Synthesis and antibacterial activities of heterocyclic ring-fused 20(S)-protopanaxadiol derivatives.

Multidrug-resistant (MDR) bacterial infections are becoming a life-threatening issue in public health; therefore, it is urgent to develop novel antibacterial agents for treating infections caused by MDR bacteria. The 20(S)-protopanaxadiol (PPD) derivative 9 was identified as a novel antibacterial hit compound in screening of our small synthetic natural product-like (NPL) library. A series of novel PPD derivatives with heterocyclic rings fused at the C-2 and C-3 positions of the A-ring were synthesized and their antibacterial activities against Staphylococcus aureus (S. aureus) Newman strain and MDR S. aureus strains (USA300, NRS-1, NRS-70, NRS-100, NRS-108, NRS-271, XJ017, and XJ036) were evaluated. Among these compounds, quinoxaline derivative 56 (SH617) exhibited the highest activity with MICs of 0.5-4 µg/mL against the S. aureus Newman strain and the eight MDR S. aureus strains. Its antibacterial activity was comparable to that of the positive control, vancomycin. In the zebrafish, 56 revealed no obvious toxicity even at a high administered dose. In vivo, following a lethal infection induced by USA300 strains in zebrafish, 56 exhibited significantly increased survival rates in a dose-dependent manner.

MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.

3D nanocake-like Au-MXene/Au pallet structure-based label-free electrochemical aptasensor for paraquat determination.

3D nanocake-like Au-MXene and Au pallet (Au-MXene/AuP) nanocomposite-modified screen-printed carbon electrodes (SPCEs) were utilized to construct an ultrasensitive label-free electrochemical aptasensor through a self-assembly procedure for trace paraquat (PQ) residue detection. Benefiting from the excellent electrochemical (EC) performances (e.g., high conductivity and large surface area) of Au-MXene nanocomposites and AuP substrate, the developed Apt/Au-MXene/AuP/SPCE-based EC aptasensor displayed excellent specificity and anti-interference ability, good repeatability, and stability. A linear relationship between the log value of the change in current intensity [lg (ΔI)] and the log value of the concentration of PQ [lg (CPQ)] was obtained in the range 0.05-1000 ng/mL. The limit of detection was 0.028 ng/mL, and the sensitivity was 255.5 µA/(µM·cm2). Practical applications in malt and mint samples confirmed the accuracy of the EC aptasensor in complex matrices for PQ detection, providing a universal analytical tool for other trace pesticides in different food samples by simply replacing the corresponding aptamers.

Dedifferentiated chondrsarcoma: a clinicopathologic analysis of 25 cases.

BACKGROUND: To investigate the clinical, imaging and pathological features of dedifferentiated chondrosarcoma for better diagnosis. METHODS: Patients who had been confirmed to have dedifferentiated chondrosarcoma were enrolled in this study and analyzed in the clinical, imaging and pathological data. RESULTS: Twenty-five patients had pathologically confirmed dedifferentiated chondrosarcoma including 15 males and 10 females with an age range of 24-74 (median 58, interquartile range 49-65). Ten patients had the tumor at the femur, four at the ilium, two at the humerus, two at the tibia, two at cotyle, and one at each of the following locations: scapula, sacrum, rib, pubic branch, and calcaneus. Twenty-one patients had local pain and a soft tissue mass while the other four patients had only local pain without a soft tissue mass. Four patients had pathological fractures. Imaging showed extensive bone destruction with calcification inside the lesion and possible pathological fractures. On gross observation of the specimen, the chondrosarcoma components were usually located inside the bone, and the dedifferentiated sarcoma components were mainly located outside the bone. Microscopy showed the dedifferentiated tumor had two components: well-differentiated chondrosarcoma and poorly differentiated non-chondral sarcoma including malignant fibrous histiocytoma in eleven cases, osteosarcoma in ten cases, fibrosarcoma in two, liomyosarcoma in one, and lipoblastoma in the remaining one.. Followed up from 3 moths to 60 months (mean 15.6), eight patients died with a survival time of 10-23 months (mean 16), and the other 17 patients survived with the survival duration from three to 60 months (15). CONCLUSION: Dedifferentiated chondrosarcoma is a fatal disease with multiple components, and most of the cases have dual morphological and imaging features of chondrosarcoma and non-chondrosarcoma. The imaging presentations are primarily of common central chondrosarcoma, combined with cortical destruction, soft tissue mass, and pathological fractures.

