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Genetic modification of non–β-cells to produce insulin is a promising therapeutic strategy for type 1 diabetes; however, it is associated with issues, including biosafety and precise regulation of insulin supply. In this study, a glucose-activated single-strand insulin analog (SIA) switch (GAIS) was constructed to achieve repeatable pulse activation of SIA secretion in response to hyperglycemia. In the GAIS system, the conditional aggregation domain–furin cleavage sequence–SIA fusion protein was encoded by the intramuscularly delivered plasmid and temporarily kept in the endoplasmic reticulum (ER) because it binds to the GRP78 protein; then, upon hyperglycemia, the SIA was released and secreted into the blood. In vitro and in vivo experiments systematically demonstrated the effects of the GAIS system, including glucose-activated and repeatable SIA secretion, long-term precise blood glucose control, recovered HbA1c levels, improved glucose tolerance, and ameliorated oxidative stress. Additionally, this system offers sufficient biosafety, as evidenced by the assays of immunological and inflammatory safety, ER stress, and histological evaluation. Compared with the viral delivery/expression system, the ex vivo implantation of engineered cells, and the exogenous inducer system, the GAIS system combines the advantages of biosafety, effectiveness, persistence, precision, and convenience, providing therapeutic potential for the treatment of type 1 diabetes. Article Highlights We undertook this study to establish a glucose-responsive single-strand insulin analog (SIA) self-supply system in vivo. We sought to determine whether the endoplasmic reticulum (ER) can serve as a safe and temporary repository to store designed fusion proteins and release SIAs under hyperglycemic conditions for efficient blood glucose regulation. The intramuscularly expressed plasmid-encoded conditional aggregation domain–furin cleavage sequence–SIA fusion protein can be temporarily stored in the ER, and the SIA can be released under the stimulation of hyperglycemia, resulting in efficient and long-term regulation of stable blood glucose in mice with type 1 diabetes (T1D). The glucose-activated SIA switch system provides applicable potential for T1D therapy, integrating regulation and monitoring of blood glucose levels.

Photocatalytic H2O2 production is significantly accelerated in microdroplets, benefiting from O2 availability improvement, interfacial electric field, and reaction energy decrease.

Genetic modification of non-β cells to produce insulin is a promising therapeutic strategy for type 1 diabetes, however, it is associated with issues including biosafety and precise regulation of insulin supply. In this study, a glucose-activated single-strand insulin analogue (SIA) switch (GAIS) was constructed to achieve repeatable pulse activation of SIA secretion in response to hyperglycemia. In the GAIS system, the CAD-FCS-SIA fusion protein was encoded by the intramuscularly delivered plasmid and temporarily kept in the endoplasmic reticulum (ER) as it binds to the GRP78 protein, then upon hyperglycemia, SIA was released and secreted into the blood. In vitro and in vivo experiments systematically demonstrated the effects of the GAIS system, including glucose-activated and repeatable SIA secretion, long-term precise blood glucose control, recovered HbA1c level, improved glucose tolerance, and ameliorated oxidative stress. Additionally, this system offers sufficient biosafety as evidenced by the assays of immunological and inflammatory safety, ER stress, histological evaluation, etc. Compared with the viral delivery/expression system, the ex vivo implantation of engineered cells, and the exogenous inducer system, the GAIS system combined the advantages of biosafety, effectiveness, persistence, precision, and convenience, providing therapeutic potential for the treatment of type 1 diabetes.

Nanoplastics (1000 nm) have been evidenced to be universal in a variety of environmental media. They pose a potential cytotoxicity and health risk due to their tiny size, which allows them to easily penetrate biological barriers and enter cells. Here, we briefly review the various prevalent analytical techniques or tools for identifying nanoplastics, and further move to focus on their advantages and disadvantages. Surface-enhanced Raman spectroscopy (SERS) has been implemented for the identification of individual nanoparticles because of its high sensitivity to molecules and ease of rapid characterization. Therefore, we introduce the SERS technique in the following aspects, (1) principles of SERS; (2) strategies and advances in SERS detection of nanoplastics; and (3) applying SERS to real environmental samples. We put our effort into the summarization of efficient SERS substrates that essentially enable the better detection of nanoplastics, and extend to discuss how the reported nanoplastics pretreatment methodologies can bring SERS analysis to practical applications. A further step moving forward is to investigate the problems and challenges of currently applied SERS detection methods and to look at future research needs in nanoplastics detection employing SERS analysis.

