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Ultrasound (US) has been introduced to computer-assisted orthopedic surgery for bone registration owing to its advantages of nonionizing radiation, low cost, and noninvasiveness. However, the registration accuracy is limited by US image distortion caused by variations in the acoustic properties of soft tissues. This paper proposes a soft-tissue sound-speed-aware registration method to overcome the above challenge. First, the feature enhancement strategy of multi-channel overlay is proposed for U 2 -net to improve bone segmentation performance. Secondly, the sound speed of soft tissue is estimated by simulating the bone surface distance map for the update of US-derived points. Finally, an iterative registration strategy is adopted to optimize the registration result. A phantom experiment was conducted using different registration methods for the femur and tibia/fibula. The fiducial registration error (femur, 0.98 ± 0.08 mm (mean ± SD); tibia/fibula, 1.29 ± 0.19 mm) and the target registration error (less than 2.11 mm) showed the high accuracy of the proposed method. The experimental results suggest that the proposed method can be integrated into navigation systems that provide surgeons with accurate 3D navigation information., (© 2024. International Federation for Medical and Biological Engineering.)

In order to obtain the real material parameters of heterogeneous rock, the material parameters of red sandstone specimens under uniaxial compression tests are inverted based on the Digital Image Correlation (DIC) method and the Finite Element Model Updating (FEMU) method. The DIC method is employed to calculate the displacement field of red sandstone specimens during uniaxial compression loading. Concurrently, a uniaxial compression elastic-plastic finite element numerical model with non-uniform material parameters is developed based on the FEMU method. The model adopts the Mohr-Coulomb yield criterion and adjusts the boundary conditions in real-time to maintain consistency with the test. The vertical displacement field of the numerical model is juxtaposed with that of the test to construct the objective function. Optimization is achieved using the Artificial Fish Swarm algorithm, which enables the acquisition of the non-uniform distribution and evolution process of the material parameters of specimens at different loading moments. The results indicate that this method can spatially obtain the non-uniform distribution field of material parameters and temporally track the evolution of material parameters during the loading process. This research lays a solid foundation for enhancing the accuracy of intelligent coal mining and dynamic disaster monitoring and early warning in coal mines., (© 2023. The Author(s).)

A microseismic localization algorithm that combines global search and local optimization is proposed. The Fewer Conditions Trigger Difference (FCTD) objective function of global search and local optimization is constructed, the execution process of the algorithm is described by numerical simulation, and the global search and local optimization microseismic localization algorithm is verified and applied by field data analysis. The results show that: (1) the global search and local optimization methods have fast search speed in the global range, high convergence accuracy and stable localization results in the local range, and high localization accuracy and stability without relying on the velocity model and initial values in the process of search. (2) By comparing the localization results of different localization methods, the global search and local optimization algorithms have better localization results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Purpose: Computer-assisted high tibial osteotomy (HTO) is a frequently used treatment technique for lower extremity orthopedics, and its small incision and low exposure area are major limitations in tibial registration. This work combines skin surface features and gives a suitable registration algorithm based on Iterative Closest Points (ICP) algorithm to improve registration results. Furthermore, the precision, stability and efficiency of the described method is evaluated., Methods: After the initialization stage, the bone surface and skin surface data are combined to construct registration features. Then, a steepest perturbation search method is performed after the ICP algorithm (SPS-ICP) to obtain the optimal transformation through several iterations. Finally, the registration result is evaluated by establishing ground-truth through manual landmarks., Results: Phantom experiments including simulated human tissue show that the proximal fiducial registration error (FRE) of our method can reach 0.80 ± 0.30 mm (mean ± SD) with an overall rotational error < 1° and translational error < 1.5 mm. Furthermore, it remains stable when the point set is sparse. The average registration time is less than 40 s to ensure the high efficiency of surgical operation., Conclusions: The approach fully describes a well-defined framework without additional imaging acquisition equipment for Computer-assisted HTO. By the experiment on the basis of a phantom with simulated soft tissue, the proposed method enables the accurate and robust registration of the tibia, and its computation time meets the demands of surgery., (© 2022. CARS.)

A pre folded energy absorbing device, which is the key device of energy absorption anti impact for roadway support, is tested by quasi-static compression and simulated. The energy absorbing device is divided into zones, and the influence of the area on the load displacement curve of the energy absorbing device is studied according to the area. It is found that the error of numerical simulation is within 5%, indicating that the finite element modeling procedure is appropriate for the problem analyzed here. The device crushes following the pre folded origami pattern in a stable progressive. The device was divided into four areas: the upper and lower opening region of the concave surface four corner parts; the other areas of opening regions; the middle fold edge; the surrounding four sides edge. Each area has effect on the first drop stage and the second rise stage of the load displacement curve. The middle fold edge area has an effect on the peak load value of load displacement curve. Four indicators of peak load, average load, load efficiency, and specific energy absorption were generated from the results of numerical simulation. The strength enhancement of corner region can ensure the energy absorbing device with low peak load and high mean crushing load. The other areas of opening regions affect the first descending and second ascending of the curve. The first rising stage bears the load from the middle edge., (© 2022. The Author(s).)

