Moringa oleifera leaf extracts improve exercise performance in young male adults: A pilot study.

BACKGROUND: Moringa oleifera leaves are rich in bioactive substances. PURPOSE: The purpose of this study was to evaluate the effects of Moringa oleifera leaf aqueous extract supplements on energy metabolism and antioxidant function in young male adults. METHODS: Forty-four young male adults (26.3 ± 3.5 years) were randomly assigned to two groups: a supplement group (n = 23) receiving aqueous extract of Moringa oleifera leaves and a placebo group (n = 21). The supplementation period lasted for 30 days. Baseline measurements were taken at the beginning of the study, and further measurements were taken at the end of the supplementation period. Changes in upper- and lower-body strength, treadmill endurance, and certain blood biochemical parameters were evaluated. RESULTS: After 30 days of supplementation, participants in the supplement group exhibited enhanced performance in push-ups and treadmill exhaustion tests compared to the placebo group. Levels of glucose, urea, malondialdehyde, and glutathione peroxidase activity in serum were also improved in the supplement group. CONCLUSION: The findings suggest that Moringa oleifera leaf aqueous extracts have the potential to improve post-exercise energy metabolism and antioxidant function in young male adults.

Catalyst-Free Visible Light-Driven Hydrosulfonylation of Alkenes and Alkynes with Sulfonyl Chlorides in Water.

A convenient and sustainable method for synthesizing sulfonyl-containing compounds through a catalyst-free aqueous-phase hydrosulfonylation of alkenes and alkynes with sulfonyl chlorides under visible light irradiation is presented. Unactivated alkenes, electron-deficient alkenes, alkyl and aryl alkynes can be hydrosulfonylated with various sulfonyl chlorides at room temperature with excellent yields and geometric selectivities by using tris(trimethylsilyl)silane as a hydrogen atom donor and silyl radical precursor to activate sulfonyl chlorides. Mechanistic studies revealed that the photolysis of tris(trimethylsilyl)silane in aqueous solution to produce silyl radical is crucial for the success of this reaction.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.

Vitamin D3 Regulates Energy Homeostasis under Short-Term Fasting Condition in Zebrafish (Danio Rerio).

Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.

Electron-transferring flavoprotein and its dehydrogenase contributed to growth development and virulence in Beauveria bassiana.

Electron-transferring flavoprotein (Etf) and its dehydrogenase (Etfdh) are integral components of the electron transport chain in mitochondria. In this study, we characterize two putative etf genes (Bbetfa and Bbetfb) and their dehydrogenase gene Bbetfdh in the entomopathogenic fungus Beauveria bassiana. Individual deletion of these genes caused a significant reduction in vegetative growth, conidiation, and delayed conidial germination. Lack of these genes also led to abnormal metabolism of fatty acid and increasing lipid body accumulation. Furthermore, the virulence of Bbetfs and Bbetfdh deletion mutants was severely impaired due to decreasing infection structure formation. Additionally, all deletion strains showed reduced ATP synthesis compared to the wild-type strain. Taken together, Bbetfa and Bbetfb, along with Bbetfdh, play principal roles in fungal vegetative growth, conidiation, conidial germination, and pathogenicity of B. bassiana due to their essential functions in fatty acid metabolism.

Suppression of JAK2/STAT3 Pathway by Notoginsenoside R1 Reduces Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer.

It has bene reported that a novel saponin-notoginsenoside R1 (NGR1) possesses strong anti-tumor activities. This study aimed to investigate the role and mechanism of NGR1 in non-small cell lung cancer (NSCLC). NSCLC cell viability, proliferation, migration, and invasiveness were assessed using the ex vivo assays. NSCLC xenograft mouse models were constructed to confirm the role of NGR1 in vivo. Epithelial-mesenchymal transition (EMT)-related proteins and key markers in the JAK2/STAT3 pathway were examined using immunoblotting and immunohistochemistry analyses. NGR1 treatment suppressed NSCLC cell growth ex vivo and in vivo. It also decreased the migratory and invasive capacities of NSCLC cells. Additionally, NGR1 increased E-cadherin expression and reduced N-cadherin, vimentin, and snail expression in TGF-ß1-treated NSCLC cells and xenograft tumors. JAK2/STAT3 pathway was inhibited by NGR1. Moreover, a specific inhibitor of JAK2, AG490, or STAT3 silencing significantly enhanced the effects of NGR1 against the EMT process in NSCLC cells. NGR1 restrains EMT process in NSCLC by inactivating JAK2/STAT3 signaling, suggesting the potential of NGR1 in anti-NSCLC therapy.

