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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.)

The advent of three dimensionally (3D) printed customized bone grafts using different biomaterials has enabled repairs of complex bone defects in various in vivo models. However, studies related to their clinical translations are truly limited. Herein, 3D printed poly(lactic- co -glycolic acid)/β-tricalcium phosphate (PLGA/TCP) and TCP scaffolds with or without recombinant bone morphogenetic protein -2 (rhBMP-2) coating were utilized to repair primate's large-volume mandibular defects and compared efficacy of prefabricated tissue-engineered bone (PTEB) over direct implantation (without prefabrication). 18 F-FDG PET/CT was explored for real-time monitoring of bone regeneration and vascularization. After 3-month's prefabrication, the original 3D-architecture of the PLGA/TCP-BMP scaffold was found to be completely lost, while it was properly maintained in TCP-BMP scaffolds. Besides, there was a remarkable decrease in the PLGA/TCP-BMP scaffold density and increase in TCP-BMP scaffolds density during ectopic (within latissimus dorsi muscle) and orthotopic (within mandibular defect) implantation, indicating regular bone formation with TCP-BMP scaffolds. Notably, PTEB based on TCP-BMP scaffold was successfully fabricated with pronounced effects on bone regeneration and vascularization based on radiographic, 18 F-FDG PET/CT, and histological evaluation, suggesting a promising approach toward clinical translation.

Multidrug-resistant Mycobacterium tuberculosis ( Mtb ) infection seriously endangers global human health, creating an urgent need for new treatment strategies. Efficient genome editing tools can facilitate identification of key genes and pathways involved in bacterial physiology, pathogenesis, and drug resistance mechanisms, and thus contribute to the development of novel treatments for drug-resistant tuberculosis . Here, we report a two-plasmid system, MtbCBE , used to inactivate genes and introduce point mutations in Mtb . In this system, the assistant plasmid pRecX-NucS E107A expresses RecX and NucS E107A to repress RecA-dependent and NucS-dependent DNA repair systems, and the base editor plasmid pCBE expresses a fusion protein combining cytidine deaminase APOBEC1, Cas9 nickase (nCas9), and uracil DNA glycosylase inhibitor (UGI). Together, the two plasmids enabled efficient G:C to A:T base pair conversion at desired sites in the Mtb genome. The successful development of a base editing system will facilitate elucidation of the molecular mechanisms underlying Mtb pathogenesis and drug resistance and provide critical inspiration for the development of base editing tools in other microbes., 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., (Copyright © 2021 Ding, Li, Geng, Yan, Li, Zhang and Sun.)

To reveal the speciation and pollution status of heavy metal(loid) s (HMs) in the dewatered sewage sludge(SS) of municipal wastewater treatment plants(MWTPs) in China, SS samples were collected from 40 MWTPs located in different regions of China. The total concentrations and geochemical fractions of As, Cd, Cr, Cu, Ni, Pb, and Zn in the SS samples were analyzed. The ecological risks induced by HMs in the SS were assessed based on the toxicity characteristic leaching procedure(TCLP), risk assessment code(RAC), and potential ecological risk index(RI). The median values of HMs in SS followed the order Zn > Cu > Cr > Pb > Ni > As > Cd. The general attainment rates of HMs in SS were satisfactory(>90%). As showed a generally even distribution among all the fractions; Cd and Zn mainly existed in the reducible fraction; Cr mainly occurred in the residual fraction, followed by oxidizable and reducible fractions; Cu mainly occurred in the oxidizable fraction; Ni occurred mainly as exchangeable forms; and Pb mainly occurred in the reducible and residual fractions, with its exchangeable form being the lowest fraction. According to the RAC method, the environmental risks induced by HMs in the SS followed the order Ni > As > Zn > Cd > Cu > Cr > Pb. The ecological risk of Ni was high; Zn, As, and Cd had a medium level of risk; Cr and Cu had a low level of risk; and the risk of Pb was negligible. According to the RI method, Cd and Cu showed the highest potential ecological risk, indicating that these are the primary HM pollutants in the SS. However, if the agricultural application of SS is carried out in accordance with the national standards, the overall level of risk from soil HM pollution is considered relatively low.

