Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 µm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1ß. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for  PM2.5 air pollutants  and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.

Mutation of putative glycosyl transferases PslC and PslI confers susceptibility to antibiotics and leads to drastic reduction in biofilm formation in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic, multidrug-resistant pathogen capable of adapting to numerous environmental conditions and causing fatal infections in immunocompromised patients. The predominant lifestyle of P. aeruginosa is in the form of biofilms, which are structured communities of bacteria encapsulated in a matrix containing exopolysaccharides, extracellular DNA (eDNA) and proteins. The matrix is impervious to antibiotics, rendering the bacteria tolerant to antimicrobials. P. aeruginosa also produces a plethora of virulence factors such as pyocyanin, rhamnolipids and lipopolysaccharides among others. In this study we present the molecular characterization of pslC and pslI genes, of the exopolysaccharide operon, that code for putative glycosyltransferases. PslC is a 303 amino acid containing putative GT2 glycosyltrasferase, whereas PslI is a 367 aa long protein, possibly functioning as a GT4 glycosyltransferase. Mutation in either of these two genes results in a significant reduction in biofilm biomass with concomitant decline in c-di-GMP levels in the bacterial cells. Moreover, mutation in pslC and pslI dramatically increased susceptibility of P. aeruginosa to tobramycin, colistin and ciprofloxacin. Additionally, these mutations also resulted in an increase in rhamnolipids and pyocyanin formation. We demonstrate that elevated rhamnolipids promote a swarming phenotype in the mutant strains. Together these results highlight the importance of PslC and PslI in the biogenesis of biofilms and their potential as targets for increased antibiotic susceptibility and biofilm inhibition.

Immunomodulatory fibrous hyaluronic acid-Fmoc-diphenylalanine-based hydrogel induces bone regeneration.

AIM: To investigate the potential of an ultrashort aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration. MATERIALS AND METHODS: Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm-diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate hydrogel or left unfilled. Eight weeks after implantation, histology and micro-computed tomography analyses were performed. Immunohistochemistry was performed in six rats to assess the hydrogel's immunomodulatory effect. RESULTS: A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46 KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone. CONCLUSIONS: FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration.

Prediction of surfactant requirement in Indian preterm infants by lung ultrasound scores: a diagnostic accuracy study from a developing country.

The purpose of this study is to validate lung ultrasound score (LUS) for prediction of surfactant replacement therapy (SRT) in Indian infants of 27-336/7 weeks gestational age (GA). This prospective diagnostic accuracy study was conducted in a level 3 neonatal care unit in India. Consecutively born preterm infants with respiratory distress syndrome (RDS) were enrolled. Surfactant was administered if oxygen requirement exceeded > 30%. Baseline characteristics, respiratory parameters, and lung ultrasound images were recorded soon after admission and compared between surfactant and non-surfactant groups. Adjusted odds ratio (OR) and diagnostic accuracy of LUS were calculated for SRT. Among 78 infants with RDS included in the final analysis, 62 received surfactant (79.48%). Median time of performing lung ultrasound was 50 min of life in both groups. Median LUS in the anterior and posterior chest areas of either side as well as total LUS was significantly higher in the surfactant group. After adjusting for other confounders, LUS was found to be a significant predictor of SRT (adjusted OR (95%CI): 1.55 (1.15-2.087)). Diagnostic accuracy of LUS was determined by receiver operating characteristic (ROC) curve analysis (AUC (95% CI): 0.751 (0.64-0.842), p < 0.001). A cutoff score of ≥ 9 for LUS was considered optimal for SRT (sensitivity (95%CI): 70.97% (57.87-81.45), specificity (95%CI): 68.75% (41.48-87.87)). CONCLUSION: Lung ultrasound is a valid diagnostic tool for SRT in Indian setting with a cutoff score ≥ 9. TRIAL REGISTRATION: CTRI/2021/11/038269. WHAT IS KNOWN: • Surfactant requirement in preterm infants with RDS has been traditionally based on FiO2 criteria. • Lung ultrasound score can predict the need for surfactant although majority of the studies originated in developed countries. WHAT IS NEW: • Lung ultrasound is a valid tool for surfactant replacement therapy even in developing countries like India.

