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Insulin regulation is a hallmark of health, and impaired insulin signaling promotes metabolic diseases like diabetes mellitus. However, current assays for measuring insulin signaling in all animals remain semi-quantitative and lack the sensitivity, tissue-specificity or temporal resolution needed to quantify in vivo physiological signaling dynamics. Insulin signal transduction is remarkably conserved across metazoans, including insulin-dependent phosphorylation and regulation of Akt/Protein kinase B. Here, we generated transgenic fruit flies permitting tissue-specific expression of an immunoepitope-labelled Akt (AktHF). We developed enzyme-linked immunosorption assays (ELISA) to quantify picomolar levels of phosphorylated (pAktHF) and total AktHF in single flies, revealing dynamic tissue-specific physiological regulation of pAktHF in response to fasting and re-feeding, exogenous insulin, or targeted genetic suppression of established insulin signaling regulators. Genetic screening revealed Pp1-87B as an unrecognized regulator of Akt and insulin signaling. Tools and concepts here provide opportunities to discover tissue-specific regulators of in vivo insulin signaling responses.
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Diabetes Mellitus , Resistencia a la Insulina , Animales , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Insulina/metabolismo , Drosophila/genética , Drosophila/metabolismo , Transducción de Señal/genética , Fosforilación , Resistencia a la Insulina/genéticaRESUMEN
Securinega alkaloids, composed of more than 100 members characterized by the compact tetracyclic scaffold, have fascinated the synthetic community with their structural diversity and notable bioactivities. On the basis of the structural phenotype, oligomerizations and oxidations are major biosynthetic diversification modes of the basic Securinega framework. Despite the rich history of synthesis of basic monomeric Securinega alkaloids, the synthesis of oligomeric Securinega alkaloids, as well as oxidized derivatives, has remained relatively unexplored because of their extra structural complexity. In the first half of this Account, our synthetic studies toward high-order Securinega alkaloids are described. We aimed to establish a reliable synthetic method to form C14-C15' and C12-C15' bonds, which are prevalent connection modes between monomers. During our total synthesis of flueggenine C (9), we have invented an accelerated Rauhut-Currier reaction capable of forming the C14-C15' bond stereoselectively. Installation of the nucleophilic functionality to the Michael acceptor, which ushers the C-C bond forming conjugate addition to follow the intramolecular pathway, was the key to success. The C12-C15' linkage, which was inaccessible via an accelerated Rauhut-Currier reaction, was established by devising a complementary cross-coupling/conjugate reduction-based dimerization strategy that enabled the total synthesis of flueggenines D (11) and I (14). In this approach, the C12-C15' linkage was established via a Stille cross-coupling, and the stereochemistry of the C15' position was controlled during the following conjugate reduction step. In the later half of this Account, our achievements in the field of high-oxidation state Securinega alkaloids synthesis are depicted. We have developed oxidative transformations at the N1 and C2-C4 positions, where the biosynthetic oxidation event occurs most frequently. The discovery of a VO(acac)2-mediated regioselective Polonovski reaction allowed us to access the key 2,3-dehydroallosecurinine (112). Divergent synthesis of secu'amamine A (62) and fluvirosaones A (60) and B (61) was accomplished by exploiting the versatile reactivities of the C2/C3 enamine moiety in 112. We have also employed a fragment-coupling strategy between menisdaurilide and piperidine units, which allowed the installation of various oxygen-containing functionality on the piperidine ring. Combined with the late-stage, light-mediated epimerization and well-orchestrated oxidative modifications, collective total synthesis of seven C4-oxygenated securinine-type natural products was achieved. Lastly, the synthesis of flueggeacosine B (70) via two synthetic routes from allosecurinine (103) was illustrated. The first-generation synthesis (seven overall steps) employing Pd-catalyzed cross-coupling between stannane and thioester to form the key C3-C15' bond enabled the structural revision of the natural product. In the second-generation synthesis, we have invented visible-light-mediated, Cu-catalyzed cross-dehydrogenative coupling (CDC) between an aldehyde and electron-deficient olefin, which streamlined the synthetic pathway into four overall steps. Organisms frequently utilize dimerization (oligomerization) and oxidations during the biosynthesis as a means to expand the chemical space of their secondary metabolites. Therefore, methods and strategies for dimerizations and oxidations that we have developed using the Securinega alkaloids as a platform would be broadly applicable to other alkaloids. It is our sincere hope that lessons we have learned during our synthetic journey would benefit other chemists working on organic synthesis.