People of all ages consume salt every day, but is it really just salt? Plastic nanoparticles (nanoplastics) polluting the oceans and the atmosphere are posing an increasing environmental threat and have begun to contaminate everyday salt in consumer goods. Herein, we developed a combined Surface Enhanced Raman Scattering (SERS) and Stimulated Raman Scattering (SRS) approach that can simultaneously realize the filtration, enrichment, and detection of nanoplastics in commercial salt. SERS was used to explore the potential types of nanoplastic contaminants in salts. SRS was used to conduct imaging and to quantify the presence of nanoplastics. Nanoplastics in sea salts produced from different sources were studied, with the following nanoplastics detected: polystyrene (PS), polyethylene (PE), polypropylene (PP). We estimate that, depending on location, an average person could be ingesting as many as 63,100 nanoplastics per year through the consumption of sea salt alone. Nanoplastics can readily adsorb organic matter and heavy metal particles, so the potential harm to human health should not be underestimated.

Solar‐driven CO2 reduction reaction (CO2RR) is largely constrained by the sluggish mass transfer and fast combination of photogenerated charge carriers. Herein, we find that the photocatalysis CO2RR efficiency at the abundant gas-liquid interface provided by microdroplets is two orders of magnitude higher than that of the corresponding bulk phase reaction. Even in the absence of sacrificial agents, the production rate of HCOOH over WO3·0.33H2O mediated by microdroplets reaches 2536.23 μmol h-1g-1 (vs. 13.32 μmol h-1g-1 in bulk phase), which is significantly superior to the previously reported photocatalysis CO2RR in bulk phase water. Beyond the efficient delivery of CO2 to photocatalyst surfaces within microdroplets, we reveal that the strong electric field at the gas-liquid interface of microdroplets essentially promotes the separation of photogenerated electron-hole pairs. A scalable HCOOH photocatalysis production is further demonstrated by using an electric nebulizer to generate a large number of microdroplets. This study provides a deep understanding of ultrafast reaction kinetics mediated by the gas-liquid interface of microdroplets and a novel way of addressing the low efficiency of photocatalytic CO2 reduction.

The recognition of protospacer adjacent motif (PAM) is a key factor for the CRISPR (i.e. clustered regularly interspaced short palindromic repeats)/CRISPR-associated 9 (Cas9) system to distinguish foreign DNAs from the host genome, and also significantly restricts the targeting scope of the system during genome-editing applications. Structurally, the PAM interacting (PI) domain, which usually is located in the C-terminus of Cas9 proteins, directly binds to PAM and plays a key role in determining the recognition specificity. However, several lines of evidence showed that other regions of Cas9 protein beyond the PI domain might also play roles in PAM interaction. Here, we constructed a mosaic SpCas9 protein (xCas9-NG) by fusing the PI domain of SpCas9 PAM variant, Cas9-NG with the non-PI fragment of xCas9 protein that contains multiple amino acid substitutions. We found that non-PI fragment of xCas9 expanded PAM recognition of the Cas9-NG PI domain. In addition, xCas9-NG showed an improved editing efficiency in the majority of targets harboring xCas9 and Cas9-NG PAMs. Importantly, this finding was also successfully extended to other Cas9 variants, including SpRY and the non-G SpCas9 series. Together, our work expands the target scope of SpCas9 editing system and demonstrates the notion that the non-PI domain fragment plays an important role in PAM restriction.

It is widely accepted that the sensitivity of surface-enhanced Raman spectroscopy (SERS) is mainly manipulated by the electromagnetic enhancement mechanism (EM). Herein, we determined that the direct adsorption of the target on the SERS active surface is vital as well, through the systematic investigation of the SERS behavior of three positively charged molecules on negatively charged gold (Au) or silver nanoparticles (Ag NPs). Facilitated by the synergistic effect among the molecule, the surface, and the specific adsorbed halide ions (Cl-, Br-, and I-), high SERS sensitivity for trace target was realized, which was mainly from the directly adsorbed molecules. Noteworthy, little contribution from the nondirectly adsorbed molecules was discernible, although the EM enhancement was at the same level for these two surface species dwelling within a distance significantly less than 1 nm from the surface. Further, the related strategy for trace detection sheds light on how to realize sensitive SERS detection of new targets.

