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BackgroundCavernous hemangioma, as a rare tumor, is difficult to differentiate from retroperitoneal lymphoma and paraganglioma. They are more difficult to excise completely through open surgery and traditional laparoscopic surgery. The study aimed to evaluate the role of DaVinci surgical system in laparoscopic resection of parapelvic cavernous hemangioma.Case presentationA 46-year-old female, who diagnosed as parapelvic cavernous hemangioma accompanying with thrombosis and calcification, was performed laparoscopic resection using DaVinci surgical system under general anesthesia. The patient well recovered without recurrence or spread of the lesion after operation for 3 months as well as hydronephrosis was significantly relieved.ConclusionLaparoscopic resection of parapelvic cavernous hemangioma under the help of DaVinci surgical system was feasible and safe.

It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background‐dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA‐Rho‐associated protein kinase 2‐LIM domain kinase‐Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F‐actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation., Cavin1 deficiency causes severe hypoglycemia, dampens the storage and mobilization of glycogen in mouse liver, and results in neonatal death in C57BL/6J mice. Mechanistically, by inhibiting the dynamics of actin cytoskeleton, Cavin1 deficiency reduces the fenestrae in liver sinusoidal endothelial cells, which impairs bilateral flow between liver glycogen and blood glucose.

Germinal centers (GCs), which are the site of antibody diversification and affinity maturation, are vitally important for humoral immunity. GC B cell proliferation is essentially for these processes by providing enough templates for somatic hypermutation (SHM) and serving as a critical mechanism of positive selection. In the current study, we found a significant reduction of GC response in the spleens of GC B cell specific PHF14 knockout (PHF14GCB KO) mice compared with the wild-type control (PHF14GCB WT) when the mice were challenged with SRBCs or lymphocytic choriomeningitis virus. We also demonstrated that PHF14 did not affect the cell survival of GC B cells, but regulated the proliferation of GC B cells. In addition, PHF14 suppressed the expression of Cdkn1a (p21) though regulating the level of H3K4me3 to control the proliferation of GC B cells. Collectively, our data suggest that PHF14 plays an important role in the process of germinal center formation by regulating GC B cell proliferation in spleen.

To gain fundamental understanding of how catalyst composition and structure affects catalytic reaction chemistry is of paramount importance in the search of high-performance electrocatalysts for practical applications. Herein, we report an in-depth study of Ni–Mo–O derived electrocatalysts, a promising but less well investigated electrocatalytic material for the HER, with a focus on the correlation of phase/microstructure and HER activity. A series of Ni foam-supported Ni–Mo–O derived electrocatalysts were prepared using a simple hydrothermal method, followed by annealing treatment under a H2 atmosphere. Depending upon the annealing temperature, different Ni–Mo alloys were formed and the resulting Ni–Mo/MoO3−x nanocomposites exhibited varied HER activities under alkaline conditions following the order of Ni10Mo/MoO3−x > Ni4Mo/MoO3−x > Ni3Mo/Ni4Mo/MoO3−x. A combination of phase/structure/chemical state analyses and first-principles calculations were conducted to gain insight into the variation of apparent catalytic activity. Our study found that the variation of HER activity under alkaline conditions should stem from the intrinsic activity change, which was associated with the change of the amount of MoO3 sites and the variation of Had–alloy binding strength.

Background Angelica sinensis seedlings are grown in alpine uncultivated meadow soil with rainfed agroecosystems to ensure the quality of A. sinensis after seedling transplantation. The aim was to investigate the rhizosphere bacterial and fungal communities during the growth stages of A. sinensis seedlings. Methods The bacterial and fungal communities were investigated by HiSeq sequencing of 16S and 18S rDNA, respectively. Results Proteobacteria and Bacteroidetes were bacterial dominant phyla throughout growth stages. Fungal dominant phyla varied with growth stages, dominant phyla Ascomycota and Chytridiomycota in AM5, dominant phyla Basidiomycota, Ascomycota and Zygomycota in BM5, and dominant phyla Basidiomycota and Ascomycota in CM5. There was no significant variation in the alpha-diversity of the bacterial and fungal communities, but significant variation was in the beta-diversity. We found that the variation of microbial community composition was accompanied by the changes in community function. The relative abundance of fungal pathogens increased with plant growth. We also identified the core microbes, significant-changing microbes, stage-specific microbes, and host-specific microbes. Plant weight, root length, root diameter, soil pH, rainfall, and climate temperature were the key divers to microbial community composition. Conclusions Our findings reported the variation and environmental drivers of rhizosphere bacterial and fungal communities during the growth of A. sinensis seedlings, which enhance the understanding of the rhizosphere microbial community in this habitat.

Synthesis of high-performance and cost-effective catalysts towards the hydrogen evolution reaction (HER) is critical in developing electrochemical water-splitting as a viable energy conversion technique. For non-precious metal Co- and Ni-based catalysts, hydroxides were found to form on the surface of the catalysts under alkaline environments and benefit the catalytic performance, whereas there is limited systematic study on the explicit influence of hydroxides on the electrocatalytic mechanism and performance of these catalysts. Herein, we report a close correlation observed between the amount of the surface hydroxides formed and the resulting electrocatalytic performance of a Co-Mo-O nanocatalyst through careful comprehensive structural and property characterizations. We found that an appropriate amount of hydroxide can be moderated by simply coating the catalyst surface with carbon shells to optimize the catalytic properties. As a result, a carbon-coated Co-Mo-O nanocatalyst was successfully developed and is among the best reported non-precious HER catalysts with a superior electrocatalytic activity and outstanding durability for the HER under alkaline environment. First-principles calculations were further conducted to probe the nature of the active sites and the role of hydroxides in the Co-Mo-O@C/NF catalyst towards the HER.

Overexpression of the enzyme phosphatase (PhoN/PhoK) in the radiation-resistant bacterium Deinococcus radiodurans could be an efficient strategy for uranium remediation. However, the presence of other metals in nuclear wastes often interferes with uranium bioprecipitation. In our study, the uranium-precipitating ability of the PhoN-expressing D. radiodurans strain (Deino-phoN) significantly decreased by 45.4% in 13 h in the presence of chromium (VI); however, it was partially recovered after supplementation with chromium (III). Therefore, the reduction of chromium (VI) to chromium (III) was obtained by the co-expression of the YieF protein and PhoN in D. radiodurans (Deino-phoN-yieF). As a result, an increase in the chromium (VI) reduction (25.1%) rate was observed in 24 h. Furthermore, uranium precipitation also increased by 28.0%. For the decontamination of groundwater, we immobilized Deino-phoN-yieF cells using Polyvinyl alcohol (PVA)-sodium alginate (SA) beads, followed by incubation in a bioreactor. Approximately 99% of chromium (VI) and uranium (VI) was removed after 4 continuous cycles operated for a period of over 20 days at room temperature (25 °C). Therefore, Deino-phoN-yieF could be used as a potential biological agent for mixed radioactive nuclear waste remediation.

