ROS-induced imbalance of the miR-34a-5p/SIRT1/p53 axis triggers chronic chondrocyte injury and inflammation.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

Replantation of multiple fingertip amputations using super microsurgery: A case report and literature review.

Background: The fingertip amputation is an amputation type of the finger beyond the proximal nail fold. There is no vein available for anastomoses on the dorsal side of the finger, and the palmar vein of the finger is small and tightly attached to the skin. Therefore, it is relatively difficult to implement surgical anastomoses, which poses challenges to the clinical treatment of fingertip amputations. Case report: A 29-year-old male was admitted to the hospital due to "the amputation of the fingertips of the right index, middle, and ring fingers caused by a heavy object compression 3 h ago". The admission examination revealed that the right index, middle, and ring fingers were completely severed at the 1/2 plane of the nail bed, with irregular sections, severe contusion, and pollution. The X-ray examination showed comminuted fractures of the distal phalanges of the right index, middle, and ring fingers. Based on these findings, the patient was diagnosed with multiple severed fingertips of the right hand (Tamai Zone 1). The patient underwent debridement, vascular exploration, and replantation of the right index, middle, and ring fingertips under emergency general anesthesia. After surgery, anti-inflammatory, spasmolytic, and anticoagulant treatment and regular dressing changes were conducted. The patient did not receive a blood transfusion, and all three fingers survived. The appearance of these fingers was favorable 3 months after surgery, and the flexion and extension of these fingers were normal. Eventually, the patient achieved excellent Chen's hand function scores. Conclusions: To the best of our knowledge, this may be the first successful case regarding the replantation of three fingertips after amputations in Tamai Zone 1 with favorable outcomes. It can be maintained that super microsurgery can be used for the replantation of multiple fingertip amputations.

Unlocking the potential of exosomes: a breakthrough in the theranosis of degenerative orthopaedic diseases.

Degenerative orthopaedic diseases pose a notable worldwide public health issue attributable to the global aging population. Conventional medical approaches, encompassing physical therapy, pharmaceutical interventions, and surgical methods, face obstacles in halting or reversing the degenerative process. In recent times, exosome-based therapy has gained widespread acceptance and popularity as an effective treatment for degenerative orthopaedic diseases. This therapeutic approach holds the potential for "cell-free" tissue regeneration. Exosomes, membranous vesicles resulting from the fusion of intracellular multivesicles with the cell membrane, are released into the extracellular matrix. Addressing challenges such as the rapid elimination of natural exosomes in vivo and the limitation of drug concentration can be effectively achieved through various strategies, including engineering modification, gene overexpression modification, and biomaterial binding. This review provides a concise overview of the source, classification, and preparation methods of exosomes, followed by an in-depth analysis of their functions and potential applications. Furthermore, the review explores various strategies for utilizing exosomes in the treatment of degenerative orthopaedic diseases, encompassing engineering modification, gene overexpression, and biomaterial binding. The primary objective is to provide a fresh viewpoint on the utilization of exosomes in addressing bone degenerative conditions and to support the practical application of exosomes in the theranosis of degenerative orthopaedic diseases.

Morphological and phylogenetic analyses reveal five new species of Porotheleaceae (Agaricales, Basidiomycota) from China.

The first occurrence of Marasmiellomycena and Pulverulina in the Chinese mycobiota are reported, M.tomentosa and P.flavoalba, two new species and M.albodescendens, a new combination, revealed by phylogenetic analyses and morphological study. These newly-recorded genera, Marasmiellomycena, which can be distinguished by their agaricoid basidiomata, dark-coloured stipe, sarcodimitic tramal structure, stipitipellis with yellow to yellowish-brown pigments and yellow-pigmented thick-walled caulocystidia and Pulverulina, which differs from other genera of Porotheleaceae by its pruinose stipe, decurrent lamellae, inamyloid basidiospores and absence of hymenial cystidia. We also formally describe three other new species of Porotheleaceae collected from Chinese temperate to subtropical zones of Fujian and Zhejiang Provinces: Clitocybulafuscostriata, Gerronemabrunneosquamulosum and Leucoinocybesubglobispora. Furthermore, we include the results of a phylogenetic analysis of Porotheleaceae, based on a multi-locus (ITS, nrLSU and rpb2) dataset. According to this analysis, Chrysomycena, Clitocybula, Delicatula, Hydropodia, Hydropus, Leucoinocybe, Marasmiellomycena, Megacollybia, Pulverulina, Trogia and Vizzinia are monophyletic. However, Gerronema is identified as polyphyletic and, additionally, Porotheleum does not form a monophyletic group either because Porotheleumparvulum and Porotheleumalbidum are "unassigned" in phylogenetic analysis. The results of our phylogenetic analyses, coupled with morphological observations, confirm recognition of these new taxa. Morphological descriptions, photographs, line drawings and comparisons with closely-related taxa are presented for the new species. A key to the 22 species belonging to nine genera of Porotheleaceae in China is also provided.

