Construction of Cs2AgBiCl6/COF Heterojunction for Boosted Photocatalytic Thioester Oxidation.

Lead-free halide perovskites as a new kind of potential candidate for photocatalytic organic synthesis have attracted much attention recently. The rational heterojunction construction is regarded as an efficient strategy to delicately regulate their catalytic performances. Herein, a semi-conductive covalent organic framework (COF) nanosheet, C4N, is employed as the functional component to construct Cs2AgBiCl6/C4N (CABC/C4N) heterojunction. It is found that the C4N nanosheets with rich surface functional groups can serve as heterogeneous nucleation sites to manipulate the growth of CABC nanocrystals and afford close contact between each other, therefore facilitate the transfer and spatial separation of photogenerated charge carriers, as verified by in situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy. Moreover, the oxygen affinity of C4N endows the heterojunctions with outstanding aerobic reactivity, thus improving the photocatalytic performance largely. The optimal CABC/C4N heterojunction delivers a thioanisole conversion efficiency of 100% after 6 h, which is 2.2 and 7.7-fold of that of CABC and C4N. This work provides a new ideal for the design and application of lead-free perovskite heterojunction photocatalysts for organic reactions.

In Situ Loading of Cu Nanocrystals on CsCuCl3 for Selective Photoreduction of CO2 to CH4.

Rational design and facile synthesis of efficient environmentally friendly all-inorganic lead-free halide perovskite catalysts are of great significance in photocatalytic CO2 reduction. Aiming at photogenerated charge carrier separation and CO2 reaction dynamics, in this paper, a CsCuCl3 /Cu nanocrystals (NCs) heterojunction catalyst is designed and synthesized via a simple acid-etching solution process by using Cu2 O as the sacrificed template. Due to the disproportionation reaction of Cu2 O induced by concentrated hydrochloric acid, Cu NCs can be deposited onto the surface of CsCuCl3 microcrystals directly and tightly. As revealed by photoelectrochemical analysis, in situ Fourier transform infrared spectra, etc., the Cu NCs contribute a lot to extracting photoelectrons of CsCuCl3 to improve the charge separation efficiency, regulating the CO2 adsorption and activation, and also stabilizing the reaction intermediates. Therefore, CsCuCl3 /Cu heterojunction exhibits a total electron consumption rate of 58.77 µmol g-1 h-1 , which is 2.9-fold of that of single CsCuCl3 . Moreover, high CH4 selectivity of up to 92.7% is achieved, which is much higher than that of CsCuCl3 (50.4%) and most lead-free halide perovskite-based catalysts. This work provides an ingenious but simple strategy to rationally design cocatalysts in situ decorated perovskite catalysts for manipulating both the catalytic activity and the product selectivity.

Metagenomic analysis of viral diversity and a novel astroviruse of forest rodent.

BACKGROUND: Rodents are important virus reservoirs and natural hosts for multiple viruses. They are one of the wild animals that are extremely threatening to the spread of human viruses. Therefore, research on rodents carrying viruses and identifying new viruses that rodents carry is of great significance for preventing and controlling viral diseases. METHODS: In this study, fecal samples from six species of forest rodents in Northeast China were sequenced using metagenomics, and an abundance of virome information was acquired. Selection of important zoonotic in individual rodents for further sequence and evolutionary analysis. RESULTS: Among the top 10 most abundant viral families, RNA virus include Orthomyxoviridae, Picornaviridae, Bunyaviridae and Arenaviridae, DNA virus include Herpesviridae, Insect virus include Nodaviridae and Baculoviridae, Plant virus Tombusviridae and Phage (Myoriviridae). Except for Myoviridae, there was no significant difference in the abundance of virus families in the feces of each rodent species. In addition, a new strain of astrovirus was discovered, with an ORF and genome arrangement comparable to other rodent astroviruses.The newly identified astrovirus had the highest similarity with the rodent astrovirus isolate, CHN/100. CONCLUSIONS: The data obtained in this study provided an overview of the viral community present in these rodent fecal samples, revealing some rodent-associated viruses closely related to known human or animal pathogens. Strengthening our understanding of unclassified viruses harbored by rodents present in the natural environment could provide scientific guidance for preventing and controlling new viral outbreaks that can spread via rodents.

Long noncoding RNA HBBP1 enhances γ-globin expression through the ETS transcription factor ELK1.

