Near-Infrared, Organic Chiroptic Switch with High Dissymmetry Factors.

Here we unveil a chiral molecular redox switch derived from PDI-based twistacenes─chPDI[2] that has the remarkable attributes of high-intensity and a broadband chiral response. This material exhibits facile, stable, and reversible multistate chiroptical switching behavior over a broad active wavelength range close to 700 nm, encompassing ultraviolet, visible, and near-infrared regions. Upon reduction, chPDI[2] exhibits a substantial increase in the amplitude of its circular dichroic response, with an outstanding |ΔΔε| > 300 M-1 cm-1 and a high dissymmetry factor of 3 × 10-2 at 960 nm. DFT calculations suggest that the long wavelength CD signal for doubly reduced chPDI[2] originates from excitation of the PDI backbone to the π* orbital of the bridging alkene. Importantly, the dimer's molecular contortion facilitates ionic diffusion, enabling chiral switching in solid state films. The high dissymmetry factors and near-infrared response establish chPDI[2] as a unique chiroptic switch.

Single Nucleotide Polymorphism in Cell Adhesion Molecule L1 Affects Learning and Memory in a Mouse Model of Traumatic Brain Injury.

The L1 cell adhesion molecule (L1) has demonstrated a range of beneficial effects in animal models of spinal cord injury, neurodegenerative disease, and ischemia; however, the role of L1 in TBI has not been fully examined. Mutations in the L1 gene affecting the extracellular domain of this type 1 transmembrane glycoprotein have been identified in patients with L1 syndrome. These patients suffer from hydrocephalus, MASA (mental retardation, adducted thumbs, shuffling gait, aphasia) symptoms, and corpus callosum agenesis. Clinicians have observed that recovery post-traumatic brain injury (TBI) varies among the population. This variability may be explained by the genetic differences present in the general population. In this study, we utilized a novel mouse model of L1 syndrome with a mutation at aspartic acid position 201 in the extracellular domain of L1 (L1-201). We assessed the impact of this specific single nucleotide polymorphism (SNP) localized to the X-chromosome L1 gene on recovery outcomes following TBI by comparing the L1-201 mouse mutants with their wild-type littermates. We demonstrate that male L1-201 mice exhibit significantly worse learning and memory outcomes in the Morris water maze after lateral fluid percussion (LFP) injury compared to male wild-type mice and a trend to worse motor function on the rotarod. However, no significant changes were observed in markers for inflammatory responses or apoptosis after TBI.

Evaluation of laboratory and environmental exposure systems for protein modification upon gas pollutants and environmental factors.

Chemical modifications of proteins induced by ambient ozone (O3) and nitrogen oxides (NOx) are of public health concerns due to their potential to trigger respiratory diseases. The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere. Using bovine serum albumin (BSA) as a model protein, we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study. In the laboratory simulation system, the generated gaseous pollutants showed negligible losses. Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%. For environmental exposure experiment, quartz fiber filter was selected as the upper filter with low gaseous O3 (8.0%) and NO2 (1.7%) losses, and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%. The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions, while environmental factors (e.g., molecular oxygen and ultraviolet) may cause greater protein monomer losses. Based on the evaluation, the study exemplarily applied the two systems to protein modification and both showed that O3 promotes the protein oligomerization and nitration, while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples. The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions. A combination of the two will further reveal the actual mechanism of protein modifications.

Mapping the Contribution of Biomass Burning to Persistent Organic Pollutants in the Air of the Indo-China Peninsula Based on a Passive Air Monitoring Network.

Biomass burning (BB) is an important source of atmospheric persistent organic pollutants (POPs) across the world. However, there are few field-based regional studies regarding the POPs released from BB. Due to the current limitations of emission factors and satellites, the contribution of BB to airborne POPs is still not well understood. In this study, with the simultaneous monitoring of BB biomarkers and POPs based on polyurethane foam-based passive air sampling technique, we mapped the contribution of BB to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the Indo-China Peninsula. Spearman correlations between levoglucosan and 16 PCBs (rs = 0.264-0.767, p < 0.05) and 2 OCPs (rs = 0.250-0.328, p < 0.05) confirmed that BB may facilitate POP emissions. Source apportionment indicated that BB contributed 9.3% to the total PCB and OCP mass. The high contribution of positive matrix factorization-resolved BB to PCBs and OCPs was almost consistent with their concentration distributions in the open BB season but not completely consistent with those in the pre-monsoon and/or monsoon seasons. Their contribution distributions may reflect the use history and geographic distribution in secondary sources of POPs. The field-based contribution dataset of BB to POPs is significant in improving regional BB emission inventories and model prediction.