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Alcaloides , Securinega , Estereoisomerismo , PiperidinasRESUMEN
Fibrosis, characterized by excessive extracellular matrix accumulation, disrupts normal tissue architecture, causes organ dysfunction, and contributes to numerous chronic diseases. This review focuses on Krüppel-like factor 10 (KLF10), a transcription factor significantly induced by transforming growth factor-ß (TGF-ß), and its role in fibrosis pathogenesis and progression across various tissues. KLF10, initially identified as TGF-ß-inducible early gene-1 (TIEG1), is involved in key biological processes including cell proliferation, differentiation, apoptosis, and immune responses. Our analysis investigated KLF10 gene and protein structures, interaction partners, and context-dependent functions in fibrotic diseases. This review highlights recent findings that underscore KLF10 interaction with pivotal signaling pathways, such as TGF-ß, and the modulation of gene expression in fibrotic tissues. We examined the dual role of KLF10 in promoting and inhibiting fibrosis depending on tissue type and fibrotic context. This review also discusses the therapeutic potential of targeting KLF10 in fibrotic diseases, based on its regulatory role in key pathogenic mechanisms. By consolidating current research, this review aims to enhance the understanding of the multifaceted role of KLF10 in fibrosis and stimulate further research into its potential as a therapeutic target in combating fibrotic diseases.
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Fibrosis , Factores de Transcripción de Tipo Kruppel , Humanos , Factores de Transcripción de la Respuesta de Crecimiento Precoz/genética , Fibrosis/metabolismo , Fibrosis/patología , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , AnimalesRESUMEN
All-solid-state lithium batteries have been developed to secure safety by substituting a flammable liquid electrolyte with a non-flammable solid electrolyte. However, owing to the nature of solids, interfacial issues between cathode materials and solid electrolytes, including chemical incompatibility, electrochemo-mechanical behavior, and physical contact, pose significant challenges for commercialization. Herein, critical factors for understanding the performance of all-solid-state batteries in terms of solid interfaces and non-zero lattice strains are identified through a strategic approach. The initial battery capacity can be increased via surface coating and electrode-fabrication methods; however, the increased lattice strain causes significant stress to the solid interface, which degrades the battery cycle life. However, this seesaw effect can be alleviated using a more compacted electrode microstructure between the solid electrolyte and oxide cathode materials. The compact solid interfaces contribute to low charge-transfer resistance and a homogeneous reaction between particles, thereby leading to improved electrochemical performance. These findings demonstrate, for the first time, a correlation between the uniformity of the electrode microstructure and electrochemical performance through the investigation of the reaction homogeneity among particles. Additionally, this study furthers the understanding of the relationship between electrochemical performance, non-zero lattice strain, and solid interfaces.
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BACKGROUND: The mechanism by which incompletely absorbed fructose causes gastrointestinal symptoms is not fully understood. In this study, we investigated the immunological mechanisms of bowel habit changes associated with fructose malabsorption by examining Chrebp-knockout mice exhibiting defective fructose absorption. METHODS: Mice were fed a high-fructose diet (HFrD), and stool parameters were monitored. The gene expression in the small intestine was analyzed by RNA sequencing. Intestinal immune responses were assessed. The microbiota composition was determined by 16S rRNA profiling. Antibiotics were used to assess the relevance of microbes for HFrD-induced bowel habit changes. RESULTS: Chrebp-knockout (KO) mice fed HFrD showed diarrhea. Small-intestine samples from HFrD-fed Chrebp-KO mice revealed differentially expressed genes involved in the immune pathways, including IgA production. The number of IgA-producing cells in the small intestine decreased in HFrD-fed Chrebp-KO mice. These mice showed signs of increased intestinal permeability. Chrebp-KO mice fed a control diet showed intestinal bacterial imbalance, which the HFrD exaggerated. Bacterial reduction improved diarrhea-associated stool parameters and restored the decreased IgA synthesis induced in HFrD-fed Chrebp-KO mice. CONCLUSIONS: The collective data indicate that gut microbiome imbalance and disrupting homeostatic intestinal immune responses account for the development of gastrointestinal symptoms induced by fructose malabsorption.
