Continuously tunable ultrasonic focusing by Moiré metalenses.

Tunable ultrasonic focusing holds great significance in both medicine and engineering. Recent advancements in metalenses have introduced approaches for tunable acoustic focusing, but their complex configurations and limited tuning range remain challenges. Here, acoustic Moiré metalenses (AMMs) are proposed to achieve continuously tunable ultrasonic focusing in water. Two cascading metasurfaces that can function as Moiré diffractive elements make up the AMM. By mutually rotating the metasurface, the focal point of the AMM can be continuously tuned in a large range. The focal length can be adjusted continuously from ∼14.3λ0to ∼50λ0for the axial focusing. We further show that the well-designed AMM can achieve the continuously tunable lateral focusing, with the deflection angle of the focal point being tunable between approximately -40°,40°. Both simulation and experimental results confirm the excellent tunable focusing performances of the AMMs. The proposed AMMs with continuously tunable focusing capability may have potential applications in ultrasonic imaging and ultrasound treatment.

Intestinal Akkermansia muciniphila is Beneficial to Functional Recovery Following Ischemic Stroke.

Recent studies have demonstrated the interaction between gut microbiota and brain on ischemic stroke, but the roles of gut microbiota in the pathophysiology of ischemic stroke remain largely unclear. In this study, we detected a significant increase of intestinal Akkermansia muciniphila (AKK) following ischemic stroke by a rose bengal photothrombosis model. To investigate the function and mechanism of AKK on ischemic stroke, we performed the AKK administration prior to stroke surgery. The results showed that mice treated with AKK gained significantly higher body weight and behaved better than those in PBS group at 3 days after ischemic stroke. Consistently, AKK administration remarkably decreased the infarct volumes as well as the density of degenerating neurons and apoptotic cells after ischemic stroke. Notably, AKK is a potential therapeutic target in immune-related disorders connected to the microbiota, and inflammation is crucially involved in the pathophysiological process of ischemic stroke. For the determination of underlying mechanisms of this protective effect, we investigated whether there are associations between AKK and neuroinflammation following ischemic stroke. The results suggested that AKK administration significantly reduced the activation of astrocytes and microglia but up-regulated multiple anti-inflammatory factors following ischemic stroke. Therefore, our study highlighted the beneficial roles of intestinal AKK on ischemic stroke and provided a new perspective for the treatment of ischemic stroke.

Tumor-related factor complement Clq/TNF-related protein 6 affects the development of digestive system tumors through the phosphatidylinositol 3-kinase pathway.

In this editorial, we review the work of Razali et al published in World J Gastroenterology, with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase (PI3K) pathway and buparlisib on colitis-associated cancer. The role of PI3K in promoting cancer progression has been widely recognized, as it is involved in regulating the survival, differentiation, and proliferation of cancer cells. The complement Clq/TNF-related protein 6 (CTRP6) is a newer tumor-associated factor. Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer, hepatocellular carcinoma, colorectal cancer, and other gastrointestinal tumors through the PI3K pathway. This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.

Essential Number of Principal Components and Nearly Training-Free Model for Spectral Analysis.

Learning-enabled spectroscopic analysis, promising for automated real-time analysis of chemicals, is facing several challenges. Firstly, a typical machine learning model requires a large number of training samples that physical systems can not provide. Secondly, it requires the testing samples to be in range with the training samples, which often is not the case in the real world. Further, a spectroscopy device is limited by its memory size, computing power, and battery capacity. That requires highly efficient learning models for on-site analysis. In this paper, by analyzing multi-gas mixtures and multi-molecule suspensions, we first show that orders of magnitude reduction of data dimension can be achieved as the number of principal components that need to be retained is the same as the independent constituents in the mixture. From this principle, we designed highly compact models in which the essential principal components can be directly extracted from the interrelations between the individual chemical properties and principal components; and only a few training samples are required. Our model can predict the constituent concentrations that have not been seen in the training dataset and provide estimations of measurement noises. This approach can be extended as an effectively standardized method for principle component extraction.