Background: Early rehabilitation training after ankle fracture surgery is critical to healing and avoiding complications. Inappropriate or excessive motion may impede healing or even lead to secondary injury. Currently, there is a lack of scientific quantitative postoperative rehabilitation methods after ankle fracture. Our purpose was to develop a universal method of quantifying early passive rehabilitation training after surgery by finite element (FE) analysis., Methods: A three-dimensional (3D) FE model of normal ankle was reconstructed from a computed tomography scan of a healthy male adult. Six types of ankle fractures were considered based on AO classification. We exerted joint motion load to explore the effect of movement on ankle joint mechanics after surgery. The corresponding relationship between the Inter-bone displacement and range of motion was measured to quantifying the ankle range of motion. The 44A3.3 fracture was used as an example to describe the implementation process in detail., Results: During ankle movement, most of the stress was sustained by the internal fixation devices, and the ratio of stress borne by the implants ranged from 67.9 to 94.9%. Flexion/extension exercise did not cause extra stress on the ankle contact surfaces. Ligament traction was the reason for ankle load during flexion/extension motion. The range of early passive postoperative rehabilitation training for six types of ankle fractures (AO classification) were provided., Conclusion: A quantitative method of early passive rehabilitation training after ankle fracture surgery was developed using FE analysis. This modeling method has universality for any fracture that can be reconstructed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The inherently heterogeneous microstructures of rocks lead to heterogeneity of the deformation distribution within the rock volume. In this study, experiments were conducted on red sandstone specimens with four different pre-existing crack inclinations stressed under uniaxial loading to investigate these features. Acoustic emission and digital image correlation techniques were used to confirm the damage process and obtaining deformation fields, respectively. The results showed that the heterogeneity of the deformation fields in the rock specimens amplifies with increasing stress magnitude, i.e., the displacement field heterogeneity shows two dense bands around the pre-existing crack, and the strain field heterogeneity shows localized regions with a numerical difference (quantified by the normalized standard deviation) and spatial concentration (quantified by the spatial correlation coefficient). The variations in the normalized standard deviation and spatial correlation coefficient were closely related to the damage process. The normalized standard deviation presented four evolution stages: relatively constant low value, steady growth, significant growth, and high rate growth. The spatial correlation coefficient changed from increasing at a relatively constant rate to increasing at a gentle rate and finally increasing rapidly. The evolution rate along with the strain showed two sharp fluctuations. The first could be used as precursor information of the damage. Finally, we confirmed the feasibility of the damage variable obtained from the heterogeneous deformation indicators used to calibrate or form damage evolution laws., (© 2022. The Author(s).)

In this study, a novel poly (lactic-co-glycolic acid) (PLGA)-based micelle was synthesized, which could improve the therapeutic effect of the antitumor drug doxorubicin hydrochloride (DOX) and reduce its toxic and side effects. The efficient delivery of DOX was achieved by active targeting mediated by double receptors and stimulating the reduction potential in tumor cells. FA-HA-SS-PLGA polymer was synthesized by amidation reaction, and then DOX-loaded micelles were prepared by dialysis method. The corresponding surface method was used to optimize the experimental design. DOX/FA-HA-SS-PLGA micelles with high drug loading rate and encapsulation efficiency were prepared. The results of hydrophilic experiment, critical micelle concentration determination, and hemolysis test all showed that DOX/FA-HA-SS-PLGA micelles had good physicochemical properties and biocompatibility. In addition, both in vitro reduction stimulus response experiment and in vitro release experiment showed that DOX/FA-HA-SS-PLGA micelles had reduction sensitivity. Molecular docking experiments showed that it can bind to the target protein. More importantly, in vitro cytology studies, human breast cancer cells (MCF-7), human non-small cell lung cancer cells (A549), and mouse colon cancer cells (CT26) were used to demonstrate that the dual receptor-mediated endocytosis pathway resulted in stronger cytotoxicity to tumor cells and more significant apoptosis. In and in vivo antitumor experiment, tumor-bearing nude mice were used to further confirm that the micelles with double targeting ligands had better antitumor effect and lower toxicity. These experimental results showed that DOX/FA-HA-SS-PLGA micelles have the potential to be used as chemotherapeutic drugs for precise tumor treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Jiang, Hao, Yang, Gao, Zhang, Zhang and Song.)

