Boundary quantitative characterization of the top-coal limit equilibrium zone in fully mechanized top-coal caving stope along the strike direction of working face.

In the process of fully mechanized top-coal caving mining, the top-coal is affected by mining-induced stress, and the stress varies along the strike direction of working face, so the boundary position of its entering the limit equilibrium state changes accordingly. The determination of the boundary along the strike direction of working face can provide scientific guidance for the stability control of support-surrounding rock in fully mechanized top-coal caving face. Using the research methods of theoretical analysis, physical similarity simulation experiment and numerical simulation experiment, the stress state analysis model of the boundary position of the top-coal limit equilibrium zone under macro-scale conditions was established, the stress state characterization method of the boundary of the top-coal limit equilibrium zone along the strike direction of working face was given, and the quantitative characterization of the boundary of the top-coal limit equilibrium zone along the strike direction of working face was realized by combining with the mining-induced stress path, and the distance relationship between the boundary of the top-coal limit equilibrium zone and the langwall face along the strike direction of working face was revealed. The results show that after critical mining in fully mechanized top-coal caving face, the distance between the boundary of top-coal limit equilibrium zone and the langwall face along the strike direction of working face presents a relationship of increasing from top to bottom. The distance between the top-coal upper boundary and the langwall face was 2.85 m and the distance between the top-coal lower boundary and the langwall face was 5.39 m. The boundary of top-coal limit equilibrium zone along the strike direction of working face was verified by the top-coal elastic-plastic zone boundary and the boundary of the peak position of front abutment pressure in different layers of top-coal. The results show that the quantitative characterization of the top-coal limit equilibrium zone boundary along the strike direction of working face was reasonable. In order to improve mine production efficiency, optimization measures were put forward for hard coal seam and soft coal seam respectively.

Internal stress transfer characteristics of coal-rock medium under concentrated force based on particle flow method.

To solve the problem that the macroscopic deformation and failure of coal-rock medium under external loads are easy to be observed while the internal stress transfer mode and path are unclear. Based on the discrete element idea, the numerical models for pure coal or rock samples and coal-rock combination samples with different lithologies and combination methods under concentrated force are established by PFC2D software. Then the influence of coal or rock strength and combination methods on the internal stress transfer law and distribution evolution characteristics of coal-rock medium are discussed from the perspectives of macroscopic stress and mesoscopic force chain, respectively. The results showed that under concentrated load, the macroscopic stress transfer paths within pure coal or rock samples and coal-rock combination samples are primarily in the form of 'point source radiation'. However, when transferring between coal-rock interfaces, there is a certain interface effect. For pure coal or rock samples, differences in lithology does not change the transfer rules and macro distribution patterns of internal stress, but it can cause changes in internal unit transfer stress value and local area transfer direction. For coal-rock combination samples, the greater the difference in lithology between the two sides of the interface, the more likely the interface effect will occur. In addition, the internal stress transfer is also influenced by the relative stratigraphic relationships of coal and rock. When the stress is transferred from a higher-strength rock to a lower-strength coal mass, the interface effect will be more significant. However, regardless of the combination pattern, the locations where significant stress surges occur are always within the higher strength rock mass near the interface. The findings are helpful to understand the mechanical properties and failure mechanism of mining coal and rock mass, and provide a theoretical basis for the study of the mining-induced mechanical behavior of the floor under the action of the coal pillar.

Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration.

MAP4K1 has been identified as a cancer immunotherapy target. Whether and how cancer cell-intrinsic MAP4K1 contributes to glioblastoma multiforme (GBM) progression remains unclear. We found that MAP4K1 was highly expressed in the glioma cells of human GBM specimens. High levels of MAP4K1 mRNA were prevalent in IDH-WT and 1p/19q non-codeletion gliomas and correlated with poor prognosis of patients. MAP4K1 silencing inhibited GBM cell proliferation and glioma growth. Transcriptome analysis of GBM cells and patient samples showed that MAP4K1 modulated cytokine‒cytokine receptor interactions and chemokine signaling pathway, including IL-18R and IL-6R Importantly, MAP4K1 loss down-regulated membrane-bound IL-18R/IL-6R by inhibiting the PI3K-AKT pathway, whereas MAP4K1 restoration rescued this phenotype and therefore GBM cell proliferation. MAP4K1 deficiency abolished GBM cell pro-proliferation responses to IL-18, suggesting an oncogenic role of MAP4K1 via the intrinsic IL-18/IL-18R pathway. In addition, GBM cell-derived MAP4K1 impaired T-cell migration and reduced CD8+ T-cell infiltration in mouse glioma models. Together, our findings provide novel insight into the pathological significance of GBM cell-intrinsic MAP4K1 in driving tumor growth and immune evasion by remodeling cytokine-chemokine networks.

