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1.
High-fat diet (HFD) is demonstrated to disturb the bile acid metabolism. The rhythm of bile acid metabolism can also be affected by uridine, whose metabolism exhibits a daily rhythm. However, the mechanism of dynamic uridine administration affecting bile acid during HFD remains unclear. In this study, C57BL/6J mice were fed HFD (the control group; CON) or HFD with oral administration of uridine in the daytime (DUR) and nighttime (NUR) to investigate the mechanism of the effect of uridine on the bile acid. This study showed that the mRNA expression of uridine transporters and circadian clock genes in the jejunum was affected by zeitgeber time (ZT) (P < 0.001). Genes related to the metabolism of pyrimidines in the liver showed a high dependence on daily rhythm (P < 0.01), and DUR remarkably up-regulated the expression of ribonucleotide reductase regulatory subunit M2 (RRM2) (P < 0.05) compared to the CON group. Importantly, the mRNA expression of bile acids nuclear receptors, bile acid synthesis, and transporters in the liver showed significantly rhythmically changed (P < 0.05), and the expression of cholesterol 7-alpha-hydroxylase (CYP7A1), fibroblast growth factor receptor 4 (FGFR4), Na+/taurocholate co transporting polypeptide (NTCP), and bile salt export pump (BSEP) mRNAs of mice with uridine administration increased significantly (P < 0.05). The mRNA expression of the transporters of cholesterol and bile acids in the ileum was also affected by ZT (P < 0.01) and significantly dependent on uridine administration (P < 0.05). The expression of FXR and SHP was significantly affected by ZT and uridine, respectively. In conclusion, dynamic administration of uridine could regulate the rhythm of gene expression of pyrimidine and bile acid metabolism in the liver and ileum of HFD-fed mice, which contributed to the further study of circadian rhythmic physiological and pathological changes of bile acids. 相似文献
2.
This work aimed to study the beneficial role of human umbilical cord blood-derived mesenchymal stem cellconditioned medium (MSC-CM) in hypoxia-induced apoptosis in H9c2 cardiomyoblasts, in which the serine/heroine
kinases (Akt) pathway would be involved. For this, CM was collected by culturing MSCs in serum-free DMEM
medium for 24 h, and paracrine factors were analyzed by protein chip. H9c2 cells were divided into the following
groups: control group, hypoxia group, MSC-CM intervention group (CM group), MSC-CM + Akt phosphorylation
inhibitor (LY294002) group (LY group). Apoptosis of the H9c2 cells was tested with chromatin dye Hoechst 33342
and FITC-conjugated Annexin V apoptosis detection kit by flow cytometer after a hypoxia/serum deprivation (H/SD)
for 24 h. The apoptosis-related proteins were evaluated by Western blot. MSC-CM displayed significantly elevated
levels of growth factors, anti-inflammatory, and anti-apoptosis cytokines. On Hoechst 33342 apoptosis staining, the
H9c2 cell morphology displayed a lower proportion of apoptosis in the CM group than those in the hypoxia group,
while apoptosis was increased in LY group. Flow cytometer analysis revealed the apoptosis ratio in the CM group was
lower than the hypoxia group (12.34 ± 2.00% vs. 21.73 ± 2.58%; p < 0.05), while the LY group was significantly higher
(22.54 ± 3.89%). Active caspase-3 expression was increased in hypoxia group than control group (p < 0.05), but
decreased in CM group (p < 0.01). Umbilical cord blood-derived mesenchymal stem cell-conditioned media secrete
multiple paracrine factors that are able to inhibit hypoxia-induced H9c2 cardiomyoblasts apoptosis, and in which the
activation of Akt phosphorylation is involved to achieve the protective effect. 相似文献
3.