Objectives: The study aimed to compare the accuracy of implant placement between static and dynamic computer-assisted systems (CAS) in a partially edentulous mandible model., Materials & Methods: A total of 80 implants was placed in mandible models. The implants were placed using either static or dynamic computer-assisted system. Deviations of implant hex, apex and angulation were measured between preoperative planning and postoperative CBCT in planning software., Results: The mean deviations of implant hex, apex and angulation in static CAS group were 1.15 ± 0.34 mm, 1.37 ± 0.38 mm and 2.60 ± 1.11 degree, while in dynamic CAS group were 0.40 ± 0.41 mm, 0.34 ± 0.33 mm and 0.97 ± 1.21 degree, respectively. Implant placement with dynamic CAS showed less deviations of shoulder, apex and angulation than with static CAS significantly., Conclusions: The implant accuracy using CAS system could be influenced by the guiding technique., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This study evaluated the accuracy of implant placement with surgical-template guidance both in vitro and in vivo. Virtual surgical planning was performed based on the data from CBCT scans and an intraoral scanner. Surgical templates were designed according to the planned implants and manufactured with stereolithography. In vitro, 60 implants were placed in 15 resin models. In vivo, 74 implants were placed in 54 patients. The implants were scanned with CBCT postoperatively. Implant accuracy was evaluated by measuring the following parameters: central deviation at the apex and shoulder, horizontal deviation at the apex and shoulder, vertical deviation at the apex and shoulder, and angular deviation. There were statistically significant in vitro and in vivo deviations for all parameters, and the implant deviations in vivo were significantly greater than those in vitro. When using a mucosa-supported template, horizontal deviations at the apex were significantly greater than when a teeth-supported template was used. Within the limitation of the study design, inaccuracy existed in implant placement guided with a surgical template. More studies are needed to investigate the value of the procedure in future.

Purpose: Implant location is performed after placement to verify that the safety of neighboring anatomic structure and the realizability of prosthetic plan. Routine postoperative location is based on radiological scanning and raises the concerns on radiation exposure and inconveniency in practice. In the present study a location method based on surface scanning was introduced and the accuracy of this method was assessed in vitro., Material and Methods: A total of 40 implants were placed in 10 resin mandible models. The models were scanned with intraoral scanner (IS group) and extraoral scanner (ES group). The implant position was located with fusing the images of surface scanning and cone beam computerized tomography (CBCT) after implant placement. Deviations were measured between positions located by surface scanner and postoperative CBCT with the parameters: central deviation at apex (cda), central deviation at hex (cdh), horizontal deviation at apex (hda), horizontal deviation at hex (hdh), vertical deviation at apex (vda), vertical deviation at hex (vdh) and angular deviation (ad)., Results: In IS group, the mean value of cda, cdh, hda, hdh, vda, vdh and ad was 0.27 mm, 0.23 mm, 0.12 mm, 0.10 mm, 0.21 mm, 0.19 mm and 0.72°, respectively. In ES group, the mean value of cda, cdh, hda, hdh, vda, vdh and ad was 0.28 mm, 0.25 mm 0.14 mm, 0.11 mm, 0.22 mm, 0.20 mm and 0.68°, respectively. The implant deviations in IS and ES groups were of no significant difference for any of the measurements., Conclusions: Dental implant can be located via surface scanner with acceptable accuracy for postoperative verification. Further clinical investigation is needed to assess the feasibility of the method.

Background: Poly Ether Ether Ketone (PEEK) has been considered as a potential alternative material for endosseous dental implants, for its low elastic modulus, biocompatibility, and low cost in customized device manufacture. Hydroxyapatite-incorporation is supposed to improve the poor osseointegration of PEEK., Methods: In the present study we analyzed the in vivo response of hydroxyapatite-incorporated PEEK (PEEK-HA) implants in canine tibia. PEEK-HA and PEEK implants were implanted and were examined 4 weeks and 12 weeks after implantation with radiology and histology. Commercial titanium dental implants served as controls., Results: The ratio of bone volume to tissue volume of PEEK-HA implants was higher than that of PEEK implants 4 weeks after implantation in the μ-CT analysis. The bone implant contact of PEEK and PEEK-HA implants showed no statistical difference in the histological examination, but newly-formed bone around PEEK-HA implants showed more signs of mineralization than that around PEEK implants., Conclusion: The study suggested that bone formation was improved with hydroxyapatite-incorporation in PEEK. Hydroxyapatite-incorporated PEEK implants may represent a potential material for endosseous dental implant.