Assessment of myocardial function in late preterm and term infants with transient tachypnea of the newborn using tissue Doppler imaging - a pilot observational study.

The aim of this study was to compare conventional and tissue Doppler echocardiography parameters between transient tachypnea of the newborn (TTN) and healthy control infants. This cross sectional pilot observational study was conducted in a level 3 neonatal care unit of India. Consecutively born late preterm and term infants (LPTI) with TTN were eligible for enrollment. Control group was selected from healthy LPTI. Conventional and tissue Doppler (myocardial velocities, myocardial performance index (MPI)) echocardiography was done within first 12 h (D1) and 48-72 h (D3) of life. Conventional echocardiography parameters were fractional shortening (FS), ejection fraction (EF), ventricular output, E/A ratio, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), and pulmonary artery acceleration to ejection time ratio (PATET). Baseline characteristics and echocardiography images were compared between TTN and control groups. Out of 60 infants enrolled, 34 from TTN and 20 from control group were finally analyzed. Mean (SD) gestational age and birth weight of the study population was 366/7(1.8) weeks and 2398(376) g respectively. Left ventricular (LV) parameters were similar between both groups. On D1, right ventricular (RV)e' was smaller (6.42(1) cm/s vs. 7.68(1.68) cm/s, p 0.022), and E/e' (7.79(1.51) vs. 6.08(2.59), p 0.037) was larger in TTN group, indicating RV diastolic dysfunction. RV MPI (0.61(0.11) vs. 0.44(0.12), p < 0.001) was also larger, signifying RV global myocardial dysfunction. Similar findings were observed on D3. PATET was lower in TTN group on both D1 (0.34 (0.05) vs. 0.42 (0.05), p < 0.001) and D3 (0.38 (0.05) vs. 0.43 (0.02), p 0.004) suggesting persistently raised pulmonary arterial pressure, although only 2 infants developed pulmonary hypertension identified by standard echocardiography.   Conclusion: Myocardial tissue Doppler imaging of TTN infants revealed occult right ventricular diastolic dysfunction secondary to persistently raised pulmonary arterial pressure. What is Known: •Transient tachypnea of the newborn may be associated with pulmonary arterial hypertension. What is New: •Tissue Doppler imaging in infants with transient tachypnea of the newborn revealed occult right ventricular diastolic dysfunction secondary to raised pulmonary arterial pressure, not detected by standard echocardiography.

A Spectroscopically Observed Iron Nitrosyl Intermediate in the Reduction of Nitrate by a Surface-Conjugated Electrocatalyst.

We report an iron-based graphite-conjugated electrocatalyst (GCC-FeDIM) that combines the well-defined nature of homogeneous molecular electrocatalysts with the robustness of a heterogeneous electrode. A suite of spectroscopic methods, supported by the results of DFT calculations, reveals that the electrode surface is functionalized by high spin (S = 5/2) Fe(III) ions in an FeN4Cl2 coordination environment. The chloride ions are hydrolyzed in aqueous solution, with the resulting cyclic voltammogram revealing a Gaussian-shaped wave assigned to 1H+/1e- reduction of surface Fe(III)-OH surface. A catalytic wave is observed in the presence of NO3-, with an onset potential of -1.1 V vs SCE. At pH 6.0, GCC-FeDIM rapidly reduces NO3- to ammonium and nitrite with 88 and 6% Faradaic efficiency, respectively. Mechanistic studies, including in situ X-ray absorption spectroscopy, suggest that electrocatalytic NO3- reduction involves an iron nitrosyl intermediate. The Fe-N bond length (1.65 Å) is similar to that observed in {Fe(NO)}6 complexes, which is supported by the results of DFT calculations.

PPARgamma agonism inhibits progression of premalignant lesions in a murine lung squamous cell carcinoma model.

