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Fluorescent organic dots (O-dots) recently have emerged as a new class of promising contrast reagents for two-photon fluorescence (TPF) imaging. However, most of these developed two-photon absorption (TPA) O-dots have no tumor-targeting group, which hampers their wide application for targeted tumor imaging. Herein, we fabricated Sgc8c aptamer-mediated TPA O-dots as a proof-of-concept of the sensing platform for targeted imaging in live cells or deep tissues. The O-dots composed of trans -4-[p-(N, N-diethylamino)styryl]-4'-(dimethyl amino) stilbene (DEAS) emerged as TPA organic emissive cores and encapsulation by using poly (methyl methacrylate-co-methacrylic acid) (PMMA-co-MAA) as polymeric encapsulating matrix to form DEAS/PMMA-co-MAA O-dots via a co-precipitation strategy. The obtained O-dots enabled an extremely high TPA absorption cross-section, bright two-photon fluorescence (excitation at 720 nm; emission at 412 nm and 434 nm), excellent cell-permeability and high penetration depth. Sgc8c aptamer, as a protein tyrosine kinase-7 (PTK7) receptor-targetable ligand, was further anchored on the surface of O-dots to obtain DEAS/PMMA-co-MAA@Sgc8c nanoprobes by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)-mediated coupling reaction. Guided by Sgc8c aptamer, DEAS/PMMA-co-MAA@Sgc8c nanoprobes could be rapidly internalized into target acute lymphoblastic leukemia cells (CEM) cells with high specificity and great efficiency. It was also performed that two-photon images of TPA nanoprobes exhibited high two-photon brightness not only in target CEM cells, but also in mouse liver tissue slices even a depth of up to 210 μm. In our perception, it is highly promising that this nanoprobe provides a valuable tool for in vivo targeted imaging. Image 1 • A versatile and scalable strategy to aptamer-modified two-photon DEAS/PMMA-co-MAA O-dots for targeted imaging was proposed. • The DEAS/PMMA-co-MAA O-dots enabled higher two-photon brightness (45-fold enhancement). • Sgc8c acts as a tumor-specific ligand is introduced to TP nanoprobes, applying for precision targeting and imaging in cells. • This novel targeted nanoprobes was capable of two-photon imaging up to 210 μm in liver tissue slices. [ABSTRACT FROM AUTHOR]

A growing number of molecular epidemiological studies have been conducted to evaluate the association between human papillomavirus (HPV) infection and the malignancy of sinonasal inverted papilloma (SNIP). However, the results remain inconclusive. Here, a meta -analysis was conducted to quantitatively assess this association. Case-control studies investigating SNIP tissues for presence of HPV DNA were identified. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method. An assessment of publication bias and sensitivity analysis were also performed. We calculated a pooled OR of 2.16 (95% CI = 1.46–3.21, P < 0.001) without statistically significant heterogeneity or publication bias. Stratification by HPV type showed a stronger association for patients with high-risk HPV (hrHPV) types, HPV-16, HPV-18, and HPV-16/18 infection (OR = 8.8 [95% CI: 4.73–16.38], 8.04 [95% CI: 3.34–19.39], 18.57 [95% CI: 4.56–75.70], and 26.24 [4.35–158.47], respectively). When only using PCR studies, pooled ORs for patients with hrHPV, HPV-16, and HPV18 infection still reached statistical significance. However, Egger’s test reflected significant publication bias in the HPV-16 sub-analysis (P = 0.06), and the adjusted OR was no longer statistically significant (OR = 1.65, 95%CI: 0.58–4.63). These results suggest that HPV infection, especially hrHPV (HPV-18), is significantly associated with malignant SNIP. [ABSTRACT FROM AUTHOR]

A variety of non-noble electrocatalysts (Fe(III)Nx/C and Fe(II)N6/C) have been fabricated by pyrolyzing nitrogen-rich compounds (ethylenediamine, tetraethylenepetamine and pentaethylenehexamine) and iron precursors (iron(III) chloride and iron(II) ammonium sulphate) on carbon blacks (Vulcan XC-72) in a nitrogen atmosphere. The catalytic performance (activity and durability) toward oxygen reduction reaction (ORR) is comparatively examined by rotating disk electrode and chronoamperometric techniques. The results show that nitrogen precursors play a crucial role on the chemical microstructure and performance of electrocatalysts. The influence of various nitrogen and iron precursors on the properties of electrocatalysts has been analyzed by X-ray based spectroscopies including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS). Among all the Fe(III)Nx/C and Fe(II)N6/C catalysts, Fe(III)N6/C catalysts which pentaethylenehexamine and iron(III) chloride are used as starting precursors possess the superior electrocatalytic ORR activity and durability probably due to their higher surface Fe/C and N/C atomic ratios with the pyridinic-N and quaternary-N active sites for the formation of the FeN4 species, as verified by XPS and XAS analyses. [ABSTRACT FROM AUTHOR]

