Obstructive Sleep Apnea Screening and Effects of Surgery in Acromegaly: A Prospective Study.

Background: To identify a screening tool for obstructive sleep apnea (OSA) and evaluate the effects of endoscopic transsphenoidal surgery on improving OSA in patients with acromegaly. Methods: We prospectively enrolled adults with acromegaly scheduled for endoscopic transsphenoidal surgery. All measurements were conducted when participants were admitted for a baseline work-up for acromegaly before surgery and surveillance approximately 3 to 6 months after surgery. Respiratory event index (REI) was used as a surrogate for apnea-hypopnea index (Trial Registration: NCT03526016). Results: Of the 35 patients with acromegaly (median age, 47 years; 40% men; median body mass index, 24.4 kg/m2), 24 (68.6%) had OSA (REI ≥5/hour), 15 (42.9%) had moderate-to-severe OSA (REI ≥15/hour). At baseline, serum insulin-like growth factor 1 (IGF-1) levels were positively correlated with the REI (ρ=0.53, P=0.001). The sensitivity and negative predictive value of a Snoring, Tiredness, Observed apnea, high blood Pressure-Body mass index, age, Neck circumference, and Gender (STOP-Bang) score ≥ 3 were 93.3% and 87.5%, respectively, detecting moderate-to-severe OSA. Biochemical acromegaly remission was achieved in 32 (91.4%) patients. The median difference in the REI was -9.5/hour (95% confidence interval, -13.3 to -5.3). Half of the 24 patients diagnosed with OSA preoperatively had REI <5/hour postoperatively. In a linear mixed-effects model, changes in the REI across surgery were related to changes in IGF-1 levels. Conclusion: The STOP-Bang questionnaire is a reliable tool for OSA among patients with acromegaly. Improvement in OSA severity after surgery is related to decreased IGF-1 levels.

Association of obstructive sleep apnea with risk of lung cancer: a nationwide cohort study in Korea.

Current knowledge regarding the relationship between obstructive sleep apnea (OSA) and the risk of lung cancer is limited. This study aimed to evaluate associations between OSA and the incidence of lung cancer based on the Korean National Health Information Database. The study outcome was the incidence of newly diagnosed lung cancer, and a Cox proportional hazards model was used for analysis. A total of 181,070 adult patients newly diagnosed with OSA between 2011 and 2018 were matched with those without OSA by up to 1:5 propensity score matching based on age and sex. During follow-up over (mean ± standard deviation) 9.1 ± 2.0 years, 2614 incident cases of lung cancer were identified. The incidence rate was 39.51 per 100,000 person-years in the OSA group, and 24.93 per 100,000 person-years in the control group. After adjusting for income and the presence of comorbidities, the association remained significant (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.74-2.18, p-value < 0.001). The adjusted HR for incident lung cancer was 2.14 (95% CI 1.69-2.70) in female patients with OSA, and 1.90 (95% CI 1.67-2.16) in male patients with OSA. The risk of incident lung cancer increased with age, with a HR of 2.99 (95% CI 2.46-3.64) in those aged ≥ 65 years. This nationwide study showed an independent association between OSA and an increased risk of lung cancer in the Korean population.

Effect of the human papillomavirus vaccine on the risk of genital warts: a nationwide cohort study of Korean adolescent girls.

OBJECTIVES: The purpose of this study was to assess the effectiveness of human papillomavirus (HPV) vaccination administered to adolescent girls through Korea's National Immunization Program. METHODS: This retrospective cohort study included patients who were 12-13 years old, whether vaccinated or unvaccinated, between July 2016 and December 2017. The incidence of genital warts (GWs) was monitored through 2021. Time-stratified hazard ratios (HRs) were estimated, adjusting for birth year, socioeconomic status, and the level of urbanization of the region, and were presented with 95% confidence intervals (CIs). Data were sourced from the Immunization Registry Integration System, linked with the National Health Information Database. RESULTS: The study included 332,062 adolescent girls, with an average follow-up period of approximately 4.6 years. Except for the first year, the HRs for the vaccinated group were lower than those for the unvaccinated group. The HRs for specific cut-off years were as follows: year 2, 0.62 (95% CI, 0.31 to 1.13); year 3, 0.58 (95% CI, 0.35 to 0.96); and year 4 and beyond, 0.39 (95% CI, 0.28 to 0.52). CONCLUSIONS: Our findings indicate that HPV vaccination was associated with a reduction in the risk of GWs among adolescent girls. Notably, this reduction became significant as the incidence of GWs increased with age.

