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- ArticleHong J, Liu Z, Zhu H, Zhang X, Liang Y, Yao S, Wang F, Xie X, Zhang B, Tan T, Fu L, Nie J, Cheng C.Oncotarget. 2014 Jul 30;5(14):5602-14.Esophageal quamous cell carcinoma (ESCC) is the predominant histological type of esophageal carcinoma in Asian populations. To date, few biomarkers have been identified for ESCC. In present study, we found a tumor suppressor, NUMB isoform 1 (NUMB-1), as a promising prognostic biomarker for patients with ESCC. NUMB-1 mRNA was downregulated in 66.7% of primary ESCC tissues when compared with matched adjacent non-tumor tissues. The low expression of NUMB-1 was significantly associated with high tumor recurrence (p=0.029) and poor post-operative overall survival (p=0.016). To further explore the underlying mechanisms by which NUMB-1 regulates ESCC, we demonstrated that ectopic expression of NUMB-1 inhibited cell proliferation through inducing G2/M phase arrest, which was accompanied by an increase in p21 and cyclin B1-cdc2 levels. However, it had no impact on apoptosis of ESCC cells. In addition, overexpression of NUMB-1 prevented epithelial-mesenchymal transition, inhibited invasion of ESCC cells and NOTCH pathway, suppressed Aurora-A activity by preventing phosphorylation of Aurora-A at T288 which resulted in cell cycle arrest. Taken together, our findings suggested NUMB-1 functions as a tumor-suppressor and serves as a prognositc biomarker for ESCC patients; thus, NUMB-1 may be a potential novel therapeutic target for treatment of ESCC.
- ArticleLu C, Li JY, Ge Z, Zhang L, Zhou GP.Oncogene. 2013 Dec 12;32(50):5602-13.Although the intensification of therapy for children with T-cell acute lymphoblastic leukemia (T-ALL) has substantially improved clinical outcomes, T-ALL remains an important challenge in pediatric oncology. Here, we report that the cooperative synergy between prostate apoptosis response factor-4 (Par-4) and THAP1 induces cell cycle and apoptosis regulator 1 (CCAR1) gene expression and cellular apoptosis in human T-ALL cell line Jurkat cells, CEM cells and primary cultured neoplastic T lymphocytes from children with T-ALL. Par-4 and THAP1 collaborated to activate the promoter of CCAR1 gene. Mechanistic investigations revealed that Par-4 and THAP1 formed a protein complex by the interaction of their carboxyl termini, and THAP1 bound to CCAR1 promoter though its zinc-dependent DNA-binding domain at amino terminus. Par-4/THAP1 complex and Notch3 competitively bound to CCAR1 promoter and competitively modulated alternative pre-mRNA splicing of CCAR1, which resulted in two different transcripts and played an opposite role in T-ALL cell survival. Despite Notch3 induced a shift splicing from the full-length isoform toward a shorter form of CCAR1 mRNA by splicing factor SRp40 and SRp55, Par-4/THAP1 complex strongly antagonized this inductive effect. Our finding revealed a mechanistic rationale for Par-4/THAP1-induced apoptosis in T-ALL cells that would be of benefit to develop a new therapy strategy for T-ALL.
- ArticleDalmaschio CJ, da Silveira Firmiano EG, Pinheiro AN, Sobrinho DG, Farias de Moura A, Leite ER.Nanoscale. 2013 Jun 21;5(12):5602-10.Close-packed arrays of ZrO2 nanocrystals (NCs) have been self-assembled from a colloidal solution in a withdrawal dip coating process. A benzyl alcohol route was used to obtain NCs of narrowly controlled size, and then the capping layer was replaced by oleate using solvothermal treatment. The oleate solubility was explored in chloroform, hexane and toluene to prepare thin films of NCs using a dip coating process. From TEM images, the final structures show that increasing the solvent polarity improved self-assembly to prepare mono- and multi-layer superlattices, during solvent evaporation in a short time. The entangled organic chain in the NC surface offsets the limitations of the faceted NCs, improving the assembly quality, allowing the NC assembly to approach the formation of a hard sphere model, resulting in a FCC close-packed structure. Furthermore, the low interaction of chloroform with the capping layer reduces the shrinkage effect during the solvent evaporation preserving the array in the final self-assembled structure. Molecular dynamics simulations with soft potentials supported the conclusion that hexane interacts with the organic capping ligand, increasing the apparent radius of each NC and stabilizing the colloidal suspension, whereas chloroform is partially removed from the capping layer during the aggregation process, forming an array of nanoparticles.
