Seasonal patterns, fate and ecological risk assessment of pharmaceutical compounds in a wastewater treatment plant with Bacillus bio-reactor treatment.

Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.

Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress.

BACKGROUND: L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue. Therefore, we hypothesized that amlodipine, a long-acting dihydropyridine L-type calcium channel blocker, may inhibit the occurrence and development of esophageal cancer (EC). AIM: To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum (ER) stress. METHODS: Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined. Subsequently, the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays. In vivo experiments were performed using murine xenograft model. To elucidate the underlying mechanisms, in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine. RESULTS: The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues. Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose- and time-dependent manner. In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice. Additionally, amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition (EMT). Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT. Moreover, amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein. The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis, EMT, and autophagy. Furthermore, blocking autophagy increases the ratio of apoptosis and migration. CONCLUSION: Collectively, we demonstrate for the first time that amlodipine promotes apoptosis, induces autophagy, and inhibits migration through ER stress, thereby exerting anti-tumor effects in EC.

MiR-4521 affects the propagation of Cryptosporidium parvum in HCT-8 cells through targeting foxm1 by regulating cell apoptosis.

Cryptosporidium parvum could regulate the expression of microRNAs of epithelial cells to facilitate its intracellular propagation. MiR-4521 has been reported to play an important role during the development and progression of tumors and infectious diseases by regulating cell proliferation, apoptosis, and autophagy. However, the implication of miR-4521 during C. parvum infection was still unknown. In this study, the expression of miR-4521 was found to be upregulated in HCT-8 cells infected with C. parvum from 8 h post-infection (pi) to 48 hpi, and its upregulation would be related with the TLR/NF-κB signal pathway during C. parvum infection. One potential target of miR-4521, foxm1, was down-regulated in HCT-8 cells from 24 hpi to 48 hpi, and the expression of foxm1 was negatively regulated by miR-4521. The target relationship between miR-4521 and foxm1 was further validated by using dual luciferase reporter assay. Further studies showed that miR-4521 promoted the propagation of C. parvum in HCT-8 cells through targeting foxm1 by regulating BCL2-mediating cell apoptosis. These results contribute to further understanding of the regulatory mechanisms of host miRNAs during Cryptosporidium infection.

High genotype diversity and zoonotic potential of Enterocytozoon bieneusi in yaks (Bos grunniens) from Ganzi Tibetan Autonomous Prefecture, Sichuan Province.

Enterocytozoon bieneusi is a common pathogen in humans and various animals, threatening the breeding industry and public health. However, there is limited information on the molecular characteristics of E. bieneusi in yaks, an economically important animal mainly domesticated in the Qinghai Tibet Plateau in China. In the present study, nested PCR targeting the ITS gene region was applied to investigate the positive rates and genetic diversity of E. bieneusi in 223 faecal samples of yaks from three locations in Ganzi Tibetan Autonomous Prefecture, Sichuan Province. The total positive rate of E. bieneusi was 23.8% (53/223). Significant differences in positive rates were identified among yaks from three locations (χ2 = 8.535, p = 0.014) and four age groups (χ2 = 17.259, p = 0.001), with the highest positive rates in yaks from Yajiang and aged < 6 months, respectively. Sequence analysis identified seven known (EbpC, LW1, LQ10, PigEBITS5, ESH-01, J and BEB4) and five novel (Ganzi1-5) ITS genotypes. Phylogenetic analysis showed eight genotypes (EbpC, LW1, LQ10, PigEBITS5, ESH-01, Ganzi1, Ganzi2 and Ganzi4) in group 1 and three genotypes (J, BEB4 and Ganzi3) in group 2, indicating high genotype diversity and zoonotic potential of E. bieneusi in yaks from Ganzi. Considering the increasing zoonotic genotypes in yaks in the present study compared with previous findings, interventions should be developed to reduce the potential transmission of E. bieneusi between humans and animals.