Serine-rich repeat glycoproteins identified from streptococci and staphylococci are important for bacterial adhesion and biofilm formation. Two putative glycosyltransferases, Gtf1 and Gtf2, from Streptococcus parasanguinis form a two-protein enzyme complex that is required for glycosylation of a serine-rich repeat adhesin, Fap1. Gtf1 is a glycosyltransferase; however, the function of Gtf2 is unknown. Here, we demonstrate that Gtf2 enhances the enzymatic activity of Gtf1 by its chaperone-like property. Gtf2 interacted with Gtf1, mediated the subcellular localization of Gtf1, and stabilized Gtf1. Deletion of invariable amino acid residues in a conserved domain of unknown function (DUF1975) at the N terminus of Gtf2 had a greater impact on Fap1 glycosylation than deletion of the C-terminal non-DUF1975 residues. The DUF1975 deletions concurrently reduced the interaction between Gtf1 and Gtf2, altered the subcellular localization of Gtf1, and destabilized Gtf1, suggesting that DUF1975 is crucial for the chaperone activity of Gtf2. Homologous GtfA and GtfB from Streptococcus agalactiae rescued the glycosylation defect in the gtf1gtf2 mutant; like Gtf2, GtfB also possesses chaperone-like activity. Taken together, our studies suggest that Gtf2 and its homologs possess the conserved molecular chaperone activity that mediates protein glycosylation of bacterial adhesins. [ABSTRACT FROM AUTHOR]

Abstract: In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10μM PAN-811 (an optimal neuroprotective concentration) for 1h, 4h, or 24h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection. [Copyright &y& Elsevier]

Abstract: Cellular injury can involve the aberrant stimulation of cell cycle proteins in part through activation of phosphodiesterases (PDEs) and downstream expression of cell-cycle components such as cyclin D1. In mature non-proliferating cells activation of the cell cycle can lead to the induction of programmed cell death. In the present study, we investigated the in vitro neuroprotective efficacy and mechanism of action of vinpocetine (PDE1 inhibitor), trequinsin (PDE3 inhibitor), and rolipram (PDE4 inhibitor) in four mechanistically-distinct models of injury to primary rat cortical neurons as related to cell cycle regulation and apoptosis. Cellular injury was induced by hypoxia/hypoglycemia, veratridine (10μM), staurosporine (1μM), or glutamate (100μM), resulting in average neuronal cell death rates of 43–48% as determined by MTT assay. Treatment with each PDE inhibitor (PDEI) resulted in a similar concentration-dependent neuroprotection profile with maximal effective concentrations of 5–10μM (55–77% neuroprotection) in all four neurotoxicity models. Direct cytotoxicity due to PDE inhibition alone was not observed at concentrations below 100μM. Further studies indicated that PDEIs can suppress the excitotoxic upregulation of cyclin D1 similar to the effects of flavopiridol, a cyclin-dependent kinase inhibitor, including suppression of pro-apoptotic capase-3 activity. Overall, these data indicate that PDEIs are broad-spectrum neuroprotective agents acting through modulation of cell cycle elements and may offer a novel mode of therapy against acute injury to the brain. [Copyright &y& Elsevier]

We have found that several aliphatic and alicyclic diols induce melanogenesis in cultured S91 mouse melanoma cells and normal human epidermal melanocytes (NHEM). In addition, these compounds induce melanogenesis when applied to guinea pig skin, with transfer of melanin to keratinocytes and formation of “supranuclear caps,” as occurs in naturally pigmented skin. The relative order of potency of some of these diols in NHEM is 5‐norbornene‐2,2‐dimethanol bg 3,3‐dimethyl‐1,2‐butanediol bg cis‐1,2‐cyclopentanediol bg 2,3‐dimethyl‐2,3‐butanediol bg 1,2‐propanediol. Following treatment with these diols or 3‐isobutyl‐1‐methylxanthine, melanin and tyrosinase activity are increased within S91 cells and NHEM; however, for cultured NHEM, the largest increases of melanin and tyrosinase occur in an extracellular particulate fraction, shown by electron microscopy to consist almost entirely of stage III and IV melanosomes. These results indicate that cultured NHEM treated with diols export melanosomes in a fashion that is commensurate with natural melanogenic processes. In contrast, S91 mouse melanoma cells exhibit aberrant melanosomal trafficking, in accordance with the known defect in myosin‐V mediated melanosomal transport. Both S91 cells and NHEM exhibit morphologic changes and growth arrest indicative of differentiation following treatment with diols. The diols described in this report are candidates for use as cosmeceutical tanning agents. [ABSTRACT FROM AUTHOR]

Near field inter-body coupling communication (NF-IBCC) is a short-distance wireless communication centered on the human body. It uses the electric field within close proximity of the human body to establish a channel, when electrodes as a radiation source keep in contact with the human body. NF-IBCC can achieve much higher data security and lower power consumption than traditional radio frequency communications, which is a potential communication technology applied to the internet of body (IoB). However, its channel model is not totally clear so far. In this letter, we propose a channel model. Then, the accuracy of the proposed model is verified. Finally, the effect of distances, postures, angles, and heights on the channel characteristics is analyzed and discussed. Our work lays a theoretical foundation for the system design of NF-IBCC and will promote its application to IoB. [ABSTRACT FROM AUTHOR]