- ArticleLi F, Wang Y, Yu L, Cao S, Wang K, Yuan J, Wang C, Wang K, Cui M, Fu ZF.J Virol. 2015 May;89(10):5602-14.UNLABELLED: Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB.
IMPORTANCE: Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not JEV infection per se, but the inflammatory cytokines/chemokines induced by JEV infection that inhibit the expression of TJ proteins and ultimately result in the enhancement of BBB permeability. Neutralization of gamma interferon (IFN-γ) ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting that IFN-γ could be a potential therapeutic target. This study would lead to identification of potential therapeutic avenues for the treatment of JEV infection. - ArticleChen XY, Ling T, Du XW.Nanoscale. 2012 Sep 21;4(18):5602-7.Hierarchical nanostructures involving primary wide-band-gap nanowires and secondary narrow-band-gap branches are promising for photovoltaic application due to their excellent properties for light harvesting and fast carrier transport. In the present work, we developed a low-temperature process for facile synthesis of ZnO/CdS hierarchical nanowires, where the primary ZnO nanowires were first prepared via a hydrothermal route and then the secondary single-crystal CdS tips were grown on the ZnO nanowires by electrochemical deposition. The as-grown hierarchical ZnO/CdS nanowires are superior in charge separation as well as carrier transport, thus achieving higher open circuit voltage, short circuit current and final conversion efficiency than the common coaxial nanocables with CdS nanocrystal shell on core ZnO nanowires.
- ArticleWimsatt JH, Montgomery C, Thomas LS, Savard C, Tallman R, Innes K, Jrebi N.PeerJ. 2018;6:e5602.Colorectal cancer ranks third among the most commonly diagnosed cancers in the United States. Current therapies have a range of side effects, and the development of a reliable animal model to speed the discovery of safe effective preventative therapies would be of great value. A cross-sectional study in a large Appalachian population recently showed an association between low circulating levels of perfluorooctane sulfonate (PFOS) and a reduced prevalence of colorectal cancer. A study using APCmin (C57BL/6J-ApcMin/J) mice prone to familial adenomatous polyposis found PFOS was protective when exposure occurred during tumor development. To test the possible benefit of PFOS on spontaneous colorectal cancer, we developed a mouse model utilizing primary patient colorectal cancer implants into NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl /Sz) mice. Study goals included: (1) to assess potential factors supporting the successful use of colorectal cancer from heterogeneous tumors for PDX studies; and, (2) evaluate PFOS as a therapy in tumor matched pairs of mice randomized to receive PFOS or vehicle. The time in days for mice to grow primary tumors to 5 mm took almost 2 months (mean = 53.3, se = 5.7, range = 17-136). Age of mice at implantation, patient age, gender and race appeared to have no discernable effect on engraftment rates. Engraftment rates for low and high-grade patient tumors were similar. PFOS appeared to reduce tumor size dramatically in one group of tumors, those from the right ascending colon. That is, by 5 weeks of treatment in two mice, PFOS had eliminated their 52.4 mm3 and 124.6 mm3 masses completely, an effect that was sustained for 10 weeks of treatment; in contrast, their corresponding matched vehicle control mice had tumors that grew to 472.7 mm3 and 340.1 mm3 in size respectively during the same period. In a third xenograft mouse, the tumor growth was dramatically blunted although not eliminated, and compared favorably to their matched vehicle controls over the same period. These preliminary findings suggested that this mouse model may be advantageous for testing compounds of potential value in the treatment of colorectal cancer, and PFOS may have utility in selected cases.
- ArticleSpindler X, Hofstetter O, McDonagh AM, Roux C, Lennard C.Chem Commun (Camb). 2011 May 21;47(19):5602-4.Enantioselective anti-L-amino acid antibodies conjugated to gold nanoparticles are shown to facilitate the detection of latent fingermarks by interacting with amino acids present in friction ridge secretions. This antibody-based system is particularly effective for the enhancement of aged and dried fingermarks on non-porous surfaces, an area unexploited by current techniques.
- ArticleLiu T, Xiong SJ, Cao XZ, Su QP, Yang CP.Opt Lett. 2015 Dec 01;40(23):5602-5.Compared with a qubit, a qutrit (i.e., three-level quantum system) has a larger Hilbert space and thus can be used to encode more information in quantum information processing and communication. Here, we propose a method to transfer an arbitrary quantum state between two flux qutrits coupled to two resonators. This scheme is simple because it only requires two basic operations. The state-transfer operation can be performed fast because only resonant interactions are used. Numerical simulations show that the high-fidelity transfer of quantum states between the two qutrits is feasible with current circuit-QED technology. This scheme is quite general and can be applied to accomplish the same task for other solid-state qutrits coupled to resonators.