Preeclampsia is a common pregnancy-specific disorder characterized by elevated blood pressure and proteinuria. Activation of the maternal immune system and impaired placental angiogenesis are thought to contribute to the pathogenesis of preeclampsia. TLR9 (Toll-like receptor 9) plays a role in innate immunity, defending the organism against infection. The purpose of this study was to determine whether TLR9 inhibits angiogenesis at the fetomaternal interface under conditions of preeclampsia. We confirmed the downregulation of VEGFA (vascular endothelial growth factor A) and upregulation of TLR9 and sFLT1 (soluble vascular endothelial growth factor receptor 1) in placentas from preeclamptic women. Then, we established a mouse model with preeclampsia-like symptoms using the synthetic TLR9 agonist CpG (cytidine–phosphate–guanosine)-ODN (oligodeoxynucleotide; ODN1826). We observed the downregulation of VEGFA and the upregulation of sFLT1 in placentas from the preeclampsia-like animal model and in trophoblasts treated with CpG-ODN (ODN2006). In addition, silencing TLR9 promoted the migration and invasion of HTR8/SVneo cells. In conclusion, TLR9 is capable of robustly suppressing angiogenesis by differentially regulating the expression of VEGFA and sFLT1 at the fetomaternal interface, potentially contributing to the development of preeclampsia.

Electrochemical enzyme biosensors based on various modified electrodes have been developed for bisphenol A detection. However, enzyme activity loss and high cost limit their application. In this study, an electrochemical biosensor was developed for bisphenol A detection by displaying tyrosinase on the surface of Escherichia coli cells, followed by adsorption onto a glassy-carbon electrode. The biosensor exhibited a linear relationship between the concentration range of 0.01-100 nM BPA (R2 = 0.9958) and the current peak. The detection limit was 0.01 nM, which is higher than that of other chemically modified tyrosinase biosensors. For the detection of bisphenol A in tea and juice samples, the fabricated biosensor presented respectable accuracy comparable to that of high-performance liquid chromatography. Furthermore, high recovery rates (97.78%-100.32%) were obtained. Therefore, this biosensor could be a promising and reliable analytical tool for the detection of bisphenol A.

Cell division cycle 42 (CDC42) plays important roles in polarity establishment and maintenance as well as cell cycle progression and cell division. Although disruption of cell polarity is a prerequisite in epithelial tumor initiation, the roles of CDC42 in tumorigenesis are still poorly understood. Here we find that Cdc42 deficiency inhibits the Kras G12D -induced lung alveoli tumor formation, while conversely promotes bronchiole tumor formation in mice. Bronchial Cdc42 loss destroys contact inhibition potentially through cell polarity disruption, and results in increased tumor formation. In contrast, deletion of Cdc42 in alveoli cells prevents Kras G12D -induced cell proliferation, which leads to reduced tumor formation. Further analyses of clinical specimens uncover a significant positive correlation between CDC42 and type II alveolar epithelial cells marker SP-A, indicating the potential importance of CDC42 in this specific subset of lung cancer. Collectively, we identify the lineage-specific function of CDC42 in lung tumorigenesis potentially through the regulation of cell polarity integrity.

Electrochemically splitting water to produce clean hydrogen fuel requires high-performance electrocatalysts. Here, we report transition metal-boron alloy Co-W−B is an active electrocatalyst for water electrolysis. The Co-W−B catalyst can be readily deposited on nickle foam (NF) using a simple electroless plating method. A combination of phase/chemical state/microstructural analyses of the Co-W−B electrocatalyst was conducted using XRD, TEM, Raman spectroscopy and XPS techniques. The properly annealed Co-W−B/NF catalyst with an optimal composition exhibits a low overpotential along with a high stability for the hydrogen evolution reaction (HER) in alkaline solution, which is among the best reported levels for non-noble HER catalysts. In addition, the Co-W−B/NF catalyst also shows moderate activity towards the oxygen evolution reaction (OER). These study results highlight the potential of transition metal-boron alloys as high-performance and low-cost electrocatalyst for water splitting.

BACKGROUND We investigated the influence of Resolvin D1 (RvD1) on the inflammatory response in PC12 cells (a cell model of Parkinson disease, PD). MATERIAL AND METHODS 4 mmol/L 1-methyl-4-phenylpyridinium ion (Mpp+) was used in PC12 cells for an in vitro PD model. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to explore PC12 cell viability. Western blot (WB) experiments were used to identify nuclear factor-κB (NF-κB), phosphorylated extracellular signal-regulated kinase (p-ERK)/p-Jun N-terminal kinase (JNK)/p-P38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 protein levels. Transcription levels of inflammatory factors, for instance, TNF-α and IL-6, were explored by real-time quantitative polymerase chain reaction (RT-QPCR). Lactic dehydrogenase (LDH) level was detected by enzyme-linked immunosorbent (ELISA). Cell apoptosis was assessed by Annexin-V Fluorescein (FITC) kit. RESULTS RvD1 dose-dependently inhibited MPP+ induced upregulation of PC12 cell apoptosis/cellular damage/TNF-α and p-P38/p-ERK/NF-κB as well as downregulation of PC12 cell viability. CONCLUSIONS We can draw the conclusion that RvD1 attenuates PD via inhibiting Mpp+-induced inflammation in PC12 cells.