Imaging features of hemangioma in long tubular bones.

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.

Polymethylated Phloroglucinol Meroterpenoids from Rhodomyrtus tomentosa and Their Antibacterial and Acetylcholinesterase Inhibitory Effects.

Rhotomentodiones C-E, three new polymethylated phloroglucinol meroterpenoids with diverse configurations, were isolated from the twigs and leaves of Rhodomyrtus tomentosa. Their structures and absolute configurations were established mainly by means of comprehensive spectroscopic data and electron circular dichroism (ECD) calculation. Among them, Rhotomentodione D (2) exhibited both antibacterial activity with an MIC value of 12.5 µg/mL against Propionibacterium acnes and AChE inhibitory activity with an IC50 value of 22.9 µm.

Extracorporeal membrane oxygenation for avian influenza A (H7N9) patient with acute respiratory distress syndrome: a case report and short literature review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is performed as an acceptable life-saving bridging procedure in patients with severe acute respiratory distress syndrome (ARDS).To patients with avian influenza A (H7N9)-associated ARDS, ECMO could be adopted as a feasible therapeutic solution. We present our successful experience with ECMO utilized in a respiratory failure patient with H7N9 infection. CASE PRESENTATION: A 44 years-old female with H7N9-induced ARDS was admitted to intensive care unit (ICU) and was treated with veno-venous ECMO for six days, antiviral therapy, prolonged corticosteroid infusion and other therapies. She suffered significant hemorrhage requiring transfusion of platelets and multidrug-resistant Acinetobacter Baumannii infection during ECMO support. Bleeding and infection almost killed the patient's life. Fortunately, she was alive at last and completly recovered after 38 days of ICU stay. CONCLUSIONS: ECMO was effective in this H7N9 patient with a fatal respiratory failure. Mechanical circulatory support was the only chance for our patient with H7N9-associated ARDS to survive until respiratory function recovery. Early detection and rapid response are essential to these serious ECMO-associated complications such as hemorrhage, thrombosis and infection.

Bioengineering Novel Chimeric microRNA-34a for Prodrug Cancer Therapy: High-Yield Expression and Purification, and Structural and Functional Characterization.

Development of anticancer treatments based on microRNA (miRNA/miR) such as miR-34a replacement therapy is limited to the use of synthetic RNAs with artificial modifications. Herein, we present a new approach to a high-yield and large-scale biosynthesis, in Escherichia coli using transfer RNA (tRNA) scaffold, of chimeric miR-34a agent, which may act as a prodrug for anticancer therapy. The recombinant tRNA fusion pre-miR-34a (tRNA/mir-34a) was quickly purified to a high degree of homogeneity (>98%) using anion-exchange fast protein liquid chromatography, whose primary sequence and post-transcriptional modifications were directly characterized by mass spectrometric analyses. Chimeric tRNA/mir-34a showed a favorable cellular stability while it was degradable by several ribonucleases. Deep sequencing and quantitative real-time polymerase chain reaction studies revealed that tRNA-carried pre-miR-34a was precisely processed to mature miR-34a within human carcinoma cells, and the same tRNA fragments were produced from tRNA/mir-34a and the control tRNA scaffold (tRNA/MSA). Consequently, tRNA/mir-34a inhibited the proliferation of various types of human carcinoma cells in a dose-dependent manner and to a much greater degree than the control tRNA/MSA, which was mechanistically attributable to the reduction of miR-34a target genes. Furthermore, tRNA/mir-34a significantly suppressed the growth of human non-small-cell lung cancer A549 and hepatocarcinoma HepG2 xenograft tumors in mice, compared with the same dose of tRNA/MSA. In addition, recombinant tRNA/mir-34a had no or minimal effect on blood chemistry and interleukin-6 level in mouse models, suggesting that recombinant RNAs were well tolerated. These findings provoke a conversation on producing biologic miRNAs to perform miRNA actions, and point toward a new direction in developing miRNA-based therapies.

Differentiation of noncalculous periampullary obstruction: comparison of CT with negative-contrast CT cholangiopancreatography versus MRI with MR cholangiopancreatography.

