Association between Weight Changes over a 4-Year Period and Health-Related Quality of Life in Middle-Aged and Older Adults in Korea: The Korean Genome and Epidemiology Study Cohort.

Background: The relationship between weight change and quality of life remains controversial. This study aimed to investigate whether changes in body weight among participants in different baseline body mass index categories are associated with physical and mental health functioning. Methods: We conducted an analysis involving 5,106 adults who participated in the Korean Genome and Epidemiology Study, a cohort comprising Korean adults aged 40 to 69 years. We categorized participants into three groups based on body weight change, and physical and mental health were assessed using the 12-Item Short-Form Health Survey in year 4. We employed logistic regression analysis to assess the association between body weight change and poor functioning at year 4. We also utilized a generalized estimating equation to determine the relationship between weight changes and mental component summary (MCS) scores over the study period for each weight group. Results: Weight gain in both the normal weight (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.13-3.11; P=0.01) and overweight groups (OR, 1.75; 95% CI, 1.05-2.91; P=0.03) was associated with poor MCS. Normal weight weight-losers were associated with a greater increase (2.69 points; 95% CI, 0.50-4.88) in MCS compared to weightmaintainers. Significant differences in mean MCS were observed for overweight weight-losers, obese weight-gainers, and underweight weight-gainers when compared to weight maintainers in each respective weight group. Conclusion: Different patterns of relationships between weight change and mental health-related quality of life were observed. Hence, it is crucial to focus on the mental health of middle-aged and older adults when assessing body weight changes.

hsa-miR-CHA2, a novel microRNA, exhibits anticancer effects by suppressing cyclin E1 in human non-small cell lung cancer cells.

Despite considerable therapeutic advancements, the global survival rate for lung cancer patients remains poor, posing challenges in developing an effective treatment strategy. In many cases, microRNAs (miRNAs) exhibit abnormal expression levels in cancers, including lung cancer. Dysregulated miRNAs often play a crucial role in the development and progression of cancer. Therefore, understanding the mechanisms underlying aberrant miRNA expression during carcinogenesis may provide crucial clues to develop novel therapeutics. In this study, we identified and cloned a novel miRNA, hsa-miR-CHA2, which is abnormally downregulated in non-small cell lung cancer (NSCLC)-derived cell lines and tissues of patients with NSCLC. Furthermore, we found that hsa-miR-CHA2 regulates the post-transcriptional levels of Cyclin E1 (CCNE1) by binding to the 3'-UTR of CCNE1 mRNA. CCNE1, a cell cycle regulator involved in the G1/S transition, is often amplified in various cancers. Notably, hsa-miR-CHA2 overexpression led to the alteration of the Rb-E2F pathway, a significant signaling pathway in the cell cycle, by targeting CCNE1 in A549 and SK-LU-1 cells. Subsequently, we confirmed that hsa-miR-CHA2 induced G1-phase arrest and exhibited an anti-proliferative effect by targeting CCNE1. Moreover, in subcutaneous xenograft mouse models, intra-tumoral injection of polyplexed hsa-miR-CHA2 mimic suppressed tumor growth and development. In conclusion, hsa-miR-CHA2 exhibited an anticancer effect by targeting CCNE1 both in vitro and in vivo. These findings suggest the potential role of hsa-miR-CHA2 as an important regulator of cell proliferation in molecular-targeted therapy for NSCLC.

Advances in Heterostructures for Optoelectronic Devices: Materials, Properties, Conduction Mechanisms, Device Applications.

Atomically thin 2D transition metal dichalcogenides (TMDs) have recently been spotlighted for next-generation electronic and photoelectric device applications. TMD materials with high carrier mobility have superior electronic properties different from bulk semiconductor materials. 0D quantum dots (QDs) possess the ability to tune their bandgap by composition, diameter, and morphology, which allows for a control of their light absorbance and emission wavelength. However, QDs exhibit a low charge carrier mobility and the presence of surface trap states, making it difficult to apply them to electronic and optoelectronic devices. Accordingly, 0D/2D hybrid structures are considered as functional materials with complementary advantages that may not be realized with a single component. Such advantages allow them to be used as both transport and active layers in next-generation optoelectronic applications such as photodetectors, image sensors, solar cells, and light-emitting diodes. Here, recent discoveries related to multicomponent hybrid materials are highlighted. Research trends in electronic and optoelectronic devices based on hybrid heterogeneous materials are also introduced and the issues to be solved from the perspective of the materials and devices are discussed.

Zero Dimensional-Two Dimensional Hybrid Photodetectors Using Multilayer MoS2 and Lead Halide Perovskite Quantum Dots with a Tunable Bandgap.

