MdPP2C24/37, Protein Phosphatase Type 2Cs from Apple, Interact with MdPYL2/12 to Negatively Regulate ABA Signaling in Transgenic Arabidopsis.

The phytohormone abscisic acid (ABA) plays an important role in the ability of plants to cope with drought stress. As core members of the ABA signaling pathway, protein phosphatase type 2Cs (PP2Cs) have been reported in many species. However, the functions of MdPP2Cs in apple (Malus domestica) are unclear. In this study, we identified two PP2C-encoding genes, MdPP2C24/37, with conserved PP2C catalytic domains, using sequence alignment. The nucleus-located MdPP2C24/37 genes were induced by ABA or mannitol in apple. Genetic analysis revealed that overexpression of MdPP2C24/37 in Arabidopsis thaliana led to plant insensitivity to ABA or mannitol treatment, in terms of inhibiting seed germination and overall seedling establishment. The expression of stress marker genes was upregulated in MdPP2C24/37 transgenic lines. At the same time, MdPP2C24/37 transgenic lines displayed inhibited ABA-mediated stomatal closure, which led to higher water loss rates. Moreover, when exposed to drought stress, chlorophyll levels decreased and MDA and H2O2 levels accumulated in the MdPP2C24/37 transgenic lines. Further, MdPP2C24/37 interacted with MdPYL2/12 in vitro and vivo. The results indicate that MdPP2C24/37 act as negative regulators in response to ABA-mediated drought resistance.

Hypseudohenrins I - K: three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum pseudohenryi.

Three previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) derivatives, hypseudohenrins I-K (1-3), along with a known analogue hyphenrone X (4), were isolated from the aerial part of Hypericum pseudohenryi. The structures of the new compounds were elucidated by NMR spectroscopy and ECD calculation. The anti-inflammatory activity of the compounds was evaluated. Compounds 1-3 showed mild anti-inflammatory activity while hyphenrone X showed prominent anti-inflammatory activity.[Formula: see text].

Two new polycyclic polyprenylated acylphloroglucinols derivatives from Hypericum acmosepalum.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) were mainly obtained from the plants of Hypericum genus of Guttiferae family, and possessed intriguing chemical structures and appealing biological activities. Two new PPAPs derivatives, hyperacmosin C (1) and hyperacmosin D (2) were isolated from H. acmosepalum. Their structures were established by NMR, HREIMS, and experimental electronic circular dichroism spectra. Besides, compound 1 showed significant hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage and compound 2 could moderately increase the relative glucose consumption.

Hyperacmosins H-J, three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum acmosepalum.

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1-3), with four known compounds (4-7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.[Formula: see text].

Current perspectives of cancer-associated fibroblast in therapeutic resistance: potential mechanism and future strategy.

The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial role in inducing drug resistance besides cancer development and progression. Recently, many efforts have been devoted to understand the role of tumor microenvironment in cancer drug resistance as it provides the shelter, nutrition, and paracrine niche for cancer cells. Cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, reside in symbiotic relationship with cancer cells, supporting them to survive from cancer drugs. The present review summarizes the recent understandings in the role of CAFs in drug resistance in various tumors. Acknowledging the fact that drug resistance depends not only upon cancer cells but also upon the microenvironment niche could guide us to formulate novel cancer drugs and provide the optimal cancer treatment.

An unusual case of ectopic corticotrophin-releasing hormone syndrome caused by an adrenal noncatecholamine-secreting pheochromocytoma: a case report.

