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Abstract Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti‐ vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real‐world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR‐TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first‐line EGFR‐TKI with anti‐VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high‐grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti‐VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR‐TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large‐scale registry‐based cohort studies may be needed to validate our findings.

Inserting underlying reduced graphene oxide (rGO) into Co aims to regulate the chemical integrity and catalytic ability of the Co upper layer for hydrogen evolution reaction (HER) as a green-hydrogen goal. Principally, an operando mass spectrometer indicates 3.8 times more considerable hydrogen generation in Co/rGO than in Co. The spectroscopical approaches, combining operando soft and hard X-ray probing, illustrate the chemical oxidation evolution of electronic Co-3d and Co-4p states differently regarding the underlying rGO contribution. A unique examination is regarded as the phase transition from the initial middle to high oxidation and to deoxidation, related to the intermediate Co^{0} existence and H_{2} generation. The chemical adsorption of Co–O(H), Co–H_{ads}, and H_{2} molecules desorption have been assigned their spectral significances. The rGO mediation indicates two significant metal Co and Co–O(H) blocks in the two-dimensional R-k domain. Density-functional-theory (DFT) calculation provides the regeneration, sustained stability, and decreasing energy barrier of Co–H_{ads} catalysts due to the rGO incorporation, thereby augmenting the HER enhancement through the alternative Volmer-Heyrovsky process. The in-situ experiment, including mass spectrometer, soft, and hard X-ray, provides evidence regarding the catalyst’s HER enhancement. This study offers insights into the chemical composition, electronic structure, and active role of Co bonded with or without the extinct OH and H bonds, advancing our comprehension of electrocatalytic reactions, thus taking our knowledge of composite materials to stepwise electrocatalytic reactions forward. This cutting-edge experiment under in-situ environment and DFT studies gives critical information regarding the catalytic mechanism and chemical stability of the Co and rGO materials.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase overexpressed in various cancer types that plays a critical role in tumor progression. Accumulating evidence suggests that targeting FAK, either alone or in combination with other agents, may serve as an effective therapeutic strategy for numerous cancers. In addition to retarding proliferation, metastasis, and angiogenesis, FAK inhibition triggers cellular senescence in lung cancer cells. However, the detailed mechanism remains enigmatic. In the present study, we found that FAK inhibition not only elicits DNA-damage signaling but also downregulates enhancer of zeste homolog 2 (EZH2) expression. The manipulation of FAK expression influences EZH2 expression and corresponding signaling in vitro. Immunohistochemistry shows that active FAK signaling corresponds with the activation of the EZH2-mediated signaling cascade in lung-cancer-cells-derived tumor tissues. We also found that ectopic EZH2 expression attenuates FAK-inhibition-induced cellular senescence in lung cancer cells. Our results identify EZH2 as a critical downstream effector of the FAK-mediated anti-senescence pathway. Targeting FAK-EZH2 axis-induced cellular senescence may represent a promising therapeutic strategy for restraining tumor growth.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

In-situ X-ray Absorption Spectroscopy (XAS), Raman Spectroscopy, AFM and XPS have been used to investigate the effect of reactions occurring in aqueous electrolytes on the structure of a single-layer graphene produced by CVD. It was found that defects are readily and irreversibly produced by application of electrode voltages. The defects and the products were identified also by new features in the XAS spectra. Our findings show the poor stability of the CVD graphene, which could be a challenge in applications such as super-capacitors, fuel-cells, batteries and photo-catalysis. [ABSTRACT FROM AUTHOR]

The electronic structure of the titanium dioxide (Ti02)-fluorine-doped tin dioxide (Sn02:F) interface is investigated by soft x-ray absorption spectroscopy using synchrotron radiation. The measurements probe the site- and symmetry-selected unoccupied density of states and reflect the interaction between an early transition-metal-oxide (d0) semiconductor and a post-transition-metal-oxide (d10) degenerate semiconductor. The distinct interfacial electronic structure of Ti02-Sn02:F is established by contrasting spectra with those for anatase and rutile Ti02, Sn02:F, and ZnO-Sn02:F and CdO-Sn02:F interfaces. Oxygen is absorption spectra, which relate to the O 2p partial density of states of the conduction band, indicate that the interface is associated with a reduction in Ti d-0 p orbital hybridization and an alteration of the Ti02 crystal field. These observations are consistent with measured titanium 2p absorption spectra, which in addition provide evidence for distortion of long-range order around the cation site in the interfacial Ti02. The Ti02-Sn02:F interface is a functional component of a number of optoelectronic devices, perhaps most notably within the anode structure of solar cell architectures. In nonequilibrium conditions, such as those found in operating solar cells, interfacial electronic structure directly influences performance by modifying, for instance, the quasi-Fermi level electrons and the potential distribution at the transparent electrode. [ABSTRACT FROM AUTHOR]