ß-Thalassemia is an autosomal recessive genetic disease caused by defects in the production of adult hemoglobin (HbA, α2ß2), which leads to an imbalance between α- and non-α-globin chains. Reactivation of γ-globin expression is an effective strategy to treat ß-thalassemia patients. Previously, it was demonstrated that hemoglobin subunit beta pseudogene 1 (HBBP1) is associated with elevated fetal hemoglobin (HbF, α2γ2) in ß-thalassemia patients. However, the mechanism underlying HBBP1-mediated HbF production is unknown. In this study, using bioinformatics analysis, we found that HBBP1 is involved in γ-globin production, and then preliminarily confirmed this finding in K562 cells. When HBBP1 was overexpressed, γ-globin expression was increased at the transcript and protein levels in HUDEP-2 cells. Next, we found that ETS transcription factor ELK1 (ELK1) binds to the HBBP1 proximal promoter and significantly promotes its activity. Moreover, the synthesis of γ-globin was enhanced when ELK1 was overexpressed in HUDEP-2 cells. Surprisingly, ELK1 also directly bound to and activated the γ-globin proximal promoter. Furthermore, we found that HBBP1 and ELK1 can interact with each other in HUDEP-2 cells. Collectively, these findings suggest that HBBP1 can induce γ-globin by enhancing ELK1 expression, providing some clues for γ-globin reactivation in ß-thalassemia.

Upregulation of oncogene Activin A receptor type I by Helicobacter pylori infection promotes gastric intestinal metaplasia via regulating CDX2.

BACKGROUND: Activin A receptor type I (ACVR1) is involved in tumorigenesis. However, the underlying molecular mechanisms of ACVR1 in gastric cancer (GC) and its association with Helicobacter pylori remained unclear. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database were utilized to explore the ACVR1 expression in GC and normal control and its association with survival. The ACVR1 was knocked out using CRISPR/Cas-9; RNA sequencing analysis was performed in AGS cells with ACVR1 knockout and normal control. Functional experiments (CCK-8, colony-forming, and transwell assays) were conducted to demonstrate the role of ACVR1 in cell proliferation, invasion, and metastasis. H. pylori-infected C57/BL6 models were established. ACVR1, p-Smad1/5, and CDX2 were detected in AGS cells cocultured with H. pylori strains. The CDX2 and key elements of BMP signaling pathway were detected in AGS cells with ACVR1 knockout and normal control. In addition, Immunohistochemistry was performed to detect the ACVR1 and CDX2 expression in gastric samples. RESULTS: ACVR1 expression was higher in GC than normal control from TCGA, GEPIA, and samples collected from our hospital (p < 0.05). ACVR1 promoted cell proliferation, migration, and invasion in vitro. Both cagA+ and cagA- H. pylori could upregulate the expression ACVR1 (p < 0.05). Downregulation of ACVR1 inhibited the H. pylori-induced cell proliferation, migration, and invasion (p < 0.05). H. pylori increased the expression of p-Smad 1/5 and CDX2. The CDX2 and key elements of BMP signaling pathway were downregulated in AGS cells with ACVR1 knockout. ACVR1 and CDX2 were upregulated in the stage of intestinal metaplasia (IM). Moreover, ACVR1 and CDX2 expressions were higher in H. pylori-positive group than H. pylori-negative group (p < 0.05). CONCLUSION: Our data indicate that H. pylori infection increases ACVR1 expression, promoting gastric IM via regulating CDX2, which is an essential step in H. pylori carcinogenesis.

Knockdown of YKL-40 inhibits angiogenesis through regulation of VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer.

Studies have demonstrated that small interfering RNA (siRNA) targeting YKL-40 (siYKL-40) inhibits the proliferation, migration, invasion, and induces antiapoptotic abilities of endometrial cancer (EC) HEC-1A cells. However, its effect on angiogenesis is unclear. The present study aimed to investigate the role of YKL-40 in endometrial cancer and the related molecular mechanisms. YKL-40 was knocked down by transfection with siYKL-40 and the effects on angiogenesis, cell viability, and signaling pathways were investigated. The results showed that siYKL-40 inhibited VEGFA levels and tube formation in endothelial cells. Additionally, inhibition of YKL-40 decreased the expression levels of vascular endothelial growth factor (VEGF), phosphorylated vascular endothelial growth factor receptor 2 (pVEGFR2), and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2). Furthermore, a nude mice xenograft model of EC showed that siYKL-40 inhibited tumor growth. Inhibition of YKL-40 led to suppression of angiogenesis and reduction of microvessel density through VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer cells. Taken together, this study demonstrated novel molecular mechanisms for role of YKL-40 in EC.

