Achieving high sensitivity in solid-state gas sensors can allow the precise detection of chemical agents. In particular, detection of volatile organic compounds (VOCs) at the parts per billion (ppb) ...level is critical for the early diagnosis of diseases. To obtain high sensitivity, two requirements need to be simultaneously satisfied: (i) low electrical noise and (ii) strong signal, which existing sensor materials cannot meet. Here, we demonstrate that 2D metal carbide MXenes, which possess high metallic conductivity for low noise and a fully functionalized surface for a strong signal, greatly outperform the sensitivity of conventional semiconductor channel materials. Ti3C2Tx MXene gas sensors exhibited a very low limit of detection of 50-100 ppb for VOC gases at room temperature. Also, the extremely low noise led to a signal-to-noise ratio 2 orders of magnitude higher than that of other 2D materials, surpassing the best sensors known. Our results provide insight in utilizing highly functionalized metallic sensing channels for developing highly sensitive sensors.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Abstract
Vitamin D
3
(25OHD
3
) insufficiency and fibroblast growth factor 23 (FGF23) elevation are usually attenuated after kidney transplantation (KT). However, elevated FGF23 may be associated ...with poor graft outcomes and vitamin D insufficiency after KT. This study investigated the effect of pretransplant FGF23 levels on post-KT 25(OH)D
3
status and graft outcomes. Serum FGF23 levels from 400 participants of the KoreaN Cohort Study for Outcome in Patients With Kidney Transplantation were measured. Annual serum 25(OH)D
3
levels, all-cause mortality, cardiovascular event, and graft survival were assessed according to baseline FGF23 levels. Serum 25(OH)D
3
levels were initially increased 1 year after KT (12.6 ± 7.4
vs.
22.6 ± 6.4 ng/mL). However, the prevalence of post-KT vitamin D deficiency increased again after post-KT 3 years (79.1% at baseline, 30.8% and 37.8% at 3 and 6 years, respectively). Serum FGF23 level was decreased 3 years post-KT. When participants were categorized into tertiles according to baseline FGF23 level (low, middle, high), 25(OH)D
3
level in the low FGF23 group was persistently low at a median follow-up of 8.3 years. Furthermore, high baseline FGF23 level was a risk factor for poor graft survival (HR 5.882, 95% C.I.; 1.443–23.976,
P
= 0.013). Elevated FGF23 levels are associated with persistently low post-transplant vitamin D levels and poor graft survival.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Based on a high incidence of genomic alteration in the cell cycle and DNA damage and response (DDR)‐related pathways in small cell lung cancer (SCLC), the clinical efficacy of the ...DDR‐targeting agent olaparib (PARP inhibitor) as monotherapy and in combination with ceralasertib (ATR inhibitor) in relapsed or refractory SCLC was evaluated.
Methods
As part of a phase 2 biomarker driven umbrella study, patients with SCLC and predefined DDR gene alterations who failed to benefit from prior platinum‐based regimens were allocated to the olaparib monotherapy arm and nonbiomarker‐selected patients were allocated to the olaparib and ceralasertib combination arm.
Results
In the olaparib monotherapy arm (n = 15), the objective response rate was 6.7% (one partial response), and the disease control rate was 33.3%, including three patients with stable disease. The median progression‐free survival was 1.3 months (95% CI, 1.2–NA). In the combination arm (n = 26), the objective response rate and disease control rate were 3.8% and 42.3%, respectively, with one partial response and 10 patients with stable disease. The median progression‐free survival was 2.8 months (95% CI, 1.8–5.4). Treatment was generally well tolerated except for one fatal case of neutropenic fever in the combination arm.
Conclusions
Targeting DDR pathways with olaparib as a single agent or in combination with ceralasertib did not meet the predefined efficacy end point. However, disease stabilization was more evident in the combination arm. Further investigation of the combination of olaparib in SCLC should be performed with diverse combinations and patient selection strategies to maximize efficacy.
This study provides clinical evidence that current approaches targeting DNA damage and response pathway as either olaparib alone or in combination with ceralasertib therapy are insufficient to achieve a satisfactory response in small cell lung cancer. However, this study supports the evidence for further investigation, searching for an appropriate combination partner of DNA damage and response pathway targeting agent and relevant predictive biomarkers in small cell lung cancer.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cicadae Periostracum (CP), derived from the slough of
, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and ...antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
A high percentage of small cell lung cancer (SCLC) cases harbor cell cycle–related gene mutations and RICTOR amplification. Based on underlying somatic mutations, the authors have ...conducted a phase 2 biomarker‐driven, multiarm umbrella study.