Native PLGA nanoparticles attenuate Aß-seed induced tau aggregation under in vitro conditions: potential implication in Alzheimer's disease pathology.

Evidence suggests that beta-amyloid (Aß)-induced phosphorylation/aggregation of tau protein plays a critical role in the degeneration of neurons and development of Alzheimer's disease (AD), the most common cause of dementia affecting the elderly population. Many studies have pursued a variety of small molecules, including nanoparticles conjugated with drugs to interfere with Aß and/or tau aggregation/toxicity as an effective strategy for AD treatment. We reported earlier that FDA approved PLGA nanoparticles without any drug can attenuate Aß aggregation/toxicity in cellular/animal models of AD. In this study, we evaluated the effects of native PLGA on Aß seed-induced aggregation of tau protein using a variety of biophysical, structural and spectroscopic approaches. Our results show that Aß1-42 seeds enhanced aggregation of tau protein in the presence and absence of heparin and the effect was attenuated by native PLGA nanoparticles. Interestingly, PLGA inhibited aggregation of both 4R and 3R tau isoforms involved in the formation of neurofibrillary tangles in AD brains. Furthermore, Aß seed-induced tau aggregation in the presence of arachidonic acid was suppressed by native PLGA. Collectively, our results suggest that native PLGA nanoparticles can inhibit the Aß seed-induced aggregation of different tau protein isoforms highlighting their therapeutic implication in the treatment of AD.

Differential Diagnosis of Pleural Effusion Using Machine Learning.

Rationale: Differential diagnosis of pleural effusion is challenging in clinical practice. Objectives: We aimed to develop a machine learning model to classify the five common causes of pleural effusions. Methods: This retrospective study collected 49 features from clinical information, blood, and pleural fluid of adult patients who underwent diagnostic thoracentesis between October 2013 and December 2018. Pleural effusions were classified into the following five categories: transudative, malignant, parapneumonic, tuberculous, and other. The performance of five different classifiers, including multinomial logistic regression, support vector machine, random forest, extreme gradient boosting, and light gradient boosting machine (LGB), was evaluated in terms of accuracy and area under the receiver operating characteristic curve through fivefold cross-validation. Hybrid feature selection was applied to determine the most relevant features for classifying pleural effusion. Results: We analyzed 2,253 patients (training set, n = 1,459; validation set, n = 365; extra-validation set, n = 429) and found that the LGB model achieved the best performance in both validation and extra-validation sets. After feature selection, the accuracy of the LGB model with the selected 18 features was equivalent to that with all 49 features (mean ± standard deviation): 0.818 ± 0.012 and 0.777 ± 0.007 in the validation and extra-validation sets, respectively. The model's mean area under the receiver operating characteristic curve was as high as 0.930 ± 0.042 and 0.916 ± 0.044 in the validation and extra-validation sets, respectively. In our model, pleural lactate dehydrogenase, protein, and adenosine deaminase levels were the most important factors for classifying pleural effusions. Conclusions: Our LGB model showed satisfactory performance for differential diagnosis of the common causes of pleural effusions. This model could provide clinicians with valuable information regarding the major differential diagnoses of pleural diseases.

Impact of the COVID-19 pandemic on adherence to positive airway pressure treatment in patients with obstructive sleep apnea: systematic review and meta-analysis.

