Associations of change in body fat percentage with baseline body composition and diabetes remission after bariatric surgery.

OBJECTIVE: The objective of this study was to determine the role of body fat percentage (BFP) changes in diabetes remission (DR) and the association between baseline body composition and its changes after bariatric surgery. METHODS: We analyzed 203 patients with type 2 diabetes who underwent Roux-en-Y gastric bypass. Body composition was measured using a gold-standard-derived predictive equation and magnetic resonance imaging. Body composition changes were calculated as 100 × (baseline value - follow-up value)/baseline value. We verified the results in a laparoscopic sleeve gastrectomy cohort with 311 patients. RESULTS: Compared with non-remission patients in the Roux-en-Y gastric bypass cohort, those who achieved DR showed a higher baseline fat-free mass index (FFMI) and experienced the most significant changes in BFP (p < 0.001). In comparative analyses, BFP changes were significantly better than BMI changes in identifying short- and long-term DR. Linear regression analysis identified FFMI as the most significant baseline variable correlated with BFP changes (p < 0.001). Baseline BMI was positively correlated with changes in BFP but negatively correlated with changes in FFMI. These findings were replicated in the laparoscopic sleeve gastrectomy cohort. CONCLUSIONS: BFP changes determine DR after bariatric surgery, and baseline FFMI is crucial for BFP changes. A low initial BMI is associated with a smaller BFP reduction and greater FFMI loss after bariatric surgery.

Mechanism of the Effect of Scopolamine on Breast Cancer: Determination by Network Pharmacology and Bioinformatics.

BACKGROUND: To a certain extent, traditional Chinese medicine (TCM)-based anesthesia has replaced opiate administration in recent years. Preliminary drug screening has revealed that scopolamine may affect breast cancer (BC) metastasis by an unknown mechanism. METHODS: Network pharmacology, bioinformatics, and protein-protein interaction (PPI) topological analysis were implemented to identify the core genes linking scopolamine and BC. The core genes were then subjected to gene expression profiling interactive analysis (GEPIA). The top ten pathways were detected by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The impact of immune infiltration on the core gene difference and survival analyses was then determined. Molecular docking was then performed on the core genes and the main active components. RESULTS: Protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), heat shock protein 90 alpha class A (HSP90AA1), caspase 3 (CASP3), and estrogen receptor 1 (ESR1) were the key genes in the interaction between scopolamine and BC cells. The KEGG enrichment analysis disclosed that the top ten pathways significantly associated with the scopolamine response in BC included "protein glycosylation," "phosphoinositide 3-kinase (PI3K)-Akt signaling," "mitogen- activated protein kinase (MAPK) signaling" and others. The AKT1, EGFR, and especially the HSP90AA1 expression levels were correlated with survival in patients with BC. Immune infiltration also influenced the survival outcome. Molecular docking demonstrated that scopolamine bound and formed stable complexes with the protein products of all five aforementioned genes. CONCLUSION: Scopolamine has multiple targets regulating BC cell function and may increase the risk of metastasis during treatment. Therefore, it should be preoperatively administered with caution to patients with BC.

Associations of Serum Uric Acid to High-Density Lipoprotein Cholesterol Ratio with Trunk Fat Mass and Visceral Fat Accumulation.

Background: It has been reported recently that the ratio of uric acid to high-density lipoprotein cholesterol (UHR) is correlated with several metabolic disorders. The present study aimed to investigate the associations of UHR with body fat content and distribution. Methods: This study enrolled 300 participants (58 men and 242 women) aged 18 to 65 years. The levels of serum uric acid and high-density lipoprotein cholesterol were measured by standard enzymatic methods. The overall fat content and segmental fat distribution were assessed with an automatic bioelectrical impedance analyzer. In the population with obesity, the visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. Results: Among the study population, 219 individuals (73.0%) were with obesity. The median level of UHR in individuals with obesity was 33.7% (26.2% - 45.9%), which was significantly higher than that in those without obesity [22.6% (17.0% - 34.4%), P < 0.01]. UHR was positively associated with overall fat content and segmental fat distribution parameters (all P < 0.01). In multivariate linear regression analysis, compared with body mass index, waist circumference was more closely associated with UHR (standardized ß = 0.427, P < 0.001) after adjusting for confounding factors. Additionally, total fat mass (standardized ß = 0.225, P = 0.002) and trunk fat mass (standardized ß = 0.296, P = 0.036) were more closely linked to UHR than total fat-free mass and leg fat mass, respectively. In the population with obesity, VFA was independently correlated with UHR (P < 0.01), while SFA was not associated with UHR. Conclusion: UHR was significantly associated with overall fat content and trunk fat accumulation. In the population with obesity, UHR was positively associated with VFA. Attention should be paid to the role of excessive trunk fat mass in the relationship between UHR and metabolic disorders.

