Flower color polymorphism of a wild Iris on the Qinghai-Tibet plateau.

BACKGROUND: Flower color plays a crucial role in attracting pollinators and facilitating environmental adaptation. Investigating the causes of flower color polymorphism and understanding their potential effects on both ecology and genetics can enhance our understanding of flower color polymorphism in wild plant. RESULTS: In this study, we examined the differences of potential male and female fitness between purple- and yellow- flower individuals in Iris potaninii on the Qinghai-Tibet Plateau, and screened key genes and positively selective genes involved in flower color change. Our results showed that yellow flower exhibited a higher pollen-to-ovule ratio. Yellow flowers were derived from purple flowers due to the loss of anthocyanins, and F3H could be an essential gene affecting flower color variation though expression regulation and sequence polymorphism in this species. Furthermore, our findings suggest that genes positively selected in yellow-flowered I. potaninii might be involved in nucleotide excision repair and plant-pathogen interactions. CONCLUSIONS: These results suggest that F3H induces the flower color variation of Iris potaninii, and the subsequent ecological and additive positive selection on yellow flowers may further enhance plant adaptations to alpine environments.

[Application value of a metamorphic mechanism-based special dressing system for patients after scrotal surgery].

OBJECTIVE: To investigate the application of a metamorphic mechanism-based special dressing system (MMDS) in improving the prognosis and comfort of the patient after scrotal surgery. METHODS: We included 48 cases of scrotal surgery using the traditional method for postoperative dressing from June 2017 to June 2018 (the control group) and another 48 cases employing MMDS postoperatively from July 2018 to June 2019 (the MMDS group). We observed the differences between the two groups of patients in the incidence of scrotal edema, pain score, hospitalization days, patients' satisfaction, and dressing time. RESULTS: The scrotal edema score showed no statistically significant difference between the MMDS and control groups at 24 hours after operation (P > 0.05) but remarkably lower in the former than in the latter group at 48 hours (1.42 ± 0.5 vs 2.27 ± 0.7, P < 0.05) and 72 hours postoperatively (1.35 ± 0.2 vs 2.25 ± 0.7, P < 0.05). The MMDS group, compared with the controls, also exhibited a lower pain score (2.2 ± 1.0 vs 3.4 ± 1.5, P < 0.05), shorter hospitalization time (ï¼»5.96 ± 1.2ï¼½ vs ï¼»9.13 ± 2.3ï¼½ d, P < 0.05) and higher satisfaction score (98.1 ± 1.6 vs 92.8 ± 2.8, P < 0.05), as well as shorter dressing time at 24, 48 and 72 hours after operation (P < 0.05). CONCLUSIONS: The metamorphic mechanism-based special dressing system is a safe, efficient, simple and feasible method for dressing after scrotal surgery, which can effectively promote recovery and improve the quality of life of the patients.

Intrinsically Safe Lithium Metal Batteries Enabled by Thermo-Electrochemical Compatible In Situ Polymerized Solid-State Electrolytes.

In situ polymerized solid-state electrolytes have attracted much attention due to high Li-ion conductivity, conformal interface contact, and low interface resistance, but are plagued by lithium dendrite, interface degradation, and inferior thermal stability, which thereby leads to limited lifespan and severe safety hazards for high-energy lithium metal batteries (LMBs). Herein, an in situ polymerized electrolyte is proposed by copolymerization of 1,3-dioxolane with 1,3,5-tri glycidyl isocyanurate (TGIC) as a cross-linking agent, which realizes a synergy of battery thermal safety and interface compatibility with Li anode. Functional TGIC enhances the electrolyte polymeric level. The unique carbon-formation mechanism facilitates flame retardancy and eliminates the battery fire risk. In the meantime, TGIC-derived inorganic-rich interphase inhibits interface side reactions and promotes uniform Li plating. Intrinsically safe LMBs with nonflammability and outstanding electrochemical performances under extreme temperatures (130 °C) are achieved. This functional polymer design shows a promising prospect for the development of safe LMBs.

A Dynamically Stable Mixed Conducting Interphase for All-Solid-State Lithium Metal Batteries.