Identification of ClpB, a molecular chaperone involved in the stress tolerance and virulence of Streptococcus agalactiae.

Bacterial ClpB is an ATP-dependent disaggregate that belongs to the Hsp100/Clp family and facilitates bacterial survival under hostile environmental conditions. Streptococcus agalactiae, which is regarded as the major bacterial pathogen of farmed Nile tilapia (Oreochromis niloticus), is known to cause high mortality and large economic losses. Here, we report a ClpB homologue of S. agalactiae and explore its functionality. S. agalactiae with a clpB deletion mutant (∆clpB) exhibited defective tolerance against heat and acidic stress, without affecting growth or morphology under optimal conditions. Moreover, the ΔclpB mutant exhibited reduced intracellular survival in RAW264.7 cells, diminished adherence to the brain cells of tilapia, increased sensitivity to leukocytes from the head kidney of tilapia and whole blood killing, and reduced mortality and bacterial loads in a tilapia infection assay. Furthermore, the reduced virulence of the ∆clpB mutant was investigated by transcriptome analysis, which revealed that deletion of clpB altered the expression levels of multiple genes that contribute to the stress response as well as certain metabolic pathways. Collectively, our findings demonstrated that ClpB, a molecular chaperone, plays critical roles in heat and acid stress resistance and virulence in S. agalactiae. This finding provides an enhanced understanding of the functionality of this ClpB homologue in gram-positive bacteria and the survival strategy of S. agalactiae against immune clearance during infection.

A Cascaded Multimodule Image Enhancement Framework for Underwater Visual Perception.

Underwater images usually exhibit severe color cast, hazy appearance, and/or dark regions because of the complex lighting absorption and scattering in water. How to increase the quality of these degraded underwater images has emerged as a key issue for various underwater application tasks. Recent efforts have been made to deal with single type degradation, however, it is still challenging to deal with multiple degradations that usually coexist in an underwater image with a general network. The degradations in underwater images can be divided into medium-agnostic (hazy or low-light which also encountered in in-air images) and medium-specific (color distortion caused by the specific light attenuation property in water) ones. According to this observation, this article proposes a cascaded multimodule underwater image enhancement (UIE) framework to address the coexisted multiple degradations. In the proposed framework, an in-air image enhancement module and a novel proposed adaptive color channel compensation network (AC 3 Net) are cascaded, in which the former focuses primarily on solving medium-agnostic degradations and the latter is for handling the medium-specific degradation. This framework has good flexibility by cascading different types of in-air image enhancement networks with AC 3 Net to achieve various UIE. The effectiveness of the proposed framework has been extensively validated on various degraded underwater images as well as different underwater visual perception tasks.

Interfacial Super-Assembly of Vacancy Engineered Ultrathin-Nanosheets toward Nanochannels for Smart Ion Transport and Salinity Gradient Power Conversion.

Ion-selective nanochannel membranes assembled from two-dimensional (2D) nanosheets hold immense promise for power conversion using salinity gradient. However, they face challenges stemming from insufficient surface charge density, which impairs both permselectivity and durability. Herein, we present a novel vacancy-engineered, oxygen-deficient NiCo layered double hydroxide (NiCoLDH)/cellulose nanofibers-wrapped carbon nanotubes (VOLDH/CNF-CNT) composite membrane. This membrane, featuring abundant angstrom-scale, cation-selective nanochannels, is designed and fabricated through a synergistic combination of vacancy engineering and interfacial super-assembly. The membrane shows interlayer free-spacing of ~3.62 Å, which validates the membrane size exclusion selectivity.This strategy, validated by DFT calculations and experimental data, improves hydrophilicity and surface charge density, leading to the strong interaction with K+ ions to benefit the low ion transport resistance and exceptional charge selectivity. When employed in an artificial river water|seawater salinity gradient power generator, it delivers a high-power density of 5.35 W/m2 with long-term durability (20,000s), which is almost 400% higher than that of the pristine NiCoLDH membrane. Furthermore, it displays both pH- and temperature-sensitive ion transport behavior, offering additional opportunities for optimization. This work establishes a basis for high-performance salinity gradient power conversion and underscores the potential of vacancy engineering and super-assembly in customizing 2D nanomaterials for diverse advanced nanofluidic energy devices.

Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1α and ERK1/2 signaling pathways in bone regeneration.

Angiogenesis plays a crucial role in bone regeneration. Hypoxia is a driving force of angiogenesis at the initial stage of tissue repair. The hypoxic microenvironment could activate the hypoxia-inducible factor (HIF)-1α signaling pathway in cells, thereby enhancing the proliferation, migration and pro-angiogenic functions of stem cells. However, long-term chronic hypoxia could inhibit osteogenic differentiation and even lead to apoptosis. Therefore, shutdown of the HIF-1α signaling pathway and providing oxygen at later stage probably facilitate osteogenic differentiation and bone regeneration. Herein, an oxygen tension regulating hydrogel that sequentially activate and deactivate the HIF-1α signaling pathway were prepared in this study. Its effect and mechanism on stem cell differentiation were investigated both in vitro and in vivo. We proposed a gelatin-based hydrogel capable of sequentially delivering a hypoxic inducer (copper ions) and oxygen generator (calcium peroxide). The copper ions released from the hydrogels significantly enhanced cell viability and VEGF secretion of BMSCs via upregulating HIF-1α expression and facilitating its translocation into the nucleus. Additionally, calcium peroxide promoted alkaline phosphatase activity, osteopontin secretion, and calcium deposition through the activation of ERK1/2. Both Cu2+ and calcium peroxide demonstrated osteogenic promotion individually, while their synergistic effect within the hydrogels led to a superior osteogenic effect by potentially activating the HIF-1α and ERK1/2 signaling pathways.

A vision chip with complementary pathways for open-world sensing.

Image sensors face substantial challenges when dealing with dynamic, diverse and unpredictable scenes in open-world applications. However, the development of image sensors towards high speed, high resolution, large dynamic range and high precision is limited by power and bandwidth. Here we present a complementary sensing paradigm inspired by the human visual system that involves parsing visual information into primitive-based representations and assembling these primitives to form two complementary vision pathways: a cognition-oriented pathway for accurate cognition and an action-oriented pathway for rapid response. To realize this paradigm, a vision chip called Tianmouc is developed, incorporating a hybrid pixel array and a parallel-and-heterogeneous readout architecture. Leveraging the characteristics of the complementary vision pathway, Tianmouc achieves high-speed sensing of up to 10,000 fps, a dynamic range of 130 dB and an advanced figure of merit in terms of spatial resolution, speed and dynamic range. Furthermore, it adaptively reduces bandwidth by 90%. We demonstrate the integration of a Tianmouc chip into an autonomous driving system, showcasing its abilities to enable accurate, fast and robust perception, even in challenging corner cases on open roads. The primitive-based complementary sensing paradigm helps in overcoming fundamental limitations in developing vision systems for diverse open-world applications.

Enhanced osteogenic and ROS-scavenging MXene nanosheets incorporated gelatin-based nanocomposite hydrogels for critical-sized calvarial defect repair.

The healing of critical-sized bone defects is a major challenge in the field of bone tissue engineering. Gelatin-related hydrogels have emerged as a potential solution due to their desirable properties. However, their limited osteogenic, mechanical, and reactive oxygen species (ROS)-scavenging capabilities have hindered their clinical application. To overcome this issue, we developed a biofunctional gelatin-Mxene nanocomposite hydrogel. Firstly, we prepared two-dimensional (2D) Ti3C2 MXene nanosheets using a layer delamination method. Secondly, these nanosheets were incorporated into a transglutaminase (TG) enzyme-containing gallic acid-imbedded gelatin (GGA) pre-gel solution to create an injectable GGA-MXene (GM) nanocomposite hydrogel. The GM hydrogels exhibited superior compressive strength (44-75.6 kPa) and modulus (24-44.5 kPa) compared to the GGA hydrogels. Additionally, the GM hydrogel demonstrated the ability to scavenge reactive oxygen species (OH- and DPPH radicals), protecting MC3T3-E1 cells from oxidative stress. GM hydrogels were non-toxic to MC3T3-E1 cells, increased alkaline phosphatase secretion, calcium nodule formation, and upregulated osteogenic gene expressions (ALP, OCN, and RUNX2). The GM400 hydrogel was implanted in critical-sized calvarial defects in rats. Remarkably, it exhibited significant potential for promoting new bone formation. These findings indicated that GM hydrogel could be a viable candidate for future clinical applications in the treatment of critical-sized bone defects.

