Shaoxia: a web-based interactive analysis platform for single cell RNA sequencing data.

BACKGROUND: In recent years, Single-cell RNA sequencing (scRNA-seq) is increasingly accessible to researchers of many fields. However, interpreting its data demands proficiency in multiple programming languages and bioinformatic skills, which limited researchers, without such expertise, exploring information from scRNA-seq data. Therefore, there is a tremendous need to develop easy-to-use software, covering all the aspects of scRNA-seq data analysis. RESULTS: We proposed a clear analysis framework for scRNA-seq data, which emphasized the fundamental and crucial roles of cell identity annotation, abstracting the analysis process into three stages: upstream analysis, cell annotation and downstream analysis. The framework can equip researchers with a comprehensive understanding of the analysis procedure and facilitate effective data interpretation. Leveraging the developed framework, we engineered Shaoxia, an analysis platform designed to democratize scRNA-seq analysis by accelerating processing through high-performance computing capabilities and offering a user-friendly interface accessible even to wet-lab researchers without programming expertise. CONCLUSION: Shaoxia stands as a powerful and user-friendly open-source software for automated scRNA-seq analysis, offering comprehensive functionality for streamlined functional genomics studies. Shaoxia is freely accessible at http://www.shaoxia.cloud , and its source code is publicly available at https://github.com/WiedenWei/shaoxia .

Metformin overcomes chemoresistance by regulating stemness via KLF4 in oral squamous cell carcinoma.

OBJECTIVE: Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms. METHODS: Cellular models resistant to chemotherapy were established, and their viability and sphere-forming ability were assessed using CCK-8 and soft agar formation assays, respectively. RNA-seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted. RESULTS: Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel-like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice. CONCLUSION: Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.

Type 17 immune response promotes oral epithelial cell proliferation in periodontitis.

OBJECTIVES: This study aims to investigate the effects of type 17 immune response on the proliferation of oral epithelial cells in periodontitis. DESIGN: A time-dependent ligature induced periodontitis mouse model was utilized to explore gingival hyperplasia and the infiltration of interleukin 17A (IL-17A) positive cells. Immunohistochemistry and flow cytometry were employed to determine the localization and expression of IL-17A in the ligature induced periodontitis model. A pre-existing single-cell RNA sequencing dataset, comparing individuals affected by periodontitis with healthy counterparts, was reanalyzed to evaluate IL-17A expression levels. We examined proliferation markers, including proliferating cell nuclear antigen (PCNA), signal transducer and activator of transcription (STAT3), Yes-associated protein (YAP), and c-JUN, in the gingival and tongue epithelium of the periodontitis model. An anti-IL-17A agent was administered daily to observe proliferative changes in the oral mucosa within the periodontitis model. Cell number quantification, immunofluorescence, and western blot analyses were performed to assess the proliferative responses of human normal oral keratinocytes to IL-17A treatment in vitro. RESULTS: The ligature induced periodontitis model exhibited a marked infiltration of IL-17A-positive cells, alongside significant increase in thickness of the gingival and tongue epithelium. IL-17A triggers the proliferation of human normal oral keratinocytes, accompanied by upregulation of PCNA, STAT3, YAP, and c-JUN. The administration of an anti-IL-17A agent attenuated the proliferation in oral mucosa. CONCLUSIONS: These findings indicate that type 17 immune response, in response to periodontitis, facilitates the proliferation of oral epithelial cells, thus highlighting its crucial role in maintaining the oral epithelial barrier.

Comparative genomics sheds light on the predatory lifestyle of accipitrids and owls.

Raptors are carnivorous birds including accipitrids (Accipitridae, Accipitriformes) and owls (Strigiformes), which are diurnal and nocturnal, respectively. To examine the evolutionary basis of adaptations to different light cycles and hunting behavior between accipitrids and owls, we de novo assembled besra (Accipiter virgatus, Accipitridae, Accipitriformes) and oriental scops owl (Otus sunia, Strigidae, Strigiformes) draft genomes. Comparative genomics demonstrated four PSGs (positively selected genes) (XRCC5, PRIMPOL, MDM2, and SIRT1) related to the response to ultraviolet (UV) radiation in accipitrids, and one PSG (ALCAM) associated with retina development in owls, which was consistent with their respective diurnal/nocturnal predatory lifestyles. We identified five accipitrid-specific and two owl-specific missense mutations and most of which were predicted to affect the protein function by PolyPhen-2. Genome comparison showed the diversification of raptor olfactory receptor repertoires, which may reflect an important role of olfaction in their predatory lifestyle. Comparison of TAS2R gene (i.e. linked to tasting bitterness) number in birds with different dietary lifestyles suggested that dietary toxins were a major selective force shaping the diversity of TAS2R repertoires. Fewer TAS2R genes in raptors reflected their carnivorous diet, since animal tissues are less likely to contain toxins than plant material. Our data and findings provide valuable genomic resources for studying the genetic mechanisms of raptors' environmental adaptation, particularly olfaction, nocturnality and response to UV radiation.