Forecast for peak infections in the second wave of the Omicron after the adjustment of zero-COVID policy in the mainland of China.

On December 7, 2022, the Chinese government optimized the current epidemic prevention and control policy, and no longer adopted the zero-COVID policy and mandatory quarantine measures. Based on the above policy changes, this paper establishes a compartment dynamics model considering age distribution, home isolation and vaccinations. Parameter estimation was performed using improved least squares and Nelder-Mead simplex algorithms combined with modified case data. Then, using the estimated parameter values to predict a second wave of the outbreak, the peak of severe cases will reach on 8 May 2023, the number of severe cases will reach 206,000. Next, it is proposed that with the extension of the effective time of antibodies obtained after infection, the peak of severe cases in the second wave of the epidemic will be delayed, and the final scale of the disease will be reduced. When the effectiveness of antibodies is 6 months, the severe cases of the second wave will peak on July 5, 2023, the number of severe cases is 194,000. Finally, the importance of vaccination rates is demonstrated, when the vaccination rate of susceptible people under 60 years old reaches 98%, and the vaccination rate of susceptible people over 60 years old reaches 96%, the peak of severe cases in the second wave of the epidemic will be reached on 13 July 2023, when the number of severe cases is 166,000.

Study of CFD-DEM on the Impact of the Rolling Friction Coefficient on Deposition of Lignin Particles in a Single Ceramic Membrane Pore.

The discrete element method coupled with the computational fluid dynamic (CFD-DEM) method is effective for studying the micro-flow process of lignin particles in ceramic membranes. Lignin particles may exhibit various shapes in industry, so it is difficult to model their real shapes in CFD-DEM coupled solutions. Meanwhile, the solution of non-spherical particles requires a very small time-step, which significantly lowers the computational efficiency. Based on this, we proposed a method to simplify the shape of lignin particles into spheres. However, the rolling friction coefficient during the replacement was hard to be obtained. Therefore, the CFD-DEM method was employed to simulate the deposition of lignin particles on a ceramic membrane. Impacts of the rolling friction coefficient on the deposition morphology of the lignin particles were analyzed. The coordination number and porosity of the lignin particles after deposition were calculated, based on which the rolling friction coefficient was calibrated. The results indicated that the deposition morphology, coordination number, and porosity of the lignin particles can be significantly affected by the rolling friction coefficient and slightly influenced by that between the lignin particles and membranes. When the rolling friction coefficient among different particles increased from 0.1 to 3.0, the average coordination number decreased from 3.96 to 2.73, and the porosity increased from 0.65 to 0.73. Besides, when the rolling friction coefficient among the lignin particles was set to 0.6-2.4, the spherical lignin particles could replace the non-spherical particles.

Impacts of climate change on vegetation pattern: Mathematical modeling and data analysis.

Climate change has become increasingly severe, threatening ecosystem stability and, in particular, biodiversity. As a typical indicator of ecosystem evolution, vegetation growth is inevitably affected by climate change, and therefore has a great potential to provide valuable information for addressing such ecosystem problems. However, the impacts of climate change on vegetation growth, especially the spatial and temporal distribution of vegetation, are still lacking of comprehensive exposition. To this end, this review systematically reveals the influences of climate change on vegetation dynamics in both time and space by dynamical modeling the interactions of meteorological elements and vegetation growth. Moreover, we characterize the long-term evolution trend of vegetation growth under climate change in some typical regions based on data analysis. This work is expected to lay a necessary foundation for systematically revealing the coupling effect of climate change on the ecosystem.

CYP4 subfamily V member 2 (CYP4V2) polymorphisms were associated with ischemic stroke in Chinese Han population.