Neck circumference as a potential indicator of pre-sarcopenic obesity in a cohort of community-based individuals.

BACKGROUND & AIMS: ESPEN/EASO advocates screening for sarcopenic obesity based on the concomitant presence of an elevated body mass index (BMI) or waist circumference. Neck circumference (NC) is another simple and reliable anthropometric measurement for estimating obesity; however, its ability to detect sarcopenic obesity has not yet been established. The aim of the present study was to explore the association between NC and sarcopenic obesity in a Shanghai community population. METHODS: The study included 1542 participants (622 men and 920 women) with a mean age of 58 years who underwent an examination for the detection of obesity at baseline in 2013-2014 and received a re-examination in 2015-2016. An automatic bioelectric impedance analyzer was used to estimate body composition, and magnetic resonance imaging was used to measure abdominal fat distribution. The definition of pre-sarcopenic obesity combined low skeletal muscle mass adjusted by weight (SMM/W) with obesity which defined according to overall adiposity or fat distribution as BMI ≥25 kg/m2, fat percentage (fat%) ≥ 25% in men and 30% in women, or visceral fat area (VFA) ≥ 80 cm2, respectively. RESULTS: In both men and women, subjects with low SMM/W had a higher level of NC than those without (both P < 0.01). In turn, participants with elevated NC had a higher proportion of pre-sarcopenic obesity in both men and women, regardless of adiposity status assessed by BMI, fat%, or VFA (all P < 0.01). During an average follow up of 2.1 years, for each 1 cm increase in NC, multivariable-adjusted hazard ratios of pre-sarcopenic obesity in which adiposity status assessed by high BMI were 1.40 (1.11-1.76) in men and 1.32 (1.13-1.56) in women; in addition, such association remained between NC and pre-sarcopenic obesity assessed by high fat% or high VFA. CONCLUSION: NC is closely associated with the incidence of sarcopenic obesity, suggesting that it could be helpful for screening sarcopenic obesity in a community-based population.

Submonolayer biolasers for ultrasensitive biomarker detection.

Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson's disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity.

Interaction between serum neutrophil gelatinase associated lipocalin and visceral fat area on cardiovascular health in a cohort of community-based individuals.

BACKGROUND: We assessed the predictive values of neutrophil gelatinase-associated lipocalin (NGAL), fat distribution, and their interaction on the development of major adverse cardiovascular events (MACE) in a community-based cohort of middle-aged and older individuals. METHODS: This prospective study involved 1349 adults (43.2% men) aged 50-80 y, without baseline cardiovascular diseases, from communities in 2013-2014. All participants were followed up for a mean of 7.6 y via phone calls and medical records. Serum NGAL concentrations were analyzed at baseline. Fat distribution, including subcutaneous fat area and visceral fat area (VFA), was assessed by magnetic resonance imaging. RESULTS: In fully-adjusted Cox regression models, baseline high NGAL concentrations were related to an increased risk of MACE in women [HR 1.75, 95% CI 1.03-2.99], compared with low NGAL concentrations. After stratification by VFA concentrations, the observed association was more predominant in women with baseline low VFA (HR 1.24, 95% CI 1.11-1.38). Moreover, the association between NGAL and MACE was interacted by VFA, strengthening the association at low VFA concentrations (Pinteraction < 0.05). CONCLUSIONS: Serum NGAL determined at baseline predicts the development of MACE, and the association is modified by VFA in women.

