Genomic and transcriptomic landscape to decipher the genetic basis of hyperpigmentation in Lanping black-boned sheep (Ovis aries).

BACKGROUND: Lanping black-boned sheep (LPB) represent a distinctive mammalian species characterized by hyperpigmentation, resulting in black bone and muscle features, in contrast to their conventional counterparts exhibiting red muscle and white bone. The genetic basis underlying LPB hyperpigmentation has remained enigmatic. METHODS: In this study, we conducted whole-genome sequencing of 100 LPB and 50 Lanping normal sheep (LPN), and integrated this data with 421 sequenced datasets from wild and domestic sheep, shedding light on the genetic backdrop and genomic variations associated with LPB. Furthermore, we performed comparative RNA-Seq analysis using liver sample to pinpoint genes implicated in the pigmentation process. We generated a comprehensive dataset comprising 97,944,357 SNPs from 571 sheep, facilitating an in-depth exploration of genetic factors. RESULTS: Population genetic structure analysis revealed that the LPB breed traces its origin back to LPN, having evolved into a distinct breed. The integration of positively selected genes with differentially expressed genes identified two candidates, ERBB4 and ROR1, potentially linked to LPB hyperpigmentation. Comparative analysis of ERBB4 and ROR1 mRNA relative expression levels in liver, spleen, and kidney tissues of LPB, in comparison to Diqing sheep, revealed significant upregulation, except for ERBB4 in the liver. Gene expression heatmaps further underscored marked allelic frequency disparities in different populations. CONCLUSION: Our findings establish the evolutionary lineage of the LPB breed from LPN and underscore the involvement of ERBB4 and ROR1 genes in melanin synthesis. These results enhance our comprehension of the molecular basis of hyperpigmentation and contribute to a more comprehensive depiction of sheep diversity.

Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Resequencing of Rosa rugosa accessions revealed the history of population dynamics, breed origin, and domestication pathways.

BACKGROUND: Rosa rugosa is a shrub that originated in China and has economic and ecological value. However, during the development of R. rugosa, the genetic background was chaotic, and the genetic structure among different wild populations was unclear, as well as wild and cultivated accessions. Here, we report whole-genome resequencing of wild and cultivated R. rugosa accessions. RESULTS: A total of 19,041,284 SNPs were identified in 188 R. rugosa accessions and 3 R. chinensis accessions by resequencing. Population genetic analysis revealed that cultivated and wild groups were separated very early. All R. rugosa accessions were divided into 8 categories based on genetic structure: (1) Weihai, Yantai, and Liaoning category, (2) Jilin category, and (3) Hammonasset category (above three are wild); (4) traditional varieties, (5) hybrids between R. rugosa and R. chinensis, (6) Zizhi Rose, (7) Kushui Rose, (8) hybrids between R. rugosa and R. multiflora. We found that the heterozygosity and genetic diversity of wild accessions were generally lower than those of cultivated individuals. The genes that were selected during cultivation were identified, and it was found that these genes were mainly related to environmental adaptation and growth. CONCLUSIONS: The Jilin population was the oldest population and later migrated to Liaoning and then migrated to Yantai and Weihai by sea regression in the Bohai Basin. The Hammonasset naturalized population probably originated from the Jilin population and then experienced separate differentiation. The long-term asexual reproduction pattern of R. rugosa decreased genetic diversity in the wild population. During R. rugosa cultivation, the ancestors of the Jilin population were involved in breeding traditional varieties, after which almost no wild individuals were engaged in breeding. However, in recent decades, cross breeding of R. rugosa started the utilization of wild germplasms. In comparison, some other species play important roles in variety formation. Few genes related to economic traits were selected, suggesting no directional domestication in the R. rugosa cultivation process.

Two High-Quality Cygnus Genome Assemblies Reveal Genomic Variations Associated with Plumage Color.

