Enrichment analysis indicated the importance of the glucose level and pathogen attacks to growth performance in the "iron prawn." Finally, a comparison of the molt performance showed that the length of the molt cycle in the "iron prawn" was comparable to normal prawns with the same size, but the specific growth was **** lower in the "iron prawn." This result suggested that lower body weight gain per molt cycle should be responsible for growth retardation in the "iron prawn," but not in the longer molt cycle. The results in this study provided fundamental information about the mechanism behind growth retardation in M. rosenbergii. Functionally graded NiTi orthodontic archwire was tested to assess the evolution of the actuation force as a function of the temperature. Varying actuation forces on the same orthodontic wire allow the optimization of repositioning of the different types of teeth, according its radicular support. The wire was separated into three segments Incisive, Premolar and Molar. The functionally graded NiTi orthodontic archwire segments have distinct structural and mechanical behavior as confirmed by differential scanning calorimetry, synchrotron-based X-ray diffraction, and thermomechanical analysis. The mechanical behavior was analyzed by three-point bending tests at four different temperatures (5, 20, 25 and 37 °C). In parallel, three-point bending tests were performed by TMA analysis in a temperature range from 5 °C (from cold water) to 40 °C (hot meal). This study showed the comparison of the different segments on the same archwire, providing a better understanding of the behavior of these functionally graded materials. PURPOSE The purpose of this study was to analyze mechanical behaviors of a topologically optimized and 3D-printed mandibular bone block with polyetherketoneketone (PEKK) for surgical mandibular reconstruction. MATERIALS AND METHODS 3D virtual mandibular models were reconstructed from cone beam computed tomography images. A proposed mandibular resection of the mandibular body (40 mm anterior-posteriorly) was segmented. Internal structure of the resected bone was designed with topological optimization. Dental implants and implant-supported crowns were integrated into the design. A second 3D virtual model was created with the same size and location of the defect but was reconstructed with a fibular graft and implant-supported crowns. The biomechanical behaviors of the two models were compared by finite element method (FEM) under the same boundary constraints and three loading locations, namely, central incisors, lower left and right side first molar areas. RESULTS The FEM results showed the maximum stresses and displacements of the topology optimized model were **** lower than those of the model with fibular bone graft. The highest stress of the optimized mandibular model was located on the lower edge of the posterior border of bone analog, and fixation screws. The maximum displacement occurred at the lower edge of the proximal mandibular stump or the lower edge of the distal mandibular body on the contralateral site. Under the same three loading locations, the maximum stress of the optimized model significantly decreased by 67.9%, 71.9% and 68.6% compared to the fibular graft model. CONCLUSIONS The 3D printed bone analog with topological optimization is patient-specific and has advantages over the conventional fibular bone graft for surgical mandibular reconstruction. The optimized PEKK bone analog model creates more normal stress-strain trajectories than the fibular graft model and likely provides better functional and cosmetic outcomes. BACKGROUND Macrophages (Mф) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like Mф are thought to be important in asthma pathogenesis, and M1-like in anti-infective immunity, however their roles in virus-induced asthma exacerbations are unknown. Our objectives were (i) to assess polarised Mф phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess Mф phenotypes in healthy subjects and people with asthma before and during experimental RV infection in vivo. METHODS We investigated characteristics of polarized/unpolarized human monocyte-derived Mф (MDM, from 3-6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) Mф in experimental RV-induced asthma exacerbation in 7 healthy controls and 17 (at baseline) and 18 (at day 4 post infection) people with asthma. FINDINGS We observed in vitro M1-like but not M2-like or unpolarized MDM are potent producers of type I and III interferons in response to RV infection (P less then 0.0001), and M1-liant 260895, RSF grant 19-15-00272, Megagrant No 14.W03.31.0024. BACKGROUND Cystic echinococcosis (CE), a condition caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu stricto, is a globally distributed zoonotic disease. Current treatment options for CE are limited, and an effective and safe anti-echinococcal drug is urgently required. METHODS Drug repurposing strategy was employed to identify new therapeutic agents against echinococcal cysts. An in vitro protoscolicidal assay along with in vivo murine models was applied in the drug screening. A microinjection procedure was employed to mimic the clinical PAIR (puncture, aspiration, injection and reaspiration) technique to evaluate the potential application of the candidate drug in clinical practice. FINDINGS We repurposed pyronaridine, an approved antimalarial drug, for the treatment of CE. Following a three-dose intraperitoneal regimen (57 mg/kg, q.d. for 3 days), pyronaridine caused 100% cyst mortality. Oral administration of pyronaridine at 57 mg/kg, q.d. for 30 days significantly reduced the parasitic burden in the pre-infected **** compared with albendazole group (p less then 0.001). https://www.selleckchem.com/products/mevastatin.html Using a microinjection of drug into cysts, pyronaridine (200 μM) showed highly effective in term of inhibition of cyst growth (p less then 0.05, compared with saline group). Pharmacokinetic analysis revealed that pyronaridine was highly distributed in the liver and lungs, the most affected organs of CE. Function analysis showed that pyronaridine inhibited the activity of topoisomerase I (IC50 = 209.7 ± 1.1 μM). In addition, classical apoptotic hallmarks, including DNA fragmentation and caspase activation, were triggered. INTERPRETATION Given its approved clinical safety, the repurposing of pyronaridine offers a rapidly translational option for treating CE including PAIR. FUND National Natural Science Foundation of China and International Cooperation Project of the Qinghai Science and Technology Department.
