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Yu Long - Top 30 Publications

Fabrication of a graphene/C60 nanohybrid via γ-cyclodextrin host-guest chemistry for photodynamic and photothermal therapy.

The wonderful chemical structures and characteristics of low-dimensional carbon materials have exciting applications in life sciences. In the present study, we developed a facile strategy to conjugate C60 with graphene via host-guest chemistry for targeted phototherapy. A versatile carrier based on folic acid-functionalized graphene (GO-FA) and comprising γ-cyclodextrin (γ-CD) at its surface was assembled via π-π interaction, creating hybrid structures with drug storage and tumor targeting properties. This γ-CD-modified graphene (GO-FA/Py-γ-CD) is capable of hosting pristine C60 molecules for the fabrication of a GO-FA/Py-γ-CD/C60 nanohybrid. The hybridization of GO-FA, γ-CD, and C60 hinders the aggregation of C60, promotes cellular uptake, enhances light absorption, and finally demonstrates enhanced phototherapy effects of GO-FA/Py-γ-CD/C60. Under Xe lamp irradiation (2 W cm(-2)) for 4 min, GO-FA/Py-γ-CD/C60 simultaneously causes heating and intracellular ROS production, which further significantly reduces the cell viability to 16.2% at low content of loading (30 μg mL(-1)). Moreover, it represents an excellent tumor killing efficiency, better than that of the other reported graphene/C60 nanohybrids; thus, this material is suitable for applications in phototherapy of cancer.

Knockout of the Nogo-B Gene Attenuates Tumor Growth and Metastasis in Hepatocellular Carcinoma.

Human hepatocellular carcinoma (HCC) is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4) family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells. Nogo-B knockout, via the CRISPR-Cas9 technique, resulted in significant suppression of HCC cell proliferation and tumor growth. Next-generation sequencing analysis showed that Nogo-B knockout have effects on interleukin-6 (IL-6) signaling pathway. Furthermore, we observed that IL-6 induced phosphorylation of STAT3 (pSTAT3) in wild-type HCC cells, but Nogo-B knockout could reduce IL-6-induced increase of pSTAT3, supporting that Nogo-B affects HCC tumor progression possibly via regulating the IL-6/STAT3 signaling pathway. In conclusion, Nogo-B is expressed aberrantly in HCCs and plays an oncogenic role. These findings support that Nogo-B may be a novel anti-HCC therapeutic target.

Catalytic Oxidation of Chlorobenzene over MnxCe1-xO2/HZSM-5 Catalysts: A Study with Practical Implications.

Industrial-use catalysts usually encounter severe deactivation after long-term operation for catalytic oxidation of chlorinate volatile organic compounds (CVOCs), which becomes a "bottleneck" for large-scale application of catalytic combustion technology. In this work, typical acidic solid-supported catalysts of MnxCe1-xO2/HZSM-5 were investigated for the catalytic oxidation of chlorobenzene (CB). The activation energy (Ea), Brønsted and Lewis acidities, CB adsorption and activation behaviors, long-term stabilities, and surficial accumulation compounds (after ageing) were studied using a range of analytical techniques, including XPS, H2-TPR, pyridine-IR, DRIFT, and O2-TP-Ms. Experimental results revealed that the Brønsted/Lewis (B/L) ratio of MnxCe1-xO2/HZSM-5 catalysts could be adjusted by ion exchange of H• in HZSM-5 with Mnn+ (where the exchange with Ce4+ did not distinctly affect the acidity); the long-term aged catalysts could accumulate ca. 14 organic compounds at surface, which included highly toxic tetrachloromethane, trichloroethylene, tetrachloroethylene, o-Dichlorobenzene, etc.; high humid operational environment could ensure a stable performance for MnxCe1-xO2/HZSM-5 catalysts; this was due to the effective removal of Cl• and coke accumulations by H2O washing, and the distinct increase of Lewis acidity by the interaction of H2O with HZSM-5. This work gives an in-depth view into the CB oxidation over acidic solid-supported catalysts and might provide practical guidelines for the rational design of reliable catalysts for industrial applications.