As an exemplary model for examining molecular mechanisms responsible for extreme phenotypic variations, plumage color has garnered significant interest. The Cygnus genus features two species, Cygnus olor and Cygnus atratus, that exhibit striking disparities in plumage color. However, the molecular foundation for this differentiation has remained elusive. Herein, we present two high-quality genomes for C. olor and C. atratus, procured using the Illumina and Nanopore technologies. The assembled genome of C. olor was 1.12 Gb in size with a contig N50 of 26.82 Mb, while its counterpart was 1.13 Gb in size with a contig N50 of 21.91 Mb. A comparative analysis unveiled three genes (TYR, SLC45A2, and SLC7A11) with structural variants in the melanogenic pathway. Notably, we also identified a novel gene, PWWP domain containing 2A (PWWP2A), that is related to plumage color, for the first time. Using targeted gene modification analysis, we demonstrated the potential genetic effect of the PWWP2A variant on pigment gene expression and melanin production. Finally, our findings offer insight into the intricate pattern of pigmentation and the role of polygenes in birds. Furthermore, these two high-quality genome references provide a comprehensive resource and perspective for comparative functional and genetic studies of evolution within the Cygnus genus.

Core-shell Cu@C@ZIF-8 composite: a high-performance electrode material for electrochemical sensing of nitrite with high selectivity and sensitivity.

Herein, an efficient electrochemical sensing platform is proposed for selective and sensitive detection of nitrite on the basis of Cu@C@Zeolitic imidazolate framework-8 (Cu@C@ZIF-8) heterostructure. core-shell Cu@C@ZIF-8 composite was synthesized by pyrolysis of Cu-metal-organic framework@ZIF-8 (Cu-MOF@ZIF-8) in Ar atmosphere on account of the difference of thermal stability between Cu-MOF and ZIF-8. For the sensing system of Cu@C@ZIF-8, ZIF-8 with proper pore size allows nitrite diffuse through the shell, while big molecules cannot, which ensures high selectivity of the sensor. On the other hand, Cu@C as electrocatalyst promotes the oxidation of nitrite, thereby resulting high sensitivity of the sensor. Accordingly, the Cu@C@ZIF-8 based sensor presents excellent performance for nitrite detection, which achieves a wide linear response range of 0.1-300.0µM, and a low limit of detection of 0.033µM. In addition, the Cu@C@ZIF-8 sensor possesses excellent stability and reproducibility, and was employed to quantify nitrite in sausage samples with recoveries of 95.45%-104.80%.

Prussian blue-carboxylated MWCNTs/ZIF-67 composite: a new electrochemical sensing platform for paracetamol detection with high sensitivity.

In this study, the composite of Prussian blue-carboxylated MWCNTs/ZIF-67 (PB-MWCNTs-COOH/ZIF-67) was synthesized and used as modified electrode material to fabricate an electrochemical sensor for the determination of paracetamol (PAR). In this sensor system, negatively charged MWCNTs-COOH as support for the immobilization of positively charged PB can effectively avoid the agglomeration of PB and enhance the stability, conductivity and catalytic activity of the composite. ZIF-67 particles coating outside PB-MWCNTs-COOH promotes the concentration of PAR. Benefiting from the synergistic effect, the PB-MWCNTs-COOH/ZIF-67 based sensor exhibits significantly improved electrochemical sensing behavior toward the oxidation of PAR. Under the optimum conditions, the PAR sensor presents wide linear ranges of 0.01-70 µM with a low limit of detection of 3.3 nM (S/N = 3). The method also possesses long-term stability, good reproducibility and selectivity, and was employed to the determination of PAR contents in PAR tablets sample.

Sensitive electrochemical platform for trace determination of Pb2+ based on multilayer Bi-MOFs/reduced graphene oxide films modified electrode.