Title: Grande diversité génotypique et potentiel zoonotique d'Enterocytozoon bieneusi chez les yaks (Bos grunniens) de la préfecture autonome tibétaine de Ganzi, province du Sichuan. Abstract: Enterocytozoon bieneusi est un agent pathogène courant chez l'homme et chez divers animaux, menaçant l'industrie de l'élevage et la santé publique. Cependant, il existe peu d'informations sur les caractéristiques moléculaires d'E. bieneusi chez les yaks, un animal important pour l'économie, principalement domestiqué sur le plateau du Qinghai au Tibet en Chine. Dans la présente étude, une PCR imbriquée ciblant la région du gène ITS a été appliquée pour étudier la positivité et la diversité génétique d'E. bieneusi dans 223 échantillons fécaux de yaks provenant de trois sites de la préfecture autonome tibétaine de Ganzi, province du Sichuan. Le taux total de positivité pour E. bieneusi était de 23,8 % (53/223). Des différences significatives dans les taux positifs ont été identifiées parmi les yaks de trois emplacements (χ2 = 8,535, P = 0,014) et de quatre groupes d'âge (χ2 = 17,259, P = 0,001), avec les taux positifs les plus élevés respectivement chez les yaks de Yajiang et ceux âgés de moins de 6 mois. L'analyse de séquence a identifié sept génotypes ITS connus (EbpC, LW1, LQ10, PigEBITS5, ESH-01, J et BEB4) et cinq nouveaux (Ganzi1­5). L'analyse phylogénétique a montré huit génotypes (EbpC, LW1, LQ10, PigEBITS5, ESH-01, Ganzi1, Ganzi2 et Ganzi4) dans le groupe 1 et trois génotypes (J, BEB4 et Ganzi3) dans le groupe 2, indiquant une diversité génotypique élevée et un potentiel zoonotique d'E. bieneusi chez les yaks de Ganzi. Compte tenu de l'augmentation des génotypes zoonotiques chez les yaks dans la présente étude par rapport aux résultats précédents, des interventions devraient être développées pour réduire la transmission potentielle d'E. bieneusi entre les humains et les animaux.

Design of diversified chimeric antigen receptors through rational module recombination.

Chimeric antigen receptor (CAR)-T cells have shown great promise in cancer therapy. However, the anti-tumor efficiency is limited due to the CAR-induced T cell apoptosis or exhaustion. The intracellular domain of CAR comprised of various signaling modules orchestrates CAR-T cell behaviors. The modularity of CAR signaling domain functions as the "mainboard" to assemble diversified downstream signaling components. Here, we implemented the modular recombination strategy to construct a library of CARs with synthetic co-signaling modules adopted from immunoglobin-like superfamily (IgSF) and tumor necrosis factor receptor superfamily (TNFRSF). We quantitatively characterized the signaling behaviors of these recombinants by both NFAT and NF-κB reporter, and identified a set of new CARs with diverse signaling behaviors. Specifically, the 28(NM)-BB(MC) CAR-T cells exhibited improved cytotoxicity and T cell persistence. The synthetic approach can promote our understanding of the signaling principles of CAR molecule, and provide a powerful tool box for CAR-T cell engineering.

Characterization of CpCaM, a protein potentially involved in the growth of Cryptosporidium parvum.

Cryptosporidium parvum is an important apicomplexan parasite causing severe diarrhea in both humans and animals. Calmodulin (CaM), a multifunctional and universal calcium-binding protein, contributes to the growth and development of apicomplexan parasites, but the role of CaM in C. parvum remains unknown. In this study, the CaM of C. parvum encoded by the cgd2_810 gene was expressed in Escherichia coli, and the biological functions of CpCaM were preliminarily investigated. The transcriptional level of the cgd2_810 gene peaked at 36 h post infection (pi), and the CpCaM protein was mainly located around the nucleus of the whole oocysts, in the middle of sporozoites and around the nucleus of merozoites. Anti-CpCaM antibody reduced the invasion of C. parvum sporozoites by 30.69%. The present study indicates that CpCaM is potentially involved in the growth of C. parvum. Results of the study expand our knowledge on the interaction between host and Cryptosporidium.

