Trifunctional L-Cysteine Assisted Construction of MoO2/MoS2/C Nanoarchitecture Toward High-Rate Sodium Storage.

The volume collapse and slow kinetics reaction of anode materials are two key issues for sodium ion batteries (SIBs). Herein, an "embryo" strategy is proposed for synthesis of nanorod-embedded MoO2/MoS2/C network nanoarchitecture as anode for SIBs with high-rate performance. Interestingly, L-cysteine which plays triple roles including sulfur source, reductant, and carbon source can be utilized to produce the sulfur vacancy-enriched heterostructure. Specifically, L-cysteine can combine with metastable monoclinic MoO3 nanorods at room temperature to encapsulate the "nutrient" of MoOx analogues (MoO2.5(OH)0.5 and MoO3·0.5H2O) and hydrogen-deficient L-cysteine in the "embryo" precursor affording for subsequent in situ multistep heating treatment. The resultant MoO2/MoS2/C presents a high-rate capability of 875 and 420 mAh g-1 at 0.5 and 10 A g-1, respectively, which are much better than the MoS2-based anode materials reported by far. Finite element simulation and analysis results verify that the volume expansion can be reduced to 42.8% from 88.8% when building nanorod-embedded porous network structure. Theoretical calculations reveal that the sulfur vacancies and heterointerface engineering can promote the adsorption and migration of Na+ leading to highly enhanced thermodynamic and kinetic reaction. The work provides an efficient approach to develop advanced electrode materials for energy storage.

The GTPase activity and isoprenylation of Swine GBP1 are critical for inhibiting the production of Japanese Encephalitis Virus.

Japanese encephalitis virus (JEV) is a flavivirus that cause severe neurological deficits. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on many RNA and DNA viruses via diverse mechanisms, however, the roles and the action modes of GBP1 in the antiviral effect on the production of JEV RNA and infectious virions remain to be clarified. In this study, we found that the RNA levels of swine GBP1 (sGBP1) in PK15 cells were up-regulated at the late stage of JEV infection. The overexpression of sGBP1 significantly inhibited the production of JEV while the knockdown of sGBP1 promoted the production of JEV. The GTPase activity and isoprenylation of sGBP1 both are critical for anti-JEV activity. The GTPase activity of sGBP1 is responsible for inhibiting the production of JEV genomic RNA. The isoprenylation of sGBP1 inhibited the expression and cleavage of JEV prM to decrease the yields of infectious virions, which may be associated with the interaction between sGBP1 and cellular proprotein convertase furin. Taken together, the study dissected the action modes of sGBP1with potent anti-JEV activity in more details.

An improved luciferase immunosorbent assay for ultrasensitive detection of antibodies against African swine fever virus.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a fatal infectious disease of pigs and causes great socioeconomic losses globally. The reliable diagnostic method is critical for prevention and control of the disease. In this study, an improved Luciferase immunosorbent assay (LISA) for detecting ASF was developed using the cell lysates containing ASFV p35 protein fused with a reporter Nano-luciferase (p35-Luc protein). The improved method avoids the complicate procedures of immobilizing the serum samples with protein G in the normal LISA method, and replaced by directly coating the serum samples with carbonate buffer, therefore reduces the productive cost and simplifies the operation procedures. The p35-Luc LISA exhibited high specificity for anti-ASFV sera while no cross-reactions with the sera against other swine viruses. The detection limit of the p35-Luc LISA was shown to be at least four times higher than that of the p35 based indirect ELISA established in our lab. The receiver operating characteristic (ROC) analysis showed the 96.36% relative specificity and 96.97% relative sensitivity of the p35-Luc LISA with the cutoff values of 3.55 as compared to the commercial Ingezim p72-ELISA kit. Furthermore, a total of 248 serum samples were tested by both the p35-Luc LISA and commercial Ingezim p72-ELISA kit, and there was a high degree of agreement (97.6%, kappa = 0.9753) in the performance of the two assays. Collectively, the improved LISA based on the p35-Luc protein could be used as a rapid, ultrasensitive, cost-effective and reliable diagnostic tool for serological survey of ASF in pig farms.

Enhancing K2S2O8 electrochemiluminescence based on silver nanoparticles and zinc metal-organic framework composite (AgNPs@ZnMOF) for the determination of l-cysteine.