An MRI radiomics approach to predict survival and tumour-infiltrating macrophages in gliomas.

Preoperative MRI is one of the most important clinical results for the diagnosis and treatment of glioma patients. The objective of this study was to construct a stable and validatable preoperative T2-weighted MRI-based radiomics model for predicting the survival of gliomas. A total of 652 glioma patients across three independent cohorts were covered in this study including their preoperative T2-weighted MRI images, RNA-seq and clinical data. Radiomic features (1731) were extracted from preoperative T2-weighted MRI images of 167 gliomas (discovery cohort) collected from Beijing Tiantan Hospital and then used to develop a radiomics prediction model through a machine learning-based method. The performance of the radiomics prediction model was validated in two independent cohorts including 261 gliomas from the The Cancer Genomae Atlas database (external validation cohort) and 224 gliomas collected in the prospective study from Beijing Tiantan Hospital (prospective validation cohort). RNA-seq data of gliomas from discovery and external validation cohorts were applied to establish the relationship between biological function and the key radiomics features, which were further validated by single-cell sequencing and immunohistochemical staining. The 14 radiomic features-based prediction model was constructed from preoperative T2-weighted MRI images in the discovery cohort, and showed highly robust predictive power for overall survival of gliomas in external and prospective validation cohorts. The radiomic features in the prediction model were associated with immune response, especially tumour macrophage infiltration. The preoperative T2-weighted MRI radiomics prediction model can stably predict the survival of glioma patients and assist in preoperatively assessing the extent of macrophage infiltration in glioma tumours.

Fusing perylene diimide with helicenes.

Incorporating perylene diimide (PDI) units into helicene structures has become a useful strategy for giving access to non-planar electron acceptors as well as a method of creating molecules with unique and intriguing chiroptical properties. This minireview describes this fusion of PDIs with helicenes.

Remote Control of Dynamic Twistacene Chirality.

We report a reliable way to manipulate the dynamic, axial chirality in perylene diimide (PDI)-based twistacenes. Specifically, we reveal how chiral substituents on the imide position induce the helicity in a series of PDI-based twistacenes. We demonstrate that this remote chirality is able to control the helicity of flexible [4]helicene subunits by UV-vis, CD spectroscopy, X-ray crystallography, and TDDFT calculations. Furthermore, we have discovered that both the chiral substituent and the solvent each has a strong impact on the sign and intensity of the CD signals, highlighting the control of the dynamic helicity in this flexible system. DFT calculations suggest that the steric interaction of the chiral substituents is the important factor in how well a particular group is at inducing a preferred helicity.

Single-Handed Helicene Nanoribbons via Transfer of Chiral Information.

Here we show the access to single-handed helicene nanoribbons by utilizing a [6]helicene building block to induce diastereoselective, photochemical formation of [5]helicene units. Specifically, we have synthesized nanoribbons P1 and P2 with different ratios of [6]helicene "sergeants" to [5]helicene "soldiers", which on average consist of between ∼50 and 60 ortho-annulated benzene rings. These are the longest, optically active helicene backbones that have been prepared to date. The chiroptic properties of P1 and P2 reveal the transfer of stereochemical information from "sergeants" to "soldiers". To gain further insight into the stereo-information relay, we apply the same molecular design to discrete, model oligomers 1-5 and confirm that they also preferentially adopt homochiral geometries.

Molecular subtyping reveals immune alterations in IDH wild-type lower-grade diffuse glioma.

Isocitrate dehydrogenase (IDH) wild-type diffuse lower-grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression-based molecular classification of IDH wild-type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild-type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy-three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild-type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up-regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A/CDKN2B, DMRTA1, C9orf53, and MTAP. Furthermore, we developed and validated a five-gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild-type diffuse LGGs and deepen our molecular understandi-g of this tumor entity. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Characterization and prognostic significance of alternative splicing events in lower-grade diffuse gliomas.