Enrichment analysis indicated the importance of the glucose level and pathogen attacks to growth performance in the "iron prawn." Finally, a comparison of the molt performance showed that the length of the molt cycle in the "iron prawn" was comparable to normal prawns with the same size, but the specific growth was much lower in the "iron prawn." This result suggested that lower body weight gain per molt cycle should be responsible for growth retardation in the "iron prawn," but not in the longer molt cycle. The results in this study provided fundamental information about the mechanism behind growth retardation in M. rosenbergii. Functionally graded NiTi orthodontic archwire was tested to assess the evolution of the actuation force as a function of the temperature. Varying actuation forces on the same orthodontic wire allow the optimization of repositioning of the different types of teeth, according its radicular support. The wire was separated into three segments Incisive, Premolar and Molar. The functionally graded NiTi orthodontic archwire segments have distinct structural and mechanical behavior as confirmed by differential scanning calorimetry, synchrotron-based X-ray diffraction, and thermomechanical analysis. The mechanical behavior was analyzed by three-point bending tests at four different temperatures (5, 20, 25 and 37 °C). In parallel, three-point bending tests were performed by TMA analysis in a temperature range from 5 °C (from cold water) to 40 °C (hot meal). This study showed the comparison of the different segments on the same archwire, providing a better understanding of the behavior of these functionally graded materials. PURPOSE The purpose of this study was to analyze mechanical behaviors of a topologically optimized and 3D-printed mandibular bone block with polyetherketoneketone (PEKK) for surgical mandibular reconstruction. MATERIALS AND METHODS 3D virtual mandibular models were reconstructed from cone beam computed tomography images. A proposed mandibular resection of the mandibular body (40 mm anterior-posteriorly) was segmented. Internal structure of the resected bone was designed with topological optimization. Dental implants and implant-supported crowns were integrated into the design. A second 3D virtual model was created with the same size and location of the defect but was reconstructed with a fibular graft and implant-supported crowns. The biomechanical behaviors of the two models were compared by finite element method (FEM) under the same boundary constraints and three loading locations, namely, central incisors, lower left and right side first molar areas. RESULTS The FEM results showed the maximum stresses and displacements of the topology optimized model were much lower than those of the model with fibular bone graft. The highest stress of the optimized mandibular model was located on the lower edge of the posterior border of bone analog, and fixation screws. The maximum displacement occurred at the lower edge of the proximal mandibular stump or the lower edge of the distal mandibular body on the contralateral site. Under the same three loading locations, the maximum stress of the optimized model significantly decreased by 67.9%, 71.9% and 68.6% compared to the fibular graft model. CONCLUSIONS The 3D printed bone analog with topological optimization is patient-specific and has advantages over the conventional fibular bone graft for surgical mandibular reconstruction. The optimized PEKK bone analog model creates more normal stress-strain trajectories than the fibular graft model and likely provides better functional and cosmetic outcomes. BACKGROUND Macrophages (Mф) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like Mф are thought to be important in asthma pathogenesis, and M1-like in anti-infective immunity, however their roles in virus-induced asthma exacerbations are unknown. Our objectives were (i) to assess polarised Mф phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess Mф phenotypes in healthy subjects and people with asthma before and during experimental RV infection in vivo. METHODS We investigated characteristics of polarized/unpolarized human monocyte-derived Mф (MDM, from 3-6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) Mф in experimental RV-induced asthma exacerbation in 7 healthy controls and 17 (at baseline) and 18 (at day 4 post infection) people with asthma. FINDINGS We observed in vitro M1-like but not M2-like or unpolarized MDM are potent producers of type I and III interferons in response to RV infection (P less then 0.0001), and M1-liant 260895, RSF grant 19-15-00272, Megagrant No 14.W03.31.0024. BACKGROUND Cystic echinococcosis (CE), a condition caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu stricto, is a globally distributed zoonotic disease. Current treatment options for CE are limited, and an effective and safe anti-echinococcal drug is urgently required. METHODS Drug repurposing strategy was employed to identify new therapeutic agents against echinococcal cysts. An in vitro protoscolicidal assay along with in vivo murine models was applied in the drug screening. A microinjection procedure was employed to mimic the clinical PAIR (puncture, aspiration, injection and reaspiration) technique to evaluate the potential application of the candidate drug in clinical practice. FINDINGS We repurposed pyronaridine, an approved antimalarial drug, for the treatment of CE. Following a three-dose intraperitoneal regimen (57 mg/kg, q.d. for 3 days), pyronaridine caused 100% cyst mortality. Oral administration of pyronaridine at 57 mg/kg, q.d. for 30 days significantly reduced the parasitic burden in the pre-infected mice compared with albendazole group (p less then 0.001). https://www.selleckchem.com/products/mevastatin.html Using a microinjection of drug into cysts, pyronaridine (200 μM) showed highly effective in term of inhibition of cyst growth (p less then 0.05, compared with saline group). Pharmacokinetic analysis revealed that pyronaridine was highly distributed in the liver and lungs, the most affected organs of CE. Function analysis showed that pyronaridine inhibited the activity of topoisomerase I (IC50 = 209.7 ± 1.1 μM). In addition, classical apoptotic hallmarks, including DNA fragmentation and caspase activation, were triggered. INTERPRETATION Given its approved clinical safety, the repurposing of pyronaridine offers a rapidly translational option for treating CE including PAIR. FUND National Natural Science Foundation of China and International Cooperation Project of the Qinghai Science and Technology Department.
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