Design, Control, and Validation of a Symmetrical Hip and Straight-Legged Vertically-Compliant Bipedal Robot.

This paper presents the development, modeling, and control of L03, an underactuated 3D bipedal robot with symmetrical hips and straight legs. This innovative design requires only five actuators, two for the legs and three for the hips. This paper is divided into three parts: (1) mechanism design and kinematic analysis; (2) trajectory planning for the center of mass and foot landing points based on the Divergent Component of Motion (DCM), enabling lateral and forward walking capabilities for the robot; and (3) gait stability analysis through prototype experiments. The primary focus of this study is to explore the application of underactuated symmetrical designs and determine the number of motors required to achieve omnidirectional movement of a bipedal robot. Our simulation and experimental results demonstrate that L03 achieves simple walking with a stable and consistent gait. Due to its lightweight construction, low leg inertia, and straight-legged design, L03 can achieve ground perception and gentle ground contact without the need for force sensors. Compared to existing bipedal robots, L03 closely adheres to the characteristics of the linear inverted pendulum model, making it an invaluable platform for future algorithm research.

[Retracted] MicroRNA­136 inhibits prostate cancer cell proliferation and invasion by directly targeting mitogen­activated protein kinase kinase 4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion assay data shown in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors at different research institutes, some of which have been retracted. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 4803­4810, 2018; DOI: 10.3892/mmr.2018.8417].

Spring damping based control for a novel lower limb rehabilitation robot with active flexible training planning.

BACKGROUND: During neurological rehabilitation training for patients with lower limb dysfunction, active rehabilitation training based on interactive force recognition can effectively improve participation and efficiency in rehabilitation training. OBJECTIVE: This study proposes an active training strategy for lower-limb rehabilitation robots based on a spring damping model. METHODS: The active training strategy included a kinetic model of the human-machine system, calculated and verified using a pull-pressure force sensor We used a dynamic model of the human-machine system and tensile force sensors to identify the human-machine interaction forces exerted by the patient Finally, the spring damping model is used to convert the active interaction force into the offset angle of each joint, obtaining the active interaction force followed by the active movement of the lower limbsRESULTS:The experimental results showed that the rehabilitation robot could follow the active interaction force of the subject to provide assistance, thus generating the following movement and effectively helping patients improve joint mobility. CONCLUSION: The active flexibility training control strategy based on the virtual spring damping model proposed in this study is feasible, and motion is stable for patients with lower limb dysfunction after stroke Finally, the proposed active training method can be implemented in future work in other rehabilitation equipment and combined virtual reality technology to improve rehabilitation training experience and increase patient participation.

Prognostic value of miR-339-5p in patients with prostate cancer and its effects on tumor progression.

Prostate cancer places a serious health burden on males. The present study aimed to explore the potential prognostic significance and biological function of microRNA (miR)-339-5p in patients with prostate cancer. The expression of miR-339-5p was detected in prostate cancer tissues and cell lines by using reverse transcription-quantitative PCR. Kaplan-Meier survival curves and Cox regression analyses were used to investigate the prognostic significance of miR-339-5p in prostate cancer. The Cell Counting Kit-8 assay was used to determine the effect of miR-339-5p on prostate cancer cell proliferation. Transwell assays were used to assess the effect of miR-339-5p on cell migration and invasion. The results indicated that the expression of miR-339-5p was downregulated in prostate cancer tissues and cell lines. Downregulation of miR-339-5p was significantly associated with the Gleason score, lymph node metastasis and TNM stage. Patients with high miR-339-5p expression levels had a longer survival time than those with low expression levels. Multivariate Cox regression analysis indicated that miR-339-5p may be an independent prognostic factor for the overall survival of patients with prostate cancer. Overexpression of miR-339-5p inhibited the proliferation, migration and invasion of prostate cancer cells. Taken together, these results indicated that miR-339-5p functions as a suppressor gene in prostate cancer and acts by inhibiting cell proliferation, migration and invasion of prostate cancer cells. miR-339-5p may serve as an independent prognostic biomarker and therapeutic target for the treatment of prostate cancer.

PLP2 Expression as a Prognostic and Therapeutic Indicator in High-Risk Multiple Myeloma.

