ABSTRACT
Predicting protein function is crucial for understanding biological life processes, preventing diseases and developing new drug targets. In recent years, methods based on sequence, structure and biological networks for protein function annotation have been extensively researched. Although obtaining a protein in three-dimensional structure through experimental or computational methods enhances the accuracy of function prediction, the sheer volume of proteins sequenced by high-throughput technologies presents a significant challenge. To address this issue, we introduce a deep neural network model DeepSS2GO (Secondary Structure to Gene Ontology). It is a predictor incorporating secondary structure features along with primary sequence and homology information. The algorithm expertly combines the speed of sequence-based information with the accuracy of structure-based features while streamlining the redundant data in primary sequences and bypassing the time-consuming challenges of tertiary structure analysis. The results show that the prediction performance surpasses state-of-the-art algorithms. It has the ability to predict key functions by effectively utilizing secondary structure information, rather than broadly predicting general Gene Ontology terms. Additionally, DeepSS2GO predicts five times faster than advanced algorithms, making it highly applicable to massive sequencing data. The source code and trained models are available at https://github.com/orca233/DeepSS2GO.
Subject(s)
Algorithms , Computational Biology , Neural Networks, Computer , Protein Structure, Secondary , Proteins , Proteins/chemistry , Proteins/metabolism , Proteins/genetics , Computational Biology/methods , Databases, Protein , Gene Ontology , Sequence Analysis, Protein/methods , SoftwareABSTRACT
ELKS proteins play a key role in organizing intracellular vesicle trafficking and targeting in both neurons and non-neuronal cells. While it is known that ELKS interacts with the vesicular traffic regulator, the Rab6 GTPase, the molecular basis governing ELKS-mediated trafficking of Rab6-coated vesicles, has remained unclear. In this study, we solved the Rab6B structure in complex with the Rab6-binding domain of ELKS1, revealing that a C-terminal segment of ELKS1 forms a helical hairpin to recognize Rab6B through a unique binding mode. We further showed that liquid-liquid phase separation (LLPS) of ELKS1 allows it to compete with other Rab6 effectors for binding to Rab6B and accumulate Rab6B-coated liposomes to the protein condensate formed by ELKS1. We also found that the ELKS1 condensate recruits Rab6B-coated vesicles to vesicle-releasing sites and promotes vesicle exocytosis. Together, our structural, biochemical, and cellular analyses suggest that ELKS1, via the LLPS-enhanced interaction with Rab6, captures Rab6-coated vesicles from the cargo transport machine for efficient vesicle release at exocytotic sites. These findings shed new light on the understanding of spatiotemporal regulation of vesicle trafficking through the interplay between membranous structures and membraneless condensates.
Subject(s)
Adaptor Proteins, Signal Transducing , Coated Vesicles , Nerve Tissue Proteins , rab GTP-Binding Proteins , Adaptor Proteins, Signal Transducing/chemistry , Adaptor Proteins, Signal Transducing/metabolism , Coated Vesicles/chemistry , Coated Vesicles/metabolism , Exocytosis , Liposomes , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/metabolism , Neurons/cytology , Neurons/metabolism , rab GTP-Binding Proteins/chemistry , rab GTP-Binding Proteins/metabolismABSTRACT
Rice OsBBX17 encodes a B-box zinc finger transcription factor in which the N-terminal B-box structural domain interacts with OsMPK1. In addition, it directly binds to the G-box of OsHAK2 and OsHAK7 promoters and represses their transcription. Under saline-alkaline conditions, the expression of OsBBX17 was inhibited. Meanwhile, activation of the OsMPK1-mediated mitogen-activated protein kinase cascade pathway caused OsMPK1 to interact with OsBBX17 and phosphorylate OsBBX17 at the Thr-95 site. It reduced OsBBX17 DNA-binding activity and enhanced saline-alkaline tolerance by deregulating transcriptional repression of OsHAK2 and OsHAK7. Genetic assays showed that the osbbx17-KO had an excellent saline-alkaline tolerance, whereas the opposite was in OsBBX17-OE. In addition, overexpression of OsMPK1 significantly improved saline-alkaline tolerance, but knockout of OsMPK1 caused an increased sensitivity. Further overexpression of OsBBX17 in the osmpk1-KO caused extreme saline-alkaline sensitivity, even a quick death. OsBBX17 was validated in saline-alkaline tolerance from two independent aspects, transcriptional level and post-translational protein modification, unveiling a mechanistic framework by which OsMPK1-mediated phosphorylation of OsBBX17 regulates the transcription of OsHAK2 and OsHAK7 to enhance the Na+ /K+ homeostasis, which partially explains light on the molecular mechanisms of rice responds to saline-alkaline stress via B-box transcription factors for the genetic engineering of saline-alkaline tolerant crops.