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Diarrea , Fructosa , Ratones , Animales , ARN Ribosómico 16S , Diarrea/etiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Intestino Delgado , Hábitos , Inmunoglobulina ARESUMEN
Liver fibrosis is a progressive and debilitating condition characterized by the excessive deposition of extracellular matrix proteins. Stellate cell activation, a major contributor to fibrogenesis, is influenced by Transforming growth factor (TGF-ß)/SMAD signaling. Although Krüppel-like-factor (KLF) 10 is an early TGF-ß-inducible gene, its specific role in hepatic stellate cell activation remains unclear. Our previous study demonstrated that KLF10 knockout mice develop severe liver fibrosis when fed a high-sucrose diet. Based on these findings, we aimed to identify potential target molecules involved in liver fibrosis and investigate the mechanisms underlying the KLF10 modulation of hepatic stellate cell activation. By RNA sequencing analysis of liver tissues from KLF10 knockout mice with severe liver fibrosis induced by a high-sucrose diet, we identified ATF3 as a potential target gene regulated by KLF10. In LX-2 cells, an immortalized human hepatic stellate cell line, KLF10 expression was induced early after TGF-ß treatment, whereas ATF3 expression showed delayed induction. KLF10 knockdown in LX-2 cells enhanced TGF-ß-mediated activation, as evidenced by elevated fibrogenic protein levels. Further mechanistic studies revealed that KLF10 knockdown promoted TGF-ß signaling and upregulated ATF3 expression. Conversely, KLF10 overexpression suppressed TGF-ß-mediated activation and downregulated ATF3 expression. Furthermore, treatment with the chemical chaperone 4-PBA attenuated siKLF10-mediated upregulation of ATF3 and fibrogenic responses in TGF-ß-treated LX-2 cells. Collectively, our findings suggest that KLF10 acts as a negative regulator of the TGF-ß signaling pathway, exerting suppressive effects on hepatic stellate cell activation and fibrogenesis through modulation of ATF3 expression. These results highlight the potential therapeutic implications of targeting the KLF10-ATF3 axis in liver fibrosis treatment.
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Células Estrelladas Hepáticas , Cirrosis Hepática , Humanos , Animales , Ratones , Cirrosis Hepática/genética , Factor de Crecimiento Transformador beta , Ratones Noqueados , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de la Respuesta de Crecimiento Precoz/genética , Factor de Transcripción Activador 3/genéticaRESUMEN
Insulin is a major regulator of metabolism in metazoans, including the fruit fly Drosophila melanogaster. Genome-wide association studies (GWAS) suggest a genetic basis for reductions of both insulin sensitivity and insulin secretion, phenotypes commonly observed in humans with type 2 diabetes mellitus (T2DM). To identify molecular functions of genes linked to T2DM risk, we developed a genetic tool to measure insulin-like peptide 2 (Ilp2) levels in Drosophila, a model organism with superb experimental genetics. Our system permitted sensitive quantification of circulating Ilp2, including measures of Ilp2 dynamics during fasting and re-feeding, and demonstration of adaptive Ilp2 secretion in response to insulin receptor haploinsufficiency. Tissue specific dissection of this reduced insulin signaling phenotype revealed a critical role for insulin signaling in specific peripheral tissues. Knockdown of the Drosophila orthologues of human T2DM risk genes, including GLIS3 and BCL11A, revealed roles of these Drosophila genes in Ilp2 production or secretion. Discovery of Drosophila mechanisms and regulators controlling in vivo insulin dynamics should accelerate functional dissection of diabetes genetics.