Research on fault diagnosis of rolling bearing based on improved convolutional neural network with sparrow search algorithm.

Traditional approaches to the intelligent fault diagnosis of rolling bearings have predominantly relied on manual expertise for feature extraction, a practice that compromises robustness. In addition, the existing convolutional neural network (CNN) is characterized by an overabundance of parameters and a substantial requirement for training samples. To address these limitations, this study introduces a novel fault diagnosis algorithm for rolling bearings, integrating a one-dimensional convolutional neural network (1DCNN) with a support vector machine (SVM) to form an enhanced 1DCNN-SVM model. This model is further refined using the sparrow search algorithm (SSA) for the optimal adjustment of the parameters of 1DCNN-SVM. Specifically, by substituting the CNN's final softmax layer with an SVM, the model becomes better suited for processing limited data volumes. In addition, the incorporation of batch normalization and dropout layers within the CNN framework significantly augments its fault classification accuracy for rolling bearings, concurrently mitigating the risk of overfitting. The SSA is subsequently applied to refine three principal hyper-parameters: batch size, initial learning rate, and the L2 regularization coefficient, thereby overcoming the challenges associated with manually adjusting parameters, such as extended processing times and unpredictable outcomes. Empirical tests on Case Western Reserve University (CWRU) datasets revealed the model's superior performance, with the SSA-optimized 1DCNN-SVM showcasing diagnostic accuracies over 98%, marked improvements over conventional models, and a significant reduction in processing times. This method not only marks a significant advancement in intelligent fault diagnosis for rolling bearings but also demonstrates the potential of integrating machine learning for more precise and efficient diagnostics. The SSA-1DCNN-SVM model, optimized for accuracy and minimal data use, sets a new standard in fault diagnosis, relevant for machinery health monitoring and maintenance strategies across various industries.

Development of an on-site diagnostic LAMP assay for rapid differentiation of the invasive pest Phthorimaea absoluta (Meyrick) using insect tissues.

BACKGROUND: The tomato leafminer, Phthorimaea absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a destructive invasive pest that originated in South America and has spread within China since 2017. A rapid method for on-site identification of P. absoluta is urgently needed for interception of this pest across China. RESULTS: We developed a loop-mediated isothermal amplification (LAMP) technique to differentiate P. absoluta from Liriomyza sativae, Chromatomyia horticola, and Phthorimaea operculella using extracted genomic DNA, which was then refined to create an on-site LAMP diagnostic method that can be performed under field conditions without the need for laboratory equipment. CONCLUSION: In the present research, we developed an on-site diagnostic method for rapid differentiation of P. absoluta from other insects with similar morphology or damage characteristics in China. © 2024 Society of Chemical Industry.

Optimal probiotic combinations for treating nonalcoholic fatty liver disease: A systematic review and network meta-analysis.

BACKGROUND: Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients. METHODS: The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS: A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74). CONCLUSION: This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies.

Appropriate Prescribing for older adults with Multimorbidity (Pro-M): protocol for a feasibility study.