Expression of Iron Metabolism Genes Is Potentially Regulated by DOF Transcription Factors in Dendrocalamus latiflorus Leaves.

Transcription factors (TFs) are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of TFs with extensive roles in plant growth and development. Our previous research indicated that iron content varies among bamboo leaves of different colors. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism related (IMR) genes in bamboo and determined the TFs that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF TFs in D. latiflorus.

Directional Construction of Low-Coordination Fe-N3 Coupled with Intrinsic Carbon Defects for High-Efficiency Oxygen Reduction.

Regulating the coordination environment of Fe-Nx sites is an efficient but challenging approach for promoting the intrinsic catalytic activity of single-atom Fe/N-codoped carbon (Fe-N-C) toward the oxygen reduction reaction (ORR). Herein, low-coordination Fe-N3 sites coupled with carbon vacancies (Fe-N3/CV) are directionally constructed in Fe-N-C via pyrolysis of a metal-organic framework (MOF) precursor with N3-Zn-O-Fe moieties, which are delicately prefabricated by chemically anchoring Fe3+ onto a H2O-etching induced linker-missing Zn-N3 site in the MOF precursor. The optimized Fe-N-C with the Fe-N3/CV sites displays a high ORR half-wave potential of 0.92 V (vs RHE), which is attributed to the optimized electronic structure and binding strengths of the active Fe center toward the ORR intermediates stemming from the synergy of the asymmetric configuration of Fe-N3 as well as the adjacent carbon vacancies. This work could be enlightening for the design and construction of high-activity coupling sites in metal and nitrogen-codoped carbon catalysts.

Microcystin-LR prenatal exposure induces coronary heart disease through macrophage polarization imbalance mediated by trophoblast-derived extracellular vesicles.

Microcystin-leucine arginine (MC-LR) has been reported to exhibit placental toxicity, leading to potential adverse pregnancy outcomes. Placental abnormalities often coincide with congenital heart defects (CHD). However, the extent to which MC-LR-induced placental abnormalities contribute to CHD and the cellular mechanisms underlying this association remain unknown. In this study, we observed abnormal polarization of placental macrophages in pregnant mice exposed to MC-LR during pregnancy, and the embryos developed cardiac developmental defects that persisted into adulthood. Trophoblast-derived extracellular vesicles (T-EVs) increase in number during pregnancy and act as a critical signal in macrophage polarization. However, MC-LR significantly affected the miRNA expression profile of T-EVs. Upon internalization into macrophages, T-EV-derived miR-377-3p specifically targets the 3'UTR region of NR6A1 to inhibit gene expression. Silencing of transcription suppressor NR6A1 leads to abnormal activation of the downstream mTOR/S6K1/SREBP pathway, inducing metabolic reprogramming and ultimately leading to M1 polarization of macrophages. This study elucidated the placental mechanism underlying MC-LR-induced CHD for the first time, providing insights into the environmental risks associated with CHD.

Relationship between childhood trauma and non-suicidal self-injury in high school students: the mediating role of the stress perception and the moderating role of teacher-student relationship.

This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280-0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P < 0.01). Thirdly, stress perception functioned as a mediator in the relationship between childhood trauma and NSSI among high school students (t = 4.65, P < 0.01). The mediation effect occupies 26.56% of the total effect. Furthermore, the teacher-student relationship moderated the mediating effect of stress perception on the link between childhood trauma and NSSI (ß = 0.0736, P < 0.01). Notably, individuals with strong teacher-student relationships exhibited a significant elevation in stress perception upon exposure to childhood trauma. The findings of this study support a moderated mediation model in the association between childhood trauma and NSSI, suggesting profound implications for the development of targeted interventions and prevention strategies among high school students.

Nonlinear dynamics and onset of steady precession of a ring on a vertical rod.