Through the improvement of supporting structure and the utilization of the interaction between surrounding rock and supporting structure, the synergistic system of energy-absorbing yielding anti-impact supporting structure and surrounding rock is established. The process of energy absorption device, energy-absorbing yielding anti-impact supporting structure and synergistic system under impact is simulated to analyze the properties of them. The following conclusions could be drawn. The deformation and yielding process under compression of energy absorption device is divided into five stages. Compared with the traditional supporting structure, the energy-absorbing yielding anti-impact supporting structure has the reaction force with lower value and smaller fluctuation range before the deformation of the energy absorption device reaches the third ascending section. The synergy between surrounding rock and supporting structure plays an important role in roadway support. Compared with the supporting structure without surrounding rock, the reaction force of the supporting structure in the synergistic system is lower, and a stationary stage is added in the early stage of the reaction force curve., (© 2022. The Author(s).)

The objective of this paper was to develop a PLGA carrier Ticagrelor sustained-release microspheres preparation, which was expected to continue to release Ticagrelor for 14 days with a high encapsulation rate. Ticagrelor microspheres were prepared successfully with average diameter of 7.31 µm, drug loading of 12.49 ± 0.32% and EE up to 79.09 ± 1.69%. In the release medium of PH7.4 PBS, the microspheres showed good drug release behavior in vitro. In vivo release results also showed that the sustained-release microspheres could effectively control drug release in vivo and maintain a relatively stable blood drug concentration for about 2 weeks. The results indicate that Ticagrelor sustained-release microspheres can be used for long-term treatment of acute coronary syndrome., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

When the rock burst occurs, energy absorption support is an important method to solve the impact failure. To achieve constant resistance performance of energy absorption device, as an important component of the support, the mechanical properties of one kind of prefolded tube is analyzed by quasi-static compression test. The deformation process of compression test is simulated by ABAQUS and plastic strain nephogram of the numerical model are studied. It is found that the main factors affecting the fluctuation of force-displacement curve is the stiffness of concave side wall. The original tube is improved to constant resistance by changing the side wall. The friction coefficient affects the folding order and form of the energy absorbing device. Lifting the concave side wall stiffness can improve the overall stiffness of energy absorption device and slow down the falling section of force-displacement curve. It is always squeezed by adjacent convex side wall in the process of folding, with large plastic deformation. Compared with the original one, the improved prefolded tube designed in this paper can keep the maximum bearing capacity ( P max ), increase the total energy absorption ( E ), improve the specific energy absorption (SEA), and decrease the variance ( S 2) of force-displacement curve.

Puerarin (Pue) is the most abundant isoflavonoid in kudzu root. It has been widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, poor-bioavailability of puerarin is the main obstacle to its widespread clinical applications. In this paper, HA-ADH-PS nanomicelles were prepared by chemical modification, noncovalent modification and etc, and characterized by means of FT-IR, ultraviolet (UV) and thermogravimetric analysis (TG). The encapsulation efficiency and drug loading of Pue-loaded HA-ADH-PS nanomicelles were 45.1% and 19.89% by UV, respectively. It could be observed from the transmission electron microscopy (TEM) images that HA-ADH-PS micelles appeared obvious spherical structure in the water. The particle size of HA-ADH-PS nanomicelles and Pue-loaded HA-ADH-PS nanomicelles were about 136.8 nm and 119.5 nm with a PDI of 0.237 and 0.272, respectively. The fluorescence probe method was used to characterize the critical micelle concentration, the critical micelle concentration (CMC) value of the nanomicells was 0.002 g/L and the results met the requirements and ensured the stability of micelles after dilution. DPPH assay suggested that Pue-loaded HA-ADH-PS nanomicelles had an obvious radical scavenging effect in vitro. MTT test showed that Pue-loaded HA-ADH-PS nanomicelles was non-toxic and had good biocompatibility. Thus, Pue-loaded HA-ADH-PS nanomicelles could be used as a potential drug carrier for puerarin., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This work aims to study the construction of reverse aspirin-loaded micelles prepared from amphiphilic PEG-PLA-SA triblock copolymers and the optimization of the preparation process. Using polyethylene glycol (PEG) as the initiator, ring-opening polymerization of L-lactide (L-LA) was used to prepare PEG-PLA diblock copolymers. Final product PEG-PLA-SA triblock copolymers were prepared by the reaction of stearic acid (SA) and PEG-PLA catalyzed by 4-dimethylaminopyridine (DMAP) and N,N'-Dicyclohexylcarbodiimide (DCC). Fourier transform infrared spectrometer (FT-IR) was used to characterize the product structure. PEG-PLA-SA triblock copolymers self-assembled in toluene/ethanol/water system to form reverse micelles, which could encapsulate aspirin into a hydrophilic core. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to determine the size and morphology of reverse micelles. The results showed that the reverse micelles are spherical, with a particle size of less than 70 nm. Response surface analysis method was applied to optimize the preparation process of PEG-PLA-SA. In vitro drug release was achieved by embedding reverse aspirin-loaded micelles in the biocompatible membrane in phosphate buffer saline (PBS) at 37°C. In the first 8 h, the drug release rate of the triblock copolymers was slower than that of the diblock copolymers. After 8 h, the drug release rate of both tended to be flat. The stability of aspirin-loaded reverse micelles was studied through accelerated test. These results indicate that reverse micelle PEG-PLA-SA may be a promising carrier for hydrophilic drugs like aspirin., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Papillary carcinoma is the most common type of thyroid cancer responsible for significant number of mortalities across the globe. This study was conducted to investigate the role and therapeutic implications of microRNA-7 in human papillary carcinoma. Gene expression analysis was carried out through quantitative real time PCR method. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to determine the cell proliferation. Clonogenic assay was used to assess the colony forming ability of cancer cells. Cell apoptosis was analyzed by 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB) and annexin V/PI staining assays. Migration of cancer cells was estimated through scratch heal assay and cell invasion was determined by transwell assay method. Western blotting was done to examine the protein expression. Xenografted mice models were employed to examine the effects of miR-7 overexpression in vivo . Results showed miR-7 to be significantly ( P < 0.05) repressed in papillary carcinoma. Cancer cell proliferation was inhibited by miR-7 through induction of apoptotic cell death as revealed by DAPI, AO/EB and annexin V/PI staining assays. The colony forming potential of cancer cells also decreased under miR-7 overexpression. miR-7 overexpression also inhibited the migration and invasion of cancer cells. Bcl-2 was identified as the intracellular target of miR-7 and regulatory effects of miR-7 were seen to be exerted through translation repression of Bcl-2. The results of xenograft study revealed miR-7 overexpression significantly ( P < 0.05) suppressed the growth of the tumor in vivo . The results point towards the therapeutic implications of miR-7 in the management of papillary carcinoma., Competing Interests: None., (AJTR Copyright © 2020.)