Tumor Associated with CD70 Expression is Involved in Promoting Tumor Migration and Macrophage Infiltration in GBM.

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth, and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM. This article is protected by copyright. All rights reserved.

Pressure-Enabled Synthesis of Hetero-Dimers and Hetero-Rods through Intraparticle Coalescence and Interparticle Fusion of Quantum-Dot-Au Satellite Nanocrystals.

This report presents the fabrication and pressure-driven processing of heterostructural nanocrystal superlattices (HNC-SLs) self-assembled from quantum-dot-Au (QD-Au) satellite-type HNCs. In situ small/wide-angle X-ray scattering and electron microscopic measurements showed that the HNC-SLs underwent structural transformation at both atomic- and mesoscales during the pressure processing. Upon deviatoric stress-driven orientational migration, the intraparticle coalescence of Au satellites at QD surfaces transforms individual HNCs into heterodimers, whereas the interparticle fusion drives assembled HNCs into ordered heterorod arrays. These results demonstrate high-pressure-processing as a clean and fast means for conversion of HNCs into novel heteromaterials that are difficult to achieve through conventional synthetic routes.

Prognostic value of Notch receptors in postsurgical patients with hepatitis B virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and a major cause of cancer involved death worldwide. Prognosis remains poor because of high recurrence rates and lack of effective relapse prevention strategies. Notch pathway plays an important role in tumor progression and metastasis, and it is associated with the prognosis of cancer. A total of 465 hepatitis B virus (HBV)-related HCC patients who underwent surgery were enrolled. Single nucleotide polymorphisms (SNP) of Notch pathway receptors were genotyped using Sanger DNA sequencing. Kaplan-Meier curves and the Cox proportional hazards regression model were adopted to analyze the association of polymorphisms and mRNA expression with clinical and pathological features, respectively. Four SNPs (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) were significantly associated with overall survival (OS) (P = 0.023, P = 0.042, P = 0.028, and P = 0.001 respectively). Patients carrying the AA genotype in rs1043996 and TT/TC genotypes in rs422951 and rs520692 significantly decreased risks of death, compared to those carrying the AG/GG genotype in rs1043996 and CC genotype in rs422951 and rs520692, respectively. Patients carrying the TT genotype in rs3830041 showed poorer OS, compared with those carrying the TC/CC genotype. A haplotype block (rs422951 was in strong LD with rs520692, r(2)  = 0.843) was identified in Notch4. Notch3 mRNA expression significantly increased in tumor tissue, compared with nontumor normal tissue (P < 0.0001). Moreover, higher expression of Notch3 was associated with poorer OS (HR = 2.11, 95% CI = 1.32-3.37, P = 0.002) and shorter recurrence time of HBV-related HCC (HR = 1.96, 95% CI = 1.31-2.93, P = 0.001). Our findings collectively indicate that Notch receptors variants (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) are independent predictive targets for OS in HBV-related HCC patients. Notch3 expression is a potential prognostic biomarker of OS and recurrence-free survival (RFS) prediction in HBV-related HCC patients following surgical treatment.

Safety and Efficacy Study of an Ozone Laser Combined Therapy Using Puncture Needle in the Treatment of Patients With Cervical Spondylosis.

Fifty-eight patients with cervical spondylosis (CS) were treated with patented technology of ozone laser combined therapy using puncture needle between August 2008 and February 2010. Visual Analogue Scale (VAS) score changes before and 6 months after surgery and MacNab score criteria 6 months after surgery were analyzed.

NF90 regulates PARP1 mRNA stability in hepatocellular carcinoma.

Poly (ADP-ribose) polymerase 1 (PARP1) is an ADP- ribosylation enzyme and plays important roles in a variety of cellular processes, including DNA damage response and tumor development. However, the post-transcriptional regulation of PARP1 remains largely unknown. In this study, we identified that the mRNA of PARP1 is associated with nuclear factor 90 (NF90) by RNA immunoprecipitation plus sequencing (RIP-seq) assay. The mRNA and protein levels of PARP1 are dramatically decreased in NF90-depleted cells, and NF90 stabilizes PARP1's mRNA through its 3'UTR. Moreover, the expression levels of PARP1 and NF90 are positively correlated in hepatocellular carcinoma (HCC). Finally, we demonstrated that NF90-depleted cells are sensitive to PARP inhibitor Olaparib (AZD2281) and DNA damage agents. Taken together, these results suggest that NF90 regulates PARP1 mRNA stability in hepatocellular carcinoma cells, and NF90 is a potential target to inhibit PARP1 activity.