BACKGROUND: The adverse effects of the COVID-19 pandemic on sleep have been well studied. However, whether the COVID-19 pandemic impacted positive airway pressure (PAP) adherence in patients with obstructive sleep apnea (OSA) remains unclear. OBJECTIVES: To evaluate the impact of the COVID-19 pandemic on adherence to PAP therapy in patients with OSA. DESIGN: A retrospective cohort study, systematic review, and meta-analysis. DATA SOURCES AND METHODS: The retrospective study included adults with OSA who received PAP prescriptions within the year before and the year after the start date of COVID-19 social distancing (22 March 2020) in South Korea. The threshold of clinical significance for PAP adherence was defined as 0.5 h/day. We also searched for relevant studies published up to 15 January 2023 using the MEDLINE and Embase databases. We performed a random-effects meta-analysis of our findings with the identified studies regarding the standardized mean change (SMC) with a 95% CI of PAP adherence. RESULTS: Our study included a total of 306 patients (mean age, 59.7 years; men, 73.5%). The average daily PAP usage was 5.10 ± 1.63 h before the COVID-19 pandemic and 4.79 ± 1.96 h during the pandemic (mean difference, -0.31 h/day; 95% CI, -0.46 to -0.15 h/day; p < 0.001 using paired t-test). After identifying 10 observational before-and-after studies through a systematic review, we conducted a meta-analysis that included our original data and showed that adherence to PAP treatment was not different before and during the COVID-19 pandemic (SMC, 0.01; 95% CI, -0.18 to 0.19; p = 0.952). CONCLUSION: Although the COVID-19 pandemic had a statistically negative impact on adherence to PAP treatment in South Korea, the effect was not clinically relevant in patients with OSA. According to our meta-analysis, adherence to PAP treatment was not different before and during the COVID-19 pandemic in patients with OSA. TRIAL REGISTRATION: PROSPERO database; No.: CRD42023414268; URL: https://www.crd.york.ac.uk/PROSPERO.

Modeling-Experiment-Theory Analysis of Reactions Initiated from Cl + Methyl Formate.

Methyl formate (MF; CH3OCHO) is the smallest representative of esters, which are common components of biodiesel. The present study characterizes the thermal dissociation kinetics of the radicals formed by H atom abstraction from MF─CH3OCO and CH2OCHO─through a combination of modeling, experiment, and theory. For the experimental effort, excimer laser photolysis of Cl2 was used as a source of Cl atoms to initiate reactions with MF in the gas phase. Time-resolved species profiles of MF, Cl2, HCl, CO2, CH3, CH3Cl, CH2O, and CH2ClOCHO were measured and quantified using photoionization mass spectrometry at temperatures of 400-750 K and 10 Torr. The experimental data were simulated using a kinetic model, which was informed by ab initio-based theoretical kinetics calculations and included chlorine chemistry and secondary reactions of radical decomposition products. We calculated the rate coefficients for the H-abstraction reactions Cl + MF → HCl + CH3OCO (R1a) and Cl + MF → HCl + CH2OCHO (R1b): k1a,theory = 6.71 × 10-15·T1.14·exp(-606/T) cm3/molecule·s; k1b,theory = 4.67 × 10-18·T2.21·exp(-245/T) cm3/molecule·s over T = 200-2000 K. Electronic structure calculations indicate that the barriers to CH3OCO and CH2OCHO dissociation are 13.7 and 31.6 kcal/mol and lead to CH3 + CO2 (R3) and CH2O + HCO (R5), respectively. The master equation-based theoretical rate coefficients are k3,theory (P = ∞) = 2.94 × 109·T1.21·exp(-6209/T) s-1 and k5,theory (P = ∞) = 8.45 × 108·T1.39·exp(-15132/T) s-1 over T = 300-1500 K. The calculated branching fractions into R1a and R1b and the rate coefficient for R5 were validated by modeling of the experimental species time profiles and found to be in excellent agreement with theory. Additionally, we found that the bimolecular reactions CH2OCHO + Cl, CH2OCHO + Cl2, and CH3 + Cl2 were critical to accurately model the experimental data and constrain the kinetics of MF-radicals. Inclusion of the kinetic parameters determined in this study showed a significant impact on combustion simulations of larger methyl esters, which are considered as biodiesel surrogates.

Delivery of siRNA using cationic rosette nanotubes for gene silencing.