RONGXUE WEI CHUNCHUN HAN FENGJIANG YE SHOUHAI WEI FANG HE HEHE LIU LIANG LI HONGYONG XU SHENQIANG HU XIANYIN ZENG 《Biocell》2022,46(1):171-183
In order to explore the role of forkhead box protein O1 (FoxO1) in the lipid metabolism and cell proliferation, goose primary hepatocytes were isolated and incubated with insulin or PI3K-Akt-mTOR pathway dual inhibitor NVP-BEZ235, and then transfected with FoxO1 interference plasmid. The related parameters of lipid metabolism and cell proliferation were measured. The results firstly showed that FoxO1 interference increased the intracellular TG and lipids concentration (P < 0.05); and increased the proliferative index (PI), cell DNA synthesis, protein expression of Cyclin D1 in goose primary hepatocytes (P < 0.05). Secondly, the co-treatment of insulin and FoxO1 interference increased the mRNA level and protein content of Cyclin D1 (P < 0.05); however, there was no significant difference between the insulin treatment and the co-treatment of insulin and miR-FoxO1 interference in the intracellular TG and lipids concentration and PI (P > 0.05). Lastly, the decrease of intracellular TG and lipids concentration and PI induced by NVP-BEZ235 was up-regulated by FoxO1 interference significantly (P < 0.05). In summary, FoxO1 could regulate the lipids metabolism and cell proliferation mediated by PI3K-Akt-mTOR signaling pathway in goose primary hepatocytes. Further investigations are required to highlight the potential role of FoxO1 in the lipid metabolism and cell proliferation mediated by insulin in goose primary hepatocyte. 相似文献
4.
Vitiligo results in an autoimmune disorder destructing skin pigment cells, melanocytes (Mcs). This study aimed
to investigate whether Astragaloside IV (AIV) could efficiently induce differentiation of bone marrow mesenchymal stem
cells (BMMSCs) into Mcs. BMMSCs were induced and differentiated into Mcs with 0.1, 0.2, and 0.4 mg/L AIV during
150-day. Morphologic changes of differentiated cells were observed. Levels of some melanocytic specific genes (TRP-1,
TRP-2, MART-1, Mitf) were measured with quantitative polymerase chain reaction (qPCR) at 90, 120, and 150 days
of induction. After 90-day induction, the differentiated cells with 0.4 mg/L AIV demonstrated the typical morphology
of Mcs, positive 3,4 dihydroxyphenylalanine staining, and positive staining of TRP-1, TRP-2, MART-1, and Mitf.
After 90- and 120- days’ induction with 0.4 mg/L AIV, TRP-1 expression was significantly elevated (p < 0.01), and
TRP-2 expression was significantly increased in 0.4 mg/L AIV-treated group compared to negative control (p < 0.01),
0.1 mg/L (p < 0.01), and 0.2 mg/L (p < 0.01) AIV-treated groups. Moreover, MART-1 expression was significantly
up-regulated in 0.4 mg/L AIV-treated group compared to negative control, but without difference compared to 0.1
mg/L (p > 0.05) and 0.2 mg/L (p > 0.05) AIV-treated groups. During 90 to 150- day induction, there were no
significant differences for Mitf levels between AIV-treated groups and negative control (p > 0.05). In conclusion,
90-day induction with 0.4 mg/L AIV up-regulated TRP-1, TRP-2, and MART-1 expression, indicating that AIV can
efficiently induce Mcs differentiation from BMMSCs. These results provide experimental and theoretic evidence for
AIV application in clinical vitiligo repigmentation treatment. 相似文献
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Presenilin (Psn) protein is associated with organismal aging. Mutations in the Psn gene may lead to Alzheimer’s
disease (AD), dilated cardiomyopathy (DCM), and many age-dependent degenerative diseases. These diseases seriously
affect the quality of life and longevity of the population and place a huge burden on health care and economic systems
around the world. Humans have two types of Psn, presenilin-1 (PSEN1) and presenilin-2 (PSEN2). Mutations in the
genes encoding PSEN1, PSEN2, and amyloid precursor protein (APP) have been identified as the major genetic
causes of AD. Psn is a complex gene strongly influenced by genetic and environmental factors. The effects of exercise,
training, and a high-fat diet on the Psn gene expressed in the heart and its related pathways are not fully understood.