Effect of regional body composition changes on bone density remodeling after sleeve gastrectomy.

Background: Sleeve gastrectomy (SG) results in bone mineral density (BMD) loss and varying body composition parameters. However, the effects of body compositions on bone health are controversial. In order to accurately demonstrate their relationship and provide new insights into the causes of BMD loss after sleeve gastrectomy, this study is aimed to investigate the role of changes in body composition in BMD loss 12 months after SG. Methods: 41 Chinese individuals with obesity (25 women and 16 men) who underwent SG were prospectively examined for at least 12 months. Measurements of anthropometrics, body composition, BMD and blood samples were collected. Results: For 12 months, the femoral neck (FN) BMD and total hip (TH) BMD decreased significantly compared with baseline in both sexes but not lumbar spine (LS) BMD. Greater TH BMD loss was observed in men than in women. For the first 6 months post-SG, the FN BMD loss was positively associated with the estimated fat free mass index (eFFMI) reduction in women (adjusted ß = 0.77, P = 0.004) and positively associated with reduction of subcutaneous fat area (SFA) in men (r = 0.931, P = 0.007). For 12 months post-SG, the FN BMD loss was negatively associated with visceral fat area (VFA) reduction in women (adjusted ß = -0.58, P = 0.027) and men (adjusted ß = -0.68, P = 0.032). TH BMD loss was positively associated with waist circumference reduction in women (r = 0.448, P = 0.028). Conclusion: FN and TH BMD decrease after SG in both women and men. The changes in body compositions are associated with BMD loss at different time points and bone sites. Our data emphasize the limitation of simply taking the total weight loss (% TWL) as an influencing factor of bone mineral density and the necessity of delineating body composition in relevant studies.

Non-Hermitian Chiral Heat Transport.

Exceptional point (EP) has been captivated as a concept of interpreting eigenvalue degeneracy and eigenstate exchange in non-Hermitian physics. The chirality in the vicinity of EP is intrinsically preserved and usually immune to external bias or perturbation, resulting in the robustness of asymmetric backscattering and directional emission in classical wave fields. Despite recent progress in non-Hermitian thermal diffusion, all state-of-the-art approaches fail to exhibit chiral states or directional robustness in heat transport. Here we report the first discovery of chiral heat transport, which is manifested only in the vicinity of EP but suppressed at the EP of a thermal system. The chiral heat transport demonstrates significant robustness against drastically varying advections and thermal perturbations imposed. Our results reveal the chirality in heat transport process and provide a novel strategy for manipulating mass, charge, and diffusive light.

Advances in the Mechanism of Luteolin against Hepatocellular Carcinoma Based on Bioinformatics and Network Pharmacology.

As one of the most common malignant tumors, hepatocellular carcinoma (HCC) has a rising incidence rate and also seriously endangers human life and health. According to research reports, hepatitis B, hepatitis C, intake of aflatoxin in the diet, and the effects of alcohol and other chemicals can induce an increase in the incidence of liver cancer. However, in the current clinical treatment of HCC, most of the drugs are chemical drugs, which have relatively large side effects and are prone to drug resistance. Therefore, the development of natural compounds to treat HCC has become a new treatment strategy. Several studies have shown that flavonoids have shown outstanding effects and exhibit strong tumor growth inhibitory effects in vivo experimental studies. Luteolin, as a natural flavonoid, has anti-tumor, anti-inflammatory, anti-viral, anti-oxidation, immune regulation, and other pharmacological effects. The anti-cancer mechanism of luteolin mainly directly acts on tumor cells to inhibit their growth, induce cell apoptosis, reduce tumor tissue angiogenesis, regulate long non-coding RNA, affect immunogenic cell death, and regulate autophagy. As well as improving the curative effect of radiotherapy and chemotherapy and chemoprevention. In this study, we evaluated the function of luteolin in regulating cancer cell proliferation, migration, and invasion will summarize and analyze luteolin and its mechanism of regulating HCC to improve the role of luteolin in the clinical prevention and treatment of HCC.

Soliton Microcombs Multiplexing Using Intracavity-Stimulated Brillouin Lasers.