Subject(s)
Oryza , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Oryza/metabolism , Phosphorylation , Salt Tolerance/genetics , MAP Kinase Signaling System , Plant Proteins/metabolism , Gene Expression Regulation, PlantABSTRACT
PURPOSE: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle. METHODS: In a prospective cohort of 86 PCa patients undergoing short-term ADT, this study evaluated the prognostic potential of [18F]DCFPyL PET/CT scans. Comprehensive data encompassing clinical profiles, baseline prostate-specific antigen (PSA) levels, and imaging metrics were assessed. We developed predictive models for assessing decreases in PSA levels (PSA50 and PSA70) based on a combination of PET-related parameters and clinical factors. Kaplan-Meier survival analysis was utilized to ascertain the prognostic value of PET-based metrics. RESULTS: In this study, elevated [18F]DCFPyL uptake within the primary tumor, as indicated by a SUV ≥ 6.78 (p = 0.0024), and a reduction in the tumor volume (TV) of primary PSMA-avid tumor with PSMA-TV < 41.96 cm3 (p = 0.038), as well as an increased burden of metastatic PSMA-avid tumor, with PSMA-TV (PSMA-TV ≥ 71.39 cm3) (p = 0.012) were identified in association with diminished progression-free survival (PFS). PET and clinical parameters demonstrated constrained predictive capacity for PSA50 response as indicated by an area under the curve (AUC) of 0.442. CONCLUSION: Our study revealed that pretreatment [18F]DCFPyL uptake in primary or metastatic tumor sites is prognostically relevant in high-risk PCa patients undergoing ADT. Further research is needed to develop robust predictive models in this multifaceted landscape of PCa management.
Subject(s)
Lysine , Positron Emission Tomography Computed Tomography , Prostate-Specific Antigen , Prostatic Neoplasms , Urea , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Aged , Prostate-Specific Antigen/blood , Lysine/analogs & derivatives , Urea/analogs & derivatives , Urea/therapeutic use , Middle Aged , Androgen Antagonists/therapeutic use , Recurrence , Treatment OutcomeABSTRACT
Herein, a series of polyimide (PI)/titanium dioxide (TiO2) organic-inorganic flexible composite microfibers with high photocatalytic performance and good reusability were prepared by combining electrospinning technology and a hydrothermal method. Under simulated sunlight, the photocatalytic characteristics of the as-prepared PI nanofibers, TiO2 nanorods, and PI/TiO2 microfibers were evaluated with photocatalytic degradation of Rhodamine B (RhB) solution. Among the tested samples, PI/TiO2-3 mL hydrochloric acid-160 °C-14 h (PI/TiO-3-160-14) (100%) exhibited a superior photocatalytic degradation rate compared to pure PI (84.0%) and TiO2 (62.2%). The enhancement of the photocatalytic performance was attributed to the Z-scheme heterojunction mechanism. When the interface was irradiated by simulated sunlight, the band edge bending, built-in electric field, and Coulomb interaction synergistically facilitated the separation and transport of electron-hole pairs in the heterojunction. This enhanced the oxidation and reduction abilities of the valence and conduction bands of PI/TiO2. These results were adequately verified by X-ray photoelectron spectroscopy (XPS) analyses and radical trapping experiments. Additionally, PI/TiO2 microfibers also demonstrated excellent photocatalytic activity toward methylene blue (MB, 81.4%), methyl orange (MO, 95.9%), and malachite green (KG, 98.9%), underscoring the versatile applicability of PI/TiO2. Further supplementary investigations illustrated that PI/TiO2 microfibers also possess excellent photostability during our extensive recycling photocatalytic experiments.