Nickel-iron oxyhydroxide (Ni(1-x)Fe(x)OOH) is well recognized as the best-performing oxygen evolution reaction (OER) catalyst in alkaline electrolytes, however its analogue cobalt-iron oxyhydroxide (Co(1-x)Fe(x)OOH) is surprisingly less explored despite their structural similarity. Inspired by our recent study on high-performance HER catalyst using the nanostructured CoMoO(4)•nH(2)O precursor, herein, we report a facile synthesis of Co(1-x)Fe(x)OOH catalyst derived from the same precursor and its excellent electrocatalytic properties towards the OER in alkaline electrolytes. A core-shell structured nanocatalyst consisting of disordered Co(1-x)Fe(x)OOH layer over the surface of crystalline CoMoO(4)•nH(2)O nanosheets was synthesized using a simple hydrothermal method followed by anodic electrooxidation. Thus-prepared catalyst exhibited extraordinarily high and stable activity towards the OER in alkaline electrolyte, which outperformed most Co-based OER catalysts. Combined with the HER catalyst derived from the same CoMoO(4)•nH(2)O precursor as the cathode, we further developed and tested a simple water-splitting cell, which significantly surpasses the benchmarking IrO(2)–Pt/C couple (1.63 V) and requires a voltage of only 1.517 V to afford 10 mA cm(−2) in 1.0 M KOH solution. Density functional theory calculations were conducted to gain insight into the Fe-doping induced improvement of OER activity.

The reaction of CO2 with epoxides to produce cyclic carbonates requires high-performance, low-cost, and facilely recycled catalysts. Here, we report a heterogeneous catalyst (MIL-101-N(Bnme2)Br) based on metal-organic frameworks (MOFs) for catalytic CO2 conversion into cyclic carbonates. The MIL-101-N(Bnme2)Br catalyst was prepared as follows: A MOFs precursor (MIL-101-NH2) was firstly synthesized using a method of hydrothermal synthesis, then coupled with the quaternary ammonium salt ionic liquid (N(BzBnme2)Br) via aldehyde-amide condensation. A series of comparative experiments revealed that MIL-101-N(Bnme2)Br catalyst has high activity for catalyzing the cycloaddition reaction to produce cyclic carbonates in the absence of solvents and co-catalysts. As was exampled by the synthesis of propylene carbonate, a high yield (93 %) and selectivity (99 %) was achieved under the optimized conditions (0.93 mol% MIL-101-N(Bnme2)Br catalyst, 1.4 MPa CO2 pressure, 17 mmol propylene oxide, 100 °C, 5 h). More impressive, the MIL-101-N(Bnme2)Br catalyst could be recycled easily by filtration and was reusable up to several times without a significant activity decay. Furthermore, our density functional theory (DFT) calculations suggested that such high catalytic activity mainly resulted from the cooperative catalysis between the coordinatively unsaturated Cr3+ sites and Br anions in MIL-101-N(Bnme2)Br catalyst. Meanwhile, a possible mechanism for the cycloaddition reaction catalyzed by MIL-101-N(Bnme2)Br catalyst was also proposed.

Electrochemically splitting water to produce clean hydrogen fuel requires high-performance electrocatalysts. Here, we report that ternary transition metal boride Co–Ni–B is an active candidate catalyst for water splitting. The Co–Ni–B nanoparticles were deposited on Ni foam (NF) by a facile electroless plating method. After being properly calcined under an Ar atmosphere, the Co–Ni–B@NF catalyst exhibits a low overpotential along with high stability in alkaline solutions for the oxygen evolution reaction, which is among the best reported levels for non-precious metal catalysts. Furthermore, the properly annealed Co–Ni–B@NF catalyst also shows good activity towards the hydrogen evolution reaction. The potential of Co–Ni–B@NF as a bifunctional catalyst for the overall water splitting was demonstrated, with 10 mA cm−2 achieved at 1.72 V. The favorable combination of high catalytic activity, facile preparation and low cost makes Co–Ni–B@NF a very promising bifunctional catalyst for electrochemical water splitting.

P-nitrophenol is one of the most common contaminants in chemical industrial wastewater, and in situ real-time monitoring of PNP cannot be achieved by conventional analytical techniques. Here, a two-chamber microbial fuel cell with an aerobic anode chamber was tested as a biosensor for in situ real-time monitoring of PNP. Pseudomonas monteilii LZU-3, which was used as the biological recognition element, can form a biofilm on the anode electrode using PNP as a sole substrate. The optimal operation parameters of the biosensor were as follows: external resistance 1000Ω, pH 7.8, temperature 30°C, and maximum PNP concentration 50mgL(-1). Under these conditions, the maximum voltages showed a linear relationship with PNP concentrations ranging from 15±5 to 44±4.5mgL(-1). Furthermore, we developed a novel portable device for in situ real-time monitoring of PNP. When the device was applied to measure PNP in wastewater containing various additional aromatic compounds and metal ions, the performance of the biosensor was not affected and the correlation between the maximum voltages and the PNP concentrations ranging from 9±4mgL(-1) to 36 ± 5mgL(-1) was conserved. The results demonstrated that the MFC biosensor provides a rapid and cost-efficient analytical method for real-time monitoring of toxic and recalcitrant pollutants in environmental samples.

High‐load flaxseed oil microcapsule is prepared with the Maillard reaction products (MRPs) of sodium caseinate and isomaltooligosaccharide as wall material. It is found that the emulsifying activity index and emulsion stability index of MRPs are increased by 31.32% and 34.11% respectively at the appropriate degree of graft (26.30%) compared with the mixture of sodium caseinate and isomaltooligosaccharide. Smaller droplet size and lower polydispersity index can be achieved in the flaxseed oil emulsions coated by MRPs, due to the change of sodium caseinate molecular weight and spatial structure. The microencapsulation efficiency of the microcapsules coated by MRPs is highly improved up to 98.22% at oil load of 58.43%, compared with the control group. Furthermore, MRPs as coating material can protect flaxseed oil against lipid oxidation at 50 °C for 4 weeks. More importantly, the smooth, round, and compact external surface structures of microcapsule powder support its physical necessity for industrial usage. Due to its high microencapsulation efficiency and good oxidation stability, MRPs formed with sodium caseinate and isomaltooligosaccharide show great application potential in preparing high load oil microcapsule. Practical Applications: Findings in this research could be utilized for developing microencapsulation loaded with higher concentration of flaxseed oil, a rich source of α‐linoleic acid and lignans. Application of MRPs (Maillard reaction products) formed through interaction between sodium caseinate and isomaltooligosaccharide by heating improved both its physicochemical properties and oxidative stability. It is a novel approach for developing microcapsule with higher percentages of oils with better oxidative stability.

