Cylindrical Nanopore Electrode and Its Application to the Study of Electrochemical Reaction in Several Hundred Attoliter Volume

A method to fabricate cylindrical nanopore electrodes is presented. The volume of the cavity formed in the cylindrical nanopore electrode can be as small as several hundred attoliters. It has been characterized by using scanning electron microscopy and electrochemical methods. Our results show that the radius of the cavity can affect the diffusion coefficient of a redox species in the cavity. The cylindrical nanopore electrode has also been used to study charge transfer across the interface between an aqueous phase of several hundred attoliters in volume and a bulk chloroform phase. Compared with the same charge-transfer reaction across the interface between a bulk aqueous phase and a bulk chloroform phase, the potential of the charge-transfer reaction has a negative shift. The effect of the phase ratio on the distribution of the supporting electrolyte in the aqueous and organic phases has been used to explain the shift

Xps Study of Neutral Mixed Valence Ru Dimer: [(acac)2Ru]2(Bpz4) and Afm Study of Water Meniscus Between an Afm Tip and Nacl Substrate

This thesis consists of two parts. In the first part, X-ray photoelectron spectroscopy (XPS) was used to study a new neutral mixed valence complex: [((acac)2Ru)2B(pz)4]. XPS study of the a powder sample of the Ru dimer indicated only one group of Ru signals with binding energies close to those of RuIII in Creutz-Taube-type complexes, which suggested that the Ru dimer used was possibly oxidized RuIII/RuIII during the experiment. Surface attachment of the Ru dimer was measured on self-assembled monolayers of alkanethiols with various terminal groups. Contact angle, ellipsometry and XPS measurements suggested that the Ru dimer molecules form self-limiting monolayers on hydrophilic surfaces and not bind detectably to hydrophobic surface. Additionally, an anchoring group 4-mercaptopyrazole was studied by XPS, demonstrating that the adsorption of the molecules on gold surface is self-limiting. In the second part, water meniscus condensed between an AFM tip and a NaCl substrate was studied in various conditions, including ambient, dry nitrogen and ultra-high vacuum (UHV). Water meniscus formation was measured by probing the ability of the meniscus to dissolve the NaCl near the contact point and evaluating the pull-off point as a function of water partial pressures. These studies are consistent with the formation of water meniscus under ambient and dry conditions

Electrochemistry of Individual Molecules in Zeptoliter Volumes

Electrochemical experiments were carried out in a nanometer-sized cylindrical thin layer cell (TLC) formed by etching the surface of a disk-type platinum nanoelectrode (5- to 150-nm radius). Using high frequency ac voltage, the surface of such an electrode was etched to remove a very thin (≥1-nm-thick) layer of Pt. The resulting zeptoliter-scale cavity inside the glass sheath was filled with aqueous solution containing redox species, and the etched electrode was immersed in a dry (no external solution) pool of mercury to produce a TLC. Several approaches based on steady-state voltammetry and scanning electrochemical microscopy (SECM) were developed to independently evaluate the electrode radius and the etched volume. The number of redox molecules in the TLC could be varied between one and a few hundred by changing its volume and solution concentration. In this way, the transition between a random and deterministic number of trapped molecules was observed. High quality steady-state voltammograms of ≥1 molecules were obtained for different neutral and charged redox species and different concentrations of supporting electrolyte. The analysis of such voltammograms yields information about mass transfer, adsorption, electron transfer kinetics, and double-layer effects on the nanoscale