Background: The objective of this systematic review was to explore the association between private health insurance and health care utilization., Methods: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases for relevant articles since 2010. Studies were eligible if they described original empirical research on the utilization of public health care by individuals with private health insurance, compared with individuals without private insurance. A pooled measure of association between insurance status with health care utilization was assessed through meta-analysis., Results: Twenty-six articles were included in the final analysis. We found that patients with private insurance did not use more public health care than people without private insurance (P < 0.05). According to the subgroup analysis, people with private insurance were more likely to be hospitalized than people with no insurance (OR 1.67; 95% CI, 1.18 to 2.36)., Conclusions: People with private insurance did not increase their use of health care (outpatient services), compared to those without private insurance. Private health insurance coverage may ease the financial burden on patients and on the public health insurance system.

The kisspeptin system is a central modulator of the hypothalamic-pituitary-gonadal axis in vertebrates. Its existence outside the vertebrate lineage remains largely unknown. Here, we report the identification and characterization of the kisspeptin system in the sea cucumber Apostichopus japonicus. The gene encoding the kisspeptin precursor generates two mature neuropeptides, AjKiss1a and AjKiss1b. The receptors for these neuropeptides, AjKissR1 and AjKissR2, are strongly activated by synthetic A. japonicus and vertebrate kisspeptins, triggering a rapid intracellular mobilization of Ca 2+ , followed by receptor internalization. AjKissR1 and AjKissR2 share similar intracellular signaling pathways via G αq /PLC/PKC/MAPK cascade, when activated by C-terminal decapeptide. The A. japonicus kisspeptin system functions in multiple tissues that are closely related to seasonal reproduction and metabolism. Overall, our findings uncover for the first time the existence and function of the kisspeptin system in a non-chordate species and provide new evidence to support the ancient origin of intracellular signaling and physiological functions that are mediated by this molecular system., Competing Interests: TW, ZC, ZS, JY, XC, ZY, KX, XX, QY, YS, WW, YT, LS, LZ, SG, NZ No competing interests declared, (© 2020, Wang et al.)