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Diabetes Mellitus Tipo 2/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Insulina/metabolismo , Animales , Proteínas Portadoras/genética , Proteínas de Unión al ADN , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Ayuno , Técnicas de Silenciamiento del Gen , Estudio de Asociación del Genoma Completo , Humanos , Insulina/biosíntesis , Insulina/genética , Resistencia a la Insulina/genética , Secreción de Insulina , Neuropéptidos , Proteínas Nucleares/genética , Proteínas Represoras , Transducción de Señal/genética , Transactivadores , Factores de Transcripción/genéticaRESUMEN
Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriología , Células Neuroendocrinas/citología , Sistemas Neurosecretores/embriología , Receptores Notch/metabolismo , Proteínas Represoras/metabolismo , Transactivadores/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Tipificación del Cuerpo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulación del Desarrollo de la Expresión Génica , Glucosa/metabolismo , Mesodermo/citología , Mesodermo/metabolismo , Células Neuroendocrinas/metabolismo , Sistemas Neurosecretores/citología , Receptores Notch/genética , Proteínas Represoras/genética , Transducción de Señal , Transactivadores/genéticaRESUMEN
The isolation of a natural product conventionally precedes its chemical synthesis. Often, the isolation and structure determination of a natural product present in minute quantities in its natural source pose formidable challenges, akin to finding "a needle in a haystack." On the other hand, leveraging plausible biosynthetic insights and biomimetic synthetic expertise would allow for the prior synthesis of presumed natural products, followed by their verification in natural sources. In this study, we unveil two novel securinega alkaloids, securingines H and I, employing the natural product anticipation through synthesis approach. Structural analysis of securingines H and I suggests that they are biosynthetic derivatives of secu'amamine E and securinol A, respectively. We posit that this "synthesis first" strategy represents a valuable approach to the discovery of new natural products.
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Glucose transporter 5 (GLUT5), the main fructose transporter in mammals, is primarily responsible for absorbing dietary fructose in the small intestine. The expression of this intestinal gene significantly increases in response to developmental and dietary cues that reach the glucocorticoid receptor and carbohydrate response element-binding protein (ChREBP), respectively. Our study demonstrates that ChREBP is involved in the dexamethasone (Dex)-induced expression of GLUT5 in Caco-2BBE cells and the small intestine of both wild-type and ChREBP-knockout mice. Dex, a glucocorticoid, demonstrated an increase in GLUT5 mRNA levels in a dose- and time-dependent manner. While the overexpression of ChREBP moderately increased GLUT5 expression, its synergistic increase in the presence of Dex was noteworthy, whereas the suppression of ChREBP significantly reduced Dex-induced GLUT5 expression. Dex did not increase ChREBP protein levels but facilitated its nuclear translocation, thereby increasing the activity of the GLUT5 promoter. In vivo experiments conducted on 14-day-old mice pups treated with Dex for three days revealed that only wild-type mice (not ChREBP-knockout mice) exhibited Dex-mediated Glut5 gene induction, which further supports the role of ChREBP in regulating GLUT5 expression. Collectively, our results provide insights into the molecular mechanisms involved in the regulation of GLUT5 expression in response to developmental and dietary signals mediated by glucocorticoids and ChREBP. General significance: The transcription factor ChREBP is important for Dex-mediated Glut5 gene expression in the small intestine.
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CRISPR/Cas9 methods are a powerful in vivo approach to edit the genome of Drosophila melanogaster. To convert existing Drosophila GAL4 lines to LexA driver lines in a secondary school classroom setting, we applied the CRISPR-based genetic approach to a collection of Gal4 'driver' lines. The integration of the yellow+ coat color marker into homology-assisted CRISPR knock-in (HACK) enabled visual selection of Gal4-to-LexA conversions using brightfield stereo-microscopy available in a broader set of standard classrooms. Here, we report the successful conversion of eleven Gal4 lines with expression in neuropeptide-expressing cells into corresponding, novel LexA drivers. The conversion was confirmed by LexA- and Gal4-specific GFP reporter gene expression. This curriculum was successfully implemented in a summer course running 16 hours/week for seven weeks. The modularity, flexibility, and compactness of this course should enable development of similar classes in secondary schools and undergraduate curricula, to provide opportunities for experience-based science instruction, and university-secondary school collaborations that simultaneously fulfill research needs in the community of science.
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In vivo genome editing with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 generates powerful tools to study gene regulation and function. We revised the homology-assisted CRISPR knock-in method to convert Drosophila GAL4 lines to LexA lines using a new universal knock-in donor strain. A balancer chromosome-linked donor strain with both body color (yellow) and eye red fluorescent protein (RFP) expression markers simplified the identification of LexA knock-in using light or fluorescence microscopy. A second balancer chromosome-linked donor strain readily converted the second chromosome-linked GAL4 lines regardless of target location in the cis-chromosome but showed limited success for the third chromosome-linked GAL4 lines. We observed a consistent and robust expression of the yellow transgene in progeny harboring a LexA knock-in at diverse genomic locations. Unexpectedly, the expression of the 3xP3-RFP transgene in the "dual transgene" cassette was significantly increased compared with that of the original single 3xP3-RFP transgene cassette in all tested genomic locations. Using this improved screening approach, we generated 16 novel LexA lines; tissue expression by the derived LexA and originating GAL4 lines was similar or indistinguishable. In collaboration with 2 secondary school classes, we also established a systematic workflow to generate a collection of LexA lines from frequently used GAL4 lines.