BACKGROUND: CYP4 subfamily V member 2 (CYP4V2) polymorphisms are related to venous thromboembolism. However, the influence of CYP4V2 polymorphisms on the susceptibility to ischemic stroke (IS) remains undetermined. METHODS: We selected and genotyped five polymorphisms of CYP4V2 in 575 cases and 575 controls to test whether CYP4V2 variants were associated with the risk for IS in a Chinese Han population. Genotyping of CYP4V2 polymorphisms was performed using the Agena MassARRAY platform. Logistic regression analysis was used to assess the association between CYP4V2 polymorphisms and IS risk by calculating odds ratios (ORs) and 95% confidence interval (CI). False-positive report probability analysis was applied to assess the noteworthy relationship of the significant findings. RESULTS: CYP4V2 rs1398007 might be a risk factor for IS (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Specially, confounding factors (age, gender, smoking and drinking status) might affect the relationship between rs1398007 and IS susceptibility. Moreover, rs1053094 and rs56413992 were associated with IS risk in males. Multifactor dimensionality reduction analysis showed the combination of rs13146272 and rs3736455 had the strongest interaction effect (information gain value of 0.40%). Furthermore, genotypes of rs1398007 (p = 0.006) and rs1053094 (p = 0.044) were associated with the levels of high-density lipoprotein cholesterol (HDL-C) among healthy controls. CONCLUSION: Our results first provided evidence that CYP4V2 rs1398007 might be a risk factor for IS, which provides instructive clues for studying the mechanisms of CYP4V2 to the pathogenesis of IS.

Clinical Effects of Outpatient Health Education on Fall Prevention and Self-health Management of Elderly Patients with Chronic Diseases.

Background: Elderly patients with chronic diseases (CDs) have a higher predilection for falls, with more severe consequences once they fall. Therefore, it is necessary to explore an effective way to prevent falls in elderly patients with CDs. Objective: To clarify the clinical effects of outpatient health education on fall prevention and self-health management in elderly patients with CDs. Methods: This retrospective study enrolled 102 elderly patients with CDs who received treatment in the School of Medicine, Sir Run Run Shaw Hospital of Zhejiang University, between January 2019 and December 2020. Patients intervened by routine nursing were assigned to the regular group (n = 48), and those additionally treated with outpatient health education were included in the research group (n = 54). Assessment of patients' negative emotions (NEs) adopted the Self-Rating Anxiety/Depression Scale (SAS/SDS), determination of their sense of self-efficacy employed the Falls Efficacy Scale International (FES-I), and their self-care capacity evaluation used the Exercise of Self-Care Agency (ESCA). Patients' falls, hospitalization time, fall prevention knowledge, fall prevention-related health behavior, and nursing satisfaction were recorded. Results: After the nursing intervention, lower SAS, SDS, and FES-I scores were determined in the research group versus the regular group; the total ESCA score assessed from various dimensions was higher in the research group; the research group also exhibited a markedly lower incidence of falls, and shorter hospitalization time than the regular group, with better mastery of fall prevention knowledge, fall prevention-related health behavior and nursing satisfaction. Conclusions: Outpatient health education intervention can prevent senile patients with CDs from falling, promote their rehabilitation, and enhance their mastery of fall prevention knowledge; moreover, it can improve patients' healthy behaviors to prevent falls, mitigate their NEs, and improve their sense of self-efficacy and self-care ability, which has high clinical application value.

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression.

The therapy role of mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) in cartilage regeneration has been well studied. Herein, we tried to analyze the role of human umbilical cord MSC- (hUCMSC-) EVs carrying microRNA- (miR-) 181c-5p in repair of cartilage injury. After successful isolation of hUCMSCs, the multidirectional differentiation abilities were analyzed. Then, the EVs were isolated and identified. After coculture of PKH26-labled EVs with bone marrow MSCs (BMSCs), the biological behaviors of which were detected. The relationship between the predicted early posttraumatic osteoarthritis-associated miRNA, miR-181c-5p, and SMAD7 was verified. Gain- and loss-of functions were performed for investing the role of miR-181c-5p and SMAD7 in BMP-induced chondrogenesis in vitro and in vivo. hUCMSC-EVs could be internalized by BMSCs and promote the proliferative, migratory, and chondrogenic differentiation potentials of BMSCs. Additionally, miR-181c-5p could target and inhibit SMAD7 expression to promote the bone morphogenic protein 2- (BMP2-) induced proliferative, migratory, and chondrogenic differentiation potentials of BMSCs. Also, overexpression of SMAD7 inhibited the repairing effect of BMP2, and overexpression of BMP2 and miR-181c-5p further promoted the repair of cartilage injury in vivo. Our present study highlighted the repairing effect of hUCMSC-EVs carrying miR-181c-5p on cartilage injury.