Temporal transcriptomic changes in microRNAs involved in the host immune response and metabolism during Neospora caninum infection.

BACKGROUND: Neospora caninum infection is a major cause of abortion in cattle, which results in serious economic losses to the cattle industry. However, there are no effective drugs or vaccines for the control of N. caninum infections. There is increasing evidence that microRNAs (miRNAs) are involved in many physiological and pathological processes, and dysregulated expression of host miRNAs and the biological implications of this have been reported for infections by various protozoan parasites. However, to our knowledge, there is presently no published information on host miRNA expression during N. caninum infection. METHODS: The expression profiles of miRNAs were investigated by RNA sequencing (RNA-seq) in caprine endometrial epithelial cells (EECs) infected with N. caninum at 24 h post infection (pi) and 48 hpi, and the functions of differentially expressed (DE) miRNAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The transcriptome data were validated by using quantitative real-time polymerase chain reaction. One of the upregulated DEmiRNAs, namely chi-miR-146a, was selected to study the effect of DEmiRNAs on the propagation of N. caninum tachyzoites in caprine EECs. RESULTS: RNA-seq showed 18 (17 up- and one downregulated) and 79 (54 up- and 25 downregulated) DEmiRNAs at 24 hpi and 48 hpi, respectively. Quantitative real-time polymerase chain reaction analysis of 13 randomly selected DEmiRNAs (10 up- and three downregulated miRNAs) confirmed the validity of the RNA-seq data. A total of 7835 messenger RNAs were predicted to be potential targets for 66 DEmiRNAs, and GO and KEGG enrichment analysis of these predicted targets revealed that DEmiRNAs altered by N. caninum infection may be involved in host immune responses (e.g. Fc gamma R-mediated phagocytosis, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-ß signaling pathway, mitogen-activated protein kinase signaling pathway) and metabolic pathways (e.g. lysine degradation, insulin signaling pathway, AMP-activated protein kinase signaling pathway, Rap1 signaling pathway, calcium signaling pathway). Upregulated chi-miR-146a was found to promote N. caninum propagation in caprine EECs. CONCLUSIONS: This is, to our knowledge, the first report on the expression profiles of host miRNAs during infection with N. caninum, and shows that chi-miR-146a may promote N. caninum propagation in host cells. The novel findings of the present study should help to elucidate the interactions between host cells and N. caninum.

A Chimeric Conjugate of Antibody and Programmable DNA Nanoassembly Smartly Activates T Cells for Precise Cancer Cell Targeting.

Synthetically directing T-cells against tumors emerges as a promising strategy in immunotherapy, while it remains challenging to smartly engage T cells with tunable immune response. Herein, we report an intelligent molecular platform to engineer T-cell recognition for selective activation to potently kill cancer cells. To this end, we fabricated a hybrid conjugate that uses a click-type DNA-protein conjugation to equip the T cell-engaging antibody with two distinct programmable DNA nanoassemblies. By integrating multiple aptameric antigen-recognitions within a dynamic DNA circuit, we achieved combinatorial recognition of triple-antigens on cancer cells for selective T-cell activation after high-order logic operation. Moreover, by coupling a DNA nanostructure, we precisely defined the valence of the antigen-binding aptamers to tune avidity, realizing effective tumor elimination in vitro and in vivo. Together, we present a versatile and programmable strategy for synthetic immunotherapy.

Genistein reverses the effect of 17ß-estradiol on exacerbating experimental occlusal interference-induced chronic masseter hyperalgesia in ovariectomised rats.