Multiple myeloma (MM) is a devastating cancer with a highly heterogeneous outcome. Because of the heterogeneity of myeloma cells, risk stratification is important for making therapeutic regimens. Nevertheless, no immunohistochemical predictive and prognostic marker has been constructed yet. In the present study, we explored the prognostic value of proteolipid protein 2 (PLP2) in MM patients using immunohistochemistry (IHC). We assessed PLP2 expression in bone marrow (BM) biopsy specimens obtained from 87 newly diagnosed MM (NDMM) patients. Correlations between PLP2 expression and clinicopathological features were analyzed. PLP2 expression was present in high-risk MM patients, which was increased with disease progression and poor prognosis. PLP2 was increasing in parallel with high beta-2 microglobulin (ß2-MG) and lactate dehydrogenase (LDH). Furthermore, MM patients with low PLP2 expression could achieve a favorable treatment response. PLP2 may be a novel biomarker for prognostic prediction and a therapeutic target for anti-MM treatments.

Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment.

INTRODUCTION: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increase risk of transformation to acute myeloid leukemia (AML). Daunorubicin (DNR) is an indispensable drug for the treatment of MDS and AML. However, its side effects including cardiac toxicity and bone marrow suppression severely limit clinical application. Many researches reported high expression of CD123 antigen on high-risk MDS cells, so we constructed a novel drug delivery system comprising daunorubicin-loaded CdTe QDs conjugated with anti-CD123 mAbs (DNR-CdTe-CD123) to develop targeted combination chemotherapy for MDS. METHODS: CdTe conjugated antiCD123 through amide bond, co-loaded with DNR with electrostatic bonding. Then, we determined characterization and release rate of DNR-CdTe-CD123. The therapeutic effect and side effect of drug delivery system were evaluated through in vitro and in vivo experiments. RESULTS: CdTe showed appropriate diameter and good dispersibility and DNR was loaded into CdTes with high encapsulation efficiency and drug loading. The maximum drug loading and encapsulation efficiency were 42.08 ± 0.64% and 74.52 ± 1.81%, respectively, at DNR concentration of 0.2mg/mL and anti-CD123 mAbs volume of 5ul (100ug/mL). Flow cytometry (FCM) showed that CD123 antigen was highly expressed on MUTZ-1 cells, and its expression rate was 72.89 ± 10.67%. In vitro experiments showed that the inhibition rate and apoptosis rate of MUTZ-1 cells treated with DNR-CdTe-CD123 were higher than those in the other groups (P<0.05). Compared with the other groups, the level of apoptosis-related protein (P53, cleaved caspase-9, Bax and cleaved caspase-3) were upregulated in DNR-CdTe-CD123 group (P<0.05). In vivo experiments, DNR-CdTe-CD123 can effectively inhibit the tumor growth of MDS-bearing nude mice and reduce the side effects of DNR on myocardial cells. CONCLUSION: The system of DNR-CdTe-CD123 enhances the therapeutic effects and reduce the side effects of DNR, thus providing a novel platform for MDS treatment.

Increased expression of TNFRSF14 indicates good prognosis and inhibits bladder cancer proliferation by promoting apoptosis.

