Background: Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies, yet biopsies can only provide baseline information. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest.Design: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1negative, PD-L1low, PD-L1medium and PD-L1high). 35 patients with different advanced gastrointestinal tumors were enrolled in a phase 1 trial of a PD-1 inhibitor, IBI308. The CTC numeration and the PD-L1 expression levels were analyzed.Results: Prior the treatment of IBI308, 97% (34/35) patients had CTCs, ranging from1 to 70 (median 7). 74% (26/35) had PD-L1positive CTCs, and 60% (21/35) had at least one PD-L1high CTCs. The disease control (DC) rate in PD-L1high patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1high CTCs had even higher DC rate of 64% (9/14), with only 14% DC rate for the rest (3/21). We also observed that the count changes of total CTC, PD-L1postive CTC and PD-L1high CTC correlate quite well with disease outcome (P<0.001, P = 0.002 and 0.007, respectively). In addition, the abundance of PD-L1high CTCs at baseline had predicative significance for progression free survival (PFS).Conclusions: We revealed that the abundance of PD-L1high CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies and measuring the dynamic changes of CTC could indicate the therapeutic response at early time.
Carbon nanotubes (CNTs) as well‐known nanomaterials are extensively studied and widely applied in various fields. Nitric acid (HNO3) is often used to treat CNTs for purification purposes and preparing oxidized CNTs for various applications. However, too little attention is paid to investigating the effect of HNO3 treatment on the optical properties of CNTs. In this work, it is observed for the first time that HNO3‐oxidized multiwalled carbon nanotubes (ox‐MWCNTs) have strong electrochemiluminescence (ECL) activity, which enables ox‐MWCNTs to become new and good ECL carbon nanomaterials after carbon quantum dots (CQDs) and graphene quantum dots (GQDs). Various characterization technologies, such as transmission electron microscope (TEM), X‐ray photoelectron spectroscopy (XPS), and Raman spectroscopy, are used to reveal the relationship between ECL activity and surface states. The ECL behaviors of ox‐MWCNTs are investigated in detail and a possible ECL mechanism is proposed. Finally, the new ECL nanomaterials of ox‐MWCNTs are envisioned to have promising applications in sensitive ECL sensing and in the study of CNT‐based catalysts.
Aurein1.2 is a 13-residue antimicrobial peptide secreted by the Australian tree frog Litoria aurea. In order to improve its stabilities, the helical contents and corresponding biological activities of Aurein1.2 (a series of stapled analogues) were synthesized, and their potential antifungal activities were evaluated. Not surprisingly, the stapled Aurein1.2 peptides showed higher proteolytic stability and helicity than the linear counterpart. The minimum inhibitory concentration (MIC) of ten stapled peptides against six strains of common pathogenic fungi was determined by the microscale broth dilution method recommended by CLSI. Of them, Sau-1, Sau-2, Sau-5, and Sau-9 exhibited better inhibitory effects on the fungi than the linear peptide. These stapled Aurein1.2 peptides may serve as the leading compounds for further optimization and antifungal therapy.
In the event of a public health crisis, highly effective and sustainable antimicrobial materials and equipment will be urgently needed. Here, the preparation is reported by electrospinning of broad-spectrum antibacterial nanofibers embedded in a photoactive hydrogen-bonded organic framework (HOF) of rod-like nanocrystals ≈60 nm in length. The resulting HOF@PVDF-HFP nanofibers maintain excellent tensile and breathability characteristics while shielding HOF nanocrystals against acid and alkali corrosion. A series of nanofibers embedded with different amounts and types of HOF nanocrystals are prepared to optimize their efficiency of singlet oxygen ( 1 O 2 ) generation. The 0.5 wt.
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