Preparation of single crystalline AlN thin films on ZnO nanostructures by atomic layer deposition at low temperature.

The growth of hetero-epitaxial ZnO-AlN core-shell nanowires (NWs) and single crystalline AlN films on non-polar ZnO substrate at temperature of 380 °C by atomic layer deposition (ALD) was investigated. Structural characterization shows that the AlN shells have excellent single-crystal properties. The epitaxial relationship of [0002]ZnO//[0002]AlN, and [10-10]ZnO//[10-10]AlNbetween ZnO core and AlN shell has been obtained. The ZnO NW templates were subsequently removed by annealing treatment in forming gas, resulting in ordered arrays of AlN single-crystal nanotubes. The impact factors on the epitaxial growth of AlN films are thoroughly investigated. It turned out that the growth parameters including lattice mismatch between substrate and AlN, growth temperature, and the polarity of ZnO substrate play important roles on the growth of single-crystal AlN films by ALD. Finally, non-polar AlN films with single-crystalline structure have been successfully grown onm-plane ZnO (10-10) single-crystal substrates. The as-grown hollow AlN nanotubes arrays and non-polar AlN films with single-crystalline structures are suggested to be highly promising for applications in nanoscale devices. Our research has developed a potential method to obtain other inorganic nanostructures and films with single-crystalline structure at fairly low temperature.

UBL4A Augments Innate Immunity by Promoting the K63-Linked Ubiquitination of TRAF6.

Human UBL4A/GdX, encoding an ubiquitin-like protein, was shown in this study to be upregulated by viral infection and IFN stimulation. Then the functions of UBL4A in antiviral immune response were characterized. Overexpression of UBL4A promoted RNA virus-induced ISRE or IFN-ß or NF-κB activation, leading to enhanced type I IFN transcription and reduced virus replication. Consistently, knockdown of UBL4A resulted in reduced type I IFN transcription and enhanced virus replication. Additionally, overexpression of UBL4A promoted virus-induced phosphorylation of TBK1, IRF3, and IKKα/ß. Knockdown of UBL4A inhibited virus-induced phosphorylation of TBK1, IRF3, and IKKα/ß. Coimmunoprecipitation showed that UBL4A interacted with TRAF6, and this interaction was enhanced upon viral infection. Ubiquitination assays showed that UBL4A promoted the K63-linked ubiquitination of TRAF6. Therefore, we reveal a novel positive feedback regulation of UBL4A in innate immune response combating virus invasion by enhancing the K63-linked ubiquitination of TRAF6.

Solution-Processed Anatase Titania Nanowires: From Hyperbranched Design to Optoelectronic Applications.

The utilization of solar energy and the development of its related optoelectronic devices have become more important than ever. Solar cells or photoelectrochemical (PEC) cells that require the design of light harvesting assemblies for efficiently converting solar light into electricity or solar fuels are of particular interest. Semiconductor TiO2, serving as the photoelectrode for photovoltaic devices (e.g., dye- or quantum dot-sensitized solar cells (DSSCs/QDSSCs) or perovskite solar cells (PSCs)) and PEC cells, has aroused intense research interest owing to its inherent characteristics of wide band gap and promising optical and electrical properties. TiO2 nanowires (TNWs) have been widely used in optoelectronic devices due to their unique 1D geometry and salient optical and electrical properties. However, the insufficient surface area resulting from the relatively large diameter of NWs and considerable free space between adjacent NWs restricts their optoelectronic performance. Hence, it is desirable to explore every feasible aspect of TNWs in terms of structural design and optical management, aiming to further improve the performance of optoelectronic devices. In this Account, we present a brief survey of strategies for designing branched or hyperbranched TNW-based photoelectrodes and their applications in solar cells and PEC cells. The general strategies (e.g., alkaline/acid hydrothermal method, lift-off transfer, and self-assembly approach) are discussed to address the challenges associated with fabricating TNWs on transparent conducting oxide (TCO) substrates. A series of strategies to fabricate judiciously designed 3D branched array architectures, including length tuning and sequential surface branched or hyperbranched modification, are proposed. The versatile implantation of the TNWs onto other backbones (nanosheets, nanotubes, hollow spheres, or multilayered electrodes) and substrates (fiber-shaped metal wire or mesh, flexible metal foil, or plastic sheet) is demonstrated to construct a new class of the TNW-embedded composite electrode materials with desired morphological characteristics and optoelectronic properties, for example, favorable energy level alignment for cascade charge transfer and rational homogeneous/heterogeneous interfacial engineering. The functionalities of TNW-based electrodes include enlarged surface area and superior light scattering for maximized light harvesting, as well as facilitated charge transport and suppressed charge recombination for enhanced charge collection, which are promising in optoelectronic fields such as solar cells, photocatalysis, and PEC cells. Beyond TNWs, one can also integrate other types of semiconductor (e.g., Fe2O3 or WO3) NWs into rationally designed structures for preparing novel photocatalytic materials with panchromatic absorption, efficient charge transfer, and excellent catalytic properties. Finally, an insightful perspective for rational design of advanced NW-based materials is provided.

