Microstructure reconstruction of 2D/3D random materials via diffusion-based deep generative models.

Microstructure reconstruction serves as a crucial foundation for establishing process-structure-property (PSP) relationship in material design. Confronting the limitations of variational autoencoder and generative adversarial network within generative models, this study adopted the denoising diffusion probabilistic model (DDPM) to learn the probability distribution of high-dimensional raw data and successfully reconstructed the microstructures of various composite materials, such as inclusion materials, spinodal decomposition materials, chessboard materials, fractal noise materials, and so on. The quality of generated microstructure was evaluated using quantitative measures like spatial correlation functions and Fourier descriptor. On this basis, this study also achieved the regulation of microstructure randomness and the generation of gradient materials through continuous interpolation in latent space using denoising diffusion implicit model (DDIM). Furthermore, the two-dimensional microstructure reconstruction was extended to three-dimensional framework and integrated permeability as a feature encoding embedding. This enables the conditional generation of three-dimensional microstructures for random porous materials within a defined permeability range. The permeabilities of these generated microstructures were further validated through the application of the lattice Boltzmann method. The above methods provide new ideas and references for material reverse design.

Gaussian random field-based characterization and reconstruction of cancellous bone microstructure considering the constraint of correlation structure.

The macro scale physical properties of cancellous bone materials are governed by the microstructural features, which is of great significance for the multi-scale research of cancellous bone and the inverse design of bone-mimicking materials. Therefore, it is essential to characterize the natural cancellous bone samples, and reconstruct the microstructures with the biomimetic osteointegration and mechanical properties. In this research, a novel approach for the characterization and reconstruction of cancellous bone was proposed, based on the medical image analysis and anisotropic three-dimensional Gaussian random field (GRF). The geometric similarity, i.e. the interface curvature distribution (ISD), was meticulously studied, which is important to the osteointegration ability. And the mechanical properties were validated by the stress-strain curves under the large compressive strain simulated by the smoothed particle hydrodynamic (SPH) method. In addition, the effects of the generation parameters of GRF-based biomimetic microstructures on the apparent properties were analyzed. The ISD results demonstrated that both GRF and micro-CT groups had the similar columnar morphological properties, while the latter had more hyperbolic features. And it was found that the GRF-based biomimetic microstructures and the natural bone samples based on micro-CT (MCT) had the similar failure mode. The concordance correlation coefficient between MCT and GRF pairs was 0.8685, with a Pearson ρ value of 0.8804, and significance level p<0.0001. The Bland-Altman LoA was 0.1647 MPa with 95 % (1.96SD) lower and upper bound value between -0.2892 and 0.6185 MPa. The two groups had almost the same elastic modulus with the mean absolute percentage error (MAPE) of 7.84 %. While the yield stress and total conversion energy of the GRF-based samples were lower than those of the natural bone samples, and the MAPE were 16.99 % and 16.27 %, respectively. Although it meant the lower structural efficiency, the huge design space of this approach and advanced 3D printing technology can provide great potential for the design of orthopedic implants.

Exploring the thalamus: a crucial hub for brain function and communication in patients with bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is an eating disorder characterized by recurrent binge eating and compensatory behaviors. The thalamus plays a crucial role in the neural circuitry related to eating behavior and needs to be further explored in BN. METHODS: In this study, 49 BN patients and 44 healthy controls (HCs) were recruited. We applied the fractional amplitude of low-frequency fluctuation to investigate regional brain activity in the thalamus and functional connectivity (FC) to examine the synchronization of activity between thalamic subregions and other brain regions in both groups. All results underwent false discovery rate (p < 0.05, FDR correction) correction. Pearson correlation analysis was performed to assess the relationship between the patients' abnormal clinical performance and the thalamic alterations (p < 0.05, FDR correction). RESULTS: We found no significant differences in neural activity between BN patients and HCs in the sixteen thalamic subregions. However, compared to the HCs, the individuals with BN showed decreased FC between the thalamic subregions and several regions, including the bilateral prefrontal cortex, right inferior parietal lobule, right supplementary motor area, right insula, cingulate gyrus and vermis. Additionally, BN patients showed increased FC between the thalamic subregions and visual association regions, primary sensorimotor cortex, and left cerebellum. These altered FC patterns in the thalamus were found to be correlated with clinical variables (the frequency of binge eating/purging per week and external eating behavior scale scores) in the BN group. All results have passed FDR correction. CONCLUSIONS: Our study provides evidence that there is disrupted FC between thalamic subregions and other brain regions in BN patients during resting state. These regions are primarily located within the frontoparietal network, default mode network, somatosensory, and visual network. These findings elucidate the neural activity characteristics underlying BN and suggest that thalamic subregions have potential as targets for future neuromodulation interventions.