ABSTRACT
PURPOSE: To analyze the characteristics of overlapping meta-analyses based on randomized controlled trials (RCTs) which reported PD-1/PD-L1 inhibitors in non-small cell cancer (NSCLC). METHODS: Meta-analyses were identified from English and Chinese databases until January 1, 2022. Differences in characteristics of overlapping meta-analyses that conducted in China and other countries were compared to assess their publication propensity. The corrected covered area (CCA) and coverage of relevant RCTs were analyzed for subtopics according to detailed intervention types. The waste and redundancy of evidence were assessed in the case of PD-1/PD-L1 inhibitor monotherapy for second-line treatment for NSCLC. RESULTS: Fifty-nine meta-analyses published in English and 17 meta-analyses published in Chinese reporting 26 RCTs were identified. Fifty-three (69.74%) meta-analyses were conducted in China. The overlapping meta-analyses in China were more likely to be from hospitals, supported by government funding, integrate first and second-line therapies. Five of the six subtopics had overlapping meta-analyses according to specific types of interventions. The CCA of overlapping meta-analyses ranged from 33.33 to 63.19%, and the coverage of relevant RCTs ranged from 63.64 to 100%. All the conclusions of overlapping meta-analyses have been consistent in the subtopic of PD-1/PD-L1 inhibitor monotherapy for second-line treatment since 2017. CONCLUSION: Overlapping meta-analyses of PD-1/PD-L1 inhibitors in NSCLC hints that meta-analyses under this topic probably exist serious redundancy. Future research should focus on prospective registration of protocols for systematic reviews/meta-analyses, scientific designed PICO, and cumulative meta-analysis to reduce redundant and wasted studies. Journals should strengthen the requirement for reviewing previously published evidence in manuscript review.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Programmed Cell Death 1 Receptor , Systematic Reviews as TopicABSTRACT
Calcium (Ca2+ )/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of antioxidant defenses and tolerance against oxidative stress. However, the underlying molecular mechanisms are largely unknown. Here, we report that the rice (Oryza sativa) CCaMK (OsDMI3) physically interacts with and phosphorylates OsUXS3, a cytosol-localized UDP-xylose synthase. Genetic and biochemical evidence demonstrated that OsUXS3 acts downstream of OsDMI3 to enhance the oxidative stress tolerance conferred by higher catalase (CAT) activity. Indeed, OsUXS3 interacted with CAT isozyme B (OsCATB), and this interaction was required to increase OsCATB protein abundance under oxidative stress conditions. Furthermore, we showed that OsDMI3 phosphorylates OsUXS3 on residue Ser-245, thereby further promoting the interaction between OsUXS3 and OsCATB. Our results indicate that OsDMI3 promotes the association of OsUXS3 with OsCATB to enhance CAT activity under oxidative stress. These findings reveal OsUXS3 as a direct target of OsDMI3 and demonstrate its involvement in antioxidant defense.
Subject(s)
Oryza , Antioxidants/metabolism , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Gene Expression Regulation, Plant , Oryza/metabolism , Oxidative Stress , Phosphorylation , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
A noble-metal-free and highly efficient bifunctional catalyst for overall water splitting is greatly desirable to generate clean and sustainable energy carriers such as hydrogen, but enormous challenges remain. Herein, porous interconnected iron-nickel nitride nanosheets are designed and grown on carbon fiber cloth (FeNi-N/CFC); combining a facile electrodeposition method and in situ nitriding process. The as-synthesized FeNi-N/CFC, with a low mass loading of 0.25â mg cm-2 , exhibits excellent catalytic activities for both the oxygen evolution reaction (OER) with 20â mA cm-2 at an overpotential (η) of 232â mV and also the hydrogen evolution reaction (HER) with 10â mA cm-2 at η=106â mV. As a bifunctional electrocatalyst for overall water splitting FeNi-N/CFC only requires a cell voltage of 1.55â V to drive a current density (j) of 10â mA cm-2 and shows robust long-term durability at j>360â mA cm-2 with a negligible change in current density over 60â h; revealing its promising application in commercial electrolyzers.