Triazophos (TAP), methamidophos (MAP) and carbofuran (CF) pesticides are highly toxic, soluble and absorbable. Efficient co-degradation of multi-pesticides is rare reported. The objectives of this study were to investigate TAP, MAP and CF co-degradative ability of Enterobacter sp. Z1 and study the degradation mechanisms. Strain Z1 was shown to efficiently co-degrade TAP, MAP and CF when they were used as primary carbon sources. The degradation occurred over a wide range of temperatures, pH values and pesticide concentrations and followed first-order kinetics. Under the optimum conditions (37 °C, pH 7 and 100 mg/L of each pesticide), the degradation efficiencies were 100%, 100%, and 95.3% for TAP, MAP and CF, respectively. In addition, strain Z1 could simultaneously degrade TAP, MAP, CF and total nitrogen in wastewater in a batch bioreactor, with high removal efficiencies of 98.3%, 100%, 98.7% and 100%, respectively. Genomics, proteomics, qRT-PCR and gene overexpression analyses revealed that the degradation mechanisms involved the activities of multiple proteins, among which, organophosphorus hydrolase (Oph) and 3-hydroxyacyl-CoA dehydrogenase (PaaC) are primarily responsible for TAP and MAP degradation, while carbofuran hydrolase (Mcd) and amidohydrolase (RamA) primarily degrade CF. Among these enzymes, PaaC and RamA are newly identified pesticide-degrading enzymes. Toxicity assays of strain Z1 using reporter recombinase gene (recA) and zebrafish showed that there was no accumulation of toxic metabolites during the degradation process. Biosafety test using zebrafish showed that the strain was nontoxic toward zebrafish. Strain Z1 provides a good purification effect for pesticides-containing wastewater and novel microbial pesticide-degrading mechanisms were discovered.

Electrochemical synthesis of NH3, when coupled with renewable energy, provides an attractive alternative to the energy- and capital-intensive Haber-Bosch process. Crucial to enabling this vision is the development of highly active and selective catalysts for the electrochemical nitrogen reduction reaction (ENRR). Herein, we report a facile synthesis of hollow and solid bismuth (Bi) nanospheres catalysts using a one-pot solvothermal method. As a consequence of its hierarchical macroporous-mesoporous architecture, Bi hollow nanospheres catalyst exhibited significantly improved catalytic performance towards the ENRR compared with its solid counterpart. Remarkably, the Bi nanocatalyst enabled ammonia electrosynthesis with a yield of 23.4 ± 1.3 μg h−1 mg−1cat. and a corresponding FE as high as 19.8 ± 1.1% at ambient conditions, which outperformed most ENRR catalysts reported up to date.

Biodegradation of recalcitrant organic compounds in microbial fuel cell (MFC) is limited, due to its strong electron affinity and persisted in anaerobic condition. In this study, Pseudomonas monteilii LZU-3 degraded p-nitrophenol (PNP) and generated current at 100 mg L-1 of PNP in anode MFC with the addition of oxygen. The highest PNP degradation was 4, 37.75, and 99.89% in anaerobic, aerobic, and aerated anode of MFC respectively, at 7 h. The maximum voltage generation in aerated anode was 183 mV, which was comparatively higher than aerobic (150 mV) and anaerobic (68 mV). The qRT-PCR results confirmed that the oxygenase genes in strain LZU-3 were up-regulated from 17.51 to 39.39-fold at 1.6-4.5 mg L-1 of oxygen concentrations resulted in PNP degradation in anode MFC. This study demonstrated that supplementation of oxygen into the anode MFC might be a potential approach for biodegradation of recalcitrant compounds and electricity generation.

In this study, a sediment microbial fuel cell (SMFC) system for the simultaneous biodegradation of organic matter and detoxification of hexavalent chromium Cr (VI) was investigated. The total organic carbon (TOC) removal rate of the SMFC with Cr (VI) was 30.07%, which was significantly higher than that in a SMFC without Cr (VI) (13.74%). In the SMFC with Cr (VI), the maximum values of open-circuit voltage (OCV) and power density were 408 mV and 4.8 mW/m 2 , respectively. During the long-term operation of the SMFC with Cr (VI), 25 mg/L of Cr (VI) were completely reduced from all four consecutive batches over 48 days. MiSeq sequencing revealed that the biofilm microbial community of the anode comprised of Bacteroidetes (42.9%), Proteobacteria (33.6%), Chloroflexi (7.5%), and Euryarchaeota (7.5%) as the predominant phyla. Compared with that of the sediment, certain families were enriched; they included Pseudomonadaceae (46.88-fold), Flavobacteriaceae (5.05-fold), and Syntrophaceae (4.48-fold), which are organic matter-degrading bacteria. These results suggest that SMFCs are useful for TOC removal and detoxification of heavy metals in remediation of contaminated lakes.

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RNA interference (RNAi) is a nucleic acid metabolism system utilized for the post‐translational regulation of endogenous genes or for defense against exogenous RNA or transposable elements. Double‐stranded RNA (dsRNA)‐mediated RNAi shows broad application prospects to improve existing plant traits and combat invading pathogens or pests. To improve dsRNA transcriptional efficiency using a prokaryotic expression system, Trxz gene, an essential gene for the early development of chloroplasts in Arabidopsis thaliana, was chosen for a functional study. Two types of recombinant expression vectors, pDP‐Trxz and phP‐Trxz‐N/L, were constructed to generate dsTrxz, the dsRNA which specifically induces Trxz gene silencing. Gel electrophoresis tests showed that phP vectors performed better and produced more dsRNA than the pDP vector under the same conditions. Purification of dsTrxz by enzymatic digestion indicated that highly purified dsRNA can be obtained through the use of DNase enzymatic hydrolysis assay. To confirm the knockdown effect of the dsRNA, a root immersion assay was performed, and we found that the root immersion culture could continue to affect the growth and development of A. thaliana. This included inhibiting the development of new leaves, causing weak plant development, leaf whitening, and other symptoms. This indicated that in vitro expressed dsRNA can be absorbed through Arabidopsis roots and can continue to trigger Trxz gene silencing. To delay dsRNA degradation and extend the effectiveness of RNAi, nanomaterial layered double hydroxide (LDH)‐mediated BioClay was performed. We found that LDH‐mediated BioClay alleviates the degree of dsRNA degradation, which provides a new idea for the storage and transportation of dsRNA.