The quest for new therapeutic treatments for hereditary diseases has led to many advances in RNA interference (RNAi) and gene silencing. While this technique has the potential to address many problems, the key to its continued use is the development of effective delivery strategies that would reduce cellular toxicity and increase silencing efficiency. Rosette nanotubes (RNTs) are biomimetic supramolecular nanostructures formed through the self-assembly of hybrid guanine-cytosine (G∧C) DNA bases. Here, we used bioactive RNTs for siRNA delivery and gene silencing. Fifteen lysine-functionalized twin-G∧C motifs (KnT, n = 1 to 15) were synthesized using solid phase peptide synthesis to produce building blocks that self-assembled to produce cationic RNTs under physiological conditions. The intracellular uptake of siRNA delivered by the oligo-L-lysine RNTs was examined and it was found that the complexation of siRNA was affected by the cationic charges from the lysine residues and the length of RNTs formed, with the higher charged KnT RNTs delivering siRNA to the cells at a faster rate. In addition, by protecting siRNA from serum degradation, KnT RNTs were shown to deliver their cargo to the cells effectively via the endocytic pathway. A reduction in the expression (∼70%) of the target stat3 protein was observed during gene expression analysis in HCT116 and A549 cell lines.

Preclinical evaluation of manufacturable SARS-CoV-2 spike virus-like particles produced in Chinese Hamster Ovary cells.

BACKGROUND: As the COVID-19 pandemic continues to evolve, novel vaccines need to be developed that are readily manufacturable and provide clinical efficacy against emerging SARS-CoV-2 variants. Virus-like particles (VLPs) presenting the spike antigen at their surface offer remarkable benefits over other vaccine antigen formats; however, current SARS-CoV-2 VLP vaccines candidates in clinical development suffer from challenges including low volumetric productivity, poor spike antigen density, expression platform-driven divergent protein glycosylation and complex upstream/downstream processing requirements. Despite their extensive use for therapeutic protein manufacturing and proven ability to produce enveloped VLPs, Chinese Hamster Ovary (CHO) cells are rarely used for the commercial production of VLP-based vaccines. METHODS: Using CHO cells, we aimed to produce VLPs displaying the full-length SARS-CoV-2 spike. Affinity chromatography was used to capture VLPs released in the culture medium from engineered CHO cells expressing spike. The structure, protein content, and glycosylation of spikes in VLPs were characterized by several biochemical and biophysical methods. In vivo, the generation of neutralizing antibodies and protection against SARS-CoV-2 infection was tested in mouse and hamster models. RESULTS: We demonstrate that spike overexpression in CHO cells is sufficient by itself to generate high VLP titers. These VLPs are evocative of the native virus but with at least three-fold higher spike density. In vivo, purified VLPs elicit strong humoral and cellular immunity at nanogram dose levels which grant protection against SARS-CoV-2 infection. CONCLUSIONS: Our results show that CHO cells are amenable to efficient manufacturing of high titers of a potently immunogenic spike protein-based VLP vaccine antigen.

Virus-like particles (VLPs) have a structure that is similar to viruses but they cannot cause infection or illness. If VLPs are injected into the body they produce an immune response similar to that seen following infection by a virus. This means that VLPs can be used as vaccines against viruses that cause illness in people. Many drugs, named biologics, are manufactured using living cells, including cells that were originally derived from Chinese Hamster Ovaries (CHO cells). We developed a simple method to produce VLPs similar to the SARS-CoV-2 virus in CHO cells. We show that vaccination of rodents with these VLPs prevents them from becoming ill following infection with SARS-CoV-2. These VLPs could become a part of an alternative, easily produced vaccine for the prevention of COVID-19 in humans.

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators.

