Manipulation of the polarization state of the focus based on a slab plasmon waveguide.

A focusing nanostructure with tailored polarization properties based on a metal-dielectric slab waveguide combined with plasmonic slits and gratings is proposed. The polarization state of the focus light can be controlled with overlapping a transverse magnetic (TM) focus and a transverse electric (TE) focus, which are formed by focusing the waveguide modes into free space via grating coupling, extraordinary transmission, and plasmonic beaming. We demonstrated that it is possible to achieve either multiple foci or a single focal spot of the transmitted light with tailored polarization states by judicious design of the structure parameter and the polarization state of the incident light.

Osteoclast-derived exosomal miR-212-3p suppressed the anabolism and accelerated the catabolism of chondrocytes in osteoarthritis by targeting TGF-ß1/Smad2 signaling.

Osteoarthritis (OA) is a common aging-related disease affecting entire joint structures, encompassing articular cartilage and subchondral bone. Although senescence and dysfunction of chondrocytes are considered crucial factors in the occurrence of OA, the exact pathogenesis remains to be investigated. In our study, chondrocytes were incubated with a conditioned medium obtained from osteoclasts at different differentiation stages, suggesting that osteoclasts and osteoclast precursors suppressed anabolism and promoted the catabolism of chondrocytes in vitro. In contrast, the function of osteoclasts was more significant than osteoclast precursors. Further blocking of osteoclast exosome secretion by using GW4869 abolished the effect of osteoclasts on chondrocytes. Functionally, exosomal transfer of osteoclast-derived miR-212-3p inhibited Smad2 to mediate chondrocyte dysfunction, thus accelerating cartilage matrix degradation in OA via TGF-ß1/Smad2 signaling. The mechanism was also confirmed within the articular cartilage in OA patients and surgery-induced OA mice. Our study provides new information on intercellular interactions in the bone microenvironment within articular cartilage and subchondral bone during OA progression. The miR-212-3p/Smad2 axis is a potential target for the prevention and therapy of OA.

Selective Stereoretention of Carbohydrates upon C-C Cleavage Enabling D-Glyceric Acid Production with High Optical Purity over a Ag/γ-Al2O3 Catalyst.

Chiral carboxylic acid production from renewable biomass by chemocatalysis is vitally important for reducing our carbon footprint, but remains underdeveloped. We herein establish a strategy that make use of a stereogenic center of biomass to achieve a rare example of D-glyceric acid production with the highest yield (86.8 %) reported to date as well as an excellent ee value (>99 %). Unlike traditional asymmetric catalysis, chiral catalysts/additives are not required. Ample experiments combined with quantum chemical calculations established the origins of the stereogenic center and catalyst performance. The chirality at C4 in D-xylose was proved to be retained and successfully delivered to C2 in D-glyceric acid during C-C cleavage. The remarkable cooperative-roles of Ag+ and Ag0 in the constructed Ag/γ-Al2O3 catalyst are disclosed as the crucial contributors. Ag+ was responsible for low-temperature activation of D-xylose, while Ag0 facilitated the generation of active O* from O2. Ag+ and active O* cooperatively promoted the precise cleavage of the C2-C3 bond, and more importantly O* allowed the immediate fast oxidization of the D-glyceraldehyde intermediate to stabilize D-glyceric acid, thereby inhibiting the side reaction that induced racemization. This strategy makes a significant breakthrough in overcoming the limitation of poor enantioselectivity in current chemocatalytic conversion of biomass.

Sympathetic Activation Promotes Cardiomyocyte Apoptosis in a Rabbit Susceptibility Model of Hyperthyroidism-Induced Atrial Fibrillation via the p38 MAPK Signaling Pathway.