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).

New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with Au(I)-MPO, a novel gold inhibitor, together with inhibition assays were performed.

Caspase polymorphisms and prognosis of hepatocellular carcinoma.

The aim of our study was to determine the impact of genetic polymorphisms in the caspase (CASP) genes on prognosis of hepatocellular carcinoma (HCC). We genotyped 7 potentially functional polymorphisms in CASP3, CASP7, CASP8, CASP9, CASP10 genes in 362 HCC patients of receiving surgical resection of HCC tumor. The associations of genotype and haplotype with overall survival (OS) and disease free survival (DFS) were analyzed by using the Cox proportional hazards model. We found that the CASP9 rs4645981 C allele was significantly associated with positive effect on DFS (P = 0.011 and 0.016 for CT+CC vs. TT in univariate and multivariate analysis, respectively), CT genotype was associated with a better OS of HCC than the TT genotype both in univariate and multivariate analysis (P = 0.048 and 0.041, respectively). Moreover, the CASP3 rs2705897 GT genotype showed marginally significant association with decreased OS and DFS, compared with the GG genotype. One haplotype TT/TG in CASP3 (constructed by rs12108497 T>C and rs2705897 T>G) was significantly associated with decreased OS and DFS, compared to the common haplotype TT/TT both in univariate analysis (P = 0.021 and 0.026, respectively) and multivariate analysis (P = 0.025 and 0.030, respectively). The haplotype GT/GT in CASP9 (constructed by rs4645978 A>G and rs4645981 C>T) was significantly associated with decreased DFS both in univariate and multivariate analysis (P = 0.012 and 0.010, respectively). In conclusion, the CASP9 rs4645981 polymorphism, CASP3 and CASP9 haplotypes may be useful prognosis markers for HCC patients with surgical resection of tumor.

Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate cancer.

Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one of the most frequently mutated genes in primary prostate cancer, suggesting SPOP is a potential driver of prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. ER-localized isoform of the formin protein inverted formin 2 (INF2) mediates actin polymerization at ER-mitochondria intersections and facilitates DRP1 recruitment to mitochondria, which is a critical step in mitochondrial fission. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. INF2 mutant escaping from SPOP-mediated ubiquitination is more potent in prompting mitochondrial fission. Moreover, prostate cancer-associated SPOP mutants increase INF2 localization in ER and promote mitochondrial fission, probably through a dominant-negative effect to inhibit endogenous SPOP. Moreover, INF2 is important for SPOP inactivation-induced prostate cancer cell migration and invasion. These findings reveal novel molecular events underlying the regulation of INF2 function and localization, and provided insights in understanding the relationship between SPOP mutations and dysregulation of mitochondrial dynamics in prostate cancer.

miR‑196a‑5p modulates gastric cancer stem cell characteristics by targeting Smad4.

Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self-renewal, and a multilineage differentiation potential. Clinical evidence suggests that CSCs in a tumor mass are the cellular determinants to promote cancer invasion and metastasis. MicroRNAs (miRNAs) have emerged as important modulators of cancer stem cell characteristics. Unveiling the candidate miRNAs that regulate CSCs may provide novel therapeutic targets against cancer. We analyzed the miRNA expression profiles regulating the cancer stem-like cell characteristics in gastric cancer. Gastric cancer stem cells (GCSCs) were sorted using the stem cell marker CD44 by fluorescence-activated cell sorting. Functional studies revealed that CD44(+) cells formed more sphere colonies and showed higher invasiveness than CD44(-) cells. miRNA microarray analysis revealed that miR‑196a‑5p was significantly upregulated in CD44(+) cells than CD44(-) cells. Suppression of miR‑196a‑5p led to decreased colony formation and invasion of GCSCs. miR‑196a‑5p decreased the expression of Smad4 by targeting 3'-UTR of the mRNA. The expression of Smad4 in gastric cancer tissues was correlated with differentiation state of tumors, TNM stage and depth of invasion. The stimulation of epithelial-mesenchymal transition (EMT) by miR‑196a‑5p in cancer stem-like cells was abolished by overexpression of Smad4. Collectively, these data demonstrate that miR‑196a‑5p has a key role in EMT and invasion by targeting Smad4 in GCSCs. miR‑196a‑5p may serve as a potential target for gastric cancer therapy.