[Change laws of water absorption in Chinese herbal pieces and prediction model of relative density for Chinese medicine decoction].

This study aims to explore the change laws of water absorption in Chinese herbal pieces and establish the prediction model of relative density for Chinese medicine compound decoction. Firstly, fitted equations of water absorption and decocting time was established by observing the change laws of water absorption in 36 kinds of Chinese herbal pieces in 12 groups(according to the drug-parts) with decocting time. The r value of the mineral group and other type group was 0.691 2 and 0.663 3, respectively. The r value of the remaining 10 groups was 0.802 2-0.925 4. All P values were less than 0.05(n=21). The formula of the amount of water added was optimized by combining the fitted equations with determined water absorption, and the liquid yield could be controlled in a range of 100%±10%. Secondly, it was determined that the liquid density tester could be used for the rapid determination of relative density of Chinese medicine decoction after methodological study and comparison with the pycnometer method. The linear regression equation between the corrected relative density(y) and extraction ratio(%, x) was built by measuring and analyzing the related parameters such as liquid yield, relative density and extraction ratio in 46 kinds of Chinese herbal pieces. The established equation was y=0.041 3x+1.003 7, r=0.930 9(P <0.01, n=46), with linear range of 1.94%-65.75%. Based on this, the prototype model for predicting relative density of Chinese medicine decoction was established, and the relative densities of 8 Chinese medicine decoctions were within the prediction interval of this model in verification. This study lays a foundation for database construction of Chinese medicine decoction, implementation of personalized decocting mode and rapid quality control of Chinese medicine decoction.

In Situ Construction of a Cs2SnI6 Perovskite Nanocrystal/SnS2 Nanosheet Heterojunction with Boosted Interfacial Charge Transfer.

Heterojunction engineering has played an indispensable role in the exploitation of innovative artificial materials with exceptional properties and has consequently triggered a new revolution in achieving high-performance optoelectronic devices. Herein, an intriguing halide perovskite (PVK) and metal dichalcogenide (MD) heterojunction, i.e., a lead-free Cs2SnI6 perovskite nanocrystal/SnS2 nanosheet hybrid, was fabricated in situ for the first time. Comprehensive investigations with experimental characterizations and theoretical calculations demonstrate that cosharing of the Sn atom enables intimate contact in the Cs2SnI6/SnS2 hybrid together with a type II band alignment structure. Additionally, ultrafast carrier separation between SnS2 and Cs2SnI6 has been observed in the Cs2SnI6/SnS2 hybrid by transient absorption measurements, which efficiently prolongs the lifetime of the photogenerated electrons in SnS2 (from 1290 to 3080 ps). The resultant spatial charge separation in the Cs2SnI6/SnS2 hybrid evidenced by Kelvin probe force microscopy (KPFM) significantly boosts the photocatalytic activity toward CO2 reduction and the photoelectrochemical performance, with 5.4-fold and 10.6-fold enhancements compared with unadorned SnS2. This work provides a facile and effective method for the in situ preparation of PVK-MD heterojunctions, which may significantly stimulate the synthesis of various perovskite-based hybrid materials and their further optoelectronic applications.

USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.

