Activatable Heavy-Atom-Free Photosensitizer with Large Stokes Shift and a NIR-II Emission Harnessing Rhodamine Ring-Opening Strategy.

Activatable photosensitizers (PSs) generating 1O2 only under specific conditions can minimize concomitant injury to normal tissues. Heavy-atom-free PSs hold the merits of low dark toxicity, long triplet-state lifetimes, good photostability, and relatively low cost. PSs with emission in the second near-infrared (NIR-II) window are highly valuable for deep-tissue, high-contrast imaging. Herein, we have designed and synthesized a series of heavy-atom-free PSs by a one-step reaction between an easily accessible rhodamine derivative and commercially available thiophene aldehydes. One of the as-prepared PSs, 2b-3T, exhibits emission maxima at 810 nm and tails to the NIR-II region at 1140 nm, together with large Stokes shift (178 nm). Importantly, the newly developed PSs, featuring functional carboxylic acid groups, present promising opportunities as versatile platforms for creating activatable PSs. To validate our concept, we developed Cu2+/pH-activatable PSs using the spirocyclization mechanism of rhodamine. Ultimately, we showcased the effectiveness of these innovative PSs in photodynamic therapy through in vitro experiments.

First Report of Penicillium oxalicum Causing Postharvest Fruit Rot on Citrus in China.

Ougan (Citrus reticulata cv. Suavissima) is a distinct citrus cultivar local to Zhejiang province, China. (Guo et al. 2021). In November 2021, an unknown postharvest fruit rot was observed in the Sanyang wetland Ougan planting area, Wenzhou City of Zhejiang Province (27.96 °N, 120.69 °E). About 3% of diseased fruits with similar fruit rot symptoms were observed in 900 mandarin fruits from four commercial storages. Initially, the symptoms appeared as light brown lesions that turned deep brown as the lesions expanded. To identify the pathogen, segments (5 mm2) from margins of rotted tissue were excised from 5 symptomatic fruits, surface disinfested twice with 75% ethanol, rinsed three times with sterilized water, placed aseptically onto potato dextrose agar (PDA) medium and incubated for 7 days at 25℃ in darkness for identification. Five fungal isolates with the same morphology were obtained using the single spore method (Leslie and Summerell 2006). Initially, the fungus produced fluffy and white aerial mycelium that eventually turned green on PDA medium after 3 days. Conidiophores were broom-shaped (17.5 ± 2.5 µm) (n=50). Conidia were unicellular and ellipsoid (3.5 to 5.0 ×2.5 to 4.0 µm) (n=50). These morphological characteristics were consistent with Penicillium species (Wu et al. 2022). WZU-OG1 was chosen as a representative isolate for further study. For molecular identification, PCR amplification and DNA sequencing were performed using primers ITS1/ITS4 (White et al. 1990), bt2a/bt2b (Glass and Donaldson 1995), and RPB2-5F/RPB2-7R (Liu et al. 1999) to amplify the complete internal transcribed spacer (ITS) region, ß-tubulin gene (TUB), and a portion of RNA polymerase second largest subunit (RPB2). The ITS, TUB, and RPB2 gene sequences of isolate WZU-OG1 were deposited in the GenBank database with acc. nos. ON332735, ON428245, and ON524171, respectively. BLASTn analysis respectively showed 561/561 (MH855125), 414/427 (KF296462), and 936/954 (JN121456) matching with Penicillium oxalicum CBS 219.30. A neighbor-joining phylogenetic analysis based on the concatenated nucleotide sequences (ITS, TUB, and RPB2) grouped this isolate in the Penicillium oxalicum species complex clade at 100% bootstrap support. To verify pathogenicity, 20 healthy mandarin fruit of cultivar Sanyang were superficially disinfested with 75% ethanol and then washed with distilled water. A conidial suspension of 1 × 105 conidia/ml from a 5-day-old culture of WZU-OG1 was injected into 10 fruits (10 µL per fruit). An equal number of fruits inoculated with sterile water were used as the negative control. The inoculated fruits were stored in a constant temperature incubator under the conditions of 28 ℃, 90% humidity, and incubated in a 12-h light/12-h dark cycle for 12 days. Symptoms similar to those on the naturally infected fruit began 5 days after inoculation, whereas no symptoms occurred on the controls. The experiment was repeated three times, and similar symptoms were observed in all diseased fruits. Then, the fungus was reisolated from these infected fruits and identified as P. oxalicum by the morphological and molecular methods described above. This is the first report of P. oxalicum causing postharvest mandarin decay and this study will enable us to rapidly diagnose this disease, identify the occurrence of this disease and develop adequate management strategies to control it in China.