Alternative splicing (AS) is assumed to play important roles in the progression and prognosis of cancer. Currently, the comprehensive analysis and clinical relevance of AS in lower-grade diffuse gliomas have not been systematically addressed. Here, we gathered alternative splicing data of lower-grade diffuse gliomas from SpliceSeq. Based on the Percent Spliced In (PSI) values of 515 lower-grade diffuse glioma patients from the Cancer Genome Atlas (TCGA), we performed subtype-differential AS analysis and consensus clustering to determine robust clusters of patients. A total of 48 050 AS events in 10 787 genes in lower-grade diffuse gliomas were profiled. Subtype-differential splicing analysis and functional annotation revealed that spliced genes were significantly enriched in numerous cancer-related biological phenotypes and signalling pathways. Consensus clustering using AS events identified three robust clusters of patients with distinguished pathological and prognostic features. Moreover, each cluster was also associated with distinct genomic alterations. Finally, we developed and validated an AS-related signature with Cox proportional hazards model. The signature, significantly associated with clinical and molecular features, could serve as an independent prognostic factor for lower-grade diffuse gliomas. Thus, our results indicated that AS events could discriminate molecular subtypes and have prognostic impact in lower-grade diffuse gliomas.

Unexpectedly High Indoor HONO Concentrations Associated with Photochemical NO2 Transformation on Glass Windows.

Nitrous acid (HONO) is an important gaseous pollutant contributing to indoor air pollution because it causes adverse health effects and is the main source of hydroxyl radicals (OH). Here, we present direct measurements of HONO produced through light-induced heterogeneous reactions of NO2 with grime adsorbed on glass window. The uptake coefficients of NO2 [γ(NO2)] on the glass plates from the kitchen increased markedly from (2.3 ± 0.1) × 10-6 at 0% RH to (4.1 ± 0.5) × 10-6 at 90% RH. We report a significant quantity of daytime HONO produced in the kitchen, compared to the living room and bedroom. Kinetic modeling suggests that phase state and bulk diffusivity play important roles in the NO2 uptake; the best fit to the measured uptake coefficients is obtained with fixed diffusion coefficients. Photon scattering may be occurring at the surface of the films, leading to enhanced photon-excitation rates of polycyclic aromatic hydrocarbons. By taking these effects into account, the results from this study indicate that the HONO yields obtained in this study can explain the missing HONO in the photochemical models describing the indoor air chemistry.

Light-Enhanced Heterogeneous Conversion of NO2 to HONO on Solid Films Consisting of Fluorene and Fluorene/Na2SO4: An Impact on Urban and Indoor Atmosphere.

Polycyclic aromatic hydrocarbons (PAHs) as constituents of urban grime and indoor surfaces can impact the photochemical conversion of nitrogen dioxide (NO2) to nitrous acid (HONO) thereby impacting the oxidation capacity of the atmosphere. In this study we investigate the effect of relative humidity (RH%), light intensity, and NO2 concentrations on uptake coefficients (γ) of NO2 on solid film consisting of fluorene (FL) and a mixture of FL and Na2SO4 as a proxy for urban and indoor grime at ambient pressure and temperature. γ(NO2) on solid FL increased markedly from (5.7 ± 1.7) × 10-7 at 0% RH to (4.6 ± 1.0) × 10-6 at 90% RH. The NO2 to HONO conversion yield, (ΔHONO/ΔNO2)%, increases with RH from 40% at 0% RH up to 80% at 60-90% RH, indicating that the water molecules favor the formation of HONO up to 60% RH. These results suggest that the heterogeneous photochemical reaction of NO2 on FL and FL/Na2SO4 can be an important source of HONO in the urban environment and indoor atmosphere and should be considered in photochemical models.

Molecular classification of IDH-mutant glioblastomas based on gene expression profiles.

Isocitrate dehydrogenase (IDH) mutant glioblastoma (GBM), accounts for ~10% GBMs, arises from lower grade diffuse glioma and preferentially appears in younger patients. Here, we aim to establish a robust gene expression-based molecular classification of IDH-mutant GBM. A total of 33 samples from the Chinese Glioma Genome Atlas RNA-sequencing data were selected as training set, and 21 cases from Chinese Glioma Genome Atlas microarray data were used as validation set. Consensus clustering identified three groups with distinguished prognostic and molecular features. G1 group, with a poorer clinical outcome, mainly contained TERT promoter wild-type and male cases. G2 and G3 groups had better prognosis differed in gender. Gene ontology analysis showed that genes enriched in G1 group were involved in DNA replication, cell division and cycle. On the basis of the differential genes between G1 and G2/G3 groups, a six-gene signature was developed with a Cox proportional hazards model. Kaplan-Meier analysis found that the acquired signature could differentiate the outcome of low- and high-risk cases. Moreover, the signature could also serve as an independent prognostic factor for IDH-mutant GBM in the multivariate Cox regression analysis. Gene ontology and gene set enrichment analyses revealed that gene sets correlated with high-risk group were involved in cell cycle, cell proliferation, DNA replication and repair. These finding highlights heterogeneity within IDH-mutant GBMs and will advance our molecular understanding of this lethal cancer.