Ubiquitination and deubiquitination are important post-translational regulatory mechanisms responsible for fine tuning the antiviral signaling. In this study, we identified a deubiquitinase, the ubiquitin-specific peptidase 7/herpes virus associated ubiquitin-specific protease (USP7/HAUSP) as an important negative modulator of virus-induced signaling. Overexpression of USP7 suppressed Sendai virus and polyinosinic-polycytidylic acid and poly(deoxyadenylic-deoxythymidylic)-induced ISRE and IFN-ß activation, and enhanced virus replication. Knockdown or knockout of endogenous USP7 expression had the opposite effect. Coimmunoprecipitation assays showed that USP7 physically interacted with tripartite motif (TRIM)27. This interaction was enhanced after SeV infection. In addition, TNF receptor-associated factor family member-associated NF-kappa-B-binding kinase (TBK)-1 was pulled down in the TRIM27-USP7 complex. Overexpression of USP7 promoted the ubiquitination and degradation of TBK1 through promoting the stability of TRIM27. Knockout of endogenous USP7 led to enhanced TRIM27 degradation and reduced TBK1 ubiquitination and degradation, resulting in enhanced type I IFN signaling. Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1.-Cai, J., Chen, H.-Y., Peng, S.-J., Meng, J.-L., Wang, Y., Zhou, Y., Qian, X.-P., Sun, X.-Y., Pang, X.-W., Zhang, Y., Zhang, J. USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.

[Effects of CSN4 knockdown on proliferation and apoptosis of breast cancer MDA-MB-231 cells].

Breast cancer is one of the most common malignant tumors endangering women. It has been found that the subunits of the COP9 complex are closely related to the occurrence and development of malignant tumors, and the CSN4 subunit plays an important role in regulating the whole complex. In the breast cancer cell line MDA-MB-231, we successfully established a lentivirus-mediated CSN4-knockdown cell line. CCK8 cell proliferation assays and colony formation experiments confirmed that CSN4 knockdown significantly decreased the cellular proliferation rate. Cell cycle analysis showed that CSN4 knockdown increased sub-G1 population and induced apoptosis. In addition, Western blotting assays confirmed that CSN4 regulates the expression of CDK6 and Caspase3, suggesting that CSN4 modulates the proliferation and apoptosis of breast cancer cells by regulating the expression of CDK6 and Caspase3 genes and thereby tumorigenesis. This study has deepened our understanding of the molecular mechanism of apoptosis and cell growth in breast cancers, and further revealed the role and mechanism of CSN4 in cancer biology.

Intrinsic Self-Trapped Emission in 0D Lead-Free (C4 H14 N2 )2 In2 Br10 Single Crystal.

Low-dimensional lead halide perovskite materials recently have drawn much attention owing to the intriguing broadband emissions; however, the toxicity of lead will hinder their future development. Now, a lead-free (C4 H14 N2 )2 In2 Br10 single crystal with a unique zero-dimensional (0D) structure constituted by [InBr6 ]3- octahedral and [InBr4 ]- tetrahedral units is described. The single crystal exhibits broadband photoluminescence (PL) that spans almost the whole visible spectrum with a lifetime of 3.2 µs. Computational and experimental studies unveil that an excited-state structural distortion in [InBr6 ]3- octahedral units enables the formation of intrinsic self-trapped excitons (STEs) and thus contributing the broad emission. Furthermore, femtosecond transient absorption (fs-TA) measurement reveals that the ultrafast STEs formation together with an efficient intersystem crossing has made a significant contribution to the long-lived and broad STE-based emission behavior.

A Highly Red-Emissive Lead-Free Indium-Based Perovskite Single Crystal for Sensitive Water Detection.

Low-dimensional luminescent lead halide perovskites have attracted tremendous attention for their fascinating optoelectronic properties, while the toxicity of lead is still considered a drawback. Herein, we report a novel lead-free zero-dimensional (0D) indium-based perovskite (Cs2 InBr5 ⋅H2 O) single crystal that is red-luminescent with a high photoluminescence quantum yield (PLQY) of 33 %. Experimental and computational studies reveal that the strong PL emission might originate from self-trapping excitons (STEs) that result from an excited-state structural deformation. More importantly, the in situ transformation between hydrated Cs2 InBr5 ⋅H2 O and the dehydrated form is accompanied with a switchable dual emission, which enables it to act as a PL water-sensor in humidity detection or the detection of traces of water in organic solvents.