Kinetics of Electron-Transfer Reactions at Nanoelectrodes

The kinetics of several fast heterogeneous electron-transfer reactions were investigated by steady-state voltammetry at nanoelectrodes and scanning electrochemical microscopy (SECM). The disk-type, polished Pt nanoelectrodes (3.7−400-nm radius) were characterized by a combination of voltammetry, scanning electron microscopy, and SECM. A number of experimental curves were obtained at the same nanoelectrode to attain the accuracy and reproducibility similar to those reported previously for micrometer-sized probes. A new analytical approximation was developed and used for analysis of steady-state tip voltammograms. The self-consistent kinetic parameter values with the uncertainty margin of ∼10% were obtained for electrodes of different radii and for a wide range of the SECM tip/substrate separation distances. The determined standard rate constants are compared to those previously measured at the electrodes of different dimensions, and the correlation between the heterogeneous and self-exchange rate constants is discussed

Image_2_Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report.jpeg

Thymic carcinoma is a rare and aggressive disease with poor outcome. There is no established treatment regimen for advanced thymic carcinoma. While the efficacy of pembrolizumab was proved to be promising, as a single agent, in patients with refractory/recurrent thymic carcinoma that progressed after chemotherapy, the efficacy and safety of combination of pembrolizumab and chemotherapy as front-line treatment in metastatic thymic carcinoma have not been explored yet. Herein, we report the first two cases of metastatic thymic squamous cell carcinoma receiving the combined approaches of pembrolizumab and chemotherapy as first-line treatment. Of the two patients, one had a complete radiological response of mediastinal masses with sustained remission over 3 years, and the other one with widespread disease had a good partial response over 20 months and achieved no evidence of disease radiologically after undergoing percutaneous radiofrequency ablation for residual liver metastases. Next-generation sequencing (NGS) showed low tumor mutation burden and MSS in both patients. Immunohistochemistry analysis of the tumor showed high PD-L1 expression in patient 1 and low PD-L1 expression in patient 2. Pembrolizumab combined with chemotherapy may be an attractive strategy for the first-line treatment of metastatic thymic carcinoma and thus warrants further evaluation.</p

Image_1_Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report.jpeg

Thymic carcinoma is a rare and aggressive disease with poor outcome. There is no established treatment regimen for advanced thymic carcinoma. While the efficacy of pembrolizumab was proved to be promising, as a single agent, in patients with refractory/recurrent thymic carcinoma that progressed after chemotherapy, the efficacy and safety of combination of pembrolizumab and chemotherapy as front-line treatment in metastatic thymic carcinoma have not been explored yet. Herein, we report the first two cases of metastatic thymic squamous cell carcinoma receiving the combined approaches of pembrolizumab and chemotherapy as first-line treatment. Of the two patients, one had a complete radiological response of mediastinal masses with sustained remission over 3 years, and the other one with widespread disease had a good partial response over 20 months and achieved no evidence of disease radiologically after undergoing percutaneous radiofrequency ablation for residual liver metastases. Next-generation sequencing (NGS) showed low tumor mutation burden and MSS in both patients. Immunohistochemistry analysis of the tumor showed high PD-L1 expression in patient 1 and low PD-L1 expression in patient 2. Pembrolizumab combined with chemotherapy may be an attractive strategy for the first-line treatment of metastatic thymic carcinoma and thus warrants further evaluation.</p

Image_3_Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report.jpeg

Thymic carcinoma is a rare and aggressive disease with poor outcome. There is no established treatment regimen for advanced thymic carcinoma. While the efficacy of pembrolizumab was proved to be promising, as a single agent, in patients with refractory/recurrent thymic carcinoma that progressed after chemotherapy, the efficacy and safety of combination of pembrolizumab and chemotherapy as front-line treatment in metastatic thymic carcinoma have not been explored yet. Herein, we report the first two cases of metastatic thymic squamous cell carcinoma receiving the combined approaches of pembrolizumab and chemotherapy as first-line treatment. Of the two patients, one had a complete radiological response of mediastinal masses with sustained remission over 3 years, and the other one with widespread disease had a good partial response over 20 months and achieved no evidence of disease radiologically after undergoing percutaneous radiofrequency ablation for residual liver metastases. Next-generation sequencing (NGS) showed low tumor mutation burden and MSS in both patients. Immunohistochemistry analysis of the tumor showed high PD-L1 expression in patient 1 and low PD-L1 expression in patient 2. Pembrolizumab combined with chemotherapy may be an attractive strategy for the first-line treatment of metastatic thymic carcinoma and thus warrants further evaluation.</p

