Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Associations between femoral 3D curvature and sagittal imbalance of spine.

Background: The sagittal imbalance (SI) of spine triggers compensatory mechanisms (CMs) of lower extremity (LE) to restore trunk balance. These CMs can cause long-period stress on the femur and may possibly alter the femoral morphology. This cross-sectional observational study aimed to answer the following questions: (a) Do SI subjects exhibit greater femoral bowing compared to subjects with sagittal balance? (b) Are there associations between femoral bowing and CMs of LE in SI subjects? Methods: Subjects who underwent biplanar full body radiographs with the EOS imaging system between January 2016 and September 2021 were recruited. Sagittal parameters included T1-pelvic angle (TPA), pelvic incidence (PI), pelvic tilt (PT), sacral slope, lumbar lordosis (LL), PI-LL, and PT/PI ratio. LE parameters were femoral obliquity angle (FOA), knee flexion angle (KA), and ankle dorsiflexion angle. Femoral bowing was quantified as 3D radius of femoral curvature (RFC). Associations between 3D RFC and the radiographic parameters were analyzed. Results: A total of 105 subjects were included, classified into balance group (TPA < 14°, n = 40), SI group (TPA ≥ 14° and KA <5°, n = 30), and SI with knee flexion group (TPA ≥ 14° and KA ≥ 5°, n = 35). 3D RFC was significantly lower in SI with knee flexion group compared to the other two groups (both p < 0.001). Stepwise linear regression showed that age, SI and knee flexion, femoral length (FL), FOA, and KA were independent predictors for 3D RFC. Conclusion: Greater femoral bowing is observed in subjects with SI and knee flexion compared to the balanced population. CM parameters, including KA and FOA, are associated with 3D RFC. Further longitudinal study is needed to investigate the cause-and-effect relationship between SI, CMs of LE, and femoral bowing.

Generative Adversarial Network (GAN) for Automatic Reconstruction of the 3D Spine Structure by Using Simulated Bi-Planar X-ray Images.

In this study, we modified the previously proposed X2CT-GAN to build a 2Dto3D-GAN of the spine. This study also incorporated the radiologist's perspective in the adjustment of input signals to prove the feasibility of the automatic production of three-dimensional (3D) structures of the spine from simulated bi-planar two-dimensional (2D) X-ray images. Data from 1012 computed tomography (CT) studies of 984 patients were retrospectively collected. We tested this model under different dataset sizes (333, 666, and 1012) with different bone signal conditions to observe the training performance. A 10-fold cross-validation and five metrics-Dice similarity coefficient (DSC) value, Jaccard similarity coefficient (JSC), overlap volume (OV), and structural similarity index (SSIM)-were applied for model evaluation. The optimal mean values for DSC, JSC, OV, SSIM_anteroposterior (AP), and SSIM_Lateral (Lat) were 0.8192, 0.6984, 0.8624, 0.9261, and 0.9242, respectively. There was a significant improvement in the training performance under empirically enhanced bone signal conditions and with increasing training dataset sizes. These results demonstrate the potential of the clinical implantation of GAN for automatic production of 3D spine images from 2D images. This prototype model can serve as a foundation in future studies applying transfer learning for the development of advanced medical diagnostic techniques.

Clinical application of mask region-based convolutional neural network for the automatic detection and segmentation of abnormal liver density based on hepatocellular carcinoma computed tomography datasets.

The aim of the study was to use a previously proposed mask region-based convolutional neural network (Mask R-CNN) for automatic abnormal liver density detection and segmentation based on hepatocellular carcinoma (HCC) computed tomography (CT) datasets from a radiological perspective. Training and testing datasets were acquired retrospectively from two hospitals of Taiwan. The training dataset contained 10,130 images of liver tumor densities of 11,258 regions of interest (ROIs). The positive testing dataset contained 1,833 images of liver tumor densities with 1,874 ROIs, and negative testing data comprised 20,283 images without abnormal densities in liver parenchyma. The Mask R-CNN was used to generate a medical model, and areas under the curve, true positive rates, false positive rates, and Dice coefficients were evaluated. For abnormal liver CT density detection, in each image, we identified the mean area under the curve, true positive rate, and false positive rate, which were 0.9490, 91.99%, and 13.68%, respectively. For segmentation ability, the highest mean Dice coefficient obtained was 0.8041. This study trained a Mask R-CNN on various HCC images to construct a medical model that serves as an auxiliary tool for alerting radiologists to abnormal CT density in liver scans; this model can simultaneously detect liver lesions and perform automatic instance segmentation.