ABSTRACT
Endochondral ossification plays a crucial role in the limb development of amphibians. This study explored the ossification sequence in the hindlimb of Rana zhenhaiensis tadpoles and the correlation between thyroid hormones (THs) and endochondral ossification via histomorphology and transcriptional analyses. Our results suggest that ossification of the femur and tibiofibula was initiated during the period of high THs activity (metamorphosis climax). In addition, the results of differentially expressed gene analyses in the hindlimb and tail showed that systemic factors, transcription factors, and locally secreted factors interacted with each other during the metamorphosis climax to regulate the occurrence of endochondral ossification. These results will enrich the morphological data of anurans and provide scientific reference for the evolutionary history of vertebrates.
ABSTRACT
Nectin-4 is a Ca2+-independent immunoglobulin-like protein that exhibits significantly elevated expression in malignant tumors while maintaining extremely low levels in healthy adult tissues. In recent years, overexpression of Nectin-4 has been implicated in tumor occurrence and development of various cancers, including breast cancer, urothelial cancer, and lung cancer. In 2019, the Food and Drug Administration approved enfortumab vedotin, the first antibody-drug conjugate targeting Nectin-4, for the treatment of urothelial carcinoma. This has emphasized the value of Nectin-4 in tumor targeted therapy and promoted the implementation of more clinical trials of enfortumab vedotin. In addition, many new drugs targeting Nectin-4 for the treatment of malignant tumors have entered clinical trials, with the aim of exploring potential new indications. However, the exact mechanisms by which Nectin-4 affects tumorigenesis and progression are still unclear, and the emergence of drug resistance and treatment-related adverse reactions poses challenges. This article reviews the diagnostic potential, prognostic significance, and molecular role of Nectin-4 in tumors, with a focus on clinical trials in the field of Nectin-4-related tumor treatment and the development of new drugs targeting Nectin-4.
ABSTRACT
Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.
Subject(s)
Apoptosis , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Morpholines , Ocular Hypertension , Pyrroles , Retinal Ganglion Cells , TRPV Cation Channels , Tumor Necrosis Factor-alpha , Animals , Rats , Apoptosis/drug effects , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Disease Models, Animal , Glaucoma/drug therapy , Ocular Hypertension/drug therapy , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/pathology , TRPV Cation Channels/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , Morpholines/pharmacology , Morpholines/therapeutic use , Pyrroles/pharmacology , Pyrroles/therapeutic useABSTRACT
Overly Na+ ion in soil caused by salt stress has a significant negative impact on the growth and production of crops, especially rice (Oryza sativa L.). Therefore, it is vital for us to clarify how salt stress tolerance in rice is caused by Na+ ion toxicity. The UDP-glucuronic acid decarboxylase (UXS) is a critical enzyme in the biosynthesis of UDP-xylose, which is the key substrate of cytoderm synthesis in plants. In this study, we found that OsUXS3, a rice UXS, is a positive regulator to regulate Na+ ion toxicity under salt stress by interacting with OsCATs (Oryza sativa catalase; OsCAT). The expression of OsUXS3 was significantly up-regulated under NaCl and NaHCO3 treatments of rice seedlings. Meanwhile, by the genetic and biochemical evidence, knockout of OsUXS3 significantly increased reactive oxygen species (ROS) levels and decreased CAT activity under NaCl and NaHCO3 treatments in tissue. Furthermore, knockout of OsUXS3 caused excessive accumulation of Na + ion and rapid loss of K+ ion and disrupts Na+/K+ homeostasis under NaCl and NaHCO3 treatments. Based on the results above, we can conclude that OsUXS3 might regulate CAT activity by interacting with OsCATs, which is not only characterized for the first time but also regulating Na+/K+ homeostasis, positively regulating the Na+ ion toxicity tolerance under salt stress in rice.
Subject(s)
Oryza , Oryza/metabolism , Sodium Chloride/pharmacology , Sodium Chloride/metabolism , Salt Stress , Sodium/metabolismABSTRACT
Laser cladding technology is used to fabricate CoCrFeNi HEA/WC composite coatings with different mass fractions of WC on the surface of 316L stainless steel. The microstructures of HEA/WC composite coatings were analyzed by combining multiple characterization techniques. The results show that the HEA/WC composite coatings have good surface formation without pores and hot cracks, and the metallurgical bonding is well formed between the coating and the 316L SS substrate. Under the action of a laser beam and molten pool, WC particles partially or slightly melt and diffuse to the matrix, which hinders the orderly growth of grains and forms multiple strengthening. The phase structure of the HEA/WC composite coatings is composed of a main phase with FCC. The hardness and corrosion resistance of the HEA/WC composite coatings are clearly enhanced, and the HEA/WC composite coating with 5% WC has optimum properties.