Prognostic power of a lipid metabolism gene panel for diffuse gliomas.

Lipid metabolism reprogramming plays important role in cell growth, proliferation, angiogenesis and invasion in cancers. However, the diverse lipid metabolism programmes and prognostic value during glioma progression remain unclear. Here, the lipid metabolism-related genes were profiled using RNA sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. Gene ontology (GO) and gene set enrichment analysis (GSEA) found that glioblastoma (GBM) mainly exhibited enrichment of glycosphingolipid metabolic progress, whereas lower grade gliomas (LGGs) showed enrichment of phosphatidylinositol metabolic progress. According to the differential genes of lipid metabolism between LGG and GBM, we developed a nine-gene set using Cox proportional hazards model with elastic net penalty, and the CGGA cohort was used for validation data set. Survival analysis revealed that the obtained gene set could differentiate the outcome of low- and high-risk patients in both cohorts. Meanwhile, multivariate Cox regression analysis indicated that this signature was a significantly independent prognostic factor in diffuse gliomas. Gene ontology and GSEA showed that high-risk cases were associated with phenotypes of cell division and immune response. Collectively, our findings provided a new sight on lipid metabolism in diffuse gliomas.

Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma.

BACKGROUND: Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown. METHODS: Here, we profiled differentially expressed antisense lncRNAs in glioma using RNA sequencing data from Chinese Glioma Genome Atlas database. Cox regression was performed to evaluate the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were used for functional analysis of antisense LncRNAs. RESULTS: Expression profiling identified 169 aberrantly expressed antisense lncRNAs between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM), 113 antisense lncRNAs between LGG IDH-wt and IDH-mut samples, and 70 antisense lncRNAs between GBM IDH-wt and IDH-mut samples, respectively. Among them, three antisense lncRNAs (WDFY3-AS2, MCM3AP-AS1 and LBX2-AS1) were significantly associated with prognosis and malignant progression of patients. WDFY3-AS2, the top one of downregulated antisense lncRNAs in GBM with fold change of 0.441 (P < 0.001), showed specific decreased expression in classical, mesenchymal, LGG IDH-wt, GBM IDH-wt or MGMT promoter unmethylated stratified patients. Chi square test found that WDFY3-AS2 was significantly associated with the clinical and molecular features of glioma. Univariate and multivariate Cox regression analysis indicated that WDFY3-AS2 was independently correlated with overall survival (OS) of patients. Kaplan-Meier analysis found that patients with high WDFY3-AS2 expression had longer OS than the low expression ones in the stratified cohorts. Additionally, GO and GSEA showed that gene sets correlated with WDFY3-AS2 expression were involved in regulation of synaptic transmission, glutamate receptor and TNF signaling pathway. CONCLUSION: Our findings provided convincing evidence that WDFY3-AS2 is a novel valuable prognostic biomarker for diffuse glioma.

Using Polyurethane Foam-Based Passive Air Sampling Technique to Monitor Monosaccharides at a Regional Scale.

Monosaccharides are important tracers of pollution aerosol from biomass burning. Air sampling of monosaccharides is often conducted using active samplers. However, applicability of sampling monosaccharides using polyurethane foam passive air samplers (PUF-PASs) has not been investigated, since passive air samplers are often applied to monitor semivolatile organic contaminants in large scale and remote area. Our study successfully collected atmospheric monosaccharides using PUF-PASs, providing a valuable tool for monosaccharides sampling. PUF-PAS sampling rates for individual monosaccharides were calibrated using an active sampler for 92 days, and were 1.1, 1.5, and 1.1 m3/d for levoglucosan, mannosan, and galactosan, respectively. Degradation of monosaccharides in PUF-PAS was demonstrated to be negligible by spike test of 13C-labeled levoglucosan. Furthermore, passive sampling was carried out at 11 sites in the Pearl River Delta of Southern China from January to April and July to September of 2015. Monosaccharide concentrations derived from PUF-PASs were comparable with the reported data obtained by active sampling, demonstrating that the PUF-PAS approach is valid for monosaccharides monitoring. On the basis of our approach, we found that there is a clear correlation between the monosaccharide concentrations and the MODIS fire activities during January-April.

