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The goal when imaging bioprocesses with optical microscopy is to acquire the most spatiotemporal information with the least invasiveness. Deep neural networks have substantially improved optical microscopy, including image super-resolution and restoration, but still have substantial potential for artifacts. In this study, we developed rationalized deep learning (rDL) for structured illumination microscopy and lattice light sheet microscopy (LLSM) by incorporating prior knowledge of illumination patterns and, thereby, rationally guiding the network to denoise raw images. Here we demonstrate that rDL structured illumination microscopy eliminates spectral bias-induced resolution degradation and reduces model uncertainty by five-fold, improving the super-resolution information by more than ten-fold over other computational approaches. Moreover, rDL applied to LLSM enables self-supervised training by using the spatial or temporal continuity of noisy data itself, yielding results similar to those of supervised methods. We demonstrate the utility of rDL by imaging the rapid kinetics of motile cilia, nucleolar protein condensation during light-sensitive mitosis and long-term interactions between membranous and membrane-less organelles. Rationalized deep learning improves image reconstruction by incorporating prior knowledge of illumination patterns.

Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing tissue composition, spatial expression patterns, and cellular interactions. Furthermore, single-cell RNAseq data can be integrated for spatial cell-type enrichment analysis. The visualization module allows users to interactively visualize analysis outputs and imaging features. To demonstrate its general applicability, we apply Giotto to a wide range of datasets encompassing diverse technologies and platforms.

Circular hollow steel tubes (CHST) are widely employed as short columns in various infrastructure applications. This study comprehensively investigates the mechanical behavior of CFRP-Confined CHST (CFRP-CHST) short columns under axial compression through theoretical research, finite element analysis, and existing experimental data. New theoretical formulas for calculating the yield and ultimate bearing capacities of CFRP-CHST short columns under axial loading are developed based on continuum mechanics and the limit equilibrium method. The accuracy and reliability of these formulas are validated through comparisons with finite element simulations and experimental results. Theoretical analysis reveals that CFRP provides only a modest enhancement to the yield-bearing capacity of CHST short columns. However, within a certain range of CFRP layers, the ultimate bearing capacity is significantly improved, albeit with limitations. The concept of the CFRP confinement coefficient is introduced to define the effective range in which CFRP reinforcement substantially enhances the bearing capacity of CHST short columns. The mechanisms restricting this enhancement are investigated in detail through experimental data and finite element analysis. This research offers valuable design and analysis methods for the engineering applications of CFRP-CHST short columns.

Objective Catalpol (CAT) has various pharmacological activities and plays a protective role in cerebral ischemia. It has been reported that CAT played a protective role in cerebral ischemia by upregulaing NRF1 expression. Bioinformatics analysis reveals that NRF1 can be used as a transcription factor to bind to the histone acetyltransferase KAT2A. However, the role of KAT2A in cerebral ischemia remains to be studied. Therefore, we aimed to investigate the role of CAT in cerebral ischemia and its related mechanism. Methods In vitro, a cell model of oxygen and glucose deprivation/reperfusion (OGD/R) was constructed, followed by evaluation of neuronal injury and the expression of METTL3, Beclin-1, NRF1, and KAT2A. In vivo, a MCAO rat model was prepared by means of focal cerebral ischemia, followed by assessment of neurological deficit and brain injury in MCAO rats. Neuronal autophagy was evaluated by observation of autophagosomes in neurons or brain tissues by TEM and detection of the expression of LC3 and p62. Results In vivo, CAT reduced the neurological function deficit and infarct volume, inhibited neuronal apoptosis in the cerebral cortex, and significantly improved neuronal injury and excessive autophagy in MCAO rats. In vitro, CAT restored OGD/R-inhibited cell viability, inhibited cell apoptosis, LDH release, and neuronal autophagy. Mechanistically, CAT upregulated NRF1, NRF1 activated METTL3 via KAT2A transcription, and METTL3 inhibited Beclin-1 via m 6 A modification. Conclusion CAT activated the NRF1/KAT2A/METTL3 axis and downregulated Beclin-1 expression, thus relieving neuronal injury and excessive autophagy after cerebral ischemia.

MAC5 is a component of the conservedMOS4-associated complex. It plays critical roles in development and immunity. Here we report that MAC5 is required for microRNA (miRNA) biogenesis. MAC5 interacts with Serrate (SE), which is a core component of the microprocessor that processes primary miRNA transcripts (pri-miRNAs) into miRNAs and binds the stem-loop region of pri-miRNAs. MAC5 is essential for both the efficient processing and the stability of primiRNAs. Interestingly, the reduction of pri-miRNA levels in mac5 is partially caused by XRN2/XRN3, the nuclear-localized 5′-to-3′ exoribonucleases, and depends on SE. These results reveal that MAC5 plays a dual role in promoting pri-miRNA processing and stability through its interaction with SE and/or pri-miRNAs. This study also uncovers that pri-miRNAs need to be protected from nuclear RNA decay machinery, which is connected to the microprocessor.

