The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila.

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.

cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila.

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells1-5. Animal genomes typically encode multiple proteins with predicted homology to cGAS6-10, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.

Two cGAS-like receptors induce antiviral immunity in Drosophila.

In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes1 and eukaryotes2-5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections6-8. Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-κB-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3'2'-cGAMP, whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2'3'-cGAMP.

Effects of multiple firings on metal-ceramic bond strength of Co-Cr alloy fabricated by selective laser melting.

STATEMENT OF PROBLEM: Selective laser melting (SLM) is a new technique for fabricating dental restorations, but the metal-ceramic bond strength of the restorations after multiple firings must be considered because adequate bond strength is a clinical requirement for long-term performance. PURPOSE: The purpose of this study was to investigate the effects of repeated firing on the metal-ceramic bond strength of an SLM Co-Cr alloy. MATERIAL AND METHODS: Thirty-six SLM-fabricated (Group SLM) and conventional lost wax cast (Group Cast) Co-Cr metal bars were prepared. Eighteen bars from each group were molded into dimensions of 25×3×0.5 mm, following International Organization for Standardization (ISO) standard 9693:2012. In the center of each bar, a 1.1-mm thickness of porcelain was fused onto an 8×3-mm rectangular area. In each group, specimens were divided into 3 subgroups based on the number of firing cycles (3, 5, 7) for the veneering process. Metal-ceramic bond strength, fracture mode analysis, and area fraction of adherence porcelain (AFAP) of each subgroup was evaluated with a 3-point bend test and by measuring the Si content of specimens with scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). The results were statistically analyzed first with the Shapiro-Wilk test, where a P value of .364 was considered normally distributed, and then with the Student t test to determine significant differences (α=.05). RESULTS: Student t test results showed no statistical differences between the metal-ceramic bond strength of SLM and that of conventionally cast groups after firing 3, 5, and 7 times (P>.05). However, after SEM/EDS analyses, the SLM group showed significantly more porcelain adherence than that of the control group (P<.05) after 5 or 7 firings. CONCLUSIONS: The SLM group showed superior metal-ceramic bond strength that exceeded ISO 9691:1999 (E) requirements at all firing periods. Also, the bond showed better behavior in terms of AFAP than the conventional cast group, especially after 5 or 7 firings.

Research progress on the surface modification of carbon fiber.

Carbon fiber (CF) has high strength, high modulus, and excellent high-temperature resistance and chemical stability; therefore, it is used in diverse fields. However, due to the lack of active functional groups on the surface of CF and surface defects generated during the preparation of CF, the wettability of the fiber surface is poor, which seriously affects the interface performance between the fiber and a resin matrix. In recent years, extensive research has been conducted on the surface modification of CF. In this review, studies on the surface modification of CF are summarized, including the various methods utilized, such as dry modification, wet modification, and nanomodification, as well as their current application status. As interest in this material increases, high-performance CFs will likely play an important role in many fields in the future.

Correctable Landmark Discovery Via Large Models for Vision-Language Navigation.

Vision-Language Navigation (VLN) requires the agent to follow language instructions to reach a target position. A key factor for successful navigation is to align the landmarks implied in the instruction with diverse visual observations. However, previous VLN agents fail to perform accurate modality alignment especially in unexplored scenes, since they learn from limited navigation data and lack sufficient open-world alignment knowledge. In this work, we propose a new VLN paradigm, called COrrectable LaNdmark DiScOvery via Large ModEls (CONSOLE). In CONSOLE, we cast VLN as an open-world sequential landmark discovery problem, by introducing a novel correctable landmark discovery scheme based on two large models ChatGPT and CLIP. Specifically, we use ChatGPT to provide rich open-world landmark cooccurrence commonsense, and conduct CLIP-driven landmark discovery based on these commonsense priors. To mitigate the noise in the priors due to the lack of visual constraints, we introduce a learnable cooccurrence scoring module, which corrects the importance of each cooccurrence according to actual observations for accurate landmark discovery. We further design an observation enhancement strategy for an elegant combination of our framework with different VLN agents, where we utilize the corrected landmark features to obtain enhanced observation features for action decision. Extensive experimental results on multiple popular VLN benchmarks (R2R, REVERIE, R4R, RxR) show the significant superiority of CONSOLE over strong baselines. Especially, our CONSOLE establishes the new state-of-the-art results on R2R and R4R in unseen scenarios.

A novel virus-induced cyclic dinucleotide, 2'3'-c-di-GMP, mediates STING-dependent antiviral immunity in Drosophila.