The reliability and effectiveness of fibre-optical current transformer (FOCT) is significantly affected by the noise interference from internal system components and external environment. Therefore, this paper proposes an optimized variational mode decomposition (OVMD) based denoising algorithm to improve FOCT’s performance in the situation with high-level noise. The VMD parameter is adaptively optimized based on target signal and the effective decomposed sub-signals are further denoised with stationary wavelet transform functions. In order to investigate the feasibility of the proposed algorithm, both simulated current signal in PSCAD/EMTDC environment and recorded data of current in converter station of Zhangbei dc gird are considered in this paper. The test result indicates that the proposed denoising algorithm could filter out noise and retain sufficient feature information in FOCT’s output.

Directed base substitution with base editing technology enables efficient and programmable conversion of C:G or A:T base pairs to T:A or G:C in the genome. Although this technology has shown great potentials in a variety of basic research, off-target editing is among one of the biggest challenges toward its way to clinical application. Base editing tools, especially the tools converting C to T, caused unpredictable off-target editing throughout the genome, which raise the concern that long-term application of these tools would induce genomic instability or even tumorigenesis. To overcome this challenge, we designed an inducible base editing tool that was active only in the presence of a clinically safe chemical, rapamycin. In the guidance of structural information, we designed four split-human APOBEC3A (A3A) -BE3 base editors in which these A3A deaminase enzymes were split at sites that were opposite to the protein-nucleotide interface. We showed that by inducible deaminase reconstruction with a rapamycin responsible interaction system (FRB and FKBP); three out of four split-A3A-derived base editors showed robust inducible base editing. However, in the absence of rapamycin, their editing ability was dramatically inhibited. Among these split editors, splicing at Aa85 of A3A generated the most efficient inducible editing. In addition, compared to the full-length base editor, the splitting did not obviously alter the editing window and motif preference, but slightly increased the product purity. We also expanded this strategy to another frequently used cytosine deaminase, rat APOBEC1 (rA1), and observed a similar induction response. In summary, these results demonstrated the concept that splitting deaminases is a practicable method for timely controlling of base editing tools.

Hydrogenation of α,β-unsaturated aldehydes to unsaturated alcohols suffers a huge challenge in chemoselectivity. Herein, surface decoration by FeOx is introduced to remarkably improve the selectivity of cinnamyl alcohol (COL) in cinnamaldehyde (CAL) hydrogenation on Pt/MoO3-y . The enhanced acidity on Pt-FeOx interfaces is beneficial for the chemisorption and activation of C=O bonds, promoting selective hydrogenation. The optimal catalysts with defined FeOx decoration afford efficient and chemoselective CAL hydrogenation (91.3 % selectivity) under mild conditions (PH2 =1 MPa, T=30 °C). Moreover, such innovation is further extended to develop other efficient metal (Ir, Rh and Pd) catalysts, identifying a universal promotion to Pt-group metals. This work is anticipated to inspire the rational design of high-performance catalysts via effective surface/interface engineering.

Tribulus terrestris L. (Zygophyllaceae) (TT) is usually used as a cardiotonic, diuretic, and aphrodisiac, as well as for herbal post-stroke rehabilitation in traditional Chinese medicine. However, little is known about the renoprotective effects of TT on obesity-related glomerulopathy (ORG). In this study, 340 monomeric compounds were identified from TT extracts obtained with ethyl acetate combined with 50% methanol. In vitro, IC50 of TT was 912.01 mg/L, and the appropriate concentration of TT against oxidized-low density lipoprotein (ox-LDL) induced human renal glomerular endothelial cells (HRGECs) was 4 mg/L. TT significantly increased the viability (63.2%) and migration (2.33-fold increase) of HRGECs. ORG model rats were induced by a chronic high-fat diet (45%) for 20 weeks and were then treated with TT extract (2.8 g/kg/d) for 8 weeks. Subsequently, the kidneys were removed and their differentially expressed protein profile was identified using two-dimensional electrophoresis coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)-TOF MS. Molecular categorization and functional analysis of bioinformatic annotation suggested that excessive energy metabolism, decreased response to stress and low immunity were the potential etiologies of ORG. After TT administration for 8 weeks, body weight, blood pressure, serum cystatin C and cholesterol were decreased. Additionally, TT significantly enhanced the resistance of rats to ORG, decreased energy consumption and the hemorrhagic tendency, and improved the response to acute phase reactants and immunity. In conclusion, TT may play a protective role against ORG in rats.

