Activation of autophagy by inflammatory signals limits IL-1ß production by targeting ubiquitinated inflammasomes for destruction.

Autophagosomes delivers cytoplasmic constituents to lysosomes for degradation, whereas inflammasomes are molecular platforms activated by infection or stress that regulate the activity of caspase-1 and the maturation of interleukin 1ß (IL-1ß) and IL-18. Here we show that the induction of AIM2 or NLRP3 inflammasomes in macrophages triggered activation of the G protein RalB and autophagosome formation. The induction of autophagy did not depend on the adaptor ASC or capase-1 but was dependent on the presence of the inflammasome sensor. Blocking autophagy potentiated inflammasome activity, whereas stimulating autophagy limited it. Assembled inflammasomes underwent ubiquitination and recruited the autophagic adaptor p62, which assisted their delivery to autophagosomes. Our data indicate that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasomes.

Accuracy of robotic surgery for dental implant placement: A systematic review and meta-analysis.

OBJECTIVES: To systematically analyze the accuracy of robotic surgery for dental implant placement. MATERIALS AND METHODS: PubMed, Embase, and Cochrane CENTRAL were searched on October 25, 2023. Model studies or clinical studies reporting the accuracy of robotic surgery for dental implant placement among patients with missing or hopeless teeth were included. Risks of bias in clinical studies were assessed. Meta-analyses were undertaken. RESULTS: Data from 8 clinical studies reporting on 109 patients and 242 implants and 13 preclinical studies were included. Positional accuracy was measured by comparing the implant plan in presurgery CBCT and the actual implant position in postsurgery CBCT. For clinical studies, the pooled (95% confidence interval) platform deviation, apex deviation, and angular deviation were 0.68 (0.57, 0.79) mm, 0.67 (0.58, 0.75) mm, and 1.69 (1.25, 2.12)°, respectively. There was no statistically significant difference between the accuracy of implants placed in partially or fully edentulous patients. For model studies, the pooled platform deviation, apex deviation, and angular deviation were 0.72 (0.58, 0.86) mm, 0.90 (0.74, 1.06) mm, and 1.46 (1.22, 1.70)°, respectively. No adverse event was reported. CONCLUSION: Within the limitation of the present systematic review, robotic surgery for dental implant placement showed suitable implant positional accuracy and had no reported obvious harm. Both robotic systems and clinical studies on robotic surgery for dental implant placement should be further developed.

Asiaticoside ameliorates DSS-induced colitis in mice by inhibiting inflammatory response, protecting intestinal barrier and regulating intestinal microecology.

Ulcerative colitis (UC) is one of the most prevalent inflammatory bowel diseases and poses a serious threat to human health. Currently, safe and effective preventive measures are unavailable. In this study, the protective effects of asiaticoside (AS) on dextran sodium sulfate (DSS)-induced colitis in mice and the underlying molecular mechanism were investigated. In this experiment, colitis was induced in mice with DSS. Subsequently, the role of AS in colitis and its underlying mechanisms were examined using H&E staining, immunofluorescence staining, western blot, Elisa, FMT, and other assays. The results showed that AS significantly attenuated the related symptoms of DSS-induced colitis in mice. In addition, AS inhibited the activation of signaling pathways TLR4/NF-κB and MAPK reduced the release of inflammatory factors, thereby attenuating the inflammatory response in mice. AS administration also restored the permeability of the intestinal barrier by increasing the levels of tight junction-associated proteins (claudin-3, occludin, and ZO-1). In addition, AS rebalanced the intestinal flora of DSS-treated mice by increasing the diversity of the flora. AS can alleviate DSS-induced ulcerative colitis in mice by maintaining the intestinal barrier, thus inhibiting the signaling pathways TLR4/NF-κB and MAPK activation, reducing the release of inflammatory factors, and regulating intestinal microecology.

Microwave-Assisted Grafting of Coal onto Nitrogen-Doped Carbon Dots with a High Quantum Yield and Enhanced Photoluminescence Properties.

