Preparation of Light‐Responsive Aliphatic Polycarbonate via Versatile Polycondensation for Controlled Degradation

Starting from (2,2,5‐trimethyl‐1,3‐dioxan‐5‐yl)methanamine with light‐responsive 4,5‐dimethoxy‐2‐nitrobenzyl protecting groups, a variety of light‐responsive copolycarbonates (LrPCs) are synthesized by a general two‐step polycondensation using lithium acetylacetonate (LiAcac) as catalyst. UV/Vis, ¹H nuclear magnetic resonance (NMR), and size exclusion chromatography (SEC) confirm the rapid decomposition of these polymers in response to irradiation with UV light. Stable and monodisperse nanoparticles with hydrodynamic diameters of 100 nm, formulated from 25% LrPC and 75% poly(lactic‐co‐glycolic acid) (PLGA), undergo rapid disruption upon triggering with UV light, while standard PLGA nanoparticles remain stable. Moreover, differing from the ring‐opening polymerization (ROP) of trimethylene carbonate‐based monomers, direct polycondensation of 1,3‐propanediol‐based monomers with pendent functional groups and other diols will enable the introduction of various properties into the polycarbonate backbone, and expand the family of biodegradable synthetic polymers for potential biomedical applications.     

Aligned Tubular Conjugated Microporous Polymer Films for the Aggregation‐Induced Emission‐Based Sensing of Explosives

This work shows the sensing performance of conjugated microporous polymer (CMP) tubes. Aligned tubular CMP films (CMP‐AT) are synthesized by a template method. The Sonogashira coupling of tetra(4‐ethynyl)phenylethylene with 1,4‐diiodobenzene in the cylindrical pores of anodic aluminum oxide (AAO) plates and the etching of templates result in the CMP‐AT films. Due to the tetraphenylethylene moieties in the materials, the CMP‐AT films show aggregation‐induced emission (AIE). Based on emission‐quenching behavior, the sensing performance of CMP‐AT films toward model explosives, nitrotoluenes, is studied. The CMP‐AT films having longer CMP tubes with thinner wall thickness show better sensing performance with the Stern–Volmer constant (K_sv) values up to 92 400 M^?1 toward 2,4‐dinitrotoluene. The reduced diffusion pathway of substrates by the thin wall of the CMP tubes is critical for the AIE quenching‐based sensing of nitrotoluenes. These observations indicate that the functionality of CMP materials can be further enhanced by their morphological engineering. Due to the chemical stability of CMP materials, the CMP‐AT‐5 film can be recycled at least five times, maintaining the original sensing performance and tubular morphology.     

Chain Features and Their Influence on the Thermal Stability of Poly(propylene‐co‐1‐nonene) Copolymers

The thermal stability of several isotactic polypropylenes and propylene‐co‐1‐nonene copolymers is assessed under nitrogen by means of thermogravimetric analysis (TGA). The samples involve wide ranges of molecular weight, isotactic average length, and 1‐nonene content, in order to perform a comprehensive analysis of the effect that chain features exert on the apparent activation energy (E_a), in the initial stages of the molten state degradation. The degradation process correlates with chain mobility and, accordingly, with chain features that are linked to. Thus, microstructure and chain size are found to play a key role. In fact, isotactic average length of propylene sequences and molecular weight are driving factors in the E_a required for main chain thermal scission.     

Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well‐documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.     

Adoptive transfer of IFN-γ-induced M-MDSCs promotes immune tolerance to allografts through iNOS pathway

Inflammation Research - Efficient production of monocytic myeloid-derived suppressor cells (M-MDSCs) with stable immunosuppressive function is crucial for immunomodulatory cell therapy for many...     

Genomic instability in fragile sites—still adding the pieces

Common fragile sites (CFSs) are specific genomic regions in normal chromosomes that exhibit genomic instability under DNA replication stress. As replication stress is an early feature of cancer development, CFSs are involved in the signature of genomic instability found in malignant tumors. The landscape of CFSs is tissue‐specific and differs under different replication stress inducers. Nevertheless, the features underlying CFS sensitivity to replication stress are shared. Here, we review the events generating replication stress and discuss the unique characteristics of CFS regions and the cellular responses aimed to stabilizing these regions.     

Early detection of the PAX3‐FOXO1 fusion gene in circulating tumor‐derived DNA in a case of alveolar rhabdomyosarcoma

Cell‐free DNA (cfDNA), which are small DNA fragments in blood derived from dead cells including tumor cells, could serve as useful biomarkers and provide valuable genetic information about the tumors. cfDNA is now used for the genetic analysis of several types of cancers, as a surrogate for tumor biopsy, designated as “liquid biopsy.” Rhabdomyosarcoma (RMS), the most frequent soft tissue tumor in childhood, can arise in any part of the body, and radiological imaging is the only available method for estimating the tumor burden, because no useful specific biological markers are present in the blood. Because tumor volume is one of the determinants of treatment response and outcome, early detection at diagnosis as well as relapse is essential for improving the treatment outcome. A 15‐year‐old male patient was diagnosed with alveolar RMS of prostate origin with bone marrow invasion. The PAX3‐FOXO1 fusion was identified in the tumor cells in the bone marrow. After the diagnosis, cfDNA was serially collected to detect the PAX3‐FOXO1 fusion sequence as a tumor marker. cfDNA could be an appropriate source for detecting the fusion gene; assays using cfDNA have proved to be useful for the early detection of tumor progression/recurrence. Additionally, the fusion gene dosage estimated by quantitative polymerase chain reaction reflected the tumor volume during the course of the treatment. We suggest that for fusion gene‐positive RMSs, and other soft tissue tumors, the fusion sequence should be used for monitoring the tumor burden in the body to determine the diagnosis and treatment options for the patients.     

Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Primary lymphomas of the central nervous system (PCNSL) are diffuse large B‐cell lymphomas (DLBCLs) confined to the central nervous system (CNS). We here performed array‐based DNA methylation analyses of 26 PCNSL and 78 DLBCL and validated our findings in an independent dataset. We identified 2847 CpGs differentially methylated between PCNSL and non‐CNS‐DLBCL. Neither a supervised analysis using these CpGs nor application of 3 CpG classifiers selected for class separation unambiguously separated PCNSL from non‐CNS‐DLBCL. Remarkably, 6/78 non‐CNS‐DLBCL consistently segregated with PCNSL, which displayed molecular features typical for PCNSL. Our findings suggest that a subset of non‐CNS‐DLBCL exists which molecularly resembles PCNSL.