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis.

Brain-Inspired Learning, Perception, and Cognition: A Comprehensive Review.

The progress of brain cognition and learning mechanisms has provided new inspiration for the next generation of artificial intelligence (AI) and provided the biological basis for the establishment of new models and methods. Brain science can effectively improve the intelligence of existing models and systems. Compared with other reviews, this article provides a comprehensive review of brain-inspired deep learning algorithms for learning, perception, and cognition from microscopic, mesoscopic, macroscopic, and super-macroscopic perspectives. First, this article introduces the brain cognition mechanism. Then, it summarizes the existing studies on brain-inspired learning and modeling from the perspectives of neural structure, cognitive module, learning mechanism, and behavioral characteristics. Next, this article introduces the potential learning directions of brain-inspired learning from four aspects: perception, cognition, understanding, and decision-making. Finally, the top-ten open problems that brain-inspired learning, perception, and cognition currently face are summarized, and the next generation of AI technology has been prospected. This work intends to provide a quick overview of the research on brain-inspired AI algorithms and to motivate future research by illuminating the latest developments in brain science.

An Adaptive Migration Collaborative Network for Multimodal Image Classification.

The multispectral (MS) and the panchromatic (PAN) images belong to different modalities with specific advantageous properties. Therefore, there is a large representation gap between them. Moreover, the features extracted independently by the two branches belong to different feature spaces, which is not conducive to the subsequent collaborative classification. At the same time, different layers also have different representation capabilities for objects with large size differences. In order to dynamically and adaptively transfer the dominant attributes, reduce the gap between them, find the best shared layer representation, and fuse the features of different representation capabilities, this article proposes an adaptive migration collaborative network (AMC-Net) for multimodal remote-sensing (RS) images classification. First, for the input of the network, we combine principal component analysis (PCA) and nonsubsampled contourlet transformation (NSCT) to migrate the advantageous attributes of the PAN and the MS images to each other. This not only improves the quality of images themselves, but also increases the similarity between the two images, thereby reducing the representational gap between them and the pressure on the subsequent classification network. Second, for the interaction on the feature migrate branch, we design a feature progressive migration fusion unit (FPMF-Unit) based on the adaptive cross-stitch unit of correlation coefficient analysis (CCA), which can make the network automatically learn the features that need to be shared and migrated, aiming to find the best shared-layer representation for multifeature learning. And we design an adaptive layer fusion mechanism module (ALFM-Module), which can adaptively fuse features of different layers, aiming to clearly model the dependencies among multiple layers for different sized objects. Finally, for the output of the network, we add the calculation of the correlation coefficient to the loss function, which can make the network converge to the global optimum as much as possible. The experimental results indicate that AMC-Net can achieve competitive performance. And the code for the network framework is available at: https://github.com/ru-willow/A-AFM-ResNet.

RAB21 controls autophagy and cellular energy homeostasis by regulating retromer-mediated recycling of SLC2A1/GLUT1.

The endosomal system maintains cellular homeostasis by coordinating multiple vesicular trafficking events, and the retromer complex plays a critical role in endosomal cargo recognition and sorting. Here, we demonstrate an essential role for the small GTPase RAB21 in regulating retromer-mediated recycling of the glucose transporter SLC2A1/GLUT1 and macroautophagy/autophagy. RAB21 depletion mis-sorts SLC2A1 to lysosomes and affects glucose uptake, thereby activating the AMPK-ULK1 pathway to increase autophagic flux. RAB21 depletion also increases lysosome function. Notably, RAB21 depletion does not overtly affect retrograde transport of IGF2R/CI-M6PR or WLS from endosomes to the trans-Golgi network. We speculate that RAB21 regulates fission of retromer-decorated endosomal tubules, as RAB21 depletion causes accumulation of the SNX27-containing retromer complex on enlarged endosomes at the perinuclear region. Functionally, RAB21 depletion sensitizes cancer cells to energy stress and inhibits tumor growth in vivo, suggesting an oncogenic role for RAB21. Overall, our study illuminates the role of RAB21 in regulating endosomal dynamics and maintaining cellular energy homeostasis and suggests RAB21 as a potential metabolic target for cancer therapy.

CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1.

Failures to treat triple-negative breast cancer (TNBC) are mainly due to chemoresistance or radioresistance. We and others previously discovered that zinc finger E-box-binding homeobox 1 (ZEB1) is a massive driver causing these resistance. However, how to dynamically modulate the intrinsic expression of ZEB1 during cell cycle progression is elusive. Here integrated affinity purification combined with mass spectrometry and TCGA analysis identify a cell cycle-related E3 ubiquitin ligase, checkpoint with forkhead and ring finger domains (CHFR), as a key negative regulator of ZEB1 in TNBC. Functional studies reveal that CHFR associates with and decreases ZEB1 expression in a ubiquitinating-dependent manner and that CHFR represses fatty acid synthase (FASN) expression through ZEB1, leading to significant cell death of TNBC under chemotherapy. Intriguingly, a small-molecule inhibitor of HDAC under clinical trial, Trichostatin A (TSA), increases the expression of CHFR independent of histone acetylation, thereby destabilizes ZEB1 and sensitizes the resistant TNBC cells to conventional chemotherapy. In patients with basal-like breast cancers, CHFR levels significantly correlates with survival. These findings suggest the therapeutic potential for targeting CHFR-ZEB1 signaling in resistant malignant breast cancers.

LncRNA XIST mediates bovine mammary epithelial cell inflammatory response via NF-κB/NLRP3 inflammasome pathway.

OBJECTIVES: The correlations between long non-coding RNAs (lncRNAs) and diverse mammal diseases have been clarified by many researches, but the cognition about bovine mastitis-related lncRNAs remains limited. This study aimed to investigate the potential role of lncRNA X-inactive specific transcript (XIST) in the inflammatory response of bovine mammary epithelial cells. MATERIALS AND METHODS: Two inflammatory bovine mammary alveolar cell-T (MAC-T) models were established by infecting the cells with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The expressions of pro-inflammatory cytokines were measured, and the proliferation, viability and apoptosis of the inflammatory cells were evaluated after XIST was knocked down by an siRNA. The relationship among XIST, NF-κB pathway and NOD-like receptor protein 3 (NLRP3) inflammasome was investigated using an inhibitor of NF-κB signal pathway. RESULTS: The expression of XIST was abnormally increased in bovine mastitic tissues and inflammatory MAC-T cells. Silencing of XIST significantly increased the expression of E. coli or S. aureus-induced pro-inflammatory cytokines. Additionally, knockdown of XIST could inhibit cell proliferation, suppress cell viability and promote cell apoptosis under inflammatory conditions. Furthermore, XIST inhibited E. coli or S. aureus-induced NF-κB phosphorylation and the production of NLRP3 inflammasome. CONCLUSIONS: The expression of XIST was promoted by activated NF-κB pathway and, in turn, XIST generated a negative feedback loop to regulate NF-κB/NLRP3 inflammasome pathway for mediating the process of inflammation.

SDF-1 in Mammary Fibroblasts of Bovine with Mastitis Induces EMT and Inflammatory Response of Epithelial Cells.

Fibroblasts constitute the majority of the stromal cells within bovine mammary gland, yet the functional contributions of these cells to mastitis and fibrosis and the mechanism are poorly understood. In this study, we demonstrate that inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis had different expression pattern regarding to several extracellular matrix (ECM) proteins, chemokines and cytokines compared to normal fibroblasts (NFs) from dairy cows during lactation. The INFs induced epithelial-mesenchymal transition (EMT) and inflammatory responses of mammary epithelial cells in a vitro co-culture model. These functional contributions of INFs to normal epithelial cells were mediated through their ability to secrete stromal cell-derived factor 1 (SDF-1). SDF-1 was highly secreted/expressed by INFs, lipopolysaccharide (LPS) -treated NFs, lipoteichoic acid (LTA) -treated NFs, as well as mastitic tissue compared to their counterparts. Exogenous SDF-1 promoted EMT on epithelial cells through activating NF-κB pathway, induced inflammation response and inhibited proliferation of epithelial cells. In addition, SDF-1 was able to induce mastitis and slight fibrosis of mouse mammary gland, which was attenuated by a specific inhibitor of the receptor of SDF-1. Our findings indicate that stromal fibroblasts within mammary glands with mastitis contribute to EMT and inflammatory responses of epithelial cells through the secretion of SDF-1, which could result in the inflammation spread and fibrosis within mammary gland.