Activated Notch signaling augments cell growth in hepatocellular carcinoma via up-regulating the nuclear receptor NR4A2.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional therapies are limited due to the human liver being such a unique organ and easily showing side-effects. The unclear molecular mechanisms are tough challenges for scientists searching for new and effective anti-HCC targeting drugs. We identified that the nuclear receptor NR4A2 is a novel oncogene in HCC progression. In this study, we show that NR4A2 and the notch recceptor Notch1 were expressed highly in primary HCC tissues and immortal HCC cells by using qPCR, western blot and immuno-histochemistry assays. Both genes were observed to stimulate HCC cell proliferation, anti-apoptosis and cell cycle arrest by using cell proliferation assays and FACS assays. We also observed that the four notch receptor subtypes (Notch1-4) displayed different effects on HCC cell growth. The over-expression of Notch1 by transiently transfecting the intracellular domain of Notch1 (ICN1, Notch1 active form) increased the expression of NR4A2, with the knockdown of Notch1 decreasing NR4A2. This indicates that NR4A2 is one of the Notch-mediated downstream genes. Moreover, both NR4A2 and Notch1 suppressed the expression of tumor suppressors p21 and p63. These findings support that Notch1/NR4A2 co-regulate HCC cell functions by playing oncogenic roles and regulating the associated downstream signaling pathways. Novel Notch1/NR4A2-mediated oncogenic signaling may provide us a great opportunity for anti-HCC drug development.

PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy.

Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum α-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level ≥ 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.

Probable pulmonary Blastomyomycocis in an immunocompetent person.

The current case report presents a 29-year old man who worked as a hotel guard in a city in China. The patient had fever and dry cough before and after hospitalization. Chest X-ray and CT revealed nodular and patchy lesions in both lower lungs. There were no abnormal findings in the examination of sputum and bronchoalveoular lavage fluid (BALF). He was diagnosed with pulmonary blastomycosis by histological examination of lung biopsy and treated with fluconazole. Follow-up chest CT examination demonstrated that the patient was recovered through appropriate antifungal treatment.

Multi-layer mucilage of Plantago ovata seeds: Rheological differences arise from variations in arabinoxylan side chains.

Mucilages are hydrocolloid solutions produced by plants for a variety of functions, including the creation of a water-holding barrier around seeds. Here we report our discovery of the formation of three distinct mucilage layers around Plantago ovata seeds upon their hydration. Each layer is dominated by different arabinoxylans (AXs). These AXs are unusual because they are highly branched and contain β-1,3-linked xylose in their side chains. We show that these AXs have similar monosaccharide and linkage composition, but vary in their polymer conformation. They also exhibit distinct rheological properties in aqueous solution, despite analytical techniques including NMR showing little difference between them. Using enzymatic hydrolysis and chaotropic solvents, we reveal that hydrogen bonding and side chain distribution are key factors underpinning the distinct rheological properties of these complex AXs.

Association of native T1 times with biventricular function and hemodynamics in precapillary pulmonary hypertension.