Solitons in microresonators have spurred intriguing nonlinear optical physics and photonic applications. Here, by combining Kerr and Brillouin nonlinearities in an over-modal microcavity, we demonstrate spatial multiplexing of soliton microcombs under a single external laser pumping operation. This demonstration offers an ideal scheme to realize highly coherent dual-comb sources in a compact, low-cost and energy-efficient manner, with uniquely low beating noise. Moreover, by selecting the dual-comb modes, the repetition rate difference of a dual-comb pair could be flexibly switched, ranging from 8.5 to 212 MHz. Beyond dual-comb, the high-density mode geometry allows the cascaded Brillouin lasers, driving the co-generation of up to 5 space-multiplexing frequency combs in distinct mode families. This Letter offers a novel physics paradigm for comb interferometry and provides a widely appropriate tool for versatile applications such as comb metrology, spectroscopy, and ranging.

Ceftazidime-Avibactam Treatment for Severe Post-Neurosurgical Meningitis and Abscess Caused by Extended-Spectrum ß-Lactamase Escherichia coli in a Pediatric Patient: A Case Report.

Post-neurosurgical infections caused by multidrug-resistant Enterobacterales are difficult to treat due to limited therapeutic options. Ceftazidime-avibactam (CAZ-AVI), a combination of cephalosporin and a novel ß-lactamase inhibitor, has exhibited potential activity against multi/extensive drug-resistant (MDR/XDR) gram-negative bacilli. Several reports have described the successful treatment of central infections caused by MDR/XDR Pseudomonas aeruginosa or Enterobacterales. However, data on the efficacy and effective drug distribution of CAZ-AVI in the central nervous system (CNS), particularly in children, are lacking. We report a case of a 4-year-old girl with post-neurosurgical meningitis and abscess caused by extended-spectrum ß-lactamase-producing Escherichia coli successfully treated with CAZ-AVI. CAZ-AVI therapeutic drug monitoring was performed to evaluate its efficacy and effective drug distribution in the CNS. We measured CAZ (15.6, 7.1, and 3.5 µg/mL) and AVI (4.0, 2.1, and 1.2 µg/mL) in cerebrospinal fluid (CSF) samples obtained 3, 5, and 7 h after the administration of the 15th CAZ-AVI dose (2.5 g, q8h, iv), respectively. We also measured CAZ (57.0 and 25.8 µg/mL) and AVI (11.3 and 4.5 µg/mL) in serum samples obtained 3 and 5 h after the administration, respectively. CAZ-AVI achieved an adequate CSF concentration throughout the drug interval. Our case provides evidence for using CAZ-AVI to treat CNS infections.

Trapping photons with optical black hole.

An optical black-hole cavity based on transformation optics enables Q-factor enhancement and strong field confinement, by eliminating the intrinsic radiation loss of the conventional whispering-gallery modes, holding potential for applications in energy harvesting and optoelectronics.

Phase-Transition Microcavity Laser.

Liquid-crystal microcavity lasers have attracted considerable attention because of their extraordinary tunability and sensitive response to external stimuli, and because they operate generally within a specific phase. Here, we demonstrate a liquid-crystal microcavity laser operated in the phase transition in which the reorientation of liquid-crystal molecules occurs from aligned to disordered states. A significant wavelength shift of the microlaser is observed, resulting from the dramatic changes in the refractive index of liquid-crystal microdroplets during the phase transition. This phase-transition microcavity laser is then exploited for sensitive thermal sensing, enabling a two-order-of-magnitude enhancement in sensitivity compared with the nematic-phase microlaser operated far from the transition point. Experimentally, we demonstrate an exceptional sensitivity of -40 nm/K and an ultrahigh resolution of 320 µK. The phase-transition microcavity laser features compactness, softness, and tunability, showing great potential for high-performance sensors, optical modulators, and soft matter photonics.

Nonreciprocal Frequency Conversion and Mode Routing in a Microresonator.