All-solid-state lithium (Li) metal batteries (ASSLMBs) employing sulfide solid electrolytes have attracted increasing attention owing to superior safety and high energy density. However, the instability of sulfide electrolytes against Li metal induces the formation of two types of incompetent interphases, solid electrolyte interphase (SEI) and mixed conducting interphase (MCI), which significantly blocks rapid Li-ion transport and induces uneven Li deposition and continuous interface degradation. In this contribution, a dynamically stable mixed conducting interphase (S-MCI) is proposed by in situ stress self-limiting reaction to achieve the compatibility of Li metal with composite sulfide electrolytes (Li6 PS5 Cl (LPSCl) and Li10 GeP2 S12 (LGPS)). The rational design of composite electrolytes utilizes the expansion stress induced by the electrolyte decomposition to in turn constrain the further decomposition of LGPS. Consequently, the S-MCI inherits the high dynamical stability of LPSCl-derived SEI and the lithiophilic affinity of Li-Ge alloy in LGPS-derived MCI. The Li||Li symmetric cells with the protection of S-MCI can operate stably for 1500 h at 0.5 mA cm-2 and 0.5 mAh cm-2 . The Li||NCM622 full cells present stable cycling for 100 cycles at 0.1 C with a high-capacity retention of 93.7%. This work sheds fresh insight into constructing electrochemically stable interphase for high-performance ASSLMBs.

HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection.

BACKGROUND: PIWI protein family was found to play an important role in stem cell self-renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear. METHODS: HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n = 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n = 168) for survival analysis. RESULTS: Levels of HIWI protein and mRNA were up-regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P = .047) and intrahepatic metastasis (P = .027) and was an independent risk factor for overall survival (P = .007) and recurrence-free survival (P = .036), particularly in patients with low serum α-fetoprotein and low Edmondson-Steiner grade. CONCLUSIONS: HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well-differentiated HCC.

[Distribution Characteristics and Risk Assessment of Accumulated Heavy Metals in Bioretention Systems].

Topsoil samples (0-10 cm) from four bioretention systems with different land-use types were collected, including parking lot, roadside, residential area, and industrial park systems. The accumulation contents of As, Hg, Cd, Cr, Pb, Cu, Ni, and Zn were analyzed and evaluated, as were the influencing factors, pollution level, potential ecological risk, and human health risk. The results showed that there were significant differences in the accumulated contents of eight heavy metals. The average ω(As), ω(Hg), ω(Cd), ω(Cr), ω(Pb), ω(Cu), ω(Ni), and ω(Zn) were 8.92, 0.25, 0.10, 31.56, 14.81, 21.27, 23.69, and 62.75 mg·kg-1, respectively, and the average contents of As and Hg were 1.26 and 5.21 times the soil background values, respectively. Correlation analysis showed that the contents of the eight heavy metals were positively correlated with soil organic matter, pH value (except Hg), and phosphorus content (except As). The results of the Nemerow Comprehensive Pollution Index and Hakanson Potential Ecological Index showed that the pollution level and ecological risk of the other seven heavy metals were relatively low, whereas the pollution level and ecological risk of Hg reached the level of severe pollution and strong ecological risk, respectively. Affected by Hg, the comprehensive pollution level and ecological risk were relatively high; thus, Hg was a potential threat to the soil environment. The non-carcinogenic risks of heavy metals in the four systems were acceptable, but the carcinogenic risks were all beyond 10-6 though lower than 10-4, which indicated that these four systems had a certain carcinogenic risk, in which As was the main risk factor. Among these four land-use types, the accumulated pollutant contents, pollution levels, ecological risk, and human health risk of parking lots and roadside bioretention systems were much higher than those of residential areas and industrial parks.

Phalaenopsismedogensis (Orchidaceae, Epidendroideae, Vandeae), a new species from Xizang, China.