We report on the unexpected precessional motion that occurs when a small, rigid ring is rotated on a vertical smooth rod. Using high-speed imaging, two distinct regimes of motion are observed experimentally. (i) Oscillatory motion when the ring has a single contact with the rod (transient motion). (ii) Steady state (terminal velocity) when the ring has two instantaneously stationary contacts with the rod. These two regimes and the transition between them are analyzed through qualitative, analytical, and numerical means. One key feature of the steady-state motion is energy dissipation through rolling resistance and air drag. Our model predicts that steady-state motion occurs only when certain geometric conditions (the ratio of the radii of a ring and a rod, and the tilt angle) are fulfilled. As the steady-state regime is often found to be the preferred final state, the dynamic stability of the single contact configuration is investigated through bifurcation, phase-space, and linear stability analyses. Our numerical simulation accounts for the stick-slip transition at the contact point, and is in good agreement with experimental data across all experiments. Our findings have potential applications in various engineering fields, such as studying the vibrational detachment of threaded fasteners and developing gravity-driven centrifuges.

The Biosynthesis, Structure Diversity and Bioactivity of Sterigmatocystins and Aflatoxins: A Review.

Sterigmatocystins and aflatoxins are a group of mycotoxins mainly isolated from fungi of the genera Aspergillus. Since the discovery of sterigmatocystins in 1954 and aflatoxins in 1961, many scholars have conducted a series of studies on their structural identification, synthesis and biological activities. Studies have shown that sterigmatocystins and aflatoxins have a wide range of biological activities such as antitumour, antibacterial, anti-inflammatory, antiplasmodial, etc. The sterigmatocystins and aflatoxins had been shown to be hepatotoxic and nephrotoxic in animals. This review attempts to give a comprehensive summary of progress on the chemical structural features, synthesis, and bioactivity of sterigmatocystins and aflatoxins reported from 1954 to April 2024. A total of 72 sterigmatocystins and 20 aflatoxins are presented in this review. This paper reviews the chemical diversity and potential activity and toxicity of sterigmatocystins and aflatoxins, enhances the understanding of sterigmatocystins and aflatoxins that adversely affect humans and animals, and provides ideas for their prevention, research and development.

Hif3α Plays Key Roles in the Progression of Alzheimer's Disease Caused by Circadian Rhythm Disruption through Regulating the m6A/KDM3A/TGF-ß1 Axis.

Disrupted circadian rhythms are associated with the onset of chronic diseases and impairments, including cancer, diabetes, and hypertension. However, whether circadian disruptions accelerate the progression of Alzheimer's disease and the respective pathway remains unclear. In this study, we constructed animal models using male C57BL/6N and APP/PS1 mice. Irregular illumination during sleeping hours was administered to the mice in our intervention groups to consistently disrupt their circadian rhythms. The impact of the intervention was evaluated through body weight tracking, cerebral index determination, histopathological staining, and biochemical marker analysis. Transcriptomic sequencing identified critical genes, with the data subsequently validated using RNA m6A detection and site analysis. The evaluations revealed that circadian disruptions impaired normal weight gain, liver and kidney functions, neuronal cells, and overall brain function. Transcriptomic sequencing data revealed a trend of elevating expression of Hif3α mRNA in the intervention groups. Further analysis of specific gene sites revealed that m6A methylation of the Hif3α gene at m6A site 3632 primarily drove the observed variations in HIF3A protein expression in our model. Furthermore, the expression of proteins in PC12 cells, N2a cells, and mice brains validated that an increase in HIF3A expression decreased KDM3A and TGF-ß1 protein expression. Our study reveals a hitherto unknown pathway through which the disruption of circadian rhythms, by triggering m6A methylation at m6A site 3632 in the Hif3α gene, leads to the initiation and acceleration of AD. These findings provide valuable insights and guidelines for treating AD patients and enhancing caregiving by professionals.

Bioactive Metal Ion-Coordinated Dynamic Hydrogel with Antibacterial, Immunomodulatory, and Angiogenic Activities for Infected Wound Repair.