BACKGROUND: Pheochromocytoma, especially for noncatecholamine-secreting pheochromocytoma, is an extremely rare cause of ectopic corticotrophin-releasing hormone (CRH) syndrome. CASE PRESENTATION: A 27-year-old Chinese woman was administered dexamethasone for a skin allergy, but her general condition rapidly deteriorated over a month. She was subsequently hospitalized for typical clinical features of Cushing's syndrome. Endocrinological investigation confirmed severe hypercortisolism along with elevated plasma adrenocorticotropin hormone (ACTH). However, magnetic resonance imaging (MRI) revealed no pituitary adenoma. Abdominal contrast-enhanced computed tomography (CT) revealed a 6.5 cm heterogeneous right adrenal mass with mildly contrast enhancement. The tumor was found during a routine physical check-up at a local hospital 16 months ago; however, the patient did not have any symptoms and did not seek further medical attention at that time. Laparoscopic resection of the right adrenal tumor led to a rapid remission of Cushing's syndrome. Based on pathological findings and the presence of normal catecholamine metabolites in her serum and urine, the patient was diagnosed with noncatecholamine-secreting pheochromocytoma. Immunohistochemical staining of the adrenal tumor revealed positive staining for CRH and negative staining for ACTH. CONCLUSIONS: This is an extremely rare case of ectopic CRH syndrome caused by an adrenal noncatecholamine-secreting pheochromocytoma. Both ectopic ACTH syndrome and ectopic CRH syndrome should be considered in patients presenting with ACTH-dependent Cushing's syndrome caused by extrapituitary diseases.

Fabrication of multifunctional Gd2O3/Au hybrid nanoprobe via a one-step approach for near-infrared fluorescence and magnetic resonance multimodal imaging in vivo.

Facile fabrication of multimodal imaging probes is highly desired for bioimaging application due to their integrated advantages of several imaging modalities. Here, we report a simple and one-step mild strategy to fabricate a multifunctional Gd2O3/Au hybrid nanoprobe. Bovine serum albumin (BSA) was used as the template in the biomineralization synthesis. The fabricated BSA-Gd2O3/Au nanoprobe showed excellent chemical stability, intense near-infrared (NIR) fluorescence, and good magnetic resonance imaging (MRI) ability. The multimodal imaging potential of the prepared multifunctional nanoprobe was demonstrated by successful NIR fluorescent and magnetic resonance blood pool imaging. Further modification of BSA-Gd2O3/Au with arginine-glycine-aspartic acid peptide c(RGDyK) (RGD) enabled the nanoprobe for targeted tumor imaging in vivo.

Incorporation of computed tomography and magnetic resonance imaging function into NaYF4:Yb/Tm upconversion nanoparticles for in vivo trimodal bioimaging.

Rational design and fabrication of multimodal imaging nanoprobes are of great significance for in vivo imaging. Here we report the fabrication of a multishell structured NaYF4:Yb/Tm@NaLuF4@NaYF4@NaGdF4 nanoprobe via a seed-mediated epitaxial growth strategy for upconversion luminescence (UCL), X-ray computed tomography (CT), and magnetic resonance (MR) trimodal imaging. Hexagonal phase NaYF4:Yb/Tm is used as the core to provide UCL, while the shell of NaLuF4 is epitaxially grown on the core not only to provide an optically inert layer for enhancing the UCL but also to serve as a contrast agent for CT. The outermost NaGdF4 shell is fabricated as a thin layer to give the high longitudinal relaxivity (r1) desired for MR imaging. The transition shell layer of NaYF4 not only provides an interface to facilitate the formation of NaGdF4 shell but also inhibits the energy transfer from inner upconversion activator to surface paramagnetic Gd(3+) ions. The fabricated multishell structured nanoprobe shows intense near-infrared UCL, high r1 value of 3.76 mM(-1) s(-1), and in vitro CT contrast effect. The multishell structured nanoprobe offers great potential for in vivo UCL/CT/MR trimodal imaging. Further covalent bonding of folic acid makes the multishell structured nanoprobe promising for in vivo targeted UCL imaging of tumor-bearing mice.

The heparan sulfate mimetic Muparfostat aggravates steatohepatitis in obese mice due to its binding affinity to lipoprotein lipase.