The transportation of photons and phonons typically obeys the principle of reciprocity. Breaking reciprocity of these bosonic excitations will enable the corresponding nonreciprocal devices, such as isolators and circulators. Here, we use two optical modes and two mechanical modes in a microresonator to form a four-mode plaquette via radiation pressure force. The phase-controlled nonreciprocal routing between any two modes with completely different frequencies is demonstrated, including the routing of phonon to phonon (megahertz to megahertz), photon to phonon (terahertz to megahertz), and especially photon to photon with frequency difference of around 80 THz for the first time. In addition, one more mechanical mode is introduced to this plaquette to realize a phononic circulator in such single microresonator. The nonreciprocity is derived from interference between multimode transfer processes involving optomechanical interactions in an optomechanical resonator. It not only demonstrates the nonreciprocal routing of photons and phonons in a single resonator but also realizes the nonreciprocal frequency conversion for photons and circulation for phonons, laying a foundation for studying directional routing and thermal management in an optomechanical hybrid network.

Obesity-Induced Hepatic Steatosis Is Partly Mediated by Visceral Fat Accumulation in Subjects with Overweight/Obesity: A Cross-Sectional Study.

INTRODUCTION: We explored whether visceral fat accumulation mediates the development of hepatic steatosis in individuals living with overweight and obesity. METHODS: This cross-sectional study enrolled 769 outpatients with overweight and obesity aged 18-65 years. The controlled attenuation parameter (CAP) was used to quantify the degree of hepatic steatosis. Visceral fat accumulation, represented by the visceral fat area (VFA), was measured using magnetic resonance imaging. The associations of body mass index (BMI), VFA, and CAP with each other were assessed by univariate analysis, multivariate linear regression, and mediation analysis, respectively. RESULTS: Compared with women, male subjects had higher BMI, VFA, and CAP levels. In both sex, CAP was positively correlated with BMI and VFA by the univariate analysis. After adjusting for demographic and serum characteristics, the linear correlation coefficients between BMI and CAP were 1.738 (95% confidence interval (CI): 1.100, 2.377), 1.524 (95% CI: 0.798, 2.249), and 2.650 (95% CI: 1.292, 4.009) in all subjects, females, and males, respectively, while those between VFA and CAP were 0.190 (95% CI: 0.133, 0.247), 0.184 (95% CI: 0.117, 0.252), and 0.194 (95% CI: 0.086, 0.301). Mediation analysis showed that visceral fat accumulation contributed to 51.37%, 53.85%, and 26.51% of obesity-induced hepatic steatosis in the total, female, and male subjects, respectively. CONCLUSION: Visceral fat accumulation partially mediates obesity-induced hepatic steatosis in individuals with overweight and obesity, especially in women. More focus on visceral fat reduction is needed in individuals with obesity.

Sex-specific differences in bone mineral density loss after sleeve gastrectomy.

Background: Sleeve gastrectomy is an effective bariatric procedure; however, sleeve gastrectomy-related adverse skeletal outcomes have been increasingly reported. High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes. The aim of this study was to identify sex-specific changes in BMD following sleeve gastrectomy and to evaluate the role of SHBG in this process. Methods: This retrospective study included 19 middle-aged men and 30 non-menopausal women with obesity who underwent sleeve gastrectomy in China. Anthropometrics, bone turnover markers, calciotropic hormones, BMD, SHBG, and gonadal steroids were measured preoperatively and at 6 and 12 months postoperatively. Longitudinal changes in BMD, bone turnover markers and SHBG were compared between sexes by linear mixed models. Multiple stepwise regression analysis was used to identify the predictors of BMD loss at the investigated bone sites. Results: Over the 12-month study period, total hip and femoral neck BMD decreased, while lumbar spine BMD remained largely unchanged in both sexes. Linear mixed models revealed significant sex × time interaction effects in total hip BMD and SHBG, showing that men had a significantly greater reduction in total hip BMD and less increase in SHBG after sleeve gastrectomy than women. In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted ß = -0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women (adjusted ß = 0.508, P = 0.01) but not men. Conclusion: Significant sex-specific BMD changes were observed after sleeve gastrectomy in the current study. Sleeve gastrectomy-related increase in SHBG may be a specific risk factor for total hip BMD loss in men. Our results indicate that sex-specific screening may be warranted to facilitate personalized postoperative bone care in this population.