The present study aimed to investigate the role of lysosomal‑associated transmembrane protein 5 (LAPTM5) in osteoclast differentiation induced by osteoblasts. The results demonstrated that the expression levels of LAPTM5 were downregulated following runt‑related transcription factor 2 (RUNX2) silencing and upregulated following RUNX2 overexpression in ST2 cells. Chromatin immunoprecipitation analysis identified the binding of RUNX2 to the LAPTM5 promoter at the ‑1176 to ‑1171 position. Dual‑luciferase reporter assays confirmed that RUNX2 directly activated the LAPTM5 gene. The concentration of receptor activator of nuclear factor‑κB ligand (RANKL) protein in the cytoplasm and in the media was significantly increased following LAPTM5 knockdown. LAPTM5 silencing in ST2 cells enhanced osteoclastic differentiation of co‑cultured RAW264.7 cells. The present study indicated that expression of LAPTM5 was regulated by the interaction of RUNX2 with its promoter region and that LAPTM5 was involved in the trafficking of RANKL. These findings suggested a possible coupling mechanism between osteogenesis and osteoclastogenesis in which RUNX2 may be involved in osteoclast differentiation through the regulation of the lysosome‑associated genes that modulate RANKL expression.

Objectives: The aim of the present retrospective study was to assess the long-term clinical outcome of sandwich osteotomy in pre-implant augmentation of atrophic mandible., Materials and Methods: Sandwich osteotomies were performed in partially and fully edentulous mandibles of 63 consecutive patients in the present study. The vertical bone gain, graft stability, and marginal bone loss were measured radiographically. Implant survival and success rates were estimated in the follow-up ranged from 2 to 144 months (mean, 58 months)., Results: A total of 75 procedures were reviewed. After an average healing time of 148 days, 220 implants were placed in 74 procedures. Perioperative complications included intraoperative fracture (1/75), transient paresthesia (18/75), wound healing disturbance (18/75), and keratinized tissue deficiency (14/75). The average vertical bone gain was 5.4 mm at the time of implant placement. Significant marginal bone loss occurred during the first 6 months, after which the resorption remained stable. The implant survival rate was estimated as 96.7%, and the success rate was 95.3%. Implant survival and success showed no significant correlation with higher age, anticoagulation therapy, cardiovascular disease, or thyroid disorder. Smoking was correlated with significant lower success rate., Conclusion: Sandwich osteotomy is a suitable augmentation procedure for atrophic mandible, allowing for implant placement with promising outcome., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reconstruction of bone loss in the alveolar ridge has long been challenging. Autologous bone grafts are considered as the "golden standard," while little research has focused on how to repair pronounced alveolar bone defects after autologous bone graft failure. The aim of this study was to detail a method based on the titanium mesh technique coupled with particulate coral hydroxyapatite to solve the onlay graft failure. With bone deficiency in the No. 11 and No. 24-25 regions, we harvested 2 autologous bone blocks for reconstruction. Two weeks after transplantation, the graft in the No. 11 region had healed uneventfully, while the graft in the anterior mandible became infected because of soft tissue dehiscence. After removal of the failed autologous bone block, pure coral hydroxyapatite stabilized within titanium mesh was used for alveolar rehabilitation. Six months later, the width of the local alveolar bone was evaluated. After the titanium mesh was removed, a biopsy was performed to study bone regeneration by micro computerized tomography and histology, following by a standard Straumann implant insertion. Although there was wound dehiscence 14 days after bone augmentation, repeated local rinsing and anti-inflammation therapy controlled the inflammatory reaction. The total horizontal bone gain was 4.2 ± 0.5 mm. Micro computerized tomography revealed that the closer the coral hydroxyapatite was to the host bone, the more was resorbed and the more bone regenerated. Histology showed mature lamellar bone structures, with evident residual coral hydroxyapatite. A 3-year follow-up revealed stable bone around the dental implant and successful function of the implant-born prosthesis. This study proposes that the method of particulate coral hydroxyapatite sheltered by titanium mesh is a promising solution in handling alveolar bone augmentation failure. More cases are needed for further research to form an efficient treatment procedure.