The efficacy and safety of traditional Chinese medicine are global concerns. Here, we selected a traditional medicinal powder Ruyi Jinhuang San as a research subject and employed DNA metabarcoding technology to identify its ingredients. First, 161 specimens constituting the ingredients of Ruyi Jinhuang San and their adulterants were collected. In addition, 154 ITS2 sequences belonging to the closed related species of these ingredients were extracted from the published literatures. First, a DNA barcode reference library of Ruyi Jinhuang San, comprising 119 species belonging to 10 genera, was constructed. Second, three different batches of Ruyi Jinhuang San were collected, and ITS2 was selected as a DNA barcode. PCR products were sequenced with the Illumina HiSeq sequencing platform using PE250 libraries. Taxonomy assignments were completed with the help of the above-mentioned DNA barcode reference library. The results indicated that all ingredients of Ruyi Jinhuang San can be successfully detected except Houppo. The medicine Cangzu had been contaminated with Atractylodes koreana . The medicine Tiannanxing had been substituted with Pinellia pedatisecta . The contamination and substitution of medicinal ingredients are potential threats to consumer safety and medicinal effectiveness. The authentication results of different samples are repeatable and stable. In conclusion, DNA metabarcoding is a valuable technology to validate the efficacy and safety of traditional Chinese medicine and has the potential to be a new method for identifying traditional Chinese medicine ingredients.

As promising supports, reducible metal oxides afford strong metal-support interactions to achieve efficient catalysis, which relies on their band states and surface stoichiometry. In this study, in situ and controlled hydrogen doping (H doping) by means of H2 spillover was employed to engineer the metal-support interactions in hydrogenated MoOx -supported Ir (Ir/H-MoOx ) catalysts and thus promote furfural hydrogenation to furfuryl alcohol. By easily varying the reduction temperature, the resulting H doping in a controlled manner tailors low-valence Mo species (Mo5+ and Mo4+ ) on H-MoOx supports, thereby promoting charge redistribution on Ir and H-MoOx interfaces. This further leads to clear differences in H2 chemisorption on Ir, which illustrates its potential for catalytic hydrogenation. As expected, the optimal Ir/H-MoOx with controlled H doping afforded high activity (turnover frequency: 4.62 min-1 ) and selectivity (>99 %) in furfural hydrogenation under mild conditions (T=30 °C, PH2 =2 MPa), which means it performs among the best of current catalysts.

As promising catalyst supports, hydrogenated metal-oxides can afford engineered surface architectures and electronic configurations to promote catalytic turnover on loading metals. Herein, hydrogenated TiO2 (H-TiO2) fabricated via NaBH4 reduction is successfully introduced to boost the catalytic oxidation of formaldehyde (HCHO), which is one of the most common and harmful indoor volatile organic compounds. Distinct from the parent TiO2, H-TiO2 features enriched surface hydroxyls and enhanced metal–support interactions upon loading Ir, which are responsible for remarkable promotion in HCHO oxidation. In particular, the abundant hydroxyls on H-TiO2 promote the generation of HCOO−, which is believed to be the rate-determining step in HCHO oxidation. This discovery is anticipated to pave the way for exploring high-performance metal catalysts on oxide supports via surface and interfacial engineering.

Background Several lines of evidence indicate that cold stimulation may not only activate brown adipose tissue (BAT) and the white adipose tissue (WAT), but also regulate the lipid metabolism and influence the development of atherosclerosis. However, the study of cold exposure affecting cholesterol metabolism have opposite results in different experiments, and Apolipoprotein E (ApoE) may play an important role. There is still a lack of complete research to illustrate this problem. Methods In this study, we first analyzed and discussed the activation of interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) under cold exposure (4 °C) in male wild-type C57BL/6 J (WT) and ApoE-deficient mice (ApoE−/−) fed high-fat diet (HFD) for 4 weeks. Subsequently, we investigated the effect of cold exposure on blood lipid profiles in both models. We further explored whether cold exposure can reduce serum cholesterol. Results In both WT and ApoE−/− mice, cold exposure activates iBAT and iWAT, as well as hardly affects eWAT. In WT mice,4 weeks cold exposure (4 °C) reduces serum triglyceride by 28%, cholesterol by 30% and LDL-cholesterol by 63%. In ApoE−/− mice, cold stimulation decreases serum triglyceride by 59%, but increases cholesterol by 20% and LDL-cholesterol by 25%. Conclusions Based on these findings, we conclude that cold exposure decreases serum cholesterol is dependent upon the existence of ApoE.