The aim of this study was to investigate the chemically defined nutritional requirements for Lactobacillus plantarum in milk. Twenty amino acids, five nucleotide precursors, ten vitamins, and ten mineral salts were added to skim milk. The selective removal of individual nutrient groups led to the identification of amino acids and nucleotide precursors as essential nutrients for L. plantarum growth. Mineral salts were not essential but had a growth-stimulating effect on L. plantarum . Further single-omission growth experiments revealed six key amino acids (isoleucine, leucine, valine, tyrosine, methionine, and phenylalanine) and at least one purine required as minimal nutrient for L. plantarum growth in milk. L. plantarum grew and propagated well in the fortified milk supplementation with six amino acids and adenine. The pH values of the fortified milk fermented using L. plantarum ST-III, WCFS1 and LPHS were 3.93, 3.84 and 4.02 at 72 h, respectively. However, the pH values of the control-fermented milk using L. plantarum ST-III, WCFS1 and LPHS were only 5.73, 5.61 and 5.84 at 72 h. The identification of the chemically defined requirements for growth of L. plantarum in milk without complex and undefined substances contributes to the understanding of the physiological properties and metabolic pathways of bacteria.

Downregulation of E-cadherin by the transcriptional repressor Snail is associated with acquisition of metastatic potential. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, it is unclear whether Snail is involved in HCV core-induced dysregulation of E-cadherin. Herein, we investigated the mechanism by which HCV core induces E-cadherin repression and the role of Snail in HCV core-mediated invasiveness and metastasis. We found that HCV infection, especially HCV core expression, effectively induced the epithelial-mesenchymal transition (EMT) in hepatoma cells by repressing E-cadherin. HCV core interacted with Snail and enhanced its binding to the E-box in the promoter region of E-cadherin, leading to decreased E-cadherin promoter activity. We found that HCV core, Snail, and the histone deacetylases HDAC1/HDAC2 formed a co-repressor complex at the E-cadherin promoter. Moreover, HCV core was shown to stabilize Snail through activation of the PI3K/Akt/GSK3β pathway. Silencing Snail expression restored E-cadherin expression and inhibited HCV core-promoted tumor growth and distant lung metastasis in vivo. Collectively, these results demonstrated that HCV core induced EMT by interacting with the transcriptional repressor complex Snail/HDACs at the E-cadherin promoter, which led to E-cadherin repression and increased invasiveness of hepatoma cells. These findings increase understanding of factors regulating metastasis in hepatoma and may ultimately lead to the development of novel treatment strategies for HCV-associated hepatocellular carcinoma.

Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple 'driver' oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, whereas re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo. Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits transforming growth factor β-activated mitogen-activated protein kinase and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to-mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach.

Streptococcus thermophilus phages present hazards for yogurt processing. In order to avoid adverse effects, different component yogurt starters were designed. For 2-component yogurt starters consisting of an S. thermophilus sensitive and a Lactobacillus delbrueckii ssp. bulgaricus strain, phage infection was destructive. Phages resulted in increased fermentation time, unbalanced cocci to rod ratios, decreased viscosity values, and varied sensory properties. For 3-component yogurt starters consisting of S. thermophilus sensitive, S. thermophilus insensitive, and L. bulgaricus strains, phage invasion did not result in the undesirable effects of slow acidification, decreased viscosity values, and unbalanced cocci to rod ratios. The 3-component yogurt starter stabilized fermentation and improved the practical fermentation performance in the presence of phages. Combinations of different S. thermophilus strains in the design and use of yogurt starters should be considered.

The influence of several Chinese teas on the ability of Lactobacillus casei to ferment milk was assessed. The three kinds of tea significantly stimulated the growth and acidification of L. casei. The viable cell counts in tea-supplemented fermented milk were higher than those of the control and were maintained during cold storage. Flavour component content increased significantly, and an additional eight components were detected in fermented milk supplemented with 5% green tea infusion (GTI5%) compared with control fermented milk. Moreover, the increase in total free amino acids after fermentation in GTI5% was 2.5-fold higher than in the control, suggesting that tea stimulated the growth and metabolism of L. casei during milk fermentation. Higher cell numbers, reduced fermentation time, abundant flavour components and free amino acids were achieved during the tea-supplemented fermentation of L. casei. Green tea effectively enhances the growth of L. casei, therefore could be considered for industrial purposes.

N-alkyl-2-(4-hydroxybut-2-ynyl) pyridinium bromides (designated as O-n) was synthesized and characterized by 1H and 13C NMR and FTIR. Box–Behnken design (BBD)-based optimization was engaged to analyze the factors and the interaction of the factors that influence the corrosion inhibition efficiency of O-n for X70 steel. The inhibition mechanism was also probed by means of X-ray photoelectron spectroscopy (XPS), Tafel polarization and electrochemical impedance spectroscopy (EIS) techniques.

Microbial fuel cell (MFC) biosensors are self-sustainable device for monitoring of various substrates; however, for heavy metals detection are still scarce. In this study, E. coli BL21 was engineered to express the zntR, ribB, and oprF genes with PzntA promoter, which could sense zinc (Zn2+) for riboflavin and porin production. The engineered strain produced high levels of riboflavin (2.4–3.6 μM) and improved cell membrane permeability, with a positive correlation of Zn2+ (0–400 μM). The strain was then employed in MFC biosensor under the following operational parameters: external resistance 1000 Ω, pH 9, and temperature 37 °C for Zn2+ sensing. The maximum voltages (160, 183, 260, 292, and 342 mV) of the constructed MFC biosensor have a linear relationship with Zn2+ concentrations (0, 100, 200, 300, and 400 μM, respectively) (R2 = 0.9777). An Android App was developed for the biosensor system that could sense Zn2+ in real-time and in situ. The biosensor was applied to wastewater with different Zn2+ concentrations and the results showed that the detection range for Zn2+ was 20–100 μM, which covers common Zn2+ safety standards. The results obtained with developed MFC biosensor were comparable to conventional methods such as colorimetric, flame atomic absorption spectroscopy (FAAS), and inductively coupled plasma optical emission spectroscopy (ICP-OES). In summary, MFC biosensor with biosynthetic strain is an efficient and affordable system for real-time monitoring and sensing of heavy metals.