- ArticleNilewski C, Le Chapelain C, Wolfrum S, Carreira EM.Org Lett. 2015 Nov 20;17(22):5602-5.This study documents that chlorinated analogs of leukotoxin diol 1, in which the vic-diol has been replaced with vic-chlorides (2), induce caspase 3 activity and apoptosis on HepG2 cells in a dose-dependent manner in analogy to the parent diol. This suggests that chlorides may substitute for hydroxyls in certain lipids as bioisosteres in defined biological settings.
- ArticleSantos A, Pal S, Chacón J, Meraz K, Gonzalez J, Prieto K, Rosas-Acosta G.J Virol. 2013 May;87(10):5602-20.Our pioneering studies on the interplay between the small ubiquitin-like modifier (SUMO) and influenza A virus identified the nonstructural protein NS1 as the first known SUMO target of influenza virus and one of the most abundantly SUMOylated influenza virus proteins. Here, we further characterize the role of SUMOylation for the A/Puerto Rico/8/1934 (PR8) NS1 protein, demonstrating that NS1 is SUMOylated not only by SUMO1 but also by SUMO2/3 and mapping the main SUMOylation sites in NS1 to residues K219 and K70. Furthermore, by using SUMOylatable and non-SUMOylatable forms of NS1 and an NS1-specific artificial SUMO ligase (ASL) that increases NS1 SUMOylation ~4-fold, we demonstrate that SUMOylation does not affect the stability or cellular localization of PR8 NS1. However, NS1's ability to be SUMOylated appears to affect virus multiplication, as indicated by the delayed growth of a virus expressing the non-SUMOylatable form of NS1 in the interferon (IFN)-competent MDCK cell line. Remarkably, while a non-SUMOylatable form of NS1 exhibited a substantially diminished ability to neutralize IFN production, increasing NS1 SUMOylation beyond its normal levels also exerted a negative effect on its IFN-blocking function. This observation indicates the existence of an optimal level of NS1 SUMOylation that allows NS1 to achieve maximal activity and suggests that the limited amount of SUMOylation normally observed for most SUMO targets may correspond to an optimal level that maximizes the contribution of SUMOylation to protein function. Finally, protein cross-linking data suggest that SUMOylation may affect NS1 function by regulating the abundance of NS1 dimers and trimers in the cell.
- ArticleHirvonen LM, Festy F, Suhling K.Opt Lett. 2014 Oct 01;39(19):5602-5.A 1 MHz frame rate complementary metal-oxide semiconductor (CMOS) camera was used in combination with an image intensifier for wide-field time-correlated single-photon counting (TCSPC) imaging. The system combines an ultrafast frame rate with single-photon sensitivity and was employed on a fluorescence microscope to image decays of ruthenium compound Ru(dpp) with lifetimes from around 1 to 5 μs. A submicrowatt excitation power over the whole field of view is sufficient for this approach, and compatibility with live-cell imaging was demonstrated by imaging europium-containing beads with a lifetime of 570 μs in living HeLa cells. A standard two-photon excitation scanning fluorescence lifetime imaging (FLIM) system was used to independently verify the lifetime for the europium beads. This approach brings together advantageous features for time-resolved live-cell imaging such as low excitation intensity, single-photon sensitivity, ultrafast camera frame rates, and short acquisition times.
- ArticleIkegami S, Uehara M, Tokida R, Nishimura H, Sakai N, Horiuchi H, Kato H, Takahashi J.Sci Rep. 2024 03 07;14(1):5602.This investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant's criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman's rho: 0.23 to 0.36, P < 0.05). Our study showed that Grade 1 mild vertebral fractures in males lacked pathological significance, while in females they potentially indicated fragility fractures and were related to poor lumbopelvic alignment.
- ArticleNotario-Estévez A, Kozlov SM, Viñes F, Illas F.Chem Commun (Camb). 2015 Apr 04;51(26):5602-5.Rational design of improved transition metal based materials mostly relies on their electronic structure descriptors, typically estimated by density functional theory and so unduly affected by self-interaction or static correlation errors. Here we show for all 30 transition metals that original or width-corrected d-band centers, and Hilbert transform highest peak descriptors are unaffected by self-interaction, while poor treatment of static correlation by hybrid functionals leads to an unbalanced description. Thus, descriptors have a general validity unbiased by a specific computational method.
