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We report herein that three facile rearrangements of epoxy ketones can be employed for the efficient and practical synthesis of cephalotaxine, the parent member of the family of Cephalotaxus alkaloids. The Meinwald rearrangement of epoxy ketone (90%) was used for the preparation of the dense functional groups in the cyclopentane ring of cephalotaxine. A novel acid-catalyzed umpolung S N 2' rearrangement and the Wharton transposition reaction of epoxy ketones were also developed to synthesize the Mori intermediate via the key azaspiro allylic alcohols in a stereodivergent manner.

Selective serotonin reuptake inhibitor correlates with decreased bone mineral density and impedes orthodontic tooth movement. The present study aimed to examine the effects of fluoxetine on osteoclast differentiation and function. Human peripheral blood mononuclear cells (hPBMCs) and murine RAW264.7 cells were cultured with RANKL to stimulate osteoclast differentiation. The resulting multinucleated cells displayed characteristics of mature osteoclasts. Fluoxetine at 0.01-1 μM did not impact cellular viability or oxidative stress. However, 10 μM fluoxetine significantly reduced clonal growth, cell viability, and increased cytotoxicity and lipid peroxidation in RAW 264.7 cells. Further, application of 0.1 μM fluoxetine potently suppressed osteoclast differentiation of both RAW264.7 and hPBMCs, with reduced osteoclast numbers and downregulation of osteoclastic genes matrix metalloproteinase-9, cathepsin K, and integrin β3 at mRNA and protein levels. Fluoxetine also disrupted F-actin ring formation essential for osteoclast resorptive function. Mechanistically, fluoxetine inhibited NF-kB signaling by reducing phosphorylation of pathway members IκBα and p65, preventing IκBα degradation and blocking p65 nuclear translocation. In conclusion, this study demonstrates fluoxetine suppressing osteoclast differentiation in association with disrupting NF-kB activation, providing insight into orthodontic treatment planning for patients taking fluoxetine., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Near-infrared (NIR) irradiation has shown potential to stimulate osteogenic differentiation, but the mechanisms are not fully understood. The study is to investigate the effects of NIR laser irradiation on osteoblastic differentiation. Human periodontal ligament stem cells (hPDLSCs) were cultured in osteogenic medium and exposed to 810 nm NIR laser at 0.5 J/cm 2 every 48 h. The transient receptor potential vanilloid (TRPV1) channel inhibitor capsazepine (CPZ) was used to evaluate the role of calcium influx. Osteogenic differentiation was assessed by proliferation (CCK-8), alkaline phosphatase (ALP) activity, mineralization (Alizarin Red), and expression of bone markers by PCR and Western blot over 2 weeks. Intracellular calcium was measured by Fluo-4M dye and flow cytometry. Results showed that NIR irradiation enhanced hPDLSC proliferation, ALP activity, mineralization, and bone marker expression, indicating increased osteogenic differentiation. These effects were inhibited by CPZ. NIR induced a transient rise in intracellular calcium peaking at 3 min, which was blocked by CPZ. In conclusion, this study demonstrates that NIR laser irradiation promotes osteogenic differentiation of PDLSCs through the activation of TRPV1 channels and subsequent calcium signaling. Further research is warranted to optimize the treatment parameters and elucidate the detailed signaling pathways involved, paving the way for the clinical application of NIR therapy in the treatment of bone disorders and periodontal disease.

Objective: This clinical study aimed to evaluate the practical value of integrating an AI diagnostic model into clinical practice for caries detection using intraoral images., Methods: In this prospective study, 4,361 teeth from 191 consecutive patients visiting an endodontics clinic were examined using an intraoral camera. The AI model, combining MobileNet-v3 and U-net architectures, was used for caries detection. The diagnostic performance of the AI model was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, with the clinical diagnosis by endodontic specialists as the reference standard., Results: The overall accuracy of the AI-assisted caries detection was 93.40%. The sensitivity and specificity were 81.31% (95% CI 78.22%-84.06%) and 95.65% (95% CI 94.94%-96.26%), respectively. The NPV and PPV were 96.49% (95% CI 95.84%-97.04%) and 77.68% (95% CI 74.49%-80.58%), respectively. The diagnostic accuracy varied depending on tooth position and caries type, with the highest accuracy in anterior teeth (96.04%) and the lowest sensitivity for interproximal caries in anterior teeth and buccal caries in premolars (approximately 10%)., Conclusion: The AI-assisted caries detection tool demonstrated potential for clinical application, with high overall accuracy and specificity. However, the sensitivity varied considerably depending on tooth position and caries type, suggesting the need for further improvement. Integration of multimodal data and development of more advanced AI models may enhance the performance of AI-assisted caries detection in clinical practice., (© 2024. The Author(s).)