Arctigenin Triggers Apoptosis and Autophagy via PI3K/Akt/mTOR Inhibition in PC-3M Cells.

Arctigenin (ARG), a natural lignans compound isolated from Arctium lappa L. In this study, the anti-tumor effect of ARG on prostate cancer cell PC-3M and the mechanism of apoptosis and autophagy induced by phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were discussed, and further confirmed by the joint treatment of ARG and PI3K inhibitor LY294002. Here, the effect of ARG on cell viability was evaluated in PC-3M cells by Cell Counting Kit-8 reagent (CCK-8) assay. After the treatment of ARG, colony formation assay was used to detect the anti-proliferation effect. Annexin V-fluoresceine isothiocyanate/propidium iodide (FITC/PI) kit and 4',6-diamidino-2-phenylindole (DAPI) staining were used to detect the apoptosis level, and cell cycle changes were analyzed by flow cytometry. The expression of autophagy was detected by acridine orange staining. In addition, the expression levels of apoptosis and autophagy-related proteins were analyzed by Western blot. The result showed that different concentrations of ARG inhibited the proliferation of PC-3M cells. DAPI staining and flow cytometry showed that ARG induced PC-3M cell apoptosis and arrested cell in G0/G1 phase. Acridine orange staining showed that ARG induced autophagy in PC-3M cells. Western blot experiments showed that ARG inhibited the expression of Bcl-2, promoted the expression of Bax and cleaved caspase-3. At the same time, the expression of autophagy-related proteins LC3B-II and Beclin-1 increased after ARG treatment, but P62 decreased. In addition, further studies have shown that treatment with LY294002 enhanced the effects of ARG on the expression of proteins associated with apoptosis and autophagy, indicating that ARG may induce apoptosis and autophagy through PI3K/Akt/mTOR pathway.

[Optimization of the Parameters for Microalgae Immobilization and Analysis of Its Recovery Potential for Ammonia Nitrogen in Wastewater].

Application of microalgae in wastewater treatment is regarded as a potential green technology. However, its engineering application has been largely hindered because of the difficulty of biomass separation and harvesting. This study aimed to identify the key parameters influencing the process of microalgae immobilization. To do this, the study focused on immobilization technology and Scenedesmus obliquus, and employed the response surface methodology (RSM) and the Box-Behnken design (BBD). In an evaluation of the performance of microalgae beads, the fixing agent concentration, the cross-linking agent concentration, and the cross-linking time were selected as the independent variables, and the mechanical strength, the mass transfer rate, and the growth rate of immobilized microalgae beads were the response values. The optimal conditions and the uptake potential of the microalgae beads with respect to ammonia nitrogen (NH4+-N) were further explored and analyzed. The results showed that the optimal parameters for the preparation of immobilized microalgae beads were 5%, 2%, and 16 h, and the maximum removal capacity was obtained using mixotrophic cultivation with an embedding density of 1×106 cells·mL-1 and an organic matter concentration of 300 mg·L-1. In addition, the removal capacity of immobilized microalgae with respect to high concentrations of NH4+-N was significantly higher than for free-living microalgae. When the initial concentrations of NH4+-N were approximately 50 and 70 mg·L-1, NH4+-N was removed by the immobilized microalgae (after a 5-day mixotrophic cultivation) at a rate of (96.6±0.1)% and (65.2±4.5)%, respectively. With an initial NH4+-N concentration of 30 mg·L-1, the dominance of free-living microalgae was clear, with a removal rate of (97.8±0.6)% after a 3-day cultivation. However, under heterotrophic cultivation, the removal rate of NH4+-N by immobilized microalgae was generally low and gradually decreased with increasing concentrations. When the initial concentration was approximately 30 mg·L-1, the removal rate was only (49.0±3.1)%. This study provides new prospects for sustainable urban wastewater treatment, a new approach for resource recycling, and a strong theoretical foundation for the popularization and application of microalgae in wastewater treatment.