A new species of Orchidaceae, Phalaenopsismedogensis, from Motuo, Xizang, is described and illustrated based on morphological characters and molecular phylogenetics analysis. Molecular phylogenetic analysis and morphological characters indicate that P.medogensis is close to P.deliciosa, P.gibbosa and P.lobbii, but differs from them by having triangular wings on the column foot, rhombic lip mid-lobe with a fleshy-horned appendage at the base, and concave lip lateral lobes, the lower part white with a deep purplish-red spot and hairy, the upper part pale yellow with dense rust spots.

Validity of plasma macrophage migration inhibitory factor for diagnosis and prognosis of hepatocellular carcinoma.

We performed our study to determine whether plasma macrophage migration inhibitory factor (MIF) levels have diagnostic and prognostic value in hepatocellular carcinoma (HCC) patients. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to measure the expression of MIF in plasma and tissues, respectively. Plasma MIF levels were compared to HCC occurrence, clinicopathological features and outcomes. Cutpoints of plasma MIF levels for diagnosis and prognosis were, respectively, determined by receiver operating characteristic analysis and X-tile in corresponding training cohort, and then were confirmed in the validation cohort. The postoperative plasma MIF levels of HCC patients were detected in an independent cohort (80 HCC patients). As a result, MIF expression in situ was mainly observed in the cytoplasm of HCC cells. Intratumoral MIF expression was positively correlated with plasma MIF levels (r = 0.759, p < 0.001). Compared to serum α-fetoprotein (AFP), plasma MIF had a higher diagnostic value for discrimination of HCC from controls at 35.3 ng/ml. With determined cutpoints, plasma MIF levels demonstrated a significant association with overall survival (OS) and disease-free survival (DFS) of HCC patients even in patients with normal serum AFP levels and Tumor Node Metastasis (TNM) stage I. In addition, the plasma MIF levels were identified as an independent factor for OS [hazard ratio (HR) = 1.754; p = 0.012] and DFS (HR = 2.121; p < 0.001). Plasma MIF levels decreased markedly within 30 days after tumor resection (p < 0.001). Therefore, plasma MIF levels have potential as a diagnostic and prognostic factor for HCC.

[The establishment of a systematic site-specific metastasis model of human hepatocellular carcinoma in nude mouse].

To establish a systematic site-specific metastatsis model of human hepatocellular carcinoma (HCC) in nude mouse. HCCLM3-R cells were seeded into mice liver to establish xenograft mouse models. With the help of RFP, metastasis foci in lungs and lymph nodes in mice were detected using fluorescent stereomicroscopy and were removed. Cells derived from the metastasis foci were named HCCLM3-R-LM1 and HCCLM3-R-LnM1 respectively. HCCLM3-R-LM1 and HCCLM3-R-LnM1 cells were seeded into mice livers to analyze the lung and lymph node metastasis. Lungs of all tested mice were collected, examined by pathological evaluation and counted lung metastasis. Both lung and lymph node metastasis were found in HCCLM3-R-LM1, HCCLM3-R and HCCLM3-R-LnM1 cells and a significant difference was found between the lung and the lymph node metastasis levels in the three cells. The fluorescent areas (pixels) of lung and lymph node metastasis were 8687.00+/-1844.63 versus 2570.00+/-318.20 (P = 0.0031) in HCCLM3-R-LM1 cells, 6457.67+/-832.62 versus 10 994.33+/-2 212.31 (P = 0.0036) in HCCLM3-R cells, and 2968.67+/-2571.00 versus 24 416.00+/-7 186.13 (P = 0.0094) in HCCLM3-R-LnM1 cells, respectively. The middle numbers of microscopic lung metastatic foci were 775, 430 and 310 in HCCLM3-R-LM1, HCCLM3-R and HCCLM3-R-LnM1 cells (P less than 0.001), respectively, consist with the results quantified by RFP. We established the systematic site-specific metastasis models which demonstrates lung- and lymph node-specific metastasis potential in nude mice and can be used as a model for researches on site-specific metastasis of HCC.

U-Shaped Association of Aspect Ratio and Single Intracranial Aneurysm Rupture in Chinese Patients: A Cross-Sectional Study.