Background: Neuroendocrine neoplasm is a rare solid tumor. Metastatic pattern of the gastrointestinal neuroendocrine neoplasm (GI-NEN) has not been fully explored., Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (SEER-9 registry) from 1973 to 2015. Incidence was estimated by Joinpoint regression analyses. Data with additional treatment fields of GI-NEN were extracted from the SEER-18 registry from 1 January 2010 to 31 December 2015. A total of 14 685 GI-NEN patients were included in this study. Statistical analyses were performed with SPSS 25.0, the Intercooled Stata SE 15.0, and GraphPad Prism 7., Results: Incidence of GI-NENs increased from 0.51 per 100 000 patients in 1973 to 6.20 per 100 000 patients in 2015. Of them, 2003 patients were stage IV GI-NEN at the time of diagnosis, including 1459 (72.84%) patients with liver metastasis, 144 (7.19%) lung metastasis, 115 (5.74%) bone metastasis, and 27 (1.35%) brain metastasis. Esophageal NEN had the highest risk of metastasis (52.68%). The median survival for patients with liver, lung, bone, and brain metastasis was 38, 6, 9, and 2 months, respectively. The presence of lung or liver metastasis indicated higher risk of concurrent existence of bone and brain metastasis than those without., Conclusion: Bone and brain metastasis should be screened in the GI-NEN patients if they had lung or liver metastasis. Findings of the current study could help clinicians to identify distant metastasis of GI-NENs as early as possible, and by which, to improve survival rate of GI-NENs., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Tafazzin has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of Tafazzin and mitochondrial homeostasis in thyroid cancer have not been explored. The aim of our study is to investigate the influences of Tafazzin on thyroid cancer apoptosis with a focus on mitochondrial fission. Our results indicated that Tafazzin deletion induced death in thyroid cancer via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, was activated by Tafazzin deletion. Furthermore, we found that Tafazzin affected mitochondrial stress by triggering inverted formin 2 (INF2)-related mitochondrial fission. The loss of INF2 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that Tafazzin regulated INF2 expression via the JNK signaling pathway; moreover, the blockade of JNK prevented Tafazzin-mediated INF2 expression and improved cancer cell survival. Taken together, our results highlight the key role of Tafazzin as a master regulator of thyroid cancer viability via the modulation of INF2-related mitochondrial fission and the JNK signaling pathway. These findings defined Tafazzin deletion and INF2-related mitochondrial fission as tumor suppressors that act by promoting cancer apoptosis via the JNK signaling pathway, with potential implications for new approaches to thyroid cancer therapy., (© 2019 Wiley Periodicals, Inc.)

A series of novel 2-(6-thioxo-1,3,5-thiadiazinan-3-yl)-N'-phenylacethydrazide derivatives were designed, synthesized and evaluated for their antifungal activities against Fusarium graminearum (Fg), Rhizoctonia solani (Rs), Botrytis cinerea (Bc) and Colletotrichum capsici (Cc). The bioassay results in vitro showed that most of the title compounds exhibited impressive antifungal activities against the above plant fungi. Particularly, the compounds 5c, 5f, 5g, 5i, 5m and 5p displayed desirable anti-Rs activities, with the corresponding EC 50 values of 0.37, 0.32, 0.49, 0.50, 0.46 and 0.45 µg/mL, respectively, which are superior to the positive control carbendazim (0.55 µg/mL). Further in vivo bioassay results showed that the anti-Rs activity of title compound 5f at 200 µg/mL reached 95.84% on detached rice leaves and 93.96% on rice plants. Featuring convenient synthesis, novel structures and desirable antifungal activity, these 2-(6-thioxo-1,3,5-thiadiazinan-3-yl)-N'-phenylacethydrazide derivatives could be further studied as the potential candidates of novel agricultural fungicides.

In order to improve the adhesion between a PGA scaffold and islet cells, it is necessary to find a suitable method to modify the scaffold. In this study, the PGA scaffold surface was modified by plasma, polylysine coating and plasma combined with polylysine coating (P-P-PGA). The surface adhesion of the modified PGA scaffold was examined, and the stretchability and infiltration of the PGA scaffold were also tested. Then, the PGA scaffold treated under the optimal treatment conditions was selected to co-culture with rat islet cells, and the survival activity of the rat islet cells on the untreated PGA scaffold and the P-P-PGA scaffold was examined via the MTT method. Rhodamine staining and DAPI staining were used to detect the number of islet cells adhered to four groups of scaffolds at different culture time points. The PGA-islet graft in the leg muscle of rats was stained with HE to perform the PGA-islet graft pathological examination. The experimental results showed that when the plasma treatment power was 240 W, the processing time was 4 min; the concentration of the polylysine coating solution was 2 mg ml -1 , the tensile strength of the PGA scaffold was 320.45 MPa and the amount of infiltration of the PGA scaffold by the serum medium presented the maximum value: 3.17 g g -1 . The MTT survival activity test results showed that after 3 d of culture, the survival activity of the islet cells of the treated PGA scaffold culture group (2.02 ± 0.13) was significantly different from the survival activity of the islet cells of the untreated PGA scaffold culture group (1.93 ± 0.10). The survival activities of the islet cells in the experimental groups (1.60 ± 0.13, 1.40 ± 0.12) were still higher than those of the control groups (0.96 ± 013, 0.69 ± 0.09) at 15 and 21 d. The results of the rhodamine and DAPI staining showed that with the increase in culture time, the number of the adherent cells in each group increased, and the number of the adherent islet cells in the experimental group was higher than that in the untreated group. The HE staining results showed that the islet cells on the P-P-PGA scaffold were more than those on the untreated PGA scaffold. After modification of the PGA scaffold, the adhesion of the islet cells improved, which was conducive to the growth of islet cells. These results confirmed that the plasma combined with polylysine coating treatment could enhance the adhesion of the PGA scaffold surface, so that the scaffold and the islet cells exhibited better adhesion and biocompatibility, and the modified PGA scaffold (P-P-PGA) could be used as a promising islet cell scaffold., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chitosan (CS)-acetylsalicylic acid (ASA) nanoparticles, which are well dispersed and stable in aqueous solution, have been prepared by interpolymer complexation of ASA in CS solution. The physicochemical properties of nanoparticles were investigated by using FT-IR, 1 H NMR, scanning electron microscope（SEM）, dynamic light scattering, and UV spectrophotometer. It was found that the carboxyl group of the ASA had firmly integrated on the amino group of CS and the ASA-CS nanoparticles were almost spherical in shape with an average diameter of less than (79.3 ± 24.6) nm in high reproducibility and showed high chemical stability against environmental changes. It was also found that the prepared nanoparticles carried a positive charge and showed the size in the range from 700 to 150 nm. The surface structure and zeta potential of nanoparticles can be controlled by different preparation processes. The factor experiment results indicated that the ASA-CS nanoparticles had satisfactory loading capacity (LC) and encapsulation efficiency (EE), 27.27% and 46.88% (data not shown), respectively. The experiments of in vitro ASA release showed that these nanoparticles provided a sustained and pH-dependent drug release manner, and the release behavior was influenced by the pH value of the medium. Preliminary pharmacology experiment exhibited prolonged circulation and higher bioavailability than that of ASA. All the results indicated that ASA/CS nanoparticles may have promising pharmaceutical application, and further pharmacological research is needed to confirm these beneficial effects.