Despite advances in management, bladder cancer remains a principal cause of cancer­associated complications. Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) is dysregulated in certain types of cancer; however, limited data are available on the expression and function of TNFRSF14 in bladder cancer. In the present study, the aim was to evaluate the expression and biological functions of TNFRSF14 in bladder cancer. Firstly, the expression levels of TNFRSF14 in bladder cancer tissue were examined using The Cancer Genome Atlas (TCGA) database. Secondly, reverse transcription­quantitative polymerase chain reaction was utilized to investigate the expression levels of TNFRSF14 in the T24, SW780 and EJ­M3 bladder cancer cell lines. Transfection and Cell Counting kit­8 (CCK­8) assay was used to evaluate whether TNFRSF14 overexpression or silencing would have an effect on cell proliferation of T24 and EJ­M3 cells. In addition, TNFRSF14­induced apoptotic cells were identified using Annexin V­fluorescein isothiocyanate and propidium iodide staining. Western blot analysis was used to detect proteins associated with the phosphatidylinositol 3­kinase pathway. According to the TCGA dataset, the expression levels TNFRSF14 were decreased in bladder cancer tissue compared with in normal control samples. Patients with bladder cancer exhibiting low expression levels of TNFRSF14 had a worse prognosis compared to those with high expression levels of TNFRSF14. Overexpression of TNFRSF14 in T24 cells led to increased apoptosis and inhibited cell proliferation in vitro. Western blotting demonstrated that TNFRSF14 overexpression increased the expression levels of caspase3­p17 in T24 cells, but significantly decreased the expression levels of phosphorylated (p)­protein kinase B (AKT) and P70 S6 kinase (P70). TNFRSF14 silencing in EJ­M3 cells enhanced cell growth, inhibited cell apoptosis, increased the expression levels of p­AKT and P70, and decreased the expression levels of caspase3­p17. In conclusion, TNFRSF14 may serve a tumor suppressive role in bladder cancer by inducing apoptosis and suppressing proliferation, and act as a novel prognostic biomarker for bladder cancer.

Inhibition of miR-1247 on cell proliferation and invasion in bladder cancer through its downstream target of RAB36.

Recently, microRNA-1247 (miR-1247) has been reported to function as tumour suppressor in several cancer types, including pancreatic cancer, hepatocellular cancer and lung cancer. However, the biological function of miR-1247 in bladder cancer and the underlying mechanisms have remained largely uncovered. In this study, the expression of miR-1247 was significantly downregulated, while RAB36 protein was remarkably upregulated in bladder cancer tissues and cell lines compared with that in paired adjacent normal tissues or normal cell line (SU-HUC-1). The function of miR-1247 and RAB36 in the cell viability, proliferation and invasion of bladder cancer cells (T24 and J82) was assessed by CCK-8, colony formation and Transwell assay, respectively. Gain of function studies showed that upregulation of miR-1247 significantly inhibited cell proliferation and invasion capacity of bladder cancer cells. Consistently, downregulation of RAB36 mimicked the suppressive effects of miR-1247 overexpression in bladder cancer cells. Importantly, miR-1247 was confirmed to target the 30untranslated region (UTR) of RAB36 and downregulated its expression using luciferase reporter assay and Western blot assays. In conclusion, these results provide the first clues regarding the role of miR-1247 might be a potential therapeutic agent and diagnostic marker of bladder cancer by inhibiting RAB36 expression.

Transcription factor FoxM1 is the downstream target of c-Myc and contributes to the development of prostate cancer.

BACKGROUND: Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified. METHODS: In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells. Whether c-Myc could bind to FoxM1 promoter was identified by ChIP assay. Finally, the migratory, invasive, and proliferative abilities in FoxM1 overexpressing and silencing PC-3 cells were detected by wound healing, transwell assay, CCK-8 assays, and Ki-67 protein level. RESULTS: We found that the expression level of FoxM1 and c-Myc were both increased in prostate cancer samples compared with para-cancer samples. The expression level of FoxM1 was changed consistent with the protein level of c-Myc. ChIP assay detected the direct binding of c-Myc in FoxM1 gene promoter. Lastly, overexpression of FoxM1 increased the migratory, invasive, and proliferative abilities of PC-3 cells, and its downregulation significantly decreased the migratory, invasive, and proliferative abilities. CONCLUSIONS: In conclusion, FoxM1 was significantly increased in prostate cancer samples, and it could regulate the proliferative and invasive ability of prostate cancer cells which might be a new target for prostate cancer. Besides, c-Myc could regulate the expression level of FoxM1 by directly binding to its gene promoter.

MicroRNA­136 inhibits prostate cancer cell proliferation and invasion by directly targeting mitogen­activated protein kinase kinase 4.