BACKGROUND: Potentially inappropriate prescribing is common among older adults with multimorbidity due to various reasons, from concurrent application of multiple single-disease clinical guidelines to fragmentation of care. Interventions such as medication review have been implemented worldwide to reduce inappropriate prescribing for older adults. However, the implementability of such interventions are underexplored in the outpatient clinics in Singapore's public hospitals. Hence, the Pro-M study aims to assess the feasibility of implementing a physician-pharmacist collaborative care intervention in geriatric medicine outpatient clinics to facilitate appropriate prescribing for older adults in Singapore. METHODS: This is a single-arm, non-randomised feasibility study using a pre-post evaluation design. This study consists of two parts: (1) implementation phase of the intervention (6 months) and an (2) evaluation phase (3 months). Eligible patients will be recruited from geriatric medicine outpatient clinics at two public hospitals in Singapore through convenience sampling. The main components of the Pro-M intervention are: (1) pharmacist-facilitated medication reviews with feedback on any medication issues and potential recommendations to physicians, and (2) physicians communicating changes to other relevant prescribers. The evaluation phase will involve surveying and interviewing physicians and pharmacists involved in the implementation of the intervention. A mixed-method approach will be employed for data collection and analysis. The quantitative and qualitative findings will be triangulated and reported using Proctor's implementation outcomes: appropriateness, penetration, acceptability, fidelity, feasibility, and sustainability. A basic cost analysis will be conducted alongside the study. DISCUSSION: This is a phase 2 study to test the feasibility of implementing an intervention that was co-created with stakeholders during phase 1 development of an intervention to optimise prescribing for older adults with multimorbidity. The implementation will be assessed using Proctor's implementation outcomes to provide insights on the process and the feasibility of implementing medication reviews for older adults with multimorbidity as a routine practice in outpatient clinics. Data collected from this study will inform a subsequent scale-up study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05756478. Registered on 06 March 2023.

Assessment of optimal combinations of therapeutic probiotics for depression, anxiety, and stress.

BACKGROUND: Accumulating data show that probiotics may be beneficial for reducing depressive, anxiety, and stress symptoms. However, the best combinations and species of probiotics have not been identified. The objective of our study was to assess the most effective combinations and components of different probiotics through network meta-analysis. METHOD: A systematic search of four databases, PubMed, Web of Science, Cochrane, and Embase, was conducted from inception to 11 January 2024. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS: We deemed 45 trials eligible, these included 4053 participants and 10 types of interventions. The quality of evidence was rated as high or moderate. The NMA revealed that Bifidobacterium exhibited a greater probability of being the optimal probiotic species for improving anxiety symptoms (SMD = -0.80; 95% CI -1.49 to -0.11), followed by Lactobacillus (SMD = -0.49; 95% CI -0.85 to -0.12). In addition, for multiple strains, compared with the other interventions, Lactobacillus + Bifidobacterium (SMD = -0.41; 95% CI -0.73 to -0.10) had a positive effect on depression. CONCLUSION: The NMA revealed that Lactobacillus and Bifidobacterium had prominent efficacy in the treatment of individuals with anxiety, depression, and combination of Lactobacillus + Bifidobacterium had a similar effect. With few direct comparisons available between probiotic species, this NMA may be instrumental in shaping the guidelines for probiotic treatment of psychological disorders.

[Research Status of Nanomaterial Medical Device and Discussion on Biological Evaluation].

In recent years, China has made great progress in basic nanomedicine, nanotoxicology and nanobiology research. Nanotechnology has been continuously applied in biomaterial and medical device, more and more medical devices applying nanomaterials are developed and manufactured. In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices, this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad, and discussed the current challenges in biological evaluation of nanomaterial medical devices, with a view to providing ideas for the safety evaluation and research of related products.

Vitamin D promotes the folate transport and metabolism in zebrafish (Danio rerio).

Vitamin D (VD) is a fat-soluble sterol that possesses a wide range of physiological functions. The present study aimed to evaluate the effects of VD on folate metabolism in zebrafish and further investigated the underlying mechanism. Wild-type (WT) zebrafish were fed with a diet containing 0 IU/kg VD3 or 800 IU/kg VD3 for 3 wk. Meanwhile, cyp2r1 mutant zebrafish with impaired VD metabolism was used as another model of VD deficiency. Our results showed that VD deficiency in zebrafish suppressed the gene expression of folate transporters, including reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) in the intestine. Moreover, VD influenced the gene expression of several enzymes related to cellular folate metabolism in the intestine and liver of zebrafish. Importantly, VD-deficient zebrafish contained a remarkably lower level of folate content in the liver. Notably, VD was incapable of altering folate metabolism in zebrafish when gut microbiota was depleted by antibiotic treatment. Further studies proved that gut commensals from VD-deficient fish displayed a lower capacity to produce folate than those from WT fish. Our study revealed the potential correlation between VD and folate metabolism in zebrafish, and gut microbiota played a key role in VD-regulated folate metabolism in zebrafish.NEW & NOTEWORTHY Our study has identified that VD influences intestinal uptake and transport of folate in zebrafish while also altering hepatic folate metabolism and storage. Interestingly, the regulatory effects of VD on folate transport and metabolism diminished after the gut flora was interrupted by antibiotic treatment, suggesting that the regulatory effects of VD on folate metabolism in zebrafish are most likely dependent on the intestinal flora.

