Numerical evaluation of spinal reconstruction using a 3D printed vertebral body replacement implant: effects of material anisotropy.

Background and objective: Artificial vertebral implants have been widely used for functional reconstruction of vertebral defects caused by tumors or trauma. However, the evaluation of their biomechanical properties often neglects the influence of material anisotropy derived from the host bone and implant's microstructures. Hence, this study aims to investigate the effect of material anisotropy on the safety and stability of vertebral reconstruction. Material and methods: Two finite element models were developed to reflect the difference of material properties between linear elastic isotropy and nonlinear anisotropy. Their biomechanical evaluation was carried out under different load conditions including flexion, extension, lateral bending and axial rotation. These performances of two models with respect to safety and stability were analyzed and compared quantitatively based on the predicted von Mises stress, displacement and effective strain. Results: The maximum von Mises stress of each component in both models was lower than the yield strength of respective material, while the predicted results of nonlinear anisotropic model were generally below to those of the linear elastic isotropic model. Furthermore, the maximum von Mises stress of natural vertebra and reconstructed system was decreased by 2-37 MPa and 20-61 MPa, respectively. The maximum reductions for the translation displacement of the artificial vertebral body implant and motion range of whole model were reached to 0.26 mm and 0.77°. The percentage of effective strain elements on the superior and inferior endplates adjacent to implant was diminished by up to 19.7% and 23.1%, respectively. Conclusion: After comprehensive comparison, these results indicated that the finite element model with the assumption of linear elastic isotropy may underestimate the safety of the reconstruction system, while misdiagnose higher stability by overestimating the range of motion and bone growth capability.

Calcium silicate/gelatin composite scaffolds with controllable degradation behavior: Fabrication and evaluation.

Calcium silicate can be used as an excellent material for biodegradable bone scaffolds because it can provide bioactive ions to promote bone regeneration. However, the brittleness and rapid degradation of calcium silicate scaffolds have significantly limited their clinical application. In this work, the calcium silicate scaffolds printed by DLP technology were immersed in a gelatin solution under high vacuum condition to obtain calcium silicate/gelatin composite scaffolds with good mechanical and biological properties. Then, genipin was used as a cross-linker for gelatin to control the degradation properties of the composite scaffolds. The initial compressive strength and toughness of the composite scaffolds were 5.0 times and one order of magnitude higher than those of the pure calcium silicate scaffolds, respectively. The gelatin on the surface of the scaffolds could effectively act as a protective layer to regulate the degradation behaviors of the calcium silicate substrate through controlling the crosslinking degree of the gelatin. After degrading for 14 days, the composite scaffolds at 1.0 % genipin concentration exhibited the highest compressive strength of 8.6 ± 0.8 MPa, much higher than that of the pure ceramic scaffold (1.5 ± 0.3 MPa). It can be found that the toughness of the composite scaffolds were almost over 13.2 times higher than that of the pure ceramic scaffold during degradation, despite the higher toughness loss for the former. Furthermore, the composite scaffolds showed enhanced cell biocompatibility and viability. These results demonstrate that the calcium silicate/gelatin composite scaffolds can be a promising candidate in bone tissue regeneration.

[Corrigendum] Celecoxib inhibits the epithelial­to­mesenchymal transition in bladder cancer via the miRNA­145/TGFBR2/Smad3 axis.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the Transwell migration assays shown in Figs. 1B and 3B on p. 685 and p. 688 respectively, the images selected for the '5637 / DMSO' experiment in Fig. 1B and the DMSO experiment in Fig. 3B were apparently the same, such that these data appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that the 5637 DMSO data panel in Fig. 3B had been selected incorrectly. The revised version of Fig. 3, showing the correct data for the DMSO experiment in Fig. 3B, is shown on the next page. The authors regret that these errors went unnoticed prior to the publication of this article, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 683­683, 2019; DOI: 10.3892/ijmm.2019.4241].

Controlled Growth Cu2S Nanoarrays with High-Performance Photothermal Properties.

