S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca2+ binding proteins belonging to the S100 family. They often exist in the form of heterodimer, while homodimer exists very little because of the stability. S100A8/A9 is constitutively expressed in neutrophils and monocytes as a Ca2+ sensor, participating in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, S100A8/A9 is released actively and exerts a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate biomarker for diagnosis and follow-up as well as a predictive indicator of therapeutic responses to inflammation-associated diseases. As blockade of S100A8/A9 activity using small-molecule inhibitors or antibodies improves pathological conditions in murine models, the heterodimer has potential as a therapeutic target. In this review, we provide a comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 and highlight its application as a diagnostic and therapeutic target in inflammation-associated diseases.

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.

Organometal halide perovskite materials have triggered enormous attention for a wide range of high-performance optoelectronic devices. However, their stability and toxicity are major bottleneck challenges for practical applications. Substituting toxic heavy metal, that is, lead (Pb), with other environmentally benign elements, for example, tin (Sn), could be a potential solution to address the toxicity issue. Nevertheless, even worse stability of Sn-based perovskite material than Pb-based perovskite poses a great challenge for further device fabrication. In this work, for the first time, three-dimensional CHNHSnI perovskite nanowire arrays were fabricated in nanoengineering templates, which can address nanowire integration and stability issues at the same time. Also, nanowire photodetectors have been fabricated and characterized. Intriguingly, it was discovered that as the nanowires are embedded in mechanically and chemically robust templates, the material decay process has been dramatically slowed down by up to 840 times, as compared with a planar thin film. This significant improvement on stability can be attributed to the effective blockage of diffusion of water and oxygen molecules within the templates. These results clearly demonstrate a new and alternative strategy to address the stability issue of perovskite materials, which is the major roadblock for high-performance optoelectronics.

Alluring optical and electronic properties have made organometallic halide perovskites attractive candidates for optoelectronics. Among all perovskite materials, inorganic CsPbX (X is halide) in black cubic phase has triggered enormous attention recently owing to its comparable photovoltaic performance and high stability as compared to organic and hybrid perovskites. However, cubic phase stabilization at room temperature for CsPbI still survives as a challenge. Herein we report all inorganic three-dimensional vertical CsPbI perovskite nanowires (NWs) synthesized inside anodic alumina membrane (AAM) by chemical vapor deposition (CVD) method. It was discovered that the as-grown NWs have stable cubic phase at room temperature. This significant improvement on phase stability can be attributed to the effective encapsulation of NWs by AAM and large specific area of these NWs. To demonstrate device application of these NWs, photodetectors based on these high density CsPbI NWs were fabricated demonstrating decent performance. Our discovery suggests a novel and practical approach to stabilize the cubic phase of CsPbI material, which will have broad applications for optoelectronics in the visible wavelength range.

An amperometric glucose biosensor based on the direct electron transfer of glucose oxidase (GOx) was developed by electrochemically entrapping GOx onto the inner wall of highly ordered polyaniline nanotubes (nanoPANi), which was synthesized using anodic aluminum oxide (AAO) membrane as a template. The cyclic voltammetric results indicated that GOx immobilized on the nanoPANi underwent direct electron transfer reaction, and the cyclic voltammogram displayed a pair of well-defined and nearly symmetric redox peaks with a formal potential of -405 +/- 5 mV and an apparent electron transfer rate constant of 5.8 +/- 1.6 s(-1). The biosensor had good electrocatalytic activity toward oxidation of glucose and exhibited a rapid response (approximately 3 s), a low detection limit (0.3 +/- 0.1 microM), a useful linear range (0.01-5.5 mM), high sensitivity (97.18 +/- 4.62 microA mM(-1) cm(-2)), higher biological affinity (the apparent Michaelis-Mentan constant was estimated to be 2.37 +/- 0.5 mM) as well as good stability and repeatability. In addition, the common interfering species, such as ascorbic acid, uric acid, and 4-acetamidophenol, did not cause any interference due to the use of a low detection potential (-0.3 V vs SCE). The biosensor can also be used for quantification of the concentration of glucose in real clinical samples.

