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Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

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JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

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Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

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JOURNAL/nrgr/04.03/01300535-202505000-00027/figure1/v/2024-07-28T173839Z/r/image-tiff Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia. We also examined the role of exercise-induced circulating factors in these effects. Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion. We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area, inhibited gliogenesis, protected synaptic proteins, and improved novel object and spatial memory function. Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise. Agonist activation of adiponectin receptors by AdipoRon mimicked the effects of exercise, while inhibiting receptor activation abolished the exercise effects. In summary, our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

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Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown origin that can cause significant disability and morbidity with its progression. Due to the unique nature of CD, surgery is often necessary for many patients during their lifetime, and the incidence of postoperative complications is high, which can affect the prognosis of patients. Therefore, it is essential to identify and manage postoperative complications. Machine learning (ML) has become increasingly important in the medical field, and ML-based models can be used to predict postoperative complications of intestinal resection for CD. Recently, a valuable article titled "Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study" was published by Wang et al. We appreciate the authors' creative work, and we are willing to share our views and discuss them with the authors.

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In order to discuss the clinical and MRI features, diagnosis, and prevention of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), we reported an adult case of MOG antibody-related disease misdiagnosed as cerebral infarction. This patient's first clinical symptom was limb weakness, that different from previous reports of MOG antibody-related diseases, such as brainstem encephalitis, neuromyelitis optical, and transverse myelitis. The main treatment plan is high-dose corticosteroid therapy combined with immunoglobulin therapy. This case indicated that some MOGAD patients lack of specificity in the clinical manifestations and imaging perhaps would be misdiagnosed as cerebral infarction, encephalitis, immune peripheral neuropathy, MS, NMOSD, and other diseases. For patients with atypical clinical manifestations or imaging, it is especially important to take antibody detection as early as possible to make correct diagnosis and active treatment in time to avoid disability.

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Objective To analyze the clinical features of 17 patients with primary angiitis of the central nervous system (PACNS) and thus facilitate the early diagnosis and treatment,reduce the recurrence and mortality,and improve the prognoses of this disease. Methods We collected the data of patients with PACNS diagnosed by brain biopsy from January 2009 to June 2023 and analyzed their clinical presentations,laboratory and imaging manifestations,electrophysiological and pathological changes,and treatment regimens and prognosis. Results The 17 patients diagnosed with PACNS via brain biopsy included one child and 16 adults.The subtyping results showed that 10,2,3,2,1,and 1 patients had tumorous,spinal cord-involved,angiography-positive,rapidly progressive,hemorrhagic,and amyloid ß-related PACNS,respectively.Eleven (64.7%) of the patients were complicated with secondary epilepsy.All the patients exhibited abnormal manifestations in head MRI,with 94.1% showing lesions with uneven enhancement around the lesions or in the leptomeninges. Magnetic resonance angiography revealed large vessel abnormalities in 3 patients,and spinal cord involvement was observed in 2 patients.Histopathological typing revealed 7 (43.7%) patients with lymphocytic vasculitis and 5 (31.2%) patients with necrotizing vasculitis.Eleven patients were treated with glucocorticoids and cyclophosphamide,which resulted in partial lesion disappearance and symptom amelioration in 6 patients upon reevaluation with head MRI after 3 months of maintenance therapy.Two,1,and 3 patients experienced rapid disease progression,death,and recurrence within 1 year,respectively.Three patients showed insensitivity to hormonotherapy and residual disabilities.Two patients received rituximab after relapse and remained clinically stable during a follow-up period of 0.5-1 year. Conclusion Tumorous PACNS was more prone to epilepsy,mainly occurring in males.The most common histopathological type was necrotizing vasculitis,which responded to hormonotherapy and had favorable outcomes.Therefore,for the young patients with epilepsy and intracranial tumorous lesions,the possibility of PACNS should be considered.Spinal cord involvement in PACNS was often located in the thoracic and cervical cords,suggesting a poorer prognosis.Electromyography commonly revealed neural conduction abnormalities in the anterior horn or roots,providing clues for differential diagnosis.For suspected spinal cord involvement,comprehensive electromyography is recommended.Rapidly progressive PACNS often presented infratentorial lesions,such as lesions in the pons and medulla,with a higher mortality rate.Hemorrhagic PACNS was rare,and a multifocal hemorrhagic lesion with enhancement in the intracranial region,particularly in young patients,should raise suspicion.For the patients with recurrent or progressive disease,rituximab is a recommended therapeutic option.

