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During assisted reproductive technology (ART) treatment, the aged women, especially those over 35 years old, have fewer mature oocytes and poorer quality of the oocytes comparing with the young women. In vitro maturation (IVM) technology facilitates the usage of immature oocytes, which is clinically important for the aged women. However, the maturation rate is low for the oocytes from the aged women. Human umbilical cord mesenchymal stem cells derived exosomes (HUCMSCs-exosomes), as important mediators of intercellular communication, have been widely used to restore ovarian function and improve female fertility. In this study, we isolated HUCMSCs-exosomes and collected the immature germinal vesicle oocytes from the naturally aged mouse model. And we added these HUCMSCs-exosomes to the conventional IVM culture system. The effects of HUCMSCs-exosomes on IVM oocytes were observed and analyzed from multiple aspects including maturation rate, spindle morphology, mitochondria function, and development potential. We found the quality of oocytes was improved by HUCMSCs-exosomes. Based on the results, we propose that HUCMSCs-exosomes may provide a novel and cell free strategy in the improvement of the IVM in elderly infertile women in the future. [ABSTRACT FROM AUTHOR]

Invasive plants have been shown to alter ecosystem functions. However, there is limited information available on the effect of the invasive species litter input on native litter decomposition and home-field advantage (HFA, increased decomposition at a home environment compared to a guest environment). To investigate this, we conducted a field experiment using leaves of native Trapa natans and Typha orientalis with and without invasive species Alternanthera philoxeroides and then incubated them at T. natans and T. orientalis habitats in a eutrophic lake for 50 days. In control and treatment, the decomposition and N release rate of T. natans were significantly higher than that in T. orientalis species litter at two habitats, indicating no HFA occurrence. A. philoxeroides litter input promoted the decomposition and N decay rate of T. orientalis, not T. natans. The mean decomposition rate of T. orientalis in control and treatment were 0.0138 and 0.0342 day−1; for T. natans, it was 0.0703 and 0.0754 day−1, respectively. The mean N decay rate of T. orientalis in control and treatment were 0.0235 and 0.0468 day−1; for T. natans, it was 0.0511 and 0.0544 day−1, respectively. Invasive species presence increased microbial respiration rate of T. orientalis, but not for T. natans species litter in two habitats. These results suggested that A. philoxeroides litter input accelerated low quality litter decomposition though increased microbial activity. However, it did not influence the HFA performance, which may be closely related to the lake eutrophication. [ABSTRACT FROM AUTHOR]

The purpose of the study is to investigate the metabolic characteristics of placental tissue in patients diagnosed with gestational diabetes mellitus (GDM). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively analyze the metabolites in placental tissues obtained from 25 healthy pregnant women and 25 pregnant women diagnosed with GDM. Multilevel statistical methods are applied to process intricate metabolomics data. Meanwhile, we applied machine learning techniques to identify biomarkers that could potentially predict the risk of long-term complications in patients with GDM as well as their offspring. We identified 1902 annotated metabolites, out of which 212 metabolites exhibited significant differences in GDM placentas. In addition, the study identifies a set of risk biomarkers that effectively predict the likelihood of long-term complications in both pregnant women with GDM and their offspring. The accuracy of this panel was measured by the area under the receiver operating characteristic curve (ROC), which was found to be 0.992 and 0.960 in the training and validation sets, respectively. This study enhances our understanding of GDM pathogenesis through metabolomics. Furthermore, the panel of risk markers identified could prove to be a valuable tool in predicting potential long-term complications for both GDM patients and their offspring. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a critical feature in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Hesperetin can exert anti-inflammatory, antioxidant and other neuroprotective effects. In this study, the scopolamine (SCOP)-induced cognitive dysfunction in mice model was used to evaluate the neuroprotective effects of hesperetin. Behavioral tests (Morris water maze, open field, and novel object recognition tests) were conducted to evaluate the effect of hesperetin on cognitive dysfunction behaviors. Nissl staining and Immunofluorescence were used to evaluate hippocampal neuronal damage and microglial activation in mice. The levels of proinflammatory factors, oxidant stress, and the cholinergic neurotransmitter were detected by real-time quantitative fluorescence PCR (RT-qPCR) or biochemical reagent kits. Western blotting was used to detect the relative protein expression of the sirtuin 6 (SIRT6) / NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. Results showed that hesperetin could ameliorate SCOP-induced cognitive impairment and neuronal damage, and regulate the levels of cholinergic neurotransmitters in the hippocampal of AD mice. Hesperetin could also enhance antioxidant defense by regulating the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Hesperetin exerted anti-neuroinflammation effects through inhibiting of microglia activation and down-regulating the mRNA transcript levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Meanwhile, hesperetin could attenuate the expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), thioredoxin-interacting protein (TXNIP), and caspase-1 p20 and upregulate the expression of SIRT6 in SCOP-induced mice. Overall, our study suggested that hesperetin might ameliorate SCOP-induced cognitive dysfunction by improving cholinergic system dysfunction and suppressing oxidative stress and attenuating neuroinflammation via SIRT6/NLRP3 pathway in mice. [ABSTRACT FROM AUTHOR]

Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence. [ABSTRACT FROM AUTHOR]

Minimal residual disease (MRD) is termed as the small numbers of remnant tumor cells in a subset of patients with tumors. Liquid biopsy is increasingly used for the detection of MRD, illustrating the potential of MRD detection to provide more accurate management for cancer patients. As new techniques and algorithms have enhanced the performance of MRD detection, the approach is becoming more widely and routinely used to predict the prognosis and monitor the relapse of cancer patients. In fact, MRD detection has been shown to achieve better performance than imaging methods. On this basis, rigorous investigation of MRD detection as an integral method for guiding clinical treatment has made important advances. This review summarizes the development of MRD biomarkers, techniques, and strategies for the detection of cancer, and emphasizes the application of MRD detection in solid tumors, particularly for the guidance of clinical treatment. [ABSTRACT FROM AUTHOR]

A distinct population of skeletal stem/progenitor cells (SSPCs) has been identified that is indispensable for the maintenance and remodeling of the adult skeleton. However, the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined. Here, we established models of premature aging by conditional depletion of Zmpste24 (Z24) in mice and found that Prx1-dependent Z24 deletion, but not Osx-dependent Z24 deletion, caused significant bone loss. However, Acan-associated Z24 depletion caused only trabecular bone loss. Single-cell RNA sequencing (scRNA-seq) revealed that two populations of SSPCs, one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells, were significantly decreased in Prx1-Cre; Z24f/f mice. Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation. Physical exercise reversed the effects of Z24 depletion on cellular apoptosis, extracellular matrix expression and bone mass. This study identified two populations of SSPCs that are responsible for premature aging-related bone loss. The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging. [ABSTRACT FROM AUTHOR]

The human pose estimation has been greatly improved with the development of deep neural network. However, there are some challenges in this task, such as the occlusions in images and various scales of the human body. In this study, we propose a novel convolutional neural network architecture based on dual attention mechanism and multi-scale feature fusion to generate keypoints prediction and estimate the location of human body parts in images. Firstly, the feature enhancement module(FEM) performs local feature enhancement process for each feature map of the network using the double-attention mechanism, where channel attention is used to filter out the channels that need more attention and spatial attention is used to enhance the local features of each feature map at the spatial level. Secondly, we design a multi-scale feature fusion(MSFF) module by using the cascade of atrous convolution to aggregate contextual information and enhance the expressiveness of features. The multi-scale contextual information is increased by expanding the perceptual field, which helps to detect adjacent keypoints. Finally, we introduce an improved upsampling module that jointly uses upsampling2D and transposed convolution to better regress the obtained feature maps to higher resolution and output heatmaps. Extensive experiments on MPII and COCO human pose estimation benchmarks demonstrate the effectiveness of our network. [ABSTRACT FROM AUTHOR]