BACKGROUND: Oro-facial pain is more prevalent in women than in men, and oestrogen may underlie this sex difference. Genistein reversed the potentiation of 17ß-estradiol (E2) on glutamate-induced acute masseter nociceptive behaviour, but its role in dental experimental occlusal interference (EOI)-induced chronic masseter hyperalgesia remains unclear. OBJECTIVE: This study aimed to investigate sex differences, and to explore the role and underlying mechanisms of genistein in E2-potentiated EOI-induced chronic masseter hyperalgesia in rats. METHODS: Female and male rats were prepared to compare the sex differences of masseter hyperalgesia induced by EOI using a 0.4-mm-thick metal crown. Female rats were ovariectomised (OVX) and treated with E2 and genistein, followed by EOI. The head withdrawal threshold (HWT) was examined to assess masseter sensitivity. The protein expression of transient receptor potential vanilloid-1 (TRPV1) in the trigeminal ganglion (TG) was detected using western blotting. Immunofluorescence staining was used to reveal the colocalisation of oestrogen receptors (ERs) with TRPV1 and the percentage of TRPV1-positive neurons in the TG. RESULTS: To some extent, female rats displayed enhanced sensitivity to EOI-induced chronic masseter hyperalgesia compared with males. Female rats showed the lowest HWT in the pro-oestrus phase. Pre-treatment with genistein antagonised E2 potentiation in EOI-induced masseter hyperalgesia and blocked the effect of E2 by downregulating TRPV1 protein expression and the percentage of TRPV1-positive neurons in the TG. CONCLUSION: Female rats showed greater masseter hyperalgesia than males under EOI. Genistein antagonised the facilitation of EOI-induced chronic masseter hyperalgesia by E2 probably through inhibiting TRPV1 in the TG.

17ß-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats.

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17ß-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.

Experimental validation of finite element simulation of a new custom-designed fixation plate to treat mandibular angle fracture.

BACKGROUND: The objective of the study was to validate biomechanical characteristics of a 3D-printed, novel-designated fixation plate for treating mandibular angle fracture, and compare it with two commonly used fixation plates by finite element (FE) simulations and experimental testing. METHODS: A 3D virtual mandible was created from a patient's CT images as the master model. A custom-designed plate and two commonly used fixation plates were reconstructed onto the master model for FE simulations. Modeling of angle fracture, simulation of muscles of mastication, and defining of boundary conditions were integrated into the theoretical model. Strain levels during different loading conditions were analyzed using a finite element method (FEM). For mechanical test design, samples of the virtual mandible with angle fracture and the custom-designed fixation plates were printed using selective laser sintering (SLS) and selective laser melting (SLM) printing methods. Experimental data were collected from a testing platform with attached strain gauges to the mandible and the plates at different 10 locations during mechanical tests. Simulation of muscle forces and temporomandibular joint conditions were built into the physical models to improve the accuracy of clinical conditions. The experimental vs the theoretical data collected at the 10 locations were compared, and the correlation coefficient was calculated. RESULTS: The results show that use of the novel-designated fixation plate has significant mechanical advantages compared to the two commonly used fixation plates. The results of measured strains at each location show a very high correlation between the physical model and the virtual mandible of their biomechanical behaviors under simulated occlusal loading conditions when treating angle fracture of the mandible. CONCLUSIONS: Based on the results from our study, we validate the accuracy of our computational model which allows us to use it for future clinical applications under more sophisticated biomechanical simulations and testing.

Pharmacodynamic elucidation of glutamate & dopamine in ketamine-induced anaesthesia.