The hydrogenation of functionalized nitroarenes to the corresponding anilines is of great importance in the fine chemical industry and requires high-performance catalysts with a good activity and selectivity. Herein, hydrogenated MoOx (H-MoOx) supported bimetallic Pt-Sn (Pt-Sn/H-MoOx) was developed to accomplish selective and efficient hydrogenation. In the case of 4-nitrostyrene, an outstanding selectivity to 4-vinylaniline (≈93 %) with a high turnover frequency (0.094 s−1) was achieved under mild conditions (T=30 °C, PH2 =1 atm). The metal–support interactions contributed to the efficient turnover on the ultrafine nanoparticles, and the atom-rearranged bimetallic Pt-Sn surface promoted the selectivity because of the preferred adsorption of the nitro group. The good efficiency for various functionalized nitroarenes further verified the promise of Pt-Sn/H-MoOx in chemoselective hydrogenation.

The hydrogenation of nitroarenes to value-added aromatic amines requires active and selective catalysts. Due to the good efficiency, economic cost and high earth-abundance, Ni-based nanostructures emerge as the promising catalysts, which are however limited by the poor dispersion and unsatisfied durability. Herein, Mo2C nanowires was introduced as a versatile support towards the highly dispersive Ni owing to the strong metal-support interactions on carbide surface, accomplishing the high activity in the hydrogenation of 3-nitrobenzoic acid, 4-nitrobenzoic acid and nitrobenzene. However, the presence of water that promoted the selective hydrogenation unfortunately deactivated Ni species. An effective carbon coating was further introduced to remarkably enhance the stability, protecting active Ni from corrosive H+ and H2O. This work elucidates a feasible way towards efficient and stable catalysts by the introduction of both carbide supports and carbon coating, shedding some light on the development of high-performance catalysts.

As reducible supports, metal oxides present the varied charge effect after hydrogen doping and partial reduction, accomplishing the tunable metal-support interactions and the promoted catalytic turnover in heterogeneous catalysis. Herein, the one-pot fabrication of hydrogenated MoO x (H-MoO x ) nanorods supported Ir (Ir/H-MoO x ) was developed, which simultaneously combined the generation of active centers (Ir) and the hydrogen doping on supports (H-MoO x ). Because of the accumulated electrons around MoO 6 octahedras after hydrogen doping, the electronic perturbations arising from H-MoO x supports led to the negatively charge Ir δ− species being beneficial for the selective hydrogenation of C O moiety in α,β-unsaturated aldehydes. In the hydrogenation of cinnamaldehyde to cinnamyl alcohol, Ir/H-MoO x delivered selectivity as high as ∼93%, performing among the best of current metal-based catalysts. Additionally, the efficacy for various substrates with multiple groups further verified our Ir/H-MoO x system to be competitive for chemoselective hydrogenation.

Acupuncture at specific acupoints reduces elevated blood pressure. We have shown that 8-week electroacupuncture (EA) at P5-6 and St36-37 decreases blood pressure in men (38–75 year) with mild to mo...

Drought is one of the most severe abiotic stresses, the damage due to which, various plant species mitigate by activating mechanisms that are not yet well understood. Caragana korshinskii is a xerophytic shrub found in the semi-arid regions of northwest China with high tolerance to several abiotic stresses, including drought. Based on the de novo transcriptome data from C. korshinskii leaflets collected along a precipitation gradient on the Loess Plateau (China), most of the differentially expressed genes were explored using trend analysis along the precipitation gradient. Gene ontological analysis showed that “phenylpropanoid biosynthesis process → secondary metabolite biosynthetic process” terms were the most significant gene ontologies, whereas Kyoto Encyclopedia of Genes and Genomes-based analysis indicated that the biosynthesis of secondary metabolites was a significant metabolic pathway. Real-time polymerase chain reaction and enzyme activity analyses confirmed the increased transcription of the phenylalanine ammonialyase (PAL) gene in C. korshinskii under drought stress in field and laboratory conditions. These results suggested that C. korshinskii adjusts its secondary metabolism to water-deficit environments and activates PAL by drought stress. Therefore, further studies on the obtained data can expand the current understanding of the molecular and genetic mechanisms responsible for the drought endurance in C. korshinskii.