- ArticleLee HG, Milner PJ, Buchwald SL.Org Lett. 2013 Nov 01;15(21):5602-5.The stable Pd(0) species [(1,5-cyclooctadiene)(L·Pd)2] (L = AdBrettPhos) has been prepared and successfully evaluated as a precatalyst for the fluorination of aryl triflates derived from biologically active and heteroaryl phenols, challenging substrates for our previously reported catalyst system. Additionally, this precatalyst activates at room temperature under neutral conditions, generates 1,5-cyclooctadiene as the only byproduct, and leads to overall cleaner reaction profiles.
- ArticleJiang Y, Zhu C, Wang S, Wang F, Sun Z.Sci Rep. 2023 04 05;13(1):5602.Scutellaria baicalensis has been one of the most commonly used traditional Chinese medicinal plants in China for more than 2000 years. The three new varieties cultivated could not be distinguished by morphology before flowering. It will hinder the promotion of later varieties. Chloroplast DNA has been widely used in species identification. Moreover, previous studies have shown that complete chloroplast genome sequences have been suggested as super barcodes for identifying plants. Therefore, we sequenced and annotated the complete chloroplast genomes of three cultivated varieties. The chloroplast genomes of SBW, SBR, and SBP were 151,702 bp, 151,799 bp, and 151,876 bp, which contained 85 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The analysis of the repeat sequences, codon usage, and comparison of chloroplast genomes shared a high degree of conservation. However, the sliding window results show significant differences among the three cultivated varieties in matK-rps16 and petA-psbJ. And we found that the matK-rps16 sequence can be used as a barcode for the identification of three varieties. In addition, the complete chloroplast genome contains more variations and can be used as a super-barcode to identify these three cultivated varieties. Based on the protein-coding genes, the phylogenetic tree demonstrated that SBP was more closely related to SBW, in the three cultivated varieties. Interestingly, we found that S. baicalensis and S. rehderiana are closely related, which provides new ideas for the development of S. baicalensis. The divergence time analysis showed that the three cultivated varieties diverged at about 0.10 Mya. Overall, this study showed that the complete chloroplast genome could be used as a super-barcode to identify three cultivated varieties of S. baicalensis and provide biological information, and it also contributes to bioprospecting.
- ArticleYao K, Zhou E, Schaafsma E, Zhang B, Cheng C.Cancer Med. 2023 03;12(5):5590-5602.BACKGROUND: Immune checkpoint proteins play critical functions during the immune response to cancer and have been targeted by immune checkpoint blockade therapy. V-domain Ig suppressor of T cell activation (VSIR) is one of these immune checkpoint genes and has been investigated extensively in recent years due to its conflicting roles in cancer immunity. Specifically, in acute myeloid leukemia (AML), the prognostic value of VSIR is debated.
RESULTS: In both patient tumor samples and cancer cell lines we find that VSIR has the highest expression in AML out of all cancer types and, in AML, has the highest expression out of all other immune checkpoint genes. Survival analysis indicated that AML patients with higher VSIR expression have significantly shorter survival than those patients with lower expression, even within established AML subgroups (e.g., FAB subtypes). Importantly, VSIR expression is predictive of progression from myelodysplastic syndromes (MDS) patients into AML, suggesting its potential role during the very early stage of AML development and progression. In addition to AML, VSIR also demonstrates prognostic values in other cancer types, including multiple myeloma and mesothelioma.
CONCLUSION: In summary, our analyses revealed the prognostic value of VSIR and its potential as a target for immunotherapy, especially in AML. - ArticleRodríguez-Rodríguez CE, Jelić A, Llorca M, Farré M, Caminal G, Petrović M, Barceló D, Vicent T.Bioresour Technol. 2011 May;102(10):5602-8.For safe biosolid-land-applying, sludge should be contaminant-free. However, it may contain important amounts of micropollutants, not removed in the wastewater-treatment-processes. An alternative treatment with the fungus Trametes versicolor was applied in sterile solid-phase systems consisting of sludge and a lignocellulosic substrate. Fungal colonization and activity were demonstrated during the process, according to monitoring of ergosterol, laccase activity and the naproxen-degradation test (ND24). Fourteen out of 43 analyzed pharmaceuticals were found in the raw sludge. After treatment, phenazone, bezafibrate, fenofibrate, cimetidine, clarithromycin, sulfamethazine and atenolol were completely removed, while removals between 42% and 80% were obtained for the remaining pharmaceuticals. Toxicological analyses (Daphnia magna, Vibrio fischeri and seed germination) showed an important reduction in sludge toxicity after treatment. Results suggest that a solid-phase treatment with T. versicolor may reduce the ecotoxicological impact of micropollutants present in sewage sludge. This is the first report of a fungal-approach for elimination of emerging pollutants from biosolids.
