Search

Activating FLT3 mutations plays a crucial role in leukemogenesis, but identifying the optimal candidates for FLT3 inhibitor therapy remains controversial. This study aims to explore the impacts of FLT3 mutations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and to compare the mutation profiles between the two types to inspire the targeted application of FLT3 inhibitors. We retrospectively analyzed 243 ALL and 62 AML cases, grouping them into FLT3-mutant and wild-type categories, respectively. We then assessed the associations between FLT3 mutations and the clinical manifestations, genetic characteristics, and prognosis in ALL and AML. Additionally, we compared the distinct features of FLT3 mutations between ALL and AML. In ALL patients, those with FLT3 mutations predominantly exhibited hyperdiploidy (48.6% vs. 14.9%, p < 0.001) and higher FLT3 expression (108.02 [85.11, 142.06] FPKM vs. 23.11 [9.16, 59.14] FPKM, p < 0.001), but lower expression of signaling pathway-related genes such as HRAS, PIK3R3, BAD, MAP2K2, MAPK3, and STAT5A compared to FLT3 wild-type patients. There was no significant difference in prognosis between the two groups. In contrast, AML patients with FLT3 mutations were primarily associated with leucocytosis (82.90 [47.05, 189.76] G/L vs. 20.36 [8.90, 55.39] G/L, p = 0.001), NUP98 rearrangements (30% vs. 4.8%, p = 0.018), elevated FLT3 expression (74.77 [54.31, 109.46] FPKM vs. 34.56 [20.98, 48.28] FPKM, p < 0.001), and upregulated signaling pathway genes including PIK3CB, AKT1, MTOR, BRAF, and MAPK1 relative to FLT3 wild-type, correlating with poor prognosis. Notably, internal tandem duplications were the predominant type of FLT3 mutation in AML (66.7%) with higher inserted base counts, whereas they were almost absent in ALL (6.3%, p < 0.001). In summary, our study demonstrated that the forms and impacts of FLT3 mutations in ALL differed significantly from those in AML. The gene expression profiles of FLT3-related pathways may provide a rationale for using FLT3 inhibitors in AML rather than ALL when FLT3 mutations are present. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a method for accurately evaluating the quality of splicing seams in tiled transparent MicroLED displays, replacing subjective human observation with a quantitative indicator. The study utilized the validated Structural Similarity (SSIM) index method, which enabled precise guidance in the production process and established common measurement standards for defining splicing seam quality. This study would significantly contribute to the advancement of panel technology development by providing a standardized and objective evaluation approach for assessing splicing seam quality. [ABSTRACT FROM AUTHOR]

The objective of this paper was to investigate the quality of see‐through images on transparent MicroLED displays. Transparent displays have gained significant attention in various applications. However, evaluating the quality of see‐through images presented challenges, as there was no universal metric available for assessment. Image analysis methods were employed in this study, and common optical measurement metrics were also compared. The results showcased that CW‐SSIM exhibited higher sensitivity and aligned well with visual observations. This suggests the potential of CW‐SSIM as a universal metric for assessing the quality of see‐through images on transparent displays. [ABSTRACT FROM AUTHOR]

Aim: Guanylate‐binding protein 5 (GBP5) is an interferon (IFN)‐inducible GTPase that plays a crucial role in the cell‐autonomous immune response against microbial infections. In this study, we investigated the immunoregulatory role of GBP5 in the pathogenesis of dental pulpitis. Methodology: Gene‐set enrichment analysis (GSEA) was utilized to evaluate the IFN‐γ signalling pathway, and the differential expression of GBP mRNA in normal versus inflamed dental pulp tissues was screened, based on Gene Expression Omnibus (GEO) datasets associated with pulpitis. Both normal pulp tissues and inflamed pulp tissues were used for experiments. The expression of IFNs and GBPs was determined by qRT–PCR. Immunoblotting and double immunofluorescence were performed to examine the cellular localization of GBP5 in dental pulp tissues. For the functional studies, IFN‐γ priming or lentivirus vector‐delivered shRNA was used to, respectively, overexpress or knock down endogenous GBP5 expression in human dental pulp stem cells (HDPSCs). Subsequently, LPS was used to stimulate HDPSCs (overexpressing or with knocked‐down GBP5) to establish an in vitro model of inflammation. qRT–PCR and ELISA were employed to examine the expression of proinflammatory cytokines (IL‐6, IL‐8 and IL‐1β) and cyclooxygenase 2 (COX2). Every experiment has three times of biological replicates and three technical replicates, respectively. Statistical analysis was performed using the Student's t‐test and one‐way ANOVA, and a p‐value of <.05 was considered statistically significant. Results: GSEA analysis based on the GEO dataset revealed a significant activation of the IFN‐γ signalling pathway in the human pulpitis group. Among the human GBPs evaluated, GBP5 was selectively upregulated in inflamed dental pulp tissues and predominantly expressed in dental pulp cells. In vitro experiments demonstrated that IFN‐γ robustly induced the expression of GBP5 in HDPSCs. Knockdown of GBP5 expression in HDPSCs significantly amplified the LPS‐induced upregulation of inflammatory mediators (IL‐6, IL‐8, IL‐1β and COX2) both with and without IFN‐γ priming. Conclusion: Our findings demonstrated that GBP5 partook in the pathogenesis of dental pulpitis. The involvement of GBP5 in pulpitis appeared to coordinate the regulation of inflammatory cytokines. Knockdown of GBP5 contributed to the exacerbation of LPS‐mediated inflammation. [ABSTRACT FROM AUTHOR]