Molecular-level carbon traits underlie the multidimensional fine root economics space.

Carbon influences the evolution and functioning of plants and their roots. Previous work examining a small number of commonly measured root traits has revealed a global multidimensionality of the resource economics traits in fine roots considering carbon as primary currency but without considering the diversity of carbon-related traits. To address this knowledge gap, we use data from 66 tree species from a tropical forest to illustrate that root economics space co-varies with a novel molecular-level traits space based on nuclear magnetic resonance. Thinner fine roots exhibit higher proportions of carbohydrates and lower diversity of molecular carbon than thicker roots. Mass-denser fine roots have more lignin and aromatic carbon compounds but less bioactive carbon compounds than lighter roots. Thus, the transition from thin to thick fine roots implies a shift in the root carbon economy from 'do-it-yourself' soil exploration to collaboration with mycorrhizal fungi, while the shift from light to dense fine roots emphasizes a shift from acquisitive to conservative root strategy. We reveal a previously undocumented role of molecular-level carbon traits that potentially undergird the multidimensional root economics space. This finding offers new molecular insight into the diversity of root form and function, which is fundamental to our understanding of plant evolution, species coexistence and adaptations to heterogeneous environments.

Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 µM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Long-Term Consumption of Purified Water Altered Amino Acid, Fatty Acid and Energy Metabolism in Livers of Rats.

The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were investigated with a metabolomics-based strategy. Compared with the tap water group, 74 metabolites were significantly changed in the purified water group (6 increased and 68 decreased), including 29 amino acids, 11 carbohydrates, 10 fatty acids, 7 short chain fatty acids (SCFAs), and 17 other biomolecules. Eight metabolic pathways were significantly changed, namely aminoacyl-tRNA biosynthesis; nitrogen metabolism; alanine, aspartate and glutamate metabolism; arginine and proline metabolism; histidine metabolism; biosynthesis of unsaturated fatty acids; butanoate metabolism; and glycine, serine and threonine metabolism. These changes suggested that consumption of purified water induced negative nitrogen balance, reduced expression of some polyunsaturated fatty acids and SCFAs, and disturbed energy metabolism in rats. These metabolic disturbances may contribute to low-mineral-water-associated health risks. The health risk of consuming low-mineral water requires attention.

Omeprazole and risk of osteoarthritis: insights from a mendelian randomization study in the UK Biobank.

BACKGROUND: A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. METHODS: The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. RESULTS: The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings. CONCLUSION: This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.

Protocol for identifying stressed granulocytes from septic mice.

Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

MiR-339-5p Inhibits Ferroptosis by Promoting Autophagic Degradation of FTH1 Through Targeting ATG7 in Liver Cancer Cells.

Background: Liver cancer has a high incidence and mortality rate worldwide, and there is an urgent need to identify new therapeutic strategies and predictive targets to improve the clinical outcomes of advanced liver cancer. Ferroptosis holds promise as a novel strategy for cancer therapy. Epigenetic dysregulation is a hallmark of cancer, and noncoding RNAs are tightly involved in cell fate determination. Therefore, we aimed to identify a novel ferroptosis regulator from aberrantly expressed microRNAs that may serve as a novel biomarker and therapeutic target for liver cancer. Methods: The expression signature and prognostic value of miR-339 was assessed using TCGA data set. The role of miR-339/ATG7/FTH1 axis in liver cancer cells were evaluated through growth curve, colony formation, 7-AAD staining. The role of miR-339 in regulation of ferroptosis was determined by immunofluorescence staining, flow cytometry, and Elisa kits. Results: Here, we showed that miR-339 is aberrantly overexpressed in patients with liver cancer. In addition, miR-339 inhibition dramatically suppresses liver cancer progression. Furthermore, miR-339 silencing drives cell death and inhibits liver cancer progression, indicating that miR-339 may serve as a novel ferroptosis suppressor. Mechanistically, we demonstrated that miR-339 targets ATG7 to facilitate the autophagic degradation of FTH1 and prevent ferroptosis in liver cancer cells. Conclusions: We provide important evidence that the miR-339 inhibition activates of the autophagy pathway to promote ferroptosis by degrading FTH1 in liver cancer cells. We found that miR-339 regulates the balance between ferroptosis and autophagy in liver cancer cells.