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Drosophila , Edición Génica , Animales , Edición Génica/métodos , Drosophila/genética , Transgenes , Genoma , Sistemas CRISPR-CasRESUMEN
Controlling built-in potential can enhance the photoresponse performance of self-powered photodetectors. Among the methods for controlling the built-in potential of self-powered devices, postannealing is simpler, more efficient, and less expensive than ion doping and alternative material research. In this study, a CuO film was deposited on a ß-Ga2O3 epitaxial layer via reactive sputtering with an FTS system, and a self-powered solar-blind photodetector was fabricated through a CuO/ß-Ga2O3 heterojunction and postannealed at different temperatures. The postannealing process reduced the defects and dislocations at the interface between each layer and affected the electrical and structural properties of the CuO film. After postannealing at 300 °C, the carrier concentration of the CuO film increased from 4.24 × 1018 to 1.36 × 1020 cm-3, bringing the Fermi level toward the valence band of the CuO film and increasing the built-in potential of the CuO/ß-Ga2O3 heterojunction. Thus, the photogenerated carriers were rapidly separated, increasing the sensitivity and response speed of the photodetector. The as-fabricated photodetector with 300 °C postannealing exhibited a photo-to-dark current ratio of 1.07 × 103; responsivity and detectivity of 30.3 mA/W and 1.10 × 1012 Jones, respectively; and fast rise and decay times of 12 ms and 14 ms, respectively. After three months of storage in an open-air space, the photocurrent density of the photodetector was maintained, indicating good stability with aging. These results suggest that the photocharacteristics of CuO/ß-Ga2O3 heterojunction self-powered solar-blind photodetectors can be improved through built-in potential control using a postannealing process.
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A Ag:AZO electrode was used as an electrode for a self-powered solar-blind ultraviolet photodetector based on a Ag2O/ß-Ga2O3 heterojunction. The Ag:AZO electrode was fabricated by co-sputtering Ag and AZO heterogeneous targets using the structural characteristics of a Facing Targets Sputtering (FTS) system with two-facing targets, and the electrical, crystallographic, structural, and optical properties of the fabricated thin film were evaluated. A photodetector was fabricated and evaluated based on the research results that the surface roughness of the electrode can reduce the light energy loss by reducing the scattering and reflectance of incident light energy and improving the trapping phenomenon between interfaces. The thickness of the electrodes was varied from 20 nm to 50 nm depending on the sputtering time. The optoelectronic properties were measured under 254 nm UV-C light, the on/off ratio of the 20 nm Ag:AZO electrode with the lowest surface roughness was 2.01 × 108, and the responsivity and detectivity were 56 mA/W and 6.99 × 1011 Jones, respectively. The Ag2O/ß-Ga2O3-based solar-blind photodetector with a newly fabricated top electrode exhibited improved response with self-powered characteristics.
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In the photo-Fenton reaction, highly reactive oxygen species are generated on UV irradiation of ß-FeOOH, which contributes significantly to hydrogen production. The production process was performed by adjusting the pH of the solution. The effect of acid concentration on hydrogen production was analyzed in this study, and the difference in the amount of hydrogen gas produced in each sample with different pH values was determined. X-ray powder diffraction (XRD) measurements of the samples corresponding to the peaks of ß-FeOOH were compared with the reference data, and crystallite sizes were calculated by the Scherrer equation using XRD patterns. The rod-like structure of the sample particles was revealed by scanning electron microscopy. A higher amount of hydrogen was produced at lower pH, and these results confirmed that pH plays an important role in hydrogen production.