A multilayer Bi-BTC/reduced graphene oxide (Bi-BTC/rGO) (BTC, 1,3,5-benzenetricarboxylic acid) film electrode was adopted to construct a highly sensitive Pb2+ electrochemical sensor. The multilayer Bi-BTC/rGO films were prepared via alternate cast of Bi-BTC and graphene oxide (GO) on a glassy carbon electrode, followed by electro-reduction of the GO components. Bi-BTC has porous broom-like structure and its organic ligand has abundant functional groups, which are favorable for Pb2+ adsorption and preconcentration. The introduction of rGO layer improves the conductivity of the MOFs material. Moreover, the multilayer composite structure greatly increased the exposure of active sites and the surface area of reactive contact, finally realizing the highly sensitive detection of Pb2+. Pb2+ was determined by differential pulse anodic stripping voltammetry and the response current was recorded at - 0.62 V. The [Bi-BTC/rGO]2 electrode provides a wide linear response ranging from 0.062 to 20.72 µg/L and a low limit of detection (LOD) of 0.021 µg/L (S/N = 3) for Pb2+, which is lower than the guideline value proposed by the World Health Organization. The method has been applied to determine Pb2+ in industrial wastewater with recoveries of 99.2-104% and RSDs of 3.4-4.0% (n = 3). Graphical abstract Graphical abstract Schematic representation of an electrochemical sensor for the detection of Pb2+ was designed based on long broom-like structure bismuth(II) metallic organic framework/reduced graphene oxide ([Bi-BTC /rGO]2).

Self-template synthesis of flower-like hierarchical graphene/copper oxide@copper(II) metal-organic framework composite for the voltammetric determination of caffeic acid.

Flower-like graphene/CuO@Cu-BTC (GR/CuO@Cu-BTC) composite was employed as electrode material for the voltammetric determination of caffeic acid (CA) in the wine. The composite material was prepared via the self-template method. In this synthetic process, budlike CuO not only acts as the template, but also provides Cu2+ ions for in situ growth of the Cu-BTC shell. The utilization of GR as petal greatly boosts the stability and electronic conductivity of CuO@Cu-BTC. The GR/CuO@Cu-BTC composite possesses unique structural features with high specific surface area and good conductivity, exhibiting excellent electrocatalytic activity towards the oxidation of CA. Under optimized conditions, the sensor shows a good linear response to CA concentration over the range 0.020-10.0 µM, together with a low limit of detection (LOD) of 7.0 nM. Selectivity, reproducibility, and stability were investigated, and the method has been applied for the determination of CA in wine samples. Graphical abstract Schematic representation of electrochemical sensor for the detection of caffeic acid was designed based on flower-like graphene/copper oxide@copper(II) metal-organic framework (GR/CuO@Cu-BTC) composite electrode material.

High-performance voltammetric sensor for dichlorophenol based on ß-cyclodextrin functionalized boron-doped graphene composite aerogels.

2, 2-methylenebis (4-chlorophenol) (dichlorophenol, Dcp) is a priority pollutant that poses a serious health threat to the public. Thus, the sensitive analysis of Dcp is of great significance. Heteroatom-doped carbon nanomaterials modified electrodes have been proven to be good electrocatalysts for electrochemical sensing application. ß-cyclodextrin (ß-CD) as a signal amplifier has also been utilized in biosensors. Inspired by these, in this study, a new composite of ß-CD and three-dimensional (3D) boron-doped graphene aerogels (BGAs/ß-CD) has been designed as a high-performance electrochemical sensing platform for Dcp determination. Graphene aerogels possess high specific surface area, large pore volume and good conductivity, which ensure rapid mass transfer and accelerated electron transfer. Besides, boron doping causes uneven charge distribution on the graphene lattice surface, producing a large amount of flowing π electrons, which provide abundant active sites for the catalytic oxidation reaction of Dcp. In addition, Dcp molecules could be captured into ß-CD through host-guest recognition, which can effectively amplify the detection signal. Combining the merits of BGAs and ß-CD, the BGAs/ß-CD based sensor achieved sensitive detection of Dcp. Under optimized experimental conditions, the oxidation currents and the concentration of Dcp had a good linear relationship within 1.0 nM âˆ¼ 21 µM. The detection limit was estimated as 0.33 nM (S/N = 3). This study might provide a new basis for the fabrication of 3D BG-based aerogel architectural material and its application in Dcp detection.

Ratiometric electrochemical sensor for sensitive detection of sunset yellow based on three-dimensional polyethyleneimine functionalized reduced graphene oxide aerogels@Au nanoparticles/SH-ß-cyclodextrin.