Introduction: Mast cells are highly granulated tissue-resident leukocytes that require a three-dimensional matrix to differentiate and mediate immune responses. However, almost all cultured mast cells rely on two-dimensional suspension or adherent cell culture systems, which do not adequately reflect the complex structure that these cells require for optimal function. Methods: Crystalline nanocellulose (CNC), consisting of rod-like crystals 4-15 nm in diameter and 0.2-1 µm in length, were dispersed in an agarose matrix (12.5% w/v), and bone marrow derived mouse mast cells (BMMC) were cultured on the agarose/CNC composite. BMMC were activated with the calcium ionophore A23187 or immunoglobulin E (IgE) and antigen (Ag) to crosslink high affinity IgE receptors (FcεRI). Results: BMMC cultured on a CNC/agarose matrix remained viable and metabolically active as measured by reduction of sodium 3'-[1-[(phenylamino)-carbony]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT), and the cells maintained their membrane integrity as analyzed by measuring the release of lactate dehydrogenase (LDH) and propidium iodide exclusion by flow cytometry. Culture on CNC/agarose matrix had no effect on BMMC degranulation in response to IgE/Ag or A23187. However, culture of BMMC on a CNC/agarose matrix inhibited A23187-and IgE/Ag-activated production of tumor necrosis factor (TNF) and other mediators such as IL-1ß, IL-4, IL-6, IL-13, MCP-1/CCL2, MMP-9 and RANTES by as much as 95%. RNAseq analysis indicated that BMMC expressed a unique and balanced transcriptome when cultured on CNC/agarose. Discussion: These data demonstrate that culture of BMMCs on a CNC/agarose matrix promotes cell integrity, maintains expression of surface biomarkers such as FcεRI and KIT and preserves the ability of BMMC to release pre-stored mediators in response to IgE/Ag and A23187. However, culture of BMMC on CNC/agarose matrix inhibits BMMC production of de novo synthesized mediators, suggesting that CNC may be altering specific phenotypic characteristics of these cells that are associated with late phase inflammatory responses.

Trends and an Online Survey on the Use of Rigid Bronchoscopy in Korea.

BACKGROUND: Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. METHODS: We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. RESULTS: While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003-2005 to 468 in 2018-2020, that of other institutions increased from 0 to 238. The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%. The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, rs = -0.740, P = 0.003) and recent administrative difficulties were encountered (rs = -0.616, P = 0.019). CONCLUSION: This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.

Stable Anode-Free All-Solid-State Lithium Battery through Tuned Metal Wetting on the Copper Current Collector.

A stable anode-free all-solid-state battery (AF-ASSB) with sulfide-based solid-electrolyte (SE) (argyrodite Li6 PS5 Cl) is achieved by tuning wetting of lithium metal on "empty" copper current-collector. Lithiophilic 1 µm Li2 Te is synthesized by exposing the collector to tellurium vapor, followed by in situ Li activation during the first charge. The Li2 Te significantly reduces the electrodeposition/electrodissolution overpotentials and improves Coulombic efficiency (CE). During continuous electrodeposition experiments using half-cells (1 mA cm-2 ), the accumulated thickness of electrodeposited Li on Li2 Te-Cu is more than 70 µm, which is the thickness of the Li foil counter-electrode. Full AF-ASSB with NMC811 cathode delivers an initial CE of 83% at 0.2C, with a cycling CE above 99%. Cryogenic focused ion beam (Cryo-FIB) sectioning demonstrates uniform electrodeposited metal microstructure, with no signs of voids or dendrites at the collector-SE interface. Electrodissolution is uniform and complete, with Li2 Te remaining structurally stable and adherent. By contrast, an unmodified Cu current-collector promotes inhomogeneous Li electrodeposition/electrodissolution, electrochemically inactive "dead metal," dendrites that extend into SE, and thick non-uniform solid electrolyte interphase (SEI) interspersed with pores. Density functional theory (DFT) and mesoscale calculations provide complementary insight regarding nucleation-growth behavior. Unlike conventional liquid-electrolyte metal batteries, the role of current collector/support lithiophilicity has not been explored for emerging AF-ASSBs.

Bimolecular Peroxy Radical (RO2) Reactions and Their Relevance in Radical Initiated Oxidation of Hydrocarbons.

The kinetics of peroxy radical (RO2) reactions have been of long-standing interest in atmospheric and combustion chemistry. Nevertheless, the lack of kinetic studies at higher temperatures for their reactions with other radicals such as OH has precluded the inclusion of this class of reactions in detailed kinetics models developed for combustion applications. In this work, guided by the limited room-temperature experimental studies on selected alkyl-peroxy radicals and literature theoretical kinetics on the prototypical CH3O2 + OH system, we have performed parametric studies on the effect of uncertainties in the rate coefficients and branching ratios to potential product channels for RO2 + OH reactions at higher temperatures. Literature kinetics models were used to simulate autoignition delays, laminar flame speeds, and speciation profiles in flow and stirred reactors for a variety of common combustion-relevant fuels. Inclusion of RO2 + OH reactions was found to retard autoignition in fuel-lean (φ = 0.5) mixtures of ethane and dimethyl ether in air. The observed effects were noticeably more pronounced in ozone-enriched combustion of ethane and dimethyl ether. The simulations also examined the influence of ozone doping levels, pressures, and equivalence ratios for both ethane and dimethyl ether oxidation. Sensitivity and flux analyses revealed that the RO2 + OH reaction is a significant sink of RO2 radicals at the early stage of autoignition, affecting fuel oxidation through RO2 ↔ QOOH, RO2 ↔ alkene + HO2, or RO2 + HO2 ↔ ROOH + O2. Additionally, the kinetic stability of the trioxide formed from RO2 + OH reactions was investigated using master equation analyses. Last, we discuss other bimolecular reactions that are missing in literature kinetics models but are relevant to hydrocarbon oxidation initiated by external radical sources (plasma-enhanced, ozone-enriched combustion, etc.). The present simulations provide a strong motivation for better characterizing the bimolecular kinetics of peroxy radicals.

