The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials.

Angiogenesis plays a key role in the pathological process of inflammation and invasion of the synovium, and primarily drives the progression of rheumatoid arthritis (RA). Recent studies have demonstrated that the Notch signaling may represent a new therapeutic target of RA. Although the Notch signaling has been implicated in the M1 polarization of macrophages and the differentiation of lymphocytes, little is known about its role in angiogenesis in RA. In this review, we discourse the unique roles of stromal cells and adipokines in the angiogenic progression of RA, and investigate how epigenetic regulation of the Notch signaling influences angiogenesis in RA. We also discuss the interaction of the Notch-HIF signaling in RA's angiogenesis and the potential strategies targeting the Notch signaling to improve the treatment outcomes of RA. Taken together, we further suggest new insights into future research regarding the challenges in the therapeutic strategies of RA.

Phenylboronic Acid-Modified Near-Infrared Region II Excitation Donor-Acceptor-Donor Molecule for 2-Deoxy-d-Glucose Improved Starvation/Chemo/Photothermal Combination Therapy.

Synergistic chemotherapy and photothermal therapy (PTT) have emerged as a promising anticancer paradigm to achieve expected therapeutic effects while mitigating side effects. However, the chemo/PTT combination therapy suffers from limited penetration depth, thermoresistance performance of tumor cells, and low drug bioavailability. Herein, multifunctional nanoparticles (BTP/DOX/2DG NPs) coloaded with near-infrared region II (NIR-II) light excitation donor-acceptor-donor (D-A-D) small molecules, doxorubicin (DOX), and 2-deoxy-d-glucose (2-DG) are developed for reinforced starvation/chemo/NIR-II PTT combination therapy. The synthesized phenylboronic acid (PBA)-modified water-soluble D-A-D molecule (BBT-TF-PBA) not only exhibits high binding ability to DOX and 2-DG through donor-acceptor coordination interactions PBA-diol bonds but also serves as a photoactive agent for NIR-II fluorescence imaging, NIR-II photoacoustic imaging, and NIR-II PTT. Under the acidic and oxidizing conditions in the tumor microenvironment, donor-acceptor coordination interactions and PBA-diol bond are decomposed, simultaneously releasing DOX and 2-DG from BTP/DOX/2DG NPs to achieve effective chemotherapy and starvation therapy. 2-DG also effectively inhibits the expression of heat shock protein and further enhances NIR-II PTT and chemotherapy efficiency. In vitro and in vivo experiments demonstrate the combination effect of BTP/DOX/2DG NPs for chemotherapy, NIR-II PTT, and starvation therapy.

Machine learning and integrative analysis identify the common pathogenesis of azoospermia complicated with COVID-19.

Background: Although more recent evidence has indicated COVID-19 is prone to azoospermia, the common molecular mechanism of its occurrence remains to be elucidated. The aim of the present study is to further investigate the mechanism of this complication. Methods: To discover the common differentially expressed genes (DEGs) and pathways of azoospermia and COVID-19, integrated weighted co-expression network (WGCNA), multiple machine learning analyses, and single-cell RNA-sequencing (scRNA-seq) were performed. Results: Therefore, we screened two key network modules in the obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) samples. The differentially expressed genes were mainly related to the immune system and infectious virus diseases. We then used multiple machine learning methods to detect biomarkers that differentiated OA from NOA. Enrichment analysis showed that azoospermia patients and COVID-19 patients shared a common IL-17 signaling pathway. In addition, GLO1, GPR135, DYNLL2, and EPB41L3 were identified as significant hub genes in these two diseases. Screening of two different molecular subtypes revealed that azoospermia-related genes were associated with clinicopathological characteristics of age, hospital-free-days, ventilator-free-days, charlson score, and d-dimer of patients with COVID-19 (P < 0.05). Finally, we used the Xsum method to predict potential drugs and single-cell sequencing data to further characterize whether azoospermia-related genes could validate the biological patterns of impaired spermatogenesis in cryptozoospermia patients. Conclusion: Our study performs a comprehensive and integrated bioinformatics analysis of azoospermia and COVID-19. These hub genes and common pathways may provide new insights for further mechanism research.

Prognostic characterization of the pyroptosis-related subtypes and tumor microenvironment infiltration in glioma.