OBJECTIVES: The purpose of this study was to compare CT with negative-contrast CT cholangiopancreatography (nCTCP) using subvolume minimum intensity projection (MinIP) versus MRI with MRCP in differentiating noncalculous periampullary obstruction. METHODS: Sixty-four patients with clinically proven noncalculous periampullary obstructions who had undergone both MDCT and MR examinations before operation were reviewed retrospectively. Two reviewers independently interpreted the two image sets (the CT with nCTCP set [CT set] vs. the MRI with MRCP set [MRI set]) in differentiating both benign from malignant obstruction and pancreatic head carcinoma (PHC) from non-PHC, and the results were compared to the final clinical records. RESULTS: In this study, no statistically significant differences were observed in the accuracy of differentiating benign from malignant periampullary obstruction (p = 0.754 for reviewer 1 and p = 0.508 for reviewer 2) on the two image sets. The accuracy of differentiating PHC from non-PHC was also statistically insignificant (p = 0.125 for reviewer 1 and p = 1.000 for reviewer 2) on the two image sets. CONCLUSION: The CT set provides a comparable performance to that of the MRI set in differentiating noncalculous periampullary obstruction. KEY POINTS: • nCTCP with subvolume MinIP is a practical tool in evaluating biliary obstruction • Two image sets have a comparable performance in differentiating noncalculous periampullary obstruction • MDCT could serve as an alternative in patients not eligible for MRI.

No association between Y chromosomal haplogroups and severe acne in the Han Chinese population.

Severe acne presents sexual dimorphism in its incidence in Chinese population. It is more prevalent in males. To assess the possible Y chromosomal contribution to severe acne risk in Han Chinese males, we analyzed 2041 Y chromosomal SNPs (Y-SNPs) in 725 severe acne cases and 651 controls retrieved from our recent genome-wide association study data. After data filtering, we assigned 585 cases and 494 controls into 12 Y chromosomal haplogroups based on 307 high-confidence Y-SNPs. No statistically significant difference in the distribution of Y chromosomal haplogroup frequencies was observed between the case and control groups. Our results showed a lack of association between the incidence of severe acne and the different Y chromosomal haplogroup in the Han Chinese population.

Rapid production of novel pre-microRNA agent hsa-mir-27b in Escherichia coli using recombinant RNA technology for functional studies in mammalian cells.

Noncoding microRNAs (miRNAs or miRs) have been revealed as critical epigenetic factors in the regulation of various cellular processes, including drug metabolism and disposition. However, research on miRNA functions is limited to the use of synthetic RNA and recombinant DNA agents. Herein, we show that novel pre-miRNA-27b (miR-27b) agents can be biosynthesized in Escherichia coli using recombinant RNA technology, and recombinant transfer RNA (tRNA)/mir-27b chimera was readily purified to a high degree of homogeneity (>95%) using anion-exchange fast protein liquid chromatography. The tRNA-fusion miR-27b was revealed to be processed to mature miRNA miR-27b in human carcinoma LS-180 cells in a dose- and time-dependent manner. Moreover, recombinant tRNA/miR-27b agents were biologically active in reducing the mRNA and protein expression levels of cytochrome P450 3A4 (CYP3A4), which consequently led to lower midazolam 1'-hydroxylase activity. These findings demonstrate that pre-miRNA agents can be produced by recombinant RNA technology for functional studies.

Genotype-phenotype correlations in severe acne in a han Chinese population.

BACKGROUND: Two novel susceptibility gene loci (1q24.2 and 11p11.2) for severe acne have been identified in a genome-wide association study of a Han Chinese population. OBJECTIVE: The current study investigated the relationships of these gene loci with clinical phenotypes, including onset age, atrophic scarring, hypertrophic scarring and family history. Furthermore, we investigated the correlations between these four clinical phenotypes. METHODS: We used the χ2 test to compare the allele frequency among the different clinical phenotypes. We calculated Spearman's correlation coefficient to measure the relationship between the different clinical phenotypes. RESULTS: We identified significant associations between the 11p11.2 locus and disease family history (p < 0.05). We also determined that hypertrophic scarring was moderately correlated with atrophic scarring (rs = 0.315). CONCLUSIONS: This study suggests that the susceptibility gene locus 11p11.2 may contribute to the complex phenotypes of severe acne, particularly in cases of hereditary severe acne, whereas there are also correlations between the different phenotypes.