Imperatorin inhibits oxidative stress injury and neuroinflammation via the PI3K/AKT signaling pathway in the MPTP-induced Parkinson's disease mouse.

Parkinson's disease (PD) is a disorder of neurodegeneration. Imperatorin is an active natural furocoumarin characterized by antioxidant, anti-inflammatory, and potent vasodilatory properties. Therefore, we aimed to investigate the biological functions of imperatorin and its mechanisms against PD progression. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg) daily for 5 consecutive days to mimic PD conditions in vivo. The MPTP-induced PD model mice were intraperitoneally injected with imperatorin (5 mg/kg) for 25 consecutive days after MPTP administration. The motor and cognitive functions of mice were examined by rotarod test, hanging test, narrow beam test and Morris water maze test. After analysis of MWM test, the expression levels of tyrosine hydroxylase and Iba-1 in the substantia nigra pars compacta were measured by immunohistochemistry staining, immunofluorescence staining and western blotting. The expression levels of striatal dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were also measured. The protein levels of inducible nitric-oxide synthase, cyclooxygenase-2, phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in the mouse striatum were estimated by western blotting. The expression levels of proinflammatory cytokines including tumor necrosis factor, interleukin (IL)-1ß and IL-6 in the mouse striatum were measured by ELISA kits. The expression levels of superoxide dismutase, malondialdehyde and glutathione in the mouse midbrains were measured with commercially available kits. TUNEL staining was performed to identify the apoptosis of midbrain cells. Histopathologic changes in the mouse striata were assessed by hematoxylin-eosin staining. Imperatorin treatment markedly improved spatial learning and memory abilities of MPTP-induced PD mice. The MPTP-induced dopaminergic neuron loss in the mouse striata was inhibited by imperatorin. Imperatorin also suppressed neuroinflammation and neuronal oxidative stress in the midbrains of MPTP-induced PD mice. Mechanistically, imperatorin treatment inhibited the MPTP-induced reduction in the PI3K/Akt pathway. Imperatorin treatment can prevent dopaminergic neuron degeneration and improve cognitive functions via its potent antioxidant and anti-inflammatory properties in an MPTP-induced PD model in mice by regulating the PI3K/Akt pathway.

Research on the classification of early-stage brain edema by combining intrinsic optical signal imaging and laser speckle contrast imaging.

The early detection and pathological classification of brain edema are very important for symptomatic treatment. The dual-optical imaging system (DOIS) consists of intrinsic optical signal imaging (IOSI) and laser speckle contrast imaging (LSCI), which can acquire cerebral hemodynamic parameters of mice in real-time, including changes of oxygenated hemoglobin concentration ( Δ C HbO 2 ), deoxyhemoglobin concentration (ΔCHbR) and relative cerebral blood flow (rCBF) within the field of view. The slope sum of Δ C HbO 2 , ΔCHbR and rCBF was proposed to classify vasogenic edema (VE) and cytotoxic edema (CE). The slope sum values in the VE and CE group remain statistically different and the classification results provide higher accuracy of more than 93% for early brain edema detection. In conclusion, the differences of hemodynamic parameters between VE and CE in the early stage were revealed and the method helps in the classification of early brain edema.

Cognitive Profiles Stratified by Education Using Montreal Cognitive Assessment in Parkinson's Disease Patients with Freezing of Gait.