Background : Hylomecon japonica , a plant of the Papaveraceae family which is well-known for the alkaloids they produce, is a perennial plant widely distributed in the northeast, central and east regions of China. Although a variety of chemical constituents, including alkaloids, flavonoids, and megastigmoids, have been isolated from H. japonica , the investigation of saponins in H. japonica has not been reported until now. Methods : Various separation techniques, including polyporous resin column chromatography, silica gel column chromatography and hemi-preparative HPLC were applied to the isolation of triterpenoid saponins, and chemical methods such as acid hydrolysis and spectroscopic methods including HRESIMS and NMR were applied to their structure elucidation, and the XTT reduction method was used to assay cytotoxicity. Results : Two new triterpenoid saponins, named hylomeconoside A ( 1 ) and B ( 2 ) which were identified as 3- O -β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl-gypsogenin-28- O -β-d-xylopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-β-d-quinovopyranoside ( 1 ) and 3- O -β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl-gypsogenin-28- O -β-d-xylopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside ( 2 ), and two known triterpenoid saponins identified as dubioside C ( 3 ) and lucyoside P ( 4 ) on the basis of spectroscopic and chemical evidence, were isolated from H. japonica. Compound 1 exhibited moderate cytotoxicity on MGC-803 and HL-60 cells, with IC 50 values of 43.8 and 32.4 μg·mL -1 , respectively. Conclusions: Compounds 1 and 2 are new saponins, and 1 is considered to be one of the antitumor principles in this plant. This is the first time that triterpenoid saponins have been isolated from plants of the Papaveraceae family., Competing Interests: The authors declare no conflict of interest.

The aim of this study was to investigate the relationship between sleep disorders in acute thalamus stroke patients and plasma IL-17 levels and the mechanism through which inflammatory reactions develop in stroke. The study included two groups of patients: an experimental group consisting of 30 patients with thalamus stroke who received treatment at the Affiliated Hong Qi Hospital of Mu Dan Jiang Medical University during October 2015 to October 2016 and a control group consisting of 15 healthy volunteers. All the subjects included in the study were biochemically monitored for blood glucose, blood fats and IL-17 plasma levels. The sleep quality of all the subjects included in the study was evaluated [Epwort, Pittsburgh Sleep Quality Index (PSQI)] with 8-hour Polysonmography (PSG) monitoring. The experimental group was divided into 3 subgroups according to the part of the brain affected by stroke: anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group. The differences were analyzed between the experimental group and the control group in sleep quality scores, sleep structural changes, and plasma IL-17 levels. The differences in sleep structural scores were also analyzed according to different parts of the brain affected by stroke. The experimental group had a higher PSQI score compared with the control group, but this difference had no statistical significance (p>0.05). Compared with the control group, the N1 phase of the experimental group was longer while the N2 and N3 phases were shorter (p<0.05). There were no differences in sleep structure between the three regions of the brain affected by stroke (anterior thalamus nucleus group, lateral thalamus nucleus group and medial thalamus nucleus group) (p > 0.05). The plasma levels of IL-17 in the experimental group was higher compared to the control group (p<0.05). In the experimental group, the patients with hypersomnia had higher IL-17 levels than patients without hypersomnia (p<0.01). We can conclude that PSG can be used as an electrophysiology index for early detection of sleep disorders in thalamus stroke patients. Sleep disorders in patients with thalamus stroke persist a long time after the incident, therefore monitoring their sleep structure may become an important index to predict the prognosis of the disease. The increased level of IL-17 level in the experimental group shows its implication in appearance of sleep disorders of acute thalamus stroke through inflammatory mechanism.