The controlled growth of Cu2S nanoarrays was constructed by a facile two-step impregnation synthesis route. The as-synthesized Cu2S/CuO@Cu samples were precisely characterized in terms of surface morphology, phase, composition, and oxidation states. At the laser irradiation of 808 nm, Cu2S/CuO@Cu heated up to 106 °C from room temperature in 120 s, resulting in an excellent photothermal conversion performance. The Cu2S/CuO@Cu exhibited excellent cycling performance-sustaining the photothermal performance during five heating-cooling cycles. The finite difference time domain (FDTD) simulation of optical absorption and electric field distributions assured the accuracy and reliability of the developed experimental conditions for acquiring the best photothermal performance of Cu2S/CuO@Cu.

Flaps for lower limb diabetic wound reconstruction: A systematic review and meta-analysis.

BACKGROUND: The treatment of chronic diabetic wounds includes wound dressing, debridement, flap surgery, and amputation. For suitable patients with nonhealing wounds, locoregional flaps or free flaps may be used. This paper aims to review the outcomes of flap surgery and identify the risk factors for flap loss. METHODS: MEDLINE, Embase, and Cochrane Library were searched. Articles reporting flap loss outcomes for flap surgery in lower limb chronic diabetic wounds were included. Case reports and case series with fewer than five patients were excluded. A subset of articles was used for revascularization subgroup analysis and another subset for meta-analysis of risk factors for flap loss. RESULTS: In the free flap group, the total flap failure rate was 7.14% and partial flap failure rate was 7.54%. The rate of major complications requiring operative takeback was 19.0%. Early mortality was 2.76%. In the locoregional flap group, the total flap failure rate was 3.24% and partial flap failure rate was 5.36%. The rate of major complications requiring operative takeback was 13.3%. There was no early mortality. The rate of free flap loss was 18.2% with revascularization, significantly higher than 6.66% without revascularization. CONCLUSIONS: Our findings concur with previously published studies on flap loss and complications in diabetic lower limb wounds. There is an increased risk of flap loss in patients who require free flap and revascularization compared to patients who only require free flap. This could be because of the fragile and fibrotic vessels found in diabetics with comorbid atherosclerosis.

Development of Strong and Tough ß-TCP/PCL Composite Scaffolds with Interconnected Porosity by Digital Light Processing and Partial Infiltration.

Strong and tough ß-TCP/PCL composite scaffolds with interconnected porosity were developed by combining digital light processing and vacuum infiltration. The composite scaffolds were comprised of pure ß-TCP, ß-TCP matrix composite and PCL matrix composite. The porous ß-TCP/PCL composite scaffolds showed remarkable mechanical advantages compared with ceramic scaffolds with the same macroscopic pore structure (dense scaffolds). The composite scaffolds exhibited a significant increase in strain energy density and fracture energy density, though with similar compressive and flexural strengths. Moreover, the composite scaffolds had a much higher Weibull modulus and longer fatigue life than the dense scaffolds. It was revealed that the composite scaffolds with interconnected porosity possess comprehensive mechanical properties (high strength, excellent toughness, significant reliability and fatigue resistance), which suggests that they could replace the pure ceramic scaffolds for degradable bone substitutes, especially in complex stress environments.

Manipulating Charge-Transfer Kinetics of Lithium-Rich Layered Oxide Cathodes in Halide All-Solid-State Batteries.

Employing lithium-rich layered oxide (LLO) as the cathode of all-solid-state batteries (ASSBs) is highly desired for realizing high energy density. However, the poor kinetics of LLO, caused by its low electronic conductivity and significant oxygen-redox-induced structural degradation, has impeded its application in ASSBs. Here, the charge transfer kinetics of LLO is enhanced by constructing high-efficiency electron transport networks within solid-state electrodes, which considerably minimizes electron transfer resistance. In addition, an infusion-plus-coating strategy is introduced to stabilize the lattice oxygen of LLO, successfully suppressing the interfacial oxidation of solid electrolyte (Li3 InCl6 ) and structural degradation of LLO. As a result, LLO-based ASSBs exhibit a high discharge capacity of 230.7 mAh g-1 at 0.1 C and ultra-long cycle stability over 400 cycles. This work provides an in-depth understanding of the kinetics of LLO in solid-state electrodes, and affords a practically feasible strategy to obtain high-energy-density ASSBs.