Three-Dimensional Physical Similarity Simulation Experiments for a Transparent Shaft Coal Pocket Wall in Coal Mines.

To explore the variations of the loading, deformation, and loss and to determine the mechanical state, loss characteristics, and stability for the shaft coal pocket wall in coal mines under a dynamic-static load, this paper innovatively attempts to conduct a three-dimensional physical similarity test of a transparent material shaft coal pocket, as well as the experiments of loading and unloading coal in the shaft coal pocket using different bulk storage materials 80 times. Then, the deformation, pressure, the surrounding rock, and the flow pattern of the silo wall were discussed considering the existence of the warehouse wall support. The characteristics of shaft wall deformation and surrounding rock stress cracks during the unloading were analyzed with the help from multiple integrated test systems such as strain gauges, pressure sensors, borehole peeps, and other comprehensive test systems. The results indicated that different dispersion particles have a significant impact on the strain of the shaft wall. When using the coal particles as storage materials, the overpressure coefficient of the shaft wall is up to 1.95 times higher than using dry sand particles. The particle size and internal friction angle of the bulk particles impact significantly on the deformation of the wall, where the cohesive force among the dispersed particles produced by the compaction effect has a certain influence on the side pressure of the silo wall. During the unloading process, coal particles were easier to obtain an arching phenomenon than dry sand particles. In addition, the number of bulk arching could be significantly reduced under the conditions of the warehouse wall support. The "weak rock stratum" in the surrounding rock plays a major role in controlling the deformation and failure development of the shaft wall. The three-dimensional physical simulation experiment of the transparent shaft wall truly reproduces the field engineering practice, and the physical simulation results are verified by numerical simulation analysis.

Analysis on Influencing Factors of Knowledge-Based Attitude and Behavior Change of Cardiovascular Disease Nurses.

The study explores the influencing factors of knowledge, attitude, and behavior of cardiovascular disease nurses. A total of 500 CVD nurses from 10 hospitals in the province from January 2020 to 2021 are selected as the survey subjects. After reviewing the literature, a questionnaire is developed to investigate the knowledge, belief, and practice level of cardiovascular disease nurses. The demographic information, job information and knowledge, attitude, and behavior of cardiovascular disease nurses are investigated in the form of questionnaires. Univariate analysis is made on the knowledge, attitude, and behavior scores of the nurses with cardiovascular diseases in demographic characteristics and job characteristics, and multivariate stepwise analysis is made on the factors affecting the knowledge, attitude, and behavior of the nurses with cardiovascular diseases. Cardiovascular disease nurses' knowledge, attitude, and behavior are the medium level, should be regular training activities and psychological counseling, and cultivate high title, long working life, older nursing staff, and practice level.

Effect of Amniotic Membrane/Collagen-Based Scaffolds on the Chondrogenic Differentiation of Adipose-Derived Stem Cells and Cartilage Repair.