Prostate cancer (PCa) is the second most common type of cancer and the 6th leading cause of cancer­associated mortality worldwide. Accumulated evidence suggests that PCa initiation and progression are controlled by microRNAs (miRNAs). Therefore, investigating PCa­associated miRNAs may provide novel biomarkers for the diagnosis and treatment of patients with PCa. In the present study it was demonstrated that miRNA­136 (miR­136) expression was significantly downregulated in PCa tissues and cell lines. The resumption of miR­136 expression suppressed cell proliferation and invasion in PCa cells. Bioinformatics analysis predicted that mitogen­activated protein kinase kinase 4 (MAP2K4) was a direct target of miR­136. This prediction was experimentally confirmed by a luciferase reporter assay, RT­qPCR and western blot analysis. MAP2K4 was highly expressed in PCa tissues and inversely correlated with the miR­136 expression level. Additionally, the restoration of MAP2K4 expression significantly blocked the inhibitory effects of miR­136 on cell proliferation and invasion in PCa cells. Therefore, miR­136 may suppress the proliferation and invasion of PCa cells by targeting MAP2K4 and may be a novel candidate target for cancer therapy against PCa.

Regulation of the angiotensin II-p22phox-reactive oxygen species signaling pathway, apoptosis and 8-oxoguanine-DNA glycosylase 1 retrieval in hyperoxia-induced lung injury and fibrosis in rats.

The present study was designed to explore the impact of hyperoxia on lung injury and fibrosis via the angiotensin II (AngII)-p22phox-reactive oxygen species (ROS) signaling pathway, apoptosis and 8-oxoguanine-DNA glycosylase 1 (OGG1) repair enzyme. Newborn Sprague-Dawley rats were randomly divided in the newborn air group, newborn hyperoxia group and newborn intervention group, the latter of which was administered the chymotrypsin inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1, 6-dihydropyrimidine-1-yl)-N-[4-dioxo-1-phenyl-7-(2-pyridyloxy)] 2-heptyl-acetamide (NK3201). A group of adult rats also received hyperoxic treatment. Histomorphological changes in lung tissues were dynamically observed. AngII, ROS, angiotensin type 1 receptor (AT1R) and p22phox messenger RNA (mRNA) levels, and OGG1 and peroxisome proliferator-activated receptor-γ (PPARγ) protein levels in the lung tissues were detected at various times after hyperoxia. Hyperoxia led to traumatic changes in the lungs of newborn rats that resulted in decreased viability, increased mortality, morphological changes and the apoptosis of alveolar type II epithelial cells (AT-II), as well as increased expression levels of AngII, AT1R and p22phox, which would ultimately lead to secondary diseases. NK3201 significantly inhibited the hyperoxia-induced increased expression of AngII, AT1R and p22phox and further promoted OGG1 and PPARγ protein expression, thus reducing the intrapulmonary ROS level, the apoptotic index and caspase-3 levels. However, the adult hyperoxia group only exhibited tachypnea and reduced viability. This study suggested that the AngII-p22phox-ROS signaling pathway, PPARγ and OGG1 together contributed to the hyperoxia-induced lung injury and that NK3201 was able to reverse the effects of hyperoxia.

Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer.

OBJECTIVE: Solute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells. PATIENTS AND METHODS: Subcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry. Then, the associations of SLC39A14 expression with various clinicopathological features and clinical outcome of patients with PCa were statistically evaluated. Subsequently, the effects of SLC39A14 overexpression and knockdown on PCa cell proliferation and motility were, respectively, examined by Cell Counting Kit-8, transwell, and wound-healing assays. RESULTS: The immunoreactive scores of SLC39A14 protein in human PCa tissues were significantly lower than those in normal prostate tissues. Based on the Taylor dataset, SLC39A14 downregulation occurred more frequently in patients with PCa with a higher Gleason score (P<0.001), advanced clinical stage (P=0.008), presence of metastasis (P=0.009), and prostate-specific antigen failure (P=0.006). More interestingly, the survival analysis identified SLC39A14 as an independent factor for predicting the biochemical recurrence-free survival of patients with PCa (P=0.017). Functionally, the enforced expression of SLC39A14 could suppress cell proliferation, invasion, and migration of PCa cell lines in vitro, which could be reversed by the knockdown of SLC39A14. CONCLUSION: Decreased expression of SLC39A14 may lead to malignant phenotypes of PCa cells and aggressive tumor progression in patients with PCa. Importantly, SLC39A14 may function as a tumor suppressor and a biomarker for screening patients with biochemical recurrence following radical prostatectomy.