The N-nitroso-trischloroethylurea (NTCU)-induced mouse model of squamous lung carcinoma recapitulates human disease from premalignant dysplasia through invasive tumors, making it suitable for preclinical chemoprevention drug testing. Pioglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model. Female FVB/N mice were exposed to vehicle, NTCU or NTCU + oral pioglitazone for 32 weeks. NTCU induces the appearance of basal cells in murine airways while decreasing/changing their epithelial cell makeup, resulting in development of bronchial dysplasia. H&E and keratin 5 (KRT5) staining were used to detect and grade squamous lesions in formalin fixed lungs. mRNA expression of epithelial to mesenchymal transition (EMT) markers and basal cell markers were measured by qPCR. Dysplasia persistence markers desmoglein 3 and polo like kinase 1 were measured by immunohistochemistry. Basal cell markers KRT14 and p63, club cell specific protein and ciliated cell marker acetylated tubulin were measured by immunofluorescence. Pioglitazone treatment significantly reduced squamous lesions and the presence of airway basal cells, along with increasing normal epithelial cells in the airways of NTCU-exposed mice. Pioglitazone also significantly influenced EMT gene expression to promote a more epithelial, and less mesenchymal, phenotype. Pioglitazone reduced the presence of squamous dysplasia and maintained normal airway cell composition. This work increases the knowledge of mechanistic pathways in PPARγ agonism for lung cancer interception and provides a basis for further investigation to advance this chemoprevention strategy.

Effect of Antenatal Dexamethasone in Late Preterm Period on Neonatal Hypoglycemia: A Prospective Cohort Study from a Developing Country.

OBJECTIVES: This study compared the risk of hypoglycemia within 72 h of life in infants with and without exposure to antenatal dexamethasone in the late preterm period (34-366/7 week's gestational age). METHODS: This prospective cohort study was conducted in a tertiary care neonatal unit of Eastern India from May 2021 to November 2021. Babies in the exposed group received at least one dose of antenatal dexamethasone in the late preterm period between 7 days before delivery and birth. 'Complete course' of antenatal steroid was defined as four doses of injection dexamethasone at 12 h intervals and <4 doses were considered as 'Partial course'. Primary outcome was incidence of hypoglycemia within 72 h of life, defined as whole blood glucose <45 mg/dl. RESULTS: Total 298 infants (98 in control, 134 in partial and 66 in complete group) were assessed for final outcome. No significant difference in outcomes were seen in the exposed group compared to unexposed group. However, incidence of hypoglycemia within 72 h (complete vs. partial p= 0.008, complete vs. control p=0.005) and 12 h of life (complete vs. partial p=0.013, complete vs. control p=0.013) was significantly less in complete steroid group. Logistic regression analysis revealed complete course of antenatal corticosteroid significantly decreased the risk of hypoglycemia [adjusted odds ratio, 95% confidence interval (CI) 0.15 (0.03-0.69), p=0.015]. Number needed to be exposed for one additional benefit was 7 (95% CI, 6.35-22.14). CONCLUSION: Complete course of dexamethasone administered to mothers at risk of late preterm delivery reduces risk of neonatal hypoglycemia within 72 h of life.

Dynamics and control of delayed rumor propagation through social networks.

Investigation of rumor spread dynamics and its control in social networking sites (SNS) has become important as it may cause some serious negative effects on our society. Here we aim to study the rumor spread mechanism and the influential factors using epidemic like model. We have divided the total population into three groups, namely, ignorant, spreader and aware. We have used delay differential equations to describe the dynamics of rumor spread process and studied the stability of the steady-state solutions using the threshold value of influence which is analogous to the basic reproduction number in disease model. Global stability of rumor prevailing state has been proved by using Lyapunov function. An optimal control system is set up using media awareness campaign to minimize the spreader population and the corresponding cost. Hopf bifurcation analyses with respect to time delay and the transmission rate of rumors are discussed here both analytically and numerically. Moreover, we have derived the stability region of the system corresponding to change of transmission rate and delay values.

Balanced Wnt/Dickkopf-1 signaling by mesenchymal vascular progenitor cells in the microvascular niche maintains distal lung structure and function.