The repair of infected wounds is a complex physiopathologic process. Current studies on infected wound treatment have predominantly focused on infection treatment, while the factors related to delayed healing caused by vascular damage and immune imbalance are commonly overlooked. In this study, an extracellular matrix (ECM)-like dynamic and multifunctional hyaluronic acid (HA) hydrogel with antimicrobial, immunomodulatory, and angiogenic capabilities was designed as wound dressing for the treatment of infected skin wounds. The dynamic network in the hydrogel dressing was based on reversible metal-ligand coordination formed between sulfhydryl groups and bioactive metal ions. In our design, antibacterial silver and immunomodulatory zinc ions were employed to coordinate with sulfhydrylated HA and a vasculogenic peptide. In addition to the desired bioactivities for infected wounds, the hydrogel could also exhibit self-healing and injectable abilities. Animal experiments with infected skin wound models indicated that the hydrogel dressings enabled minimally invasive injection and seamless skin wound covering and then facilitated wound healing by efficient bacterial killing, continuous inflammation inhibition, and improved blood vessel formation. In conclusion, the metal ion-coordinated hydrogels with wound-infection-desired bioactivities and ECM-like dynamic structures represent a class of tissue bionic wound dressings for the treatment of infected and chronic inflammation wounds.

Effects of Crocus sativus on glycemic control and cardiometabolic parameters among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials.

Metabolic syndrome (MetS) is a cluster of clinical syndromes that is closely associated with an elevated risk of developing atherosclerotic cardiovascular disease. In a series of animal experiments and clinical trials, crocus sativus and its component crocin have demonstrated promising hypoglycemic effects. However, there is currently insufficient evidence regarding their impact on cardiometabolic parameters. Our study aimed to assess the impact of Crocus sativus and crocin on glycemic control in individuals with metabolic syndrome and associated disorders, as well as their potential effects on improving cardiometabolic parameters. We searched Cochrane Library, PubMed, Embase, and Web of Science databases to ascertain the pertinent randomized controlled trials (RCTs) until December 30, 2023. Q-test and I2 statistics were utilized to evaluate heterogeneity among the included studies. Data were merged using a random-effects model and presented as (WMD) with a 95% confidence interval (CI). The current comprehensive review and meta-analysis, encompassing 13 RCTs involving a total of 840 patients diagnosed with metabolic syndrome and associated disorders, demonstrates that Crocus sativus was superior to placebo on Hemoglobin A1c(HbA1c) (WMD: -0.31;95% CI [-0.44,-0.19]. P = 0.002) and systolic blood pressure(SBP) (WMD:-7.49;95% CI [-11.67,-3.30]. P = 0.99) respectively. Moreover, Crocus sativus improved fasting blood glucose (FBG) (WMD:-7.25;95% CI [-11.82, -2.57]. P = 0.002) when used crocin and on other chronic diseases. Crocus sativus reduced the total cholesterol (TC) among the metabolic syndromepatients (WMD:-13.64;95%CI [-26.26, -1.03]. P = 0.03). We demonstrated that Crocus sativus exerts beneficial effects on glycemic control and cardiometabolic parameters in individuals with metabolic syndrome and related disorders.

Air Corrosion of Layered Cathode Materials for Sodium-Ion Batteries: Cation Mixing and a Practical Suppression Strategy.

Layered oxide cathodes of sodium-ion batteries (SIBs) are considered promising candidates due to their fascinating high capacity, good cyclability, and environmental friendliness. However, the air sensitivity of layered SIB cathodes causes high electrode manufacturing costs and performance deterioration, hampering their practical application. Herein, a commercial O3-type layered Na(Ni1/3Fe1/3Mn1/3)O2 (NNFM) material is adopted to investigate the air corrosive problem and the suppression strategy. We reveal that once the layered material comes in contact with ambient air, cations migrate from transition metal (TM) layers to sodium layers at the near surface, although Na+ and TM ions show quite different ion radii. Experimental results and theoretical calculations show that more Ni/Na disorder occurs in the air-exposed O3-NNFM materials, owing to a lower Ni migration energy barrier. The cation mixing results in detrimental structural distortion, along with the formation of residual alkali species on the surface, leading to high impedance for Na+ diffusion during charge/discharge. To tackle this problem, an ultrathin and uniform hydrophobic molecular layer of perfluorodecyl trimethoxysilane is assembled on the O3-NNFM surface, which significantly suppresses unfavorable chemistry and structure degradation during air storage. The in-depth understanding of the structural degradation mechanism and suppression strategy presented in this work can facilitate high-energy cathode manufacturing from the perspective of future practical implementation and commercialization.