Excess thyroid hormone secretion can cause endocrine metabolic disorders, which can lead to cardiovascular diseases, including heart enlargement, atrial fibrillation (AF), and heart failure. The present study investigated the molecular mechanisms of hyperthyroidism-induced AF. A rabbit susceptibility model of hyperthyroidism-induced AF was constructed, and metoprolol treatment was administered. Norepinephrine levels were determined using enzyme-linked immunosorbent assay; quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to detect the expression of markers for sympathetic remodeling (growth associated protein 43 and tyrosine hydroxylase in atrial myocardial tissues and stellate ganglia). Primary rabbit cardiomyocytes were cultured and identified by immunofluorescence staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to measure cardiomyocyte apoptosis; western blot was used to detect the expression of apoptosis-related proteins, including Bax, Bcl-2, and cleaved caspase-3, as well as to measure the phosphorylation states of p38 mitogen-activated protein kinase (MAPK) pathway proteins. Metoprolol inhibited sympathetic activation and cardiomyocyte apoptosis in the rabbit model by inhibiting the p38 MAPK signaling pathway. Immunofluorescence staining results revealed that the rabbit cardiomyocytes were isolated successfully. Inhibition of p38 MAPK signaling alleviated norepinephrine-induced apoptosis in cardiomyocytes. Sympathetic activation promotes apoptosis in cardiomyocytes with hyperthyroidism-induced AF via the p38 MAPK signaling pathway. The results of the present study provide a novel theoretical basis for the potential clinical treatment of patients with hyperthyroidism and AF.

Geometrical and magnetic properties of small titanium and chromium clusters on monolayer hexagonal boron nitride.

Magnetic clusters on an insulating substrate are potential candidates for spin-based quantum devices. Here we investigate the geometric, electronic, and magnetic structures of small Ti and Cr clusters, from dimers to pentamers, adsorbed on a single-layer hexagonal boron nitride (h-BN) sheet within the framework of density functional theory. The stable adsorption configurations of the Ti clusters and Cr clusters composed of the same number of atoms are found to be totally different from each other. The difference in their bonding mechanisms has been revealed by the density of states and the charge density difference of the corresponding adsorption systems. While chemical bonds are formed between the Ti atoms and the supporting sheet, the Cr clusters are found in the physisorption state on the substrate. In addition, it is shown that the h-BN sheet is energetically favorable for building three-dimensional Ti clusters. These findings support the use of h-BN as a suitable decoupling substrate for manipulation of quantum spin states in small transition metal (TM) clusters and fabrication of devices based on them.

Incidence and risk factors associated with postoperative surgical site infection in younger adults with hip fractures: a case-control study.

PURPOSE: Hip fracture is associated with high morbidity and mortality. The most common complication after hip fracture is surgical site infection (SSI). The goal was to investigate risks associated with SSI in young adults who underwent surgery for hip fractures. METHODS: We conducted a case-control study enrolling 1243 patients from Jan 2015 to Dec 2019. This study investigated the multifaceted factors including demographics, lifestyles, comorbidities, surgical variables, and laboratory test results. Patients were divided into the case group (developed SSI) and control group (not developed SSI). Univariate analyses and multivariate logistic regression analyses were used to identify the risk factors independently associated with SSI. RESULTS: A total of 25 patients including 16 (1.8%) in femoral neck fracture and nine (2.5%) in intertrochanteric fracture developed SSI post-operatively, with an accumulated incidence rate of 2.0%. Among them, four cases (1.6%) were deep SSI and 21 cases (98.4%) were superficial SSI. In most cases, Staphylococcus aureus caused the infections. Diabetes mellitus (OR 4.05, 95%CI: 1.08-15.23, P = 0.038), cerebrovascular disease (OR 3.71, 95%CI: 1.14-12.03, P = 0.029), heart disease (OR 6.23, 95%CI: 1.81-21.48, P = 0.004), and operative time (OR 1.01, 95%CI: 1.01-1.02, P = 0.002) in femoral neck fractures while ALP (> upper limit) (OR 33.39, 95%CI: 2.21-504.89, P = 0.011) and CK (> upper limit) (OR 40.97, 95%CI: 1.70-989.31, P = 0.022) in intertrochanteric fractures were found to be significantly associated with SSI. CONCLUSION: Targeted pre-operative management, depending on the patients' fracture type and risk factors, should be developed to reduce post-operative SSI rates of younger adults with hip fracture.

Engineering Plasmonic Environments for 2D Materials and 2D-Based Photodetectors.