A silver nanoparticle-doped Zn(ii) metal-organic framework composite (AgNPs@ZnMOF) was investigated as an electrochemiluminescence (ECL) signal enhancer for potassium persulfate. First, ZnMOF was prepared by a one-step hydrothermal method, and then AgNPs@ZnMOF composite was obtained by depositing AgNPs on the surface and interior of ZnMOF. After the AgNPs@ZnMOF composite was modified on the glass carbon electrode (GCE), the cathode luminescence of potassium persulfate on bare GCE was enhanced by 8 times. A dual amplification mechanism provided by Zn(ii) and Ag nanoparticles in the AgNPs@ZnMOF composite has been validated by ECL spectra, fluorescence spectra, and electrochemical methods. The interaction between the sulfhydryl groups in l-cysteine (l-Cys) and AgNPs significantly affects the catalytic luminescence of the AgNPs@ZnMOF composite. Thus, a sensitive ECL method for the determination of l-Cys was developed based on the inhibition effect of l-Cys on the ECL signal within the linear range from 5.0 nM to 1.0 µM and the limit of detection was found to be 2 nM (S/N = 3). The established method has been successfully applied to the determination of l-Cys in human urine.

Complete genome sequence of a psychrotolerant and piezotolerant bacterium Parasedimentitalea marina W43T, isolated from deep sea water of the New Britain trench.

Parasedimentitalea marina W43T is a novel psychrotolerant and piezotolerant Rhodobacteraceae bacterium isolated from deep-sea water (4000 m) of the New Britain Trench. Here we present the first complete genome sequence of the bacterial genus Parasedimentitalea, which contains a circular chromosome and four plasmids. The 5,080,916 bp long genome exhibits a G + C content of 55.9 mol% and contains 5090 protein-coding and 97 RNA genes. Genomic analysis revealed abundant clues on bacterial cold and high-pressure adaptation and deep-sea lifestyle. The genome is consistent with a heterotrophic, psychrotolerant and piezotolerant lifestyle of the deep-sea environment.

Complete genome sequence of a piezophilic bacterium Salinimonas sediminis N102T, isolated from deep-sea sediment of the New Britain Trench.

Salinimonas sediminis N102T is a cold-adapted, slightly halophilic piezophile isolated from deep-sea sediment (4700 m) of the New Britain Trench. In this study, we report the complete genome sequence of S. sediminis N102T, which is comprised of 4,440,293 base pairs with a mean G + C content of 48.2 mol%. The complete genome harbors 3851 predicted protein-coding genes, 70 tRNA genes and 15 rRNA genes. Abundant genes in the genome were predicted to be linked to bacterial deep-sea lifestyle. The complete genome sequence of S. sediminis N102T provides insights into the microbial adaptation strategies to the deep-sea environment.

Comprehensive analysis of the effect of rs2295080 and rs2536 polymorphisms within the mTOR gene on cancer risk.

There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P<0.05, OR (odds ratio) <1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P<0.05, OR>1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of "population-based" control source via the allele, heterozygote, dominant, and carrier comparisons (P<0.05, OR>1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer.

Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-κB-mediated by RhoA/ROCK signalling pathway.

Advanced glycation end products (AGE) are those of the most powerful pathogenic factors that related to diabetic complications. In our study, we investigated the beneficial effects of thymol on AGE induced cell injury and apoptosis in human podocytes (HPCs) and attempted to clarify its mechanisms. Our results revealed that stimulation with AGE could significantly activate RhoA/NF-κB pathway. Results showed thymol could markedly suppress inflammatory responses, cell apoptosis and disordered cytoskeleton. Also thymol restored the expression of podocin, restrained migration capacity. Western blot analysis indicated that it could restore the expression of RhoA, ROCK and vimentin, nephrin, podocin and p65 and IκBα phosphorylation. Moreover, si-RhoA also suppressed the expression of pro-inflammatory cytokines, ROCK, and vimentin and the phosphorylation of p65 and IκBα. In conclusion, thymol inhibits AGE-induced cell injury in HPCs by suppressing the RhoA-NF-κB pathway and may be apromising therapeutic agent.