Construction of human 3D striato-nigral assembloids to recapitulate medium spiny neuronal projection defects in Huntington's disease.

The striato-nigral (Str-SN) circuit is composed of medium spiny neuronal projections that are mainly sent from the striatum to the midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of the Str-SN circuitry may cause a series of motor disabilities that are associated with neurodegenerative disorders, such as Huntington's disease (HD). Although the etiology of HD is known as abnormally expanded CAG repeats of the huntingtin gene, treatment of HD remains tremendously challenging. One possible reason is the lack of effective HD model that resembles Str-SN circuitry deficits for pharmacological studies. Here, we first differentiated striatum-like organoids from human pluripotent stem cells (hPSCs), containing functional medium spiny neurons (MSNs). We then generated 3D Str-SN assembloids by assembling striatum-like organoids with midbrain SN-like organoids. With AAV-hSYN-GFP-mediated viral tracing, extensive MSN projections from the striatum to the SN are established, which formed synaptic connection with GABAergic neurons in SN organoids and showed the optically evoked inhibitory postsynaptic currents and electronic field potentials by labeling the striatum-like organoids with optogenetic virus. Furthermore, these Str-SN assembloids exhibited enhanced calcium activity compared to that of individual striatal organoids. Importantly, we further demonstrated the reciprocal projection defects in HD iPSC-derived assembloids, which could be ameliorated by treatment of brain-derived neurotrophic factor. Taken together, these findings suggest that Str-SN assembloids could be used for identifying MSN projection defects and could be applied as potential drug test platforms for HD.

Translation, Cross-Cultural Adaptation and Validation of the Chinese Version of the High Activity Arthroplasty Score.

Background: The High Activity Arthroplasty Score (HAAS) is a validated score that assesses functional outcomes after lower limb arthroplasty, with fewer ceiling effects than other scores. The aim is to translate and cross-culturally adapt the HAAS into a Chinese version (HAAS-C) and to evaluate the psychometric properties of HAAS-C in patients after primary total knee arthroplasty (TKA). Methods: A total of 104 patients diagnosed with knee osteoarthritis who had undergone TKA at least 12 months prior were recruited. A forward and backward translation procedure was performed for developing a culturally acceptable HAAS-C. Internal consistency was assessed using Cronbach's α, and test-retest reliability was measured using the intraclass correlation coefficient (ICC) within a 10-day interval. Construct validity was assessed by examining the correlations between HAAS-C and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQoL Group's five-dimension questionnaire (EQ-5D-5L), and Oxford knee score (OKS). Results: HAAS-C demonstrated adequate Internal consistency reliability, as indicated by Cronbach's α coefficient of 0.75. Test-retest reliability yielded excellent results, with an ICC value of 0.98. Content validity indices were high, with a scale-level validity index of 0.9 and item-level validity indices greater than or equal to 0.8. HAAS-C showed a strong correlation with WOMAC (r = 0.69), a moderate correlation with EQ-5D-5L (r = 0.43), and OKS (r = 0.53) while exhibiting no floor or ceiling effects. Conclusion: The validated HAAS-C questionnaire is a valid instrument for assessing patients undergoing TKA in mainland China.

Single-Cell Transcriptome Landscape and Cell Fate Decoding in Human Brain Organoids after Transplantation.

Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single-cell sequencing is then performed. According to time-series sample comparison, transplanted cells mainly undergo neural development at 2 months post-transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine.

Dietary supplementation with ellagic acid improves the growth performance, meat quality, and metabolomics profile of yellow-feathered broiler chickens.

