TIGIT immunohistochemistry established a novel scoring system in class... Nature, scientific reports, 2021

Immune checkpoint inhibition of the PD1/PD-L1 pathway has revolutionized cancer therapy. Recent experiments demonstrate that combination therapies that target new checkpoints like TIGIT are more effective than classical PD1/PD-L1 monotherapies. Over the last two years, TIGIT has attracted the attention from pharmaceutical companies worldwide: TIGIT turned out to be the most attractive target from a so called „second wave of checkpoint modulators“. Consequently, a future challenge is to determine which patients are most suitable to receive...

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Development of a nano-drug delivery system based on mesoporous silica... Applied Nanoscience, 2020

Abstract Although current treatment strategies including systemic chemotherapy, local radiotherapy, biological immunology, and surgical resection have improved the remission rate of non-Hodgkin’s lymphoma (NHL) patients, the recurrence rate of the disease remains high, and the remission rate of retreatment after recurrence is low. Exploring and discovering new strategies for treating NHL has become a critical problem to be solved. Harmine (HM) has demonstrated anti-tumor activity; however, like most traditional Chinese medicines, it...

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An interplay between UCP2 and ROS protects cells from high-salt-induce... Cell Death and Disease, 2021

Abstract The mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneously hypertensive rat. Overexpression of UCP2 counteracts the negative effects of high-salt feeding in both animal models. We tested in vitro the ability of UCP2 to stimulate autophagy and mitophagy as a mechanism mediating its protecti...

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The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-re... PNAS, 2021

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regula...

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Catalytically potent and selective clusterzymes for modulation of neur... Nature Communications, 2021

Abstract Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au...

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Osteoprotegerin is a risk factor for mortality after kidney transplant... Clinical Nephrology, 2021

Abstract Background: Vascular calcification is common in chronic kidney disease and is associated with significant cardiovascular morbidity and mortality. One of the important factors regulating vascular calcification is osteoprotegerin (OPG). There are, however, limited data on the impact of OPG on all-cause mortality and graft loss in kidney transplant recipients so far. Given its impact on vascular calcification, the aim of our study is to analyze whether OPG was a risk factor of all-cause mortalit...

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A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent Molecular Cell, 2020

Abstract Poly (ADP-ribose) polymerase (PARP) has recently emerged as a central mediator in cancer resistance against numerous anticancer agents to include chemotherapeutic agents such as microtubule targeting agents and DNA damaging agents. Here, we describe AMXI-5001, a novel, highly potent dual PARP1/2 and microtubule polymerization inhibitor with favorable metab...

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Head-to-head comparison of clinical performance of CSF phospho-tau T18... Alzheimer's & Dementia : the Journal of the Alzheimer's Association, 2...

Abstract Introduction Phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N-terminal and mid-region p-tau181 and p-tau217 fragments are available, but head-to-head comparison in clinical settings is lacking. Methods N-terminal-directed p-tau217 (N-p-tau217), N-terminal-directed p-tau181 (N-p-tau181), and standard mid-region p-tau181 (Mid-p-tau181) biomarkers in CSF were evaluated in thre...

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Heterogeneous Escape from X Chromosome Inactivation Results in Sex Dif... Cell Reports, 2020

Abstract Immune responses differ between women and men, and type I interferon (IFN) responses following Toll-like receptor 7 (TLR7) stimulation are higher in women. The precise mechanisms driving these sex differences in immunity are unknown. To investigate possible genetic factors, we quantify escape from X chromosome inactivation (XCI) for TLR7 and four other genes (RPS6KA3, CYBB, BTK, and IL13RA1) at the single plasmacytoid dendritic cell (pDC) level. We observe escape from XCI for all investigated genes, leading to biallelic expression...

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MINSTED fluorescence localization and nanoscopy Nature Photonics, 2021

Abstract: We introduce MINSTED, a fluorophore localization and super-resolution microscopy concept based on stimulated emission depletion (STED) that provides spatial precision and resolution down to the molecular scale. In MINSTED, the intensity mini- mum of the STED doughnut, and hence the point of minimal STED, serves as a movable reference coordinate for fluorophore localization. As the STED rate, the background and the required number of fl...

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