The fluorescent nitrogen-doped carbon dots (N-CDs) were synthesized via a facile one-pot solvothermal process using coal (Jin 15 Anthracite and Shaerhu lignite) as raw materials and dimethyl formamide (DMF) as the solvent, employing a microwave pyrolysis method. This approach demonstrates remarkable efficacy in the development of nitrogen-doped carbon dots (N-CDs) with a high quantum yield (QY). The N-CDs prepared have strong photoluminescence properties. Moreover, the obtained N-CDs emit blue PL and are easily dispersed in polymethyl methacrylate (PMMA), preserving the inherent advantages of N-CDs and the PMMA matrix. The JN-CDs exhibit a high quantum yield (QY) of 49.5% and a production yield of 25.7%, respectively. In contrast, the SN-CDs demonstrate a quantum yield of 40% and a production yield of 35.1%. It is worth noting that the production yield and quantum yield of coal-based carbon dots are inversely related indices. The lower metamorphic degree of subbituminous coal favors an enhanced product yield, while the higher metamorphic degree of anthracite promotes an improved quantum yield in the product, which may be attributed to the presence of amorphous carbon within it. Consequently, we propose and discuss potential mechanisms underlying N-CD formation.

Accuracy and safety of a haptic operated and machine vision controlled collaborative robot for dental implant placement: A translational study.

OBJECTIVES: Multiple generations of medical robots have revolutionized surgery. Their application to dental implants is still in its infancy. Co-operating robots (cobots) have great potential to improve the accuracy of implant placement, overcoming the limitations of static and dynamic navigation. This study reports the accuracy of robot-assisted dental implant placement in a preclinical model and further applies the robotic system in a clinical case series. MATERIALS AND METHODS: In model analyses, the use of a lock-on structure at robot arm-handpiece was tested in resin arch models. In a clinical case series, patients with single missing teeth or edentulous arch were included. Robot-assisted implant placement was performed. Surgery time was recorded. Implant platform deviation, apex deviation, and angular deviation were measured. Factors influencing implant accuracy were analyzed. RESULTS: The in vitro results showed that with a lock-on structure, the mean (SD) of platform deviation, apex deviation, and angular deviation were 0.37 (0.14) mm, 0.44 (0.17) mm, and 0.75 (0.29)°, respectively. Twenty-one patients (28 implants) were included in the clinical case series, 2 with arches and 19 with single missing teeth. The median surgery time for single missing teeth was 23 (IQ range 20-25) min. The surgery time for the two edentulous arches was 47 and 70 min. The mean (SD) of platform deviation, apex deviation, and angular deviation was 0.54 (0.17) mm, 0.54 (0.11) mm, and 0.79 (0.22)° for single missing teeth and for 0.53 (0.17) mm, 0.58 (0.17) mm, and 0.77 (0.26)° for an edentulous arch. Implants placed in the mandible had significantly larger apex deviation than those in the maxilla. CONCLUSION: Cobot-assisted dental implant placement showed excellent positional accuracy and safety in both the in vitro study and the clinical case series. More technological development and clinical research are needed to support the introduction of robotic surgery in oral implantology. Trial registered in ChiCTR2100050885.

Analysis of preoperative influential factors and construction of a predictive nomogram of difficult thyroidectomy.

OBJECTIVE: To explore the preoperative influential factors of difficult thyroidectomy and establish a preoperative nomogram for predicting the difficulty of thyroidectomy. METHODS: A total of 753 patients who underwent total thyroidectomy with central lymph node dissection between January 2018 and December 2021 were retrospectively enrolled in this study and randomly divided into training and validation groups at a ratio of 8:2. In both subgroups, the patients were divided into difficult thyroidectomy and nondifficult thyroidectomy groups based on the operation time. Patient age, sex, body mass index (BMI), thyroid ultrasound, thyroid function, preoperative fine needle aspiration (FNA), postoperative complications and other data were collected. Logistic regression analysis was performed to identify the predictors of difficult thyroidectomy, and a nomogram predicting surgical difficulty was created. RESULTS: Multivariate logistic regression analysis demonstrated that male sex (OR = 2.138, 95% CI 1.055-4.336, p = 0.035), age (OR = 0.954, 95% CI 0.932-0.976, p < 0.001), BMI (OR = 1.233, 95% CI 1.106-1.375, p < 0.001), thyroid volume (OR = 1.177, 95% CI 1.104-1.254, p < 0.001) and TPO-Ab (OR = 1.001, 95% CI 1.001-1.002, p = 0.001) were independent risk factors for difficult thyroidectomy. The nomogram model incorporating the above predictors performed well in both the training and validation sets. A higher postoperative complication rate was found in the difficult thyroidectomy group than in the nondifficult thyroidectomy group. CONCLUSION: This study identified independent risk factors for difficult thyroidectomy and created a predictive nomogram for difficult thyroidectomy. This nomogram may help to objectively and individually predict surgical difficulty before surgery and provide optimal treatment.