- ArticleDocobo-Pérez F, Drusano GL, Johnson A, Goodwin J, Whalley S, Ramos-Martín V, Ballestero-Tellez M, Rodriguez-Martinez JM, Conejo MC, van Guilder M, Rodríguez-Baño J, Pascual A, Hope WW.Antimicrob Agents Chemother. 2015 Sep;59(9):5602-10.The aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producing E. coli strains. Human fosfomycin pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted to determine the dose ranges, including the dose ranges that suppressed the development of drug-resistant mutants, were conducted with regimens from 12 g/day to 36 g/day. The combination of fosfomycin at 4 g every 8 h (q8h) and meropenem at 1 g/q8h was selected for further assessment. The total bacterial population and the resistant subpopulations were determined. No efficacy was observed against the Ec42444 strain (fosfomycin MIC, 64 mg/liter) at doses of 12, 24, or 36 g/day. All dosages induced at least initial bacterial killing against Ec46 (fosfomycin MIC, 1 mg/liter). High-level drug-resistant mutants appeared in this strain in response to 12, 15, and 18 g/day. In the study arms that included 24 g/day, once or in a divided dose, a complete extinction of the bacterial inoculum was observed. The combination of meropenem with fosfomycin was synergistic for bacterial killing and also suppressed all fosfomycin-resistant clones of Ec2974 (fosfomycin MIC, 1 mg/liter). We conclude that fosfomycin susceptibility breakpoints (≤64 mg/liter according to CLSI [for E. coli urinary tract infections only]) should be revised for the treatment of serious systemic infections. Fosfomycin can be used to treat infections caused by organisms that demonstrate lower MICs and lower bacterial densities, although relatively high daily dosages (i.e., 24 g/day) are required to prevent the emergence of bacterial resistance. The ratio of the area under the concentration-time curve for the free, unbound fraction of fosfomycin versus the MIC (fAUC/MIC) appears to be the dynamically linked index of suppression of bacterial resistance. Fosfomycin with meropenem can act synergistically against E. coli strains in preventing the emergence of fosfomycin resistance.
- ArticleZhao TT, Shen LL, Zhang XL, Gu DY, Zhang Q, Huo XY, Tang CJ, Chen JF.Genet Mol Res. 2015 May 25;14(2):5602-14.Published data regarding the association between the cytosolic serine hydroxymethyltransferase (SHMT1) C1420T (Leu474Phe) polymorphism and solid tumor risk have shown inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 23 published studies that included 14,409 cancer cases and 16,996 controls. A comprehensive search was conducted to identify all eligible studies of the SHMT1 rs1979277 polymorphism and solid tumor risk. The pooled odds ratios (ORs) and the 95% confidence intervals (95%CIs) were calculated using a fixed- or random-effects model. Heterogeneity was represented by PH; publication bias and sensitivity analysis were also explored. Overall, no significant associations were found for any genetic models tested. However, upon stratification by cancer type, a significant decreased risk of breast cancer risk was identified in the homozygote comparison (OR = 0.79, 95%CI = 0.65-0.97 for TT versus CC). An analysis stratified by ethnicity and source of controls revealed an obvious decrease in risk among Asian groups in all genetic models, and among population-based controls only in the homozygote comparison and recessive model. Therefore, our meta-analysis suggested that the SHMT1 C1420T polymorphism was associated with decreased risk of breast cancer. Significant protective effects were found among Asian populations, but not in Caucasian groups. Due to some minor limitations, our findings should be confirmed by further studies.
- ArticleFerguson J, Zeng F, Alper H.Org Lett. 2012 Nov 02;14(21):5602-5.Palladium-catalyzed oxidative cyclocarbonylation of 2-vinylphenols constitutes a simple, direct method for the synthesis of coumarins. The reaction conditions, employing low pressures of CO, and air or 1,4- benzoquinone as the oxidant, are attractive in terms of environmental considerations and operational simplicity. Coumarins with a variety of functional groups were prepared in yields up to 85%.