This study sequenced the complete chloroplast genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor using the Illumina NovaSeq and PacBio RSII platforms. Following sequencing, the genomes were assembled, annotated, comparatively analyzed, and used to construct a phylogenetic tree to explore their phylogenetic positions. Results indicated that the chloroplast genomes of S. japonica var. timoriensis and S. japonica var. discolor both displayed a typical double-stranded circular tetrameric structure, measuring 157,609 and 157,748 bp in length, respectively. Each genome contained 130 annotated genes, with similar total GC content and relative codon usage patterns, showing a distinct preference for A/U at the third codon position. Simple sequence repeat analysis identified 207 and 211 repeats in S. japonica var. timoriensis and S. japonica var. discolor , respectively, primarily the A/T type. Boundary condition analysis indicated no significant expansion or contraction in the inverted repeat regions with consistent gene types and locations across both varieties. Nucleotide polymorphism analysis highlighted greater variation in the intergenic regions than in the coding sequences of Stephania chloroplast genomes. Phylogenetic analyses demonstrated that the species Stephania clustered into a distinct, well-supported clade. Notably, Stephania japonica , along with S. japonica var. discolor and S. japonica var. timoriensis , established a monophyletic lineage. Within this lineage, S. japonica and S. japonica var. discolor were closely related, with S. japonica var. timoriensis serving as their sister taxon.

The phenomena of intramolecular self-assembly of bidesmosidic kalopanaxsaponins was identified for the first time in this paper. NMR ( 1 H-NMR, NOESY), transmission electron microscopy (TEM), and molecular dynamics (MD) simulation techniques were used to compare the spatial structures of bidesmosidic kalopanaxsaponins and monodesmosidic kalopanaxsaponins. The results showed that the bidesmosidic kalopanaxsaponins formed a clustered and twisted structure in space, whereas the monodesmosidic kalopanaxsaponins were in an extended state. This discovery confirmed the presence of intramolecular self-assembly in bidesmosidic kalopanaxsaponins.

Guigarracailaoensis is a member of family Cyprinidae, subfamily Labeoninae (Cypriniformes) which was recently discovered in southwestern China. Following its initial description, additional information on this species has remained notably scarce. In the current study, we assemble the complete mitochondrial genome (mitogenome) of G.cailaoensis using the Illumina sequencing platform. The mitogenome is identified as a circular, double-stranded DNA sequence of 16,593 base pairs, encompassing 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a putative control region. Maximum-likelihood and Bayesian-inference approaches were used to construct phylogenetic trees for three datasets: (i) PCG sequences of the complete mitogenome (dataset 1); (ii) PCG sequences of the complete mitogenome combined with nuclear DNA (ncDNA) ( Rag1 ) sequence (dataset 2); and (iii) ncDNA ( Rag1 ) sequences (dataset 3). Phylogenetic analyses position G.cailaoensis as a sister taxon to the lineage consisting of Paraqianlabeolineatus Zhao, Sullivan, Zhang & Peng, 2014 and Pseudogyrinocheilusprochilus Fang, 1933 in dataset 1, and to Pseudogyrinocheilusprochilus in dataset 2, species lacking an oral disc on the lower lip. However, G.cailaoensis showed a close relationship to the lineage consisting of Discogobio and Discocheilus in dataset 3, species possessing an oral disc on the lower lip. Nonetheless, a variety of species with an oral disc on the lower lip are clustered into different lineages across the three datasets that may indicate that the development of the oral disc is homoplastic within the subfamily Labeoninae. The outcomes of this study have the potential to support conservation efforts for this species and to enrich our understanding of genetic resources in the area., Competing Interests: The authors have declared that no competing interests exist., (Lan-Ping Zheng, Ying-Min Geng.)