Background: Previous studies have analyzed the association of aspect ratio (AR) on the ruptured intracranial aneurysm (IA), but the findings are inconclusive and controversial. Therefore, the study aimed to derive a more detailed estimation of this association between AR and ruptured IA in Chinese IA patients. Methods: The present work was a cross-sectional study. We retrospectively collected 1,588 Chinese patients with a single IA from January 2010 to November 2017. The relationship was examined between AR at diagnosis and ruptured IA. Covariates included data of demographics, morphological parameters, lifestyle habits, clinical features, and comorbidities. Binary logistic regression and two-piecewise linear models were used to analyze independent associations of AR with ruptured IA. Results: The results suggest that the association between AR and IA rupture was U-shaped. In the AR range of 1.08-1.99, the prevalence of IA rupture was 13% lower for each 0.1-unit increment in AR [odds ratio 0.87, 95% confidence interval (CI) 0.80-0.98]. Conversely, for every 0.1-unit increase in AR, the prevalence of IA rupture increased by ~3% (odds ratio 1.03, 95% CI 1.01-1.06) in the AR range of 3.42-4.08. Conclusion: The relationship between AR and ruptured IA was U-shaped, with the negative association at AR of 1.08-1.99 and positive association at AR of 3.42-4.08.

Four new species and a new record of Orchidinae (Orchidaceae: Orchideae) from China.

Four new species of Orchidaceae from China, Heminium lijiangense, Peristylus fasciculatus, Platanthera milinensis, and Ponerorchis gongshanensis, together with a new country record, Peristylus tenuicallus, are described and illustrated based on morphological and/or phylogenetic analyses. Heminium lijiangense is closely related to H. elisabethae but differs from it by having the dorsal sepal ovate-orbicular and lip mid-lobe distinctly shorter than lateral lobes. P. fasciculatus is close to Peristylus tradescantifolius but is distinguished from it by having several fascicled and straight, root-like tubers (vs. one or two oblongoid tubers), old stems usually persistent, middle lobe of lip narrowly ligulate-lanceolate and half as long as the lateral lobes (vs. middle lobe deltoid, about a third as long as the lateral lobes or less), a raised callus at the base of each lateral lobe (vs. callus absent), spur gradually attenuate toward the apex (vs. spur clavate). Platanthera milinensis is similar to P. stenochila by sharing small green flowers and lip without a spur, but differs in having a creeping rhizome, a corymbose inflorescence, and a broadly ovate and slightly 3-lobed lip. Ponerochis gongshanensis is similar to P. faberi in its small flowers, but differs in having a linear leaf c. 3 mm wide (vs. leaf 5-13 mm wide), in the lip having collar-like raised margins on the sides of the spur entrance, and a mid-lobe which is notched at the apex but not divided into two divergent lobules that are nearly as large as the lateral lobes, as in P. faberi. All the proposed species obtained high support in phylogenetic analysis as new species. The recently described genus Apetalanthe is reduced to synonymy of Ponerorchis and a new combination is made.

Continuous positive airway pressure improves respiratory mechanics and efficiency of neural drive in stable COPD: an exploratory study.

BACKGROUND: Continuous positive airway pressure (CPAP) is a major treatment strategy for severe chronic obstructive pulmonary disease (COPD), especially with respiratory failure. However, it remains inconclusive whether CPAP affects respiratory mechanics and neural drive in stable COPD patients without respiratory failure. METHODS: Twenty-two COPD patients without respiratory failure received CPAP starting from 4 to 10 cmH2O in 1 cmH2O increments. Respiratory pattern, end expiatory lung volume (EELV), dynamic PEEPi (PEEPidyn), airway resistance (Raw), pressure-time product of diaphragmatic pressure (PTPdi) and esophageal pressure (PTPeso), root mean square (RMS) of diaphragm electromyogram (EMGdi) and ratio of ventilation (Ve) to EMGdi (i.e., Ve/RMS) were measured before and at each level of continue positive airway pressure (CPAP). A subgroup analysis was performed between patients with and without inspiratory muscle weakness. RESULTS: Nineteen patients completed the treatment. The respiratory pattern improved significantly after CPAP. Raw, PTPdi, and Pdi decreased significantly. ΔEELV decreased at 4 cmH2O (P<0.05), but increased significantly at >8 cmH2O. PEEPidyn decreased from 2.18±0.98 to 1.37±0.55 cmH2O. RMS increased while Ve/RMS improved significantly after CPAP (P<0.05). Besides, CPAP could significantly improve respiratory mechanics in patients with inspiratory muscle weakness. CONCLUSIONS: CPAP improves respiratory pattern, PEEPi, Raw, work of breathing and efficiency of neural drive in COPD patients without respiratory failure, but easily increases dynamic pulmonary hyperinflation. These effects on respiratory mechanics are significant in patients with inspiratory muscle weakness.