Background: With the significant improvement of the cure rate and survival rate of cancer patients, the survivors face quality-of-life problems, such as a significant decline in reproductive system development, ovarian reserves and function, and even fertility loss and early menopause. These problems are often highly associated with chemotherapy-induced ovarian damage in cancer treatment. However, there are no ideal treatment strategies at present. In our attempt to develop reagents and approaches for delaying ovarian aging and protecting chemotherapy-induced ovarian injury, we recently found that metformin may be the most promising drug to protect female malignant tumor patients from chemotherapy-induced ovarian injury. This trial aims to test whether administration of metformin during chemotherapy can protect the normal ovarian function of patients with early breast cancer.Methods: This study is prospective, randomized, double-blind and placebo-controlled. Female patients with early breast cancer (N = 314) will be randomly assigned to two groups (placebo, metformin 2000 mg). Metformin will be administered during and after chemotherapy for patients with stage I-IIIa breast cancer. The primary outcome will be the menstruation recovery rate 12 months after chemotherapy, defined as recovery of menstruation twice in a row within 1 year. Patients will be followed up for 5 years to observe long-term ovarian function and prognosis, such as overall survival (OS), objective response rate (ORR), and disease-free survival (DFS). Quality of life and safety will also be assessed.Discussion: Our research will provide a new treatment strategy for fertility protection, and clinical treatment guidance for cancer patients. [ABSTRACT FROM AUTHOR]

In this paper, the Cu-76 at.% Ag multilayers without a diffusion barrier component were prepared by magnetron sputtering co-deposition. The Cu–Ag multilayers are composed of sublayers whose composition changes continuously and regularly. The hardness of co-deposited multilayers is higher than that of mixed monolayer with similar average grain size, due to the component fluctuations along the direction of membrane growth hindering dislocation movement. When the compositional modulation period is reduced from 110 nm to 11 nm, the nanoindentation hardness of co-deposited multilayers increases by 41.3% from 2.35 GPa to 3.32 GPa. Compared with the sequential-deposited multilayers with the same composition, the hardness of co-deposited multilayers is lower than that of sequential-deposited multilayers during small modulation period (λ = 11, 22 nm). At small modulation periods, the contribution of compositional gradient to hardness in co-deposited multilayers is lower than that of interface strengthening in sequential-deposited multilayers, which is attributed to the higher interfacial coherence of the co-deposited multilayers. This study proposes a novel multilayers without diffusion barrier element, further elucidate the strengthening mechanism of hardness, enriching the research of binary co-deposited multilayers material systems. • The multilayered structure formed in Cu–Ag film prepared by co-deposition. • The compositional gradient in co-deposited multilayers contributes to the improvement of nanoindentation hardness. • The higher interfacial coherence of co-deposited multilayers weakens the interface strengthening effect. [ABSTRACT FROM AUTHOR]

Abstract: Tropical diseases are serious infectious diseases caused by protozoan parasites in tropical and subtropical regions. Novel, effective, safe, and inexpensive drugs are required to treat the parasites and contribute to the global goal of eradication. A series of phenothiazinium chlorides were synthesized and evaluated for in vitro activities against Plasmodium falciparum, Trypanosoma cruzi, Trypanosoma brucei rhodesiense, and Leishmania donovani. Notably, 3,7-bis(piperidinyl)phenothiazinium chloride showed IC50 of 0.097 μmol L−1 against T. cruzi and 3,7-bis(benzyl(methyl)amino)phenothiazinium chloride exhibited IC50 of 0.081 μmol L−1 against L. donovani, although the cytotoxicities of these compounds against L-6 cells were observed at low concentration. [ABSTRACT FROM AUTHOR]

The Cu-48at.%Cr film was prepared by magnetron co-sputtering deposition technique with working pressure from 0.2 Pa to 1.5 Pa. The microstructure and nanoindentation hardness were investigated. When the working pressure decreased to 0.2 Pa, the consecutive layered structure formed. The formation of layered structure was attributed to the diffusion barrier ability of Cr element and the uphill diffusion of Cu atoms. While at higher working pressure, the sputtering particles energy near the substrate was not enough to promote the Cu diffusion. Therefore, the layered structure became indistinct as the working pressure increased. Owing to the interface strengthen, this layered structure made the nanoindentation hardness increase markedly from 4.2 GPa to 9.3 GPa as the working pressure decreased from 1.5 Pa to 0.2 Pa. This study could provide a good basis for preparing the film with specific microstructure in Cu–Cr system, even in other immiscible systems. • The layered structure formed in Cu–Cr film prepared by co-sputtering deposition. • The layered structure made the film hardness increase about twice. • Interface strengthening was the main reason for the increase of hardness. [ABSTRACT FROM AUTHOR]