Two-dimensional layered materials are considered ideal platforms to study novel small-scale optoelectronic devices due to their unique electronic structures and fantastic physical properties. However, it is urgent to further improve the light-matter interaction in these materials because their light absorption efficiency is limited by the atomically thin thickness. One of the promising approaches is to engineer the plasmonic environment around 2D materials for modulating light-matter interaction in 2D materials. This method greatly benefits from the advances in the development of nanofabrication and out-plane van der Waals interaction of 2D materials. In this paper, we review a series of recent works on 2D materials integrated with plasmonic environments, including the plasmonic-enhanced photoluminescence quantum yield, strong coupling between plasmons and excitons, nonlinear optics in plasmonic nanocavities, manipulation of chiral optical signals in hybrid nanostructures, and the improvement of the performance of optoelectronic devices based on composite systems.

Mulberroside A repairs high fructose diet-induced damage of intestinal epithelial and blood-brain barriers in mice: A potential for preventing hippocampal neuroinflammatory injury.

Our previous studies showed that high fructose diet (HFrD)-driven gut dysbiosis caused fecal short-chain fatty acids (SCFAs) reduction and intestinal epithelial barrier (IEB) damage in mice, which might play an important role in hippocampal neuroinflammatory injury. Mulberroside A is reported to have neuroprotective effects in animal experiments, while the underlying mechanisms are not yet fully elucidated. Here, we investigated whether and how mulberroside A prevented HFrD-induced neuroinflammatory injury. HFrD-fed mice were treated orally with mulberroside A (20 and 40 mg/kg) for 8 weeks. Mulberroside A was found to inhibit hippocampal neuroinflammation and neurogenesis reduction in HFrD-fed mice. It reshaped gut dysbiosis, increased fecal and serum SCFAs contents, reactivated signaling of the colonic NLR family, pyrin domain containing 6 (NLRP6) inflammasome, and up-regulated Muc2 expression to prevent IEB damage, as well as subsequently, reduced serum endotoxin levels in this animal model. Additionally, mulberroside A inhibited oxidative stress in colon of HFrD-fed mice and hydrogen peroxide (H2 O2 )-stimulated Caco-2 cells. Blood-brain barrier (BBB) structure defects were also observed in HFrD-driven hippocampal neuroinflammatory injury of mice. Interestingly, mulberroside A maintained astrocyte morphology and up-regulated tight junction proteins to repair BBB structure defects in hippocampus dentate gyrus (DG). Our results demonstrated that mulberroside A was capable of preventing HFrD-induced damage of IEB and BBB in mice, which might contribute to the suppression of hippocampal neuroinflammatory injury.

Multidimensional fatigue in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: incidence, severity, and risk factors.

PURPOSE: To explore the incidence, severity, and risk factors of multidimensional fatigue in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: This prospective study included 79 patients with NPC in Guangzhou (China) from June 2015 to July 2018. Data were collected before and after CCRT, including demographic and clinical characteristics, nutritional parameters, and fatigue scores, based on completion of the Multiple Dimensional Inventory-20 Questionnaire, with five subscales: General Fatigue, Mental Fatigue, Physical Fatigue, Reduced Activity, and Reduced Motivation. RESULTS: Increased general fatigue was found to be associated with lower lymphocyte count and body mass index <23 kg/m2. Increased physical fatigue was related to age > 42 years. Higher scores for reduced activity were associated with age > 42 years, female sex, and lower serum sodium. Increased mental fatigue was related with lower lymphocyte count and unemployment; and increased total fatigue was associated with lower lymphocyte count, age > 42 years, and 3-6 courses of treatment. Furthermore, 3-6 courses of treatment was an independent predictor of severe general fatigue, while age >42 years was an independent predictor of severe physical fatigue. Importantly, cancer stage IVB and 3-6 courses of treatment could predict severe total fatigue. CONCLUSIONS: Our data demonstrate that fatigue is increased in all dimensions in NPC patients following CCRT, and that the predictors differ for each fatigue dimension. These results could guide the development of targeted interventions that may reduce the impact of cancer-related fatigue in patients with NPC.

Osteoclast-derived exosomal let-7a-5p targets Smad2 to promote the hypertrophic differentiation of chondrocytes.