The present study aimed to investigate the role of magnitude in adaptive response of osteoblasts exposed to compressive stress. Murine primary osteoblasts and MC3T3-E1 cells were exposed to compressive stress (0, 1, 2, 3, 4, and 5 g/cm 2 ) in 3D culture. Cell viability was evaluated, and expression levels of Runx2, Alp, Ocn, Rankl, and Opg were examined. ALP activity in osteoblasts and TRAP activity in RAW264.7 cells co-cultured with MC3T3-E1 cells were assayed. Results showed that compressive stress within 5.0 g/cm 2 did not influence cell viability. Both osteoblastic and osteoblast-regulated osteoclastic differentiation were enhanced at 2 g/cm 2 . An increase in stress above 2 g/cm 2 did not enhance osteoblastic differentiation further but significantly inhibited osteoblast-regualted osteoclastic differentiation. This study suggested that compressive stress regulates osteoblastic and osteoclastic differentiation through osteoblasts in a magnitude-dependent manner.

Objective: To biologically evaluate the three-dimensional(3D) printed co-poly lactic acid/glycolic acid/tri-calcium phosphate(PLGA/TCP) scaffold which could be used for repairing oral and maxillofacial bone defects, and to provide experimental evidence for its further research and clinical application. Methods: PLGA/TCP scaffolds were fabricated using low temperature rapid prototyping technique. Micro-CT and scanning electron microscope(SEM) were used to characterize the surface morphology. MC3T3-E1 cells were seeded onto the scaffold and stained with the rhodamine phalloidin and calcein acetomethoxy. After that, confocal laser scanning microscope was exploited to observe the features and viability of the cells. Moreover, the cells were co-cultured with the extract of PLGA/TCP and complete medium, respectively. The proliferation capability of the cells was assessed by the cell counting kit-8 (CCK-8) on the 1st, 2nd, and 3rd day. The PLGA/TCP scaffolds incorporated with recombinant human bone morphogenetic protein-2(rhBMP-2) of 0, 30, 60 μg(i.e. blank control group, low-dose group and high-dose group) were implanted into the latissimus dorsi muscle of the rats, and 6 weeks later, the samples were harvested to estimate the volume and pattern of new bone. Results: The 3D printed PLGA/TCP scaffold possessed a regular and well-defined porous stereo-structure with porosity of (73±3)%. Micro-CT and SEM showed that pore size were (379±32) and (453±29) μm respectively, and distance between layers were (452± 24) and (415±25) μm, and cylinder diameter were (342±24) and (350±28) μm. It also exhibited excellent cell adhesion and growth ability on the exterior and inner surface through rhodamine phalloidin and calcein acetomethoxy staining. The CCK-8 test demonstrated that the absorbance value of extract group on the 1st and 2nd day(0.51±0.08 and 0.63±0.09) were significantly higher than those in the blank control group(0.39± 0.05 and 0.53±0.05)( P< 0.05), while there was no significant difference between the extract group(0.67±0.06) and the blank control group(0.68±0.04)( P> 0.05) on the 3rd day. For in vivo test, there was obvious ectopic new bone formation on the PLGA/TCP scaffold incorporated with rhBMP-2, and this was demonstrated using the histological examination and micro-CT. The bone formation in the low-dose group was similar to the shape of the pre-implanted 3D printed scaffold, while much diversity was revealed in the high-dose group duo to over osteogenesis which was validated by the examinations of gross observation, histology and micro-CT. Conclusions: Customized PLGA/TCP scaffolds can be manufactured by 3D printing technique. The scaffold showed an excellent biocompatibility and ectopic osteogenesis when incorporated with rhBMP-2. However, further research is needed to validate it ' s effect on repairment of the oral and maxillofacial bone defects.

Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (-)-Epicatechin (1), 5,7,4'-trihydroxy-flavonoid-8-C-β-D-glucopyranoside (2), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propane-diol (erythro) (3), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (threo) (4), (R)-4-hydroxylphenol O-(6-O-oleuropeoyl)-β-D-glucopyranoside (5), (R)-3-methoxy-4-hydroxylphenol O-(6-O-oleuropeoyl)-β-D-glucopyranoside (6), quercetin-3-O-rutinoside (7). Compounds 5 and 6 are new monoterpene phenolic glycosides, compounds 1, 3 and 4 were isolated from the Viburnum genus for the first time, and compounds 2 and 7 from the Viburnum sargentii Koehne for the first time. Compounds 1-7 were also assayed for their antioxidant activities with DPPH free radicals.