Effect of chlorhexidine Mouthrinse on prevention of microbial contamination during EBUS-TBNA: a randomized controlled trial.

BACKGROUND: Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure, fatal infectious complications have been reported. However, adequate preventive strategies have not been determined. We aimed to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. METHODS: In this single-center, assessor-blinded, parallel-group randomized controlled trial, we randomly assigned adult participants undergoing EBUS-TBNA using a convex probe to gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA or to receive usual care (no chlorhexidine mouthrinse). Aspiration needle wash samples were collected immediately after completion of EBUS-TBNA by instilling sterile saline into the used needle. The primary outcome was colony forming unit (CFU) counts per mL of needle wash samples in aerobic cultures. Secondary outcomes were CFU counts per mL of needle wash samples in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. RESULTS: From January 2021 to June 2021, 106 patients received either chlorhexidine mouthrinse (n = 51) or usual care (n = 55). The median CFU counts of needle wash samples in aerobic cultures were not significantly different in the two groups (10 CFU/mL vs 20 CFU/mL; P = 0.70). There were no significant differences between the groups regarding secondary outcomes, including median CFU counts in anaerobic cultures (P = 0.41) and fever within 24 hours after EBUS-TBNA (11.8% vs 5.6%, P = 0.31). There were no infectious complications within 4 weeks in both groups. CONCLUSIONS: Chlorhexidine mouthrinse did not reduce CFU counts in needle wash samples of EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04718922 . Registered on 22/01/2021.

Synthesis and properties of multi-functionalized graphene quantum dots with tunable photoluminescence and hydrophobicity from asphaltene and its oxidized and reduced derivatives.

Graphene quantum dots (GQDs) with tunable photoluminescence (PL) and hydrophobicity were synthesized from an abundant natural carbon source containing nitrogen, sulfur, and oxygen heteroatoms. Asphaltene and its oxidized and reduced derivatives were used as precursors to produce GQDs in organic solvents (i.e., methanol, toluene, and chloroform) using a facile ultrasonication technique. Asphaltene surface chemistry was tuned by sequential oxidation and reduction to investigate the surface effects on GQD properties. Spectroscopic characterizations confirmed the presence of N, S, and O heteroatoms and different electron-donating and electron-withdrawing groups. Microscopic characterizations revealed that these crystalline carbon nanomaterials have mono-layered or multi-layered structures with lateral sizes in the range of ∼5-15 nm. The asphaltene-derived GQDs exhibit tunable PL with emission colors ranging from blue to orange, depending on the carbon precursor and the organic solvent. Solvent exchange studies also revealed that asphaltene and its derivatives contain hydrophilic and hydrophobic fractions, resulting in varied hydrophobicity of the synthesized GQDs. Adding to the appeal of the present work, PL quenching of GQD-silica hybrid materials upon exposure to nitro-aromatics confirms that these GQDs can be incorporated to different host materials for advanced sensing or optoelectronic applications.

Thyroid Dysfunction and the Effect of Iodine-Deficient Parenteral Nutrition in Very Low Birth Weight Infants: A Nationwide Analysis of a Korean Neonatal Network Database.

