Deciphering the Role of the Gut Microbiota in Exposure to Emerging Contaminants and Diabetes: A Review.

Emerging pollutants, a category of compounds currently not regulated or inadequately regulated by law, have recently become a focal point of research due to their potential toxic effects on human health. The gut microbiota plays a pivotal role in human health; it is particularly susceptible to disruption and alteration upon exposure to a range of toxic environmental chemicals, including emerging contaminants. The disturbance of the gut microbiome caused by environmental pollutants may represent a mechanism through which environmental chemicals exert their toxic effects, a mechanism that is garnering increasing attention. However, the discussion on the toxic link between emerging pollutants and glucose metabolism remains insufficiently explored. This review aims to establish a connection between emerging pollutants and glucose metabolism through the gut microbiota, delving into the toxic impacts of these pollutants on glucose metabolism and the potential role played by the gut microbiota.

Prediction of molecular-specific mutagenic alerts and related mechanisms of chemicals by a convolutional neural network (CNN) model based on SMILES split.

Structural alerts (SAs) are essential to identify chemicals for toxicity evaluation and health risk assessment. We constructed a novel SMILES split-based deep learning model (SSDL) that was trained and verified with 5850 chemicals from the ISSSTY database and 384 external test chemicals from published papers. The training accuracy was above 0.90 and the evaluation metrics (precision, recall and F1-score) all reached 0.78 or above on both internal and external test chemicals. In this model, the molecular-specific fragment importance of chemicals was first quantified independently. Then, the SA identification method based on the importance of these fragments was statistically analyzed and verified with the ISSSTY test and external test chemicals containing one of 28 typical SAs, and most of the performances were better than that of expert rules. Furthermore, a mutagenicity mechanism prediction method was developed using 237 chemicals with four known mutagenic mechanisms based on molecular similarity calibrated by the SSDL method and fragment importance, which significantly improved accuracy in three mechanisms and had comparable accuracy in the other one compared to traditional methods. Overall, the SSDL model quantifying fragment toxicity within molecules would be a novel potentially powerful tool in the determination and visualization of molecular-specific SAs and the prediction of mutagenicity mechanisms for environmental or industrial compounds and drugs.

The unimodal intransitivity-fertility relationship is not mediated by demographic trade-offs in a subtropical forest.

Intransitive competition has long been acknowledged as a potential mechanism favoring species coexistence. However, its prevalence, variance along environmental gradients, and possible underlying mechanisms (trade-offs) in plant communities (especially in forests) has seldom been examined. A recently developed "reverse-engineering" approach based on Markov Chain allowed us to estimate the competitive transition matrices and competitive intransitivity from observational abundance data. Using this approach, we estimated competitive intransitivity of five dominant species in a subtropical forest and then related it to soil fertility (soil organic matter and soil pH) and demographic trade-offs (growth-survival and stature-recruitment trade-offs). In our forest plot, intransitive competition was common among the dominant species and peaked at the intermediate level of soil organic matter. Neither the growth-survival trade-off nor the stature-recruitment trade-off was positively related to competitive intransitivity. Our study for the first time empirically supported the unimodal intransitivity-fertility relationship in forests, which, however, was not mediated by the two demographic trade-offs in our plot.

A comparative study of strontium-substituted hydroxyapatite coating on implant's osseointegration for osteopenic rats.

Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Strontium (Sr) promotes osteoblast proliferation and inhibits osteoclast proliferation and positively affects bone regeneration. The aim of this study was to confirm the effects of strontium-substituted hydroxyapatite (Sr-HA) coating via electrochemical deposition on implant's osseointegration in the osteoporotic condition. Female Sprague Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group HA; group 5 % Sr-HA; group 10 % Sr-HA; and group 20 % Sr-HA. Afterward, all rats from groups HA, 5 % Sr-HA, 10 % Sr-HA, and 20 % Sr-HA received implants with hydroxyapatite coating containing 0, 5, 10, and 20 % Sr. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All treatment groups increased new bone formation around the surface of titanium rods and push-out force; group 20 % Sr-HA showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant differences in bone formation and push-out force was observed between groups 5 % Sr-HA and 10 % Sr-HA. This finding suggests that Sr-HA coating can improve implant osseointegration, and the 20 % Sr coating exhibited the best properties for implant osseointegration among the tested coatings in osteoporosis rats.