BACKGROUND: Pyroptosis could regulate tumor cell trafficking, invasion, and metastasis, as well as the tumor microenvironment (TME). However, prognostic characteristics of pyroptosis-related genes (PRGs) and their effect on the progression of glioma remain insufficient. METHODS: The genetic, transcriptional, and survival data of patients with glioma used for bioinformatic analysis were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. RESULTS: Screening of two different molecular subtypes revealed that PRG variations were associated with characteristics of TME cell infiltration, clinicopathological characteristics, and prognosis of patients with glioma. After Cox regression of differentially expressed genes, a risk score for predicting overall survival (OS) and progression-free survival (PFS) were calculated. Its predictive accuracy in patients with glioma was validated. The high-risk group of PRG signature had a poorer OS than the low-risk group (training cohort, P< 0.001; validation cohort, P< 0.001). A high risk score implies more immune cell infiltration and better immunotherapy response to immune checkpoint blockers. In addition, the differential expression of three pyroptosis-pairs in tumor and normal tissues was identified. Furthermore, the risk score was significantly associated with chemotherapeutic drug sensitivity and cancer stem cell (CSC) index. Subsequently, a highly accurate nomogram was established to facilitate applicability in the preliminary clinical application of risk score. CONCLUSION: Our findings may provide the basis for future research targeting pyroptosis in glioma and evaluation of prognosis and development of more effective immunotherapy strategies.

B-/Si-containing electrolyte additive efficiently establish a stable interface for high-voltage LiCoO2 cathode and its synergistic effect on LiCoO2/graphite pouch cells.

An effective electrolyte additive, 3-(tert-Butyldimethylsilyoxy) phenylboronic acid (TBPB), is proposed to significantly improve the cycle stability of high voltage LiCoO2 (LCO) cathode. Experimental and computational results show that TBPB has a relatively higher oxidation activity than base electrolyte, and preferentially constructs a stable cathode electrolyte interphase (CEI) containing B-/Si- components on LCO surface. Theoretical calculation, XPS and NMR data show that TBPB-derived CEI layer contains B-F species and has the function of eliminating HF. The as-formed CEI effectively inhibits the detrimental side reactions from electrolyte decomposition and LCO surface structure reconstruction. The capacity retention of LCO/Li half-cell increases from 38.92% (base electrolyte) to 83.70% after 150 cycles at 1 C between 3.0 V and 4.5 V by adding 1% TBPB. Moreover, TBPB is also reduced prior to base electrolyte, forming an ionic conducting solid electrolyte interphase (SEI) on graphite surface. Benefiting from the synergistic effect between CEI layer on LCO cathode and SEI layer on graphite anode to effectively decrease the electrolyte decomposition, the capacity retention of commercial LCO/graphite pouch cell with 1% TBPB increases from 10.44% to 76.13% after 400 cycles at 1 C between 3.0 V and 4.5 V. This work demonstrates that TBPB can act as an effective film-forming additive for high energy density LCO cathode at high voltage, and provides novel insights for its commercial application from the aspect of synergistically interfacial stability.

Temozolomide protects against the progression of glioblastoma via SOX4 downregulation by inhibiting the LINC00470-mediated transcription factor EGR2.

OBJECTIVE: Temozolomide is extensively applied in chemotherapy for glioblastoma with unclear exact action mechanisms. This article seeks to address the potential molecular mechanisms in temozolomide therapy for glioblastoma involving LINC00470. METHODS: Bioinformatics analysis was conducted to predict the potential mechanism of LINC00470 in glioblastoma, which was validated by dual-luciferase reporter, RIP, ChIP, and RNA pull-down assays. LINC00470 expression and the predicted downstream transcription factor early growth response 2 (EGR2) were detected in the collected brain tissues from glioblastoma patients. Following temozolomide treatment and/or gain- and loss-of-function approaches in glioblastoma cells, cell viability, invasion, migration, cycle distribution, angiogenesis, autophagy, and apoptosis were measured. In addition, the expression of mesenchymal surface marker proteins was assessed by western blot. Tumor xenograft in nude mice was conducted for in vivo validation. RESULTS: Mechanistic analysis and bioinformatics analysis revealed that LINC00470 transcriptionally activated SRY-related high-mobility-group box 4 (SOX4) through the transcription factor EGR2. LINC00470 and EGR2 were highly expressed in brain tissues of glioblastoma patients. LINC00470 and EGR2 mRNA expression gradually decreased with increasing concentrations of temozolomide in glioblastoma cells, and SOX4 expression was reduced in cells by temozolomide and LINC00470 knockdown. Temozolomide treatment induced cell cycle arrest, diminished cell viability, migration, invasion, and angiogenesis, and increased apoptosis and autophagy in glioblastoma, which was counteracted by overexpressing LINC00470 or SOX4 but was further promoted by LINC00470 knockdown. Temozolomide restrained glioblastoma growth and angiogenesis in vivo, while LINC00470 or SOX4 overexpression nullified but LINC00470 knockdown further facilitated these trends. CONCLUSION: Conclusively, temozolomide repressed glioblastoma progression by repressing the LINC00470/EGR2/SOX4 axis.