Objectives: Repairing articular cartilage damage is challenging. Clinically, tissue engineering technology is used to induce stem cell differentiation and proliferation on biological scaffolds to repair defective joints. However, no ideal biological scaffolds have been identified. This study investigated the effects of amniotic membrane/collagen scaffolds on the differentiation of adipose-derived stem cells (ADSCs) and articular cartilage repair. Methods: Adipose tissue of New Zealand rabbits was excised, and ADSCs were isolated and induced for differentiation. An articular cartilage defect model was constructed to identify the effect of amniotic membrane/collagen scaffolds on cartilage repair. Cartilage formation was analyzed by imaging and toluene blue staining. Knee joint recovery in rabbits was examined using hematoxylin and eosin, toluidine, safranine, and immunohistochemistry at 12 weeks post-operation. Gene expression was examined using ELISA, RT-PCR, Western blotting, and immunofluorescence. Results: The adipose tissue was effectively differentiated into ADSCs, which further differentiated into chondrogenic, osteogenic, and lipogenic lineages after 3 weeks' culture in vitro. Compared with platelet-rich plasmon (PRP) scaffolds, the amniotic membrane scaffolds better promoted the growth and differentiation of ADSCs. Additionally, scaffolds containing the PRP and amniotic membrane efficiently enhanced the osteogenic differentiation of ADSCs. The levels of COL1A1, COL2A1, COL10A1, SOX9, and ACAN in ADSCs + amniotic membrane + PRP group were significantly higher than the other groups both in vitro and in vivo. The Wakitani scores of the ADSC + amniotic membrane + PRP group were lower than that in ADSC + PRP (4.4 ± 0.44**), ADSC + amniotic membrane (2.63 ± 0.38**), and control groups (6.733 ± 0.21) at week 12 post-operation. Osteogenesis in rabbits of the ADSC + amniotic membrane + PRP group was significantly upregulated when compared with other groups. Amniotic membranes significantly promoted the expression of cartilage regeneration-related factors (SOX6, SOX9, RUNX2, NKX3-2, MEF2C, and GATA4). The ADSC + PRP + amniotic membrane group exhibited the highest levels of TGF-ß, PDGF, and FGF while exhibiting the lowest level of IL-1ß, IL6, and TNF-α in articular cavity. Conclusion: Amniotic membrane/collagen combination-based scaffolds promoted the proliferation and cartilage differentiation of ADSCs, and may provide a new treatment paradigm for patients with cartilage injury.

Vorinostat ameliorates IL-1α-induced reduction of type II collagen by inhibiting the expression of ELF3 in chondrocytes.

Osteoarthritis (OA) is a common joint disease that ultimately causes physical disability and imposes an economic burden on society. Cartilage destruction plays a key role in the development of OA. Vorinostat is an oral histone deacetylase (HDAC) inhibitor and has been used for the treatment of T-cell lymphoma. Previous studies have reported the anti-inflammatory effect of HDAC inhibitors in both in vivo and in vitro models. However, it is unknown whether vorinostat exerts a protective effect in OA. In this study, our results demonstrate that treatment with vorinostat prevents interleukin 1α (IL-1α)-induced reduction of type II collagen at both gene and protein levels. Treatment with vorinostat reduced the IL-1α-induced production of mitochondrial reactive oxygen species (ROS) in T/C-28a2 cells. Additionally, vorinostat rescued the IL-1α-induced decrease in the expression of the collagen type II a1 (Col2a1) gene and the expression of Sry-related HMG box 9 (SOX-9). Importantly, we found that vorinostat inhibited the expression of matrix metalloproteinase-13 (MMP-13), which is responsible for the degradation of type II collagen. Furthermore, vorinostat suppressed the expression of E74-like factor 3 (ELF3), which is a key transcription factor that plays a pivotal role in the IL-1α-induced reduction of type II collagen. Also, the overexpression of ELF3 abolished the protective effects of vorinostat against IL-1α-induced loss of type 2 collagen by inhibiting the expression of SOX-9 whilst increasing the expression of MMP-13. In conclusion, our findings suggest that vorinostat might prevent cartilage destruction by rescuing the reduction of type II collagen, mediated by the suppression of ELF3.

Transcription factor ELK1 accelerates aerobic glycolysis to enhance osteosarcoma chemoresistance through miR-134/PTBP1 signaling cascade.