A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats.

Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Zinc (Zn), magnesium (Mg), and strontium (Sr) present a beneficial effect on bone growth, and positively affect bone regeneration. The aim of this study was to confirm the different effects of the fixation strength of Zn, Mg, Sr-substituted hydroxyapatite-coated (Zn-HA-coated, Mg-HA-coated, Sr-HA-coated) titanium implants via electrochemical deposition in the osteoporotic condition. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group HA; group Zn-HA; group Mg-HA and group Sr-HA. Afterwards, all rats from groups HA, Zn-HA, Mg-HA and Sr-HA received implants with hydroxyapatite containing 0%, 10% Zn ions, 10% Mg ions, and 10% Sr ions. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All treatment groups increased new bone formation around the surface of titanium rods and push-out force; group Sr-HA showed the strongest effects on new bone formation and biomechanical strength. Additionally, there are significant differences in bone formation and push-out force was observed between groups Zn-HA and Mg-HA. This finding suggests that Zn, Mg, Sr-substituted hydroxyapatite coatings can improve implant osseointegration, and the 10% Sr coating exhibited the best properties for implant osseointegration among the tested coatings in osteoporosis rats.

The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on the interface of hydroxyapatite-coated titanium rods implanted into osteopenic rats femurs.

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic implant fixation, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings. This study aims to investigate effects of PTH + SIM on implant stabilization in osteopenic rats. Fourteen weeks after chronically fed a low protein diet, osteopenic rats randomly received implants. Subsequently, the animals were randomly divided into four groups: Control, SIM, PTH and PTH + SIM. Then all rats from groups PTH, SIM and PTH + SIM received PTH (40 µg/kg, three times a week), SIM (25 mg/kg, daily), or both for 12 weeks. The results of our study indicated that all treatments promoted bone healing around implant compared to Control, but PTH + SIM treatment showed significantly stronger effects than PTH or SIM alone in histological, micro-CT, and biomechanical tests. The results indicated additive effects of PTH and SIM on implant fixation in osteoporotic rats.

Combined treatment with parathyroid hormone (1-34) and beta-tricalcium phosphate had an additive effect on local bone formation in a rat defect model.

The objective of this study was to evaluate the effect of following combined treatment with parathyroid hormone (1-34) (PTH) and beta-tricalcium phosphate (ß-TCP) on local bone formation in a rat 3-mm critical-size defect at distal femur. Twelve weeks after bilateral ovariectomy (OVX) and sham operation (sham), all animals were randomly divided into four groups: group OVX, group OVX + ß-TCP, group sham, and group sham + ß-TCP, then all rats underwent bone defect in the bilateral distal femurs, and ß-TCP were implanted into critical-sized defects for group OVX + ß-TCP and group sham + ß-TCP. After defect operation, all animals were received following subcutaneous injections with PTH (60 µg/kg, three times a week) until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that systemic usage of PTH or local usage of ß-TCP can increase the healing of defects in OVX or sham rats. Furthermore, treatments with PTH and ß-TCP showed a stronger effect on accelerating the local bone formation than used alone. Osteoporosis can limit the function of PTH and/or ß-TCP. The results from our study demonstrate that combination of PTH and ß-TCP had an additive effect on local bone formation in non-osteoporosis and/or osteoporosis rats.

Intermittent administration of human parathyroid hormone (1-34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur.

Previous studies have demonstrated the effect of human parathyroid hormone (1-34) (PTH) or strontium-doped hydroxyapatite coating (Sr-HA) on osteoporotic bone implantation. However, reports about effects of PTH plus Sr-HA on bone osseointegration of titanium implants in a state of osteoporosis were limited. This study was designed to investigate the effects of intermittent administration of human parathyroid hormone (1-34) on strontium-doped hydroxyapatite coating (Sr-HA) implant fixation in ovariectomized (OVX) rats. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups including control group, Sr group, PTH group and PTH+Sr group. Forty OVX rats accepted implant insertion in the distal femurs, control group, and PTH group with HA implants and the Sr group and PTH+Sr group with Sr-HA implants. Animals from PTH group and PTH+Sr group then randomly received PTH (60 µg/kg, 3 times a week) until death at 12 weeks. After 12-week healing period, implants from group PTH+Sr revealed improved osseointegration compared with other treatment groups, which is manifested by the exceeding increase of bone area ratio and bone-to-implant contact, the trabecular microarchitecture and the maximal push-out force displayed by tests like histomorphometry, micro-CT, and biomechanics evaluation. These results demonstrated that PTH+ Sr-HA coatings could enhance implant osseointegration in OVX rats, and suggested the feasibility of using this method to improve implant fixation in osteoporotic bone.