The high recurrence rate of bulimia nervosa (BN) poses a clinical challenge, and thus, it is crucial to improve the characterization and identification of brain functional abnormalities as direct targets for novel therapies. To investigate the neural circuitry associated with BN, the thalamus is a critical node since it serves as a higher-order relay point in the cortico-thalamo-cortical information pathway. Our findings reveal that altered functional connectivity (FC) between thalamic nuclei and other brain regions is evident throughout the whole brain, particularly within the frontoparietal network, default mode network, somatosensory, and visual network. These changes in FC are significantly associated with disordered eating behavior and the severity of illness in BN patients. Therefore, these findings help identify the neural mechanisms underlying disordered eating behavior and BN severity and suggest potential targets for future neuromodulation interventions.

Astragalus polysaccharide restores insulin secretion impaired by lipopolysaccharides through the protein kinase B /mammalian target of rapamycin/glucose transporter 2 pathway.

BACKGROUND: Lipopolysaccharide (LPS)-induced dysfunction of pancreatic ß-cells leads to impaired insulin (INS) secretion. Astragalus polysaccharide (APS) is a bioactive heteropolysaccharide extracted from Astragalus membranaceus and is a popular Chinese herbal medicine. This study aimed to elucidate the mechanisms by which APS affects INS secretion from ß-cells under LPS stress. METHODS: Rat insulinoma (INS-1) cells were treated with LPS at a low, medium, or high concentration of APS. Glucose-stimulated insulin secretion (GSIS) was evaluated using an enzyme-linked immunosorbent assay (ELISA). Transcriptome sequencing was used to assess genome-wide gene expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the signaling pathways affected by APS. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to evaluate the gene expression of glucose transporter 2 (GLUT2), glucokinase (GCK), pancreatic duodenal homeobox-1 (PDX-1), and INS. Western blot analysis was used to detect the protein expression of phosphorylated protein kinase B (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), total mTOR (t-mTOR), and GLUT2. RESULTS: LPS decreased GLUT2, GCK, PDX-1, and INS expression and reduced GSIS. These LPS-induced decreases in gene expression and GSIS were restored by APS treatment. In addition, transcriptome sequencing in combination with KEGG enrichment analysis revealed changes in the INS signaling pathway following APS treatment. LPS decreased p-Akt and p-mTOR expression, which was restored by APS treatment. The restorative effects of APS on GSIS as well as on the expression of GLUT2, GCK, PDX-1, and INS were abolished by treatment with the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin (RPM). CONCLUSIONS: APS restored GSIS in LPS-stimulated pancreatic ß-cells by activating the Akt/mTOR/GLUT2 signaling pathway.

Simultaneously Achieving Large Piezoelectricity and Low Dielectric Loss in High-Temperature BiScO3-PbTiO3-Based Ceramics.