Purpose: Parkinson's disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. This study aims to explore the cognitive profiles stratified by education using MoCA in PD patients with FOG. Patients and Methods: PD patients with FOG (FOG+, n = 52) and without FOG (FOG-, n = 71) were included in our study. MoCA items were categorized into five subsections (attention/working memory, executive function, episodic memory, language, and visuospatial function) referring to previously published criteria. Cognitive assessments were compared based on five subsections between groups stratified by three education levels (0-6 years, 7-12 years, and >12 years). The association of cognitive measurements with FOG were analyzed using binary logistic regression models with adjustment for variables. Results: The total scores and subscores of each subsection of MoCA were similar between two groups of each education level. Further detailed analysis showed that a composite measure labeled "Attention/working memory-Composite" (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition), were lower significantly in FOG+ group compared with FOG- group in patients with education year ≤6 years. The significant association of Attention-C with FOG held true when controlling for disease duration, but not for H-Y stage, MDS-UPDRS III, HAMA, and HAMD. Conclusion: Overall, our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which will need to be validated in future studies.

Radiomics of Preoperative Multi-Sequence Magnetic Resonance Imaging Can Improve the Predictive Performance of Microvascular Invasion in Hepatocellular Carcinoma.

Background: The aim of the study is to demonstrate that radiomics of preoperative multi-sequence magnetic resonance imaging (MRI) can indeed improve the predictive performance of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 206 patients with pathologically confirmed HCC who underwent preoperative enhanced MRI were retrospectively recruited. Univariate and multivariate logistic regression analysis identified the independent clinicoradiologic predictors of MVI present and constituted the clinicoradiologic model. Recursive feature elimination (RFE) was applied to select radiomics features (extracted from six sequence images) and constructed the radiomics model. Clinicoradiologic model plus radiomics model formed the clinicoradiomics model. Five-fold cross-validation was used to validate the three models. Discrimination, calibration, and clinical utility were used to evaluate the performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the prediction accuracy between models. Results: The clinicoradiologic model contained alpha-fetoprotein (AFP)_lg10, radiological capsule enhancement, enhancement pattern and arterial peritumoral enhancement, which were independent risk factors of MVI. There were 18 radiomics features related to MVI constructed the radiomics model. The mean area under the receiver operating curve (AUC) of clinicoradiologic, radiomics and clinicoradiomics model were 0.849, 0.925 and 0.950 in the training cohort and 0.846, 0.907 and 0.933 in the validation cohort, respectively. The three models' calibration curves fitted well, and decision curve analysis (DCA) confirmed the clinical usefulness. Compared with the clinicoradiologic model, the NRI of radiomics and clinicoradiomics model increased significantly by 0.575 and 0.825, respectively, and the IDI increased significantly by 0.280 and 0.398, respectively. Conclusions: Radiomics of preoperative multi-sequence MRI can improve the predictive performance of MVI in HCC.

Effects of riboflavin deficiency and high dietary fat on hepatic lipid accumulation: a synergetic action in the development of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored. METHODS: In the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique. RESULTS: The results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load. CONCLUSIONS: There is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role.

GPAT1 Deficiency in Mice Modulates NASH Progression in a Model-Dependent Manner.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), and its more severe form, nonalcoholic steatohepatitis (NASH), is the leading cause for liver failure and liver cancer. Although the etiology is likely multifactorial, genes involved in regulating lipid metabolism are enriched in human NAFLD genome-wide association studies (GWAS), pointing to dysregulated lipid metabolism as a major pathogenic factor. Glycerol-3-phosphate acyltransferase 1 (GPAT1), encoded by GPAM, converts acyl-CoAs and glycerol-3-phosphate into lysophosphatidic acid and has been shown to regulate lipid accumulation in the liver. However, its role in mediating the progression from NAFLD to NASH has not been explored. METHODS: GPAT1-deficient mice were generated and challenged with diets inducing hepatic steatosis and NASH. Effects of GPAT1 deficiency on lipid and systemic metabolic end points were evaluated. RESULTS: Ablating GPAT1 globally or specifically in mouse hepatocytes reduced hepatic steatosis in the context of diet-induced or genetic obesity. Interestingly, blunting of progression from NAFLD to NASH in global GPAT1 knockout (KO) mice was model dependent. GPAT1 KO mice were protected from choline deficient, amino acid defined high-fat diet-induced NASH development, but not from the high fat, high carbohydrate, and high cholesterol diet-induced NASH. CONCLUSIONS: Our preclinical data support the notion that lipid metabolism pathways regulated by GPAT1 in hepatocytes play an essential role in NASH progression, albeit in a model-dependent manner.