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Hearing is an extremely delicate sense that is particularly vulnerable to insults from environment, including drugs and noise. Unsurprisingly, mice of different genetic backgrounds show different susceptibility to hearing loss. In particular, CBA/CaJ (CBA) mice maintain relatively stable hearing over age while C57BL/6J (B6) mice show a steady decline of hearing, making them a popular model for early onset hearing loss. To reveal possible underlying mechanisms, we examined cellular differences in the cochlea of these two mouse strains. Although the ABR threshold and Wave I latency are comparable between them, B6 mice have a smaller Wave I amplitude. This difference is probably due to fewer spiral ganglion neurons found in B6 mice, as the number of ribbon synapses per inner hair cell (IHC) is comparable between the two mouse strains. Next, we compared the outer hair cell (OHC) function and we found OHCs from B6 mice are larger in size but the prestin density is similar among them, consistent with the finding that they share similar hearing thresholds. Lastly, we examined the IHC function and we found IHCs from B6 mice have a larger Ca current, release more synaptic vesicles and recycle synaptic vesicles more quickly. Taken together, our results suggest that excessive exocytosis from IHCs in B6 mice may raise the probability of glutamate toxicity in ribbon synapses, which could accumulate over time and eventually lead to early onset hearing loss.

The interleukin (IL)-17 family includes six structure-related cytokines (A-F). To date, majority of studies have focused on IL-17A. IL-17A plays a pivotal role in various infectious diseases, inflammatory and autoimmune disorders, and cancer. Several recent studies have indicated that IL-17A is a biomarker as well as a therapeutic target in sepsis. In the current review, we summarize the biological functions of IL-17, including IL-17-mediated responses and signal transduction pathways, with particular emphasis on clinical relevance to sepsis.

The increasing demand for disease modeling, preclinical drug testing, and long waiting lists for alternative organ substitutes has posed significant challenges to current limitations in organoid technology. Consequently, organoid technology has emerged as a cutting-edge tool capable of accurately recapitulating the complexity of actual organs in physiology and functionality. To bridge the gaps between basic research and pharmaceutical as well as clinical applications, efforts have been made to develop organoids from tissue-derived stem cells or pluripotent stem cells. These developments include optimizing starting cells, refining culture systems, and introducing genetic modifications. With the rapid development of organoid technology, organoid composition has evolved from single-cell to multi-cell types, enhancing their level of biomimicry. Tissue structure has become more refined, and core challenges like vascularization are being addressed actively. These improvements are expected to pave the way for the construction of organoid atlases, automated large-scale cultivation, and universally compatible organoid biobanks. However, major obstacles remain to be overcome before urgently proof-of-concept organoids can be readily converted to practical applications. These obstacles include achieving structural and functional summarily to native tissue, remodeling the microenvironment, and scaling up production. This review aims to summarize the status of organoid development and applications, highlight recent progress, acknowledge existing limitations and challenges, and provide insights into future advancements. It is expected that this will contribute to the establishment of a reliable, scalable, and practical platform for organoid production and translation, further promoting their use in the pharmaceutical industry and regenerative medicine.

Developing antibiotics-independent antibacterial agents is of great importance since antibiotic therapy faces great challenges from drug resistance. Graphene oxide (GO) is a promising agent due to its natural antibacterial mechanisms, such as sharp edge-mediated cutting effect. However, the antibacterial activity of GO is limited by its negative charge and low photothermal effect. Herein, the amino-functionalized GO nanosheets (AGO) with unique three-in-one properties were synthesized. Three essential properties (positive charge, strong photothermal effect, and natural cutting effect) were integrated into AGO. The positive charge (30 mV) rendered AGO a strong interaction force with model pathogen Streptococcus mutans (330 nN). The natural cutting effect of 100 µg·mL −1 AGO caused 27% loss of bacterial viability after incubation for 30 min. Most importantly, upon the near-infrared irradiation for just 5 min, the three-in-one properties of AGO caused 98% viability loss. In conclusion, the short irradiation period and the tunable antibacterial activity confer the three-in-one AGO a great potential for clinical use.

Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease. Synopsis Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis. COL has been identified as a novel efferocytosis enhancer that ameliorates mouse colitis. COL binds to and biasedly activates FPR2, leading to enhanced efferocytosis in macrophages. FPR2 emerges as a promising therapeutic target for the treatment of inflammatory diseases through modulating LC3‐associated efferocytosis in macrophages. Graphical Abstract Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis.