Methods
The SCLC Umbrella Korea StudiES (SUKSES) is an adaptive platform trial that undergoes continual modification according to the observed outcomes. This study included 286 patients with SCLC who failed platinum therapy and who had known genomic profiles based on a predesigned screening trial. Patients with MYC amplification or CDKN2A and TP53 co‐alterations were allocated to adavosertib (SUKSES protocol C SUKSES‐C; 7 patients) and those with RICTOR amplification were allocated to vistusertib (SUKSES‐D; 4 patients). Alternatively, patients who were without any predefined biomarkers were assigned to a non–biomarker‐selected arm: adavosertib (SUKSES‐N1; 21 patients) or AZD2811NP (SUKSES‐N3; 15 patients).
Results
Patients in the SUKSES‐C and SUKSES‐N1 arms demonstrated no objective response. Three patients presented with stable disease (SD) in SUKSES‐C and 6 patients in SUKSES‐N1. The median progression‐free survival (PFS) was 1.3 months (95% confidence interval, 0.9 months to not available) for SUKSES‐C and 1.2 months (95% CI, 1.1‐1.4 months) for SUKSES‐N1. Patients in the SUKSES‐D arm demonstrated no objective response and no SD, with a PFS of 1.2 months (95% CI, 1.0 months to not available). The SUKSES‐N3 arm had 5 patients with SD and a PFS of 1.6 months (95% CI, 0.9‐1.7 months), without an objective response. Grade≥3 adverse events (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) were observed as follows: 3.2% in the SUKSES‐C and SUKSES‐N1 arms and 50.0% in the SUKSES‐D arm. Target‐related neutropenia (grade≥3) was observed in approximately 60.0% of patients in the AZD2811NP arm using the current dosing schedule.
Conclusions
To the best of the authors' knowledge, the current study is the first biomarker‐driven umbrella study conducted in patients with recurrent SCLC. Although the current study demonstrated the limited clinical efficacy of monotherapy, novel biomarker approaches using other cell cycle inhibitor(s) or combinations warrant further investigation.
To the authors' knowledge, the current study is the first biomarker‐driven umbrella study in patients with recurrent and refractory small cell lung cancer (SCLC) using adavosertib, vistusertib, and AZD2811NP. Although the overall outcome of this study fails to satisfy the primary endpoint, the results provide the rationale to focus on the exploration of combination approaches for the treatment of patients with recurrent and refractory SCLC.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study aimed to compare health-related quality of life (HRQOL) over time in patients initiating hemodialysis (HD) or peritoneal dialysis (PD). A total of 989 incident patients starting HD or PD ...were included from a prospective nationwide cohort study. HRQOL was assessed 3, 12, and 24 months after the start of dialysis. The scores of questionnaires were adjusted for clinical and socioeconomic parameters. The adjusted three months scores of patients on PD showed better HRQOL in eight end-stage renal disease (ESRD), three physical component summary and one mental component summary domains compared with patients on HD. Both patients on HD and PD experienced significant decreases in different HRQOL domains over two years and the degree of changes in HRQOL over time was not different between dialysis modality. However, the scores of three (effects of kidney disease, burden of kidney disease, and dialysis staff encouragement, all P < 0.05) and two (sexual function and dialysis staff encouragement, all P < 0.05) ESRD domains were still higher in patients on PD compared with patients on HD at one and two years after initiation of dialysis, respectively. PD shows better HRQOL during the initial period after dialysis even after adjusting for clinical and socioeconomic characteristics, and the effect lasts up to two years. It was similar in terms of changes in HRQOL over time between HD and PD.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mesoporous metal oxides exhibit excellent physicochemical properties and are widely used in various fields, including energy storage/conversion, catalysis, and sensors. Although several soft‐template ...approaches are reported, high‐temperature calcination for both metal oxide formation and template removal is necessary, which limits direct synthesis on a plastic substrate for flexible devices. Here, a universal synthetic approach that combines thermal activation and oxygen plasma to synthesize diverse mesoporous metal oxides (V2O5, V6O13, TiO2, Nb2O5, WO3, and MoO3) at low temperatures (150–200 °C), which can be applicable to a flexible polymeric substrate is introduced. As a demonstration, a flexible micro‐supercapacitor is fabricated by directly synthesizing mesoporous V2O5 on an indium‐tin oxide‐coated colorless polyimide film. The energy storage performance is well maintained under severe bending conditions.