[Design of a bowel sounds acquisition system based on C8051F340 MCU].

This paper introduces an eight channels dada acquisition system. A peripheral circuit based on C8051F340 MCU has been designed and its USB controller is used to transfer data, which realizes real-time detection, display and storage of bowel sounds. The system has many advantages such as high precision and stable performance, and thus provides a new means for the bowel sounds study.

Begonia medogensis, a new species of Begoniaceae from Western China and Northern Myanmar.

Begonia medogensis JianW.Li, Y.H.Tan & X.H.Jin, a new species of Begoniaceae, is described and illustrated by colour photographs. Begonia medogensis is distributed in western China and northern Myanmar. It has erect stems, is tuberless, has many triangular to lanceolate leaves, base slightly asymmetric, margins remotely and irregularly denticulate; staminate flowers have 4 perianth segments, with outer 2 segments broadly ovate, inner 2 spathulate; pistillate flowers have 5 perianth segments, unequal, outer 4 broadly ovate, inner 1 spathulate. The new species is assigned to section Platycentrum and can easily be distinguished from the other species in the section.

[Single nucleotide polymorphism analysis on the 5' regulatory region of IGF2 gene in Wuzhishan pig].

Single nucleotide polymorphisms (SNPs) in partial 5' regulatory region of the insulin-like growth factor 2 (IGF2) gene were studied by DNA sequencing in 60 pigs from the Wuzhishan, Diannan small-ear, Xiang, Meishan and Large White pig breeds. Thirteen SNP sites were detected, including one transversion at T6029A, 4 A<---->G transitions (A5976G, G13520A, G13563A and G13669A) and 8 C<---->T transitions (C5872T, C5888T, C6010T, C6037T, C6043T, C6063T,C6112T, C6164T). These 13 SNPs formed 23 composite genotypes. The gene, genotype and composite genotype frequencies of every SNP site in the whole group and in each breed were calculated. Results showed that the predominant allele in 3 miniature pig breeds was G, T and A at A5976G, C6164T and G13669A sites respectively, but the A-C-G allele was pre-dominant in Meishan and Large White breeds. Moreover, H15 and H19 were the characteristic composite genotype for the large versus the miniature breeds, respectively. In addition, the C5888T SNP was analyzed in 123 Wuzhishan pigs by the PCR-RFLP method. Results showed that the predominant allele was C, and the predominant genotype was CC. chi2-test results indicated that the Wuzhishan pig breed was at Hardy-Weinberg equilibrium with respect to this SNP. These results provide the miniature pig breeds such as the Wuzhishan pig with certain genetic references on the regulation of growth and development, and the mechanism of its dwarfism.

α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.

PURPOSE: Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property. In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated. METHODS: Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor. Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels. RESULTS: We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells. α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect. More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo. CONCLUSIONS: The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.

[Recent Distribution and Sources of Polycyclic Aromatic Hydrocarbons in Surface Soils from Yangtze River Delta].