In precapillary pulmonary hypertension (PH) patients, we sought to (1) investigate the relationship between ventricular insertion point (VIP) T1 times, hemodynamic parameters, and biventricular function, and (2) determine the predictors of anterior and inferior VIP T1 time. Twenty-two patients with precapillary PH underwent 1.5-T cardiac MR, right heart catheterization (RHC), and echocardiography. A group of 10 healthy age- and sex-matched volunteers served as controls. Biventricular function, morphology and mass were obtained from short-axis cine images. Native T1 times at anterior, inferior VIP, septum and LV lateral wall were respectively derived from all subjects. Mixed venous oxygen saturation (SvO2) was the strongest hemodynamic parameters correlating with anterior (rp = -0.67, P = 0.001) and inferior VIP T1 time (rp = -0.81, P < 0.001). Elevated VIP T1 times were associated with reduced right ventricular (RV) ejection fraction, RV longitudinal and transverse motion, and increased RV end-diastolic and end-systolic volume index. LV diastolic function, quantified as mitral E velocity, was negatively correlated with anterior, inferior VIP (rp = -0.55, P = 0.01) and septal T1 times (rp = -0.50, P = 0.02), and positively correlated with RV systolic function and wall motion. In multivariate linear regression analyses, systolic eccentricity index (sEI) was the independent predictor of average VIPs T1 time (β= 0.47, P < 0.01), and remained significant correlation after adjustment of RHC and demographic parameters. In patients with precapillary PH, VIP T1 times are associated with biventricular function and hemodynamic parameters. Among all the parameters, sEI acts as a determinant of average VIPs T1 time.

In-Depth Analysis of Glycoprotein Sialylation in Serum Using a Dual-Functional Material with Superior Hydrophilicity and Switchable Surface Charge.

Sialylation typically occurs at the terminal of glycans, and its aberration often correlates with diseases including neurological diseases and cancer. However, the analysis of glycoprotein sialylation in complex biological samples is still challenging due to their low abundance. Herein, a histidine-bonded silica (HBS) material with a hydrophilic interaction and switchable surface charge was fabricated to enrich sialylated glycopeptides (SGPs) from the digest of proteomics samples. High selectivity toward SGPs was obtained by combining the superior hydrophilicity and switchable-charge characteristics. During the enrichment of sialylated glycopeptides from bovine fetuin digest, seven glycopeptides were detected even at the ratio of 1:5000 with the nonsialylated glycopeptides, demonstrating the high specificity of SGP enrichment by using HBS material. Then, HBS material was further utilized to selectively enrich SGPs from the protein digest of human serum, and 487 glycosites were identified from only 2 μL of human serum; 92.0% of the glycopeptides contained at least one sialic acid, indicating good performance for SGP enrichment by using HBS material. Furthermore, the prepared HBS material also has great potential applications in the analysis of glycoprotein sialylation from other complex biological samples.

Distinctive morphology effects of porous-spherical/yolk-shell/hollow Pd-nitrogen-doped-carbon spheres catalyst for catalytic reduction of 4-nitrophenol.

Pd-nitrogen-doped-carbon nanocatalysts (Pd-C/N) with different morphologies, such as porous spheres, yolk-shell and hollow structures, had been synthesized and compared. The yolk-shell Pd-nitrogen-doped-carbon nanocatalysts (YS-Pd-C/N) and hollow Pd-nitrogen-doped-carbon nanocatalysts (H-Pd-C/N) were prepared through different etch time using SiO2 spheres as hard-templates. The as-prepared catalysts were characterized thoroughly by TEM, BET, XRD, FT-IR, and XPS. Importantly, the catalysts have moderate BET specific surface area in the range from 200 to 300m(2)g(-1) and pore volume between 0.2 and 0.3cm(3)g(-1). The reduction of 4-nitrophenol is chosen as a model reaction to research the morphology effects of these prepared Pd-C/N catalysts with the same chemical compositions. Interestingly, H-Pd-C/N exhibited the best catalytic performance, which could be attributed to its high nitrogen content, the uniform distribution of abundant active sites, as well as the synergistic effect of graphitic C/N shell and Pd species for the catalytic reaction. Especially, the unique hollow morphology and porous shell of H-Pd-C/N made it to be a nanoreactor, which was beneficial to improve the catalytic activities. In addition, H-Pd-C/N nanocatalysts exhibited favorable stability in the recycling reactions.

Reconfigurable Photonic Crystals Enabled by Multistimuli-Responsive Shape Memory Polymers Possessing Room Temperature Shape Processability.