Background: To investigate the impact of nutritional iodine deficiency on thyroid dysfunction (TD) in very low birth weight (VLBW) infants, we analyzed the association between iodine-deficient parenteral nutrition (PN) and TD requiring L-thyroxine (TD-LT4). Methods: Data of VLBW infants were obtained from the Korean Neonatal Network registry. Factors including duration of PN were analyzed according to TD-LT4. Results: TD-LT4 occurred in 490 (8.7%) of 5635 infants, and more frequently occurred in infants requiring PN for ≥4 weeks (10.2%). PN ≥ 4 weeks was one of the risk factors for TD-LT4, with an odds ratio (OR) of 1.346, p = 0.002. However, multivariate analysis showed that TD-LT4 was more of a risk for infants that were small for gestational age (OR 2.987, p < 0.001) and for other neonatal morbidities such as seizures (OR 1.787, p = 0.002) and persistent pulmonary hypertension (OR 1.501, p = 0.039) than PN ≥ 4 weeks (OR 0.791, p = 0.080). Conclusions: Prolonged iodine-deficient PN might affect TD-LT4 in VLBW infants. However, the effect of nutritional iodine deficiency on TD-LT4 risk was less than that of SGA or severe neonatal morbidities in Korean VLBW infants.

Self-Assembly of Alkylamido Isophthalic Acids toward the Design of a Supergelator: Phase-Selective Gelation and Dye Adsorption.

A new series of 5-alkylamido isophthalic acid (ISA) derivatives with varying single and twin alkyl chain lengths were designed and synthesized as potential supramolecular organogelators. 5-alkylamido ISAs with linear or branched alkyl tail-groups of different lengths were effective gelators for low polarity solvents. In particular, among the presented series, a derivative with a branched, 24 carbon atom tail-group behaves as a "supergelator" with up to twenty organic solvents forming gels that are highly stable over time. The gelation behavior was analyzed using Hansen solubility parameters, and the thermal stability and viscoelastic properties of select gels were characterized. Microscopy, spectroscopy, powder X-ray diffraction, and computer modeling studies were consistent with a hierarchical self-assembly process involving the formation of cyclic H-bonded hexamers via the ISA carboxylic acid groups, which stack into elementary fibers stabilized by H-bonding of the amide linker groups and π-π stacking of the aromatic groups. These new nanomaterials exhibited potential for the phase-selective gelation of oil from oil-water mixtures and dye uptake from contaminated water. The work expands upon the design and synthesis of supramolecular self-assembled nanomaterials and their application in water purification/remediation.

Unconjugated PLGA nanoparticles attenuate temperature-dependent ß-amyloid aggregation and protect neurons against toxicity: implications for Alzheimer's disease pathology.

Conversion of ß-amyloid (Aß) peptides from soluble random-coil to aggregated protein enriched with ß-sheet-rich intermediates has been suggested to play a role in the degeneration of neurons and development of Alzheimer's disease (AD) pathology. Aggregation of Aß peptide can be prompted by a variety of environmental factors including temperature which can influence disease pathogenesis. Recently, we reported that FDA-approved unconjugated poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles can have beneficial effects in cellular and animal models of AD by targeting different facets of the Aß axis. In this study, using biochemical, structural and spectroscopic analyses, we evaluated the effects of native PLGA on temperature-dependent Aß aggregation and its ability to protect cultured neurons from degeneration. Our results show that the rate of spontaneous Aß1-42 aggregation increases with a rise in temperature from 27 to 40 °C and PLGA with 50:50 resomer potently inhibits Aß aggregation at all temperatures, but the effect is more profound at 27 °C than at 40 °C. It appears that native PLGA, by interacting with the hydrophobic domain of Aß1-42, prevents a conformational shift towards ß-sheet structure, thus precluding the formation of Aß aggregates. Additionally, PLGA triggers disassembly of matured Aß1-42 fibers at a faster rate at 40 °C than at 27 °C. PLGA-treated Aß samples can significantly enhance viability of cortical cultured neurons compared to neurons treated with Aß alone by attenuating phosphorylation of tau protein. Injection of native PLGA is found to influence the breakdown/clearance of Aß peptide in the brain. Collectively, these results suggest that PLGA nanoparticles can inhibit Aß aggregation and trigger disassembly of Aß aggregates at temperatures outside the physiological range and can protect neurons against Aß-mediated toxicity thus validating its unique therapeutic potential in the treatment of AD pathology.