrial pollution control is significantly positively related to the level of urbanization and industrialization, has a U-shaped relationship with the economic development level, and has heterogeneous effects on technology, energy intensity, government influence and foreign trade. On this basis, we provide constructive suggestions for optimizing the performance of pollution control.


Asunto(s)
Desarrollo Económico , Contaminación Ambiental , China , Eficiencia , Industrias , Urbanización
16.
Biochem Biophys Res Commun ; 579: 129-135, 2021 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-34597996

RESUMEN

Phosphofructokinase B (PfkB) belongs to the ribokinase family, which uses the phosphorylated sugar as substrate, and catalyzes fructose-6-phosphate into fructose-1,6-diphosphate. However, the structural basis of Mycobacterium marinum PfkB is not clear. Here, we found that the PfkB protein was monomeric in solution, which was different from most enzymes in this family. The crystal structure of PfkB protein from M. marinum was solved at a resolution of 2.21 Å. The PfkB structure consists of two domains, a major three-layered α/ß/α sandwich-like domain characteristic of the ribokinase-like superfamily, and a second domain composed of four-stranded ß sheets. Structural comparison analysis suggested that residues G236, A237, G238, and D239 could be critical for ATP catalysis and substrate binding of PfkB. Our current work provides new insights into understanding the mechanism of the glycolysis in M. marinum.


Asunto(s)
Mycobacterium marinum/enzimología , Fosfofructoquinasa-2/metabolismo , Catálisis , Cromatografía en Gel , Cristalografía por Rayos X , Escherichia coli , Fructosafosfatos/química , Glucólisis , Concentración de Iones de Hidrógeno , Conformación Molecular , Simulación del Acoplamiento Molecular , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Dispersión de Radiación , Temperatura
17.
Phys Rev Lett ; 126(7): 072001, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33666473

RESUMEN

We present for the first time complete next-to-next-to-leading-order coefficient functions to match flavor nonsinglet quark correlation functions in position space, which are calculable in lattice QCD, to parton distribution functions (PDFs). Using PDFs extracted from experimental data and our calculated matching coefficients, we predict valence-quark correlation functions that can be confronted by lattice QCD calculations. The uncertainty of our predictions is greatly reduced with higher order matching coefficients. By performing Fourier transformation, we also obtain matching coefficients for corresponding quasi-PDFs and pseudo-PDFs. Our method of calculations can be readily generalized to evaluate the matching coefficients for sea-quark and gluon correlation functions, making the program to extract partonic structure of hadrons from lattice QCD calculations comparable with and complementary to that from experimental measurements.

18.
BMC Cancer ; 21(1): 1297, 2021 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-34863141

RESUMEN

BACKGROUND: Colorectal cancer is a malignant gastrointestinal cancer, in which some advanced patients would develop cancer cachexia (CAC). CAC is defined as a multi-factorial syndrome characterized by weight loss and muscle loss (with or without fat mass), leading to progressive dysfunction, thereby increasing morbidity and mortality. ApcMin/+ mice develop spontaneous intestinal adenoma, which provides an established model of colorectal cancer for CAC study. Upon studying the ApcMin/+ mouse model, we observed a marked decrease in weight gain beginning around week 15. Such a reduction in weight gain was rescued when ApcMin/+ mice were crossed with MMP12-/- mice, indicating that MMP12 has a role in age-related ApcMin/+-associated weight loss. As a control, the weight of MMP12-/- mice on a weekly basis, their weight were not significantly different from those of WT mice. METHODS: ApcMin/+; MMP12-/- mice were obtained by crossing ApcMin/+ mice with MMP12 knockout (MMP12 -/-) mice. Histological scores were assessed using hematoxylin-eosin (H&E) staining. MMP12 expression was confirmed by immunohistochemistry and immunofluorescence staining. ELISA, protein microarrays and quantitative Polymerase Chain Reaction (qPCR) were used to investigate whether tumor could up-regulate IL-6. Cell-based assays and western blot were used to verify the regulatory relationship between IL-6 and MMP12. Fluorescence intensity was measured to determine whether MMP12 is associated with insulin and insulin-like growth factor 1 (IGF-1) in vitro. MMP12 inhibitors were used to explore whether MMP12 could affect the body weight of ApcMin/+ mice. RESULTS: MMP12 knockout led to weight gain and expansion of muscle fiber cross-sectional area (all mice had C57BL/6 background) in ApcMin/+ mice, while inhibiting MMP12 could suppress weight loss in ApcMin/+ mice. MMP12 was up-regulated in muscle tissues and peritoneal macrophages of ApcMin/+ mice. IL-6 in tumor cells and colorectal cancer patients is up-regulation. IL-6 stimulated MMP12 secretion of macrophage. CONCLUSIONS: MMP12 is essential for controlling body weight of Apc Min/+ mice. Our study shows that it exists the crosstalk between cancer cells and macrophages in muscle tissues that tumor cells secrete IL-6 inducing macrophages to up-regulate MMP12. This study may provide a new perspective of MMP12 in the treatment for weight loss induced by CAC.