The well-described Wnt inhibitor Dickkopf-1 (DKK1) plays a role in angiogenesis as well as in regulation of growth factor signaling cascades in pulmonary remodeling associated with chronic lung diseases (CLDs) including emphysema and fibrosis. However, the specific mechanisms by which DKK1 influences mesenchymal vascular progenitor cells (MVPCs), microvascular endothelial cells (MVECs), and smooth muscle cells (SMCs) within the microvascular niche have not been elucidated. In this study, we show that knockdown of DKK1 in Abcg2pos lung mouse adult tissue resident MVPCs alters lung stiffness, parenchymal collagen deposition, microvessel muscularization and density as well as loss of tissue structure in response to hypoxia exposure. To complement the in vivo mouse modeling, we also identified cell- or disease-specific responses to DKK1, in primary lung chronic obstructive pulmonary disease (COPD) MVPCs, COPD MVECs, and SMCs, supporting a paradoxical disease-specific response of cells to well-characterized factors. Cell responses to DKK1 were dose dependent and correlated with varying expressions of the DKK1 receptor, CKAP4. These data demonstrate that DKK1 expression is necessary to maintain the microvascular niche whereas its effects are context specific. They also highlight DKK1 as a regulatory candidate to understand the role of Wnt and DKK1 signaling between cells of the microvascular niche during tissue homeostasis and during the development of chronic lung diseases.

Experimental Demonstration of an Electrostatic Orbital Angular Momentum Sorter for Electron Beams.

The component of orbital angular momentum (OAM) in the propagation direction is one of the fundamental quantities of an electron wave function that describes its rotational symmetry and spatial chirality. Here, we demonstrate experimentally an electrostatic sorter that can be used to analyze the OAM states of electron beams in a transmission electron microscope. The device achieves postselection or sorting of OAM states after electron-material interactions, thereby allowing the study of new material properties such as the magnetic states of atoms. The required electron-optical configuration is achieved by using microelectromechanical systems technology and focused ion beam milling to control the electron phase electrostatically with a lateral resolution of 50 nm. An OAM resolution of 1.5ℏ is realized in tests on controlled electron vortex beams, with the perspective of reaching an optimal OAM resolution of 1ℏ in the near future.

Deciphering the synergistic impact of elevated temperature and oil pollution on meiobenthic community structure: A benthocosm study.

Meiobenthos has been considered as an excellent tool for biomonitoring assessment. Elevated temperature and oil pollution are considered as the most pervasive aspects of global environmental changes and matter of concern for contemporary society. Presently, very limited information is available about the synergistic effect of these stressors on meiobenthic community structure and tolerance potential from tropical intertidal environment. Here, we assessed their impacts on meiobenthic community by conducting a 60 days long benthocosm experiment selecting three sets of temperature (25°, 30° and 35 °C) and two sets of diesel oil (low and high) combinations. Gradual changes in their community composition were revealed discernibly with exposures to both the disturbances after 30 and 60 days of experimental period. Diversity profiles for the nematodes were less affected, but copepods showed a graded response of decreasing density with increasing dose of both the stressors. Other meiobenthic taxa such as halacarid mite, turbellaria and polycheate juveniles were adversely affected and eliminated from the treatments, howbeit abundance of ostracods, foraminiferans and bivalve settlers varied significantly. A 3-factor PERMANOVA indicated a significant effect of temperature, diesel, between their interaction and interaction among stressors and time on meiofaunal abundances. In case of free-living nematodes, temperature rise and diesel contamination synchronously led to an elimination of k-selected species like Halalaimus gracilis, H. longicaudatus, Oxystomina aesetosa and Pomponema sp. with a significant decrease in abundance of H. capitulatus and Oncholaimus sp. The r-selected species Daptonema invagiferoum, Sabatieria praedatrix, Theristus acer, Monhystera sp. and Thalassomonhystera sp. had endured even at high doses of diesel treatment in three different temperatures set up. The effects were evident in term of changes in life strategies with an increment of opportunistic species and increased trophic diversity of deposit feeders in treated sediments. Overall, elevated temperature together with diesel oil contamination were found to alter species dynamics within shallow intertidal meiobenthic communities, which might have significant Armageddon on benthic ecosystem functioning.