Aim: Dental pulp is richly innervated by nerve fibres, which are mainly involved in the sensation of pain. Aside from pain sensation, little is known regarding the role of dental innervation in reparative dentine formation. We herein generated a mouse model of experimental dentine injury to examine nerve sprouting within the odontoblast and subodontoblastic layers and investigated the potential effects of this innervation in reparative dentinogenesis. Methodology: Mouse tooth cavity model (bur preparation + etching) was established, and then nerve sprouting, angiogenesis and reparative dentinogenesis were determined by histological and immunofluorescent staining at 1, 3, 7, 14 and 28 days postoperatively. We also established the mouse‐denervated molar models to determine the role of sensory and sympathetic nerves in reparative dentinogenesis, respectively. Finally, we applied calcitonin gene‐related peptide (CGRP) receptor antagonist to analyse the changes in angiogenesis and reparative dentinogenesis. Results: Sequential histological results from dentine‐exposed teeth revealed a significant increase in innervation directly beneath the injured area on the first day after dentine exposure, followed by vascularisation and reparative dentine production at 3 and 7 days, respectively. Intriguingly, abundant type H vessels (CD31+Endomucin+) were present in the innervated area, and their formation precedes the onset of reparative dentine formation. Additionally, we found that sensory denervation led to blunted angiogenesis and impaired dentinogenesis, while sympathetic denervation did not affect dentinogenesis. Moreover, a marked increase in the density of CGRP+ nerve fibres was seen on day 3, which was reduced but remained elevated over the baseline level on day 14, whereas the density of substance P‐positive nerve fibres did not change significantly. CGRP receptor antagonist‐treated mice showed similar results as those with sensory denervation, including impairments in type H angiogenesis, which confirms the importance of CGRP in the formation of type H vessels. Conclusions: Dental pulp sensory nerves act as an essential upstream mediator to promote angiogenesis, including the formation of type H vessels, and reparative dentinogenesis. CGRP signalling governs the nerve‐vessel‐reparative dentine network, which is mostly produced by newly dense sensory nerve fibres within the dental pulp. [ABSTRACT FROM AUTHOR]

Aim: Dentinal tubules serve as disease‐causing channels for infiltration and penetration of bacteria and their by‐products; which are regarded as the major driver of pathogenesis in pulpal inflammation and infection. In this study, we aimed to evaluate the transdentinal potential of nanoscale cetylpyridinium chloride/cholesterol (CPC/Chol) sterosomes, which are a recently developed type of cationic non‐phospholipid liposomal nanocarrier; as well as their intrinsic and universal antibacterial activity. Methodology: Cetylpyridinium chloride/cholesterol sterosomes were formulated, with a hydrodynamic diameter of 134 ± 4 nm, a low polydisperse index of 0.161 ± 0.007, and a positive zeta potential of 41 ± 3 mV at pH 7.4. Transdentinal diffusion ability of sterosomes was evaluated using human dentine blocks in vitro, and Wistar rat molar teeth in vivo. The intrinsic antibacterial activities of CPC/Chol sterosomes against Enterococcus faecalis, Streptococcus mutans, Fusobacterium nucleatum, and Porphyromonas gingivalis were further examined. Results: Cetylpyridinium chloride/cholesterol sterosomes successfully penetrated through the dentinal tubules, and diffused into the pulp, which could be internalized by dental pulp cells with a high efficiency. In addition, they exhibited substantial levels of intrinsic antibacterial activity against these Gram‐positive and Gram‐negative endodontic bacteria and their biofilms. Conclusions: Given its high penetration and diffusion ability through the dentine and pulp, great potential for multi‐drug delivery, and distinct intrinsic antibacterial activity; sterosome‐based nanocarriers might serve as a promising therapeutic strategy aimed at targeting various specific pathways associated with pulpal diseases. This will help determine and characterize the most appropriate prophylactic and therapeutic targets for early intervention in our future dentistry practice. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA), is a rare but potentially life-threatening disease characterized by pancytopenia and a hypocellular bone marrow. Pulmonary mucormycosis (PM) is a rare but life-threatening fungal infection observed in immunocompromised patients, particularly those with neutropenia and those using corticosteroids, with a high mortality rate from 40 to 80%. However, PM diagnosis and treatment remain challenging. This study reports a case of very severe aplastic anemia (VSAA) in a male child with PM. The innovation of this article lies in the following aspects: the patient exhibited typical clinical manifestations, the reverse halo sign (RHS) on chest computed tomography (CT), and a positive metagenomic next-generation sequencing (mNGS) analysis; despite aggressive anti-infective treatment and left lower lobectomy, he experienced a poor clinical outcome. Reflecting on cases with poor prognosis can indeed offer valuable insights and opportunities for learning. This study underlines the diagnostic challenges in mucormycosis, which should be considered in persistent fever that is unresponsive to standard antibiotic and antifungal therapies, and conduct a comprehensive examination to achieve early detection, diagnosis and treatment. It was concluded that, in addition to antifungal treatment, early surgery is essential for treating mucormycosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Huang, Jiang, Ren, Peng and Wu.)