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This study aimed to identify different symptom trajectories based on the severity of depression symptoms within a 2-month follow-up, and to explore predictive factors for different symptom trajectories. Three hundred and ninety-two adults diagnosed with major depressive disorder (MDD) were recruited from two longitudinal cohorts. Patients received antidepressant treatment as usual, and the depression symptoms were evaluated by the 17-item Hamilton depression rating scale (HAMD-17) at baseline, two weeks, and eight weeks. Based on the HAMD-17 scores, different trajectories of symptom change were distinguished by applying Growth Mixture Modeling (GMM). Furthermore, the baseline sociodemographic, clinical, and cognitive characteristics were compared to identify potential predictors for different trajectories. Through GMM, three unique depressive symptom trajectories of MDD patients were identified: (1) mild-severity class with significant improvement (Mild, n = 255); (2) high-severity class with significant improvement (High, n = 39); (3) moderate-severity class with limited improvement (Limited, n = 98). Among the three trajectories, the Mild class had a relatively low level of anxiety symptoms at baseline, whereas the High class had the lowest education level and the worst cognitive performance. Additionally, participants in the Limited class exhibited an early age of onset and experienced a higher level of emotional abuse. MDD patients could be categorised into three distinct latent subtypes through different symptom trajectories in this study, and the characteristics of these subtype patients may inform identifications for trajectory-specific intervention targets.

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BACKGROUND: Rotational atherectomy (RA) remains an integral tool for the treatment of severe coronary calcified lesions despite emergence of newer techniques. We aimed to evaluate the contemporary clinical practices and outcomes of RA in China. METHODS: The Rota China Registry (NCT03806621) was an investigator-initiated, prospective, multicenter registry based on China Rota Elite Group. Consecutive patients treated with RA were recruited. A pre-designed, standardized protocol was recommended for the RA procedure. The primary safety endpoint was major adverse cardiovascular events (MACE: composite of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) at 30 days. The primary efficacy endpoint was procedural success. RESULTS: Between July 2018 and December 2020, 980 patients were enrolled at 19 sites in China. Mean patient age was 68.4 years, and 61.4% were men. Radial access was used in 79.1% patients, and 32.7% procedures were guided by intravascular imaging. A total of 22.6% procedures used more than 1 burr, and the maximal burr size was ≥1.75 mm in 24.4% cases, with burr upsizing in 19.3% cases, achieving a final burr-to-artery ratio of 0.52. Procedural success was achieved in 91.1% of patients, and the rate of 30-day and 1-year MACE was 4.9% and 8.2%, respectively. Multivariable analysis identified the total lesion length (HR 1.014, 95% CI: 1.002-1.027; p = 0.021) as predictor of 30-day MACE, and renal insufficiency (HR 1.916, 95% CI: 1.073-3.420; p = 0.028) as predictor of 1-year MACE. CONCLUSIONS: In this contemporary prospective registry in China, the use of RA was effective in achieving high procedural success rate with good short- and long-term outcomes in patients with severely calcified lesions.

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T-2 toxin is a trichothecene mycotoxin and is considered as an extremely inevitable pollutant with potent hepatotoxicity. However, the approach to alleviation of T-2 toxin-triggered hepatotoxicity has been recognized as a serious challenge. Resveratrol (Res) is a polyphenol natural product isolated from various plant species, but its protective effect against T-2 toxin hepatotoxicity and detailed mechanism remains obscure. In the present study, the effect of Res against the hepatotoxicity was evaluated, and the underlying mechanisms were further revealed in mice. Functionally, Res inhibited liver injury, oxidative damage, and mitochondrial dysfunction induced by T-2 toxin. Mechanistically, Res modulated Nrf2-mediated antioxidant pathway and glutathione synthesis inhibition. Collectively, our findings first showed beyond doubt that Res ameliorated T-2 toxin-triggered liver injury by regulating Nrf2 pathways in mice.

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Phenylpyrazoles are widely used pesticides in the food industry. It is highly desirable to develop efficient pre-treatment and analysis methods to extract and detect phenylpyrazoles in complex food matrices. Herein, the study reports novel squaraine-linked zwitterionic core-shell magnetic covalent organic frameworks (MCOFs),  which are found to be excellent pretreatment materials for the detection of trace phenylpyrazoles in samples. By coupling MCOFs to magnetic solid-phase extraction (MSPE) with Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) analysis, the detection of phenylpyrazoles (fipronil, fipronil sulfone, fipronil sulfide, fipronil de-sulfoxide, fipronil desulfinyl, ethiprole, and flufiprole) is achieved and shows good linearity at concentrations of 1-800 µg L-1 (R2 ≥ 0.9930). The limit of detection (LOD), limit of quantification (LOQ), and recovery rates are 0.01-0.50 µg kg-1, 0.04-1.72 µg kg-1, and 70.96-115.32%, respectively. More importantly, this method is successfully applied to determine the phenylpyrazoles in commercial egg, poultry, milk, jujube, cabbage, tea, and rice with a detection rate of ≈0.04%. Therefore, the developed method may contribute to a new strategy for the purification and multi-target extraction of complex food matrices.

