Constructing N-Containing Poly(p-Phenylene) (PPP) Films Through A Cathodic-Dehalogenation Polymerization Method.

Developing the films of N-containing unsubstituted poly(p-phenylene) (PPP) films for diverse applications is significant and highly desirable because the replacement of sp2 C atoms with sp2 N atoms will bring novel properties to the as-prepared polymers. In this research, an electrochemical-dehalogenation polymerization strategy is employed to construct two N-containing PPP films under constant potentials, where 2,5-diiodopyridine (DIPy) and 2,5-dibromopyrazine (DBPz) are used as starting agents. The corresponding polymers are named CityU-23 (for polypyridine) and CityU-24 (for polypyrazine). Moreover, it is found that both polymers can form films in situ on different conductive substrates (i.e., silicon, gold, ITO, and nickel), satisfying potential device fabrication. Furthermore, the as-obtained thin films of CityU-23 and CityU-24 exhibit good performance of alkaline hydrogen evolution reaction with the overpotential of 212.8 and 180.7 mV and the Tafel slope of 157.0 and 122.4 mV dec-1, respectively.

Association of blood cadmium concentration with chronic obstructive pulmonary disease progression: a prospective cohort study.

BACKGROUND: Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. METHODS: Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. RESULTS: Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. CONCLUSION: Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.

Arsenic exposure and pulmonary function decline: Potential mediating role of TRAIL in chronic obstructive pulmonary disease patients.

BACKGROUND: Environmental arsenic (As) exposure is strongly related to the progression of chronic obstructive pulmonary disease (COPD). Pulmonary epithelial cells apoptosis is implicated in the pathophysiological mechanisms of COPD. However, the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one biomarker of apoptosis, remains unclear in As-mediated pulmonary function alternations in COPD patients. METHODS: This study included 239 COPD patients. The serum level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was measured by enzyme-linked immunosorbent assay (ELISA). The blood As level was determined through inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Blood As levels exhibited a negative and dose-dependent correlation with pulmonary function. Per unit elevation of blood arsenic concentrations was related to reductions of 0.339 L in FEV1, 0.311 L in FVC, 1.171% in FEV1/FVC%, and 7.999% in FEV1% in COPD subjects. Additionally, a positive dose-response correlation of blood As with serum TRAIL was found in COPD subjects. Additionally, the level of serum TRAIL was negatively linked to lung function. Elevated TRAIL significantly mediated As-induced decreases of 11.05%, 13.35%, and 31.78% in FVC, FEV1, and FEV1%, respectively among the COPD patients. CONCLUSION: Blood As level is positively correlated with pulmonary function decline and serum TRAIL increase in individuals with COPD. Our findings suggest that elevated TRAIL levels may serve as a mediating mechanism through which As contributes to declining lung function in COPD patients.

Serum TRAIL predicts severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can trigger the apoptosis pathways through binding to relative death receptors. However, the relationship of TRAIL with community-acquired pneumonia (CAP) was unclear. This study aims at exploring the relationships between circulatory TRAIL with severity and prognosis in CAP patients through a prospective cohort study. The whole of 239 CAP patients was enrolled. Demographic characteristics and clinical information were analyzed. TRAIL and inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Circulatory TRAIL was gradually increased in accord with CAP severity scores. Spearman or Pearson correlative analysis indicated that circulatory TRAIL was strongly associated with physiologic indicators among CAP patients. Mixed logistic and linear regression models revealed that circulatory TRAIL was positively correlated with the severity scores in CAP patients. After adjusting for confounders, higher levels of circulatory TRAIL on admission significantly elevated the risks of ICU admission, mechanical ventilation, longer hospital stays, or even death during hospitalization. The predictive capacities of serum TRAIL for death were higher compared with CAP severity scores, inflammatory and infectious indicators. There are obviously positive dose-response relationships between circulatory TRAIL on admission with the severity and poor prognostic outcomes in CAP patients. Circulatory TRAIL on admission may be used as a potential biomarker in predicting the severity and poor prognosis for CAP patients.

Cross-sectional and longitudinal associations of serum Cysteine-rich 61 with severity and prognosis among community-acquired pneumonia patients in China.

Background: Cysteine-rich 61 (CYR61) is implicated in many pulmonary diseases. However, the relationship between CYR61 and community-acquired pneumonia (CAP) patients was unknown. This research aimed to estimate the correlations of serum CYR61 with severity and prognosis in CAP patients through a prospective cohort study. Methods: All 541 CAP patients were enrolled in this study. Fasting venous blood was collected. Clinical characteristics and demographic information were obtained. CYR61 and inflammatory cytokines were detected in serum using ELISA. Results: Serum CYR61 was gradually increased in parallel with severity scores in CAP patients. Correlative analysis indicated that serum CYR61 was strongly associated with many clinical parameters in CAP patients. Moreover, mixed logistic and linear regression models found that there were positive correlations between serum CYR61 and CAP severity scores after adjusted for age, BMI, and respiratory rate. Stratified analyses suggested that age affected the associations between serum CYR61 and severity scores. On admission, higher serum CYR61 levels elevated the risks of mechanical ventilation, vasoactive agent, ICU admission, death, and longer hospital stays during hospitalization. Moreover, serum CYR61 in combination with severity scores upregulated the predictive capacities for severity and death than single serum CYR61 or severity scores in CAP patients. Conclusion: There are significantly positive dose-response associations of serum CYR61 on admission with the severity and adverse prognostic outcomes, demonstrating that CYR61 is involved in the pathophysiology of CAP. Serum CYR61 may be used as a potential biomarker for the diagnosis and prognosis in CAP patients.