Improved Anatomical Specificity of Non-invasive Neuro-stimulation by High Frequency (5 MHz) Ultrasound.

Low frequency ultrasound (<1 MHz) has been demonstrated to be a promising approach for non-invasive neuro-stimulation. However, the focal width is limited to be half centimeter scale. Minimizing the stimulation region with higher frequency ultrasound will provide a great opportunity to expand its application. This study first time examines the feasibility of using high frequency (5 MHz) ultrasound to achieve neuro-stimulation in brain, and verifies the anatomical specificity of neuro-stimulation in vivo. 1 MHz and 5 MHz ultrasound stimulation were evaluated in the same group of mice. Electromyography (EMG) collected from tail muscles together with the motion response videos were analyzed for evaluating the stimulation effects. Our results indicate that 5 MHz ultrasound can successfully achieve neuro-stimulation. The equivalent diameter (ED) of the stimulation region with 5 MHz ultrasound (0.29 ± 0.08 mm) is significantly smaller than that with 1 MHz (0.83 ± 0.11 mm). The response latency of 5 MHz ultrasound (45 ± 31 ms) is also shorter than that of 1 MHz ultrasound (208 ± 111 ms). Consequently, high frequency (5 MHz) ultrasound can successfully activate the brain circuits in mice. It provides a smaller stimulation region, which offers improved anatomical specificity for neuro-stimulation in a non-invasive manner.

Cloning and expression of thermo-alkali-stable laccase of Bacillus licheniformis in Pichia pastoris and its characterization.

A thermo-alkali-stable laccase gene from Bacillus licheniformis was cloned and expressed in Pichia pastoris. The recombinant laccase was secreted into the culture medium with a maximum activity of 227.9 U/L. The purified laccase is a monomeric glycoprotein, and its molecular weight was estimated to be 65 kDa on SDS-PAGE after deglycosylation. Optimal enzyme activity was observed at pH 6.2 and 70°C with syringaldazine as substrate. The recombinant laccase was highly stable in the pH range 7-9 after 10 days at 30°C. The enzyme displayed remarkable thermostability at 50-70°C, with a half-life of inactivation at 70°C of 6.9 h. It also exhibited high tolerance to NaCl and organic solvents like the native spore laccase. The purified laccase could rapidly decolorize reactive blue 19, reactive black 5 and indigo carmine in the presence of acetosyringone. More than 93% of the tested dyes were decolorized in 4 h at pH 9.0.

The Ethanol Extract of Osmanthus fragrans Flowers Reduces Oxidative Stress and Allergic Airway Inflammation in an Animal Model.

The Osmanthus fragrans flower, a popular herb in Eastern countries, contains several antioxidant compounds. Ben Cao Gang Mu, traditional Chinese medical literature, describes the usefulness of these flowers for phlegm and stasis reduction, arrest of dysentery with blood in the bowel, and stomachache and diarrhea treatment. However, modern evidence regarding the therapeutic efficacy of these flowers is limited. This study was aimed at assessing the antioxidative effects of the ethanol extract of O. fragrans flowers (OFE) in vivo and evaluating its antioxidant maintenance and therapeutic effect on an allergic airway inflammation in mice. After OFE's oral administration to mice, the values obtained in the oxygen radical absorbance capacity assay as well as the glutathione concentration in the lungs and spleens of mice increased while thiobarbituric acid reactive substances decreased significantly, indicating OFE's significant in vivo antioxidant activity. OFE was also therapeutically efficacious in a mouse model of ovalbumin-induced allergic airway inflammation. Orally administered OFE suppressed ovalbumin-specific IgE production and inflammatory cell infiltration in the lung. Moreover, the antioxidative state of the mice improved. Thus, our findings confirm the ability of the O. fragrans flowers to reduce phlegm and suggest that OFE may be useful as an antiallergic agent.