Exploring the differences of antibiotic resistance genes profiles between river surface water and sediments using metagenomic approach.

To better understand the potential genic communication and dissemination of antibiotic resistance genes (ARGs) in different environmental matrices, the differences of ARG profiles between river surface water and sediments were explored. Metagenomic analysis was applied to investigate the comprehensive ARG profiles in water and sediment samples collected from the highly human-impacted catchment of the Beijiang River and its river source. A total of 135 ARG subtypes belonging to 18 ARG types were identified. Generally, ARGs in surface water were more diverse and abundant than those in sediments. ARG profiles in the surface water and sediment samples were distinct from each other, but some ARGs were shared by the surface water and sediments. Results revealed that multidrug and bacitracin resistance genes were the predominant ARGs types in both surface water (0.30, 0.17 copies/cell) and sediments (0.19, 0.15 copies/cell). 73 ARG subtypes were shared by the water and sediment samples and had taken over 90% of the total detected ARG abundance. Most of the shared ARGs are resistant to the clinically relevant antibiotics. Furthermore, significant correlations between the ARGs and 21 shared genera or mobile genetic elements (MGEs) (plasmids and integrons) were found in surface water and sediments, suggesting the important role of genera or MGEs in shaping ARGs profiles, propagation and distribution. These findings provide deeper insight into mitigating the propagation of ARGs and the associated risks to public health.

Characterizing the antibiotic resistance genes in a river catchment: Influence of anthropogenic activities.

Previous studies on environmental antibiotics resistance genes (ARGs) have focused on the pollution sources such as wastewater treatment plants, aquaculture and livestock farms, etc. Few of them had addressed this issue in a regional scale such as river catchment. Hence, the occurrence and abundances of 23 ARGs were investigated in surface water samples collected from 38 sites which located from the river source to estuary of the Beijiang River. Among them, 11 ARGs were frequently detected in this region and 5 ARGs (sulI, sulII, tetB, tetC, and tetW) were selected for their distribution pattern analysis. The abundances of the selected ARGs were higher in the upstream (8.70×106copies/ng DNA) and downstream areas (3.17×106copies/ng DNA) than those in the midstream areas (1.23×106copies/ng DNA), which was positively correlated to the population density and number of pollution sources. Pollution sources of ARGs along the Beijiang River not only had a great impact on the abundances and diversity, but also on the distribution of specific ARGs in the water samples. Both sulI and sulII were likely originated from aquaculture farms and animal farms, tetW gene was possibly associated with the mining/metal melting industry and the electric waste disposal and tetC gene was commonly found in the area with multiple pollution sources. However, the abundance of tetB was not particularly related to anthropogenic impacts. These findings highlight the influence of pollution sources and density of population on the distribution and dissemination of ARGs at a regional scale.

One-dimensional rainbow thermometry system by using slit apertures.

A new rainbow thermometry system by using slit apertures and a laser light sheet, called a one-dimensional rainbow thermometry (ORT) system, has been developed as an extension of global rainbow thermometry (GRT). This system is capable of one-dimensional or line measurements of the size and refractive index of droplets in the spray space, while the conventional GRT system is normally considered a typical "single-point" or "small volume" measurement method. The performance of this new system was tested and verified with both water and ethanol spray. The results show the feasibility and potential of ORT in simultaneous and one-dimensional measurement of the size and refractive index of liquid droplets, especially in the research field of spray evaporation and combustion.

Evaluation of twin fetal exposure to radiofrequency field during magnetic resonance imaging.

Fetal development is essential to the human lifespan. As more and more multifetal gestations have been reported recently, clinical diagnosis using magnetic resonance imaging (MRI), which introduced radiofrequency (RF) exposure, raised public concerns. The present study developed two whole-body pregnant models of 31 and 32 gestational weeks (GWs) with twin fetuses and explored RF exposure by 1.5 and 3.0 T MRI. Differences in the relative position of the fetus and changes in fetal weight can cause differences in fetal peak local specific absorption rate averaged over 10 g tissue (pSAR10g). Variation of pSAR10g due to different fetal positions can be ~35%. Numerically, twin and singleton fetal pSAR10g results were not significantly different, however twin results exceeded the limit in some cases (e.g. fetuses of 31 GW at 1.5 T), which indicated the necessity for further research employing anatomically correct twin-fetal models coming from various GWs and particular sequence to be applied.