AC099850.3/NCAPG Axis Predicts Poor Prognosis and is Associated with Resistance to EGFR Tyrosine-Kinase Inhibitors in Lung Adenocarcinoma.

Background: TKI-acquired resistance markedly interferes with treatment of lung cancer patients with EGFR mutant features. Long non-coding RNAs (lncRNAs) modify EGFR-TKI resistance during tumor progression. Non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) is a mitosis-related protein that is involved in tumorigenesis. We investigated the potential regulatory lncRNAs of NCAPG in lung adenocarcinoma (LUAD) and assessed their roles in EGFR-TKI resistance. Methods: Data for 1678 lung cancer patients were retrieved from TCGA and GEO databases and used to evaluate NCAPG and lncRNAs expressions, as well as their prognostic significance in LUAD. Protein levels of NCAPG in LUAD were validated by immuno-histochemistry. To assess the relationship between NCAPG levels and EGFR-TKIs sensitivity, a cohort of 57 LUAD patients administered with EGFR-TKIs was used. Results: Both NCAPG and lncRNA AC099850.3 were over-expressed in LUAD tissues, and correlated with tumor progression and poor prognosis in LUAD. LncRNA AC099850.3 was identified as a potential regulator of NCAPG expressions. The AC099850.3/NCAGP axis was markedly correlated with EGFR mutations and IC50 of EGFR-TKIs. Besides, elevated NCAPG levels were associated with EGFR-TKIs resistance in 57 LUAD patients undergoing TKIs treatment. Gene set enrichment analysis revealed that both AC099850.3 and NCAGP were abundant in the cell cycle and the p53 signaling pathway. Conclusion: The AC099850.3/NCAPG axis is a potential prognostic predictor and therapeutic biomarker for EGFR-TKIs in LUAD.

The Grain Growth Control of ZnO-V2O5 Based Varistors by PrMnO3 Addition.

In this study, the grain growth behaviour of ZnO-V2O5-based ceramics with 0.25-0.75 mol% additions of PrMnO3 was systematically investigated during sintering from 850 °C to 925 °C. with the aim to control the ZnO grain size for their application as varistors. It was found that with the increased addition of PrMnO3, in addition to the decrease in the average grain size, the grain size distribution also narrowed and eventually changed from a bimodal to unimodal distribution after a 0.75 mol% PrMnO3 addition. The grain growth control was achieved by a pinning effect of the secondary ZnCr2O4 and PrVO4 phases at the ZnO grain boundaries. The apparent activation energy of the ZnO grain growth in these ceramics was found to increase with increased additions of PrVO4, hence the observed reduction in the ZnO grain sizes.

Integrated bioinformatic analysis identifies COL4A3, COL4A4, and KCNJ1 as key biomarkers in Wilms tumor.

Wilms tumor (WT) is one of the most common pediatric solid tumors, affecting 1 in 10,000 children, worldwide. A subset of WT patients has poor prognosis, which is associated with a high risk of advanced and/or recurrent disease. Therefore, candidate markers are urgently needed for the diagnosis and effective treatment of WT. We evaluated three mRNA microarray datasets to identify the differences between normal kidney tissue and WT tissue. Gene expression profiling revealed 130 differentially expressed genes (DEGs). Enrichment analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs. Subsequently, we established a protein-protein interaction (PPI) network to reveal the associations among the DEGs and selected 10 hub genes, all of which were downregulated in WT. The expression of COL4A3, COL4A4, KCNJ1, MME, and SLC12A1 in WT tissues was significantly lower than that in normal renal tissues. Survival analyses using the Kaplan-Meier method showed that patients with WT and low expression of COL4A3, COL4A4, and KCNJ1 exhibited remarkably poor overall survival. The correlations among COL4A3, COL4A4, and KCNJ1 in WT were analyzed using cBioPortal; COL4A3, COL4A4, and KCNJ1 were positively correlated with each other. Thus, these genes were considered clinically significant and might therefore play important roles in carcinogenesis and the development of WT.

The Effect of Patient Education and Telemedicine Reminders on Adherence to Eye Drops for Glaucoma.