BACKGROUND AND PURPOSE: Heparanase is the only confirmed endoglycosidase that cleaves heparan sulfate (HS), a ubiquitous glycosaminoglycan with various essential roles in multiple pathological processes. Thus, the development of heparanase inhibitors has become an attractive strategy for drug discovery, especially in tumour therapy, in which HS mimetics are the most promising compounds. The various biological effects of heparanase also suggest a role for HS mimetics in many non-cancer indications, such as type 1 diabetes. However, the potential benefits of HS mimetics in obesity-related type 2 diabetes have not been elucidated. EXPERIMENTAL APPROACH: In this study, we investigated muparfostat (PI-88), a developed HS mimetic currently enrolled in Phase III clinical trials, in obese mouse models and in vitro cultured murine hepatocytes. KEY RESULTS: Daily administration of muparfostat for 4 weeks caused hyperlipidaemia and aggravated hepatic steatosis in obese mice models, but not in lean animals. In cultured hepatocytes, muparfostat did not alter lipid accumulation. Acute tests suggested that muparfostat binds to lipoprotein lipase in competition with HS on vascular endothelial cell surfaces, thereby reducing the degradation of circulating triglycerides by lipoprotein lipase and subsequent uptake of fatty acids into vascular endothelial cells and causing hyperlipidaemia. This hyperlipidaemia aggravates hepatic steatosis and causes liver injury in muparfostat-treated obese mice. CONCLUSIONS AND IMPLICATIONS: The binding activity of HS mimetics to lipoprotein lipase should be investigated as an additional pharmacological effect during heparanase inhibitor drug discovery. This study also provides novel evidence for an increased risk of drug-induced liver injury in obese individuals.

[Differentiation of axillary inflammatory and metastatic lymph nodes with diffusion-weighted imaging in animal modes].

OBJECTIVE: To evaluate the value of diffusion-weighted imaging (DWI) in the differentiation of axillary inflammatory hyperplastic and metastatic lymph nodes. METHODS: Forty female New Zealand white rabbits were divided randomly into 2 groups (n = 20 each). And the animal models of axillary inflammatory hyperplastic and metastatic lymph nodes were established. All successfully implanted models received conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) examinations. The features of signal intensity and shapes of lymph nodes were observed in two groups. The sizes of lymph nodes were measured on the selected axial T(2)WI. The signal intensity and appearance diffusion coefficient (ADC) value of lymph nodes and dorsal muscle at the same slice were measured on the selected T(2)WI, DWI and ADC map respectively. The relative signal intensity (rSIT(2)WI, rSIDWI) and relative ADC (rADC) value of lymph nodes to dorsal muscle were calculated and compared. The diagnostic efficacy of differentiating benign and malignant lymph nodes was analyzed with rADC value through the receiver operating characteristic curve. The correlation between rADC value and cell density was assessed with pathological findings as reference standard. RESULTS: The differences of size, rSIT(2)WI and rSIDWI were not statistically significant between two groups. The rADC value of inflammatory lymph nodes was greater than that of metastatic lymph nodes (0.91 ± 0.14 vs 0.64 ± 0.18). Significant difference existed (t = 3.879, P = 0.03). But there was a little overlap between two groups. With 0.78 as the diagnostic threshold of rADC value, the sensibility and specificity was 86.2% and 74.4% respectively. The correlation between rADC value and cell density of inflammatory hyperplastic and metastatic lymph nodes was significantly inverse (r = -0.53, P = 0.003). CONCLUSIONS: As compared with the routine MRI sequence, rADC value has a higher diagnostic efficacy in the differentiation of benign and malignant lymph nodes. Cell density may be the most important influencing factor for the differences of rADC value between two groups of lymph nodes.

Prenylaromadendrane-type diterpenoids from the gum resin of Boswellia sacra flueck and their cytotoxic effects.

Two new prenylaromadendrane-type diterpenoids, and three known analogues, were isolated from the ethanol extract of the gum resin of B. sacra Flueck. The structures of the new compounds were elucidated using 1 D and 2 D NMR spectroscopic analyses, mass spectrometric data, circular dichroism spectra, and comparison with the other compounds in the literature. One diterpenoid represents the first example of an acetoxyl-substituted prenylaromadendranoid in frankincense. All compounds exhibited notable cytotoxicity against human malignant glioma (U87-MG) cell line, with inhibitory rates exceeding that of the positive control 5-fluorouracil. However, nitric oxide inhibition induced by lipopolysaccarides was not observed in primary mouse peritoneal macrophages.