Formation of peptide-based oligomers in dimethylsulfoxide: identifying the precursor of fibril formation.

The well-studied dipeptide fluorenylmethyloxycarbonyl-di-phenylalanine (FmocFF) forms a rigid hydrogel upon dissolving in dimethylsulfoxide (DMSO) and dilution in H2O. Here, we explored the pre-aggregation of the peptide in pure DMSO by vibrational spectroscopies, X-ray powder diffraction and dynamic light scattering. Our results show an equilibrium between a dominant population of amorphous oligomers (on a length scale of 2 nm) and a small number of protofibrils/fibrils (on a length scale of 30 nm in the centimolar and of 200 nm in the sub-molar region). To probe the mechanism underlying the formation of these protofilaments, we measured the 1H-NMR, IR and visible Raman spectra of DMSO containing different FmocFF concentrations, ranging between 10 and 300 mM. Our data reveal that interpeptide hydrogen bonding leads to the self-assembly of FmocFF in the centimolar region, while π-π stacking between Fmoc-groups is observed above 100 mM. The high 3J(HNHCα) coupling constant of the N-terminal amide proton indicates that the Fmoc end-cap of the peptide locks the N-terminal residue into a conformational ensemble centered at a φ-value of ca. -120°, which corresponds to a parallel ß-sheet type conformation. The 3J(HNHCα) coupling constant of the C-terminal residue is indicative of a polyproline II (pPII)/ßt mixture. Our results suggest that the gelation of FmocFF caused by the addition of a small amount of water to DMSO mixtures is facilitated by the formation of disordered protofibrils in pure DMSO.

Bi-functional peptide-based 3D hydrogel-scaffolds.

Over the last few years, hydrogels have been proposed for many biomedical applications, including drug delivery systems and scaffolds for tissue engineering. In particular, peptides have been envisioned as excellent candidates for the development of hydrogel materials, due to their intrinsic biocompatibility, ease of handling, and intrinsic biodegradability. Recently, we developed a novel hybrid polymer-peptide conjugate, PEG8-(FY)3, which is able to self-assemble into a self-supporting soft hydrogel over dry and wet surfaces as demonstrated by molecular dynamics simulation. Here, we describe the synthesis and supramolecular organization of six novel hexapeptides rationally designed by punctual chemical modification of the primary peptide sequence of the ancestor peptide (FY)3. Non-coded amino acids were incorporated by replacing the phenylalanine residue with naphthylalanine (Nal) and tyrosine with dopamine (Dopa). We also studied the effect of the modification of the side chain and the corresponding PEGylated peptide analogues, on the structural and mechanical properties of the hydrogel. Secondary structure, morphology and rheological properties of all the peptide-based materials were assessed by various biophysical tools. The in vitro biocompatibility of the supramolecular nanostructures was also evaluated on fibroblast cell lines. We conclude that the PEG8-(Nal-Dopa)3 hydrogel possesses the right properties to serve as a scaffold and support cell growth.

The Kinome of Human Alveolar Type II and Basal Cells, and Its Reprogramming in Lung Cancer.

The discovery of mutant tyrosine kinases as oncogenic drivers of lung adenocarcinomas has changed the basic understanding of lung cancer development and therapy. Yet, expressed kinases (kinome) in lung cancer progenitor cells, as well as whether kinase expression and the overall kinome changes or is reprogrammed upon transformation, is incompletely understood. We hypothesized that the kinome differs between lung cancer progenitor cells, alveolar type II cells (ATII), and basal cells (BC) and that their respective kinomes undergo distinct lineage-specific reprogramming to adenocarcinomas and squamous cell carcinomas upon transformation. We performed RNA sequencing on freshly isolated human ATII, BC, and lung cancer cell lines to define the kinome in nontransformed cells and transformed cells. Our studies identified a unique kinome for ATII and BC and changes in their kinome upon transformation to their respective carcinomas.

Fmoc-FF and hexapeptide-based multicomponent hydrogels as scaffold materials.