This study explores the use of in situ cross-linked hyaluronic acid methacryloyl (HAMA) and hydroxyapatite particles (HAP) for bone defect repair. Human periodontal ligament stem cells (PDLSCs) were isolated and co-cultured with the HAMA-HAP composite. Osteogenic differentiation was evaluated using Alizarin Red staining, alkaline phosphatase activity quantification, and polymerase chain reaction (PCR). A cranial defect was induced in Sprague-Dawley rats. This defect was then filled with the HAMA-HAP composite and cross-linked using UV light exposure. Bone formation was assessed through radiographic and histological analyses. The HAMA-HAP composite was found to promote cell viability similarly to pure HAP. It also enhanced gene expression of ALP, OPN, and Runx2, and increased ALP activity and mineralized nodule formation in vitro. Micro-CT scans showed defect restoration in the HAMA-HAP and HAP groups compared to the control group. The HAMA-HAP group exhibited higher Tb.N, Tb.Sp, Tb.Th, and BV/TV. Masson staining showed the HAMA-HAP composite restored the defect site, with new bone formation thicker than in the HAP group. The HAMA-HAP composite showed excellent biocompatibility and promoted osteogenic differentiation of PDLSCs. It effectively repaired cranial defects, indicating its potential for clinical use in bone defect repair., (© 2024 Wiley Periodicals LLC.)

Background: It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage., Methods: The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively., Results: 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (r s  = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization., Conclusions: We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression., Competing Interests: Conflict of interest There are no other potential conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Toxin-antitoxin (TA) systems are ubiquitous genetic elements in prokaryotes, but their biological importance is poorly understood. Mycobacterium smegmatis contains eight putative TA systems. Previously, seven TAs have been studied, with five of them being verified as functional. Here, we show that Ms0251-0252 is a novel TA system in that expression of the toxin Ms0251 leads to growth inhibition that can be rescued by the antitoxin Ms0252. To investigate the functional roles of TA systems in M. smegmatis, we deleted the eight putative TA loci and assayed the mutants for resistance to various stresses. Deletion of all eight TA loci resulted in decreased survival under starvation conditions and altered fitness when exposed to environmental stresses. Furthermore, we showed that deletion of the eight TA loci decreased resistance to phage infection in Sauton medium compared with the results using 7H10 medium, suggesting that TA systems might have different contributions depending on the nutrient environment. Furthermore, we found that MazEF specifically played a dominant role in resistance to phage infection. Finally, transcriptome analysis revealed that MazEF overexpression led to differential expression of multiple genes, including those related to iron acquisition. Altogether, we demonstrate that TA systems coordinately function to allow M. smegmatis to adapt to changing environmental conditions. IMPORTANCE Toxin-antitoxin (TA) systems are mechanisms for rapid adaptation of bacteria to environmental changes. Mycobacterium smegmatis, a model bacterium for studying Mycobacterium tuberculosis, encodes eight putative TA systems. Here, we constructed an M. smegmatis mutant with deletions of all eight TA-encoding genes and evaluated the resistance of these mutants to environmental stresses. Our results showed that different TA systems have overlapping and, in some cases, opposing functions in adaptation to various stresses. We suggest that complementary TA modules may function together to regulate the bacterial stress response, enabling adaptation to changing environments. Together, this study provides key insights into the roles of TA systems in resistance to various environmental stresses, drug tolerance, and defense against phage infection.

Objectives: The objective of this study was to evaluate a modified Le Fort I interpositional grafting followed by dental implants for the rehabilitation of edentulous atrophied maxillae (Cawood classes IV and V). The surgical modification was a bilateral sinus floor augmentation prior to the osteotomy. This generated a closed recipient bed which allowed the use of particulated bone grafts (xenogenic bone mineral) and a reduced amount of autologous iliac bone grafts., Materials and Methods: A total of 106 patients with maxillary interpositional bone grafts were included in this retrospective analysis between 2006 and 2020. The panoramic radiographs and lateral cephalograms were analyzed to assess the gain and stability of the maxillary bone and the peri-implant bone loss. In addition, the observational period of up to 14 years implant survival and success was evaluated., Results: A stable vertical bone height with mean 0.63 ± 1.41 mm resorption over 5 years after implant loading was observed. A mean of 0.20 ± 0.37 mm marginal bone loss was noted after 5 years. The implant survival was 96.4% after 5 years and implant success can be rated 91.7% in a mean follow-up period of 93 months and 168 months maximal observation time. Perioperative complications included sinus membrane perforation (59.43%), wound healing disturbances (25.47%), and transient primary complications (13.78%). All receded apart from two subtotal graft losses (1.8%)., Conclusions: The modified Le Fort I osteotomy with interpositional bone grafts is a predictable procedure in terms of bone and implant stability. Patients with atrophic maxillae who are fit for surgery should be informed about risks and benefits of this treatment alternative., (© 2022 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)