Currently, accumulating documents have paid great attention to the critical role of long non-coding RNAs. The long non-coding RNAs DLEU1 has been demonstrated to be dysregulated in many solid tumors and hematological malignancies. However, the detailed descriptions about its potential roles and molecular mechanism in gastric cancer (GC) are still blurry. As for our research, it was found out that DLEU1 was observably intensified in GC tissues and cell lines. And highly expressed DLEU1 was relevant to tumor size, advanced stage of pathology and lymph node metastasis in GC patients. Silenced DLEU1 obviously suppressed proliferation via leading to the cell cycle arrest and inducing cell apoptosis of GC. Furthermore, mechanistic experiments uncovered that DLEU1 could recruit LSD1 (lysine specific demethylase 1) to the promoter regions of KLF2 and then suppressed its transcription. In addition, rescue assays revealed that the oncogenic function mediated by DLEU1 in GC was partly by regulating KLF2. Collectively, our findings manifested that DLEU1 might serve as an oncogene in GC.

Background/aim: Mammalian target of rapamycin (mTOR) plays an important role in papillary thyroid carcinoma (PTC) cell progression. CZ415 is a novel, highly-efficient and specific mTOR kinase inhibitor. The current study tested the potential anti-tumor activity of CZ415 in human PTC cells., Methods: The established (TPC-1 cell line) and primary human PTC cells were treated with CZ415. Cell survival and growth were tested by Cell Counting Kit-8 assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by caspase-3/-9 activity assay, Hoechst-33342 staining assay and single-stranded DNA ELISA assay. Cell cycle progression was tested by propidium iodide-FACS assay. The mTOR signaling was tested by Western blotting assay and co-immunoprecipitation assay. The mouse xenograft tumor model was applied to study the effect of CZ415 in vivo., Results: In cultured human PTC cells, treatment with CZ415 at nM concentrations significantly inhibited cell survival and growth. CZ415 induced apoptosis activation and cell cycle arrest in human PTC cells. CZ415 disrupted assembling of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-GβL association) in TPC-1 cells, which led to de-phosphorylation of the mTORC1 substrates (S6K1 and 4E-BP1) and the mTORC2 substrate AKT (Ser-473). Further studies show that the autophagy inhibitor 3-methyladenine (3-MA) or Beclin-1 shRNA aggravated CZ415-induced cytotoxicity against PTC cells. In vivo, CZ415 oral administration inhibited TPC-1 xenograft tumor growth in mice., Conclusion: Our results show that mTOR blockage by CZ415 inhibits PTC cell growth in vitro and in vivo., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Using gas-chromatography/mass spectrometry (GC-MS) method dating data ( 210 Pb and 137 Cs) and OCPs signatures, the temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was investigated in dated sediment core from Baoxianghe reservoir in Dianchi watershed, Southwest China. The concentrations of total PAHs were in the range of 162.3-762.2 ng g -1 from 1945 to 2013. There showed an obvious increase from 1960s to 2000s. The distributions of PAHs were influenced by local population and Gross Domestic Product (GDP) during the period between1962 and 2004. PAHs sources changed from biomass or domestic coal combustion (before 1980) to liquid fossil fuel combustion (after 1980). Total toxic toxicity equivalents (TEQs) of the carcinogenic PAHs were very low (3.03-28.08 ng g -1 ).