Electrochemical methods have been deemed effective strategies for the detection of dye additive sunset yellow (SY) owing to their low cost, good stability, and high sensitivity. However, the application of the existing sensors with single electrical signal response is limited by their inadequate sensitivity and large background interference. Herein, a ratiometric electrochemical strategy with a dual signal was developed to detect SY. The strategy had an intrinsic built-in correction to the effects from the system, and thus reduced the influence of environmental change. 3D polyethyleneimine functionalized reduced graphene oxide aerogels@Au nanoparticles/SH-ß-cyclodextrin (PEI-rGAs@AuNPs/SH-ß-CD) was used as the sensing material due to its 3D macroporous microstructure with high specific surface area and excellent electronic conductivity. Guest molecule methylene blue (MB) was chosen as a probe molecule, which formed an inclusion host-guest complex with a SH-ß-CD host in advance. The target molecule SY displaced MB from the CD cavities, resulting in the decrease of MB current and the increase of SY current. With the logarithmic value of ISY/IMB as the readout signal, the detection limit of the developed ratiometric electrochemical sensor reached as low as 0.3 nM, confirming the excellent sensitivity. Furthermore, this strategy exhibited good selectivity and repeatability, and could be used for the detection of SY in a real sample.

Sensitive determination of nitrite by using an electrode modified with hierarchical three-dimensional tungsten disulfide and reduced graphene oxide aerogel.

Nanosheets of tungsten disulfide (WS2) were used to improve the physicochemical properties of reduced graphene oxide aerogel (rGA). The nanosheets were directly integrated into 3D hybrid architecture of rGA by a solvothermal mixing method by which the WS2 sheets were assembled onto the conductive graphene network. WS2 with highly exfoliated and defect-rich structure made the WS2/rGA composite possess plentiful active sites, and this enhanced the electrocatalytic capability of the composite. The introduction of poorly conductive WS2 into 3D rGA system decreases the background current of rGA when used as electrode material. This is advantageous in terms of signal to-noise ratio and analytical performance in general. The WS2/rGA electrode, best operated at a potential of 0.68 V (vs. SCE) has a linear response in the 0.01 to 130 µM nitrite concentration range with a low detection limit of 3 nM (at S/N = 3). It is selective, reproducible, stable and is successfully applied to the determination of nitrite in spiked bacon samples. Graphical Abstract Schematic presentation of an electrochemically modified electrode for the detection of nitrite based on 3D tungsten disulfide/reduced graphene oxide aerogel (WS2/rGA).

A CuO-CeO2 composite prepared by calcination of a bimetallic metal-organic framework for use in an enzyme-free electrochemical inhibition assay for malathion.

An enzyme-free electrochemical method is described for the determination of trace levels of malathion. It is based on a nanostructured copper-cerium oxide (CuO-CeO2) composite prepared by calcination of a Cu(II)/Ce(III) metal-organic framework. The morphology, crystal structure and elemental composition of composite was studied by scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The principle for malathion determination is based on the fact that the redox signal of CuO (best measured at around -0.1 V vs. SCE) (at 100 mV/s) is inhibited by malathion due to affinity between CuO and the sulfur groups of malathion. The introduction of CeO2 into the composite system further improves the analytical performance. This is attributed to the unique microstructure and the synergistic effect between CuO and CeO2. Experimental parameters like solution pH value, Cu/Ce molar ratio, accumulation potential, accumulation time, and CuO-CeO2 volume on the electrode were optimized. The assay has a linear range of 10 fM to 100 nM and a 3.3 fM detection limit (at S/N = 3). The electrode is selectively inhibited by malathion even in the presence of potentially interfering substances. Graphical abstract A sensitive and effective enzyme-free electrochemical sensor has been developed for the detection of malathion based on CuO-CeO2 composite derived from bimetallic metal-organic frameworks.

TGF-ß-mediated upregulation of Sox9 in fibroblast promotes renal fibrosis.