Moringa oleifera Lam. Isothiocyanate Quinazolinone Derivatives Inhibit U251 Glioma Cell Proliferation through Cell Cycle Regulation and Apoptosis Induction.

A major active constituent of Moringa oleifera Lam. is 4-[(α-L-rhamnose oxy) benzyl] isothiocyanate (MITC). To broaden MITC's application and improve its biological activity, we synthesized a series of MITC quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma.

AKT Regulates NLRP3 Inflammasome Activation by Phosphorylating NLRP3 Serine 5.

The cytosolic pattern recognition receptor NLRP3 senses host-derived danger signals and certain microbe-derived products in both humans and rodents. NLRP3 activation assembles an inflammasome complex that contains the adapter proteins ASC and caspase-1, whose activation triggers the maturation and release of the proinflammatory cytokines IL-1ß and IL-18. S5 phosphorylation of NLRP3 prevents its oligomerization and activation, whereas dephosphorylation of this residue by the phosphatase PP2A allows NLRP3 activation. However, the protein kinase that mediates NLRP3 S5 phosphorylation is unknown. In this study, we show that AKT associates with NLRP3 and phosphorylates it on S5, limiting NLRP3 oligomerization. This phosphorylation event also stabilizes NLRP3 by reducing its ubiquitination on lysine 496, which inhibits its proteasome-mediated degradation by the E3 ligase Trim31. Pharmacologic manipulation of AKT kinase activity reciprocally modulates NLRP3 inflammasome-mediated IL-1ß production. Inhibition of AKT reduced IL-1ß production following the i.p. injection of LPS into mice. We propose that AKT, Trim31, and PP2A together modulate NLRP3 protein levels and the tendency to oligomerize, thereby setting a tightly regulated threshold for NLRP3 activation.

A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model.

BACKGROUND: Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy. METHODS: NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated. RESULTS: Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice. CONCLUSIONS: The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy.

Accuracy and primary stability of tapered or straight implants placed into fresh extraction socket using dynamic navigation: a randomized controlled clinical trial.

OBJECTIVES: To compare the accuracy and primary stability of tapered and straight implants undergoing immediate implant placement with dynamic navigation. MATERIALS AND METHODS: Patients with compromised anterior teeth in maxilla were recruited and allocated randomly into (1) tapered implant group (TI group) and (2) straight implant group (SI group). Implants were inserted into fresh sockets with dynamic navigation. Three-dimensional platform deviation, apex deviation, angular deviation, insertion torque value (ITV) and implant stability quotient (ISQ) were recorded. RESULTS: Twenty patients with 20 implants were included. The overall platform, apex, and angular deviation were 0.87 ± 0.35 mm, 0.81 ± 0.34 mm, and 2.40 ± 1.31°, respectively. The accuracy was 0.86 ± 0.26 mm, 0.76 ± 0.33 mm, and 2.49 ± 1.54° for TI, and 0.89 ± 0.44 mm, 0.88 ± 0.36 mm, and 2.31 ± 1.01° for SI, with no significant difference (p = 0.85, 0.45, 0.76). Sagittal root position classification (SRP) class I may obtain greater error in numerical values in straight implants (0.97 ± 0.47 mm vs. 0.6 ± 0.16 mm, 0.92 ± 0.36 mm vs. 0.73 ± 0.36 mm, 2.48 ± 1.19° vs. 1.71 ± 0.14°). The overall ISQ was 60.74. ISQ was 60.48 for TI and 60.96 for SI, with no significant difference. Acceptable ITV (> 15 Ncm) was achieved in most of the included patients (SI 7/10, TI 9/10). CONCLUSIONS: High accuracy and primary stability of immediate implant placement could be achieved both in tapered and straight implants with dynamic navigation systems. CLINICAL RELEVANCE: Tapered and straight implants did not reach a consensus on which was better in immediate implant regarding to accuracy and primary stability. Our study demonstrated implant macrodesign did not affect accuracy and primary stability in immediate implant using dynamic navigation.

Copper-Catalyzed Asymmetric Diyne Cyclization via [1,2]-Stevens-Type Rearrangement for the Synthesis of Chiral Chromeno[3,4-c]pyrroles.