Accurate and efficient automatic segmentation is essential for various clinical tasks such as radiotherapy treatment planning. However, atlas-based segmentation still faces challenges due to the lack of representative atlas dataset and the computational limitations of deformation algorithms. In this work, we have proposed an atlas selection procedure (subset atlas grouping approach, MAS-SAGA) which utilized both image similarity and volume features for selecting the best-fitting atlases for contour propagation. A dataset of anonymized female pelvic Computed Tomography (CT) images demonstrated that MAS-SAGA significantly outperforms conventional multi-atlas-based segmentation (cMAS) in terms of Dice Similarity Coefficient (DSC) and 95th Percentile Hausdorff Distance (95HD) for bladder and rectum segmentation using a three-fold cross-validation strategy. The proposed procedure also reduced computation time compared to cMAS, making it a promising tool for medical image analysis applications. In addition, we have evaluated two distinct atlas selection methods: the Feature-based Atlas Selection Approach (MAS-FASA) and the Similarity-based Atlas Selection Approach (MAS-SIM). We investigate the differences between these two methods in terms of their ability to select the best fitting atlases. The findings demonstrated that MAS-FASA selected different atlases than MAS-SIM, resulting in improved segmentation performance overall. It highlighted the potential of feature-based subgrouping techniques in enhancing the efficacy of MAS algorithms in the field of medical image segmentation.

O-linked N -acetylglucosamine ( O -GlcNAc) is an essential and dynamic post-translational modification that is presented on thousands of nucleocytoplasmic proteins. Interrogating the role of O -GlcNAc on a single target protein is crucial, yet challenging to perform in cells. Herein, we developed a nanobody-fused split O -GlcNAcase (OGA) as an O -GlcNAc eraser for selective deglycosylation of a target protein in cells. After systematic cellular optimization, we identified a split OGA with reduced inherent deglycosidase activity that selectively removed O -GlcNAc from the desired target protein when directed by a nanobody. We demonstrate the generality of the nanobody-fused split OGA using four nanobodies against five target proteins and use the system to study the impact of O -GlcNAc on the transcription factors c-Jun and c-Fos. The nanobody-directed O -GlcNAc eraser provides a new strategy for the functional evaluation and engineering of O -GlcNAc via the selective removal of O -GlcNAc from individual proteins directly in cells. Fusion of a split form of the protein O -GlcNAcase with nanobodies enables the targeted removal of O -GlcNAc protein modifications, providing a tool for probing the functional roles of specific O -GlcNAc modifications in a cellular context.

Efferocytosis is the effective clearance of apoptotic cells by professional and non-professional phagocytes. The process is mechanically different from other forms of phagocytosis and involves the localization, binding, internalization, and degradation of apoptotic cells. Defective efferocytosis has been demonstrated to associate with the pathogenesis of various inflammatory disorders. In the current review, we summarize recent findings with regard to efferocytosis networks and discuss the relationship between efferocytosis and different immune cell populations, as well as describe how efferocytosis helps resolve inflammatory response and modulate immune balance. Our knowledge so far about efferocytosis suggests that it may be a useful target in the treatment of numerous inflammatory diseases.

Accurate identification of picking points remains a critical challenge for automated marigold harvesting, primarily due to complex backgrounds and significant pose variations of the flowers. To overcome this challenge, this study proposes SCS-YOLO-Seg, a novel method based on a lightweight segmentation model. The approach enhances the baseline YOLOv8n-seg architecture by replacing its backbone with StarNet and introducing C2f-Star, a novel lightweight feature extraction module. These modifications achieve substantial model compression, significantly reducing the model size, parameter count, and computational complexity (GFLOPs). Segmentation efficiency is further optimized through a dual-path collaborative architecture (Seg-Marigold head). Following mask extraction, picking points are determined by intersecting the optimized elliptical mask fitting results with the stem skeleton. Experimental results demonstrate that SCS-YOLO-Seg effectively balances model compression with segmentation performance. Compared to YOLOv8n-seg, it maintains high accuracy while significantly reducing resource requirements, achieving a picking point identification accuracy of 93.36% with an average inference time of 28.66 ms per image. This work provides a robust and efficient solution for vision systems in automated marigold harvesting.

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1 , as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3 . These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.