Glycogen synthase kinase-3ß contributes to remifentanil-induced postoperative hyperalgesia via regulating N-methyl-D-aspartate receptor trafficking.

BACKGROUND: Although remifentanil provides perfect analgesia during surgery, postoperative hyperalgesia after remifentanil administration might be a challenge to anesthesiologists. The trafficking and activation of N-methyl-D-aspartate (NMDA) receptors have a pivotal role in the development and maintenance of remifentanil-induced postoperative hyperalgesia. However, the underlying mechanisms of hyperalgesia are poorly elucidated. We designed the present study to examine the hypothesis that glycogen synthase kinase (GSK)-3ß could contribute to remifentanil-induced postoperative hyperalgesia via regulating NMDA receptor trafficking in the spinal cord. METHODS: Using a rat model of remifentanil-induced postoperative hyperalgesia, we first tested thermal and mechanical hyperalgesia at baseline (24 hours before incision) and 2, 6, 24, and 48 hours after remifentanil infusion. GSK-3ß mRNA and protein expression and NMDA receptor subunits (NR1, NR2A, and NR2B) trafficking in the spinal cord L4-L6 segments were then measured using real-time polymerase chain reaction and Western blot analysis. Furthermore, we investigated the effects of TDZD-8, a selective GSK-3ß inhibitor, on remifentanil-induced postoperative hyperalgesia and NMDA receptor subunits trafficking. RESULTS: Remifentanil induced significant postoperative hyperalgesia, as indicated by increased paw withdrawal latencies and thresholds to thermal and mechanical stimulation, which were markedly improved by pretreatment with TDZD-8. Moreover, remifentanil infusion increased the expression of GSK-3ß mRNA and protein as well as the GSK-3ß activity in the spinal cord. More importantly, intraoperative infusion of remifentanil increased NMDA receptor subunits (NR1 and NR2B) trafficking from the intracellular pool to surface pool in the spinal cord, which was significantly attenuated by TDZD-8. CONCLUSION: The above results suggest that activation of GSK-3ß contributes to remifentanil-induced postoperative hyperalgesia via regulating NMDA receptor subunits (NR1 and NR2B) trafficking in the spinal cord. Inhibition of GSK-3ß may be an effective novel option for the treatment of remifentanil-induced postoperative hyperalgesia.

[Changes of glycogen synthase kinase-3ß and its phosphorylation in spinal cord neurons in rats with incisional pain-remifentanil-induced hyperalgesia].

OBJECTIVE: To investigate the change in glycogen synthase kinase-3ß (GSK-3ß) in spinal cord neurons in rats with incisional pain (IP)-remifentanil-induced hyperalgesia. METHODS: 32 SD male rats (240 - 260 g) were randomly divided into 4 groups (n = 8 each): group R, group I, group R + I and group C. IP was established as Brennan's description. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured 24h before anesthesia and 2, 6, 24, 48 h after anesthesia. The rats were sacrificed after the last threshold measurement. The expressions of GSK-3ß mRNA in rats' spinal cord neurons were determined by real-time PCR. The expressions of GSK-3ß and pGSK-3ß in rats' spinal cord neurons were determined by Western blot. RESULTS: Remifentanil-induced hyperalgesia developed in group R, I and R + I. The expression of GSK-3ß mRNA and the expression of GSK-3ß in rats' spinal cord neurons were highest in group R + I. In addition, the ratio of pGSK-3ß/GSK-3ß was smallest in group R + I. CONCLUSION: These data indicate that the increased GSK-3ß activity in rats spinal cord neurons is involved in remifentanil-induced hyperalgesia.