Advances in the role of the GADD45 family in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders

The growth arrest and DNA damage inducible protein 45 (GADD45) family comprises stress-induced nuclear proteins that interact with DNA demethylases to facilitate DNA demethylation, thereby regulating diverse cellular processes including oxidative stress, DNA damage repair, apoptosis, proliferation, differentiation, inflammation, and neuroplasticity by modulating the expression patterns of specific genes. Widely expressed in the central nervous system, the GADD45 family plays a pivotal role in various neurological disorders, rendering it a potential therapeutic target for central nervous system diseases. This review presented a comprehensive overview of the expression patterns and potential mechanisms of action associated with each member of GADD45 family (GADD45α, GADD45β, and GADD45γ) in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders, while also explored strategies to harness these mechanisms for intervention and treatment. Future research should prioritize the development of effective modulators targeting the GADD45 family for clinical trials aimed at treating central nervous system diseases

Fabrication of Thin, Luminescent, Single-crystal Diamond Membranes

The formation of single-crystal diamond membranes is an important prerequisite for the fabrication of high-quality optical cavities in this material. Diamond membranes fabricated using lift-off processes involving the creation of a damaged layer through ion implantation often suffer from residual ion damage, which severely limits their usefulness for photonic structures. The current work demonstrates that strategic etch removal of the most highly defective material yields thin, single-crystal diamond membranes with strong photoluminescence and a Raman signature approaching that of single-crystal bulk diamond. These optically-active membranes can form the starting point for fabrication of high-quality optical resonators.Comment: To appear in AP

The medicinal mushroom Ganoderma lucidum prevents lung tumorigenesis induced by tobacco smoke carcinogens

Ganoderma lucidum (GL), commonly known as “Lingzhi”, is a well-known medicinal mushroom with antioxidant and anti-cancer activity. This study examined the effects of a commercial GL product (GLSF) containing the spore and fruiting body in a 30:8 ratio on tobacco smoke carcinogen-induced lung toxicity and carcinogenesis. The potential chemopreventive effect of GLSF was evaluated in vitro and in vivo. The non-tumorous human bronchial epithelial cells (BEAS-2B cells) were treated with GLSF extract (0.025 and 0.05 mg/mL), which significantly blocked malignant transformation induced by benzo[a]pyrene diol epoxide (BPDE) in a dose-dependent manner. To confirm its anti-carcinogenic activity in vivo, the mice were pre-treated with GLSF (2.0 g/kg of body weight) or curcumin (100 mg/kg of body weight) by oral gavage daily for 7 days and then exposed to a single dose of benzo[a]pyrene (B[a]P) (125 mg/kg of body weight). The GLSF-treated mice showed a significant reduction in B[a]P-induced lung toxicity, as indicated by decreased lactate dehydrogenase activity, malondialdehyde levels, inflammatory cell infiltration, and improved lung histopathology. We next determined the chemopreventive activity of GLSF in mice which were exposed to two weekly doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 100 mg/kg, on the 1st and 8th days) and fed with control or a modified diet containing GLSF (2.0 g/kg) or metformin (250 mg/kg) for 33 weeks. The GLSF and metformin treatments blocked NNK-induced lung tumor development by decreasing the lung weight, tumor area, and tumor burden compared to the mice exposed to NNK only. GLSF treatment also attenuated the expression of inflammatory, angiogenic, and apoptotic markers in lung tumors. Therefore, GLSF may be used for ameliorating tobacco smoke carcinogens-induced lung toxicity and carcinogenesis