TGF-ß signaling plays a principal role in renal fibrosis, but the precise mechanisms and the downstream factors are still largely unknown. Sox9 exhibits diverse roles in regulating the production of extracellular matrix proteins. Here we found that Sox9 was induced by TGF-ß in the kidney fibroblast and acted as an important downstream mediator of TGF-ß signaling in promoting renal fibrosis. TGF-ß/Smad signaling mediated the upregulation of Sox9 in kidney fibroblast by binding to a conserved enhancer. In different mouse models of renal fibrosis, as well as in the kidney biopsy tissue from patients with renal fibrosis, Sox9 expression significantly increased. Immunostaining confirmed the upregulation of Sox9 in the kidney fibroblast during renal fibrosis. Delivery of Sox9 knockdown plasmid to the kidney by ultrasound microbubble-mediated gene transfer suppressed the unilateral ureteral obstruction (UUO) or folic acid-induced mouse renal fibrosis, whereas ectopic expression of Sox9 aggravated renal fibrosis. In addition, we identified Sox9 as a direct target of miR-30. Notably, miR-30 expression was significantly inhibited by TGF-ß1 in the kidney fibroblast and the downregulation of miR-30 was observed in renal fibrosis. Mechanistically, inhibition of miR-30 independently strengthened the effect of TGF-ß/Smad signaling on Sox9 upregulation. Adenovirus-mediated ectopic expression of miR-30 in kidney fibroblast greatly reduced UUO-induced renal fibrosis by targeting Sox9. These findings link Sox9 to intrinsic mechanisms of TGF-ß signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis.

Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes.

The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis, which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri, and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus. Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.

Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments.

Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome-wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8-9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ∼5× for 75 samples and ∼42× for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (<100 m), high-altitude region (>1500 m) versus low-altitude region (<1300 m), desert (<10 mm average annual precipitation) versus highly humid region (>600 mm), and arid zone (<400 mm) versus humid zone (>400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change.

Genomic Analyses Reveal Potential Independent Adaptation to High Altitude in Tibetan Chickens.

Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200-4,100 m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome of a Tibetan chicken and resequenced whole genomes of 32 additional chickens, including Tibetan chickens, village chickens, game fowl, and Red Junglefowl, and found that the Tibetan chickens could broadly be placed into two groups. Further analyses revealed that several candidate genes in the calcium-signaling pathway are possibly involved in adaptation to the hypoxia experienced by these chickens, as these genes appear to have experienced directional selection in the two Tibetan chicken populations, suggesting a potential genetic mechanism underlying high altitude adaptation in Tibetan chickens. The candidate selected genes identified in this study, and their variants, may be useful targets for clarifying our understanding of the domestication of chickens in Tibet, and might be useful in current breeding efforts to develop improved breeds for the highlands.

Loss of MicroRNA-101 Promotes Epithelial to Mesenchymal Transition in Hepatocytes.

Epithelial-to-mesenchymal transition (EMT) has been implicated in embryonic development and various pathological events. However, the involvement of microRNA in the process of EMT remains to be fully defined in hepatocyte. ZEB1 is a well-known transcriptional repressor of E-cadherin and plays a major role in triggering EMT during organ fibrosis and cancer cell metastasis. Computational microRNA target predictions detect a conserved sequence matching to miR-101 in the 3'UTR of ZEB1 mRNA. Our results confirm that miR-101 suppresses ZEB1 expression by targeting the predicted site of ZEB1 3'UTR. Subsequent investigations show that miR-101 is significantly downregulated in the cultured hepatocytes undergoing EMT and in the hepatocytes isolated from fibrotic liver. Along with the loss of miR-101, the ZEB1 expression increases simultaneously in hepatocytes. In addition, miR-101 levels in HCC cell lines are negatively associated with the ZEB1 productions and the metastatic potentials of tumor cells. Mechanistically, we demonstrate that miR-101 significantly inhibits the TGF-ß1-induced EMT in hepatocytes, whereas inhibition of miR-101 promotes the EMT process as indicated by the changes of morphology, cell migration, and the expression profiles of EMT markers. In the fibrotic liver, ectopic expression of miR-101 can significantly downregulate ZEB1 in the hepatocyte and thereby reduces the mesenchymal marker expression. Moreover, miR-101 significantly inhibits the proliferation and migration of HCC cell. Our results demonstrate that miR-101 regulates HCC cell phenotype by upregulating the epithelial marker genes and suppressing the mesenchymal ones.