ABSTRACT
Irradiation-induced point defects and applied stress affect the concentration distribution and morphology evolution of the nanophase in Fe-Cr based alloys; the aggregation of point defects and the nanoscale precipitates can intensify the hardness and embrittlement of the alloy. The influence of normal strain on the coevolution of point defects and the Cr-enriched α' nanophase are studied in Fe-35 at.% Cr alloy by utilizing the multi-phase-field simulation. The clustering of point defects and the splitting of nanoscale particles are clearly presented under normal strain. The defects loop formed at the α/α' phase interface relaxes the coherent strain between the α/α' phases, reducing the elongation of the Cr-enriched α' phase under the normal strains. Furthermore, the point defects enhance the concentration clustering of the α' phase, and this is more obvious under the compressive strain at high temperature. The larger normal strain can induce the splitting of an α' nanoparticle with the nonequilibrium concentration in the early precipitation stage. The clustering and migration of point defects provide the diffusion channels of Cr atoms to accelerate the phase separation. The interaction of point defect with the solution atom clusters under normal strain provides an atomic scale view on the microstructure evolution under external stress.
ABSTRACT
Wafer defect recognition is an important process of chip manufacturing. As different process flows can lead to different defect types, the correct identification of defect patterns is important for recognizing manufacturing problems and fixing them in good time. To achieve high precision identification of wafer defects and improve the quality and production yield of wafers, this paper proposes a Multi-Feature Fusion Perceptual Network (MFFP-Net) inspired by human visual perception mechanisms. The MFFP-Net can process information at various scales and then aggregate it so that the next stage can abstract features from the different scales simultaneously. The proposed feature fusion module can obtain higher fine-grained and richer features to capture key texture details and avoid important information loss. The final experiments show that MFFP-Net achieves good generalized ability and state-of-the-art results on real-world dataset WM-811K, with an accuracy of 96.71%, this provides an effective way for the chip manufacturing industry to improve the yield rate.
ABSTRACT
Endocrine disruptors have been demonstrated to exert adverse effects on growth and development of amphibians by disrupting hormone levels. Tail resorption, which is one of the most remarkable events during amphibian metamorphosis, is closely associated with thyroid hormones levels. However, limited research has been conducted on the effects of endocrine disruptors on tail resorption in amphibians. This study explored the effects of NaClO4 and T4 on the growth, development and tail resorption during the metamorphosis of Rana Chensinensis. The results demonstrated that exposure to NaClO4 led to an increase in body size and a delay in metamorphosis of R. Chensinensis tadpoles. Histological analysis revealed that both NaClO4 and exogenous T4 exposure resulted in thyroid gland injury, and NaClO4 treatment delayed the degradation of notochord and muscles, thereby delaying tail resorption. Moreover, transcriptome sequencing results showed that apoptosis-related genes (APAF1, BAX and CASP6) and cell component degradation-related genes (MMP9 and MMP13) were highly expressed in the T4 exposure group, and the expression of oxidative stress-related genes (SOD and CAT) was higher in the NaClO4 exposure group. Taken together, both NaClO4 and exogenous T4 affect tail resorption in R. Chensinensis, thereby affecting their adaptation to terrestrial life. The present study will not only provide a reference for future experimental research on the effects of other endocrine disruptors on the growth, development and tail resorption of amphibians but will also provide insights into environmental protection and ecological risk assessment.