Fortunately, relevant aspects of the mutational effects on Psn can be studied experimentally in easily handled animal
models, including Drosophila, mice, and other animals, all of which share orthologous genes of Psn with humans.
Many previous studies have linked aging, exercise training, and a high-fat diet to the Psn gene. This review discusses
the interrelationship between aging, exercise training, and a high-fat diet on the Psn gene and its associated disease,
AD. The aim is to understand the adverse effects of Psn gene mutations on the body and the diseases caused by AD,
find ways to alleviate the adverse effects and provide new directions for the improvement of treatment strategies for
diseases caused by Psn gene mutations. 相似文献
9.
NINGYU LI XIAOFANG CHEN SUXIA GENG PEILONG LAI LISI HUANG MINMING LI XIN HUANG CHENGXIN DENG YULIAN WANG JIANYU WENG XIN DU 《Biocell》2023,47(1):133-141
The pathogenesis of myelodysplastic syndrome (MDS) may be related to the abnormal expression of microRNAs
(miRNAs), which could influence the differentiation capacity of mesenchymal stem cells (MSCs) towards adipogenic and
osteogenic lineages. In this study, exosomes from bone marrow plasma were successfully extracted and identified.
Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its
0.52-fold downregulation in patients with MDS compared with controls (NOR) and was downregulated 0.55-fold in
MDS-MSCs compared with NOR-MSCs. Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic
differentiation and decreased adipogenic differentiation in vitro, while inhibition of miR-103-3p showed the opposite
results in NOR-MSCs. Thus, the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs, significantly
impacting MDS-MSCs differentiation. The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while
weakening lipid differentiation, thereby providing possible target for the treatment of MDS pathogenesis. 相似文献
10.
HUOGEN LIU YUNDI SHI XIN WAN YING LIU HAILIN SHU FENGMING HUANG ZHENBIN GONG LING GU 《Biocell》2022,46(12):2671-2680
Peroxiredoxin 1 (PRDX1) participates in tumor cell proliferation, apoptosis, migration, invasion, and the epithelial-to-mesenchymal transition (EMT). This study aimed to investigate the effect of PRDX1 on the EMT of airway epithelial cells stimulated with lipopolysaccharide (LPS) and transforming growth factor-beta 1 (TGF-β1). PRDX1 overexpression significantly increased the proliferation and migration of human bronchial epithelial (BEAS-2B) cells, reduced cell apoptosis (p < 0.01), and induced EMT and collagen deposition by upregulating the expression of the matrix metallopeptidase (MMP)2, MMP9, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and twist proteins and inhibiting E-cadherin expression (p < 0.05). PRDX1 overexpression promoted TGF-β1-mediated inhibition of cell proliferation and migration and significantly enhanced the TGF-β1-induced EMT and collagen synthesis (p < 0.05). Knockdown of PRDX1 inhibited cell proliferation, migration, EMT, and collagen synthesis (p < 0.01), reversed LPS-mediated inhibition of cell proliferation and migration, and significantly suppressed LPS-induced EMT and collagen synthesis (p < 0.01). The result indicating that PRDX1 may be involved in LPS/TGF-1-induced EMT and collagen synthesis in human bronchial epithelial cells. 相似文献
11.
We investigated the diversity and composition of microflora in feces of Lycopus lucidus Turcz.-fed mice. In
addition, we evaluated the production of major cytokines (Interleukin-6 and -10) which are related to inflammation
and fatty acid composition of several tissues. 16S ribosomal DNA sequencing-based microbiome taxonomic profiling
analysis was performed utilizing the EzBioCloud data base. Male mice fed on L. lucidus showed a significantly
reduced number of lactic acid bacteria and coliform in the feces compared with the control group (p < 0.05). 16S
rDNA sequencing analysis of fecal samples showed that L. lucidus supplementation decreased the community of
harmful microflora (Enterobacteriaceae including Escherichia coli and Bacteroides sp.) in feces compared with the
control group (p < 0.05). There were no significant differences in mRNA expression of cytokine IL-6 and IL-10
between the control and L. lucidus fed groups. The fecal fatty acid composition in the L. lucidus group had
percentages of 4:0, 6:0, 8:0 and 10:0 in the intestine but those short chain fatty acids were not detected in the control
group. Our results showed that L. lucidus supplementation influenced gut environment by decreasing harmful
microflora and increased the percentages of several short fatty acids. 相似文献
12.
Pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous, making its prognosis prediction difficult. The arachidonic acid (AA) cascade is involved in carcinogenesis. Therefore, the metabolic enzymes of the AA cascade consist of lipoxygenases (LOXs), phospholipase A2s (PLA2s), and cyclooxygenases (COXs) along with their metabolic products, including leukotrienes. Nevertheless, the prognostic potential of AA metabolism-associated PDAC has not been explored. Herein, the mRNA expression patterns and the matching clinical information of individuals with PDAC were abstracted from online data resources. We employed the LASSO Cox regression model to develop a multigene clinical signature in the TCGA queue. The GEO queue and the ICGC queue were employed as the validation queue. There was differential expression of a significant number of AA metabolism-associated genes (56.8%) between PDAC and neighboring nonmalignant tissues in the TCGA queue. Univariate Cox regression demonstrated that 13 of the differentially expressed genes (DEGs) were linked to overall survival (OS) (p < 0.05). A 6-gene clinical signature was developed for stratifying the PDAC patients into two risk groups, with the high-risk group patients exhibiting remarkably lower OS than the low-risk group patients (p < 0.001 in the TCGA data set and the ICGC queue, and p = 0.001 in the GEO data set). The multivariate Cox data revealed the risk score as an independent OS predictor (HR > 1, p < 0.01). The receiver operating characteristic (ROC) curve verified the predictive potential of our signature. The expression and alteration of the six genes in PDAC were also validated using online databases. Functional analyses demonstrated that immune-linked cascades were enriched, and the immune status was remarkably different between the high- and low-risk groups. In summary, an AA metabolism-associated clinical gene signature can be applied for prognostic estimation in PDAC. 相似文献
13.
YI WANG SHANGQI CHEN PENGCHENG YU ZHEHAN BAO CAN HU YUHANG XIA RUOLAN ZHANG LI YUAN HUA RUAN JIANCHENG SUN 《Biocell》2023,47(5):991-1002
Aim: Scavenger receptor class B, type I (SR-BI) is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies, such as renal cancer, breast cancer, and prostate cancer, and is an independent prognostic factor. However, the clinical value and expression of SR-BI in GC are unknown. Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer (GC). Methods: GC tissues, paracancerous tissues, and clinicopathological data of 149 patients were collected. The expression level of SR-BI, Tumor-infiltrating lymphocytes (TILs), and PD-L1 were evaluated by immunohistochemistry (IHC). The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test. Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors. Kaplan–Meier analyses were performed to plot the survival curve. Results: Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues (p < 0.001), and patients with high levels of SR-BI expression had a worse prognosis. Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis. The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+ T cells and CD8+ T cells (CD4+ T cells, p = 0.013; CD8+ T cells, p = 0.021), and positively correlated with PD-L1 (p = 0.022). Finally, survival analysis revealed that CD4+ T cells were associated with the prognosis of GC patients (p = 0.019), and the combined survival analysis of SR-BI and CD4+ T cells was also statistically significant (p = 0.030). Conclusion: SR-BI is highly expressed in GC tissue and associated with poor prognosis. Moreover, SR-BI can also regulate the GC tumor immune microenvironment. 相似文献
14.