Treatment with b-AP15 to Inhibit UCHL5 and USP14 Deubiquitinating Activity and Enhance p27 and Cyclin E1 for Tumors with p53 Deficiency.

Background: TP53 protein is lost or mutated in about half of all types of human cancers and small molecules to regulate mutant p53 repair, or interrupt ubiquitination degradation of p53 induced by E3-ubiquitin ligase Mdm2 have a potential application in clinical application. Methods: To inhibit the deubiquitinase activity of 19S proteasome and restore the p53 protein level, in this study, we utilized p53 knockout mice to test the anti-cancer effect of a specific USP14 and UCH37 inhibitor b-AP15. Results: Our results show that UCHL5, USP14 and COPS5 are upregulated in p53-related tumors, and higher expression of these genes results in a shorter overall survival in patients with p53 deficiency. Treatment with b-AP15, a UCHL5 and USP14 deubiquitinating activity inhibitor in 19S regulatory subunit, induces tumor regression and prolong the survival period of tumor-loaded mice through down-regulation of COPS5 and its downstream AP-1 and E2F1, and up-regulation of the cell cycle-related proteins p27 and Cyclin E1. Conclusions: Thus, our results suggested that inhibition of UCHL5 and USP14 deubiquitinating activity in 19S proteasome may contribute an extensive approach to preventing tumor progress due to p53 deficiency.

Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer.

PURPOSE: Apatinib, an antiangiogenic drug, has shown beneficial effects only in a fraction of advanced gastric cancer (GC) patients. Given the recent success of immunotherapies, combination of apatinib with immune checkpoint inhibitor may provide sustained and potent antitumor responses. METHODS: Immunocompetent mice with subcutaneous MFC tumors grown were given a combination of apatinib and anti-PD-L1 antibody therapy. GC tissues from patients undergoing curative resection in China were collected, and the density of HEVs, MSI status and tumor-infiltrated lymphocytes were analyzed by immunohistochemical staining. RESULTS: Combined apatinib and PD-L1 blockade therapy synergistically delayed tumor growth and increased survival in MFC-bearing immunocompetent mice. The combination therapy promoted antitumor immunity by increasing the ratio of CD8+ cytotoxic T cells to Foxp3+ Treg cells, the accumulation of CD20+ B cells and the Th1/Th2 cytokine ratio (IFN-γ/IL-10). The combination therapy induced the formation of HEVs through activation of LTßR signaling, thus promoting CD8+ cytotoxic T cell and CD20+ B cell infiltration in tumors. In clinical GC samples, the density of HEVs positively correlated with the intratumoral infiltration of CD8+ cytotoxic T cells and CD20+ B cells. MSI-high GC showed a higher density of HEVs, CD8+ cytotoxic T cells and CD20+ B cells than MSS/MSI-low GC. GC patients with high densities of HEVs, CD8+ cytotoxic T cells and CD20+ B cells had an improved prognosis with superior overall survival. CONCLUSION: Combining apatinib with PD-L1 blockade treatment synergistically enhances antitumor immune responses and promotes HEV formation in GC.

Ten undescribed cembrane-type diterpenoids from the gum resin of Boswellia sacra and their biological activities.

Ten undescribed cembrane-type diterpenes boscartins AL-AU, as well as five known analogues were isolated from Boswellia sacra Flueck. The relative configurations of these boscartins were established by extensive spectroscopic analysis of NMR spectra, IR and MS. The absolute configurations of boscartin AL, boscartin AN and isoincensole oxide were unequivocally assigned by single crystal X-ray diffraction. Meanwhile, the absolute configurations of boscartin AM, boscartin AP and boscartin AQ were determined by an empirical in situ formed Rh-complex ECD method. Biological evaluations showed that four compounds exhibited obvious hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 µM. Regarding neuroprotective activity, some isolates displayed moderate to evident protective effects against glutamate-induced toxicity in primary cultured fetal rat cortical neurons or oxygen-glucose deprivation toxicity in SK-N-SH Cells at 10 µM.