Effect of teriparatide on repair of femoral metaphyseal defect in ovariectomized rats.

OBJECTIVE: This study aimed to investigate the effect exerted by teriparatide on the repair of femoral metaphyseal defect in ovariectomized rats. METHOD: Female Sprague-Dawley rats were ovariectomized and after 3 months a critically sized defect of 3 mm in diameter-a through-hole bone defect-was drilled into each distal femur of the ovariectomized rats. The rats were injected with teriparatide (30 µg/kg) parathyroid hormone (PTH) in the peritoneum three times per week. After 4 and 8 weeks the animals were killed and the blood and bilateral femora were harvested for biochemical analysis, histopathological observation, and micro-computed tomography (CT) examination. RESULTS: The PTH group and control group were compared 4  and 8 weeks after surgery. PTH increased bone formation in the defect area. Moreover, PTH showed the strongest effects on bone volume per total volume, trabecular number, trabecular thickness, trabecular separation, and total fluorescence-marked new bone area. Additionally, the PTH treatment group showed inhibited serum concentrations of C-terminal telopeptide of type I collagen and enhanced expression of calcium, phosphorus, and bone alkaline phosphatase. CONCLUSION: Our findings suggest a positive effect of PTH on defect healing in ovariectomized rats.

Treatment study of distal femur for parathyroid hormone (1-34) and ß-tricalcium phosphate on bone formation in critical-sized defects in osteopenic rats.

The objective of this study was to evaluate the effect of following combined treatment with parathyroid hormone (1-34) (PTH) and ß-tricalcium phosphate (ß-TCP) on local bone formation in a rat 3-mm critical-sized defect at the distal femur. Fourteen weeks were allowed to pass before defect surgery for the establishment of osteopenic animal models chronically fed a low-protein diet. All animals were randomly divided into four groups: group PTH; group ß-TCP, group PTH + ß-TCP, and a control group. All rats then underwent a surgical procedure to create bone defects in the bilateral distal femurs, and ß-TCP was implanted into critical-sized defects for the groups designated as ß-TCP and group PTH + ß-TCP. After the defect operation, all animals from group PTH and group PTH + ß-TCP received following subcutaneous injections with PTH (60 µg/kg, three times per week) until euthanasia at 4 and 8 weeks. The distal femurs and blood were collected for evaluation. The results of study showed the strongest effect on accelerating the local bone formation with treatment ß-TCP and PTH at 4 weeks and 8 weeks. The results from our study demonstrate that a combination of PTH and ß-TCP had an additive effect on local bone formation in osteopenic rats chronically fed a low-protein diet.

Minimally invasive surgical technique: Percutaneous external fixation combined with titanium elastic nails for selective treatment of tibial fractures.