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Craniopharyngioma (CP) is an intracranial tumor with high mortality and morbidity. Though biologically benign, CP will damage the hypothalamus, inducing comorbidities such as obesity, metabolic syndrome, and cognitive impairments. The roles of gut microbiome and serum metabolome in CP-associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, Eubacterium, Clostridium, and Roseburia, alongside decreased Alistipes and Bacteroides. CP-enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP-depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up-regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi-omics analysis in the Rax-CreERT2::BrafV600E/+::PtenFlox/+ mouse model validated potential involvement of increased Clostridium and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co-variated with the severity of hypothalamic comorbidities and abundance of Clostridium, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased Clostridium and up-regulated purine metabolism as signatures of CP-associated hypothalamic-comorbidities, and unveiled that elevated Clostridium, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP-associated hypothalamic-comorbidities.

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Nonspecific reactive chemicals often interfere with the interpretation of high-throughput assay results because of their promiscuity and/or cytotoxicity. Using a high-throughput assay to identify such compounds is necessary to efficiently rule out potential assay artifacts. The MSTI, (E)-2-(4-mercaptostyryl)-1,3,3-trimethyl-3H-indol-1-ium, assay uses a thiol-containing fluorescent probe to screen for electrophile reactivity and could potentially be used to determine nonspecific reactive compounds. The Tox21 10K compound library was previously screened against a panel of ∼80 cell-based and biochemical assays, including the biochemical MSTI assay. In this study, we compared the MSTI assay activity of the Tox21 10K compounds with their promiscuity and cytotoxicity as reflected by their activities across the Tox21 assay panel to determine: (1) if this assay is predictive of a compound's promiscuity and cytotoxicity and (2) what chemical features create inconsistent results between the MSTI assay activity and promiscuity/cytotoxicity (false negatives and false positives). We found that the MSTI assay can predict a chemical's promiscuity/cytotoxicity with a 0.55 sensitivity and 0.97 specificity. Out of 3,407 unique compounds evaluated, we identified 92 false positive and 227 false negative results. Several structural features such as carboxamides and alkyl halides were found to be apparent in 53% (p = 2.4 × 10-07) and 19% (p = 4.3 × 10-06) of the false positives and negatives, respectively. The results of this analysis will help identify the potential challenges of this high-throughput assay and allow researchers to identify if a compound will be cytotoxic or promiscuous in an efficient manner.

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BACKGROUND: Group A Streptococcus causes a variety of human infections, including the life-threatening necrotizing fasciitis, which may be ignored by the patient. From hours to days, the infection may progress from an apparently benign skin lesion, usually mistaken for a spider or insect bite, to a highly lethal disease. We present a case of 57-year-old male with skin lesions on swelling left upper limb. METHODS AND RESULTS: The culture of secretion from epidermis and blood were positive for Group A Streptococcus (GAS), type ß hemolytic streptococcus. Intensive anti-infection therapy was applied. However, the necrosis of the limb deteriorated rapidly. He died from multiple organ failure, streptococcal toxic shock syndrome (STSS) and disseminated intravascular coagulation 13 days later. CONCLUSIONS: Necrotizing fasciitis is a rapidly progressive, destructive bacterial infection. Early recognition is the most important factor for survival.

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Quantitative ultrasound (QUS) and ultrasound-based elastography techniques are emerging as non-invasive effective methods for assessing chronic liver disease. They are more accurate than B-mode imaging alone and more accessible than MRI as alternatives to liver biopsy. Early detection and monitoring of diffuse liver processes such as steatosis, inflammation, and fibrosis play an important role in guiding patient management. The most widely available and validated techniques are attenuation-based QUS techniques and shear-wave elastography techniques that measure shear-wave speed. Other techniques are supported by a growing body of evidence and are increasingly commercialized. This review explains general physical concepts of QUS and ultrasound-based elastography techniques for evaluating chronic liver disease. The first section describes QUS techniques relying on attenuation, backscatter, and speed of sound. The second section discusses ultrasound-based elastography techniques analyzing shear-wave speed, shear-wave dispersion, and shear-wave attenuation. With an emphasis on clinical implementation, each technique's diagnostic performance along with thresholds for various clinical applications are summarized, to provide guidance on analysis and reporting for radiologists. Measurement methods, advantages, and limitations are also discussed. The third section explores developments in quantitative contrast-enhanced and vascular ultrasound that are relevant to chronic liver disease evaluation.