Differential diagnosis of periampullary carcinomas: comparison of CT with negative-contrast CT cholangiopancreatography versus MRI with MR cholangiopancreatography.

BACKGROUND: Negative-contrast CT cholangiopancreatography (nCTCP) has been introduced into clinical practice recently. In the present study, we compared CT with nCTCP vs. MRI with MR cholangiopancreatography (MRCP) for the differential diagnosis of periampullary carcinomas. METHODS: Fifty-nine patients with pathologically proven periampullary carcinomas who had received both CT and MR examinations before operation were reviewed retrospectively. Two reviewers independently interpreted the two image sets [the two-dimensional (2D)-CT with nCTCP set (CT set) vs. the 2D-MRI with MRCP set (MRI set)] in differentiating periampullary carcinomas, and the results were compared to the final pathologic records. RESULTS: An interobserver agreement with a weighed κ value of 0.868 for the CT set and 0.701 for the MRI set was obtained for both reviewers in this study. No statistically significant differences were observed in the accuracy of identifying each of the periampullary carcinomas of four origins (P values of 0.250, 0.500, 0.500, and 1.000 for reviewer 1 in comparison with 1.000, 0.625, 0.687, and 1.000 for reviewer 2 on the two image sets, respectively). CONCLUSION: The CT set provides a comparable performance to that of the MRI set in differentiating periampullary carcinomas, and it may be an alternative to 2D-MRI with MRCP in assessing malignant biliary obstruction in patients who are not suitable for MR examinations.

High-performance electrode materials of heteroatom-doped lignin-based carbon materials for supercapacitor applications.

Supercapacitors are the preferred option for supporting renewable energy sources owing to many benefits, including fast charging, long life, high energy and power density, and saving energy. While electrode materials with environmentally friendly preparation, high performance, and low cost are important research directions of supercapacitors. At present, the growing global population and the increasingly pressing issue of environmental pollution have drawn the focus of numerous researchers worldwide to the development and utilization of renewable biomass resources. Lignin, a renewable aromatic polymer, has reserves second only to cellulose in nature. Ten million tonnes of industrial lignin are produced in pulp and paper mills annually, most of which are disposed of as waste or burned for fuel, seriously depleting natural resources and polluting the environment. One practical strategy to accomplish sustainable development is to employ lignin resources to create high-value materials. Based on the high carbon content and rich functional groups of lignin, the lignin-based carbon materials generated after carbonization treatment display specific electrochemical properties as electrode materials. Nevertheless, low electrochemical activity of untreated lignin precludes it from achieving its full potential for application in energy storage. Heteroatom doping is a common modification method that aims to improve the electrochemical performance of the electrode materials by optimizing the structure of the lignin, improving its pore structure and increasing the number of active sites on its surface. This paper aims to establish theoretical foundations for design, preparation, and optimizing the performance of heteroatom-doped lignin-based carbon materials, as well as for developing high-value-added lignin materials. The most reported the mechanism of supercapacitors, the doping process involving various types of heteroatoms, and the analysis of how heteroatoms affect the performance of lignin-based carbon materials are also detailed in this review.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

The METTL3-m6A-YTHDC1-AMIGO2 axis contributes to cell proliferation and migration in esophageal squamous cell carcinoma.

The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N6-methyladenosine (m6A) alterations on the downstream target mRNAs in esophageal squamous cell carcinoma (ESCC) are not yet fully understood. Our study revealed that silencing METTL3 resulted in a significant decrease in ESCC cell proliferation and metastasis in vitro and in vivo. Additionally, the adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a potential downstream target of both METTL3 and YTH Domain-Containing Protein 1 (YTHDC1) in ESCC cells. Functionally, AMIGO2 augmented the malignant behaviors of ESCC cells in vitro and in vivo, and its overexpression can rescue the inhibition of the proliferation and migration in ESCC cells induced by METTL3 or YTHDC1 knockdown. Furthermore, our findings revealed that knockdown of METTL3 decreased m6A modification in the 5'-untranslated regions (5'UTR) of AMIGO2 precursor mRNA (pre-mRNA), and YTHDC1 interacted with AMIGO2 pre-mRNA to regulate AMIGO2 expression by modulating the splicing process of AMIGO2 pre-mRNA in ESCC cells. These findings highlighted a novel role of the METTL3-m6A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC.