INTRODUCTION: Several techniques have been described to treat tibial fractures, which respectively remains defects. This article presents a novel intra- and extramedullary fixation technique: percutaneous external fixator combined with titanium elastic nails (EF-TENs system). The purpose of this study is to introduce this new minimally invasive surgical technique and selective treatment of tibial fractures, particularly in segmental fractures, diaphysis fractures accompanied with distal or proximal bone subfissure, or fractures with poor soft-tissue problems. METHODS: Following ethical approval, thirty-two patients with tibial fractures were treated by the EF-TENs system between January 2010 and December 2012. The follow-up studies included clinical and radiographic examinations. All relevant outcomes were recorded during follow-up. RESULTS: All thirty-two patients were achieved follow-ups. According to the AO classification, 3 Type A, 9 Type B and 20 Type C fractures were included respectively. According to the Anderson-Gustilo classification, there were 5 Type Grade II, 3 Type Grade IIIA and 2 Type Grade IIIB. Among 32 patients, 8 of them were segmental fractures. 12 fractures accompanied with bone subfissure. Results showed no nonunion case, with an average time of 23.7 weeks (range, 14-32 weeks). Among them, there were 3/32 delayed union patients and 0/32 malunion case. 4/32 patients developed a pin track infection and no patient suffered deep infection. The external fixator was removed with a mean time of 16.7 weeks (range, 10-26 weeks). Moreover, only 1/32 patient suffered with the restricted ROM of ankle, none with the restricted ROM of knee. CONCLUSION: This preliminary study indicated that the EF-TENs system, as a novel intra- and extramedullary fixation technique, had substantial effects on selective treatment of tibial fractures.

The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on osseous integration of hydroxyapatite-coated titanium implants in the femur of ovariectomized rats.

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic osseous integration of the implant, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings still limited. This study aims to investigate effects of PTH+SIM on osseous integration of the implant in OVX rats. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group control; group SIM; group PTH and group PTH+SIM. Afterwards, all OVX rats received hydroxyapatite (HA)-coated titanium rods (external diameter and length are 1.5mm and 20mm) in the femoral medullary canal. Subsequently, the animals from group SIM, group PTH and group PTH+SIM received human parathyroid hormone 1-34 (60µg/kg, three times a week), SIM (5mg/kg daily), or both for 12 weeks. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All groups increased new bone formation around the surface of titanium rods and push-out force; group PTH+SIM showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant difference observed in bone formation and push-out force between groups SIM and PTH. This finding suggests that intermittent administration of PTH or SIM alone has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition, and the additive effects of combination PTH and SIM on osseous integration of the implant in OVX rats.

Effect exerted by Teriparatide upon Repair Function of ß-tricalcium phosphate to ovariectomised rat's femoral metaphysis defect caused by osteoporosis.

In this study, we tested the effect of Teriparatide (PTH) in combination with ß-tricalcium phosphate (ß-TCP) as a bone void filler in an ovariectomised rat distal femoral metaphysis model.ß-TCP is a completely resorbable synthetic calcium phosphate and the Teriparatide is a drug that can promote bone formation in the condition of osteoporosis. A critical size defect of 3mm in diameter, a through-hole bone defect, was drilled into each distal femur of the ovariectomised rats. The hole was filled with ß-TCP and the rat was injected PTH Teriparatide (30µg/kg) in peritoneum 5 times per week. After 4and 8 weeks the animals were killed and the degree of bone healing analysed. In total, 60 animals were investigated. When the ß-TCP and PTH were used, histological, biochemistry and histomor-phometric evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. The Ovariectomised rats which suffer from femur metaphysis defect are cured by embedding ß-tricalcuim phosphate and intermittently cured by parathyroid hormone (PTH).

Treatment study of distal femur for parathyroid hormone (1-34) and ß-tricalcium phosphate on bone formation in critical size defects in rats.

The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1-34), a surgically implanted synthetic ß-tricalcium phosphate bone biomaterial serving as a matrix to support new bone formation. Twelve weeks after bilateral ovariectomy, all rats underwent bone defect in the distal femurs, and ß-tricalcium phosphate was implanted into critical sized defects. After defect operation, all animals were randomly divided into four groups and received following subcutaneous injections until death at four and eight weeks: sham rats (group ST); sham rats + parathyroid hormone, 30 µg/kg, three times a week (group SPT); OVX rats (group OT); and OVX rats + parathyroid hormone (group OPT). The distal femurs of rats were harvested for evaluation. The treatment group demonstrating the highest levels of new bone formation was the defects treated with parathyroid hormone as assessed by micro-computed tomography, biomechanical strength, and histological analysis for sham rats. Furthermore, parathyroid hormone showed a stronger effect on accelerating the degradation of ß-tricalcium phosphate. Osteoporosis can limit the function of parathyroid hormone and/or ß-tricalcium phosphate. The results from our study demonstrate that combination of parathyroid hormone and ß-tricalcium phosphate brings better effect to bone tissue repair in non-osteoporosis and/or osteoporosis status.