[Correlation between MR diffusion weighted imaging with malignant degree of rabbit liver VX2 tumor models].

OBJECTIVE: To investigate the correlation between MR diffusion weighted imaging with cellularity and PCNA-LI of rabbit liver VX2 tumor models in different periods. METHODS: 38 successful implanted rabbits were assigned randomly into 2 equal groups and were performed MR DWI in different periods (14 and 21 d) after implantation respectively. Specimens of all tumors were stained with HE and PCNA-LI after MR examination. RESULTS: (1) The ADC value (x 10(-3) mm2/s) in surrounding solid components of liver VX2 tumors in the group of 21 d was lower than that of the group of 14 d (0.77 +/- 0.19 vs 1.00 +/- 0.24, P = 0.007); (2) the cellularity and PCNA-LI in surrounding solid components of liver VX2 tumors in the group of 21 d were higher than those of the group of 14 d respectively (63% +/- 7% vs 43% +/- 10%, P = 0.011; 80% +/- 11% vs 56% +/- 8%, P = 0.008); (3) there were negative correlation between ADC value and cellularity, PCNA-LI of the solid components of the tumors (r = - 0.695, P = 0.000; r = -0. 698, P = 0.000). CONCLUSION: The cellularity may be the most important factor that affects ADC value in solid components of liver VX2 tumors. Since the degree of malignancy is closely connected with cellularity and PCNA labeling index, ADC value measurement may be a new method which could predict the degree of malignancies in vivo.

Loss accounting of environmental pollution within Pearl River Delta region, South China.

Economic development puts pressure on environment through air, water and land degradation, which in turn brings real costs to the economy. Actual economy growth should therefore consider the environmental degradation cost resulted from economic activities. Pearl River Delta (PRD) region as a typical delta area with rapid development in China, is with great significance to understand the loses resulted from environmental pollution. This study conducts an environmental economic accounting within the PRD region from 2011 to 2015 using the environmental degradation cost accounting approach. We identified and calculated the economic, agricultural, industrial and social losses resulting from air, water and waste pollution with different valuation methods, which includes shadow price, replacement costs, market value method, etc. The results showed the total environmental degradation cost ranged from 18.1 to 19.8 billion US$ and the environmental degradation index declined slightly over the years, with significant differences among cities. It implied that the environmental condition of PRD region has been continuously improved over the years, but the capacity of environment control between cities had large differences. Cities in PRD region should therefore take measures tailored to their current situation to optimize their resource endowment and industrial structure, to overcome the conflicts between economic development and environmental protection. For cities with relatively high degradation cost, it is urgent to accelerate the efforts in improving the quality of the environment and ecosystem. For cities with lower degradation cost, it is important to take actions to keep on a sustainable and ecological efficient developing path. MAIN FINDINGS: The total environmental degradation cost of the PRD region is firstly calculated with insights on environmental management.

Therapeutic Strategies Targeting Cancer Stem Cells and Their Microenvironment.

Cancer stem cells (CSCs) have been demonstrated in a variety of tumors and are thought to act as a clonogenic core for the genesis of new tumor growth. This small subpopulation of cancer cells has been proposed to help drive tumorigenesis, metastasis, recurrence and conventional therapy resistance. CSCs show self-renewal and flexible clonogenic properties and help define specific tumor microenvironments (TME). The interaction between CSCs and TME is thought to function as a dynamic support system that fosters the generation and maintenance of CSCs. Investigation of the interaction between CSCs and the TME is shedding light on the biologic mechanisms underlying the process of tumor malignancy, metastasis, and therapy resistance. We summarize recent advances in CSC biology and their environment, and discuss the challenges and future strategies for targeting this biology as a new therapeutic approach.