Traditional shape memory polymers (SMPs) are mostly thermoresponsive, and their applications in nano-optics are hindered by heat-demanding programming and recovery processes. By integrating a polyurethane-based shape memory copolymer with templating nanofabrication, reconfigurable/rewritable macroporous photonic crystals have been demonstrated. This SMP coupled with the unique macroporous structure enables unusual all-room-temperature shape memory cycles. "Cold" programming involving microscopic order-disorder transitions of the templated macropores is achieved by mechanically deforming the macroporous SMP membranes. The rapid recovery of the permanent, highly ordered photonic crystal structure from the temporary, disordered configuration can be triggered by multiple stimuli including a large variety of vapors and solvents, heat, and microwave radiation. Importantly, the striking chromogenic effects associated with these athermal and thermal processes render a sensitive and noninvasive optical methodology for quantitatively characterizing the intriguing nanoscopic shape memory effects. Some critical parameters/mechanisms that could significantly affect the final performance of SMP-based reconfigurable photonic crystals including strain recovery ratio, dynamics and reversibility of shape recovery, as well as capillary condensation of vapors in macropores, which play a crucial role in vapor-triggered recovery, can be evaluated using this new optical technology.

Vibrational Signatures of Isomeric Lithiated N-acetyl-D-hexosamines by Gas-Phase Infrared Multiple-Photon Dissociation (IRMPD) Spectroscopy.

Three lithiated N-acetyl-D-hexosamine (HexNAc) isomers, N-acetyl-D-glucosamine (GlcNAc), N-acetyl-D-galactosamine (GalNAc), and N-acetyl-D-mannosamine (ManNAc) are investigated as model monosaccharide derivatives by gas-phase infrared multiple-photon dissociation (IRMPD) spectroscopy. The hydrogen stretching region, which is attributed to OH and NH stretching modes, reveals some distinguishing spectral features of the lithium-adducted complexes that are useful in terms of differentiating these isomers. In order to understand the effect of lithium coordination on saccharide structure, and therefore anomericity, chair configuration, and hydrogen bonding networks, the conformational preferences of lithiated GlcNAc, GalNAc, and ManNAc are studied by comparing the experimental measurements with density functional theory (DFT) calculations. The experimental results of lithiated GlcNAc and GalNAc show a good match to the theoretical spectra of low-energy structures adopting a (4) C 1 chair conformation, consistent with this motif being the dominant conformation in condensed-phase monosaccharides. The epimerization effect upon going to lithiated ManNAc is significant, as in this case the (1) C 4 chair conformers give a more compelling match with the experimental results, consistent with their lower calculated energies. A contrasting computational study of these monosaccharides in their neutral form suggests that the lithium cation coordination with Lewis base oxygens can play a key role in favoring particular structural motifs (e.g., a (4) C 1 versus (1) C 4 ) and disrupting hydrogen bond networks, thus exhibiting specific IR spectral features between these closely related lithium-chelated complexes. Graphical Abstract ᅟ.

Monoclonal antibodies targeting non-small cell lung cancer stem-like cells by multipotent cancer stem cell monoclonal antibody library.

Cancer stem cells (CSCs) are a rare subset of cancer cells that play a significant role in cancer initiation, spreading, and recurrence. In this study, a subpopulation of lung cancer stem-like cells (LCSLCs) was identified from non-small cell lung carcinoma cell lines, SPCA-1 and A549, using serum-free suspension sphere-forming culture method. A monoclonal antibody library was constructed using immunized BLAB/c mice with the multipotent CSC cell line T3A-A3. Flow cytometry analysis showed that 33 mAbs targeted antigens can be enriched in sphere cells compared with the parental cells of SPCA-1 and A549 cell lines. Then, we performed functional antibody screening including sphere-forming inhibiting and invasion inhibiting assay. The results showed that two antibodies, 12C7 and 9B8, notably suppressed the self-renewal and invasion of LCSLCs. Fluorescence-activated cell sorting (FACs) found that the positive cells recognized by mAbs, 12C7 or 9B8, displayed features of LCSLCs. Interestingly, we found that these two antibodies recognized different subsets of cells and their combination effect was superior to the individual effect both in vitro and in vivo. Tissue microarrays were applied to detect the expression of the antigens targeted by these two antibodies. The positive expression of 12C7 and 9B8 targeted antigen was 84.4 and 82.5%, respectively, which was significantly higher than that in the non-tumor lung tissues. In conclusion, we screened two potential therapeutic antibodies that target different subsets of LCSLCs.