Association of HSD17B3 and HSD3B1 polymorphisms with acne vulgaris in Southwestern Han Chinese.

Acne vulgaris is a very common skin disorder. Previous studies have indicated that genetic background factors play key roles in the onset of acne. Our previous investigation implicated several genes in the androgen metabolism pathway with acne vulgaris in the Han Chinese population. Thus, we further investigated genes and genetic variants that play important roles in this pathway for their relationship with the pathology of acne. In this study, a total of 610 subjects, including 403 acne patients and 207 healthy controls, were genotyped for 15 single-nucleotide polymorphisms in HSD3B1 and HSD17B3 genes. This study shows that rs6428829 in HSD3B1 was associated with acne vulgaris in Han patients from Southwest China, even after adjusting for age and sex. The GG genotype was associated with an increased risk of acne vulgaris (p < 0.05) and G allele carriers were associated with an increased risk of acne vulgaris (p < 0.05). In addition, the haplotype AAT in HSD3B1 significantly increased the risk of acne vulgaris in the case-control study (p < 0.05). Furthermore, for another gene in this pathway, HSD17B3, the haplotype H8 was significantly associated with an increased risk of acne vulgaris. Based on these analyses, our study indicates that the cutaneous androgen metabolism-regulated genes HSD3B1 and HSD17B3 increase the susceptibility to acne vulgaris in Han Chinese from Southwest China.

Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol mediated liver fibrosis in mice.

BACKGROUND: Peroxisome proliferator activated receptor alpha (PPARα) ameliorates ethanol induced hepatic steatohepatitis. However, its role in alcoholic liver fibrosis has not been fully clarified. The aim of this study was to elucidate the effect and the molecular basis of PPARα in ethanol induced liver fibrosis in mice. METHODS: C57BL/6J mice were fed with 4% ethanol-containing Lieber-DeCarli liquid diet for eight weeks, and intraperitoneal injected with 5% carbon tetrachloride (CCl4) for the last four weeks to induce alcoholic liver fibrosis. PPARα agonist WY14643 was administered to mice during the last couple of weeks. The effects of PPARα induction on liver histology, activation of hepatic stellate cells (HSCs), as well as hepatic expression of inflammatory and fibrogenic factors were assessed. RESULTS: The ethanol plus CCl4 treated mice exhibited progressive liver injury including piecemeal necrosis of hepatocytes, severe inflammatory cells infiltration and bridging fibrosis. This was accompanied by down-regulated hepatic expression of PPARα and the protective cytokines adiponectin, heme oxygenase-1 and interleukin-10. Additionally, up-regulation of the proinflammatory cytokine tumor necrosis factor-alpha, as well as the profibrogenic genes osteopontin, transforming growth factor-beta 1, visfatin, phosphatidylinositol 3-kinase, matrix metalloproteinase-2 (MMP-2) and MMP-9 was observed. WY14643 treatment restored expression of cytokines altered by ethanol plus CCl4 treatment and concomitantly ameliorated the liver injury. CONCLUSIONS: The present study provides evidence for the protective role of PPARα induction in ameliorating ethanol mediated fibrosis through mediation of inflammatory and fibrogenic factors.

De novo intestine-specific transcriptome of the brown planthopper Nilaparvata lugens revealed potential functions in digestion, detoxification and immune response.

The brown planthopper (Nilaparvata lugens, BPH) is the most serious rice plant pests in Asia. In this study, we performed transcriptome-wide analysis on BPH intestine. We obtained more than 26 million sequencing reads that were then assembled into 53,553 unigenes with a mean size of 388 bp. Based on similarity search with the nucleotide sequences available at NCBI, BPH intestine-specific transcriptome analysis identified 21,405 sequences. Assembled sequences were annotated with gene description, gene ontology and clusters of orthologous group terms. The digestion-, defense- and xenobiotic metabolism-related genes were abundantly detected in the transcripts from BPH intestine. Many novel genes including 33 digestion-related genes, 25 immune responsive genes and 27 detoxification-related genes are first reported here. We investigated the gene expression patterns at the transcript levels in different tissues by quantitative real-time PCR analysis, which revealed that some genes had intestine-specific expression, implicating their potential significance for BPH management.