Hexavalent chromium [Cr(VI)] is one of the major environmental contaminants in the Lanzhou reaches of the Yellow River, and actinomycetes' Cr(VI) bioremediation within this area is still scarce. In the present study, twenty actinomycete strains were isolated from the Lanzhou reaches which could resist 1.2 mM Cr(VI) on Starch-Casein (SC) agar plates. Based on the 16S rRNA sequence data, sixteen strains belong to Streptomyces and four other strains belong to Gordonia, Nocardiopsis, Nocardia and Cellulosimicrobium. One strain named LZ-26-1 which is closely related to Streptomyces violaceoruber demonstrated a notable ability of Cr(VI) reduction. It could reduce 92.86% of the 0.6 mM Cr(VI) to trivalent chromium [Cr(III)] in SC liquid medium in 144 h. The optimum temperature and pH were 28 °C and 7.0 for Cr(VI) reduction. Transmission electron microscopy images showed that chromium was precipitated inside the cells. In resting cells and crude chromate reductase assays, strain LZ-26-1's Cr(VI) reduction was stimulated when NADPH was used as an electron donor and Cd2+ treatment inhibited Cr(VI) reduction. Furthermore, thioredoxin operon, which consists of three genes encoding a thioredoxin, thioredoxin reductase (NADPH) and a possible membrane protein, was upregulated by Cr(VI) treatment. These results suggested that LZ-26-1 might utilize a thioredoxin pathway to reduce Cr(VI).

The aim of this study was to investigate the diversity of phages from Chinese yoghurt plants. Restriction analysis of six isolated Streptococcus thermophilus (St) phages showed that Φ101, Φ102 and Φ108 with different origins but with the same host strain St1 were different while phages Φ901, Φ903 and Φ907 with host strain St9 from the same origin were homologous. DNA packaging mechanism analysis proved the isolated phages to be pac -type except Φ108. The sensitive strain St1 could be infected by two different packaging mechanisms. Probing and sequencing of the variable region (VR2) fragment revealed that VR2 in aggressive phages (Φ101, Φ102 and Φ108) infecting host strain St1 was deleted. Phage Φ901 has an 845 bp amplicon and the similarity coefficient of the sequence was lower than 96% compared with other reported phages, which shows phage Φ901 did not belong to any known grouping.

Development of high-performance electrocatalysts requires a comprehensive consideration of intrinsic activity, number of active sites and electrical conductivity. Herein, we report the facile synthesis of a highly active electrocatalyst towards alkaline hydrogen evolution reaction (HER), which involves a joint application of composition modulation, nanostructuring and defect engineering strategies to address the three key issues. A 3D hierarchically nanostructured Ni2−xMoxP/NiMoO4−y catalyst is synthesized using hydrothermal in combination with phosphorization methods. Phosphorization treatment of the ammonium nickel molybdate precursor results in the concurrent formation of highly dispersed Mo-doped Ni2P nanoparticles and oxygen-defect-rich NiMoO4−y substrate, which work in concert to provide synergistic active sites for alkaline HER. The presence of abundant oxygen-vacancies in NiMoO4 lattice leads to significant improvement of electrical conductivity. Furthermore, the nanoporous hierarchical structure of the catalyst promises abundance of accessible active sites and an improved reactant/product mass transfer kinetics. As a consequence of the favorable combination of these attributes, the non-precious Ni2−xMoxP/NiMoO4−y catalyst exhibits an intriguing catalytic performance towards the HER in alkaline solution, with an overpotential of ~36 mV at a current density of 10 mA cm−2 and a Tafel slope of 53 mV dec−1, which are among the best reported values of noble-metal-free electrocatalysts for alkaline HER.

Background: Trypanosoma brucei, a causative agent of African Trypanosomiasis, is known to cross the blood brain barrier during the second stage of the disease. It was previously suggested that this parasite crosses the blood brain barrier in a manner similar to that of lymphocytes. This would imply that trypanosomes possess integrins that are required to interact with adhesion molecules located on the blood brain barrier microvascular endothelial cells, as a first step in traversal. To date, no T. brucei integrin has been described. However, one T. brucei putative FG-GAP repeat containing protein (typical of integrins) encoded by the Tb927.11.720 gene, was predicted to be involved in cell-cell/cell-matrix adhesion. Therefore, this study sought to characterize a putative FG-GAP repeat containing protein (FG-GAP RCP) and to determine its cellular localization as a basis for further exploration of its potential role in cell-cell or cell-matrix adhesion. Methods: In this study, we successfully cloned, characterized, expressed and localized this protein using antibodies we produced against its VCBS domain in T. brucei. Results: Contrary to what we initially suspected, our data showed that this protein is localized to the mitochondria but not the plasma membrane. Our data showed that it contains putative calcium binding motifs within the FG-GAP repeats suggesting it could be involved in calcium signaling/binding in the mitochondrion of T. brucei. Conclusion: Based on its localization we conclude that this protein is unlikely to be a trypanosomal integrin and thus that it may not be involved in traversal of the blood brain barrier. However, it could be involved in calcium signaling in the mitochondrion.

We have synthesized a new gemini surfactant, glycol bis-N-tetradecyl nicotinate dibromide (designed as P14-1-14), and probed its combination with bovine serum albumin (BSA) by fluorescence spectroscopy, dual polarization interferometry (DPI), proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FTIR) and molecular docking. The experiments revealed, in one hand, P14-1-14 quenched the intrinsic fluorescence of BSA by way of forming BSA/P14-1-14 complex with a binding constant of 2.14 × 104 L mol−1 at 293 K, that P14-1-14 augmented the thickness, mass, the refractive index (RI) and density of BSA, and that P14-1-14 declined the contents of α-helix (from 54.01% to 29.41%) but raised the random structure (from 7.86% to 22.27%). On the other hand, BSA shifted the proton resonance signals of P14-1-14 up-field and reduced relaxation time. The molecular docking manifested P14-1-14 embedded into subdomain of BSA, which made possible the π–π stacking between the electron-deficit pyridinium rings in P14-1-14 and the electron-abundant pyrrole ring in Trp residues of BSA, and that hydrogen bonding and hydrophobic interaction also took place during the binding. Therefore, the present work offers a whole view of the interaction of BSA with a new gemini surfactant.