The removal and recovery of uranium (VI) from water solutions are critical for energy and environmental security. In this study, hydrochar at 100, 150, and 190 °C (HC100, HC150, and HC190) and pyrochar at 250 °C (BC250) were prepared from residual sludge (RS). The uranium (VI) adsorption behavior, recovery, and heavy metal risk of RS and its biochars were assessed. The sorption distribution coefficient of RS was higher than those of its biochars within the tested concentration range. The maximum adsorption capacity of uranium (VI) by HC190 was 121.26 mg/g at acidic pH (pH 4.5), which was higher than those of other tested biochars, previously reported unmodified biochars, and activated carbon. The zeta potential, FTIR, and XPS results implied that the adsorption of uranium (VI) by RS and its biochars was regulated by electrostatic attraction and the complexation with oxygen- and phosphorus-containing functional groups. Besides, partial reduction of uranium (VI) into uranium (IV) happened during the process of adsorption. More than 86% of the adsorbed uranium (VI) was recovered by 0.01 M hydrochloric acid and 100% by 0.01 M sodium carbonate. The leaching amount of heavy metals was greatly reduced after the sludge was converted to biochar, indicating that hydrothermal carbonization and pyrolysis can promote the stabilization of heavy metals. This work demonstrates that RS and its biochars can be implemented as low-cost, environment-friendly, and high-efficient materials for the purification of uranium (VI)-containing solutions by means of adsorption and desorption. [ABSTRACT FROM AUTHOR]

The wireless ultraviolet (UV) communication can be applied to assist unmanned aerial vehicles (UAVs) to complete cooperative reconnaissance, combat, defense and other tasks in the complex environment. This paper focuses on the topology optimization of UAV formation network based on UV communication. We discuss UAV flocking formation model and UAV clustering formation model. The topology optimization algorithms based on optimally rigid graph are proposed, which can reduce the communication complexity of the formation and prolong the lifetime of the network. Then, the results of different topology optimization algorithms are simulated and analyzed. It is revealed that the algorithms we proposed can improve the fault-tolerant performance of the UAV network, while reduce the formation communication compared with other algorithms. The communication complexity of the formation is reduced by 11.5% in the flocking formation. The occurrence of first node death in the clustering network is delayed by 25.1% compared with LEACH. [ABSTRACT FROM AUTHOR]

Fibroblast activation protein (Fap) is a serine protease that degrades denatured type I collagen, α2-antiplasmin and FGF21. Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin (Oln). Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis (RA). However, whether Fap plays a critical role in osteoarthritis (OA) remains poorly understood. Here, we found that Fap is significantly elevated in osteoarthritic synovium, while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice. Mechanistically, we found that Fap degrades denatured type II collagen (Col II) and Mmp13-cleaved native Col II. Intra-articular injection of rFap significantly accelerated Col II degradation and OA progression. In contrast, Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA. Genetic deletion of Oln significantly exacerbated OA progression, which was partially rescued by Fap deletion or inhibition. Intra-articular injection of rOln significantly ameliorated OA progression. Taken together, these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation. [ABSTRACT FROM AUTHOR]

Translational control is a fundamental mechanism regulating animal germ cell development. Gonadal somatic cells provide support and microenvironment for germ cell development to ensure fertility, yet the roles of translational control in gonadal somatic compartment remain largely undefined. We found that mouse homolog of conserved fly germline stem cell factor Pumilio, PUM1, is absent in oocytes of all growing follicles after the primordial follicle stage, instead, it is highly expressed in somatic compartments of ovaries. Global loss of Pum1, not oocyte-specific loss of Pum1, led to a significant reduction in follicular number and size as well as fertility. Whole-genome identification of PUM1 targets in ovarian somatic cells revealed an enrichment of cell proliferation pathway, including 48 key regulators of cell phase transition. Consistently granulosa cells proliferation is reduced and the protein expression of the PUM-bound Cell Cycle Regulators (PCCR) were altered accordingly in mutant ovaries, and specifically in granulosa cells. Increase in negative regulator expression and decrease in positive regulators in the mutant ovaries support a coordinated translational control of somatic cell cycle program via PUM proteins. Furthermore, postnatal knockdown, but not postnatal oocyte-specific loss, of Pum1 in Pum2 knockout mice reduced follicular growth and led to similar expression alteration of PCCR genes, supporting a critical role of PUM-mediated translational control in ovarian somatic cells for mammalian female fertility. Finally, expression of human PUM protein and its regulated cell cycle targets exhibited significant correlation with ovarian cancer and prognosis for cancer survival. Hence, PUMILIO-mediated cell cycle regulation represents an important mechanism in mammalian female reproduction and human cancer biology. [ABSTRACT FROM AUTHOR]