General anaesthetics are some of the most widely used and essential therapeutic agents. However, despite over a century of research, the molecular mechanisms of general anaesthesia in the central nervous system remain elusive. Ketamine (ketamine hydrochloride) has been approved for use in general anaesthesia either alone or in combination with other medications. It is a superb drug for use in short-term medical procedures that do not require skeletal muscle relaxation, and it has approval for the induction of general anaesthesia as a pre-anaesthetic to other general anaesthetic agents. However, Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the pharmacodynamic interactions between anaesthetic agents, the mechanisms of cognitive alterations that follow an anaesthetic procedure, the identification of an eventual unitary mechanism of anaesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical targets of anaesthetic agents, leading to difficulties in between-studies comparisons. Thus, the glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have proposed to contribute significantly to the pathophysiology of neuropsychiatric diseases. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. In this review, we discuss the neural circuits through which the two systems interact and how their disruption may cause psychotic symptoms. We also summarize from a molecular perspective of mechanisms of action of ketamine as general anaesthetics on ligand-gated ion channels mediated modulation of dopamine in the brain region.

Bioaccumulation of Cadmium Affects Development, Mating Behavior, and Fecundity in the Asian Corn Borer, Ostrinia furnacalis.

Heavy metal pollution is becoming an increasingly serious problem in agricultural ecosystems. Heavy metals such as cadmium (Cd) accumulate in the food chain and may lead to detrimental effects on the physiological functions of living organisms, including herbivorous insects. One such example is the Asian Corn Borer, Ostrinia furnacalis (Lepidoptera: Pyralidae). However, how Cd can affect the development and reproduction of O. furnacalis is largely unknown. In this study, we exposed larvae of O. furnacalis to a diet containing Cd and investigated the effects of Cd on the development, mating behavior, and fecundity of the insect. We showed that Cd accumulates in the larvae and inhibits development by extending larval and pupal duration and decreasing the survival rate. The excretion of Cd through multiple routes during the larval and pupal stages resulted in low levels of residual Cd in the adult insects, which were not fed with Cd. However, the mating behavior and fecundity of these insects were significantly affected, compared to control insects. This suggests that the bioaccumulation of heavy metals such as Cd has long lasting and detrimental effects on O. furnacalis over the entire life cycle, affecting fecundity, even when specimens are only exposed at an early life stage.

Clinical significance of serum total oxidant/antioxidant status in patients with operable and advanced gastric cancer.

PURPOSE: Oxidative stress was significantly associated with the development of malignancies. The purpose of this study was to evaluate the significance of serum total oxidant/antioxidant status in operable advanced gastric cancer patients. MATERIALS AND METHODS: A total of 284 patients who underwent curative resection for primary stage III gastric cancer were enrolled. Total oxidant status, total antioxidant status, and oxidative stress index (OSI) were evaluated within 24 hours before surgery, and compared with 120 healthy donors. The correlation between the OSI and survival outcome was analyzed by the Kaplan-Meier method with log-rank test and Cox's regression methods, respectively. RESULTS: Mean OSI of gastric cancer patients was higher than healthy controls (1.41±0.96 vs 0.78±0.42, P<0.001). All patients were stratified into two groups using the optimal cutoff value (1.42) of OSI using a sensitivity of 94.1% and a specificity of 64.0% as optimal conditions from receiver operating curve analysis. Patients with an OSI ≥1.42 had poorer mean overall survival (45.6 vs 29.8 months, P=0.022) and mean recurrence-free survival (43.3 vs 28.1 months, P=0.011) than patients with an OSI <1.42 in univariate analysis, and OSI was also confirmed as an independent predictor for survival for gastric cancer in multivariate analysis (hazard ratio, 0.541; 95% CI: 0.127-1.102; P=0.01). CONCLUSION: Preoperative OSI can be considered as an independent prognostic factor for operable and advanced gastric cancer.

Downregulation of miR-335-5p by Long Noncoding RNA ZEB1-AS1 in Gastric Cancer Promotes Tumor Proliferation and Invasion.