High-temperature piezoelectric materials are pivotal to technology applications fields including defense, aerospace, nuclear energy, and oil well logging. However, the acquisition of excellent piezoelectric properties is usually at the cost of temperature stability (reduced Curie temperature and increased high-temperature dielectric loss), which hinders the application of piezoelectric ceramics in harsh environments. In this study, we investigated the effect of Nb5+ donor and Mn2+/3+ acceptor doping on the dielectric and piezoelectric properties of BiScO3-PbTiO3 (BS-PT)-based ceramics. In contrast to the acceptor doping, it was found that the donor doping not only enhances the piezoelectric properties but also effectively suppresses the dielectric loss at a high temperature by reducing the oxygen vacancy concentration. Eventually, we simultaneously attained an excellent piezoelectric performance (d33 is 553 pC/N at room temperature and 1528 pC/N at 400 °C, respectively) and a low dielectric loss (less than 2% in the temperature range of 150-300 °C) but still with a high Curie temperature (TC ∼ 445 °C) in Nb5+-doped BS-PT ceramics. Furthermore, different in situ measurements were used to demonstrate the remarkable temperature stability up to a high depolarization temperature of ∼400 °C. This work represents significant progress in high-temperature piezoelectric materials and provides a guideline for future efforts on enhancing the piezoelectricity and suppressing the dielectric loss at high temperature.

Characteristics of white matter alterations along fibres in patients with bulimia nervosa: A combined voxelwise and tractography study.

Accumulating evidence supports the hypothesis that white matter (WM) abnormalities are involved in the pathophysiology of bulimia nervosa (BN); however, findings from in vivo neuroimaging studies have been inconsistent. We aimed to investigate the possible brain WM alterations, including WM volume and microstructure, in patients with BN. We recruited 43 BN patients and 31 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging. Differences in WM volume and microstructure were evaluated using voxel-based morphometry, tract-based spatial statistics, and automated fibre quantification analysis. Compared with HCs, BN patients showed significantly decreased fractional anisotropy in the middle part of the corpus callosum (nodes 31-32) and increased mean diffusivity in the right cranial nerve V (CN V) (nodes 27-33 and nodes 55-88) and vertical occipital fasciculus (VOF) (nodes 58-85). Moreover, we found decreased axial diffusivity in the right inferior fronto-occipital fasciculus (node 67) and increased radial diffusivity in the CN V (nodes 22-34 and nodes 52-89) and left VOF (nodes 60-66 and nodes 81-85). Meanwhile, WM microstructural changes were correlated with patients' clinical manifestations. We did not find any significant differences in WM volume and the main WM fibre bundle properties between BN patients and HCs. Taken together, these findings provide that BN shows significant brain WM reorganization, but primarily in microstructure (part of WM fibre bundle), which is not sufficient to cause changes in WM volume. The automated fibre quantification analysis could be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.

The impact of perceived teacher support on Chinese junior high school students' academic self-efficacy: The mediating roles of achievement goals and academic emotions.

Introduction: Teacher support is an important external factor that influences students academic self-efficacy, however, the mechanisms of the two factors are not yet fully explored. The purpose of this study was to investigate whether achievement goals and academic emotions could play a chain mediating role between perceived teacher support and academic self-efficacy. Methods: The study sample was made up of 1,074 Chinese junior high school students, and three structural equation models were constructed using data collected from on questionnaires. Results: The findings suggest that achievement goals and academic emotions can mediate the relationship between perceived teacher support and academic selfefficacy. Further analysis revealed that achievement goals and academic emotions may play a chain mediating role between perceived teacher support and academic selfefficacy. Discussion: These findings provide reference points for further refinement of the mechanism of the role of perceived teacher support on academic self-efficacy. They also serve to remind the teacher on the front line to focus on how to provide adequate teacher support to students in the context of online education, especially with regard to students academic emotions.

Safety and efficacy of sofosbuvir-velpatasvir: A meta-analysis.