To study high-frequency ultrasound features and pathological characteristics of medullary thyroid carcinoma (medullary thyroid carcinoma, MTC) with the purpose to improve the diagnostic accuracy of this disease. The clinical data of 20 cases of patients with MTC confirmed by the clinical surgery were retrospectively analyzed. And the high-frequency ultrasound features were analyzed and compared with the pathological characteristics. There were 16 cases with tumor invasion into one side of the thyroid gland; 17 cases with tumor in the middle-upper pole of the thyroid gland. And 8 cases were detected with uneven echo of high frequency ultrasound appearance and pathological manifestations of cystic degeneration to necrosis seen under the light microscope or normal thyroid tissue within part of the lump. 16 cases were tested with even echo of high frequency ultrasound appearance, and tumor cells were formed in the solid and block-like shape under the light microscope. And 18 cases were manifested with low echo, with proliferation of fibrous tissue within the intercellular substance under the light microscope. 18 cases could be seen the calcification points and often amyloid-like content deposited in the intercellular substance seen under the light microscope. In addition, the pathological manifestations of the 8 cases combined with lymph node metastasis were the "lash tumor" of the metastatic lymph nodes and primary tumor. MTC was commonly located in the middle-upper region of the thyroid gland and in one leaf of the thyroid gland, combined with lymph node metastasis. The high frequency ultrasound appearance was the even low-echo tumor in round or quasi-circular shape, with obscure boundary and often combined with rough calcification. High frequency ultrasound could be used as the prior physical diagnostic method for medullary thyroid carcinoma.

Glycine betaine (betaine) is widely distributed in nature and can be found in many microorganisms, including bacteria, archaea, and fungi. Due to its particular functions, many microorganisms utilize betaine as a functional chemical and have evolved different metabolic pathways for the biosynthesis and catabolism of betaine. As in animals and plants, the principle role of betaine is to protect microbial cells against drought, osmotic stress, and temperature stress. In addition, the role of betaine in methyl group metabolism has been observed in a variety of microorganisms. Recent studies have shown that betaine supplementation can improve the performance of microbial strains used for the fermentation of lactate, ethanol, lysine, pyruvate, and vitamin B12, during which betaine can act as stress protectant or methyl donor for the biosynthesis of structurally complex compounds. In this review, we summarize the transport, synthesis, catabolism, and functions of betaine in microorganisms and discuss potential engineering strategies that employ betaine as a methyl donor for the biosynthesis of complex secondary metabolites such as a variety of vitamins, coenzymes, and antibiotics. In conclusion, the biocompatibility, C/N ratio, abundance, and comprehensive metabolic information of betaine collectively indicate that this molecule has great potential for broad applications in microbial biotechnology.

The growth and metastasis of tumors is dependent on angiogenesis; however, the association between tumor stem cells (TSCs) and tumor angiogenesis remains to be elucidated. The present study aimed to investigate the expression of the TSC markers aldehyde dehydrogenase 1 (ALDH1) and cluster of differentiation 133 (CD133) in invasive ductal breast carcinoma, and identify their correlation with tumor angiogenesis. Stem-like cells from the breast tissue of 120 patients, who were diagnosed with invasive ductal breast carcinoma at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, Henan, China) between January 2009 and December 2010, were collected by surgical resection and analyzed using immunohistochemical double staining. The expression of the vascular markers CD34, CD105 and vascular endothelial growth factor (VEGF) were determined using single staining. Overall, 25.83% (31/120) of the specimens contained a large number of ALDH1+/CD133+ stem-like cells (ALDH1+/CD133+ tumor). ALDH1+/CD133+ expression is associated with microvessel density, VEGF-positive rate and estrogen receptor expression (P<0.05); however, ALDH1+/CD133+ expression was not associated with age, tumor diameter, lymph node metastasis, histological classification, progesterone receptor expression or human epidermal growth factor receptor 2 expression (P>0.05). The ALDH1+/CD133+ tumor phenotype and expression of VEGF were identified to be correlated in the present study (P=0.020). The present study revealed a close association between breast cancer TSC markers, including ALDH1 and CD133, and tumor angiogenesis. The results of the present study may provide a novel target and treatment strategy for future studies investigating tumor growth and metastasis.

Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate-buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF.

Driven by the increasing demands of the aircraft assemblage for the pose-adjustment equipment in the large-scale component docking, this paper carries out the topology synthesis of a 1-translational and 3-rotational (1T3R) four degrees of freedom (DoF) parallel manipulator with an articulated traveling plate. First, the articulated traveling plate is defined as that includes more than one rigid body articulated by one or more kinematic joints. Then, the relationship among the DoFs of the parallel manipulator and the articulated traveling plate and the number of the in-parts are proposed. According to the agreement of the arrangement way between the open-loop limbs and the in-parts, the topology synthesis procedure of the 1T3R 4-DoF parallel manipulator with an articulated traveling plate is proposed. Finally, their topology structures are obtained by discussing those of four types in terms of 1D-H, 1D-V type with opposite layout and 1D-H, 1D-V type with adjacent layout, in which the topology structures exist only for 1D-H and 1D-V type with opposite layout.