Photoluminescence properties of polystyrene-hosted fluorophore thin films

We report on a photo-luminescence study of four different fluorophores: Coumarin 6, 2,5-Diphenyloxazole (PPO), 1,4-Bis(5-phenyl-2-oxazolyl)benzene (POPOP) and Para-terpehnyl (PTP), doped in a polystyrene-based thin film. All of the samples are prepared by spin coating from a non-polar polymer solution at various concentrations. Their emission spectra and transient properties are characterized by photoluminescence measurements. Red-shifts in the emission spectra are observed for all four types of fluorophores as their concentration increases. We explain this phenomenon based on concentration dependence of solvatochromic effects and the results show good agreement with existing literature. We also show that the singlet-singlet annihilation processes are possibly a prevalent mechanism in the high concentration regime that affects the steady state and transient emission characteristics of the fluors. With the exception of PTP, photoluminescence quenching occurs as the fluorophore concentration in the polymer is increased. Rate equations for excited state decay mechanisms are analysed by considering different radiative and non-radiative energy transfer mechanisms. The results show consistency with our experimental observations. PTP shows the best photoluminescence results as an efficient fluor in the thin film, whereas PPO shows the strongest concentration dependent quenching and an anomalous lifetime distribution

The β-Blocker Carvedilol Prevented Ultraviolet-Mediated Damage of Murine Epidermal Cells and 3D Human Reconstructed Skin

The β-blocker carvedilol prevents ultraviolet (UV)-induced skin cancer, but the mechanism is unknown. Since carvedilol possesses antioxidant activity, this study investigated whether carvedilol prevents oxidative photodamage of skin, a precursor event in skin carcinogenesis. The effects of carvedilol, metoprolol (a β-blocker without antioxidant property), and 4-hydroxycarbazole (4-OHC, a carvedilol synthesis intermediate and a free radical scavenger) were compared on UV- or H2O2-induced cell death and reactive oxygen species (ROS) production in murine epidermal JB6 P+ cells. Although carvedilol attenuated cell death, metoprolol and 4-OHC failed to show protective effects. As expected, increased cellular ROS induced by H2O2 or UV was abolished by carvedilol and 4-OHC, but not by metoprolol. Consistently, carvedilol attenuated the formation of UV-induced cyclobutane pyrimidine dimers (CPDs) and release of prostaglandin E2 in JB6 P+ cells. Carvedilol’s activity was further confirmed in full thickness 3D human reconstituted skin, where carvedilol attenuated UV-mediated epidermal thickening, the number of Ki-67 and p53 positive cells as well as CPD formation. Based on pathway-specific Polymerase Chain Reaction (PCR) Array analysis, carvedilol treatment in many cases normalized UV-induced expression changes in DNA repair genes. Thus, carvedilol’s photoprotective activity is not attributed to β-blockade or direct ROS-scavenging capacity, but likely via DNA repair regulation

Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems

Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABABR were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABABR in the VTA and NAc

Engineered telecom emission and controlled positioning of Er3+ enabled by SiC nanophotonic structures

High-precision placement of rare-earth ions in scalable silicon-based nanostructured materials exhibiting high photoluminescence (PL) emission, photostable and polarized emission, and near-radiative-limited excited state lifetimes can serve as critical building blocks toward the practical implementation of devices in the emerging fields of nanophotonics and quantum photonics. Introduced herein are optical nanostructures composed of arrays of ultrathin silicon carbide (SiC) nanowires (NWs) that constitute scalable one-dimensional NW-based photonic crystal (NW-PC) structures. The latter are based on a novel, fab-friendly, nanofabrication process. The NW arrays are grown in a self-aligned manner through chemical vapor deposition. They exhibit a reduction in defect density as determined by low-temperature time-resolved PL measurements. Additionally, the NW-PC structures enable the positioning of erbium (Er3+) ions with an accuracy of 10 nm, an improvement on the current state-of-the-art ion implantation processes, and allow strong coupling of Er3+ ions in NW-PC. The NW-PC structure is pivotal in engineering the Er3+-induced 1540-nm emission, which is the telecommunication wavelength used in optical fibers. An approximately 60-fold increase in the room-temperature Er3+ PL emission is observed in NW-PC compared to its thin-film analog in the linear pumping regime. Furthermore, 22 times increase in the Er3+ PL intensity per number of exited Er ions in NW-PC was observed at saturation while using 20 times lower pumping power. The NW-PC structures demonstrate broadband and efficient excitation characteristics for Er3+, with an absorption cross-section (~2 × 10−18 cm2) two-order larger than typical benchmark values for direct absorption in rare-earth-doped quantum materials. Experimental and simulation results show that the Er3+ PL is photostable at high pumping power and polarized in NW-PC and is modulated with NW-PC lattice periodicity. The observed characteristics from these technologically friendly nanophotonic structures provide a promising route to the development of scalable nanophotonics and formation of single-photon emitters in the telecom optical wavelength band