Hydrogenation of α,β-unsaturated aldehydes to unsaturated alcohols suffers a huge challenge in chemoselectivity. Herein, surface decoration by FeO

Tribulus terrestris L. (Zygophyllaceae) (TT) is usually used as a cardiotonic, diuretic, and aphrodisiac, as well as for herbal post-stroke rehabilitation in traditional Chinese medicine. However, little is known about the renoprotective effects of TT on obesity-related glomerulopathy (ORG). In this study, 340 monomeric compounds were identified from TT extracts obtained with ethyl acetate combined with 50% methanol. In vitro, IC

As promising supports, reducible metal oxides afford strong metal-support interactions to achieve efficient catalysis, which relies on their band states and surface stoichiometry. In this study, in situ and controlled hydrogen doping (H doping) by means of H

A series of chiral 1-(acetylated glucopyranosyl)-3-substituted-imidazolium salts [3-substitute = n-butyl (1a), 3-bromopropyl (1b), 2-chloromethyl benzyl (1c), and 4-chloromethyl benzyl (1d)] have been synthesized. Preliminary catalytic studies show that these imidazolinium salts are remarkably efficient in Pd-catalyzed Suzuki–Miyaura reaction. Functionalized aryl boronic acids reaction with aryl halides (including aryl iodides, aryl bromides and activated aryl chlorides) using environmentally friendly conditions (ethanol aqueous and ambient). The excellent isolate yields reveal that the bulky carbohydrate unit is promising for the construction of highly active transition-metal catalyst. Four C-1 bonded sugar-containing chiral imidazolium salts 1a–d were synthesized and they all exhibited excellent catalytic activity in Pd-catalyzed Suzuki reactions. Pd/1a is most effective for the coupling of functionalized arylboronic acids with arylhalides including activated arylchlorides in ethanol aqueous under air.

We have used poly(ethylene glycol)-functionalized N-heterocyclic carbene ligands, 1-(methoxy PEG)-3-methylimidazolium iodides together with Pd(OAc)2 as efficient catalysts for the Suzuki reaction in water. The best catalytic system generated in situ from Pd(OAc)2, mPEG16MeImI, and K2CO3 is able to mediate the Suzuki coupling of a series of aryl boronic acids and aryl halides, except for deactivated aryl chlorides, in good to almost quantitative yields in water within 6 h. After extraction of the product, the catalyst containing mPEG n MeImI phase could be recycled for five times without significant loss of activity. Three PEG-modified NHC ligands with different PEG chain lengths (mPEGnMeImI, n = 7, 12, and 16) were used for Pd-catalyzed Suzuki reactions in water. The best catalytic system generated in situ from Pd(OAc)2, mPEG16MeImI, and K2CO3 is able to mediate the Suzuki coupling of a series of aryl boronic acids and aryl halides, except for deactivated aryl chlorides, in good to almost quantitative yields in water within 6 h. After extraction of the product, the catalyst containing mPEG n MeImI phase could be recycled for five times without significant loss of activity.

Aurora kinases are a family of mitotic kinases that play important roles in the tumorigenesis of a variety of cancers including pancreatic cancer. A number of Aurora kinase inhibitors (AKIs) are currently being tested in preclinical and clinical settings as anti-cancer therapies. However, the antitumor activity of AKIs in clinical trials has been modest. In order to improve the antitumor activity of AKIs in pancreatic cancer, we utilized a kinome focused RNAi screen to identify genes that, when silenced, would sensitize pancreatic cancer cells to AKI treatment. A total of 17 kinase genes were identified and confirmed as positive hits. One of the hits was the platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), which has been shown to be overexpressed in pancreatic cancer cells and tumor tissues. Imatinib, a PDGFR inhibitor, significantly enhanced the anti-proliferative effect of ZM447439, an Aurora B specific inhibitor, and PHA-739358, a pan-Aurora kinase inhibitor. Further studies showed that imatinib augmented the induction of G2/M cell cycle arrest and apoptosis by PHA-739358. These findings indicate that PDGFRA is a potential mediator of AKI sensitivity in pancreatic cancer cells.