WEI LIU ZI WANG JING LENG HENG WEI SHEN REN XIAOJIE GONG CHEN CHEN YINGPING WANG RUI ZHANG WEI LI 《Biocell》2020,44(4):655-669
Heat stress (HS) reaction can lead to serious physiological dysfunction associated with cardiovascular and
various organ diseases. Ginsenoside Rg3 (G-Rg3) is a representative component of ginseng rare saponin and can
protect against multiple organs, also used as functional food to adjust the balance of the human body, but the
therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored. The aim of
the present study, G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the
contribution of G-Rg3 to testicular injury induced exposure to HS. All mice were divided into four groups as follows:
normal group, HS group, and HS+G-Rg3 (5 and 10 mg/kg) groups. G-Rg3 was administered orally for 14 days, then
exposed to a single scrotal heat treatment (43°C, 18min) on the 7th day. After HS treatment, the morphology of testis
and epididymis changes, and caused a significant loss of multinucleated giant cells, desquamation of germ cells in
destructive seminiferous tubules, and degenerative Leydig cells, further destroying the production of sperm. After
administration G-Rg3 (5 and 10 mg/kg/day) for 2 weeks, the spermatogenic-related indexes of testosterone levels and
superoxide dismutase (SOD) activity, glutathione (GSH) content significantly (p < 0.01) increase compared with the
HS group. Moreover, G-Rg3 treatment effectively ameliorated the production of malondialdehyde (MDA) (p < 0.05 or
p < 0.01). Importantly, G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the
protein levels of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), and heat shock protein 70 (HSP70)
but also modulating the Bcl-2 family (p < 0.01 or p < 0.001) and activation of mitogen-activated protein kinase
(MAPK) signaling pathways (p < 0.01). For most of the parameters tested, the HS+G-Rg3 (10 mg/kg) group exhibited
potent effects compared with those exhibited by the low dose (5 mg/kg) group. In conclusion, the present study
demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the
MAPK-mediated oxidative stress and apoptosis in mice. 相似文献
15.
Mariana M. B. Borges Jussaro A. Duque Rafaela F. Zancan Rodrigo R. Vivan Ricardo A. Bernardes Marco A. H. Duarte 《Microscopy research and technique》2019,82(7):1057-1064
The aim of this study was to evaluate three reciprocating systems and complementary cleaning methods on filling material removal during retreatment of flattened canals. Thirty‐six mandibular incisors were prepared using rotary instruments up to size 25.08 and filled using the single‐cone technique. Subsequently, the teeth were divided into three groups (n = 12) according to retreatment procedures: Reciproc Blue (RB): 25/0.08 and 40/0.06; ProDesign R (PDR): 25/0.06 and 35/0.05; and WaveOne Gold (WOG): 25/0.07 and 35/0.06. The remaining filling volume materials were assessed by means of micro‐CT imaging before and after retreatment. After this, the specimens were subdivided into three groups according to complementary cleaning methods: XP‐Endo Shaper (30/0.01); passive ultrasonic irrigation (PUI); 60° oscillatory instrumentation with #30 H‐file, and micro‐CT scan was taken. Then, the roots were cut in half and the samples were analyzed by scanning electron microscope (SEM). The data were analyzed statistically using Kruskal–Wallis and Dunn's Multiple Comparison test with significance level of 5%. None of the reciprocating files promoted complete removal of filling material and there was no statistical difference between the groups, regardless instrument size (p > 0.05). Complementary cleaning methods increased remnant filling removal (p < 0.05). XP‐endo Shaper significantly reduced the amount of filling material in the apical and middle thirds, compared with H‐files (p < 0.05), with no difference with PUI. In the SEM, there was no statistical difference among the instruments (p > 0.05). The reciprocating systems showed similar effectiveness in removing root filling material. Complementary cleaning method with the XP‐Shaper enhanced filling material removal. 相似文献
16.
Evaluation of vascular endothelial growth factor gene and protein expression in canine metastatic mammary carcinomas
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Talita M.M. Raposo‐Ferreira Rosana C.L. Salvador Erika M. Terra Juarez H. Ferreira Ivan José Vechetti‐Junior Mirela Tinucci‐Costa Silvia R. Rogatto Renée Laufer‐Amorim 《Microscopy research and technique》2016,79(11):1097-1104
17.