Uncovering a Distinct Gene Signature in Endothelial Cells Associated With Contrast Enhancement in Glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most aggressive and lethal type of brain tumors. Magnetic resonance imaging (MRI) has been commonly used for GBM diagnosis. Contrast enhancement (CE) on T1-weighted sequences are presented in nearly all GBM as a result of high vascular permeability in glioblastomas. Although several radiomics studies indicated that CE is associated with distinct molecular signatures in tumors, the effects of vascular endothelial cells, the key component of blood brain barrier (BBB) controlling vascular permeability, on CE have not been thoroughly analyzed. METHODS: Endothelial cell enriched genes have been identified using transcriptome data from 128 patients by a systematic method based on correlation analysis. Distinct endothelial cell enriched genes associated with CE were identified by analyzing difference of correlation score between CE-high and CE-low GBM cases. Immunohistochemical staining was performed on in-house patient cohort to validate the selected genes associated with CE. Moreover, a survival analysis was conducted to uncover the relation between CE and patient survival. RESULTS: We illustrated that CE is associated with distinct vascular molecular imprints characterized by up-regulation of pro-inflammatory genes and deregulation of BBB related genes. Among them, PLVAP is up-regulated, whereas TJP1 and ABCG2 are down-regulated in the vasculature of GBM with high CE. In addition, we found that the high CE is associated with poor prognosis and GBM mesenchymal subtype. CONCLUSION: We provide an additional insight to reveal the molecular trait for CE in MRI images with special focus on vascular endothelial cells, linking CE with BBB disruption in the molecular level. This study provides a potential new direction that may be applied for the treatment optimization based on MRI features.

Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing.

Passage of systemically delivered pharmacological agents into the brain is largely blocked by the blood-brain-barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). Tumor vessels in glioblastoma (GBM), the most common malignant brain tumor in humans, are abnormally permeable, but this phenotype is heterogeneous and may differ between the tumor's center and invasive front. Here, through single-cell RNA sequencing (scRNA-seq) of freshly isolated ECs from human glioblastoma and paired tumor peripheral tissues, we have constructed a molecular atlas of human brain ECs providing unprecedented molecular insight into the heterogeneity of the human BBB and its molecular alteration in glioblastoma. We identified 5 distinct EC phenotypes representing different states of EC activation and BBB impairment, and associated with different anatomical locations within and around the tumor. This unique data resource provides key information for designing rational therapeutic regimens and optimizing drug delivery.

High-Yield Exfoliation of Ultrathin 2D Ni3 Cr2 P2 S9 and Ni3 Cr2 P2 Se9 Nanosheets.

Multinary layered 2D nanomaterials can exhibit distinct physicochemical properties and innovative applications as compared to binary 2D nanomaterials due to their unique crystal structures. However, it still remains a challenge for the high-yield preparation of high-quality multinary 2D nanosheets. Here, the high-yield and large-scale production of two quaternary metal thiophosphate nanosheets are reported, i.e., Ni3 Cr2 P2 S9 and Ni3 Cr2 P2 Se9 , via the liquid exfoliation of their layered bulk crystals. The exfoliated single-crystalline Ni3 Cr2 P2 S9 nanosheets, with a lateral size ranging from a few hundred nanometers to a few micrometers and thickness of 1.4 ± 0.2 nm, can be easily used to prepare flexible thin films via a simple vacuum filtration process. As a proof-of-concept application, the fabricated thin film is used as a supercapacitor electrode with good specific capacitance. These high-yield, large-scale, solution-processable quaternary metal thiophosphate nanosheets could also be promising in other applications like biosensors, cancer therapies, and flexible electronics.

1p/19q co-deletion status is associated with distinct tumor-associated macrophage infiltration in IDH mutated lower-grade gliomas.