The β-Blocker Carvedilol Prevents Benzo(a)pyrene-Induced Lung Toxicity, Inflammation and Carcinogenesis

The current study evaluated the effects of the β-blocker carvedilol on benzo(a)pyrene (B(a)P) and its active metabolite benzo(a)pyrene diol epoxide (BPDE)-induced lung toxicity, inflammation and carcinogenesis and explored the potential mechanisms. Carvedilol blocked the BPDE-induced malignant transformation of human bronchial epithelial cells BEAS-2B. In BEAS-2B cells, B(a)P strongly activated ELK-1, a transcription factor regulating serum response element (SRE) signaling, which was attenuated by carvedilol. Carvedilol also inhibited the B(a)P-induced AhR/xenobiotic responsive element (XRE) and mRNA expression of CYP1A1 and attenuated B(a)P-induced NF-κB activation. In a B(a)P-induced acute lung toxicity model in CD-1/IGS mice, pretreatment with carvedilol for 7 days before B(a)P exposure effectively inhibited the B(a)P-induced plasma levels of lactate dehydrogenase and malondialdehyde, inflammatory cell infiltration and histopathologic abnormalities in the lung, and upregulated the expression of GADD45α, caspase-3 and COX-2 in the lung. In a B(a)P-induced lung carcinogenesis model in A/J mice, carvedilol treatment for 20 weeks did not affect body weight but significantly attenuated tumor multiplicity and volume. These data reveal a previously unexplored role of carvedilol in preventing B(a)P-induced lung inflammation and carcinogenesis by inhibiting the cross-talk of the oncogenic transcription factors ELK-1, AhR and NF-κB

A Molecular Electronic Transducer based Low-Frequency Accelerometer with Electrolyte Droplet Sensing Body

ABSTRACT "Sensor Decade" has been labeled on the first decade of the 21st century. Similar to the revolution of micro-computer in 1980s, sensor R&D developed rapidly during the past 20 years. Hard workings were mainly made to minimize the size of devices with optimal the performance. Efforts to develop the small size devices are mainly concentrated around Micro-electro-mechanical-system (MEMS) technology. MEMS accelerometers are widely published and used in consumer electronics, such as smart phones, gaming consoles, anti-shake camera and vibration detectors. This study represents liquid-state low frequency micro-accelerometer based on molecular electronic transducer (MET), in which inertial mass is not the only but also the conversion of mechanical movement to electric current signal is the main utilization of the ionic liquid. With silicon-based planar micro-fabrication, the device uses a sub-micron liter electrolyte droplet sealed in oil as the sensing body and a MET electrode arrangement which is the anode-cathode-cathode-anode (ACCA) in parallel as the read-out sensing part. In order to sensing the movement of ionic liquid, an imposed electric potential was applied between the anode and the cathode. The electrode reaction, I 3 − + 2e − ↔ 3I − , occurs around the cathode which is reverse at the anodes. Obviously, the current magnitude varies with the concentration of ionic liquid, which will be effected by the movement of liquid droplet as the inertial mass. With such structure, the promising performance of the MET device design is to achieve 10.8 V/G (G = 9.81 m/s 2 ) sensitivity at 20 Hz with the bandwidth from 1Hz to 50 Hz, and a low noise floor of 100 μg/√Hz at 20 Hz. ii ACKNOWLEDGMENTS I wish to thank my advisor Dr. Hongyu Yu for the support and help on this research project, as well as all my committee members. I am also pleased to have this opportunity to thank my colleague