Multi-yolk-shell Bi@C nanostructures were prepared via a facile one-pot template-free hydrothermal approach. The prepared Bi@C nanostructures can act as a solid catalyst in the thermal decomposition of cyclotrimethylenetrinitramine (RDX) and display excellent catalytic activity, which highlights their application in the field of energetic materials.

We investigated the short-term and medium-term results in patients with pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) undergoing transcatheter closure. Fifteen patients with severe PAH associated with ASD who underwent successful occluder implantation from 2007 to 2010 were included. Clinical, echocardiographic, and hemodynamic data were reviewed. Severe PAH was defined as pulmonary arterial systolic pressure measured by catheterization was ≥60 mmHg and pulmonary vascular resistance (PVR) ≥6 Wood Units (WU). Compared with baseline, the 6-minwalking distance significantly increased by 29.7 ± 26.3 m (P < 0.001) at 3 months (short-term) and 65.4 ± 63.6 m (P < 0.001) at 23.4 ± 9.7 months (medium-term), World Health Organization function class considerably improved after postclosure short-term and medium-term. Repeat cardiac catheterization (n = 7) showed that mean pulmonary arterial pressure decreased from 51.6 ± 9.4 mmHg at baseline to 21.0 ± 3.8 mmHg (P < 0.001) at follow-up of 12 months. The PVR decreased by 5.6 ± 1.1 WU (P < 0.001). Through carefully selected patients with severe PAH associated with ASD, transcatheter closure can be safely performed with a promising short-term and medium-term outcome. Trial occlusion is an effective way for deciding the reversibility of severe PAH in ASD patients. The role of aerosolized iloprost for pulmonary vasoreactivity testing in patients with severe PAH secondary to ASD requires further investigation.

Objective: To investigate the frequency of leukotriene C(4) synthase gene A (LTC(4)S A) -444 C polymorphism in asthmatics of Chinese Han nationality in Southwest China and to evaluate its relevance to clinical responsiveness to leukotriene receptor antagonist., Methods: A hundred and fifty asthmatics and 146 healthy blood donors were recruited. The genotype distribution of A/C polymorphism of LTC(4)S A(-444)C gene was analyzed by RELP (restriction fragment length polymorphism). Eighty asthmatics were randomly recruited for a 4 week prospective trial of montelukast and their clinical response to montelukast was evaluated by ACQ and pulmonary function. Urine LTE(4) was detected by ELISA (enzyme linked immunosorbent assay) in asthma patients before and after treatment., Results: In the 150 asthma patients, the frequencies of A and C alleles at -444 locus of LTC(4)S gene were 83.7% and 16.3%, respectively, and the genotype frequencies of AA and AC/CC were 70.7% and 29.3%, respectively. In the 146 healthy blood donors, the frequencies of A and C alleles at -444 locus of LTC(4)S gene were 87.0% and 13.0%, respectively, and the genotype frequencies of AA and AC/CC were 76.7% and 23.3%, respectively. There was no significant difference in LTC(4)S A(-444)C polymorphism between the asthmatics and the healthy controls (chi(2) = 1.393, 1.301, P = 0.238, 0.25 4, P > 0.05). The asthmatics with the C(-444) allele were younger than the asthmatics with AA with earlier onset age and longer duration of disease compared to those with AA (both P < 0.05). However, there were no significant differences between the two groups in clinical and lung function parameters. Four-week montelukast therapeutic trial demonstrated that asthmatic patients with AC/CC genotype had better response than those with AA genotype and this difference was related to urine LTE(4) level (F = 12.01, P = 0.011)., Conclusion: In a Southwest Chinese Han population LTC(4)S A(-444)C polymorphism might be a determinant factor in the clinical response of asthma to leukotriene receptor antagonists.