172 research outputs found

    DiffNAS: Bootstrapping Diffusion Models by Prompting for Better Architectures

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    Diffusion models have recently exhibited remarkable performance on synthetic data. After a diffusion path is selected, a base model, such as UNet, operates as a denoising autoencoder, primarily predicting noises that need to be eliminated step by step. Consequently, it is crucial to employ a model that aligns with the expected budgets to facilitate superior synthetic performance. In this paper, we meticulously analyze the diffusion model and engineer a base model search approach, denoted "DiffNAS". Specifically, we leverage GPT-4 as a supernet to expedite the search, supplemented with a search memory to enhance the results. Moreover, we employ RFID as a proxy to promptly rank the experimental outcomes produced by GPT-4. We also adopt a rapid-convergence training strategy to boost search efficiency. Rigorous experimentation corroborates that our algorithm can augment the search efficiency by 2 times under GPT-based scenarios, while also attaining a performance of 2.82 with 0.37 improvement in FID on CIFAR10 relative to the benchmark IDDPM algorithm

    Multi-omics profiles refine L-dopa decarboxylase (DDC) as a reliable biomarker for prognosis and immune microenvironment of clear cell renal cell carcinoma

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    BackgroundIncreasing evidence indicates that L-dopa decarboxylase (DDC), which mediates aberrant amino acid metabolism, is significantly associated with tumor progression. However, the impacts of DDC are not elucidated clearly in clear cell renal cell carcinoma (ccRCC). This study aimed to evaluate DDC prognostic value and potential mechanisms for ccRCC patients.MethodsTranscriptomic and proteomic expressions of and clinical data including 532 patients with ccRCC (The Cancer Genome Atlas RNA-seq data), 226 ccRCC samples (Gene Expression Omnibus), 101 ccRCC patients from the E-MTAB-1980 cohort, and 232 patients with ccRCC with proteogenomic data (Fudan University Shanghai Cancer Center) were downloaded and analyzed to investigate the prognostic implications of DDC expression. Cox regression analyses were implemented to explore the effect of DDC expression on the prognosis of pan-cancer. The "limma" package identified the differentially expressed genes (DEGs) between high DDC subgroups and low DDC groups. Functional enrichments were performed based DEGs between DDC subgroups. The differences of immune cell infiltrations and immune checkpoint genes between DDC subgroups were analyzed to identify potential influence on immune microenvironment.ResultsWe found significantly decreased DDC expression in ccRCC tissues compared with normal tissues from multiple independent cohorts based on multi-omics data. We also found that DDC expression was correlated with tumor grades and stages.The following findings revealed that lower DDC expression levels significantly correlated with shorter overall survival (P <0.001) of patients with ccRCC. Moreover, we found that DDC expression significantly correlated with an immunosuppressive tumor microenvironment, higher intra-tumoral heterogeneity, elevated expression of immune checkpoint CD274, and possibly mediated malignant behaviors of ccRCC cells via the PI3k/Akt signaling pathway.ConclusionThe present study is the first to our knowledge to indicate that decreased DDC expression is significantly associated with poor survival and an immune-suppressive tumor microenvironment in ccRCC. These findings suggest that DDC could serve as a biomarker for guiding molecular diagnosis and facilitating the development of novel individual therapeutic strategies for patients with advanced ccRCC

    circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p

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    Background: As a type of non-coding RNA, circular RNAs (circRNAs) are considered to be functional molecules associated with human cancers. An increasing number of circRNAs have been verified in malignant progression in a number of cancers. The circRNA, circFBXW7, has been proven to play an important role in tumor proliferation and metastasis. However, whether circFBXW7 influences progression in lung adenocarcinoma (LUAD) remains unclear. Methods: Quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify circFBXW7 in LUAD cell lines and LUAD tissues. Kaplan-Meier analysis was then used to compare the disease-free survival (DFS) and overall survival (OS) of these LUAD patients. The biological function of circFBXW7 was examined by overexpression and knockdown of circFBXW7 using MTT assay, EdU assay, wound-healing assay, and Transwell in vitro assays. To explore the mechanism of the circFBXW7, RNA pull-down assay, dual luciferase reporter assay, and RNA immunoprecipitation (RIP) assay were employed to examine the interaction between circFBXW7 and miR-942-5p. Western blot was used to study the fundamental proteins associated with the epithelial-mesenchymal transition (EMT) pathway. In vivo studies with BALB/c nude mice subcutaneously injected with cells stably overexpressing circFBXW7 were performed to further validate the in vitro results. Results: circFBXW7 was downregulated in LUAD cell lines and tissues, and LUAD patients with lower levels had shorter DFS and OS. The in vitro study showed that circFBXW7 overexpression inhibited proliferation and migration of A549 and HCC2279 cell lines. These results were confirmed by circFBXW7 knockdown, which showed the reverse effect. The in vivo model showed that the circRNA levels influenced the tumor growth. Finally, we determined that circFBXW7 target miRNA-942-5p which regulates the EMT gene BARX2. The modulation of circFBXW7 levels produced significant changes in EMT genes in vitro and in vivo. Conclusions: Our findings showed that circFBXW7 inhibits proliferation and migration by controlling the miR-942-5p/BARX2 axis in LUAD cell lines and its levels correlates with patient survival suggesting that regulating circFBXW7 could have therapeutic value in treating LUAD patients