A total of 243 surface soil samples collected from 11 cities in the Yangtze River Delta region were analyzed for the concentrations, spatial distribution, component profiles and emission sources of 29 PAH species. The analytical results indicated the total concentrations of PAHs in Yangtze River Delta fell in the range from 21. 0 ng x g(-1) to 3 578.5 ng x g(-1) with an arithmetic mean and standard deviation of 310.6 ng x g(-1) and 459.1 ng x g(-1), respectively. Our data showed spatial distribution of PAHs concentrations varied greatly in the region. In addition, the contents of PAHs were positively correlated with the total organic carbon fractions in topsoil. The sites with the highest levels of PAHs in the 11 cities studied were located in Suzhou with 759.0 ng x g(-1) +/- 132.9 ng x g(-1) ollowed by the areas of Wuxi and Shanghai, with the total PAHs concentrations of 565. 3 ng x g(-1) +/- 705.5 ng x g(-1) and 349.4 ng g(-1) 220. 1 ng-g(-1) respectively. The profiles of different components pointed to a predominant role of the species with 2-4 rings, and especially for the low molecular weight components with 2-3 rings. A preliminary identification on emission sources of local PAHs was performed by the specific ratios of isomeric species and principal component analysis (PCA). The results designated industrial coal and biomass combustion as the main mixed emission sources of PAHs in surface soils from Yangtze River Delta, and tail gas from transport as another major source in some areas.

[Genetic analysis of 32 microsatellite loci in 13 families of Wuzhishan pig by multiplex PCR and gene scanning technique].

Wuzhishan pig is one of the rare and endangered breeds in china. They have the following characteristics such as :light body weight and small size, early sexually maturity, high meat quality and genetic identification with 6 approximately 8 pares litter size,body weight of born 0.3 approximately 0.4 kg, 15 approximately 16 kg at 6 month old, 35 kg at 2 years old, and so on. They may be used for laboratory utilization, comparative studies on human medical model, embryonic engineering, nutrition metabolism, sensitivity test on virus and bacteria, skin brut and tranfer, removing lipid, teeth and mouth cavity diseases, studies on cardiovascular model and evaluation of new medicine products. The polymorphisms of 32 microsatellites in 13 families of Wuzhishan pig in Hainan were Analysed. Number of alleles in each family was counted, mean heterozygosity and polymorphism Information content(PIC) were calculated. The results showed that number of alleles was 13.66, mean heterozygosity was 0.559 while polymorphism information content was 0.731. This revealed that genetic diversity is abundant in Wuzhishan pig in Hainan. These results have instructional significance for preserving breeds, selection and breeding, development and utilization of Wuzhishan pig in Hainan.

Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma.

Overexpression of CD147/basigin in hepatic cells promotes the progression of hepatocellular carcinoma (HCC). Whether CD147 also expressed in liver non-parenchymal cells and associated with HCC development was unknown. The aim of the study was to explore time-dependent cell expression patterns of CD147 in a widely accepted N-diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC mouse model. Liver samples collected at month 1-12 of post-DEN/PB administration were assessed the localization of CD147 in hepatocytes, endothelial cells, hepatic stellate cells, and macrophages. Immunohistochemistry analysis showed that CD147 was upregulated in liver tumors during month 1-8 of DEN/PB induction. Expression of CD147 was positively correlated with cytokeratin 18, a hepatocyte marker (r = 0.7857, P = 0.0279), CD31 (r = 0.9048, P = 0.0046), an endothelial cell marker, and CD68, a macrophage marker (r = 0.7619, P = 0.0368). A significant correlation was also observed between CD147 and alpha-smooth muscle actin (r = 0.8857, P = 0.0333) at DEN/PB initiation and early stage of tumor formation. Immunofluorescence and fluorescence in situ hybridization showed that CD147 co-expressed with cytokeratin 18, CD31, alpha-smooth muscle actin, and CD68. Moreover, there existed positive correlations between CD147 and microvessel density (r = 0.7857, P = 0.0279), CD147 and Ki-67 (r = 0.9341, P = 0.0022) in the development of DEN/PB-induced HCC. In conclusion, our results demonstrated that CD147 was upregulated in the liver parenchymal and mesenchymal cells and involved in angiogenesis and tumor cell proliferation in the development of DEN/PB-induced HCC.

Activation of TGF-ß1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

Activation of hepatic stellate cells (HSCs) by transforming growth factor-ß1 (TGF-ß1) initiates HBV-associated fibrogenesis. The mechanism of TGF-ß1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-ß1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-ß1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-ß1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-ß1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-ß1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-ß1 synthesis. These findings indicate that TGF-ß1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-ß receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.