Screening and Identification of Key Biomarkers for Bladder Cancer: A Study Based on TCGA and GEO Data.

Bladder cancer (BLCA) is a common malignant cancer, and it is the most common genitourinary cancer in the world. The recurrence rate is the highest of all cancers, and the treatment of BLCA has only slightly improved over the past 30 years. Genetic and environmental factors play an important role in the development and progression of BLCA. However, the mechanism of cancer development remains to be proven. Therefore, the identification of potential oncogenes is urgent for developing new therapeutic directions and designing novel biomarkers for the diagnosis and prognosis of BLCA. Based on this need, we screened overlapping differentially expressed genes (DEG) from the GSE7476, GSE13507, and TCGA BLCA datasets. To identify the central genes from these DEGs, we performed a protein-protein interaction network analysis. To investigate the role of DEGs and the underlying mechanisms in BLCA, we performed Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) analysis; we identified the hub genes via different evaluation methods in cytoHubba and then selected the target genes by performing survival analysis. Finally, the relationship between these target genes and tumour immunity was analysed to explore the roles of these genes. In summary, our current studies indicate that both cell division cycle 20 (CDC20) and abnormal spindle microtubule assembly (ASPM) genes are potential prognostic biomarkers for BLCA. It may also be a potential immunotherapeutic target with future clinical significance.

Up-regulation of TIF1γ by valproic acid inhibits the epithelial mesenchymal transition in prostate carcinoma through TGF-ß/Smad signaling pathway.

Valproic acid (VPA), one of the histone deacetylase inhibitors, can suppress prostate cancer (PCa) cells epithelial mesenchymal transition (EMT). Transcriptional intermediary factor 1γ (TIF1γ) which is a vital protein molecule that possesses ubiquitination enzyme activity, can mediate TGF-ß induced EMT. We aimed to investigate the detailed mechanism between VPA and EMT occurrence in PCa cells to clarify the potential mechanism of TIF1γ involved. In our vitro experiments, we first investigated the effect of VPA on the expression TIF1γ. After TIF1γ was knockdown or overexpressed by related lentivirus, EMT of PCa cells were assessed. When TIF1γ knockdown or overexpress stable cell line were established, cells were treated with additional VPA, EMT index were detected and functional experiments were also conducted to confirm whether VPA inhibited EMT of PCa cells via TIF1γ. The mono-ubiquitination of Smad4 was analyzed simultaneously. In vivo, mice were facilitated with PC3 cells or TIF1γ related knockdown or overexpress virus transfected PC3 cells with or without VPA administration. Results showed that in vitro VPA can increase the expression of TIF1γ and also induce the increase expression of E-cadherin, and the decrease of N-cadherin and vimentin. Knocking down of TIF1γ can effectively block the effect of VPA on EMT and metastasis while overexpression of TIF1γ can strengthen its role. In vivo VPA also showed its anti-growth effect including tumor growth and EMT mediated by TIF1γ coincide with in vitro experiments. In conclusion, VPA inhibits the EMT in PCa cells via up-regulating the expression of TIF1γ and the mono-ubiquitination Smad4. VPA could serve as a promising agent in PCa treatment, with new strategies based on its diverse effects on posttranscriptional regulation.

Targeting the transcription factor receptor LXR to treat clear cell renal cell carcinoma: agonist or inverse agonist?

Growing evidence indicates that clear cell renal cell carcinoma (ccRCC) is a metabolism-related disease. Changes in fatty acid (FA) and cholesterol metabolism play important roles in ccRCC development. As a nuclear transcription factor receptor, Liver X receptor (LXR) regulates a variety of key molecules associated with FA synthesis and cholesterol transport. Therefore, targeting LXR may provide new therapeutic targets for ccRCC. However, the potential regulatory effect and molecular mechanisms of LXR in ccRCC remain unknown. In the present study, we found that both an LXR agonist and an XLR inverse agonist could inhibit proliferation and colony formation and induce apoptosis in ccRCC cells. We observed that the LXR agonist LXR623 downregulated the expression of the low-density lipoprotein receptor (LDLR) and upregulated the expression of ABCA1, which resulted in reduced intracellular cholesterol and apoptosis. The LXR inverse agonist SR9243 downregulated the FA synthesis proteins sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FASN) and stearoyl-coA desaturase 1 (SCD1), causing a decrease in intracellular FA content and inducing apoptosis in ccRCC cells. SR9243 and LXR623 induced apoptosis in ccRCC cells but had no killing effect on normal renal tubular epithelial HK2 cells. We also found that SRB1-mediated high-density lipoprotein (HDL) in cholesterol influx is the cause of high cholesterol in ccRCC cells. In conclusion, our data suggest that an LXR inverse agonist and LXR agonist decrease the intracellular FA and cholesterol contents in ccRCC to inhibit tumour cells but do not have cytotoxic effects on non-malignant cells. Thus, LXR may be a safe therapeutic target for treating ccRCC patients.