During vertebrate embryonic development, the body axis formation requires the action of Wnt signals and their antagonists. Zygotic canonical wnt8 expression appears exclusively at the ventrolateral margin and mediates Wnt/β-catenin activities to promote posterior and ventral cell fate. However, the mechanisms involved in the initiation of zygotic wnt8 signals are poorly understood. Here, we identify a novel, maternally derived transcription factor, Kzp (Kaiso zinc finger-containing protein), as an important determinant for the initiation of zygotic Wnt signals in zebrafish. Kzp is a DNA-binding transcription factor that recognizes specific consensus DNA sequences, 5′-(t/a/g)t(a/t/g)nctgcca-3′, through zinc fingers and controls the initiation of zygotic wnt8 expression by directly binding to the wnt8 promoter during zebrafish embryonic development. Depletion of Kzp strongly dorsalized embryos, which was characterized by the expansion of dorsal gene expression. Overexpression of Kzp caused posteriorization. These phenotypes were highly similar to ones induced by wnt8 depletion or overexpression and were rescued by alteration of wnt8 activity. Thus, our results provide the first insight into the mechanism involved in the initiation of zygotic canonical Wnt signals by a maternally derived transcription factor.

A number of lines of evidence suggest that senescence of normal human diploid fibroblasts (HDFs) in culture is relevant to the process of aging in vivo. Using normal human skin diploid fibroblasts, we examine the changes in genes and proteins following treatment with a mild dose of H2O2, which induces premature senescence. Multidimensional Protein Identification Technology (MudPIT) in combination with mass spectrometry analyses of whole cell lysates from HDFs detected 65 proteins in control group, 48 proteins in H2O2-treated cells and 109 proteins common in both groups. In contrast, cDNA microarray analyses show 173 genes up-regulated and 179 genes down-regulated upon H2O2 treatment. Both MudPIT and cDNA microarray analyses indicate that H2O2 treatment caused elevated levels of thioredoxin reductase 1. Semi-quantitative RT-PCR and Western-blot were able to verify the finding. Out of a large number of genes or proteins detected, only a small fraction shows the overlap between the outcomes of microarray versus proteomics. The low overlap suggests the importance of considering proteins instead of transcripts when investigating the gene expression profile altered by oxidative stress.

Drought remains one of the main factors that negatively affect plant growth and development. Caragana korshinskii is widely distributed on the Loess Plateau, China, where it mediates soil and water loss and helps prevent desertification. However, little is known about the stress response mechanisms of C. korshinskii in water-starved environments. MicroRNAs (miRNAs) have been implicated in the regulation of plant responses to several types of biotic and abiotic stress. Here, we describe the miRNAs of wild C. korshinskii from Huangling, Yulin, and Dalad Banner, which occur along a precipitation gradient. Using next-generation sequencing technology, we obtained a total of 13 710 681, 15 048 945, and 15 198 442 reads for each location, respectively; after filtering and BLAST analysis, 490 conserved miRNAs and 96 novel miRNAs were characterized from the sRNAome data, with key functions determined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We also designed stem-loop qRT-PCR to validate the expression patterns of 5 conserved miRNAs (miR390, miR398, miR530, miR2119, and miR5559) that obviously responded to water stress in plants grown both under natural and experimental water stress conditions and found that the expression levels of miR2119 and miR5559 were negatively correlated with their predicted target genes. This study is the first to identify miRNAs from wild C. korshinskii and provides a basis for future studies of miRNA-mediated gene regulation of stress responses in C. korshinskii.

Summary Rock physics study shows that Jurassic gas-sand with low water saturation (Sw) is highly correlated to density properties. Moreover, density property of Jurassic gas-sand is much less than that of shale. Seismic-derived density property is used for the prediction of Jurassic gas-sand with low water saturation. Density contrast (reflectivity) is derived from 3D pre-stack time migrated CRP gather data and velocity data, and then density reflectivity are inverted to density volume. Two low density anomalies (including one new anomaly discovered) was drilled and proved to be gas-sand with low water saturation.