PURPOSE: To determine the improvement in patient adherence to topical ocular hypotensive therapy by introducing a personalized illustrated medication reference chart and telereminder. DESIGN: Prospective randomized controlled clinical trial. PARTICIPANTS: Fifty-nine patients with glaucoma who were using at least 3 or more eye drops were recruited from the ophthalmology clinic at the National University Hospital of Singapore. METHODS: Participants were randomized into 3 groups: control, reference chart only, and reference chart with telereminder. They completed a survey on demographics, barriers to glaucoma medication adherence, and self-adherence (measured by the Morisky adherence scale) before and 6 weeks after intervention. Logistic regression analysis was performed on the barriers that contribute to nonadherence and paired t tests were conducted for the preimplementation and postimplementation effects of intervention on adherence score. MAIN OUTCOME MEASURES: Changes in mean adherence score based on the Morisky adherence scale before and after intervention in participants from all 3 groups. RESULTS: In our study, 71% of participants who were nonadherent to medications had multiple barriers to adherence, with lack of self-efficacy and forgetfulness being the most common factors. Only the reference chart with telereminder group showed a statistically significant increase in mean adherence score, from 7.18 to 7.69 (P = 0.047). CONCLUSIONS: Adherence to medication in chronic diseases like glaucoma is an important healthcare issue to address. Most of these patients have poor adherence because of multiple factors, and hence interventions aimed at improving adherence should be multifaceted to target these barriers.

Development of biodegradable bioactive glass ceramics by DLP printed containing EPCs/BMSCs for bone tissue engineering of rabbit mandible defects.

Bioactive glass ceramics have excellent biocompatibility and osteoconductivity; and can form direct chemical bonds with human bones; thus, these ceramic are considered as "Smart" materials. In this study, we develop a new type of bioactive glass ceramic (AP40mod) as a scaffold containing Endothelial progenitor cells (EPCs) and Mesenchymal stem cells (BMSCs) to repair critical-sized bone defects in rabbit mandibles. For in vitro experiments: AP40mod was prepared by Dgital light processing (DLP) system and the optimal ratio of EPCs/BMSCs was screened by analyzing cell proliferation and ALP activity, as well as the influence of genes related to osteogenesis and angiogenesis by direct inoculation into scaffolds. The scaffold showed suitable mechanical properties, with a Bending strength 52.7 MPa and a good biological activity. Additionally, when EPCs/BMSCs ratio were combined at a ratio of 2:1 with AP40mod, the ALP activity, osteogenesis and angiogenesis were significantly increased. For in vivo experiments: application of AP40mod/EPCs/BMSCs (after 7 days of in vitro spin culture) to repair and reconstruct critical-sized mandible defect in rabbit showed that all scaffolds were successfully accurately implanted into the defect area. As revealed by macroscopically and CT at the end of 9 months, defects in the AP40mod/EPCs/BMSCs group were nearly completely covered by normal bone and the degradation rate was 29.9% compared to 20.1% in the AP40mod group by the 3D reconstruction. As revealed by HE and Masson staining analyses, newly formed blood vessels, bone marrow and collagen maturity were significantly increased in the AP40mod/EPCs/BMSCs group compared to those in the AP40mod group. We directly inoculated cells on the novel material to screen for the best inoculation ratio. It is concluded that the AP40mod combination of EPCs/BMSCs is a promising approach for repairing and reconstructing large load bearing bone defect.

Celecoxib inhibits the epithelial-to-mesenchymal transition in bladder cancer via the miRNA-145/TGFBR2/Smad3 axis.

Celecoxib, a selective cyclooxygenase­2 inhibitor, has chemo­preventive activity against different cancer types, including bladder cancer (BC). However, the mechanisms by which celecoxib exerts its cancer preventative effects have yet to be completely understood. In the present study, the effect of celecoxib on the epithelial­to­mesenchymal transition (EMT) of BC cells and its potential molecular mechanisms were investigated. The results of the present study demonstrated that celecoxib inhibited the proliferation, migration, invasion and EMT of BC cells. Further investigation of the underlying mechanism revealed that celecoxib inhibited EMT by upregulating microRNA (miR)­145 and downregulating the expression of transforming growth factor ß receptor 2 and SMAD family member 3. Furthermore, the combination of celecoxib with miR­145 mimics demonstrated an additive migration and invasion­inhibitory effect in BC cell lines.