The Pharmacological Heterogeneity of Nepenthone Analogs in Conferring Highly Selective and Potent κ-Opioid Agonistic Activities.

To develop novel analgesics with no side effects or less side effects than traditional opioids is highly demanded to treat opioid receptor mediated pain and addiction issues. Recently, κ-opioid receptor (KOR) has been established as an attractive target, although its selective agonists could bear heterogeneous pharmacological activities. In this study, we designed and synthesized two new series of nepenthone derivatives by inserting a spacer (carbonyl) between 6α,14α-endo-ethenylthebaine and the 7α-phenyl substitution of the skeleton and by substituting the 17-N-methyl group with a cyclopropylmethyl group. We performed in vitro tests (binding and functional assays) and molecular docking operations on our newly designed compounds. The results of wet-experimental measures and modeled binding structures demonstrate that these new compounds are selective KOR agonists with nanomolar level affinities. Compound 4 from these new derivatives showed the highest affinity (Ki = 0.4 ± 0.1 nM) and the highest selectivity (μ/κ = 339, δ/κ = 2034) toward KOR. The in vivo tests revealed that compound 4 is able to induce stronger (ED50 = 2.1 mg/kg) and much longer antinociceptive effect than that of the typical KOR agonist U50488H (ED50 = 4.4 mg/kg). Therefore, compound 4 can be used as a perfect lead compound for future design of potent analgesics acting through KOR.

An improved approach for evaluating the semicrystalline lamellae of starch granules by synchrotron SAXS.

A fitting method combined with a linear correlation function was developed as an improved approach for the SAXS analysis of the semicrystalline lamellae of starch granules. Using a power-law function with two Gaussian plus Lorentz functions, the SAXS pattern was resolved into sub-patterns of the net lamellar peak and the power-law scattering plus scattering background (PL+B). The ratio of the net lamellar peak area (Apeak) to the total scattering area (Atotal) was proposed equal to the proportion of the lamellae within the starch granule (PSL). Along with this fitting method, we obtained a better profile of linear correlation function, with the elimination of the interference of non-lamellar amorphous starch (i.e., amorphous growth rings). Then, we could accurately calculate the lamellar parameters, e.g., PSL, the thicknesses of semicrystalline (d), crystalline (dc) and amorphous (da) lamellae, and the volume fraction (φc) of crystalline lamellae within semicrystalline lamellae. Quantitative analysis revealed that PSL was positively correlated with the crystallinity (Xc) of starch. It was confirmed that the distribution of lamellar thickness was more important than the starch botanical origin in affecting the validity of the developed fitting method. We also proposed a criterion to test the validity of the proposed method. Specifically, the total SAXS pattern should be mostly tangent to the profile of PL+B at a high q tail (close to 0.2Å(-1)).

CNGC2 Is a Ca2+ Influx Channel That Prevents Accumulation of Apoplastic Ca2+ in the Leaf.

Ca(2+) is absorbed by roots and transported upward through the xylem to the apoplastic space of the leaf, after which it is deposited into the leaf cell. In Arabidopsis (Arabidopsis thaliana), the tonoplast-localized Ca(2+)/H(+) transporters CATION EXCHANGER1 (CAX1) and CAX3 sequester Ca(2+) from the cytosol into the vacuole, but it is not known what transporter mediates the initial Ca(2+) influx from the apoplast to the cytosol. Here, we report that Arabidopsis CYCLIC NUCLEOTIDE-GATED CHANNEL2 (CNGC2) encodes a protein with Ca(2+) influx channel activity and is expressed in the leaf areas surrounding the free endings of minor veins, which is the primary site for Ca(2+) unloading from the vasculature and influx into leaf cells. Under hydroponic growth conditions, with 0.1 mm Ca(2+), both Arabidopsis cngc2 and cax1cax3 loss-of-function mutants grew normally. Increasing the Ca(2+) concentration to 10 mm induced H2O2 accumulation, cell death, and leaf senescence and partially suppressed the hypersensitive response to avirulent pathogens in the mutants but not in the wild type. In vivo apoplastic Ca(2+) overaccumulation was found in the leaves of cngc2 and cax1cax3 but not the wild type under the 10 mm Ca(2+) condition, as monitored by Oregon Green BAPTA 488 5N, a low-affinity and membrane-impermeable Ca(2+) probe. Our results indicate that CNGC2 likely has no direct roles in leaf development or the hypersensitive response but, instead, that CNGC2 could mediate Ca(2+) influx into leaf cells. Finally, the in vivo extracellular Ca(2+) imaging method developed in this study provides a new tool for investigating Ca(2+) dynamics in plant cells.

ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance.

Prognostic significance of pretreatment elevated platelet count in patients with colorectal cancer: a meta-analysis.

The prognostic effect of pretreatment elevated platelet count remains controversial in colorectal cancer patients. We conducted this meta-analysis to evaluate the prognostic impact of it in these patients.

Tumor endothelial cells promote metastasis and cancer stem cell-like phenotype through elevated Epiregulin in esophageal cancer.

Tumor endothelial cells have been found to be associated with metastasis and cancer progression. In this study, we reported that human esophageal cancer endothelial cells (HECEC), unlike corresponding human esophageal normal endothelial cells (HENEC) displayed several distinct feature couple with unique gene expression profile. Further studies showed that HECEC can enhance migration, invasion and self-renewal properties of esophageal carcinoma cell in vitro by a direct cell-cell interaction. In vivo assay demonstrated that HECEC could significantly enhance the invasion and lung metastasis of esophageal cancer cells. To elucidate the molecular mechanisms of HECEC in esophageal carcinoma progression, we employed the microarray to analyze the gene expression profiles before and after treating with HECEC, HENEC or conditioned meium from HECEC. Among the highly expressed HECEC-regulated genes, we focused on Epiregulin (EREG). Further studies demonstrated that overexpression of EREG in EC9706 or Kyse30 cells can induce actin reorganization, sphere formation ability and a significantly enrichment of CD44(+) cancer stem-like cells. Moreover, up-regulation of EREG in esophageal cancer cells could enhance lung metastasis and decrease the survival time in vivo. Further study indicated that EREG could induce activation of the Src and FAK. In addition, all these effects could also be inhibited by the function-blocking anti-EREG antibody in a dose dependent manner. Immunohistochemical analysis revealed that high level of EREG was significantly correlated with lymph node metastases and poor prognosis. In summary, HECEC play key roles in enhancing the invasion, migration, cancer stem cell phenotype and metastatic potential of esophageal cancer cells through Epiregulin.

Noninvasive Imaging of Human Atrial Activation during Atrial Flutter and Normal Rhythm from Body Surface Potential Maps.

Knowledge of atrial electrophysiological properties is crucial for clinical intervention of atrial arrhythmias and the investigation of the underlying mechanism. This study aims to evaluate the feasibility of a novel noninvasive cardiac electrical imaging technique in imaging bi-atrial activation sequences from body surface potential maps (BSPMs).

E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation.

RNF12/RLIM is a RING domain-containing E3 ubiquitin ligase whose function has only begun to be elucidated recently. Although RLIM was reported to play important roles in some biological processes such as imprinted X-chromosome inactivation and regulation of TGF-β pathway etc., other functions of RLIM are largely unknown. Here, we identified RLIM as a novel E3 ubiquitin ligase for c-Myc, one of the most frequently deregulated oncoproteins in human cancers. RLIM associates with c-Myc in vivo and in vitro independently of the E3 ligase activity of RLIM. Moreover, RLIM promotes the polyubiquitination of c-Myc protein independently of Ser62 and Thr58 phosphorylation of c-Myc. However, RLIM-mediated ubiquitination does not affect c-Myc stability. Instead, RLIM inhibits the transcriptional activity of c-Myc through which RLIM restrains cell proliferation. Our results suggest that RLIM may function as a tumor suppressor by controlling the activity of c-Myc oncoprotein.