The aim of this research was to explore the effects of ellagic acid (EA) on growth performance, meat quality, and metabolomics profile of broiler chickens. 240 healthy yellow-feathered broilers were randomly divided into 4 groups (6 replicates/group and 10 broilers /replicate): 1) a standard diet (CON); 2) CON+0.01% EA; 3) CON+0.02% EA; 4) CON+0.04% EA. Compared with the CON group, dietary 0.02% EA increased linearly and quadratically the ADG and lowered F/G ratio from 29 to 56 d and from 1 to 56 d of age (P < 0.05). The EA groups had higher spleen index and showed linear and quadratic improve thymus index (P < 0.05). A total of 0.02% EA linearly and quadratically increased the leg muscle percentage and quadratically increased the breast muscle percentage (P < 0.05). Compared to the control diet, 0.02% EA decreased quadratically the L* and increased a* of breast muscle at 45 min postslaughter (P < 0.05), and quadratically decreased (P < 0.05) the b* and increased linearly and quadratically (P < 0.05) drip loss. Additionally, EA improved linearly and quadratically (P < 0.05) serum total protein concentration and reduced linearly and quadratically (P < 0.05) serum blood urea nitrogen concentration. A total of 0.02% EA quadratically increased catalase activity and decreased malondialdehyde concentration in breast muscle compared with the control diet (P < 0.05). 0.02% and 0.04% EA could linearly and quadratically increase (P < 0.05) the concentrations of histidine, leucine and essential amino acids (EAA), 0.02% EA could linearly and quadratically increase (P < 0.05) the concentrations of threonine, glutamate, and flavored amino acids in breast muscle. 0.02% EA linearly and quadratically improved the C20:3n6, C22:6n3, polyunsaturated fatty acid (PUFA) concentrations, and the ratio of PUFA to saturated fatty acids (SFA), but reduced the C16:0 and the SFA concentrations in breast muscle than the CON group (P < 0.05). The EA diet linearly increased (P = 0.035) and quadratically tended (P = 0.068) to regulate the C18:2n6c concentration of breast muscle. Metabolomics showed that alanine metabolism, aspartate and glutamate metabolism, arginine and proline metabolism, taurine and hypotaurine metabolism, and glycerophospholipid metabolism were the most differentially abundant. These results showed that EA supported moderate positive effects on growth performance, meat quality, and metabolomics profile of broilers.

Guanidinoacetic acid ameliorates hepatic steatosis and inflammation and promotes white adipose tissue browning in middle-aged mice with high-fat-diet-induced obesity.

Guanidinoacetic acid (GAA) is a naturally occurring amino acid derivative that plays a critical role in energy metabolism. In recent years, a growing body of evidence has emerged supporting the importance of GAA in metabolic dysfunction. Hence, we aimed to investigate the effects of GAA on hepatic and adipose tissue metabolism, as well as systemic inflammatory responses in obese middle-aged mice models and attempted to explore the underlying mechanism. We found that dietary supplementation of GAA inhibited inguinal white adipose tissue (iWAT) hypertrophy in high-fat diet (HFD)-fed mice. In addition, GAA supplementation observably decreased the levels of some systemic inflammatory factors, including IL-4, TNF-α, IL-1ß, and IL-6. Intriguingly, GAA supplementation ameliorated hepatic steatosis and lipid deposition in HFD-fed mice, which was revealed by decreased levels of TG, TC, LDL-C, PPARγ, SREBP-1c, FASN, ACC, FABP1, and APOB and increased levels of HDL-C in the liver. Moreover, GAA supplementation increased the expression of browning markers and mitochondrial-related genes in the iWAT. Further investigation showed that dietary GAA promoted the browning of the iWAT via activating the AMPK/Sirt1 signaling pathway and might be associated with futile creatine cycling in obese mice. These results indicate that GAA has the potential to be used as an effective ingredient in dietary interventions and thus may play an important role in ameliorating and preventing HFD-induced obesity and related metabolic diseases.