Recently, long noncoding RNAs (lncRNAs) have emerged as new gene regulators and prognostic biomarkers in several cancers, including gastric cancer (GC). In this study, we investigate the role of lncRNA ZEB1 antisense1 (ZEB1-AS1) on GC progression. In the present study, we found that ZEB1-AS1 expression was upregulated in GC tissues and cell lines. High ZEB1-AS1 expression was significantly correlated with advanced TNM stage, lymph node metastasis, and poor overall survival in GC patients. ZEB1-AS1 suppression reduced GC cell proliferation and invasion in vitro. Tumor formation assay in nude mice showed that ZEB1-AS1 inhibition suppressed GC cell growth. Quantitative real-time PCR showed that miR-335-5p expression was downregulated and negatively correlated with ZEB1-AS1 expression in GC tissues. And miR-335-5p expression was directly regulated by ZEB1-AS1. Furthermore, we found that inhibition of miR-335-5p abrogated the suppression of proliferation and invasion of GC cells induced by ZEB1-AS1 depletion. Collectively, ZEB1-AS1 is critical for the proliferation and invasion of GC cells by regulating miR-335-5p. Our findings indicated that ZEB1-AS1 might offer potential novel therapeutic targets for GC patients.

A customized fixation plate with novel structure designed by topological optimization for mandibular angle fracture based on finite element analysis.

BACKGROUND: The purpose of this study was to design a customized fixation plate for mandibular angle fracture using topological optimization based on the biomechanical properties of the two conventional fixation systems, and compare the results of stress, strain and displacement distributions calculated by finite element analysis (FEA). METHODS: A three-dimensional (3D) virtual mandible was reconstructed from CT images with a mimic angle fracture and a 1 mm gap between two bone segments, and then a FEA model, including volume mesh with inhomogeneous bone material properties, three loading conditions and constraints (muscles and condyles), was created to design a customized plate using topological optimization method, then the shape of the plate was referenced from the stress concentrated area on an initial part created from thickened bone surface for optimal calculation, and then the plate was formulated as "V" pattern according to dimensions of standard mini-plate finally. To compare the biomechanical behavior of the "V" plate and other conventional mini-plates for angle fracture fixation, two conventional fixation systems were used: type A, one standard mini-plate, and type B, two standard mini-plates, and the stress, strain and displacement distributions within the three fixation systems were compared and discussed. RESULTS: The stress, strain and displacement distributions to the angle fractured mandible with three different fixation modalities were collected, respectively, and the maximum stress for each model emerged at the mandibular ramus or screw holes. Under the same loading conditions, the maximum stress on the customized fixation system decreased 74.3, 75.6 and 70.6% compared to type A, and 34.9, 34.1, and 39.6% compared to type B. All maximum von Mises stresses of mandible were well below the allowable stress of human bone, as well as maximum principal strain. And the displacement diagram of bony segments indicated the effect of treatment with different fixation systems. CONCLUSIONS: The customized fixation system with topological optimized structure has good biomechanical behavior for mandibular angle fracture because the stress, strain and displacement within the plate could be reduced significantly comparing to conventional "one mini-plate" or "two mini-plates" systems. The design methodology for customized fixation system could be used for other fractures in mandible or other bones to acquire better mechanical behavior of the system and improve stable environment for bone healing. And together with SLM, the customized plate with optimal structure could be designed and fabricated rapidly to satisfy the urgent time requirements for treatment.

An Investigation of Two Finite Element Modeling Solutions for Biomechanical Simulation Using a Case Study of a Mandibular Bone.

The method used in biomechanical modeling for finite element method (FEM) analysis needs to deliver accurate results. There are currently two solutions used in FEM modeling for biomedical model of human bone from computerized tomography (CT) images: one is based on a triangular mesh and the other is based on the parametric surface model and is more popular in practice. The outline and modeling procedures for the two solutions are compared and analyzed. Using a mandibular bone as an example, several key modeling steps are then discussed in detail, and the FEM calculation was conducted. Numerical calculation results based on the models derived from the two methods, including stress, strain, and displacement, are compared and evaluated in relation to accuracy and validity. Moreover, a comprehensive comparison of the two solutions is listed. The parametric surface based method is more helpful when using powerful design tools in computer-aided design (CAD) software, but the triangular mesh based method is more robust and efficient.