Mining gene expression data of multiple sclerosis.

OBJECTIVES: Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example. MATERIALS AND METHODS: Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control) were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined. RESULTS: An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score. CONCLUSIONS: The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

[Measurement of properties of polypropylene copolymers by Raman spectrum].

Fourier-transform (FT) Raman spectra were measured for 7 kinds of different polypropylene copolymers and the assignments of all Raman bands were made through a detailed analysis. Ultimately, by choosing 2 700-3 100 cm(-1) as the characteristic spectral, partial least squares (PLS) regression models were set up for xylene solubles content, ethylene content and ethylene content of xylene solubles in polypropylene copolymers. The values of correlation coefficient (r) between predicted results and actual values were all greater than 0.94, and the values of average relative error (ARE) were all less than 5%. The second PLS factor was also analyzed in this paper, and it was concluded that the original information of the sample was accurately extracted by using PLS regression. This paper offered a kind of possibility for on-line measurement of xylene solubles content, ethylene content and ethylene content of xylene solubles in polypropylene copolymers.

Experimental demonstration of a free-space cylindrical cloak without superluminal propagation.

We experimentally demonstrated an alternative approach of invisibility cloaking that can combine technical advantages of all current major cloaking strategies in a unified manner and thus can solve bottlenecks of individual strategies. A broadband cylindrical invisibility cloak in free space is designed based on scattering cancellation (the approach of previous plasmonic cloaking), and implemented with anisotropic metamaterials (a fundamental property of singular-transformation cloaks). Particularly, nonsuperluminal propagation of electromagnetic waves, a superior advantage of non-Euclidian-transformation cloaks constructed with complex branch cuts, is inherited in this design, and thus is the reason of its relatively broad bandwidth. This demonstration provides the possibility for future practical implementation of cloaking devices at large scales in free space.

[Quantitative determination of PVC concentration by Raman spectrum].

Quantitative determination of polyvinyl chloride (PVC) concentration by Raman spectrum was studied in the present work. According to partial least squares (PLS) analysis, it was found that scores of PLS factor 1 were proportional to the concentrations of the sample solutions. Meanwhile, the loadings of factor 1 could reflect the contents of PVC and cyclohexanone simultaneously. The PLS regression model for PVC concentration prediction was built. The values of r and root mean square error (RMSE) between predictive results and actual values were 0.9963 and 2.775, respectively. The Raman characteristic peaks of PVC and cyclohexanone were found, including the C-Cl bond for PVC (620 and 695 cm(-1)) and the alicyclic ketone for cyclohexanone (1709 cm(-1)). By using internal standard method, another model for PVC concentration prediction was established, and the values of r and RMSE were 0.9941 and 3.151, respectively. The results indicated that it is feasible to use Raman spectrum to detect the PVC concentration, which is of significant importance to PVC recycling.

Esophageal cancer mortality trends in rural and urban China between 1987 and 2009.

Esophageal cancer is one of the most commonly diagnosed malignant tumors in China. This study aimed to examine the temporal trend of esophageal cancer mortality rates during the period 1987-2009 in both rural and urban settings and to detect the effects of year of death and year of birth on the trends using joinpoint regression analysis and an age-period-cohort model. Age-standardized mortality rates were calculated by the direct method using the world population of 1960, and joinpoint regression was performed to obtain the annual percentage change (APC) in mortality rate. Poisson regression models were fitted to evaluate the period and cohort effects after adjusting for age. During the period 1987-2009, age-standardized mortality rates showed an overall significant decrease for rural females (APC=-2.3, 95% confidence interval [CI]: -3.3%, -1.2%), urban males (APC=-1.8, 95% CI: -2.6%, -1.0%) and urban females (APC=-3.7, 95% CI: -4.9%, -2.4%), but the decrease was not statistically significant for rural males (APC=-0.9, 95% CI: -2.0%, 0.3%). After adjusting for age and with the birth cohort of 1900-1904 or period 1987-1991 as reference, the relative risk of successive cohorts decreased steadily and that of more recent periods kept relatively stable. The decreasing birth cohort effect in the recent generations could correspond to increased adoption of healthy dietary habits and life-styles in the population.