Clinical, Laboratory and Imaging Features of High Altitude Pulmonary Edema in Tibetan Plateau.

Objective To analyze characteristics of high altitude pulmonary edema (HAPE) in Chinese patients.Methods We performed a retrospective study of 98 patients with HAPE. We reviewed the medical records and summarized the clinical, laboratory and imaging characteristics of these cases, and compared the results on admission with those determined before discharge.Results Forty-eight (49.0%) patients developed HAPE at the altitude of 2800 m to 3000 m. Ninty-five (96.9%) patients were man. Moist rales were audible from the both lungs, and moist rales over the right lung were clearer than those over the left lung in fourteen patients. The white blood cells [(12.83±5.55) versus (8.95±3.23) ×10 9/L, P=0.001)] as well as neutrophil counts [(11.34±3.81) versus (7.49±2.83)×10 9/L, P=0.001)] were higher, whereas the counts of other subsets of white blood cells were lower on admission than those after recovery (all P<0.05). Serum levels of alkaline phosphatase (115.8±37.6 versus 85.7±32.4 mmol/L, P=0.020), cholinesterase (7226.2±1631.8 versus 6285.3±1693.3 mmol/L, P=0.040), creatinine (85.2±17.1 versus75.1±12.8 mmol/L, P=0.021), uric acid (401.9±114.2 versus 326.0±154.3 mmol/L, P=0.041), and uric glucose (7.20±1.10 versus 5.51±1.11 mmol/L, P=0.001) were higher, but carbondioxide combining power (CO2CP, 26.7±4.4 versus 28.9±4.5 mmol/L, P=0.042) and serous calcium (2.32±0.13 versus 2.41±0.10 mmol/L, P=0.006) were lower on admission. Arterial blood gas results showed hypoxemia and respiratory alkalosis on admission. Conclusions In the present research, men were more susceptible to HAPE than women, and in the process of HAPE, the lesions of the right lung were more serious than those of the left lung. Some indicators of routine blood test and blood biochemistry of HAPE patients changed.

A CsPbBr3 Perovskite Quantum Dot/Graphene Oxide Composite for Photocatalytic CO2 Reduction.

Halide perovskite quantum dots (QDs), primarily regarded as optoelectronic materials for LED and photovoltaic devices, have not been applied for photochemical conversion (e.g., water splitting or CO2 reduction) applications because of their insufficient stability in the presence of moisture or polar solvents. Herein, we report the use of CsPbBr3 QDs as novel photocatalysts to convert CO2 into solar fuels in nonaqueous media. Under AM 1.5G simulated illumination, the CsPbBr3 QDs steadily generated and injected electrons into CO2, catalyzing CO2 reduction at a rate of 23.7 µmol/g h with a selectivity over 99.3%. Additionally, through the construction of a CsPbBr3 QD/graphene oxide (CsPbBr3 QD/GO) composite, the rate of electron consumption increased 25.5% because of improved electron extraction and transport. This study is anticipated to provide new opportunities to utilize halide perovskite QD materials in photocatalytic applications.

Autophagy activated by duck enteritis virus infection positively affects its replication.

Duck enteritis virus (DEV) is an acute, septic, sexually transmitted disease that occurs in ducks, geese and other poultry. Autophagy is an evolutionarily ancient pathway that is important in many viral infections. Despite extensive study, the interplay between DEV and autophagy of host cells is not clearly understood. In this study, we found that DEV infection triggers autophagy in duck embryo fibroblast (DEF) cells, as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm of host cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and decreased p62/SQSTM1 indicated complete autophagy flux. Heat-inactivated DEV infection did not induce autophagy, suggesting that the trigger of autophagy in DEF cells depended on DEV replication. When autophagy was pharmacologically inhibited by LY294002 or wortmannin, DEV replication decreased. The DEV offspring yield decreased when small interference RNA was used to interfere with autophagy related to the genes Beclin-1 and ATG5. In contrast, after treating DEF cells with rapamycin, an inducer of autophagy, DEV replication increased. These results indicated that DEV infection induced autophagy in DEF cells and autophagy facilitated DEV replication.

Association between polymorphisms of autophagy pathway and responses in non-small cell lung cancer patients treated with platinum-based chemotherapy.

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.