    Ocean Acidification Impairs Foraging Behavior by Interfering With Olfactory Neural Signal Transduction in Black Sea Bream, Acanthopagrus schlegelii

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    In recent years, ocean acidification (OA) caused by oceanic absorption of anthropogenic carbon dioxide (CO2) has drawn worldwide concern over its physiological and ecological effects on marine organisms. However, the behavioral impacts of OA and especially the underlying physiological mechanisms causing these impacts are still poorly understood in marine species. Therefore, in the present study, the effects of elevated pCO2 on foraging behavior, in vivo contents of two important neurotransmitters, and the expression of genes encoding key modulatory enzymes from the olfactory transduction pathway were investigated in the larval black sea bream. The results showed that larval sea breams (length of 4.71 ± 0.45 cm) reared in pCO2 acidified seawater (pH at 7.8 and 7.4) for 15 days tend to stall longer at their acclimated zone and swim with a significant slower velocity in a more zigzag manner toward food source, thereby taking twice the amount of time than control (pH at 8.1) to reach the food source. These findings indicate that the foraging behavior of the sea bream was significantly impaired by ocean acidification. In addition, compared to a control, significant reductions in the in vivo contents of γ-aminobutyric acid (GABA) and Acetylcholine (ACh) were detected in ocean acidification-treated sea breams. Furthermore, in the acidified experiment groups, the expression of genes encoding positive regulators, the olfaction-specific G protein (Golf) and the G-protein signaling 2 (RGS2) and negative regulators, the G protein-coupled receptor kinase (GRK) and arrestin in the olfactory transduction pathway were found to be significantly suppressed and up-regulated, respectively. Changes in neurotransmitter content and expression of olfactory transduction related genes indicate a significant disruptive effect caused by OA on olfactory neural signal transduction, which might reveal the underlying cause of the hampered foraging behavior

    Advances in the research, diagnosis and treatment of renal cell carcinoma in 2022

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    Renal cell carcinoma (RCC) is one of the three major urinary system tumors. With the changes of lifestyle and the rise of obesity, hypertension and other diseases, the incidence of RCC is increasing. The onset of RCC is hidden, and RCC has strong heterogeneity. Most RCC patients are found accidentally by imaging examination, so many patients were diagnosed in the advanced stage. Although the emergence of targeted therapy and immunotherapy has greatly prolonged the survival time of patients with advanced RCC, due to many pathological types of RCC, it is still difficult for many patients to benefit from the systematic treatment. Many basic and clinical studies are devoted to the development of new targets or drugs to prolong the survival time of patients. This article reviewed the advances in the research, diagnosis and treatment of RCC in 2022

    Generation of integration-free neural progenitor cells from cells in human urine

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    Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.postprin

    Sciences for The 2.5-meter Wide Field Survey Telescope (WFST)

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    The Wide Field Survey Telescope (WFST) is a dedicated photometric survey facility under construction jointly by the University of Science and Technology of China and Purple Mountain Observatory. It is equipped with a primary mirror of 2.5m in diameter, an active optical system, and a mosaic CCD camera of 0.73 Gpix on the main focus plane to achieve high-quality imaging over a field of view of 6.5 square degrees. The installation of WFST in the Lenghu observing site is planned to happen in the summer of 2023, and the operation is scheduled to commence within three months afterward. WFST will scan the northern sky in four optical bands (u, g, r, and i) at cadences from hourly/daily to semi-weekly in the deep high-cadence survey (DHS) and the wide field survey (WFS) programs, respectively. WFS reaches a depth of 22.27, 23.32, 22.84, and 22.31 in AB magnitudes in a nominal 30-second exposure in the four bands during a photometric night, respectively, enabling us to search tremendous amount of transients in the low-z universe and systematically investigate the variability of Galactic and extragalactic objects. Intranight 90s exposures as deep as 23 and 24 mag in u and g bands via DHS provide a unique opportunity to facilitate explorations of energetic transients in demand for high sensitivity, including the electromagnetic counterparts of gravitational-wave events detected by the second/third-generation GW detectors, supernovae within a few hours of their explosions, tidal disruption events and luminous fast optical transients even beyond a redshift of 1. Meanwhile, the final 6-year co-added images, anticipated to reach g about 25.5 mag in WFS or even deeper by 1.5 mag in DHS, will be of significant value to general Galactic and extragalactic sciences. The highly uniform legacy surveys of WFST will also serve as an indispensable complement to those of LSST which monitors the southern sky.Comment: 46 pages, submitted to SCMP

    Examining the generalizability of research findings from archival data

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    This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples
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