Insulin-like growth factor-I induces chemoresistence to docetaxel by inhibiting miR-143 in human prostate cancer.

Elevated levels of insulin-like growth factor-I (IGF-I) are associated with carcinogenesis and cancer progression. However, the molecular mechanisms by which IGF-I promotes prostate cancer development remain to be elucidated. Docetaxel chemotherapy is an important therapeutic strategy in many types of human cancers including prostate cancer. In this study, we showed that IGF-I rendered PC-3 and DU145 cells more resistant to docetaxel treatment. IGF-I treatment decreased miR-143 expression, but increased the expression levels of IGF-I receptor (IGF-IR) and insulin receptor substrate 1 (IRS1), direct targets of miR-143. Overexpression of miR-143 abolished IGF-I-induced chemoresistance to docetaxel treatment, decreased expression levels of IGF-I, IRS1, and vascular endothelial growth factor (VEGF) in prostate cancer cell lines. Furthermore, docetaxel treatment significantly inhibited VEGF transcriptional activation, whereas IGF-I treatment induced VEGF transcriptional activation in a dose-dependent manner. Forced expression of IGF-IR and IRS1 cDNAs without the 3' UTR regions restored miR-143-inhibited VEGF transcriptional activation. Finally, miR-143 inhibited tumor growth and made cells more sensitive to docetaxel treatment for decreasing tumor growth in vivo. Taken together, our data demonstrates that IGF-I induces docetaxel resistance and upregulates IGF-IR and IRS1 expression through miR-143 downregulation, whereas miR-143 acts as a tumor suppressor by targeting its targets IGF-IR and IRS1.

IGF-1-mediated PKM2/ß-catenin/miR-152 regulatory circuit in breast cancer.

Dysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified ß-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both ß-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting ß-catenin and PKM2 expression. Intriguingly, IGF-1 induced ß-catenin and PKM2 expression and enhanced ß-catenin and PKM2 interaction. Subsequently, IGF-1-induced ß-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, ß-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with ß-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in ß-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future.

Monitoring the progression of renal fibrosis by T2-weighted signal intensity and diffusion weighted magnetic resonance imaging in cisplatin induced rat models.

BACKGROUND: Diffusion weighted imaging (DWI), with the applying of intravoxel incoherent motion model, has showed promising results in obtaining additional information about microperfusion and tubular flow associated with morphologic changes in chronic kidney diseases. The study aims to evaluate the potential of T2-weighted signal intensity (SI) and DWI with mono- and bi-exponential models to reflect the serial changes on cisplatin (CP) induced rat renal fibrosis models. METHODS: Magnetic resonance exams were performed prior to and 2 nd day, 4 th day, 6 th day, 8 th day, 2 nd week, 3 rd week and 4 th week after CP injection at a 3.0T with an animal coil. Besides T2-weighted images (T2WI), DWI of 13 b values from 0 to 1500 s/mm 2 was acquired. Apparent diffusion coefficient (ADC), fluid fraction f, pure diffusivity D and pseudodiffusivity DFNx01 values were calculated. The regions of interest were placed on cortex (CO), outer stripe of the outer medulla (OM) and inner stripe of the outer medulla (OM), parameters were measured and compared among different time points. Five rats were scarified at each time point for pathological examination. RESULTS: OM revealed remarkable hyperintense and broadened before it became an obscure thread, while CO demonstrated moderate hyperintense and IM didn't show significant change on T2WI. On all three stripes, ADC values decreased firstly then kept increasing since the 4 th day; f values decreased on all stripes; D values had a tendency to increase with fluctuations but the changes didn't achieve statistical significance; DFNx01 values increased at the 2 nd day then tended to be steady thereafter. Pathological findings revealed tubules epitheliums swelling followed by inflammation cells infiltration, interstitial fibrosis was observed since the 2 nd week. CONCLUSIONS: All of T2-weighted SI, ADC, and biexponential models parameters vary during fibrotic process; biexponential model is superior to monoexponential model in separating changes of microperfusion together with tubular flow from pure diffusion.