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Securinega alkaloids have fascinated the synthetic chemical community for over six decades. Historically, major research foci in securinega alkaloid synthesis have been on the efficient construction of the fused tetracyclic framework that bears a butenolide moiety and tertiary amine-based heterocycles. These "basic" securinega alkaloids have evolved to undergo biosynthetic oxidative diversifications, especially on the piperidine core. However, a general synthetic solution to access these high-oxidation state securinega alkaloids is lacking. In this study, we have completed the total synthesis of various C4-oxygenated securinine-type alkaloids including securingines A, C, D, securitinine, secu'amamine D, phyllanthine, and 4-epi-phyllanthine. Our synthetic strategy features stereocontrolled oxidation, rearrangement, and epimerization at N1 and C2-C4 positions of the piperidine core within (neo)securinane scaffolds. Our discoveries provide a fundamental synthetic solution to all known securinine-type natural products with various oxidative and stereochemical variations around the central piperidine ring.
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Alcaloides , Euphorbiaceae , Azepinas , Compuestos Heterocíclicos de Anillo en Puente , Lactonas , Piperidinas , EstereoisomerismoRESUMEN
In this study, a high-photoresponsivity self-powered deep ultraviolet (DUV) photodetector based on an Ag2O/ß-Ga2O3 heterojunction was fabricated by depositing a p-type Ag2O thin film onto an n-type ß-Ga2O3 layer. The device characteristics after post-annealing at temperatures ranging from 0 to 400 °C were investigated. Our DUV devices exhibited typical rectification characteristics. At a post-annealing temperature of 300 °C, the as-fabricated device had a low leakage current of 4.24 × 10-11 A, ideality factor of 2.08, and a barrier height of 1.12 eV. Moreover, a high photo-responsivity of 12.87 mA/W was obtained at a 100 µW/cm2 light intensity at a 254 nm wavelength at zero bias voltage, the detectivity was 2.70 × 1011 Jones, and the rise and fall time were 29.76, 46.73 ms, respectively. Based on these results, the Ag2O/ß-Ga2O3 heterojunction photodetector operates without an externally applied voltage and has high responsivity, which will help in the performance improvement of ultraviolet sensing systems.
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Self-powered deep-ultraviolet photodetectors have received considerable attention in recent years because of their efficiency, reliability, and various applications in civilian and military fields. Herein, a Ag/Ag2O layer is continuously deposited on a ß-Ga2O3 epitaxial layer by a facing target sputtering system without opening the chamber, which has an advantage in time and cost. A p-n junction photodetector was constructed through the Ag2O/ß-Ga2O3 heterojunction and by varying the thickness of the Ag film, which was controlled by the sputtering time. The effect of top electrode thickness on the photoresponse characteristics of photodetectors was studied. Because thin Ag films have low surface roughness, indicating low optical loss and good interfacial conditions, photodetectors using a thin Ag film as the top electrode exhibit high photoresponsivity. However, Ag films that were thinner than the threshold thickness, which is the minimum thickness required to form a continuous, homogeneous surface film, exhibited rather low performance owing to the high reflection and scattering caused by the inhomogeneous surface morphology. The as-fabricated photodetector with a 20 nm Ag film presents a high on/off ratio of 3.43 × 108, responsivity and detectivity of 25.65 mA/W and 6.10 × 1011 Jones, respectively, and comparable rise and decay times of 108 and 80 ms, respectively. Additionally, even after three months of storage in an ambient environment, the photoresponse of the photodetector was maintained, indicating good stability in air. These results suggest that Ag2O/ß-Ga2O3 heterojunction-based photodetectors with thin Ag films can be used in various applications requiring deep-ultraviolet detection without an external power supply.
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The existence of three independent binary systems for conditional gene expression (Gal4/UAS; LexA/LexAop; QF/QUAS) has greatly expanded versatile genetic analyses in the Drosophila melanogaster; however, the experimental application of these tools is limited by the need to generate multiple collections of noninterchangeable transgenic fly strains for each inducible gene expression system. To address this practical limitation, we developed a modular vector that contains the regulatory elements from all three binary systems, enabling Gal4-, LexA- or QF-dependent expression of transgenes. Our methods also incorporate DNA elements that facilitate independent site-specific recombination and elimination of regulatory UAS, LexAop or QUAS modules with spatial and temporal control, thus offering unprecedented possibilities and logistical advantages for in vivo genetic modulation and efficient interconversion of overexpression transgenic fly lines.