Gemini surfactant diglycol bis-N-tetradecyl nicotinate dibromide (designed as EQ14-2-14) has been synthesized. The interaction between EQ14-2-14 and bovine serum albumin (BSA) was studied by dual polarization interferometry (DPI), proton nuclear magnetic resonance spectroscopy ( 1 H NMR), Fourier transform infrared spectroscopy (FTIR) and molecular docking. Owing to the binding of EQ14-2-14, the thickness and mass of BSA increased; refractive index (RI) and density firstly raised and then tended to a plateau. In addition, a decrease of α-helix was observed from 54.01% to 31.56% with an increase in random structure from 7.86% to 21.76%. Due to BSA intertwining, the proton resonance signals of EQ14-2-14 shifted up-field and relaxation time decreased with increasing concentration of BSA. The study of molecular docking indicated that EQ14-2-14 embedded into subdomain II of BSA by π–π stacking between the electron-deficit pyridinium rings in EQ14-2-14 and the electron-abundant pyrrole ring in Trp residues of BSA, by hydrogen bonding and by hydrophobic interaction. Therefore the present work offers a whole view of the interaction of BSA with a new gemini surfactant.

Based on inhibition of acid production, 100 individual colonies of Streptococcus thermophilus isolated from commercial Direct Vat Set yoghurt starter DVS-M were typed into 2 groups of sensitive and insensitive to phage φ001, which was isolated from the lysis culture of the turbidity test. The ratio between the sensitive and insensitive isolates in DVS-M was calculated at 3:2. Whole-cell protein profile (WCPP) and randomly amplified polymorphic DNA (RAPD) analysis showed that both WCPP and RAPD patterns between sensitive and insensitive isolates were distinct, whereas isolates with the same sensitivity or insensitivity shared common WCPP and RAPD patterns. It suggested that all the sensitive isolates belong to one S. thermophilus strain and all the insensitive isolates belong to another one. This study revealed that DVS-M yoghurt starter consists of 2 S. thermophilus strains with different phage sensitivity.

The plant homeodomain (PHD) finger is identified in many chromatin-binding proteins, and functions as a ‘reader’ that recognizes specific epigenetic marks on histone tails, bridging transcription factors and their associated complexes to chromatin, and regulating gene expression. PHD finger-containing proteins perform many biological functions and are involved in many human diseases including cancer. PHF14 is predicted to code for a protein with multiple PHD fingers. However, its function is unidentified. The aim of this study is to characterize PHF14 and investigate its biological significance by employing multiple approaches including mouse gene-targeting knockout, and molecular cloning and characterization. Three transcripts of PHF14 in human cell lines were identified by reverse transcriptase polymerase chain reaction. Two isoforms of PHF14 (PHF14α and PHF14β) were cloned in this study. It was found that PHF14 was ubiquitously expressed in mouse tissues and human cell lines. PHF14α, the major isoform of PHF14, was localized in the nucleus and also bound to chromatin during cell division. Interestingly, co-immunoprecipitation results suggested that PHF14α bound to histones via its PHD fingers. Strikingly, gene-targeting knockout of PHF14 in mice resulted in a neonatal lethality due to respiratory failure. Pathological analysis revealed severe disorders of tissue and cell structures in multiple organs, particularly in the lungs. These results indicated that PHF14 might be an epigenetic regulator and play an important role in the development of multiple organs in mouse. Keywords plant homeodomain (PHD) finger; PHF14; epigenetic; knockout mice

Gemini surfactant, 1,1′-(butane-1,4-diyl)-bis(3-(tetradecyloxycarbonyl)pyridinium) dibromide (designated as N G ), and the corresponding monomer, 1-ethyl-3-(tetradecyloxycarbonyl)pyridinium bromide (N S ), were prepared and utilized to modify sodium bentonite (Na-Bt). The surfactant modified bentonites (N G -Bt for the gemini modified bentonite and N S -Bt for the monomer modified one) were then used for methyl orange (MO) removal from the wastewater. The results indicated that the gemini surfactant N G was more effective than the monomer N S at expanding the interlayer space of Na-Bt and in removing MO from wastewater. The maximum basal spacing of N G -Bt (4.02 nm) was almost twice as that of N S -Bt (2.63 nm). MO removal efficiency was 9.68% for 4.0N S -Bt and 99.88% for 4.0N G -Bt at a dosage of 0.06 g, respectively. N S easily intercalated into the interlayer of Na-Bt, however more N G mainly stayed on the solid surface owing to its bigger head. The adsorption of both N G and N S on Na-Bt obeyed the pseudo-second-order kinetic model and Langmuir isotherms. The solid-state UV–vis spectrometry evidenced the formed complex of N G /N S with MO on Na-Bt, and the stronger interaction of N G -Bt with MO.

PHF14 is a newly identified regulator of mesenchyme growth in embryonic tissues. Previous studies have shown that phf14-null mutants die just after birth due to interstitial tissue hyperplasia in major organs, including the kidneys. The aim of this study was to investigate PHF14 function in renal fibrosis. By studying the chronic kidney injury mouse model, we found that PHF14 was upregulated in fibrotic kidneys after renal insults induced by folic acid administration. Compared with wild-type mice, PHF14-null mice showed more severe renal fibrosis after pro-fibrotic stimuli. Moreover, PHF14 in rat renal fibroblasts was upregulated by transforming growth factor-β (TGF-β) stimulation; while this upregulation was inhibited when smad3 phosphorylation was blocked. A chromatin immunoprecipitation (ChIP) assay further indicated that phospho-smad3 (p-smad3) acted as a transcription factor to enhance PHF14 expression. A lack of PHF14 expression enhanced collagen I and α-smooth muscle actin (α-SMA) synthesis induced by TGF-β in vitro. PHF14 was involved in inhibition of platelet-derived growth factor (PDGF) signaling overactivation by selectively repressing PDGF receptor-α (PDGFR-α) transcription. In summary, PHF14 expression was upregulated in fibrotic models in vivo and in vitro, and the TGF-β/smad3/PHF14 pathway acted as a self-limiting mechanism in the TGF-β-dominated renal pro-fibrotic process by suppressing PDGFR-α expression.

The effects of cabbage waste (CW) addition on methane production in cow dung and corn straw co-fermentation systems were investigated. Four experimental groups, each containing 55 g of substrate, were set up as follows: 100% cow dung (C); 36% cabbage and 64% cow dung (CC); 36% straw and 64% cow dung (SC); and 18% cabbage, 18% straw, and 64% cow dung (CSC). After seven days of fermentation, the maximum methane yield was 134 mL in the CSC group, which was 2.81-fold, 1.78-fold, and 1340-fold higher than that obtained in the CC, SC, and C groups, respectively. CW treatment of the CSC group enhanced cellulase activity and enriched culturable cellulose-degrading bacterial strains. Miseq sequencing data revealed that the predominant phylum in the CSC group was Bacteroidetes, which contains most of the cellulose-degrading bacteria. Our results suggested that CW treatment elevated cellulose degradation and promoted methane production.