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP. This CDN binds to and activates the protein STING to trigger immunity. We recently discovered in the model organism Drosophila melanogaster two cGAS-like receptors (cGLRs) that activate STING-dependent antiviral immunity and can produce 3'2'-cGAMP, in addition to 2'3'-cGAMP. Here we explore CDN-mediated immunity in 14 different Drosophila species covering 50 million years of evolution and report that 2'3'-cGAMP and 3'2'-cGAMP fail to control infection by Drosophila C virus in D. serrata, D. sechellia and D. mojavensis . Using an accurate and sensitive mass spectrometry method, we discover an unexpected diversity of CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster , including a novel CDN, 2'3'-c-di-GMP. We show that 2'3'-c-di-GMP is the most potent STING agonist identified so far in D. melanogaster and that this molecule also activates a strong antiviral transcriptional response in D. serrata . Our results shed light on the evolution of cGLRs in flies and provide a basis for the understanding of the function and regulation of this emerging family of PRRs in animal innate immunity.

MicroRNA-146a downregulates interleukin-13 and inhibits the proliferation of human periodontal ligament stem cells.

OBJECTIVE: This study was carried out to investigate the interaction between microRNA-146a and interleukin-13 (IL-13) in periodontitis. DESIGN: The expression levels of microRNA-146a and IL-13 in periodontal ligament stem cells (PDLSCs) derived from periodontitis-affected teeth and healthy teeth were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A microRNA-146a mimic was transfected into PDLSCs, and proliferation and IL-13 expression were detected via a cell counting kit-8 (CCK-8) assay and western blot, respectively. RESULTS: microRNA-146a was downregulated and IL-13 was upregulated in PDLSCs derived from periodontitis-affected teeth compared to that in PDLSCs derived from healthy teeth. microRNA-146a and IL-13 were negatively correlated in periodontitis-derived PDLSCs but not in those derived from healthy teeth. The former also exhibited significantly enhanced cell proliferation. Overexpression of microRNA-146a inhibited proliferation of PDLSCs derived from both periodontitis-affected teeth and healthy teeth while downregulating IL-13. CONCLUSIONS: microRNA-146a may improve periodontitis by downregulating IL-13 and inhibiting the proliferation of human PDLSCs.

Charge-Transporting-Layer-Free, Vacuum-Free, All-Inorganic CsPbIBr2 Perovskite Solar Cells Via Dipoles-Adjusted Interface.

The inorganic perovskite has a better stability than the hybrid halide perovskite, and at the same time it has the potential to achieve an excellent photoelectric performance as the organic-inorganic hybrid halide perovskite. Thus, the pursuit of a low-cost and high-performance inorganic perovskite solar cell (PSC) is becoming the research hot point in the research field of perovskite devices. In setting out to build vacuum-free and carbon-based all-inorganic PSCs with the traits of simple fabrication and low cost, we propose the ones with a simplified vertical structure of FTO/CsPbIBr2/carbon upon interfacial modification with PEI species. In this structure, both the electron-transporting-layer and hole-transporting-layer are abandoned, and the noble metal is also replaced by the carbon paste. At the same time, FTO is modified by PEI, which brings dipoles to decrease the work function of FTO. Through our measurements, the carrier recombination has been partially suppressed, and the performance of champion PSCs has far exceeded the control devices without PEI modification, which yields a power conversion efficiency of 4.9% with an open circuit voltage of 0.9 V and a fill factor of 50.4%. Our work contributes significantly to give an available method to explore charge-transporting-layer-free, low-cost, and high-performance PSCs.

Toward High-Performance Electron/Hole-Transporting-Layer-Free, Self-Powered CsPbIBr2 Photodetectors via Interfacial Engineering.

Self-powered photodetectors (PDs) with inorganic lead halide perovskites hold multiple traits of high sensitivity, fast response, independence from external power supply, and excellent sustainability and stability, thus holding a great promise for practical applications. However, they generally contain high-temperature-processed electron-transporting layers (ETLs) and high-cost, unstable hole-transporting layers (HTLs) coupled with noble metal electrodes, which bring significant obstacles of production cost and stability for their potential commercialization. Herein, we demonstrate the building of high-performance HTL/ETL-free, self-powered CsPbIBr2 PD with simplified architecture of fluorine-doped tin oxide (FTO)/CsPbIBr2/carbon upon interfacial modification by polyethyleneimine (PEI). The optimized PD yields a dark current of 2.03 × 10-9 A, peak responsivity (R) of 0.32 A/W, maximum specific detectivity (D*) of 3.74 × 1012 Jones, and response time of 1.21 µs. These figures of merit are far beyond those of the one prepared without PEI modification and even the PD containing TiO2 ETL. Hence, our work suggests a highly feasible route to develop self-powered PDs with significantly simplified fabrication and a reduced production cost.