YUAN BI TIANQI LI HONGJIE PAN MING GUO LIANGKANG CHEN QI QI MEIXIN ZHANG LINGLING ZHANG LININ YU XIAOFENG WAN HUAJUN ZHENG RUNSHENG LI 《Biocell》2020,44(3):301-313
Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and
impotence without a clarified mechanism for many hundreds of years. In the present study, mice were received sulfur
or distilled water for 35 days by daily intragastric gavage at a dose of 250 mg/kg body weight. Then, the serum
testosterone level and genes associated with testicular testosterone biosynthesis (TTB) were detected. The gut
microbiota was also analyzed by 16S rRNA gene sequencing. Serum testosterone level was significantly increased by
291.1% in sulfur-treated mice. The H2S levels in serum and feces were significantly increased. The expression of genes
associated with TTB including StAR, p450c17, 3β-HSD, and P450scc in testes were significantly upregulated by Sulfur
and NaHS, suggesting that sulfur promotes TTB depending on H2S. In addition, sulfur increased the diversity of gut
microbiota and the abundance of several bacteria associated with sulfur metabolism, including genus Prevotella, which
might be positively associated with serum level of testosterone in boys. Five pathways including bile secretion,
carotenoid biosynthesis, lipid biosynthesis proteins, propanoate metabolism, and biosynthesis of type II polyketide
products, were identified to associate with sulfur. Together, our results suggested that sulfur upregulated testicular
testosterone biosynthesis via H2S, which was associated with alteration of gut microbiota in mice. Our study
highlights a mechanism for the treatment of late-onset hypogonadism and impotence by sulfur. 相似文献
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Post-resuscitation myocardial dysfunction (PRMD) is the most severe myocardial ischemia-reperfusion injury
(MIRI) and is characterized by difficult treatment and poor prognosis. Research has shown the protective effects of the
rational use of ivabradine (IVA) against PRMD; however, the molecular mechanisms of IVA remain unknown. In this
study, an ischemia-reperfusion injury (IRI) model was established using hypoxic chambers. The results demonstrated
that pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis. IVA attenuated mitochondrial damage,
eliminated excess reactive oxygen species (ROS), suppressed IRI-induced ATP and NAD+
, and increased the
AMP/ATP ratio. We further found that IVA increased the mRNA levels of sirtuin 1 (SIRT1) and peroxisome
proliferator-activated receptor-γ coactivator 1α (PGC-1α) and upregulated the expression levels of phosphorylated
AMP-activated protein kinase (p-AMPK)/AMPK, SIRT1, and PGC-1α proteins. Interestingly, no change in AMPK
mRNA levels was observed. Cardiomyocyte energy metabolism significantly changed after IRI. The aim of this study
was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway in
myocardial ischemia/reperfusion injury-induced in H9c2 cell. 相似文献
20.
Manuela Cesaretti Jocelyn Gal Charles Bouveyron Alberto Diaspro Eric Fontas Andrea Antonini Rodolphe Anty Antonio Iannelli Stephanie Patouraux 《Microscopy research and technique》2020,83(9):1025-1031
Macrovesicular steatosis (MS) is a major risk factor for liver graft failure after transplantation and pathological microscopic examination of a frozen tissue section remains the gold standard for its assessment. However, the latter requires an experienced in‐house pathologist for correct and rapid diagnosis as well as specific equipment that is not always available. Smartphones, which are must‐have tools for everyone, are very suitable for incorporation into promising technology to generate moveable diagnostic tools as for telepathology. The study aims to compare the microscopic assessment of nonalcoholic fatty liver disease (NAFLD) spectrum in liver allograft biopsies by a smartphone microscopy platform (DIPLE device) to standard light microscopy. Forty‐two liver graft biopsies were evaluated in transmitted light, using an iPhone X and the microscopy platform. A significant correlation was reported between the two different approaches for graft MS assessment (Spearman's correlation coefficient: r = .93; p < .001) and for steatohepatitis feature (r = .56; p < .001; r = .45; p < .001). Based on these findings, a smartphone integrated with a cheap microscopy platform can achieve adequate accuracy in the assessment of NAFLD in liver graft and could be used as an alternative to standard light microscopy when the latter is unavailable. 相似文献