This paper contains a large number of radar data information, analyzes the radar scattering characteristics of water masses in different imaging areas, such as quiet open area, wave area, agricultural area, and compares with the application of high-resolution SAR image extraction algorithm. We also use the data analysis of the data center to explore the evolution characteristics of the high-level and low-level atmospheric circulation and water vapor transport field before and after the beginning and end of the rainy season precipitation anomaly in Southwest China. Then, the low-frequency evolution characteristics of the precipitation anomaly series in the rainy season in Southwest China are analyzed, and eight phases are divided according to the 20–60 day intraseasonal oscillation of precipitation, which provides convenience for the transportation of low-frequency water and air. Thirdly, the method is applied to aerobic exercise. However, people with low blood glucose regulation are generally overweight, and drug treatment itself cannot change their health. Exercise has always been the most effective way of muscle strength training. If aerobic exercise and resistance exercise are combined, it can be combined exercise training. If the sequence and duration are long enough, excess sugar in the body can be burned. Training resistance can be used to improve muscle function and maintain strength. Therefore, the process of aerobic exercise is very important for people with poor blood glucose regulation, and it can also provide more meaningful and targeted concept development for the treatment of diabetes. In order to promote the development and application of SAR map, this paper studies the relationship between abnormal precipitation in rainy season and blood glucose regulation of teenagers during aerobic exercise, and applies it to the study of SAR map. [ABSTRACT FROM AUTHOR]

Background: The accurate interpretation of BRCA1/2 variants becomes increasingly important in breast cancer and other related cancers including ovarian cancer, prostate cancer, pancreatic cancer and so forth. In the past decades, especially before year 2015, limitations of techniques and lack of databases and guidelines have led to possible misinterpretation of the clinical significance of sequence variants of BRCA1/2. A published study reported reclassification of some BRCA1/2 variants previously classified as variants of uncertain significance (VUS) to likely pathogenic in breast or ovarian cancer patients from Korea. However, little is known about the situation in Chinese population. Methods: We retrospectively retrieved 109 publications studying about BRCA1/2 variants of Chinese population from the year 1999 to year 2019 (March). After excluding publications of meta-analysis and publications with missing data, 72 publications were eventually retained for subsequent analysis. In total, 1,351 BRCA variants (673 BRCA1 variants and 678 BRCA2 variants) derived from 42,430 Chinese cancer patients were standardized and reinterpreted using ACMG/AMP 2015 guidelines and China Expert Consensus on BRCA variant interpretation by genetic counselors. Results: Among the 1,351 BRCA variants, the majority of interpretation (91.7%, 1,239/1,351) remained the same as previously published. However, there were 112 (8.3%, 112/1,351) variants (64 BRCA1, 48 BRCA2) reclassified with different categories. Conclusions: Our results demonstrated that clinical significance of not only VUS, but also pathogenic/likely pathogenic variants varied from time to time in the Chinese population. Precise reinterpretation of BRCA1/2 variants is of crucial importance to genetic counseling or clinical decision-making for risk individuals or patients. [ABSTRACT FROM AUTHOR]

Ethylmercury (EtHg) has been widely observed in the environment due to anthropogenic contamination and/or environmental ethylation of inorganic mercury. Herein, the acute and sublethal effect of EtHg chloride on Chinese rare minnow (Gobiocypris rarus) as a fish model was studied. EtHg chloride showed an obvious toxicity to 4-month-old Chinese rare minnow (LC50 24.8 µg L−1 (as Hg) at 24 h). Histological analysis revealed that acute EtHg exposure can induce necrosis, telangiectasis and exfoliation of epithelial cells in the gill, as well as edema, vacuoles, and pyknotic nuclei in hepatocytes. Sublethal dose exposure revealed a very high accumulation of EtHg in fish, which is subsequently metabolized to inorganic mercury and eliminated after depuration. A new mercury species, possibly diethylmercury, was also observed as the metabolite of EtHg in rare minnow. The present study provides useful information for assessing the risks of EtHg and understanding its bioaccumulation in aquatic organisms. [ABSTRACT FROM AUTHOR]

