Addressing cellular heterogeneity in tumor and circulation for refined prognostication.

Despite pronounced genomic and transcriptomic heterogeneity in non-small-cell lung cancer (NSCLC) not only between tumors, but also within a tumor, validation of clinically relevant gene signatures for prognostication has relied upon single-tissue samples, including 2 commercially available multigene tests (MGTs). Here we report an unanticipated impact of intratumor heterogeneity (ITH) on risk prediction of recurrence in NSCLC, underscoring the need for a better genomic strategy to refine prognostication. By leveraging label-free, inertial-focusing microfluidic approaches in retrieving circulating tumor cells (CTCs) at single-cell resolution, we further identified specific gene signatures with distinct expression profiles in CTCs from patients with differing metastatic potential. Notably, a refined prognostic risk model that reconciles the level of ITH and CTC-derived gene expression data outperformed the initial classifier in predicting recurrence-free survival (RFS). We propose tailored approaches to providing reliable risk estimates while accounting for ITH-driven variance in NSCLC.

Protein-protected gold/silver alloy nanoclusters in metal-enhanced singlet oxygen generation and their correlation with photoluminescence.

Photoluminescent noble metal nanoclusters (NCs, core size <2 nm) have recently emerged as a new type of photosensitizers advantageous over conventional photosensitizers due to their high singlet oxygen (1O2) generation efficiency, excellent photostability and water solubility, as well as good biocompatibility for photodynamic therapy and bioimaging. However, no correlation has been established between the intrinsic 1O2 generation and photoluminescence properties of metal NCs with their size, composition, and concentration, which is important to customize the molecule-like properties of NCs for different applications. Herein, we report a systematic study to uncover the rational design of bimetallic NCs with controllable 1O2 generation efficiency by tuning their compositions through spontaneous galvanic displacement reaction. A series of ultrasmall gold/silver alloy nanoclusters (AuAgNCs) were synthesized by reacting bovine serum albumin (BSA) protein-protected Ag13NCs (13 Ag atoms/cluster) with varying concentrations of gold precursor at room temperature. It was found that the 1O2 generation efficiency of the resultant BSA-protected AuAgNCs were inversely correlated to their photoluminescence intensity. Interestingly, plasmonic gold nanoparticles (>10 nm) were also formed simultaneously by photobleaching of the BSA-AuAgNCs, leading to significant metal enhancement effect to the 1O2 generation rate much higher (~45 times) than that of the monometallic BSA-Ag13NC. This versatile two-for-one strategy to develop next generation metal-enhanced bimetallic NC photosensitizers in one pot opens up new opportunities in designing advanced hybrid nanomaterials with complementary and/or enhanced functionalities.

Optical coherence tomography angiography for the anterior segment.

Optical coherence tomography angiography (OCTA) is a rapid and non-invasive technique for imaging vasculature in the eye. As OCTA can produce high-resolution cross-sectional images and allow depth-resolved analysis for accurate localization of pathology of interest, it has become a promising method for anterior segment imaging. Furthermore, OCTA offers a more patient-friendly alternative to the conventional invasive dye-based fluorescent angiography. However, conventional OCTA systems are typically designed and optimized for the posterior segment of the eye, and thus using OCTA for anterior segment imaging can present several difficulties and limitations. In this review, we summarized the recent developments and clinical applications in anterior segment OCTA (AS-OCTA) imaging, such as for the cornea, iris, sclera and conjunctiva. We also compared commercially available OCTA systems, discussed the limitations of adapting current OCTA technology for the anterior segment imaging, and proposed possible future directions for AS-OCTA systems. AS-OCTA provides potential for future clinical applications such as diagnosis of corneal and iris pathologies, pre-operative surgical planning, assessment of new anti-angiogenic therapeutics or evaluation of limbal stem cell deficiency. With further development, OCTA for anterior segment imaging in the clinics may become common in the near future.

Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation.

Patients who suffer from subarachnoid hemorrhage (SAH) usually have long-term neurological impairments. Endogenous neurogenesis might play a potential role in functional recovery after SAH; however, the underlying neurogenesis mechanism is still unclear. We assessed the extent of neurogenesis in the subventricular zone (SVZ) to better understand the neurogenesis mechanism after SAH. We performed a rat model of SAH to examine the extent of neurogenesis in the SVZ and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid (CSF) on neural stem cells (NSCs) after SAH. In this study, the proliferation, differentiation, and migratory capacities of NSCs in the SVZ were significantly increased on days 5 and 7 post SAH. Furthermore, treatment of cultured rat fetal NSCs with the CSF collected from rats on days 5 and 7 post SAH enhanced their proliferation, differentiation, and migration. Enzyme-linked immunosorbent assay (ELISA) of the CSF detected a marked increase in the concentration of brain-derived neurotrophic factor (BDNF). Treating the cultured NSCs with recombinant BDNF (at the same concentration as that in the CSF) or with CSF from SAH rats, directly, stimulated proliferation, differentiation, and migration to a similar extent. BDNF expression was upregulated in the SVZ of rats on days 5 and 7 post SAH, and BDNF release occurred from NSCs, astrocytes, and microglia in the SVZ. These results indicate that SAH triggers the expression of BDNF, which promotes the proliferation, differentiation, and migration of NSCs in the SVZ after SAH.