Asunto(s)
Caquexia/genética , Metaloproteinasa 12 de la Matriz/metabolismo , Músculo Esquelético/metabolismo , Neoplasias/metabolismo , Animales , Genotipo , Humanos , Ratones , Ratones Noqueados
19.
Lipids Health Dis ; 19(1): 148, 2020 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-32576204

RESUMEN

BACKGROUND AND OBJECTIVES: The atherogenic index of plasma (AIP) is elevated in fatty liver disease, but its value in non-obese people with non-alcoholic fatty liver disease (NAFLD) is unclear. This study aimed to investigate the relationship between AIP and NAFLD as well as to determine whether AIP might be used as an indicator of NAFLD in non-obese individuals. METHODS: The present study involved non-obese Chinese and Japanese participants. Risk factors are evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic curve. RESULTS: In the unadjusted model, the odds ratio (OR) for every 1 standard deviation (SD) increase in AIP was 52.30. In adjusted models I and II, the OR for every 1 SD increase in AIP was 36.57 and 50.84, respectively. The area under the receiver operating characteristic curve for AIP was 0.803 and 0.802 in the development and validation groups, respectively. The best cut-off value of AIP for discrimination between NAFLD and non-NAFLD was 0.005 in the Chinese group and - 0.220 in the Japanese group. CONCLUSIONS: AIP and NAFLD are positively correlated in Chinese and Japanese populations. Therefore, AIP can be used as a new screening indicator for non-obese people with NAFLD in different nations.


Asunto(s)
Aterosclerosis/sangre , Biomarcadores/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Adulto , Pueblo Asiatico , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/sangre
20.
Biochem Biophys Res Commun ; 512(4): 838-844, 2019 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-30928093

RESUMEN

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), has threaten human health for thousands years. The chaperone trigger factor (TF) of Mtb (mtbTF), a ribosome-associated molecule, plays important roles in co-translational nascent chain folding and post-translational protein assembly. However, due to lack of structural information, the dynamic regulatory mechanism of mtbTF remains barely investigated. Herein we report the structural basis of the complex of TF and ribosomal protein S7 (mtbS7) from Mtb. The mtbTF-mtbS7 complex was obtained with high purity and homogeneity in vitro. MtbTF bound with mtbS7 in a Kd value of 1.433 µM, and formed a complex with mtbS7 at 1:2 M ratios as shown by isothermal titration calorimetry. In addition, the crystal structure of mtbS7 was solved to a resolution at 1.8 Å, which was composed of six α-helices and two ß-strands. Moreover, the molecular envelopes of mtbTF and mtbTF-mtbS7 complex were built and consisted with these homologous structures by small-angle X-ray scattering method. Our current findings might provide structural basis for understanding the molecular mechanism of TF in protein folding and the regulation of ribosomal assembly in Mtb.


Asunto(s)
Proteínas Bacterianas/química , Chaperonas Moleculares/química , Mycobacterium tuberculosis/química , Proteínas Ribosómicas/química , Proteínas Bacterianas/metabolismo , Cristalografía por Rayos X , Dispersión Dinámica de Luz , Modelos Moleculares , Chaperonas Moleculares/metabolismo , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Conformación Proteica , Proteínas Ribosómicas/metabolismo , Dispersión del Ángulo Pequeño , Difracción de Rayos X
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