The synergistic effect of thermal activation and plasma enabled low‐temperature synthesis (150–200 °C) of various mesoporous metal oxide (V2O5, V6O13, TiO2, WO3, Nb2O5, and MoO3), suitable for flexible polymeric substrates. As a proof of concept, the direct synthesis of mesoporous V2O5 is demonstrated on an indium‐tin oxide‐coated polyimide film and its application as electrode materials.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Three-dimensional visualization of cellular and subcellular-structures in histological-tissues is essential for understanding the complexities of biological-phenomena, especially with regards ...structural and spatial relationships and pathologlical-diagnosis. Recent advancements in tissue-clearing technology, such as Magnified Analysis of Proteome (MAP), have significantly improved our ability to study biological-structures in three-dimensional space; however, their wide applicability to a variety of tissues is limited by long incubation-times and a need for advanced imaging-systems that are not readily available in most-laboratories. Here, we present optimized MAP-based method for paper-thin samples, Paper-MAP, which allow for rapid clearing and subsequent imaging of three-dimensional sections derived from various tissues using conventional confocal-microscopy. Paper-MAP successfully clear tissues within 1-day, compared to the original-MAP, without significant differences in achieved optical-transparency. As a proof-of-concept, we investigated the vasculature and neuronal-networks of a variety of human and rodent tissues processed via Paper-MAP, in both healthy and diseased contexts, including Alzheimer's disease and glioma.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Display omitted
A redox-responsive and fluorescent HA-PEG(SS)-His-Diet-QD nanocarriers for active CD44-targeting intracellular protein delivery.
•CdZnSeS/ZnS core/thick-shell QDs are first applied as ...a protein delivery system.•HA-PEG(SS)-His-Diet-QD has high stability and redox-responsive property.•HA-PEG(SS)-His-Diet-QD can enhance endo/lysosomal escape and enable cell imaging.•CC-loaded-HA-PEG(SS)-His-Diet-QD can induce CD44-overexpressing cells apoptosis.
The use of multifunctional quantum dots (QDs) as smart nanocarriers has exhibited substantial promise for imaging, targeting and therapeutic functionalities. Here, we describe the synthesis of green-light emitting CdZnSeS/ZnS quantum dots (QDs) combined with redox-sensitive hyaluronic acid ligand (hyaluronic acid-disulfide-linked poly(ethylene glycol)-histamine-diethylenetriamine, HA-PEG(SS)-His-Diet) for the targeted intracellular delivery of protein drugs. The generation of HA-PEG(SS)-His-Diet-QD exhibits monodispersity with high quantum yield, negligible cytotoxicity and long-term stability at pH 7.4 and 5.5. These HA-PEG(SS)-His-Diet-QDs could effectively immobilize cytochrome C (CC) with high loading efficiency, enable target of CD44-overexpressing MCF-7 human breast tumor cells, and accelerate protein release under high intracellular glutathione concentration condition. The HA-PEG(SS)-His-Diet-QD act as a promising nanocarrier for enhanced endo/lysosomal escape, targeted delivery of proteins and real-time cellular imaging. In addition, CC-loaded-HA-PEG(SS)-His-Diet-QD could effectively induce the CD44-positive cancer cells apoptosis in vitro. Ultimately, this redox-sensitive and fluorescent QD-based nanocarrier has shown major promise for targeted intracellular protein transport.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A metabolomic investigation of depression and chronic fluoxetine treatment was conducted using a chronic unpredictable mild stress model with C57BL/6N mice. Establishment of the depressive model was ...confirmed by body weight measurement and behavior tests including the forced swim test and the tail suspension test. Behavioral despair by depression was reversed by four week-treatment with fluoxetine. Hippocampus, serum, and feces samples collected from four groups (control + saline, control + fluoxetine, model + saline, and model + fluoxetine) were subjected to metabolomic profiling based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Alterations in the metabolic patterns were evident in all sample types. The antidepressant effects of fluoxetine appeared to involve various metabolic pathways including energy metabolism, neurotransmitter synthesis, tryptophan metabolism, fatty acid metabolism, lipid metabolism, and bile acid metabolism. Predictive marker candidates of depression were identified, including β-citryl-L-glutamic acid (BCG) and docosahexaenoic acid (DHA) in serum and chenodeoxycholic acid and oleamide in feces. This study suggests that treatment effects of fluoxetine might be differentiated by altered levels of tyramine and BCG in serum, and that DHA is a potential serum marker for depression with positive association with hippocampal DHA. Collectively, our comprehensive study provides insights into the biochemical perturbations involved in depression and the antidepressant effects of fluoxetine.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