Pulmonary vascular remodeling characterized by concentric wall thickening and intraluminal obliteration is a major contributor to the elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Here we report that increased hypoxia-inducible factor 2α (HIF-2α) in lung vascular endothelial cells (LVECs) under normoxic conditions is involved in the development of pulmonary hypertension (PH) by inducing endothelial-to-mesenchymal transition (EndMT), which subsequently results in vascular remodeling and occlusive lesions. We observed significant EndMT and markedly increased expression of SNAI, an inducer of EndMT, in LVECs from patients with IPAH and animals with experimental PH compared with normal controls. LVECs isolated from IPAH patients had a higher level of HIF-2α than that from normal subjects, whereas HIF-1α was upregulated in pulmonary arterial smooth muscle cells (PASMCs) from IPAH patients. The increased HIF-2α level, due to downregulated prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase that promotes HIF-2α degradation, was involved in enhanced EndMT and upregulated SNAI1/2 in LVECs from patients with IPAH. Moreover, knockdown of HIF-2α (but not HIF-1α) with siRNA decreases both SNAI1 and SNAI2 expression in IPAH-LVECs. Mice with endothelial cell (EC)-specific knockout (KO) of the PHD2 gene, egln1 (egln1), developed severe PH under normoxic conditions, whereas Snai1/2 and EndMT were increased in LVECs of egln1 mice. EC-specific KO of the HIF-2α gene, hif2a, prevented mice from developing hypoxia-induced PH, whereas EC-specific deletion of the HIF-1α gene, hif1a, or smooth muscle cell (SMC)-specific deletion of hif2a, negligibly affected the development of PH. Also, exposure to hypoxia for 48-72 h increased protein level of HIF-1α in normal human PASMCs and HIF-2α in normal human LVECs. These data indicate that increased HIF-2α in LVECs plays a pathogenic role in the development of severe PH by upregulating SNAI1/2, inducing EndMT, and causing obliterative pulmonary vascular lesions and vascular remodeling.

Background Assessing functional impairment, therapeutic response, and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized 129Xe MRI can address this gap through its unique capability to image gas transfer three-dimensionally from airspaces to interstitial barrier tissues to RBCs. This must be validated by testing the degree to which it correlates with pulmonary function tests (PFTs) and CT scores and its spatial distribution reflects known physiology and patterns of disease. Methods 13 healthy individuals (33.6±15.7 years) and 12 IPF patients (66.0±6.4 years) underwent 129Xe MRI to generate 3D quantitative maps depicting the 129Xe ventilation distribution, its uptake in interstitial barrier tissues, and its transfer to RBCs. For each map, mean values were correlated with PFTs and CT fibrosis scores and their patterns were tested for the ability to depict functional gravitational gradients in healthy lung, and to detect the known basal and peripheral predominance of disease in IPF. Results 129Xe MRI depicted functional impairment in IPF patients, whose mean barrier uptake increased by 188% compared to the healthy reference population. 129Xe MRI metrics correlated poorly and insignificantly with CT fibrosis scores, but strongly with pulmonary function tests. Barrier uptake and RBC transfer both correlated significantly with DLCO (r=−0.75, p<0.01 and r=0.72, p<0.01), while their ratio (RBC/barrier) correlated strongly (r=0.94, p<0.01). RBC transfer exhibited significant anterior-posterior gravitational gradients in healthy volunteers, but not in IPF, where it was significantly impaired in the basal (p=0.02) and sub-pleural (p<0.01) lung. Conclusions Hyperpolarized 129Xe MRI is a rapid and well-tolerated exam that provides region-specific quantification of interstitial barrier thickness and RBC transfer efficiency. With further development, it could become a robust tool for measuring disease progression and therapeutic response in IPF patients, sensitively and non-invasively.

Intrinsic emission and persistent room temperature phosphorescence from amorphous nonaromatic polymers are observed, which can be well rationalized by the CTE mechanism.