Analysis of environmental drivers influencing interspecific variations and associations among bloom-forming cyanobacteria in large, shallow eutrophic lakes.

Non-diazotrophic Microcystis and filamentous N2-fixing Aphanizomenon and Dolichospermum (formerly Anabaena) co-occur or successively dominate freshwaters globally. Previous studies indicate that dual nitrogen (N) and phosphorus (P) reduction is needed to control cyanobacterial blooms; however, N limitation may cause replacement of non-N2-fixing by N2-fixing taxa. To evaluate potentially counterproductive scenarios, the effects of temperature, nutrients, and zooplankton on the spatio-temporal variations of cyanobacteria were investigated in three large, shallow eutrophic lakes in China. The results illustrate that the community composition of cyanobacteria is primarily driven by physical factors and the zooplankton community, and their interactions. Niche differentiation between Microcystis and two N2-fixing taxa in Lake Taihu and Lake Chaohu was observed, whereas small temperature fluctuations in Lake Dianchi supported co-dominance. Through structural equation modelling, predictor variables were aggregated into 'composites' representing their combined effects on species-specific biomass. The model results showed that Microcystis biomass was affected by water temperature and P concentrations across the studied lakes. The biomass of two filamentous taxa, by contrast, exhibited lake-specific responses. Understanding of driving forces of the succession and competition among bloom-forming cyanobacteria will help to guide lake restoration in the context of climate warming and N:P stoichiometry imbalances.

CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells.

Increased expression of CCL18 has been observed in various malignancies and in the urine samples of patients with bladder cancer (BC). However, the roles of CCL18 in the development, progression and metastasis of BC remain unclear. The present study demonstrated that CCL18 expression was significantly associated with advanced clinical stages of BC. Furthermore, exogenous CCL18 promoted cell invasion and migration, and induced cell epithelial­mesenchymal transition (EMT) in BC cells. Western blotting demonstrated that E­cadherin, an epithelial marker, was decreased, whereas matrix metalloproteinase (MMP)­2 and vascular endothelial growth factor (VEGF)­C were increased in CCL18­treated cells. Blocking CCR8 via a small molecule inhibitor or short hairpin (sh)RNA mitigated the decrease in E­cadherin, and increase in MMP­2 and VEGF­C, caused by human recombinant (r)CCL18. CCR8 knockdown by shRNA reversed rCCL18­induced cancer cell invasion, migration and EMT. In conclusion, these data suggested that CCL18 may promote migration, invasion and EMT by binding CCR8 in BC cells. Inhibition of CCL18 activity by blocking CCR8 could be a potential therapeutic strategy for preventing the progression of BC.

Seasonal dynamics of water bloom-forming Microcystis morphospecies and the associated extracellular microcystin concentrations in large, shallow, eutrophic Dianchi Lake.

The increasing occurrence of Microcystis blooms is of great concern to public health and ecosystem due to the potential hepatotoxic microcystins (MCs) produced by these colonial cyanobacteria. In order to interpret the relationships between variations of Microcystis morphospecies and extracellular MC concentrations, the seasonal dynamics of phytoplankton community composition, MC concentrations, and environmental parameters were monitored monthly from August, 2009 to July, 2010. The results indicated that Microcystis dominated total phytoplankton abundance from May to December (96%-99% of total biovolume), with toxic Microcystis viridis and non-toxic Microcystis wesenbergii dominating after July (constituting 65%-95% of the Microcystis population), followed by M. viridis as the sole dominant species from November to January (49%-93%). Correlation analysis revealed that water temperature and nutrient were the most important variables accounting for the occurrence of M. wesenbergii, while the dominance of M. viridis was related with nitrite and nitrate. The relatively low content of MCs was explained by the association with a large proportion of M. viridis and M. wesenbergii, small colony size of Microcystis populations, and low water temperature, pH and dissolved oxygen. The extracellular MC (mean of 0.5±0.2µg/L) of water samples analyzed by enzyme-linked immunosorbent assay (ELISA) demonstrated the low concentrations of MC in Dianchi Lake which implied the low potential risk for human health in the basin. The survey provides the first whole lake study of the occurrence and seasonal variability of Microcystis population and extracellular MCs that are of particular interest for water quality monitoring and management.