A modified trace metal detection test for secondary imprints on porous substrates: A preliminary study.

In the investigation of criminal cases involving metallic weapons such as firearms and knives, the trace metal detection test (TMDT) and the transfer detection technique are two effective and on-the-spot methods to link a suspect and a suspected metallic weapon. In general, these tests need to be conducted on suspects' hands or done by lifting trace metals from their hands within 3 days of the crime being committed. However, if no suspects are arrested within this period, neither of these two techniques is applicable. This paper presents preliminary development of a modified TMDT to overcome the intrinsic disadvantages of conventional TMDTs. The method primarily focuses on the secondary imprints on porous substrates that are transferred unconsciously from the palms of criminals after handling galvanized weapons. The modified TMDT was established by studying the effect of various factors on secondary imprints on porous substrates. We also tested the effectiveness of the modified TMDT for common porous substrates and galvanized weapons and its relative sensitivity in a depletion series. Additionally, the storage conditions of the developed secondary imprints as physical evidence were studied under different time lapses and light conditions. Finally, we proposed an improved procedure for detecting metal traces formed in the use of metallic weapons and subsequent activities at a crime scene. The modified TMDT provides a novel method for investigators to demonstrate the relationship between a suspect and a metallic weapon, thus reducing the heavy reliance of conventional TMDTs on suspects and the time limit available to visualize or lift metal traces. For this reason, it can be used as a complementary and remedial method for conventional TMDTs, especially when suspects are not arrested within 3 days of the commission of a crime. Furthermore, the improved procedure can serve as a guide for investigators to apply the TMDT series properly to solving the cases involving metallic weapons.

[The aspiratory resistance and filtration penetration of N95 filtering-facepiece respirators used widely in China].

OBJECTIVE: The objective of this study was to investigate the aspiratory resistance, filtration penetration and their influence factors of N95 filtering-facepiece respirators used widely in China. METHODS: The total of 6 brands and 21 models of N95 filtering-facepiece respirators which are certified and big sales on the market. The aspiratory resistance and filtration efficiency filter penetration were measured while air pump ran from 10 L/min to 100 L/min using differential pressure gauge and the PortaCount, respectively. RESULTS: The filtration penetrations for 2 of the 21 models were lower than 95%, and the qualified rate for all models was 90.47%. The filtration penetrations gradually decreased when ventilation flow of air pump increased. The negative correlation was observed between filtration penetration and ventilation flow (r(2) = 0.711, P < 0.05). The resistances of all 21 models of N95 respirators met the requirements of the national standard. The aspiratory resistance started to elevate with the increasing of ventilation flow, and a positive correlation between both (r(2) = 0.878, P < 0.05). Significant differences of filtration penetration and aspiratory resistance were observed among between different brands (P < 0.05) although no differences of filtration penetration existed among different models of one brand (P > 0.05). But the differences of the aspiratory resistance among different models of one brand were statistically significant (P < 0.05). CONCLUSION: The aspiratory resistances of all N95 filtering-facepiece respirators used in this study met the requirements of the national standard. And the qualified ratio of filtration penetration of all models was higher than 90%. The influencing factors of aspiratory resistance included materials, size and ventilation flow. And influencing factors for filtration penetration were materials and ventilation flow.

Fluorescent detection of single nucleotide polymorphism utilizing a hairpin DNA containing a nucleotide base analog pyrrolo-deoxycytidine as a fluorescent probe.