The invasion of osteoclasts into the cartilage via blood vessels advances the process of endochondral ossification, and dysregulation of dynamic intercellular interactions results in skeletal dysplasias. Although the regulation of osteoclasts by growth plate chondrocytes has been reported in detail, the effect of osteoclasts on chondrocytes remains to be determined. In this study, ATDC5 cells and bone marrow mesenchymal stem cells were differentiated into chondrocytes and treated with conditioned medium obtained from bone marrow macrophages differentiated to osteoclast precursors and osteoclasts. Exosomes were inhibited in conditioned medium or were isolated directly from osteoclasts to further determine whether osteoclast-derived exosomes play an important role in chondrocyte hypertrophy. Additionally, exosomal miRNAs were detected, and let-7a-5p was selected as an miRNA with significantly increased expression in osteoclast-derived exosomes. Experiments were performed to verify the potential target Smad2 and investigate how let-7a-5p affected chondrocytes. The results suggest that both osteoclast precursors and osteoclasts promote chondrocyte hypertrophy and that the promotive effect of osteoclasts is more significant than that of osteoclast precursors. Osteoclast-derived exosomes promote the hypertrophic differentiation of chondrocytes. Moreover, osteoclast-derived exosomal let-7a-5p inhibits Smad2 to decrease the transforming growth factor-ß-induced inhibition of chondrocyte hypertrophy. Our research reveals the role of osteoclasts in the regulation of chondrocytes and provides insights into the highly coordinated intercellular process of endochondral ossification.

Nox2 dependent redox-regulation of Akt and ERK1/2 to promote left ventricular hypertrophy in dietary obesity of mice.

BACKGROUND: A Nox2 containing NADPH oxidase (Nox2) is involved in the global oxidative stress found in dietary obesity and metabolic disorders. However, the effects of high fat diet (HFD) on cardiac Nox2 activation and signaling in left ventricular hypertrophy (LVH) remain unknown. METHODS: Left ventricular (LV) tissues isolated from C57BL/6J wild-type (WT) and Nox2 knockout (Nox2KO) mice (11 months old, n = 6 per group) after 4 months of HFD treatment were used. Cardiomyocyte sizes were measured digitally on LV cross-sections. The levels of cardiac reactive oxygen species (ROS) production was determined using lucigenin-chemiluminescence and in situ dihydroethidium (DHE) fluorescence. The levels of Nox subunit expression and redox signaling were examined by immunoblotting and immunofluorescence. RESULTS: In comparison to WT normal chow diet control hearts, WT HFD hearts had 1.8-fold increases in cardiomyocyte size, a sign of cardiac hypertrophy, and this was accompanied with ≥2-fold increase in the levels of ROS production, Nox2 expression and the phosphorylation of Akt and ERK1/2. Increased ROS production measured in HFD heart homogenates was inhibited to control levels by Tiron (a cell membrane permeable O2•-scavenger), diphenyleneiodonium (DPI, a flavohaemoprotein inhibitor) and Nox2 ds-tat (a Nox2 assembly inhibitor). However, all of these abnormalities were significantly reduced or absent in Nox2KO hearts under the same HFD. CONCLUSIONS: Nox2 activation in response to dietary obesity and metabolic disorders plays a key role in cardiac oxidative stress, aberrant redox signaling and cardiomyocyte hypertrophy. Knockout of Nox2 protects hearts from oxidative damage associated with obesity and metabolic disorders.

Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation.

Central ischemic necrosis is one of the biggest obstacles in the clinical application of traditional tissue-engineered bone (TEB) in critical-sized bone defect regeneration. Because of its ability to promote vascular invasion, endochondral ossification-based TEB has been applied for bone defect regeneration. However, inadequate chondrocyte hypertrophy can hinder vascular invasion and matrix mineralization during endochondral ossification. In light of recent studies suggesting that ceria nanoparticles (CNPs) improve the blood vessel distribution within TEB, we modified TEB scaffold surfaces with CNPs and investigated the effect and mechanism of CNPs on endochondral ossification-based bone regeneration. The CNPs used in this study were synthesized by the microemulsion method and modified with alendronate-anchored polyethylene glycol 600. We showed that CNPs accelerated new bone formation and enhanced endochondral ossification-based bone regeneration in both a subcutaneous ectopic osteogenesis model and a mouse model of critical-sized bone defects. Mechanistically, CNPs significantly promoted endochondral ossification-based bone regeneration by ensuring sufficient hypertrophic differentiation via the activation of the RNA helicase, DEAH (Asp-Glu-Ala-His) box helicase 15, and its downstream target, p38 MAPK. These results suggested that CNPs could be applied as a biomaterial to improve the efficacy of endochondral ossification-based bone regeneration in critical-sized bone defects.-Li, J., Kang, F., Gong, X., Bai, Y., Dai, J., Zhao, C., Dou, C., Cao, Z., Liang, M., Dong, R., Jiang, H., Yang, X., Dong, S. Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation.