Background This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia. Methods Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system, and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. The expression levels of LINC00240, miR-155, Nrf2, and oxidative stress and pyroptosis-related markers in in vitro and in vivo preeclampsia models were analyzed by qPCR, western blot, or ELISA assays. Blood pressure, urine protein levels, liver and kidney damages, and trophoblast markers in placenta tissues were further studied in vivo. Results Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 and increased miR-155 expression levels, and the decreased M2 macrophage polarization. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to increased Nrf2 expression and similar changes as LINC00240 overexpression in trophoblast function and macrophage polarization. Overexpression of LINC00240 in in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and induced trophoblast function and M2 macrophage polarization. Conclusion LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast function and M2 macrophage polarization. LINC00240 could be a potential therapeutic target for preeclampsia.

This study investigated the aerodynamic structures generated by transverse jet injection in supersonic flows around high-speed vehicles. The unsteady evolution of these structures was analyzed using an improved delayed detached Eddy simulation (IDDES) approach based on the Reynolds stress model (RSM). The simulations successfully reproduced experimentally observed shock systems and vortical structures. The time-averaged flow characteristics were compared with the experimental results, and good agreement was observed. The flow characteristics were analyzed, with particular emphasis on the formation of counter-rotating vortex pairs in the downstream region, as well as complex near-field phenomena, such as flow separation and shock wave/boundary layer interactions. Time-resolved spectral analysis at multiple monitoring locations revealed the presence of a global oscillation within the flow dynamics. Within these regions, pressure fluctuations in the recirculation zone lead to periodic oscillations of the upstream bow shock. This dynamic interaction modulates the instability of the windward shear layer and generates large-scale vortex structures. As these shed vortices convect downstream, they interact with the barrel shock, triggering significant oscillatory motion. To further characterize this behavior, dynamic mode decomposition (DMD) was applied to the pressure fluctuations. The analysis confirmed the presence of a coherent global oscillation mode, which was found to simultaneously govern the periodic motions of both the upstream bow shock and the barrel shock.

Gastric cancer (GC) is one of the most common malignant tumors with a poor prognosis. Ferroptosis is an distinct type of non-apoptotic cell death that is closely associated with tumor prognosis. Thus, we aimed to develop an novel prognosis risk model based on ferroptosis-related lncRNAs and excavate novel diagnostic markers. In this study, eight ferroptosis-related lncRNAs were obtained for constructing the prognosis model in GC based on TCGA database. The patients in the high-risk group had worse survival than those in the low-risk group, and the risk-grouping could be used as an independent prognostic factor for OS. Receiver operating characteristic curve analysis demonstrated this risk model was superior to traditional clinicopathological features in predicting GC prognosis. GSEA revealed that these lncRNAs were mainly involved in cell adhesion, cancer pathways, and immune function regulation. The key gene HAGLR of this risk signature was up-regulated in GC tissues and cells. Function assays showed that knockdown of HAGLR could effectively inhibit the GC cells proliferation and migration, whereas silencing HAGLR accelerated apoptosis and ferroptosis cell death process. In conclusion, we established a novel ferroptosis-related prognostic risk signature including eight lncRNAs, which may improve prognostic predictive accuracy for patients with GC.

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events. Some patients present with multiple lung tumours but it is unclear whether these are metastases or individual lesions. Here, the authors use genomics techniques to demonstrate in six patients that multiple tumours have individual genetic profiles and represent separate tumours.

MAC3A and MAC3B are conserved U-box-containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis thaliana. However, their functional mechanisms remain elusive. Here, we show that Arabidopsis MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs). However, MAC3A and MAC3B do not affect the promoter activity of genes encoding miRNAs (MIR genes), suggesting that they may not affect MIR transcription. This result, together with the fact that MAC3A associates with primiRNAs in vivo, indicates that MAC3A and MAC3B may stabilize pri-miRNAs. Furthermore, we find that MAC3A and MAC3B interact with the DCL1 complex that catalyzes miRNA maturation, promote DCL1 activity, and are required for the localization of HYL1, a component of the DCL1 complex. Besides MAC3A and MAC3B, two other MAC subunits, CDC5 and PRL1, also function in miRNA biogenesis. Based on these results, we propose that MAC functions as a complex to control miRNA levels through modulating pri-miRNA transcription, processing, and stability.