We report high-performance 0D-2D hybrid photodetectors integrated with tunable band gap perovskite (CsPbI3, CsXFAX-1PbI3, and FAPbI3) quantum dots and MOCVD-grown bilayer MoS2. In our hybrid structure, the lead halide PQDs can be utilized as an absorbing layer of light of specific wavelengths and transfer the photogenerated carriers to the MoS2 transport layer. With tunable wavelength lead halide PQDs, the 0D-2D hybrid photodetector shows a high responsivity up to 107 AW-1 and high specific detectivity exceeding 1013 Jones due to the difference in the built-in potential between PQDs and multilayer MoS2 layers. This work proposes the possibility of fabricating high-performance photodetectors by hybridizing PQDs of various band gaps with 2D materials.

Effects of Ethanol on Expression of Coding and Noncoding RNAs in Murine Neuroblastoma Neuro2a Cells.

Excessive use of alcohol can induce neurobiological and neuropathological alterations in the brain, including the hippocampus and forebrain, through changes in neurotransmitter systems, hormonal systems, and neuroimmune processes. We aimed to investigate the effects of ethanol on the expression of coding and noncoding RNAs in a brain-derived cell line exposed to ethanol. After exposing Neuro2a cells, a neuroblastoma cell line, to ethanol for 24 and 72 h, we observed cell proliferation and analyzed up- and downregulated mRNAs and long noncoding RNAs (lncRNAs) using total RNA-Seq technology. We validated the differential expression of some mRNAs and lncRNAs by RT-qPCR and analyzed the expression of Cebpd and Rnu3a through knock-down of Cebpd. Cell proliferation was significantly reduced in cells exposed to 100 mM ethanol for 72 h, with 1773 transcripts up- or downregulated by greater than three-fold in ethanol-treated cells compared to controls. Of these, 514 were identified as lncRNAs. Differentially expressed mRNAs and lncRNAs were mainly observed in cells exposed to ethanol for 72 h, in which Atm and Cnr1 decreased, but Trib3, Cebpd, and Spdef increased. On the other hand, lncRNAs Kcnq1ot1, Tug1, and Xist were changed by ethanol, and Rnu3a in particular was greatly increased by chronic ethanol treatment through inhibition of Cebpd. Our results increase the understanding of cellular and molecular mechanisms related to coding and noncoding RNAs in an in vitro model of acute and chronic exposure to ethanol.

Multiple-Route Exciton Recombination Dynamics and Improved Stability of Perovskite Quantum Dots by Plasmonic Photonic Crystal.

We have studied the excited-state exciton recombination dynamics of perovskite quantum dots (QDs) through time-resolved photoluminescence (PL), PL blinking, PL intensity-dependent lifetime modulation, and long-term photostability tests. The various spectroscopic characterizations elucidate that the perovskite QDs have multiple intrinsic exciton recombination routes even in a single QD, i.e., exciton, biexciton, and positive/negative trions, which are dissimilarly contributed to ON and OFF state emissions. We also find that the enhanced radiative recombination from placing green QDs on a photonic Ag nanotip array induces notably improved long-term PL stability. We consider that the accelerated radiative recombination of QDs by strong coupling with the plasmonics of the photonic Ag nanotip array, while eliminating nonradiative pathways, is proven to be a critical factor for improved long-term stability.

Room-Temperature Spray Deposition of Large-Area SnO2 Electron Transport Layer for High Performance, Stable FAPbI3 -Based Perovskite Solar Cells.

The performance and scalability of perovskite solar cells (PSCs) is highly dependent on the morphology and charge selectivity of the electron transport layer (ETL). This work demonstrates a high-speed (1800 mm min-1 ), room-temperature (25 °C-30 °C) deposition of large-area (62.5 cm2 ) tin oxide films using a multi-pass spray deposition technique. The spray-deposited SnO2 (spray-SnO2 ) films exhibit a controllable thickness, a unique granulate morphology and high transmittance (≈85% at 550 nm). The performance of the PSC based on spray-SnO2 ETL and formamidinium lead iodide (FAPbI3 )-based perovskite is highly consistent and reproducible, achieving a maximum efficiency of ≈20.1% at an active area (A) of 0.096 cm2 . Characterization results reveal that the efficiency improvement originates from the granular morphology of spray-SnO2 and high conversion rate of PbI2 in the perovskite. More importantly, spray-SnO2 films are highly scalable and able to reduce the efficiency roll-off that comes with the increase in contact-area between SnO2 and perovskite film. Based on the spray-SnO2 ETL, large-area PSC (A = 1.0 cm2 ) achieves an efficiency of ≈18.9%. Furthermore, spray-SnO2 ETL based PSCs also exhibit higher storage stability compared to the spin-SnO2 based PSCs.

Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide which is distributed throughout the body. PACAP influences development of various tissues and exerts protective function during cellular stress and in some tumour formation. No evidence is available on its role in neural crest derived melanocytes and its malignant transformation into melanoma. Expression of PACAP receptors was examined in human skin samples, melanoma lesions and in a primary melanocyte cell culture. A2058 and WM35 melanoma cell lines, representing two different stages of melanoma progression, were used to investigate the effects of PACAP. PAC1 receptor was identified in melanocytes in vivo and in vitro and in melanoma cell lines as well as in melanoma lesions. PACAP administration did not alter viability but decreased proliferation of melanoma cells. With live imaging random motility, average speed, vectorial distance and maximum distance of migration of cells were reduced upon PACAP treatment. PACAP administration did not alter viability but decreased proliferation capacity of melanoma cells. On the other hand, PACAP administration decreased the migration of melanoma cell lines towards fibronectin chemoattractant in the Boyden chamber. Furthermore, the presence of the neuropeptide inhibited the invasion capability of melanoma cell lines in Matrigel chambers. In summary, we provide evidence that PACAP receptors are expressed in melanocytes and in melanoma cells. Our results also prove that various aspects of the cellular motility were inhibited by this neuropeptide. On the basis of these results, we propose PACAP signalling as a possible target in melanoma progression.

Anoctamin1 Induces Hyperproliferation of HaCaT Keratinocytes and Triggers Imiquimod-Induced Psoriasis-Like Skin Injury in Mice.

Psoriasis, a long-lasting and multifactorial skin disease, is related to comorbidities such as metabolic disease, depression, and psoriatic arthritis. Psoriasis occurs due to a variety of factors including keratinocyte hyperproliferation, inflammation, and abnormal differentiation. Proinflammatory cytokines upregulated by increased activation of keratinocytes and immune cells in the skin trigger progression of psoriasis. This study aimed to investigate the effects of anoctamin1 (ANO1) on psoriasis development in vitro and in vivo. We analyzed the proliferation of HaCaT keratinocytes and ANO1-related ERK and AKT signaling pathways after ANO1 inhibitor (T16Ainh-A01 and Ani9) treatment and knock-down of ANO1. Furthermore, after applying imiquimod (IMQ) cream or coapplying IMQ cream and T16Ainh-A01 on mouse ears, we not only observed psoriatic symptoms, including ear thickening, but also quantified the effects of treatment on ERK and AKT signaling-involved proteins and proinflammatory cytokines. Inhibition of ANO1 attenuated the proliferation of HaCaT cells and induced reduction of pERK1/2. Coapplication of IMQ and T16Ainh-A01 on ears of mice reduced not only symptoms of IMQ-induced psoriasis such as thickening and erythema, but also expression of ANO1 and pERK1/2 compared to that of application of IMQ alone. In addition, the expression levels of IL-17A, IL-17F, IL-22, IL-23, IL-6, IL-1ß, and TNF-α increased after applying IMQ and were significantly reduced by coapplying IMQ and T16Ainh-A01. These results aid in understanding the underlying mechanisms of ANO1 in epidermal layer keratinocyte hyperproliferation and suggest the potential of ANO1 as a target to treat psoriasis.

Design of Anticancer 2,4-Diaminopyrimidines as Novel Anoctamin 1 (ANO1) Ion Channel Blockers.

Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine libraries based on the structure of two hit compounds that were identified through the screening of an in-house library in order to identify an inhibitor of anoctamin 1 (ANO1). ANO1 is amplified in various types of human malignant tumors, such as head and neck, parathyroid, and gastrointestinal stromal tumors, as well as in breast, lung, and prostate cancers. After initial screening and further structure optimization, we identified Aa3 as a dose-dependent ANO1 blocker. This compound exhibited more potent anti-cancer activity in the NCI-H460 cell line, expressing high levels of ANO1 compared with that in A549 cells that express low levels of ANO1. Our results open a new direction for the development of small-molecule ANO1 blockers composed of a pyrimidine scaffold and a nitrogen-containing heterocyclic moiety, with drug-like properties.

Li and Mg Co-Doped Zinc Oxide Electron Transporting Layer for Highly Efficient Quantum Dot Light-Emitting Diodes.