A novel fluorescent method for the detection of single nucleotide polymorphism (SNP) was developed using a hairpin DNA containing nucleotide base analog pyrrolo-deoxycytidine (P-dC) as a fluorescent probe. This fluorescent probe was designed by incorporating a fluorescent P-dC into a stem of the hairpin DNA, whose sequence of the loop moiety complemented the target single strand DNA (ss-DNA). In the absence of the target ss-DNA, the fluorescent probe stays a closed configuration in which the P-dC is located in the double strand stem of the fluorescent probe, such that there is weak fluorescence, attributed to a more efficient stacking and collisional quenching of neighboring bases. In the presence of target ss-DNA, upon hybridizing the ss-DNA to the loop moiety, a stem-loop of the fluorescent probe is opened and the P-dC is located in the ss-DNA, thus resulting in strong fluorescence. The effective discrimination of the SNP, including single base mismatch ss-DNA (A, T, G) and double mismatch DNA (C, C), against perfect complementary ss-DNA was achieved by increased fluorescence intensity, and verified by thermal denaturation and circular dichroism spectroscopy. Relative fluorescence intensity had a linear relationship with the concentration of perfect complementary ss-DNA and ranged from 50 nM to 3.0 µM. The linear regression equation was F/F(0)=2.73 C (µM)+1.14 (R=0.9961) and the detection limit of perfect complementary ss-DNA was 16 nM (S/N=3). This study demonstrates that a hairpin DNA containing nucleotide base analog P-dC is a promising fluorescent probe for the effective discrimination of SNP and for highly sensitive detection of perfect complementary DNA.

A signal-on electrogenerated chemiluminescent biosensor for lead ion based on DNAzyme.

A highly reproducible and sensitive signal-on electrogenerated chemiluminescence (ECL) biosensor based on the DNAzyme for the determination of lead ion was developed. The ECL biosensor was fabricated by covalently coupling 5'-amino-DNAzyme-tagged with ruthenium bis (2,2'-bipyridine) (2,2'-bipyridine-4,4'-dicarboxylic acid)-ethylenediamine (Ru1-17E') onto the surface of graphite electrode modified with 4-aminobenzoic acid, and then a DNA substrate with a ribonucleotide adenosine hybridized with Ru1-17E' on the electrode. Upon binding of Pb(2+) to the Ru1-17E' to form a complex which catalyzed the cleavage of the DNA substrate, the double-stranded DNA was dissociated and thus led to a high ECL signal. The signal linearly increases with the concentration of Pb(2+) in the range from 5.0 to 80 pM with a detection limit of 1.4 pM and a relative standard derivation of 2.3%. This work demonstrates that using DNAzyme tagged with ruthenium complex as an ECL probe and covalently coupling method for the fabrication of the ECL biosensor with high sensitivity, good stability and significant regeneration ability is promising approach.

Label-free fluorescent molecular beacon based on a small fluorescent molecule non-covalently bound to the intentional gap site in the stem moiety.

A label-free fluorescent molecular beacon (MB) based on a fluorescent molecule, 5,6,7-trimethyl-1,8-naphthyridin-2-ylamine (ATMND) which is non-covalently bound to the intentional gap site in the stem moiety of the label-free MB, was developed. In the absence of a cDNA, ATMND fluorescence is significantly quenched because it binds to the unpaired cytosine at the gap site by hydrogen bonding. As a result, the label-free MB shows almost no fluorescence. Upon hybridization with cDNA, the label-free MB undergoes a conformational change to destroy the gap site. This results in an effective fluorescent enhancement because of the release of the ATMND from the gap site to the solution. Fluorescence titration shows that ATMND strongly binds to the cytosine at the gap site (K(11)>10(6)). Circular-dichroism spectroscopy indicates that the binding of ATMND at the gap site of the stem moiety does not induce a significant conformational change to the hairpin DNA. Under optimal conditions, the fluorescent intensity of the label-free MB increases with an increase in cDNA concentration from 50 nM to 1.5 µM. A detection limit of 20 nM cDNA was achieved. A single mismatched target ss-DNA can be effectively discriminated from cDNA. The advantage of the label-free MB is that both its ends can be left free to introduce other useful functionalities. In addition, the label-free MB synthesis introduced in this paper is relatively simple and inexpensive because no label is required.