Here, we report a copper-catalyzed asymmetric cascade cyclization/[1,2]-Stevens-type rearrangement via a non-diazo approach, leading to the practical and atom-economic assembly of various valuable chiral chromeno[3,4-c]pyrroles bearing a quaternary carbon stereocenter in generally moderate to good yields with wide substrate scope and excellent enantioselectivities (up to 99 % ee). Importantly, this protocol not only represents the first example of catalytic asymmetric [1,2]-Stevens-type rearrangement based on alkynes but also constitutes the first asymmetric formal carbene insertion into the Si-O bond.

Clinical, radiographic and economic evaluation of short-6-mm implants and longer implants combined with osteotome sinus floor elevation in moderately atrophic maxillae: A 3-year randomized clinical trial.

AIM: To compare the 3-year clinical, radiographic and economic outcomes of short-6-mm implants and longer implants combined with osteotome sinus floor elevation (OSFE) in the posterior maxilla. MATERIAL AND METHODS: This study enrolled 225 patients (225 implants with diameter of 4.1 mm and 4.8 mm) with a posterior maxillary residual bone height (RBH) of 6-8 mm. Patients were randomly divided into three groups: Group 1 (6 mm implants alone), Group 2 (8 mm implants + OSFE) and Group 3 (10 mm implants + OSFE). The following outcomes were recorded at 1 and 3-year examinations: implant survival, probing pocket depth (PPD), bleeding on probing (BOP), modified plaque index (mPI), marginal bone loss (MBL), biological and technical complications, complication-free survival and treatment costs. RESULTS: At the 3-year follow-up, 199 patients (Group 1: 67; Group 2: 62; Group 3: 70) were re-examined. Implant survival rates were 91.80%, 97.08% and 100.00% in groups 1, 2 and 3. Implant survival rate in Group 1 was significantly lower than that in Group 3 (p = 0.029). A multivariate Cox model showed that the short-6-mm implants with wide diameter had a protective effect on implant survival (hazard ratio: 0.59, p = 0.001). No significant differences in BOP%, PPD, mPI, MBL and complication-free survival rate were found among the three groups. The average costs of retreatment were 8.31%, 1.96% and 0.56% of the total costs in groups 1, 2 and 3. The cost to avoid a 1% increase in implant loss associated with 6-mm implants over a 3-year period was 369 CNY (56 USD) using a 10-mm implant with OSFE and 484 CNY (74 USD) using an 8-mm implant with OSFE. CONCLUSION: In the moderately atrophic posterior maxillae, the three treatments showed acceptable clinical, radiographic and economic outcomes with up to 3-year follow-up. 10-mm implants combined with OSFE showed more favourable implant survival and fewer maintenance costs in comparison with short-6-mm implants, which were less expensive.

Application of preoperative ultrasound features combined with clinical factors in predicting HER2-positive subtype (non-luminal) breast cancer.

BACKGROUND: Human epidermal growth factor receptor2+ subtype breast cancer has a high degree of malignancy and a poor prognosis. The aim of this study is to develop a prediction model for the human epidermal growth factor receptor2+ subtype (non-luminal) of breast cancer based on the clinical and ultrasound features related with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor2. METHODS: We collected clinical data and reviewed preoperative ultrasound images of enrolled breast cancers from September 2017 to August 2020. We divided the data into in three groups as follows. Group I: estrogen receptor ± , Group II: progesterone receptor ± and Group III: human epidermal growth factor receptor2 ± . Univariate and multivariate logistic regression analyses were used to analyze the clinical and ultrasound features related with biomarkers among these groups. A model to predict human epidermal growth factor receptor2+ subtype was then developed based on the results of multivariate regression analyses, and the efficacy was evaluated using the area under receiver operating characteristic curve, accuracy, sensitivity, specificity. RESULTS: The human epidermal growth factor receptor2+ subtype accounted for 138 cases (11.8%) in the training set and 51 cases (10.1%) in the test set. In the multivariate regression analysis, age ≤ 50 years was an independent predictor of progesterone receptor + (p = 0.007), and posterior enhancement was a negative predictor of progesterone receptor + (p = 0.013) in Group II; palpable axillary lymph node, round, irregular shape and calcifications were independent predictors of the positivity for human epidermal growth factor receptor-2 in Group III (p = 0.001, p = 0.007, p = 0.010, p < 0.001, respectively). In Group I, shape was the only factor related to estrogen receptor status in the univariate analysis (p < 0.05). The area under receiver operating characteristic curve, accuracy, sensitivity, specificity of the model to predict human epidermal growth factor receptor2+ subtype breast cancer was 0.697, 60.14%, 72.46%, 58.49% and 0.725, 72.06%, 64.71%, 72.89% in the training and test sets, respectively. CONCLUSIONS: Our study established a model to predict the human epidermal growth factor receptor2-positive subtype with moderate performance. And the results demonstrated that clinical and ultrasound features were significantly associated with biomarkers.