Machine Learning-Assisted Synchronous Fluorescence Sensing Approach for Rapid and Simultaneous Quantification of Thiabendazole and Fuberidazole in Red Wine.

Rapid analysis of components in complex matrices has always been a major challenge in constructing sensing methods, especially concerning time and cost. The detection of pesticide residues is an important task in food safety monitoring, which needs efficient methods. Here, we constructed a machine learning-assisted synchronous fluorescence sensing approach for the rapid and simultaneous quantitative detection of two important benzimidazole pesticides, thiabendazole (TBZ) and fuberidazole (FBZ), in red wine. First, fluorescence spectra data were collected using a second derivative constant-energy synchronous fluorescence sensor. Next, we established a prediction model through the machine learning approach. With this approach, the recovery rate of TBZ and FBZ detection of pesticide residues in red wine was 101% ± 5% and 101% ± 15%, respectively, without resorting complicated pretreatment procedures. This work provides a new way for the combination of machine learning and fluorescence techniques to solve the complexity in multi-component analysis in practical applications.

Unravelling Li+ Intercalation Mechanism and Cathode Electrolyte Interphase of Na3 V2 (PO4 )3 and Na3 (VOPO4 )2 F Cathode as Robust Framework Towards High-Performance Lithium-Ion Batteries.

Although lithium-ion batteries (LIBs) are promising towards high energy density and superior safety energy storage systems (ESS), severe depletion of Li reserve cannot meet the ever-growing demand for LIBs due to the uneven distribution and limited amount of Li resource. Li-free polyanionic cathodes, such as Na3 V2 (PO4 )3 (NVP) and Na3 (VOPO4 )2 F (NVOPF), show intriguing electrochemical performances with prospective future for LIBs due to their appropriate crystallographic sites, robust host structure, and abundant Na resource. In this work, NVP and NVOPF were systematically investigated as cathodes for LIBs using different voltage windows of 2.5-4.3, 2.0-4.3, and 1.5-4.8 V, along with their electrochemical mechanisms, cathode electrolyte interphase properties, and electrode morphologies for comparison. Ex-situ X-ray diffraction, ex-situ X-ray photoelectron spectroscopy, and post-mortem scanning electron microscopy revealed that their mechanisms shifted from a predominant Na+ intercalation/deintercalation in the first charging/discharging to a mixed Li+ /Na+ intercalation/deintercalation at the subsequent cycling. Due to the residual Na+ acting as pillar in the structure, NVP and NVPF could serve as robust host framework, providing appropriate crystallographic sites for repeated Li+ /Na+ intercalation/deintercalation. NVP electrode delivered a higher discharge capacity of 107.6 mAh g-1 with superior capacity retention of 84.3 % after 1000 cycles (2.5-4.3 V, 100 mA g-1 ) than NVOPF electrode (97.3 mAh g-1 , 68.8 %). Electrode polarization and kinetic analysis manifested one energetically similar and two energetically nonequivalent crystallographic Na sites within the R 3 ‾ c and I4/mmm polyanionic structure of NVP and NVOPF. This work comprehensively demonstrates the feasibility and prospect of sodium-based NVP and NVOPF polyanions serving as advanced Li-free cathodes for LIBs, which provides novel insights into seeking Li-free candidates as prospective cathodes for LIBs towards a more sustainable society and a cost-effective battery manufacturing system.

Prognostic Value and Therapeutic Perspectives of CXCR Members in the Glioma Microenvironment.