BACKGROUND: Tumor-associated macrophages (TAM)s are critical regulators of glioma progression. As yet, however, TAMs in isocitrate dehydrogenase (IDH) mutated lower-grade gliomas (LGGs) have not been thoroughly investigated. The aim of this study was to determine whether 1p/19q co-deletion status affects the TAM phenotype or its prevalence in IDH mutated LGGs. METHODS: TAMs in IDH mutated LGGs were analyzed using transcriptome data from 230 samples in the TCGA database in combination with transcriptome data from single-cell RNA sequencing of IDH-mutated LGGs. Proteins potentially involved in TAM regulation were examined by immuno-staining in primary LGG samples harboring IDH mutations. Essential signaling pathways regulating TAM phenotypes were investigated in a glioma mouse model using small molecule inhibitors. RESULTS: Most of the TAMs in IDH-mutated LGGs expressed the M1 activation markers CD86 and TNF, whereas a subset of individual TAMs co-expressed both M1 and M2-related markers. Bioinformatics analysis in combination with immuno-staining of IDH-mutated patient samples revealed higher amounts of TAMs expressing M2-related markers in 1p/19q non-codeletion IDH-mutated LGGs compared to 1p/19q codeletion LGGs. The levels of transforming growth factor beta 1 (TGFß1) and macrophage colony-stimulating factor (M-CSF) were significantly higher in 1p/19q non-codeletion LGGs than in 1p/19q codeletion LGGs. M-CSF and TGFß1 signal inhibition decreased tumor growth and modulated the TAM phenotype in a glioma mouse model. CONCLUSIONS: Our data indicate that 1p/19q co-deletion status relates to distinct TAM infiltration in gliomas, which is likely mediated by M-CSF and TGFß1 signaling. M-CSF and TGFß1 signaling may play a pivotal role in regulating the TAM phenotype in glioma.

Quantitative Surface Plasmon Interferometry via Upconversion Photoluminescence Mapping.

Direct far-field visualization and characterization of surface plasmon polaritons (SPPs) are of great importance for fundamental studies and technological applications. To probe the evanescently confined plasmon fields, one usually requires advanced near-field techniques, which is typically not applicable for real-time, high-throughput detecting or mapping of SPPs in complicated environments. Here, we report the utilization of rare-earth-doped nanoparticles to quantitatively upconvert invisible, evanescently confined SPPs into visible photoluminescence emissions for direct far-field visualization of SPPs in a complicated environment. The observed interference fringes between the SPPs and the coherent incident light at the metal surface provide a quantitative measurement of the SPP wavelength and the SPP propagating length and the local dielectric environments. It thus creates a new signaling pathway to sensitively transduce the local dielectric environment change into interference periodicity variation, enabling a new design of directly measurable, spectrometer-free optical rulers for rapid, ultrasensitive label-free detection of various biomolecules, including streptavidin and prostate-specific antigen, down to the femtomolar level.

Graphene oxide scrolls on hydrophobic substrates fabricated by molecular combing and their application in gas sensing.

Well-aligned graphene oxide (GO) scrolls are prepared through the controlled folding/scrolling of single-layer GO sheets using molecular combing on hydrophobic substrates, such as aged gold substrate, polydimethylsiloxane film, poly(L-lactic acid) film, and octadecyltrimethoxysilane-modified silicon dioxide. As a proof of concept, the gas sensor fabricated with a single reduced GO scroll is used to detect NO(2) gas with a concentration as low as 0.4 ppm.

Fabrication of flexible MoS2 thin-film transistor arrays for practical gas-sensing applications.

By combining two kinds of solution-processable two-dimensional materials, a flexible transistor array is fabricated in which MoS(2) thin film is used as the active channel and reduced graphene oxide (rGO) film is used as the drain and source electrodes. The simple device configuration and the 1.5 mm-long MoS(2) channel ensure highly reproducible device fabrication and operation. This flexible transistor array can be used as a highly sensitive gas sensor with excellent reproducibility. Compared to using rGO thin film as the active channel, this new gas sensor exhibits much higher sensitivity. Moreover, functionalization of the MoS(2) thin film with Pt nanoparticles further increases the sensitivity by up to ∼3 times. The successful incorporation of a MoS(2) thin-film into the electronic sensor promises its potential application in various electronic devices.

Surface immobilized cholera toxin B subunit (CTB) facilitates vesicle docking, trafficking and exocytosis.

The subunit B of cholera toxin (CTB), which specifically binds with ganglioside GM1 enriched in membrane lipid rafts, is known to interfere with multiple cell functions. However, the specific, stable and spatially defined membrane signaling induced by CTB binding is often difficult to investigate by applying CTB molecules in bulk solution due to quick internalization, elicited intracellular reactions, and homogeneous interaction with the entire cell membrane. Here, we interfaced the neuroendocrine PC12 cells with surface immobilized and patterned CTB molecules, and interrogated the effects of CTB binding on vesicular exocytosis using integrative single-cell study methods. It was discovered that CTB binding facilitates vesicle trafficking, docking and exocytosis in a cholesterol dependent manner. And these effects are probably attributable to the increased membrane GM1 and cholesterol, and enhanced Ca(2+) signaling.

Interfacing live cells with nanocarbon substrates.

Nanocarbon materials, including single-walled carbon nanotubes (SWCNTs) and graphene, promise various novel biomedical applications (e.g., nanoelectronic biosensing). In this Letter, we study the ability of SWCNT networks and reduced graphene oxide (rGO) films in interfacing several types of cells, such as neuroendocrine PC12 cells, oligodendroglia cells, and osteoblasts. It was found that rGO is biocompatible with all these cell types, whereas the SWCNT network is inhibitory to the proliferation, viability, and neuritegenesis of PC12 cells, and the proliferation of osteoblasts. These observations could be attributed to the distinct nanotopographic features of these two kinds of nanocarbon substrates.