Zooming in and Out of Programmed Cell Death in Osteoarthritis: A Scientometric and Visualized Analysis.

During the past decade, mounting evidence has increasingly linked programmed cell death (PCD) to the progression and development of osteoarthritis (OA). There is a significant need for a thorough scientometric analysis that recapitulates the relationship between PCD and OA. This study aimed to collect articles and reviews focusing on PCD in OA, extracting data from January 1st, 2013, to October 31st, 2023, using the Web of Science. Various tools, including VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package, were employed for scientometric and visualization analyses. Notably, China, the USA, and South Korea emerged as major contributors, collectively responsible for more than 85% of published papers and significantly influencing research in this field. Among different institutions, Shanghai Jiao Tong University, Xi'an Jiao Tong University, and Zhejiang University exhibited the highest productivity. Prolific authors included Wang Wei, Wang Jing, and Zhang Li. Osteoarthritis and Cartilage had the most publications in this area. Keywords related to PCD in OA prominently highlighted 'chondrocytes', 'inflammation', and 'oxidative stress', recognized as pivotal mechanisms contributing to PCD within OA. This study presents the first comprehensive scientometric analysis, offering a broad perspective on the knowledge framework and evolving patterns concerning PCD in relation to OA over the last decade. Such insights can aid researchers in comprehensively understanding this field and provide valuable directions for future explorations.

KIF15 promotes the development and progression of chordoma via activating PI3K-AKT signalling pathway.

Aims: Despite its implication in various human cancers, the expression and functional significance of Kinesin family member 15 (KIF15) in chordomas remain unexplored. Main methods: The evaluation of KIF15 protein levels was conducted through immunohistochemistry (IHC) staining and Western blot analysis. Cell proliferation was quantified using MTT and CCK8 assays, whereas cell migration was examined using wound healing and Transwell assays. Furthermore, flow cytometric analysis was utilized to assess cell apoptosis and the cell cycle. Additionally, in vivo experiments were performed using a mouse xenograft model. Key findings: Our study revealed significantly higher expression of KIF15 in stage III chordoma tissues compared to stage II tissues. Knockdown of KIF15 led to notable inhibition of cell proliferation and migration, along with enhanced apoptosis and cell cycle arrest. In vivo studies further confirmed the inhibitory effects of KIF15 knockdown on chordoma tumour growth. In terms of mechanism, we identified the involvement of the PI3K-AKT signalling pathway mediated by KIF15 in chordomas. Notably, the anti-tumour effects of KIF15 deficiency on chordomas were partially reversed by the addition of an AKT activator. Significance: KIF15 promotes chordoma development and progression through the activation of the PI3K-AKT signalling pathway. Thus, targeting KIF15 might be a promising therapeutic strategy for treating chordomas.

Achieving single-cell-resolution lineage tracing in zebrafish by continuous barcoding mutations during embryogenesis.

Unraveling the lineage relationships of all descendants from a zygote is fundamental to advancing our understanding of developmental and stem cell biology. However, existing cell barcoding technologies in zebrafish lack the resolution to capture the majority of cell divisions during embryogenesis. A recently developed method, SMALT, successfully reconstructed high-resolution cell phylogenetic trees for Drosophila melanogaster. Here, we implement the SMALT system in zebrafish, recording a median of 14 substitution mutations on a one-kilobase-pair barcoding sequence for one-day post-fertilization embryos. Leveraging this system, we reconstruct four cell lineage trees for zebrafish fin cells, encompassing both original and regenerated fin. Each tree consists of hundreds of internal nodes with a median bootstrap support of 99%. Analysis of the obtained cell lineage trees reveals that regenerated fin cells mainly originate from cells in the same part of the fins. Through multiple times sampling germ cells from the same individual, we confirm the stability of the germ cell pool and the early separation of germ cell and somatic cell progenitors. Our system offers the potential for reconstructing high-quality cell phylogenies across diverse tissues, providing valuable insights into development and disease in zebrafish.