Tumor proliferation, drug resistance and cell stemness are major difficulties that are encountered during breast cancer therapy and are often responsible for disease progression and cancer-related mortality. β-catenin is considered to be an invasion gene in breast cancer. However, how β-catenin regulates breast cancer cell proliferation and stemness remains unclear. In the present study, β-catenin knockdown by small interfering RNA in MDA-MB-468, a highly metastatic breast cancer cell line, inhibited the expression of β-catenin , Oct3/4 (stemness), survivin (anti-apoptosis) and BCRP (drug resistance). Knockdown of β-catenin enhanced the effects of fluorouracil (5-FU) chemotherapy on the proliferation of MDA-MB-468 cells. Thus, these preliminary results indicate that β-catenin knockdown enhanced 5-FU-induced proliferation inhibition in the breast cancer cell line MDA-MB-468, and indicate that combining 5-FU with gene silencing could be an advantageous option for enhancing the curative effect of chemotherapy in breast cancer and other malignancies.

The in vitro culture of pancreatic islets reduces their immunogenicity and prolongs their availability for transplantation. Both simulated microgravity (sMG) and a polyglycolic acid scaffold (PGA) are believed to confer advantages to cell culture. Here, we evaluated the effects of sMG combined with a PGA on the viability, insulin-producing activity and morphological alterations of pancreatic islets. Under PGA-sMG conditions, the purity of the islets was ≥85%, and the islets had a higher survival rate and an increased ability to secrete insulin compared with islets cultured alone in the static, sMG, or PGA conditions. In addition, morphological analysis under scanning electron microscopy (SEM) revealed that the PGA-sMG treatment preserved the integral structure of the islets and facilitated islet adhesion to the scaffolds. These results suggest that PGA-sMG coculture has the potential to improve the viability and function of islets in vitro and provides a promising method for islet transplantation.

Significant problems existing in the islet transplantation include a poor survival ability of the islet cells cultured under static conditions in vitro, decreased secretion function, and limited transplantation efficiency. In this study, we cocultured the three-dimensional (3D) self-assembling peptide nanofiber hydrogel scaffold with the islets from adult Wistar rats. The nanofiber scaffold constructed a 3D environment for the islets culture. The results of DTZ staining showed that the purity of the islets in the scaffold was >80%. The result of the fluorescent staining with AO-PI demonstrated that the viability of the islets in the 3D culture environment (within scaffold) was greater than those in the two-dimensional (2D) culture environment (without scaffold). The islets encapsulated in the 3D peptide nanofiber scaffold exhibited better secretion function. The insulin releasing index in the 3D group was remarkably higher than that in the 2D group. By scanning electron microscopy, it was observed that the 3D self-assembling peptide nanofiber hydrogel scaffold formed a nano scale fiber with a geometric form and the islets were encapsulated in this scaffold. Our research demonstrated that this nanofiber scaffold provided a favorable 3D environment for the islets to be cultured in vitro and then improve the secretion function and prolong the survival time of the islet in vitro., ((c) 2010 Wiley Periodicals, Inc.)

Objective: To study the effect of xenotransplantation with pig parathyroid cells, which was prepared using cell microencapsulation technique, on the treatment of hypoparathyroidism in rats without immunosuppressor., Methods: Parathyroid cells were isolated from 10 healthy newborn pigs and encapsulated in alginate-polylysine-alginate (APA) membranes. Thirty-two aparathyroid Wistar rats were randomly allocated to microcapsule, non-microcapsule, empty microcapsule, and control groups. Each rat was injected intraperitoneally with encapsulated porcine parathyroid cells, free porcine parathyroid cells, empty capsules or 0.9% NaCl, respectively. Total serum calcium and parathyroid hormone levels were monitored continuously for 40 weeks. And then, the transplant beds were retrieved and subjected to morphologic and electron microscopic examination., Results: In those animals xenotransplanted with microencapsulated porcine parathyroid cells, the calcium and PTH levels were consistently within the normal range during the 40 weeks. In contrast, no therapeutic effects were observed in rats in the non-microcapsule group. Furthermore, neither empty capsules nor 0.9% NaCl were shown to have any effect on the recipient's serum calcium or PTH levels. After 40 weeks, electron microscopic examination demonstrated that the parathyroid cells within the microcapsules had survived well in vivo., Conclusions: Xenotransplantation of microencapsulated newborn pig parathyroid cells can successfully treat hypoparathyroidism in rats without using immunosuppressive drugs. The results of this study show the possible clinical use of microencapsulated porcine parathyroid cells.