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Single dyes typically exhibit limited light absorption in dye-sensitized solar cells (DSSCs). Thus, cosensitization using two or more dyes to enhance light-harvesting efficiency has been explored; however, the aggregation of dyes can adversely affect electron injection capabilities. This study focused on the design and synthesis of three dyes with a common carbazole donor for DSSCs: DZ102, TZ101, and JM102. JM102 broadens the absorption spectrum by replacing the benzoic acid electron acceptor of TZ101 with acetylenic benzoic acid. A cosensitized DSSC device based on CO-1 [DZ102:TZ101 = 1:1 (50 µM:50 µM)] achieved a short-circuit current density of 19.4 mA/cm2 and a power conversion efficiency of 10.9%. For the first time, the molecular interactions between the dyes in the photoanode were demonstrated using cyclic voltammetry, which revealed the presence of intermolecular forces. Adsorption kinetics further indicated that these forces promoted the self-assembly of dyes during adsorption, which resulted in a cosensitization adsorption amount greater than the sum of the individual dye adsorptions. This study provides novel insights into the selection of cosensitizing dyes for DSSCs.

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BACKGROUND: Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children. Several pathogens can cause lung abscesses, with the most common pathogens being anaerobes, Streptococci and Staphylococcus aureus. Streptococcus pseudopneumoniae (S. pseudopneumoniae) is a member of the Streptococcaceae family, and is mainly isolated from respiratory tract specimens. There are currently no cases of lung abscess caused by S. pseudopneumoniae in the literature. CASE SUMMARY: A 2-year-old boy was admitted to hospital due to persistent cough and fever. Lung computed tomography examination suggested the formation of a lung abscess. His diagnosis was not confirmed by testing for serum respiratory pathogens (6 items), respiratory pathogen nucleic acid (27 items), and laboratory culture. Finally, metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S. pseudopneumoniae, confirming its role in causing the lung abscess. After receiving antibiotic treatment, reexamination with lung computed tomography showed that the abscess was resorbed and the patient's outcome was good. CONCLUSION: This is the first report of a lung abscess in a child caused by S. pseudopneumoniae infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.

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Background: The global prevalence of diabetic heart complication has been on the increase, and some of the drugs that are currently used to treat diabetes mellitus (DM) have not been able to mitigate this complication. Objective: This study determines the effect of Brazil nut (Bertholletia excelsa) and metformin on diabetic cardiomyopathy (DCM) in fructose/streptozotocin (STZ)-induced type 2 diabetic rats and also characterizes using Gas Chromatography Mass Spectrophotometry and Fourier Transform Infrared the bioactive compounds in 50% aqueous ethanol extract of Brazil nut. Design: After inducing type 2 DM, 30 male albino Wistar rats were separated into five groups that comprised of six rats per group, and they were treated as follows: groups 1 (Control) and 2 (Diabetic control) rats received rat pellets and distilled water; group 3 (Diabetic + Brazil nut) received rat pellets and Brazil nut extract (100 mg/kg, orally) dissolved in distilled water, group 4 (Diabetic + metformin) received metformin (100 mg/kg, orally) dissolved in distilled water, while group 5 (Diabetic + Brazil nut + metformin) received oral administrations of Brazil nut (100 mg/kg) and metformin (100 mg/kg) dissolved in distilled water. This study lasted for 6 weeks. The dose of Brazil nut used was selected from our pilot study on the minimum therapeutic dose of different concentrations of Brazil nut extract. Results: STZ administration induced insulin resistance, hyperglycemia, loss of weight, dyslipidemia, oxidative stress, inflammation, apoptosis, alteration of mammalian target of rapamycin, mitogen-activated protein kinase, heart function markers (creatine kinase MB, lactate dehydrogenase, and aspartate amino transaminase), and heart histology of the diabetic control, which was ameliorated after treatment with Brazil nut and metformin, but their combined treatment was better than the single treatments. Conclusion: This study shows that Brazil nut contains several bioactive compounds that support its biological properties as well as its candidature as a complementary therapy to metformin in mitigating cardiac complications arising from DM in rats.

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Introduction: Gan-jiang-ling-zhu (GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating yang, activating qi and dissipating dampness, GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated. Methods: NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction. Results: GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression. Conclusion: Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC-CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.

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