Design and Implementation of a Novel Interferometric Microwave Radiometer for Human Body Temperature Measurement.

In this paper, the key technology of interferometric microwave thermometer is studied, the research can be applied to the temperature measurement of human body and subcutaneous tissue. This paper proposes a hardware architecture of interferometric microwave thermometer with 2 GHz bandwidth, in which the phase shifter is used to correct phase error and the quadrature demodulator is used to realize autocorrelation detection function. The results show that when input power is 7 dBm, the detection sensitivity can reach 176.54 mV/dBm and the temperature resolution of the microwave radiometer can reach 0.4 K. Correction algorithm is designed to improve the accuracy of temperature measurement. After correction, the phase error is reduced from 40° to 1.4° and when temperature changes 0.1 °C, the voltage value changes obviously. Step-by-step calibration and overall calibration are used to calibrate the device. Inversion algorithm can determine the relationship between physical temperature and output voltage. The mean square error of water temperature inversion by multiple linear regression algorithm is 0.607 and that of BP neural network algorithm is 0.334. The inversion accuracy can be improved by reducing the temperature range. Our work provides a promising realization of accurate, rapid and non-contact detection device of human body temperature.

Long-term outcomes of osteotome sinus floor elevation without grafting in severely atrophic maxilla: A 10-year prospective study.

OBJECTIVE: The aim of the present study was to report 10-year results of osteotome sinus floor elevation (OSFE) without grafting severely atrophic maxilla (residual bone height ≤4 mm). MATERIALS AND METHODS: Patients undergoing OSFE without grafting and implant placement were included for 10-year examinations. Implant survival, complication-free survival, modified bleeding index (mBI), modified plaque index (mPI), pocket probing depth (PPD), peri-implant marginal bone loss (MBL), endo-sinus bone gain (ESBG) and mean cost of recurrence were evaluated. RESULTS: Overall, 23 patients with 35 implants attended 10-year examination. Cemented implant crowns or implant-supported fixed dental prostheses were delivered to the patients. Kaplan-Meier implant survival was 89.2% at implant level and 84.1% at patient level. Complication-free survival was 26.0% at patient level and 37.0% at implant level. The average complication-free survival time was 74.6 months (95% CI: 63.2-86.0 months) at implant level and 69.1 months (95% CI: 54.8-83.4 months) at patient level. The mBI, mPI, PPD, MBL and ESBG at 10-year follow-up were 0.91 ± 0.58, 0.48 ± 0.51, 2.94 ± 0.79 mm, 1.63 ± 0.83 mm and 2.72 ± 0.51 mm, respectively. The cost of managing recurrence was 43.6% of the initial cost of treatment. CONCLUSION: The results of the present study indicate that OSFE without grafting is a reliable treatment option in severely atrophic maxilla. Acceptable survival rate, stable MBL and ESBG could be achieved within 10 years. Low complication-free survival and high costs of recurrence management need to be considered.

Long-term outcomes of osteotome sinus floor elevation with or without bone grafting: The 10-year results of a randomized controlled trial.