Osteosarcoma is a malignancy that primarily affects children and young adults. The poor survival is largely attributed to acquisition of chemoresistance. Thus, the current study aimed to elucidate the role of ELK1/miR-134/PTBP1 signaling cascade in osteosarcoma chemoresistance. Doxorubicin (DXR)-resistant human osteosarcoma cells were initially self-established by continuous exposure of MG-63, U2OS and HOS cells to increasing DXR doses. Osteosarcoma chemoresistance in vitro was evaluated using CCK-8 assays and EdU staining. Aerobic glycolysis was evaluated by lactic acid production, glucose consumption, ATP levels, and Western blot analysis of GLUT3, HK2 and PDK1 proteins. The nude mice were injected with 5.0 mg/kg DXR following the subcutaneous transplantation of osteosarcomas. PTBP1 was upregulated in tumor tissues derived from non-responders to DXR treatment and correlated with patient poor survival. PTBP1 enhanced chemoresistance in cultured osteosarcoma cells in vitro and in vivo by increasing aerobic glycolysis. Additionally, miR-134 inhibited translation of PTBP1. ELK1 bound to miR-134 promoter and inhibited its expression. Overexpressed ELK1 enhanced chemoresistance and increased aerobic glycolysis by downregulating miR-134 and upregulating PTBP1 in DXR-resistant cells. Altogether, the key findings of the present study highlight ELK1/miR-134/PTBP1 signaling cascade as a novel molecular mechanism underlying the acquisition of osteosarcoma chemoresistance.

Antiangiogenic effect of arsenic trioxide in HUVECs by FoxO3a-regulated autophagy.

Arsenic trioxide (ATO) has been shown to have antitumor effect in different tumors, although the underlying mechanisms are not fully understood. Autophagy plays a critical role in tumorigenesis and cancer therapy and has been found to be activated by ATO in different cells. However, the role of autophagy in the antitumor effect of ATO has not yet been elucidated. In this study, we investigated the role of autophagy in the antiangiogenic effect of ATO in human umbilical vein endothelial cells (HUVECs) in vitro and its underlying mechanism. Our data showed that ATO suppresses angiogenesis and induces autophagy in HUVECs through upregulation of forkhead box protein O3 (FoxO3a). Co-incubated with autophagy inhibitor or knockdown of FoxO3a effectively inhibited ATO-induced autophagy and reversed the antiangiogenic effect of ATO, indicating that ATO-induced autophagy plays an antiangiogenic role in HUVECs. Our results highlight the importance of autophagy in the antiangiogenic effect of ATO and provide an improved understanding of the function of ATO.

Chronic bilateral asynchronous achilles tendon rupture treated using modified whole flexor hallucis longus transfer reconstruction: A case report.

INTRODUCTION: Achilles tendon rupture is common, but bilateral ruptures are very rare. Treatment of chronic Achilles tendon rupture is very challenging due tendon retraction and atrophied. We report a case of bilateral asynchronous Achilles tendon rupture patient who was treated with modified minimally invasive whole flexor hallucis longus (FHL) tendon transfer to repair the defects. PATIENT CONCERNS: A 52-year-old male farmer presented to our hospital complaining of bilateral heel pain that had disrupted his walking for 6 months. The patient had been misdiagnosed and under-treated for 1 year. Physical examination showed that his plantar flexors were tender and weak, with marked hypotrophy of the calf muscles. Bilateral ankle radiographs of both X-ray and computed topography (CT) revealed no bone injure. DIAGNOSIS: Magnetic resonance imaging (MRI) indicated a bilateral Achilles tendon rupture. The diagnosis was further confirmed by postoperative histological examination, which revealed Achilles tendonitis accompanied by regional calcification and chondrometaplasia. INTERVENTIONS: Surgical reconstruction of the ruptured Achilles tendons was done through a modified minimally invasive whole FHL tendon transfer followed by physiotherapy. OUTCOMES: The patient was immobilized in a cast for the next 6 weeks, gradual weight bearing gradually was then encouraged for another 6 weeks, and full weight-bearing started 3 months after surgery. By 6-month postoperation, the patient could walk and jog normally returned to his pre-injury working condition. CONCLUSION: Surgical intervention is among the primary treatment of chronic Achilles tendon rupture. However, one of the challenges in its treatment is providing suitable graft for tendon reconstruction. Our case presents a successful reconstruction procedure using less-invasive whole FHL transfer technique. This surgical technique provides satisfactory clinical and functional outcome and can be considered for future therapy.

MLK3 Is Associated With Poor Prognosis in Patients With Glioblastomas and Actin Cytoskeleton Remodeling in Glioblastoma Cells.