INTRODUCTION: The sofosbuvir-velpatasvir single-tablet regimen (Epclusa) is a newly FDA-approved inhibitor of hepatitis C virus (HCV). This meta-analysis aimed to investigate the safety and efficacy of velpatasvir-sofosbuvir in the treatment of chronic HCV infection. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, EMBASE and Web of Science was conducted. Data from eligible studies were pooled in a fixed-effect meta-analysis model, using Open-Meta and RevMan software's. RESULTS: Pooled data showed that velpatasvir-sofosbuvir achieved sustained virological response (SVR12) rates of 94.2% (95% CI 90.7-97.7%, P < .001) in 1277 patients. The addition of ribavirin did not significantly increase the SVR12 (RR = 1.03, 95%CI [0.95, 1.11]) in HCV genotype-1 patients and the SVR12 (RR = 1.09, 95%CI [0.86, 1.38]) in HCV genotype-2 patients. However, adding ribavirin significantly increased SVR12 (RR = 1.13, 95% CI [1.04, 1.23]) in genotype-3 patients. CONCLUSION: In conclusion, the 12-week regimen of sofosbuvir-velpatasvir was highly effective in HCV patients. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates.

Rapid Treatment with Intramuscular Magnesium Sulfate During Cardiopulmonary Resuscitation Does Not Provide Neuroprotection Following Cardiac Arrest.

Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective compound which protects neurons from ischemic injury by reducing neuronal calcium overload via NMDA receptor modulation and preventing calcium-induced mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO4 during CPR has the potential to target these mechanisms within an early therapeutic window. We hypothesize that IM MgSO4 administrated during CPR could achieve therapeutic serum magnesium levels within 15 min after ROSC and improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Male Long Evans rats were subjected to 8-min asphyxial cardiac arrest and block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO4 IM at the onset of CPR. Serum magnesium concentrations increased rapidly with IM delivery during CPR, achieving twofold to fourfold increase by 15 min after ROSC in all magnesium dose groups. Rats subjected to cardiac arrest or sham surgery were block randomized to treatment groups for assessment of neurological outcomes. We found that IM MgSO4 during CPR had no effect on ROSC rate (p > 0.05). IM MgSO4 treatment had no statistically significant effect on 10-day survival with good neurologic function or hippocampal CA1 pyramidal neuron survival compared to placebo treatment. In conclusion, a single dose IM MgSO4 during CPR achieves up to fourfold baseline serum magnesium levels within 15 min after ROSC; however, this treatment strategy did not improve survival, recovery of neurologic function, or neuron survival. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.

Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis.

OBJECTIVE: To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms. METHODS: A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. RESULTS: FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation. CONCLUSION: BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.

Traditional Chinese medicine formula Xiaoqinglong decoction for cough caused by COVID-19: A protocol for a systematic review and meta-analysis.

BACKGROUND: Assessing the effectiveness and safety of Traditional Chinese medicine formula Xiaoqinglong decoction for cough caused by COVID-19 is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from their respective inception dates to October 1, 2020: PubMed, MEDLINE, the Cochrane Library, Embase, WorldSciNet, Ovid, the Allied and Complementary Medicine Database, the Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), the Wanfang Database, and the China Biology Medicine Disc. All published randomized controlled trials in English or Chinese related to Traditional Chinese medicine formula Xiaoqinglong decoction for cough caused by COVID-19 will be included. The primary outcome is the time and rate of appearance of coughing. The secondary outcomes are the length of hospital stay. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be conducted with RevMan V.5.2. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether traditional Chinese medicine formula Xiaoqinglong decoction is an effective intervention for patients with cough caused by COVID-19. ETHICS AND DISSEMINATION: Formal ethical approval is not necessary as the data cannot be individualized. The results of this protocol will be disseminated in a peer-reviewed journal or presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020202079.

Traditional Chinese medicine for corona virus disease 2019: A protocol for systematic review.