Distribution patterns of the contents of five active components in taproot and stolon of Glycyrrhiza uralensis.

Wild or cultivated Glycyrrhiza uralensis FISCHER (G. uralensis) are the main source of licorice, and they contain the similar compounds, such as the triterpenoid saponins and flavonoids, but above two kinds of the components contents are low level in the cultivated licorice. To produce the high quality cultivated licorices, researchers studied the affecting factors about the compounds producing in the plant of licorice, and then found that the growth years, genetic differences and water deficit are all the important factors. In this paper, we found that there were different distribution patterns of the main five active components (FAC) including glycyrrhizin, liquiritin, isoliquiritin, liquiritigenin and isoliquiritigenin in the taproot and stolon of G. uralensis and maybe they are also important influence factors to the FAC contents of the licorices. In wild G. uralensis, the contents of FAC tended to be lower in the younger parts of the stolon, and in the cultivated G. uralensis taproot, the contents of glycyrrhizin, liquiritin and isoliquiritin tended to increase from top to end, contrary to the contents of liquiritigenin and isoliquiritigenin, which increased first and then decreased. Our results will contribute to the analyses of factors which influence the quality of licorice, and provide some reference for cultivating high quality licorices for herbal medicine.

Ecological dynamics of toxic Microcystis spp. and microcystin-degrading bacteria in Dianchi Lake, China.

Toxic cyanobacterial blooms directly threaten both human safety and the ecosystem of surface waters. The widespread occurrence of these organisms, coupled with the tumor-promoting properties of the microcystin toxins that they produce, demands action to mitigate their potential impacts and, thus, a robust understanding of their ecological dynamics. In the present work, the abundance of toxic Microcystis spp. and microcystin (MC)-degrading bacteria in Dianchi Lake, located in Yunnan Province, China, was studied using quantitative PCR. Samples were taken at monthly intervals from June 2010 to December 2011 at three sampling stations within this freshwater lake. Results revealed that variation in the abundance of both total Microcystis spp. and toxic Microcystis spp. exhibited similar trends during the period of the algal bloom, including the reinvasion, pelagic growth, sedimentation, and overwintering periods, and that the proportion of toxic Microcystis was highest during the bloom and lowest in winter. Importantly, we observed that peaks in mlrA gene copy numbers of MC-degrading bacteria occurred in the months following observed peaks in MC concentrations. To understand this phenomenon, we added MCs to the MC-degrading bacteria (designated strains HW and SW in this study) and found that MCs significantly enhanced mlrA gene copy numbers over the number for the control by a factor of 5.2 for the microcystin-RR treatment and a factor of 3.7 for the microcystin-LR treatment. These results indicate that toxic Microcystis and MC-degrading bacteria exert both direct and indirect effects on each other and that MC-degrading bacteria also mediate a shift from toxic to nontoxic populations of Microcystis.

[Primary study of the threatening of unfixed planning of image guided radiotherapy to the volume margin of neck tumor].

Some patients who have neck tumor but cannot tolerate the thermoplastic immobilization may be supported by simple cushions, and are marked on the neck skin during CT simulation. We therefore set 5 mm as the spinal cord-planning risk volume margin in the intensity-modulated radiotherapy plans in our Centre. Cone beam CT (CBCT) scans were acquired for three times, and matched with the simulation CT images in each radiotherapy. The mean and the standard deviation of the individual, the root mean-square and the standard deviation of the individual were calculated. The matched results of the third CBCT were used to calculate the spinal cord- planning risk volume margin. The results showed that the interfraction error was significantly reduced and the intrafraction error was stable by CBCT guiding. CBCT and 5 mm spinal cord-planning organ is feasible and safe without threatening volume margin to high dose radiotherapy for the patients with neck tumor and not able to tolerate thermoplastic immobilization.