Impact of unhealthy lifestyle on cardiorespiratory fitness and heart rate recovery of medical science students.

BACKGROUND: Medical science students represent valuable labour resources for better future medicine and medical technology. However, little attention was given to the health and well-being of these early career medical science professionals. The aim of this study is to investigate the impact of lifestyle components on cardiorespiratory fitness and heart rate recovery measured after moderate exercise in this population. METHODS: Volunteers without documented medical condition were recruited randomly and continuously from the first-year medical science students during 2011-2014 at the University of Surrey, UK. Demographics and lifestyle components (the levels of smoking, alcohol intake, exercise, weekend outdoor activity and screen-time, daily sleep period, and self-assessment of fitness) were gathered through pre-exercise questionnaire. Cardiorespiratory fitness (VO2max) and heart rate recovery were determined using Åstrand-Rhyming submaximal cycle ergometry test. Data were analysed using SPSS version 25. RESULTS: Among 614 volunteers, 124 had completed both lifestyle questionnaire and the fitness test and were included for this study. Within 124 participants (20.6 ± 4 years), 46.8% were male and 53.2% were female, 11.3% were overweight and 8.9% were underweight, 8.9% were current smokers and 33.1% consumed alcohol beyond the UK recommendation. There were 34.7% of participants admitted to have < 3 h/week of moderate physical activity assessed according to UK Government National Physical Activity Guidelines and physically not fit (feeling tiredness). Fitness test showed that VO2max distribution was inversely associated with heart rate recovery at 3 min and both values were significantly correlated with the levels of exercise, self-assessed fitness and BMI. Participants who had < 3 h/week exercise, or felt not fit or were overweight had significantly lower VO2max and heart rate recovery than their peers. CONCLUSION: One in three new medical science students were physically inactive along with compromised cardiorespiratory fitness and heart rate recovery, which put them at risk of cardiometabolic diseases. Promoting healthy lifestyle at the beginning of career is crucial in keeping medical science professionals healthy.

Stress Reactivity Influences the Relationship between Emotional Labor Strategies and Job Burnouts among Chinese Hospital Nurses.

Extant studies mostly focused on the buffering role of social and external organizational resources and personal mental resources. However, there is no research exploring the moderating role of personal physiological resources (e.g., stress reactivity). The present study is aimed at examining the interactive effect of emotional labor and stress reactivity on job burnout. The present study utilized cortisol content in a 1 cm hair segment as the biomarker of total stress reactivity in one month. The participants were 229 female hospital nurses randomly recruited from city hospitals, China. They self-reported their emotional labor strategies and job burnout syndromes and provided 1 cm hair segments closest to the scalp two weeks later after the survey. Hair cortisol content was determined with high-performance liquid chromatography-tandem mass spectrometry. The results revealed that hair cortisol can moderate the associations of surface acting with emotional exhaustion and personal burnout; of deep acting with emotional exhaustion, depersonalization, and personal burnout; and of expression of naturally felt emotions with professional inefficacy. In particular, nurses with high cortisol levels not only showed higher emotional exhaustion than those with low cortisol levels under high surface acting but also showed lower emotional exhaustion under low surface acting. A similar situation was true for nurses' emotional exhaustion and depersonalization in the context of deep acting. Nurses with low hair cortisol levels not only showed higher professional inefficacy than those with high hair cortisol levels under low expression of naturally felt emotions but also showed lower professional inefficacy under high expression of naturally felt emotions. Additionally, nurses with high hair cortisol levels showed lower personal burnout than those with low hair cortisol levels under low surface acting or high deep acting. In summary, the interaction pattern between stress reactivity and emotional labor was varied with the nature of emotional labor strategy and job burnout.

LncRNA AK077216 promotes RANKL-induced osteoclastogenesis and bone resorption via NFATc1 by inhibition of NIP45.