Partitioning-defective 3 (Par3), a key component of the evolutionarily conserved polarity PAR complex (Par3/Par6/aPKC), controls cell polarity and contributes to cell migration, proliferation and tumor development. Emerging evidence indicates that cell polarity proteins function as upstream modulators that regulate the Hippo pathway. However, little is known about Par3’s involvement in the Hippo pathway. Here, we find Par3 and YAP dynamically co-localize in different subcellular compartments; that is, the membrane, cytoplasm and nucleus, in a cell-density-dependent manner. Interestingly, Par3 knockdown promotes YAP phosphorylation, leading to a significant impairment of YAP nuclear translocation at low cell density, but not at high density, in MDCK cells. Furthermore, via its third PDZ domain, Par3 directly binds to the PDZ-binding motif of YAP. The interaction is required for regulating YAP phosphorylation and nuclear localization. Mechanistically, Par3, as a scaffold protein, associates with LATS1 and protein phosphatase 1, α subunit (PP1A) in the cytoplasm and nucleus. Par3 promotes the dephosphorylation of LATS1 and YAP, thus enhancing YAP activation and cell proliferation. Strikingly, we also find that under the condition of PP1A knockdown, Par3 expression promotes YAP hyperphosphorylation, leading to the suppression of YAP activity and its downstream targets. Par3 expression results in differential effects on YAP phosphorylation and activation in different tumor cell lines. These findings indicate that Par3 may have a dual role in regulating the activation of the Hippo pathway, in a manner possibly dependent on cellular context or cell type in response to cell–cell contact and cell polarity signals.

Lactobacillus casei is widely used in food production and feed industry. The aim of this study was to construct the recombinant expression mannanase Lb. casei.The mature peptide gene of β-1,4-mannanase from Bacillus pumilus was cloned into expression vectors pELX1 and pELSH, then electroporated into Lb. casei, establishing an intracellular and a secretion expression mannanase Lb. casei respectively.After incubation, the specific activity of β-1,4-mannanase was 23 U/mg whole cell protein for intracellular expression and 8.8 U/mL for secretion expression in supernatant.Mannanase gene expression in Lb. casei provides application prospect and deserves further study.

// Lin Zhang 1, * , Qin Huang 1, * , Jiatao Lou 2 , Liangjian Zou 3 , Yiguo Wang 4 , Peng Zhang 1 , Guang Yang 1 , Junyi Zhang 1 , Lan Yu 1 , Dai Yan 1 , Chenyi Zhang 1 , Jing Qiao 1 , Shuting Wang 1 , Sai Wang 1 , Yongdong Xu 5 , Hongbin Ji 1, 7, 8 , Zhengjun Chen 1, 6, 7 , Zhe Zhang 1, 6 1 Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China 2 Shanghai Lung Tumor Clinical Medical Center, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China 3 Institute of Cardiothoracic Surgery, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai, China 4 Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China 5 Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China 6 Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, CAS, Shanghai, China 7 School of Life Science and Technology, Shanghai Tech University, Shanghai, China 8 CAS Center for Excellence in Molecular Cell Science, SIBCB, SIBS, CAS, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zhe Zhang, email: zhangzhe@sibcb.ac.cn Zhengjun Chen, email: zjchen@sibcb.ac.cn Keywords: PHF14, KIF4A, lung carcinogenesis, mitosis, biomarker Received: April 12, 2016 Accepted: January 03, 2017 Published: February 01, 2017 ABSTRACT The plant homeodomain (PHD) finger-containing proteins have been implicated in many human diseases including cancer. In this study, we found that PHF14, a newly identified PHD finger protein, is highly expressed in lung cancer. The high expression level of PHF14 was associated with adenocarcinoma and poor survival in lung cancer patients. Knocking down PHF14 suppressed cancer cell growth and carcinogenesis, while over-expressing PHF14 promoted cell proliferation. During cell division, PHF14 directly bound to and co-localized with KIF4A (a nuclear motor protein involved in lung carcinogenesis) to form a functional complex. Similarly to the effect of KIF4A depletion, silencing PHF14 in several cell lines caused cell mitotic defects, prolonged M phase, and inhibited cell proliferation. What’s more, these two proteins had a synergistic effect on cell proliferation and were significantly co-overexpressed in lung cancer tissues. Our data provide new insights into the biological significance of PHD finger proteins and imply that PHF14 may be a potential biomarker for lung cancer.

Bone tumor is a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered chemotherapy. Targeting anticancer drug to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. In this paper, a series of bone targeting Asp oligopeptides 5-fluorouracil conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their hydroxyapatite (HAP) affinity, drug release and cytotoxicity characteristics were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP .The efficient release of the active drug moiety occurring by the cleavage of different linkage in physiological conditions significantly reduced the number of viable human cancer cells. From in vivo distribution, we get these compounds with high bone-selectivity and long halflife. These results provided an effective entry to the development of new bone targeting chemotherapeutic drugs.

The adaptive immune CRISPR/Cas and CRISPR/Cmr systems of the crenarchaeal thermoacidophile Sulfolobus were challenged by a variety of viral and plasmid genes, and protospacers preceded by different dinucleotide motifs. The genes and protospacers were constructed to carry sequences matching individual spacers of CRISPR loci, and a range of mismatches were introduced. Constructs were cloned into vectors carrying pyrE/pyrF genes and transformed into uracil auxotrophic hosts derived from Sulfolobus solfataricus P2 or Sulfolobus islandicus REY15A. Most constructs, including those carrying different protospacer mismatches, yielded few viable transformants. These were shown to carry either partial deletions of CRISPR loci, covering a broad spectrum of sizes and including the matching spacer, or deletions of whole CRISPR/Cas modules. The deletions occurred independently of whether genes or protospacers were transcribed. For family I CRISPR loci, the presence of the protospacer CC motif was shown to be important for the occurrence of deletions. The results are consistent with a low level of random dynamic recombination occurring spontaneously, either inter-genomically or intra-genomically, at the repeat regions of Sulfolobus CRISPR loci. Moreover, the relatively high incidence of single-spacer deletions observed for S. islandicus suggests that an additional more directed mechanism operates in this organism.