Zinc-oxide (ZnO) is widely used as an n-type electron transporting layer (ETL) for quantum dot (QD) light-emitting diode (QLED) because various metal doping can be possible and ZnO nanoparticle can be processed at low temperatures. We report here a Li- and Mg-doped ZnO, MLZO, which is used for ETL of highly efficient and long lifetime QLEDs. Co-doping, Mg and Li, in ZnO increases its band gap and electrical resistivity and thus can enhance charge balance in emission layer (EML). It is found also that the O-H concentration at the oxide surface decreases and exciton decay time of QDs on the metal oxide increases by co-doping in ZnO. The inverted green QLEDs with MLZO ETL exhibits the maximum current efficiency (CEmax) of 69.1 cd/A, power efficiency (PEmax) of 73.8 lm/W, and external quantum efficiency (EQEmax) of 18.4%. This is at least two times higher compared with the efficiencies of the QLEDs with Mg-doped ZnO ETL. The optimum Li and Mg concentrations are found to be 10% each. The deep-red, red, light-blue, and deep-blue QLEDs with MLZO ETLs exhibit the CEmax of 6.0, 22.3, 1.9, and 0.5 cd/A, respectively. The MLZO introduced here can be widely used as ETL of highly efficient QLEDs.

Rubidium as an Alternative Cation for Efficient Perovskite Light-Emitting Diodes.

Incorporation of rubidium (Rb) into mixed lead halide perovskites has recently achieved record power conversion efficiency and excellent stability in perovskite solar cells. Inspired by these tremendous advances in photovoltaics, this study demonstrates the impact of Rb incorporation into MAPbBr3-based light emitters. Rb partially substitutes MA (methyl ammonium), resulting in a mixed cation perovskite with the formula MA(1- x)Rb xPbBr3. Pure MAPbBr3 crystallizes into a polycrystalline layer with highly defective sub-micrometer grains. However, the addition of a small amount of Rb forms MA(1- x)Rb xPbBr3 nanocrystals (10 nm) embedded in an amorphous matrix of MA/Rb Br. These nanocrystals grow into defect-free sub-micrometer-sized crystallites with further addition of Rb, resulting in a 3-fold increase in exciton lifetime when the molar ratio of MABr/RbBr is 1:1. A thin film fabricated with a 1:1 molar ratio of MABr/RbBr showed the best electroluminescent properties with a current efficiency (CE) of 9.45 cd/A and a luminance of 7694 cd/m2. These values of CE and luminance are, respectively, 19 and 10 times larger than those achieved by pure MAPbBr3 devices (0.5 cd/A and 790 cd/m2). We believe this work provides important information on the future compositional optimization of Rb+-based mixed cation perovskites for obtaining high-performance light-emitting diodes.

Ligand removal and photo-activation of CsPbBr3 quantum dots for enhanced optoelectronic devices.

Perovskite quantum dots have recently emerged as a promising light source for optoelectronic applications. However, integrating them into devices while preserving their outstanding optical properties remains challenging. Due to their ionic nature, perovskite quantum dots are extremely sensitive and degrade on applying the simplest processes. To maintain their colloidal stability, they are surrounded by organic ligands; these prevent efficient charge carrier injection in devices and have to be removed. Here we report on a simple method, where a moderate thermal process followed by exposure to UV in air can efficiently remove ligands and increase the photo-luminescence of the room temperature synthesized perovskite quantum dot thin films. Annealing is accompanied by a red shift of the emission wavelength, usually attributed to the coalescence and irreversible degradation of the quantum dots. We show that it is actually related to the relaxation of the quantum dots upon the ligand removal, without the creation of non-radiative recombining defects. The quantum dot surface, as devoid of ligands, is subsequently photo-oxidized and smoothened upon exposure to UV in air, which drastically enhances their photo-luminescence. This adequate combination of treatments improves by more than an order of magnitude the performances of perovskite quantum dot light emitting diodes.

Functional roles of glutamic acid E143 and E705 residues in the N-terminus and transmembrane domain 7 of Anoctamin 1 in calcium and noxious heat sensing.

Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2＋ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2＋ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2＋ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2＋ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2＋ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca2＋ and noxious heat. These results suggest that the glutamic acids (E) at 143 and 705 residues in ANO1 are critical for modulation of Ca2＋ and/or heat responses. Furthermore, these findings help to provide a better understanding of the Ca2＋-mediated activation and heat-sensing mechanism of ANO1. [BMB Reports 2018; 51(5): 236-241].

Solution-Processed Metal-Oxide p-n Charge Generation Junction for High-Performance Inverted Quantum-Dot Light-Emitting Diodes.

We report solution-processed metal-oxide p-n junction, Li-doped CuO (Li:CuO) and Li-doped ZnO (Li:ZnO), as a charge generation junction (CGJ) in quantum-dot light-emitting diode (QLED) at reverse bias. Efficient charge generation is demonstrated in a stack of air-annealed Li:CuO and Li:ZnO layers in QLEDs. Air annealing of Li:ZnO on Li:CuO turns out to be a key process to decrease oxygen vacancy (Vo) and increase the copper (II) oxide (CuO) fraction at the Li:CuO/Li:ZnO interface for efficient charge generation. Green QLEDs incorporating Li:CuO/Li:ZnO CGJ show the maximum current and power efficiencies of 35.4 cd/A and 33.5 lm/W, respectively.