This study examines Northern Hemisphere winter (DJFM) atmospheric responses to opposite strong phases of interdecadal (low frequency, LF) Pacific sea surface temperature (SST) forcing, which resembles El Niño-Southern Oscillation (ENSO) on a longer time scale, in observations and GFDL and CAM4 model simulations. Over the Pacific-North America (PNA) sector, linear observed responses of 500-hPa height (Z500) anomalies resemble the PNA teleconnection pattern, but show a PNA-like nonlinear response because of a westward Z500 shift in the negative (LF−) relative to the positive LF (LF+) phase. Significant extratropical linear responses include a North Atlantic Oscillation (NAO)-like Z500 anomaly, a dipole-like Z500 anomaly over northern Eurasia associated with warming over mid-high latitude Eurasia, and a Southern Annular anomaly pattern associated with warming in southern land areas. Significant nonlinear Z500 responses also include a NAO-like anomaly pattern. Models forced by LF+ and LF− SST anomalies reproduce many aspects of observed linear and nonlinear responses over the Pacific-North America sector, and linear responses over southern land, but not in the North Atlantic-European sector and Eurasia. Both models simulate PNA-like linear responses in the North Pacific-North America region similar to observed, but show larger PNA-like LF+ responses, resulting in a PNA nonlinear response. The nonlinear PNA responses result from both nonlinear western tropical Pacific rainfall changes and extratropical transient eddy feedbacks. With LF tropical Pacific forcing only (LFTP+ and LFTP−, climatological SST elsewhere), CAM4 simulates a significant NAO response to LFTP−, including a linear negative and nonlinear positive NAO response. [ABSTRACT FROM AUTHOR]

Interleukin-1beta (IL-1β) is a cytokine involved in the control of inflammatory responses. The functions of IL-1β have been extensively studied in many vertebrates. However, few studies focused on the functions of IL-1β in the spotted halibut (Verasper variegatus), an endangered aquatic fish that easily suffers from bacterial and viral infections. We first cloned and sequenced the IL-1β gene from V. variegatus (VvIL-1β). Its conservative interleukin-1 propeptide and interleukin-1/18 domains corresponding regions, characteristics of the IL-1 protein family and TA-rich motifs relating to inflammatory responses were similar to those of the IL-1β genes from other teleost and mammals. The phylogenetic analysis showed that VvIL-1β was homologous to the IL-1β gene of other vertebrates. Treatment with pathogen-associated molecular patterns (PAMPs) induced a significant and rapid up-regulation of VvIL-1β expression in the peripheral blood leukocytes (PBLs), revealing that VvIL-1β is actively involved in the host immune responses against bacterial and viral pathogens. The expression level of VvIL-1β was relatively high in the PBLs, gill, and intestine, indicating the immunological function of VvIL-1β. VvIL-1β also had interesting expression patterns at specific developmental stages, implying that the IL-1β of flatfishes may have some novel functions during embryonic development and metamorphosis. The 3D structure prediction also provided information about how VvIL-1β interacts with its receptor protein. These results suggested that VvIL-1β may have multiple functions in V. variegatus and provided us valuable information for understanding the novel functions of IL-1β. [ABSTRACT FROM AUTHOR]

This study investigates observed and modeled contributions of global sea surface temperature (SST) to China winter climate trends in 1960-2014, including increased precipitation, warming through about 1997, and cooling since then. Observations and Atmospheric Model Intercomparison Project (AMIP) simulations with prescribed historical SST and sea ice show that tropical Indian Ocean (TIO) warming and increasing rainfall causes diabatic heating that generates a tropospheric wave train with anticyclonic 500-hPa height anomaly centers in the TIO or equatorial western Pacific (TIWP) and northeastern Eurasia (EA) and a cyclonic anomaly over China, referred to as the TIWP-EA wave train. The cyclonic anomaly causes Indochina moisture convergence and southwesterly moist flow that enhances South China precipitation, while the northern anticyclone enhances cold surges, sometimes causing severe ice storms. AMIP simulations show a 1960-1997 China cooling trend by simulating increasing instead of decreasing Arctic 500-hPa heights that move the northern anticyclone into Siberia, but enlarge the cyclonic anomaly so it still simulates realistic China precipitation trend patterns. A separate idealized TIO SST warming simulation simulates the TIWP-EA feature more realistically with correct precipitation patterns and supports the TIWP-EA teleconnection as the primary mechanism for long-term increasing precipitation in South China since 1960. Coupled Model Intercomparison Project (CMIP) experiments simulate a reduced TIO SST warming trend and weak precipitation trends, so the TIWP-EA feature is absent and strong drying is simulated in South China for 1960-1997. These simulations highlight the need for accurately modeled SST to correctly attribute regional climate trends. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography–mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA. [ABSTRACT FROM AUTHOR]