Prognostic significance of ischemia-modified albumin for severe acute pancreatitis.

Background: Severe acute pancreatitis (SAP) is characterized by the noxious combination of severe systemic inflammation and hypoperfusion and oxidative stress. Ischemia-modified albumin (IMA) was recognized as a novel marker of oxidative stress and ischemia. The purpose of this study was to evaluate serum IMA level in patients with SAP and analyze its prognostic significance. Methods: A total of 72 patients with SAP were enrolled. Serum IMA level was measured within 24 hours of the onset of SAP, and baseline characteristics were recorded. The BISAP, APACHE II and SOFA scores were calculated. Multivariate logistic regression and receiver operating characteristic curve analyses were used to evaluate predictive ability of LMA for in-hospital mortality of SAP. Kaplan-Meier analysis was further used to compare in-hospital mortality difference between high LMA and low LMA. Results: The overall in-hospital mortality rate of all 72 SAP patients was 23.6%. Non-survivor group had higher serum IMA (107.2±10.8 VS 88.4±11.9, P<0.05) than survivor group. Otherwise, the optimal cutoff levels for the IMA predicting in-hospital mortality of patients with SAP was 112 U/ml using a sensitivity of 77.4% and a specificity of 76.2% as optimal conditions (AUC, 0.734; 95% CI: 0.615-0.852; P=0.002). IMA level also was confirmed as an independent prognostic factor for SAP in multivariate analysis. Patient with high IMA level (≥112 U/ml) had poorer survival rate than low IMA (<112 U/ml) in log-rank test of Kaplan-Meier survival analysis (P<0.05). Conclusions: Serum IMA level can be considered as an independent predictor for in-hospital mortality of patients with SAP.

Toxic metals in children's toys and jewelry: coupling bioaccessibility with risk assessment.

A total of 45 children's toys and jewelry were tested for total and bioaccessible metal concentrations. Total As, Cd, Sb, Cr, Ni, and Pb concentrations were 0.22-19, 0.01-139, 0.1-189, 0.06-846, 0.14-2894 and 0.08-860,000 mg kg(-1). Metallic products had the highest concentrations, with 3-7 out of 13 samples exceeding the European Union safety limit for Cd, Pb, Cr, or Ni. However, assessment based on hazard index >1 and bioaccessible metal showed different trends. Under saliva mobilization or gastric ingestion, 11 out of 45 samples showed HI >1 for As, Cd, Sb, Cr, or Ni. Pb with the highest total concentration showed HI <1 for all samples while Ni showed the most hazard with HI up to 113. Our data suggest the importance of using bioaccessibility to evaluate health hazard of metals in children's toys and jewelry, and besides Pb and Cd, As, Ni, Cr, and Sb in children's products also deserve attention.

Tenax as sorption sink for in vitro bioaccessibility measurement of polycyclic aromatic hydrocarbons in soils.

Physiologically based in vitro methods have been developed to measure bioaccessibility of organic contaminants in soils. However, bioaccessibility of hydrophobic organic contaminants (HOCs) can be underestimated by in vitro tests if gastrointestinal (GI) solution fails to provide sufficient sorption sink for HOCs. To circumvent this drawback, Tenax was included in GI solution as sorption sink to trap mobilized HOCs and maintain the desorption gradient between soil and GI solution. Polycyclic aromatic hydrocarbons (PAHs) were selected as target HOCs, and physiologically based extraction test (PBET) was selected as the in vitro method. Inclusion of Tenax in GI solution increased bioaccessibility of PAHs in five spiked soils from 8.25-20.8% to 55.7-65.9% and the bioaccessibility of PAHs in a field contaminated soil from 3.70-6.92% to 16.3-31.0%. Our results demonstrated the effectiveness of Tenax as sorption sink to enhance PAH mobilization in bioaccessibility measurement in soils.