Background: CXCR (CXC Chemokine Receptor) is a complex of the immune-associated protein involved in tumor activation, invasion, migration, and angiogenesis through various chemical signals in the tumor microenvironment (TME). However, significant prognostic characteristics of CXCR members and their impact on the occurrence and progression of glioma have not yet been fully elucidated. Methods: In this research, we used Oncomine, TCGA, GTEx, and CGGA databases to analyze the transcription and survival data of glioma patients. Afterward, the influence of CXCR members on the TME was explored using comprehensive bioinformatics analysis. Results: The mRNA expression levels of CXCR1/2/3/4/7 were significantly up-regulated in glioma than in normal samples, whereas the mRNA expression level of CXCR5 was decreased. We then summarized the genetic alteration landscape of CXCR and identified two molecular subtypes based on CXCR expression patterns in glioma. The characteristics of CXCRs were also investigated, including the clinicopathological parameters, TME cell infiltration, and prognosis of patients with glioma. After Lasso and multivariable Cox regression, a CR-Score for predicting overall survival (OS) was constructed and the predictive performance of the signature was validated. The high-risk group was a significantly poorer prognostic group than the low-risk group as judged by the CR-Score (TCGA cohort, p < 0.001, CGGA cohort, p < 0.001). Moreover, the CR-Score was significantly correlated to the tumor-immune infiltration and cancer stem cell (CSC) index. A risk scale-based nomogram incorporating clinical factors for individual risk estimation was established thereby. Conclusion: These findings may pave the way for enhancing our understanding of CXCR modification patterns and developing better immune therapeutic approaches for glioma.

Optimizing the Electrolyte Systems for Na3 (VO1-x PO4 )2 F1+2x (0≤x≤1) Cathode and Understanding their Interfacial Chemistries Towards High-Rate Sodium-Ion Batteries.

Invited for this month's cover is the group of Prof. Dr. Zhipeng Sun at the Guangdong University of Technology. The image shows how electrolyte composition and their interfacial chemistries play a crucial role in manipulating the cathode/electrolyte interphases (CEI) and their corresponding high-rate electrochemical performance for sodium-ion batteries. The Research Article itself is available at 10.1002/cssc.202102522.

Optimizing the Electrolyte Systems for Na3 (VO1-x PO4 )2 F1+2x (0≤x≤1) Cathode and Understanding their Interfacial Chemistries Towards High-Rate Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have been regarded as promising alternative to lithium-ion batteries (LIBs) due to the abundance of sodium resource and cost-effectiveness of electrode manufacture. Na3 (VO1-x PO4 )2 F1+2x (0≤x≤1, NVPF1+2x ) polyanionic material, a potential high-energy-density cathode, has shown superior electrochemical performances for advanced SIBs due to its high working voltage (>3.9 V). Electrolyte composition, which plays an indispensable and critical role in determining the cycle stability and the electrode/electrolyte interfacial properties, is of great significance to possess good compatibility with electrode materials, especially the NVPF1+2x cathode. Here, different electrolyte systems, including commonly used 1.0 m NaPF6 /diglyme (NP-005), 1.0 m NaPF6 /propylene carbonate (PC)/5.0 % fluoroethylene carbonate (FEC) (NP-009), 1.0 m NaClO4 /ethylene carbonate-dimethyl carbonate (EC-DMC; 1 : 1 v/v)/5.0 % FEC (NC-019), and 1.0 m NaClO4 /PC (NC-013), were systematically investigated and compared for NVPF1+2x cathode. NVPF1+2x electrode with NP-009 electrolyte showed a superior cycle stability and rate capability at 1-10 C (1 C=130 mA g-1 ) than that of NC-019 and NC-013, while NVPF1+2x electrode with NP-005 electrolyte showed the best high-rate capability at 20-50 C. The cathode/electrolyte interphase (CEI), post-mortem electrode morphology, and electrochemical kinetic characteristics of NVPF1+2x electrode with different electrolytes were profoundly investigated and compared. It demonstrated that NVPF1+2x electrode with NP-005 exhibited a thin, efficient, and NaF-rich CEI layer with less polarization, smaller interfacial resistance, and faster Na+ diffusion than that of NC-019 and NC-013 since they suffered from a thick, overgrown CEI layer due to the consecutive decomposition of FEC, NaClO4 , and/or linear DMC, resulting in inferior electrochemical performance. This work provides new insights for the battery community to gain more comprehensive understanding about the compatibility and interfacial chemistry between different electrolyte systems and various electrode surfaces.

Pan-cancer analysis of the prognostic and immunological role of Fanconi anemia complementation group E.