BACKGROUND: Assessing the effectiveness and safety of Traditional Chinese medicine for treating patients with corona virus disease 2019 (COVID-19) is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from inception to April 2020: Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, Traditional Chinese Medicine, Chinese Biomedical Literature Database, Wan-Fang Database, and Chinese Scientific Journal Database. All published randomized controlled trials in English or Chinese related to Traditional Chinese medicine for COVID-19 will be included. Primary outcomes are time of disappearance of main symptoms and serum cytokine levels. Secondary outcomes is Accompanying symptoms disappear rate, negative COVID-19 results rate on 2 consecutive occasions CT image improvement, average hospitalization time, occurrence rate of common type to severe form, clinical cure rate, and mortality. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be conducted with Review Manager Software V.5.2. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether traditional Chinese medicine is an effective intervention for COVID-19 patients. PROSPERO REGISTRATION NUMBER: CRD42020181006.

Failure mechanisms of pedicle screws and cortical screws fixation under large displacement: A biomechanical and microstructural study based on a clinical case scenario.

STUDY DESIGN: Cadaveric biomechanical with imaging analysis. OBJECTIVE: This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration. SUMMARY OF BACKGROUND DATA: Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration. METHODS: Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis. RESULTS: The average T-scores of the specimens were -4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw. CONCLUSIONS: Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis.

Physical Mechanism of Concrete Damage under Compression.

Although considerable effort has been taken regarding concrete damage, the physical mechanism of concrete damage under compression remains unknown. This paper presents, for the first time, the physical reality of the damage of concrete under compression in the view of statistical and probabilistic information (SPI) at the mesoscale. To investigate the mesoscale compressive fracture, the confined force chain buckling model is proposed; using which the mesoscale parameters concerned could be directly from nanoindentation by random field theory. Then, the mesoscale parameters could also be identified from macro-testing using the stochastic damage model. In addition, the link between these two mesoscale parameters could be established by the relative entropy. A good agreement between them from nano- and macro- testing when the constraint factor approaches around 33, indicates that the mesoscale parameters in the stochastic damage model could be verified through the present research. Our results suggest that concrete damage is strongly dependent on the mesoscale random failure, where meso-randomness originates from intrinsic meso-inhomogeneity and meso-fracture arises physically from the buckling of the confined force chain system. The mesoscale random buckling of the confined force chain system above tends to constitute the physical mechanism of concrete damage under compression.

Impact of community respiratory viral infections in urban children with asthma.

BACKGROUND: Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. OBJECTIVE: We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. METHODS: We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. RESULTS: Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. CONCLUSION: Urban children with asthma with high-symptom respiratory viral infections have reduced FEF25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.

Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children.

BACKGROUND: Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS: Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection. RESULTS: As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV1. However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV1. CONCLUSIONS: In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations.

A novel fracture mechanics model explaining the axial penetration of bone-like porous, compressible solids by various orthopaedic implant tips.

Many features of orthopaedic implants have been previously examined regarding their influence on migration in trabecular bone under axial loading, with screw thread design being one of the most prominent examples. There has been comparatively little investigation, however, of the influence that implant tip design has on migration under axial loads. We present a novel fracture mechanics model that explains how differences in tip design affect the force required for axial penetration of porous, compressible solids similar to trabecular bone. Three tip designs were considered based on typical 5 mm diameter orthopaedic locking screws: flat and conical tip designs, as well as a novel elastomeric tip. Ten axial penetration trials were conducted for each tip design. In order to isolate the effect of tip design on axial migration from that of the threads, smooth steel rods were used. Tip designs were inserted into polyurethane foam commonly used to represent osteoporotic trabecular bone tissue (ASTM Type 10, 0.16 g/cc) to a depth of 10 mm at a rate of 2 mm/min, while force and position were recorded. At maximum depth, elastomeric tips were found to require the greatest force for axial migration (mean of 248.24 N, 95% Confidence Interval [CI]: 238.1-258.4 N), followed by conical tips (mean of 143.46 N, 95% CI: 142.1-144.9 N), and flat tips (mean of 113.88 N, 95% CI: 112.2-115.5 N). This experiment was repeated in cross-section while recording video of material compaction through a transparent window. Strain fields for each tip design were then generated from these videos using digital image correlation (DIC) software. A novel fracture mechanics model, combining the Griffith with porous material compaction, was developed to explain the performance differences observed between the three tip designs. This model predicted that steady-state stress would be roughly the same (~ 4 MPa) across all designs, a finding consistent with the experimental results. The model also suggested that crack formation and friction are negligible mechanisms of energy absorption during axial penetration of porous compressible solids similar to trabecular bone. Material compaction appears to be the dominant mechanism of energy absorption, regardless of tip design. The cross-sectional area of the compacted material formed during migration of the implant tip during axial penetration was shown to be a strong determinant of the force required for migration to occur (Pearson Coefficient = 0.902, p < .001). As such, implant tips designed to maximize the cross-sectional area of compacted material - such as the elastomeric and conical tips in the present study - may be useful in reducing excessive implant migration under axial loads in trabecular bone.