Short peptides or single amino acids are interesting building blocks for fabrication of hydrogels, frequently used as extracellular matrix-mimicking scaffolds for cell growth in tissue engineering. The combination of two or more peptide hydrogelators could allow obtaining different materials exhibiting new architectures, tunable mechanical properties, high stability and improved biofunctionality. Here we report on the synthesis, formulation and multi-scale characterization of peptide-based mixed hydrogels formed by the low molecular weight Fmoc-FF (Nα-fluorenylmethyloxycarbonyl diphenylalanine) hydrogelator and of the PEG8-(FY)3 hexapeptide, containing three repetitions of the Phe-Tyr motif and a PEG moiety at its N-terminus. Mixed hydrogels were also prepared by replacing PEG8-(FY)3 with its analogue (FY)3, without the PEG moiety. Rheology analysis confirmed the improved mechanical features of the multicomponent gels prepared at two different ratios (2/1 or 1/1, v/v). However, the presence of the hydrophilic PEG polymeric moiety causes a slowing down of the gel kinetic formation (from 42 to 18 minutes) and a decrease of the gel rigidity (G' from 9 to 6 kPa). Preliminary in vitro biocompatibility and cell adhesion assays performed on Chinese hamster ovarian (CHO) cells suggest a potential employment of these multicomponent hydrogels as exogenous scaffold materials for tissue engineering.

Composite of Peptide-Supramolecular Polymer and Covalent Polymer Comprises a New Multifunctional, Bio-Inspired Soft Material.

Peptide-based supramolecular hydrogels are utilized as functional materials in tissue engineering, axonal regeneration, and controlled drug delivery. The Arg-Gly-Asp (RGD) ligand based supramolecular gels have immense potential in this respect, as this tripeptide is known to promote cell adhesion. Although several RGD-based supramolecular hydrogels have been reported, most of them are devoid of adequate resilience and long-range stability for in vitro cell culture. In a quest to improve the mechanical properties of these tripeptide-based gels and their durability in cell culture media, the Fmoc-RGD hydrogelator is non-covalently functionalized with a biocompatible and biodegradable polymer, chitosan, resulting in a composite hydrogel with enhanced gelation rate, mechanical properties and cell media durability. Interestingly, both Fmoc-RGD and Fmoc-RGD/chitosan composite hydrogels exhibit thixotropic properties. The utilization of the Fmoc-RGD/chitosan composite hydrogel as a scaffold for 2D and 3D cell cultures is demonstrated. The composite hydrogel is found to have notable antibacterial activity, which stems from the inherent antibacterial properties of chitosan. Furthermore, the composite hydrogels are able to produce ultra-small, mono-dispersed, silver nanoparticles (AgNPs) arranged on the fiber axis. Therefore, the authors' approach harnesses the attributes of both the supramolecular-polymer (Fmoc-RGD) and the covalent-polymer (chitosan) component, resulting in a composite hydrogel with excellent potential.

Exhaustion of Airway Basal Progenitor Cells in Early and Established Chronic Obstructive Pulmonary Disease.

RATIONALE: Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, prediagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired. OBJECTIVES: To examine airway basal progenitor cells and lung function in smokers with and without COPD. METHODS: Bronchial biopsies taken from smokers at risk for COPD and lung cancer were used to acquire airway basal progenitor cells. They were evaluated for count, self-renewal, and multipotentiality (ability to differentiate to basal, mucous, and ciliated cells), and progenitor count was examined for its relationship with lung function. MEASUREMENTS AND MAIN RESULTS: Basal progenitor count, self-renewal, and multipotentiality were all reduced in COPD versus non-COPD. COPD progenitors produced an epithelium with increased basal and mucous cells and decreased ciliated cells, replicating the COPD phenotype. Progenitor depletion correlated with lung function and identified a subset of subjects without COPD with lung function that was midway between non-COPD with high progenitor counts and those with COPD. CONCLUSIONS: Basal progenitor dysfunction relates to the histologic and physiologic manifestations of COPD and identifies a subset that may represent an early, prediagnostic stage of COPD, indicating that progenitor exhaustion is involved in COPD pathogenesis.