Role of Trace Amounts of Water in Transfers of Hydrophilic and Hydrophobic Ions to Low-Polarity Organic Solvents

The effect of water content in a low polarity organic phase on transfers of hydrophobic and hydrophilic ions across the liquid/liquid interface was investigated by nanopipet voltammetry. It was shown recently (J. Am. Chem. Soc. 2006, 128, 15019) that hydrophilic ions can be transferred to less polar solvents such as 1,2-dichloroethane (DCE) only in the presence of organic counterions that facilitate such processes. The addition of trace amounts of water to neat DCE induces the transfers of hydrophilic ions but practically does not affect the transfers of hydrophobic species. Although the conductivity of neat DCE decreases upon addition of water to it, the rates of hydrophilic ion transfers increase markedly with increasing concentration of water in organic phase. This observation suggests different transfer mechanisms for hydrophobic and hydrophilic ions:  while the former are transferred directly into neat organic solvents, the latter can only be transferred to aqueous clusters dispersed in organic phase

Shuttling Mechanism of Ion Transfer at the Interface between Two Immiscible Liquids

The transfers of hydrophilic ions between aqueous and organic phases are ubiquitous in biological and technological systems. These energetically unfavorable processes can be facilitated either by small molecules (ionophores) or by ion-transport proteins. In absence of a facilitating agent, ion-transfer reactions are assumed to be “simple”, one-step processes. Our experiments at the nanometer-sized interfaces between water and neat organic solvents showed that the generally accepted one-step mechanism cannot explain important features of transfer processes for a wide class of ions including metal cations, protons, and hydrophilic anions. The proposed new mechanism of ion transfer involves transient interfacial ion paring and shuttling of a hydrophilic ion across the mixed-solvent layer

Table3_A Five-Gene Signature Associated With DNA Damage Repair Molecular Subtype Predict Overall Survival for Hepatocellular Carcinoma.DOCX

Background: DNA damage repair (DDR) is an important mechanism for the occurrence and development of hepatocellular carcinoma (HCC), but its impact on prognosis has not been fully understood.Materials and methods: A total of 904 HCC patients were included in our study, TCGA (n = 370) and GSE14520 (n = 239) were merged into a large-sample training cohort (n = 609). The training cohort was clustered into C1 and C2 based on prognostic DDR-related genes, the differentially expressed genes (DEGs) between C1 and C2 were identified by the Wilcoxon signed-rank test referred to criteria (|log2FC|≥1 and FDRResults: The Kaplan–Meier survival analysis showed that the high-risk group had a significantly reduced overall survival (OS) compared to the low-risk group in the three independent cohorts, and the time-dependent ROC curve showed that the five-gene (STMN1, PON1, PLOD2, MARCKSL1, and SPP1) risk score with a high accuracy in predicting OS. The patients with AFP >300 ng/ml, tumor poor differentiation (grade 3–4), micro and macro vascular tumor invasion, advanced stage (AJCC III-IV, BCLC stage B-C, and CLIP score >2) exhibited a higher risk score. Subgroup survival analysis found that the risk score was applicable to patients with different clinical characteristics. GO and KEGG functional enrichment analysis revealed that cell cycle, p53 signaling, TNF signaling-related pathways were upregulated in the high-risk group. The higher infiltration level of activated CD4 T cell, CD56 bright natural killer cell, plasmacytoid dendritic cell, and type 2 T helper cells were found to lead an unfavorable impact on the OS of HCC patients, and these four kinds of immune cells exhibited a higher infiltration level in the high-risk group.Conclusion: The five-gene risk score proposed in the research may provide new insights into the individualized evaluation of HCC prognosis.</p