Preparation of chitosan sulfate and vesicle formation with a conventional cationic surfactant.

Chitosan of high molecular weight and 85% deacetylation was used to prepare chitosan sulfate (CHS) by employing an industrial recognized green and highly reactive sulfating agent gas SO3. FT-IR and solid-state CP-MAS 13C NMR spectra confirmed that sulfate groups were successfully introduced into chitosan chains with a sulfur content of 16.50% and the substitution degree of 1.75 according to the results of elemental analysis. The aggregation behavior of the mixture of chitosan sulfate polyelectrolyte and oppositely charged surfactant cetyltrimethylammonium bromide (CTAB) was characterized by surface tension, steady-state fluorescent, turbidity, ζ potential and transmission electron microscopy. The results indicate that the CHS/CTAB mixture has pretty high surface activity and low critical aggregation concentration. The CHS/CTAB mixture successively forms spherical aggregates, precipitation, vesicles and micelle aggregates coated by CHS chains by increasing surfactant concentration due to the cooperative hydrophobic and electrostatic interactions.

Involvement of glucose-regulated protein 78 and spliced X-box binding protein 1 in the protective effect of gliclazide in diabetic nephropathy.

AIMS: To testing whether endoplasmic reticulum (ER) stress contributes to the development of diabetic nephropathy. Investigated the effect of gliclazide, an oral antihyperglycemic agent, in a rat model of diabetic nephropathy and the underlying mechanism related to the ER stress response. METHODS: Sixty SD rats were divided into six groups. Diabetic nephropathy was induced in 30 rats with a streptozotocin (STZ) injection and high fat diet, which were then treated with saline, gliclazide or 4-PBA. 20 rats were treated with Tunicamycin (TM) one-time intraperitoneal injection, following treated with saline or gliclazide. Blood glucose, kidney index and function were evaluated. Light and transmission electron microscopy (TEM) were used to observe kidney histological changes. Quantitative real-time PCR and western blot were performed to access the mRNA and protein levels of glucose-regulated protein 78 (GRP78) and spliced X-box binding protein 1 (sXBP1) in glomeruli. RESULT: STZ-induced diabetic rats evidenced nephropathy by higher serum creatinine (sCr), blood urea nitrogen (BUN), microalbuminuria (MAU), and kidney index. Histological examination and TEM assay showed abnormal renal structures including thick glomerular basement membrane and mesangial cell expansion. The same changes were found in TM-treated rats. Gliclazide-treated had similar kidney index, but lower glucose levels, sCr, BUN, and MAU, compared with both saline and 4-PBA-treated diabetic rats or saline-treated TM rats. Synchronize with significantly lower Grp78 and sXbp1 mRNA and protein levels. CONCLUSION: Diabetes-induced nephropathy is associated with ER stress. Gliclazide treatment lessens diabetic nephropathy, probably partially by suppressing the GRP78- and sXBP1-mediated ER response.