Subject(s)
Endocrine Disruptors , Perchlorates , Animals , Endocrine Disruptors/metabolism , Thyroid Hormones/metabolism , Ranidae/metabolism , Larva , Metamorphosis, BiologicalABSTRACT
A Ni60+30%WC composite coating was prepared on the surface of Q235 steel by utilizing a high cooling rate, small thermal deformation of the substrate material, and the good metallurgical bonding characteristics of laser cladding technology. This paper focuses on the study of the composite coatings prepared under different process parameters in order to select the optimal process parameters and provide theoretical guidance for future practical applications. The macroscopic morphology and microstructure of t he composite coatings were investigated with the help of an optical microscope (OM) and a scanning electron microscope (SEM). The elemental distribution of the composite coatings was examined using an X-ray diffractometer. The microhardness and wear resistance of the composite coatings were tested using a microhardness tester, a friction tester, and a three-dimensional (3D) profilometer. The results of all the samples showed that the Ni60+30%WC composite coatings prepared at a laser power of 1600 W and a scanning speed of 10 mm/s were well formed, with a dense microstructure, and the microhardness is more than four times higher than the base material, the wear amount is less than 50% of the base material, and the wear resistance has been significantly improved. Therefore, the experimental results for the laser power of 1600 W and scanning speed of 10 mm/s are the optimal process parameters for the preparation of Ni60+30%WC.
ABSTRACT
Perchlorate, as an endocrine-disrupting chemical (EDC), is largely produced and used in the military, fireworks, fertilizers, and other industries and widely exists in water. Although perchlorate is known to destroy the normal function of thyroid hormones (THs) in amphibians and interfere with their growth and development, the impact of TH levels caused by sodium perchlorate (NaClO4) on endochondral ossification and skeletal development is poorly investigated, and the underlying molecular mechanism has not been clarified. The present study aimed to explore the potential effects of NaClO4 and exogenous thyroxine (T4) on the skeletal development of Rana chensinensis tadpoles and elucidate the related molecular mechanisms. Our results showed that histological changes occurred to the femur and tibia-fibula of tadpoles raised in 250 µg/L NaClO4 and 5 µg/L exogenous T4, and the length of their hindlimbs was significantly reduced. In addition, exogenous T4 exposure significantly interfered with the expression of Dio3, TRß, MMP9, MMP13, and Runx2, inhibiting the endochondral ossification process. Therefore, we provide robust evidence that the changes in TH levels caused by NaClO4 and exogenous T4 will adversely affect the endochondral ossification and skeletal development of R. chensinensis tadpoles.
Subject(s)
Osteogenesis , Water Pollutants, Chemical , Animals , Larva , Perchlorates/toxicity , Water Pollutants, Chemical/toxicity , Ranidae , Metamorphosis, BiologicalABSTRACT
Cardiovascular disease is the leading cause of death worldwide, and atherosclerosis is a major contributor to this etiology. The ligand-activated transcription factor, known as the aryl hydrocarbon receptor (AhR), plays an essential role in the interactions between genes and the environment. In a number of human diseases, including atherosclerosis, the AhR signaling pathway has recently been shown to be aberrantly expressed and activated. It's reported that AhR can regulate the immuno-inflammatory response and metabolism pathways in atherosclerosis, potentially serving as a bridge that links these processes. In this review, we highlight the involvement of AhR in atherosclerosis. From the literature, we conclude that AhR is a potential target for controlling atherosclerosis through precise interventions.
ABSTRACT
Coronary arterial disease (CAD) is the leading cause of mortality in the world. Hyperuricemia has recently emerged as a novel independent risk factor of CAD, in addition to the traditional risk factors such as hyperlipidemia, smoking, and obesity. Several clinical studies have shown that hyperuricemia is strongly associated with the risk, progression and poor prognosis of CAD, as well as verifying an association with traditional CAD risk factors. Uric acid or enzymes in the uric acid production pathway are associated with inflammation, oxidative stress, regulation of multiple signaling pathways and the renin-angiotensin-aldosterone system (RAAS), and these pathophysiological alterations are currently the main mechanisms of coronary atherosclerosis formation. The risk of death from CAD can be effectively reduced by the uric acid-lowering therapy, but the interventional treatment of uric acid levels in patients with CAD remains controversial due to the diversity of co-morbidities and the complexity of causative factors. In this review, we analyze the association between hyperuricemia and CAD, elucidate the possible mechanisms by which uric acid induces or exacerbates CAD, and discuss the benefits and drawbacks of uric acid-lowering therapy. This review could provide theoretical references for the prevention and management of hyperuricemia-associated CAD.