AIMS: To assess the long-term clinical and radiographic results of implants placed using osteotome sinus floor elevation (OSFE) with or without bone grafting. MATERIALS AND METHODS: Forty-five patients were randomly assigned into two groups: Group 1 (OSFE with deproteinized bovine bone mineral) and Group 2 (OSFE without grafting). The patients were recalled at 1, 3, 5 and 10 years after surgery. The implant survival, endo-sinus bone gain (ESBG), marginal bone loss (MBL), peri-implant bone height (PBH, distance from the most coronal level to the most apical level of bone-to-implant contact), prosthesis survival and hardware complications, and peri-implant soft tissue conditions were assessed. RESULTS: Forty patients attended the 10-year examination. Mean residual bone height was 4.58 ± 1.28 mm. The 10-year cumulative survival rate was 90.7% for Group 1 and 95.0% for Group 2. The PBH was 5.89 ± 1.24 mm for Group 1 and 5.74 ± 1.43 mm for Group 2 at 10 years. The ESBG of both groups remained stable after 3 years. Two-thirds of the implants were free of hardware complications. No significant differences in MBL and peri-implant tissue parameters were found. CONCLUSION: OSFE with or without grafting both yielded predictable clinical outcomes with similar PBH (ClinicalTrials.gov. NCT01619956).

Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses.

Moringa oleifera Lam. (MO) is called the "Miracle Tree" because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

Short versus longer implants with osteotome sinus floor elevation for moderately atrophic posterior maxillae: A 1-year randomized clinical trial.

PURPOSE: To compare the clinical, radiographic outcomes and patient satisfaction of short-6-mm implants and longer implants combined with osteotome sinus floor elevation (OSFE). MATERIALS AND METHODS: Two hundred and twenty-five patients with 225 implants were included and randomly assigned into three groups (each group: 75 implants) using randomizing table method: group 6 mm (6 mm implants alone), group 8 mm + O (8 mm implants + OSFE) and group 10 mm + O (10 mm implants + OSFE). Outcomes measures were as follows: implant survival, complication, resonance frequency analysis measurement, surgical time, bleeding on probing (BOP), pocket probing depth (PPD), modified plaque index (mPI), marginal bone loss (MBL) and patient satisfaction. RESULTS: The dropout rate was 3.6% at 1 year. Implant survival rates were 96%, 100% and 100% in group 6 mm, group 8 mm + O and group 10 mm + O, respectively. In group 6 mm, the survival rates of implants with diameter of 4.1 mm were 90% (27/30), while the survival rates of implants with diameter of 4.8 mm were 100% (42/42). The surgical time (min) in group 6 mm was significantly shorter than those in group 8 mm + O and group 10 mm + O (13.6 ± 2.2, 19.4 ± 3.7 and 18.3 ± 4.3, respectively, p = 0.03). No significant differences in ISQ values, BOP, PPD, mPI and MBL were found among three groups. Significant higher value of intra-operative discomfort was found in group 6 mm (p = 0.02). CONCLUSION: All treatment options provided acceptable clinical and radiographic results up to 1 year after loading. The current 1-year results must be confirmed by longer follow-ups of at least 5 years.

A novel semiautomatic segmentation protocol to evaluate guided bone regeneration outcomes: A pilot randomized, controlled clinical trial.

OBJECTIVES: The aims of this study were to (a) present a novel morphological contour interpolation (MCI) algorithm based method to evaluate grafted bone alterations following guided bone regeneration (GBR), (b) compare clinical and radiological outcomes of GBR with two different collagen membranes. MATERIALS AND METHODS: The data were retrieved from an ongoing randomized controlled trial. Patients were randomly allocated into two groups: (a) control group (CG): Bio-Gide (b) test group (TG): bovine dermis-derived collagen membrane. Cone beam computed tomography examinations were performed 1 week (T0) and 6 months after surgery (T1). PES/WES at T1, grafted bone volume and density changes from T0 to T1 were recorded. RESULTS: Thirty-six patients (16/20 in test/control group, respectively) were enrolled in the present study. Excellent inter-observer reliability (ICC ≥ 0.97) was revealed for repeated measurements using this method. Significant volumetric reduction of grafted bone were found in both groups (test group: from 0.60 to 0.39 cm3 , p < 0.01; control group: from 0.54 to 0.31 cm3 , p < 0.01). Mean bone density (gray-scale values) significantly increased from 305.12 to 456.69 in CG (p < 0.01). In TG, it slightly increased from 304.75 to 393.27 (p = 0.25). The mean PES/WES values were 13.84 (6.62/7.22) and 13.90 (6.70/7.20) for TG and CG, respectively. As for inter-group comparison, no significant differences of grafted bone volume change, density change and PES/WES were found between two groups. CONCLUSION: Within the limitations of this study, the novel MCI-based method is a reproducible tool to segment and visualize changes of grafted bone in 3D. Furthermore, both collagen membranes could be used as a barrier membrane for GBR in humans.

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.

Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.