Dissipative Acousto-optic Interactions in Optical Microcavities.

We propose and demonstrate experimentally the strong dissipative acousto-optic interaction between a suspended vibrating microfiber and a whispering-gallery microcavity. On the one hand, the dissipative response driven by an external stimulus of acoustic waves is found to be stronger than the dispersive response by 2 orders of magnitude. On the other hand, dead points emerge with the zero dissipative response at certain parameters, promising the potentials in physical sensing such as precise measurements of magnetic field and temperature. The strong dissipative acousto-optic interaction is then explored for ultrasensitive detection of broadband acoustic waves. A noise equivalent pressure as low as 0.81 Pa at 140 kHz in air is demonstrated experimentally, insensitive to cavity Q factors and does not rely on mechanical resonances.

The application of proteomics and metabolomics to reveal the molecular mechanism of Nutmeg-5 in ameliorating cardiac fibrosis following myocardial infarction.

BACKGROUND: Nutmeg-5, an ancient and classic formula in traditional Mongolian medicine comprising five kinds of traditional Chinese medicine, is widely used in the treatment of myocardial infarction (MI, called heart "Heyi" disease in Mongolian medicine). Cardiac fibrosis plays a critical role in the development and progression of heart failure after MI. However, the material basis and pharmacological mechanisms of the effect of Nutmeg-5 on cardiac fibrosis after MI remain unclear. OBJECTIVE: The aim of this study was to first explore the potential material basis and molecular mechanism of action of Nutmeg-5 in improving cardiac fibrosis after MI via a multiomics approach. METHODS: The constituents in Nutmeg-5 were identified by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). High-performance liquid chromatography (HPLC) and gas chromatography (GC)-based fingerprints of Nutmeg-5 were analysed, and characteristic peaks were identified by comparison to standard samples. A rat MI model was created by permanent ligation of the left anterior descending artery. The protective effect of Nutmeg-5 on cardiac fibrosis after MI was evaluated by tissue histology and measurement of the serum biomarkers of myocardial injury. Cardiac fibrosis levels were evaluated by Sirius red staining. Differentially expressed proteins in the myocardium and metabolites in the serum were explored by proteomic and untargeted metabolome analyses, respectively. Pearson correlation analysis was performed to explore the association between serum metabolites and myocardial proteins. RESULTS: A total of 67 constituents were identified in Nutmeg-5 by UPLC-MS/MS. Sixteen components were identified in the fingerprint of Nutmeg-5 by comparison with a standard sample. Six lactones were isolated from Nutmeg-5 and quantified by HPLC and GC. MI was significantly alleviated in Nutmeg-5-treated rats compared to MI rats, as demonstrated by their decreased mortality, improved cardiac function, and attenuated cardiac fibrosis and myocardial injury. A total of 252 significant differential metabolites were identified in plasma between model and Nutmeg-5-treated rats by untargeted metabolome analysis. Among these, 36 critical metabolites were associated with Nutmeg-5 activity. Proteomic analysis identified 338 differentially expressed proteins in the rat myocardium between MI and Nutmeg-5-treated rats, including 204 upregulated and 134 downregulated proteins. Protein set enrichment analysis revealed that Nutmeg-5 treatment significantly inhibited the extracellular matrix (ECM)-receptor interaction pathway, which was activated in the myocardium of MI rats. A significant decrease in collagen and alpha smooth muscle actin expression levels was found in the myocardium of Nutmeg-5-treated rats compared to MI rats. These results illustrated that Nutmeg-5 had a significant protective effect on cardiac fibrosis after MI. A significant correlation was found between the ECM-receptor interaction pathway in the myocardium and critical metabolites in the serum. In addition, there were positive correlations between the levels of critical metabolites and the expression levels of transforming growth factor (TGF)-ß1 and Smad2 in the rat myocardium. CONCLUSIONS: Nutmeg-5 alleviated cardiac fibrosis after MI in rats by inhibiting the myocardial ECM-receptor interaction pathway and TGF-ß1/Smad2 signalling, which was achieved by regulating plasma metabolites.