Fanconi anemia (FA) genes contribute to tumorigenesis by regulating DNA repair. Despite its importance for assembly and functionality of the FA core complex, no pan-cancer analysis of FANCE was performed. We aimed to provide a comprehensive understanding of the role of FANCE in cancers. Based on The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype Tissue-Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), and Cancer Single-cell Atlas (CancerSEA) databases, we investigated the carcinogenicity of FANCE using various bioinformatics methods, including FANCE expression and prognosis, immune invasion, tumor mutation burden, microsatellite instability, and neoantigens. We monitored Fance mutations in mice that caused tumorigenesis. FANCE expression and activity scores were upregulated in 15 and 21 cancers. High expression of FANCE affected shorter overall survival (OS) in seven cancers and longer overall survival in three cancers. It was correlated with shorter overall survival and progression-free interval (PFI) in endometrial cancer and longer overall survival and PFI in cervical cancer. FANCE expression negatively correlated with stromal/immune scores in 21 cancers including cervical cancer, endometrial cancer, and ovarian cancer. FANCE expression negatively correlated with CD8 T cells in endometrial cancer and positively correlated with M1 macrophages in cervical cancer, possibly related to cancer prognosis. FANCE positively correlated with immune checkpoint inhibitors PD-1, PD-L1, and CTLA4 in endometrial cancer and ovarian cancer. FANCE expression positively correlated with microsatellite instability, tumor mutational burden, and neoantigens in 7, 22, and five cancers, especially in endometrial cancer, potentially increasing the effectiveness of immunotherapy. Single-cell sequencing data showed FANCE was primarily expressed in cancer cells in cervical and ovarian cancer, and in fibroblasts in endometrial cancer. Fance heterozygous mutant mice had increased tumor incidences and shorter overall survival and tumor-free survival (TFS) than Fance homozygous mutant mice and wild-type mice. Conclusively, FANCE potential to serve as a biomarker for cancer prognosis and may predict cancer immunotherapy responses. Fance heterozygous mutant resulted in increased tumorigenesis and poor prognosis in mice.

Manipulating the Phase Compositions of Na3(VO1-xPO4)2F1+2x (0 ≤ x ≤ 1) and Their Synergistic Effects with Reduced Graphene Oxide toward High-Rate Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have aroused intense research and academic interest due to the natural abundance and cost-effectiveness of sodium resources. Presently, cathode materials based on the Na3(VO1-xPO4)2F1+2x (0 ≤ x ≤ 1, NVPF1+2x) polyanionic framework show intriguing electrochemical performances toward practical and advanced SIBs due to its high operating voltage (>3.9 V) and high energy density (>500 Wh kg-1). Different from conventional approaches focusing on delicate morphology design, metal ion substitution, and the conductive matrix's incorporation to overcome the low intrinsic electrical conductivity, here we adopt a one-step microwave-assisted hydrothermal approach to optimize the electrochemical performances of NVPF1+2x via manipulating its phase compositions with different vanadium sources and distinguishing the tetragonal (I4/mmm) symmetry of the Na3(VOPO4)2F phase from the orthorhombic symmetry (Amam) of the Na3V2(PO4)2F3 phase. The introduction of the conductive reduced graphene oxide (rGO) framework and its impacts on the phase compositions were systematically investigated. The rGO framework with different calcination temperature can alter the phase composition and the electrical conductivity of NVPF1+2x cathodes significantly, thus having a great impact on their electrochemical performances. Galvanostatic charge/discharge, cyclic voltammetry, electrochemical impedance spectroscopy, and the galvanostatic intermittent titration technique are adopted to compare their electrode polarization and kinetics difference and show that NVPF@rGO-600 °C possesses a high rate, small polarization, and fast kinetics electrochemical properties. This work provides new insights into manipulating phase compositions of the NVPF1+2x cathode by modulating the synthesis conditions and revealing their synergistic effect with a rGO conductive framework toward a superior rate capability and more realistic practical applications for SIBs.

Follow-up study on COVID-19 survivors one year after discharge from hospital.

OBJECTIVE: To evaluate the long-term consequences of COVID-19 survivors one year after recovery, and to identify the risk factors associated with abnormal patterns in chest imaging manifestations or impaired lung function. METHODS: COVID-19 patients were recruited and prospectively followed up with symptoms, health-related quality of life, psychological questionnaires, 6-minute walking test, chest computed tomography (CT), pulmonary function tests, and blood tests. Multivariable logistic regression models were used to evaluate the association between the clinical characteristics and chest CT abnormalities or pulmonary function. RESULTS: Ninety-four patients with COVID-19 were recruited between January 16 and February 6, 2021. Muscle fatigue and insomnia were the most common symptoms. Chest CT scans were abnormal in 71.28% of participants. The results of multivariable regression showed an increased odds in age. Ten patients had diffusing capacity of the lung for carbon monoxide (DLCO) impairment. Urea nitrogen concentration on admission was significantly associated with impaired DLCO. IgG levels and neutralizing activity were significantly lower compared with those in the early phase. CONCLUSIONS: One year after hospitalization for COVID-19, a cohort of survivors were mainly troubled with muscle fatigue and insomnia. Pulmonary structural abnormalities and pulmonary diffusion capacities were highly prevalent in surviving COVID-19 patients. It is necessary to intervene in the main target population for long-term recovery.