Mixed lineage kinase 3 (MLK3) has been implicated in human melanoma and breast cancers. However, the clinical significance of MLK3 in human gliomas and the underlying cellular and molecular mechanisms remain unclear. We found that MLK3 proteins were highly expressed in high-grade human glioma specimens and especially prevalent in primary and recurrent glioblastoma multiforme (GBM). High levels of MLK3 mRNA were correlated with poor prognosis in patients with isocitrate dehydrogenase (IDH)-wild-type (wt) gliomas. Furthermore, genetic ablation of MLK3 significantly suppressed the migration and invasion abilities of GBM cells and disrupted actin cytoskeleton organization. Importantly, MLK3 directly bound to epidermal growth factor receptor kinase substrate 8 (EPS8) and regulated the cellular location of EPS8, which is essential for actin cytoskeleton rearrangement. Overall, these findings provide evidence that MLK3 upregulation predicts progression and poor prognosis in human IDH-wt gliomas and suggest that MLK3 promotes the migration and invasion of GBM cells by remodeling the actin cytoskeleton via MLK3-EPS8 signaling.

PTEN-knockdown disrupts the morphology, growth pattern and function of Nthy-Ori 3-1 cells by downregulating PAX8 expression.

The incidence of thyroid disorders, which are common endocrine diseases, has rapidly increased in recent years. However, the etiology and pathogenesis of these disorders remain unclear. Phosphatase and tension homolog (PTEN) is a dual-specific phosphatase that is associated with multiple thyroid disorders; however, the role of PTEN in thyroid disorders remains unknown. In the present study, the human thyroid follicular epithelial cell line Nthy-Ori 3-1 was used to determine the role of PTEN in thyroid disorders. PTEN expression was knocked down using a PTEN-specific short hairpin RNA. Western blotting was subsequently used to determine protein expression, the Matrigel tube formation assay and iodide uptake assay were applied for evaluating the morphology and function of thyroid cells. The results showed that PTEN knockdown decreased the protein expression of paired box 8 (PAX8). The morphology and tubular-like growth pattern of thyroid cells were therefore disrupted, and restoration of PAX8 expression reversed these effects. Furthermore, PTEN-knockdown decreased the expression of specific thyroid proteins (thyroglobulin, TG; thyroid peroxidase, TPO; and sodium/iodide symporter, NIS) and inhibited the iodide uptake ability of thyroid cells by downregulating PAX8, suggesting that PTEN deficiency may impair the function of thyroid cells. In conclusion, the present study reported an important function of PTEN in normal thyroid cells and identified the involvement of PAX8. These results may improve understanding of the role of PTEN in the pathogenesis of thyroid disorders.

[Warm acupuncture on chronic obstructive pulmonary disease with phlegm-turbid obstructing of the lung: a randomized controlled trial].

OBJECTIVE: To verify the effect of warm acupuncture combined with western medicine in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) with phlegm-turbid obstructing of the lung. METHODS: Ninety patients with AECOPD were randomly divided into a western medicine group, a warm acupuncture group and a sham acupuncture group, 30 cases in each group. Routine treatment according to the Global initiative for chronic obstructive lung disease (GOLD) guidelines was used in the western medicine group. On the basis of the routine treatment, the warm acupuncture was applied at Fenglong (ST 40), Feishu (BL 13), Zusanli (ST 36) and other acupoints in the warm acupuncture group. In the sham acupuncture group, non-acupoints were taken on the basis of conventional treatment, and superficial acupuncture was performed for 1-3 mm, once a day for 2 weeks. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, cough and sputum assessment questionnaire (CASA), COPD assessment test (CAT), and the change of TCM syndrome score were observed before and after treatment in all groups. RESULTS: After treatment, the FEV1, FVC and FEV1/FVC in each group were higher than those before treatment (P<0.05), there was no significant difference among groups after treatment (P>0.05). The CASA score, CAT score and TCM syndrome score in each group were lower than those before treatment (P<0.05). The change of the scores before and after treatment in the warm acupuncture group was higher than that in the sham acupuncture group and the western medicine group (P<0.05). There was no significant difference between the sham acupuncture group and the western medicine group (P>0.05). CONCLUSION: Warm acupuncture has a significant effect on the improvement of symptoms in patients with AECOPD with phlegm-turbid obstructing of the lung.