MicroRNA-101 suppresses liver fibrosis by targeting the TGFß signalling pathway.

Transforming growth factor-ß (TGFß) is crucial for liver fibrogenesis and the blunting of TGFß signalling in hepatic stellate cells (HSCs) or hepatocytes can effectively inhibit liver fibrosis. microRNAs (miRNAs) have emerged as key regulators in modulating TGFß signalling and liver fibrogenesis. However, the regulation of TGFß receptor I (TßRI) production by miRNA remains poorly understood. Here we demonstrate that the miR-101 family members act as suppressors of TGFß signalling by targeting TßRI and its transcriptional activator Kruppel-like factor 6 (KLF6) during liver fibrogenesis. Using a mouse model of carbon tetrachloride (CCl4 )-induced liver fibrosis, we conducted a time-course experiment and observed significant down-regulation of miR-101 in the fibrotic liver as well as in the activated HSCs and injured hepatocytes in the process of liver fibrosis. Meanwhile, up-regulation of TßRI/KLF6 was observed in the fibrotic liver. Subsequent investigations validated that TßRI and KLF6 were direct targets of miR-101. Lentivirus-mediated ectopic expression of miR-101 in liver greatly reduced CCl4 -induced liver fibrosis, whereas intravenous administration of antisense miR-101 oligonucleotides aggravated hepatic fibrogenesis. Mechanistic studies revealed that miR-101 inhibited profibrogenic TGFß signalling by suppressing TßRI expression in both HSCs and hepatocytes. Additionally, miR-101 promoted the reversal of activated HSCs to a quiescent state, as indicated by suppression of proliferation and migration, loss of activation markers and gain of quiescent HSC-specific markers. In hepatocytes, miR-101 attenuated profibrogenic TGFß signalling and suppressed the consequent up-regulation of profibrogenic cytokines, as well as TGFß-induced hepatocyte apoptosis and the inhibition of cell proliferation. The pleiotropic roles of miR-101 in hepatic fibrogenesis suggest that it could be a potential therapeutic target for liver fibrosis.

[Study on the characteristics of radiance calibration using nonuniformity extended source].

Integrating sphere and diffuser are always used as extended source, and they have different effects on radiance calibration of imaging spectrometer with parameter difference. In the present paper, a mathematical model based on the theory of radiative transfer and calibration principle is founded to calculate the irradiance and calibration coefficients on CCD, taking relatively poor uniformity lights-board calibration system for example. The effects of the nonuniformity on the calibration was analyzed, which makes up the correlation of calibration coefficient matrix under ideal and unideal situation. The results show that the nonuniformity makes the viewing angle and the position of the point of intersection of the optical axis and the diffuse reflection plate have relatively large effects on calibration, while the observing distance's effect is small; under different viewing angles, a deviation value can be found that makes the calibration results closest to the desired results. So, the calibration error can be reduced by choosing appropriate deviation value.

[Interference hyperspectral data compression based on spectral classification and local DPCM].

In order to get a high compression ratio, according to the spatial dimension correlation and the interference spectral dimension correlation of interference hyperspectral image data, the present article provides a new compression algorithm that combines spectral classification with local DPCM. This algorithm requires spectral classification for the whole interference hyperspectral image to get a classification number matrix corresponding to the two-dimensional space and a spectral classification library corresponding to the interference spectra first, then local DPCM is performed for the spectral classification library to get a further compression. As the first step of the compression, the spectral classification is very important to the compression effect. This article analyzes the differences of compression effect with different standard and different accuracy of classification, the relative Euclidean distance standard is better than the angle standard and the interference RQE standard. Finally, this article chooses an appropriate standard of compression and achieves the combined compression algorithm with programming. Compared to JPEG2000, the compression effect of combined compression algorithm is better.