Orthodontic incisor retraction caused changes in the soft tissue chin area: a retrospective study.

BACKGROUND: To investigate the area and morphological changes around the soft tissue chin after orthodontic incisor retraction. METHODS: Fifty-nine female adults with bimaxillary protrusion requiring extraction of four premolars were included in the study. Cephalograms were taken before (T0) and after (T1) orthodontic treatment. The soft tissue changes, including the area, thickness and morphology were measured. Paired-t tests were performed for statistical comparisons. Pearson correlation analyses and backward multivariate regression analyses were used to identify the relationship between the soft tissue changes and incisor retraction. RESULTS: Following the incisor retractions (5.35 ± 1.79 mm and 4.42 ± 1.62 mm for the upper and lower, respectively), there was a significant increase in the soft tissue thickness of L1c-LL (0.64 ± 1.67 mm, P = 0.025) and Pog-Pog' (0.44 ± 1.10 mm, P = 0.022), and a significant decrease in the soft tissue thickness of B-B' (1.21 ± 1.34 mm, P <  0.01). Changes in the area of soft tissue chin and lower lip were not statistically significant (P > 0.05). Pearson coefficient between the thickness changes of B-B' and the retraction of lower incisors was - 0.376. The multiple correlations between the soft tissue thickness changes and incisor retractions were Y = 1.02-0.42a + 0.42b for L1c-LL, and Y = 0.17-0.31b for B-B'. CONCLUSIONS: The orthodontic incisor retraction could cause soft tissue thickness changes (i.e. an increase in L1c-LL and Pog-Pog' and a decrease in B-B') without area changes.

Canine edge width and height affect dental esthetics in maxillary canine substitution treatment.

BACKGROUND: To investigate the effect of canine edge width and height on dental esthetics in maxillary canine substitution treatment. METHODS: A total of 127 canine substitution treatment cases were screened and evaluated by a panel of orthodontic experts and laypersons in the pilot study. The top five subjects with the esthetically most pleasant canine substitution were included in the study, resulting in 140 computerized images displaying only the upper dentition, with different canine edge widths (0%, 12.5%, 25%, 37.5%, 50%, 62.5%, and 75% of the central clinical width) and heights (- 0.5 mm, 0 mm, 0.5 mm, and 1.0 mm vertically relative to the central incisor edge) finally used for the esthetic evaluation by 101 observers (41 orthodontists and 60 laypersons). The ordered logistic regression analysis, the univariate analysis of variance, the chi-square, and Fisher's exact tests were used for statistical analyses. RESULTS: The most esthetic canine shape for canine substitution was found to be a shape with the edge width of 62.5% of the central incisor width and the edge height of 0.5 mm gingival to the central incisor edge (P < 0.05). The canine edge width of 50-75% and height of 0.5-0 mm gingival to the central incisor edge were generally considered to be esthetic by all observers. Orthodontists and laypersons had the same ranking on the top two most esthetic canine shapes (edge width and height 62.5% and 0.5 mm gingival; 50% and 0 mm incisal) as well as the bottom two most unesthetic canine shape (0% and 0.5 mm gingival; 75% and 1 mm incisal). Male and female observers generally had similar esthetic grades and rankings on the canine shapes (P > 0.05). CONCLUSIONS: The most esthetic canine shape for canine substitution is a shape with the canine edge width of 62.5% of the central incisor width and the edge height of 0.5 mm gingival to the central incisor edge. The different collocations of the canine edge width and height affect dental esthetics of the canine during canine substitution treatment.

Genome sequences of Pseudomonas fragi strains A22 and B25.

Pseudomonas fragi A22 is a novel isolate that produces bead-like particles (A22B) in its cell wall. To explore the genetic basis for the formation of A22B, P. fragi A22 and the type strain of the species, P. fragi B25, were subjected to genome sequence analysis. Here, we report the draft genome sequences and automatic annotation of both strains. These data offer a solid base for related studies of P. fragi, including comparative genomics, proteomics, and gene mining.