Osteoclasts derived from the monocyte/macrophage hematopoietic lineage regulate bone resorption, a process balanced by bone formation in the continual renewal of the skeletal system. As dysfunctions of these cells result in bone metabolic diseases such as osteoporosis and osteopetrosis, the exploration of the mechanisms regulating their differentiation is a priority. A potential mechanism may involve long noncoding RNAs (lncRNAs), which are known to regulate various cell biology activities, including proliferation, differentiation, and apoptosis. The expression of the lncRNA AK077216 (Lnc-AK077216) is significantly upregulated during osteoclastogenesis identified by microarray and verified by qPCR. Up- and downregulation of Lnc-AK077216, respectively promotes and inhibits osteoclast differentiation, bone resorption, and the expression of related genes on the basis of tartrate-resistant acid phosphatase staining, qPCR, and western blot results. In addition, Lnc-AK077216 suppresses NIP45 expression and promotes the expression of NFATc1, an essential transcription factor during osteoclastogenesis. Besides, it was found that the expression of Lnc-AK077216 and Nfatc1 is upregulated, whereas Nip45 expression is downregulated in bone marrow and spleen tissues of ovariectomized mice. The results suggest that Lnc-AK077216 regulates NFATc1 expression and promotes osteoclast formation and function, providing a novel mechanism of osteoclastogenesis and a potential biomarker or a new drug target for osteoporosis.

MicroRNA-29b regulates hypertrophy of murine mesenchymal stem cells induced toward chondrogenesis.

OBJECTIVE: Chondrocyte hypertrophy, a terminal stage of chondrocyte differentiation, is essential to the endochondral bone formation and is one of the major pathological factors in osteoarthritis. This study investigated the role of microRNA-29b (miR-29b), which is involved in chondrogenesis, in the regulation of hypertrophy in chondrocytes. METHODS: miR-29b expression was assessed during murine mesenchymal stem cells (mMSCs) chondrogenesis. To detect whether miR-29b affects chondrocyte hypertrophy, the mMSCs induced toward chondrogenesis were transfected with miR-29b or its antisense inhibitor (antagomiR-29b). Finally, the differential effects of antagomiR-29b on chondrocytes at different differentiation stages were evaluated by loss-of-function experiments. RESULTS: miR-29b expression was low-level during the early chondrogenic differentiation, however, it was changed to high level during hypertrophy. Subsequently, the gain-of-function and loss-of-function experiments had confirmed that miR-29b promoted hypertrophy in mMSC-derived chondrocytes. In addition, we confirmed that on day 7, when cells were treated with antagomiR-29b, was the optimal intervention time for preventing hypertrophic phenotype of mMSCs in vitro. CONCLUSION: miR-29b regulated chondrogenesis homeostasis and enhance hypertrophic phenotype. These data suggest that miR-29b is a key regulator of the chondrocyte phenotype derived from mMSCs and it might be a potential target for articular cartilage repair.

Epigallocatechin-3-gallate inhibits the growth and increases the apoptosis of human thyroid carcinoma cells through suppression of EGFR/RAS/RAF/MEK/ERK signaling pathway.

BACKGROUND: Thyroid cancer is the most common type of endocrine malignancy and the incidence rate is rapidly increasing worldwide. Epigallocatechin-3-gallate (EGCG) could suppress cancer growth and induce apoptosis in many types of cancer cells. However, the mechanism of action of EGCG on the growth of human thyroid carcinoma cells has not been fully illuminated. METHODS: Cell proliferation and viability were detected by EdU and MTS assays. Cell cycle distribution was measured by flow cytometry. Migration and invasion were evaluated by scratch and transwell assays. Apoptotic levels were detected by TUNEL staining and western blotting. The protein levels of EGFR/RAS/RAF/MEK/ERK signaling pathway were detected by western blotting. The in vivo results were determined by tumor xenografts in nude mice. The in vivo proliferation, tumor microvessel density, and apoptosis were detected by immunohistochemistry. RESULTS: EGCG inhibited the proliferation, viability, and cell cycle progression in human thyroid carcinoma cells. EGCG decreased the migration and invasion, but increased the apoptosis of human thyroid carcinoma cells. EGCG reduced the protein levels of phospho (p)-epidermal growth factor receptor (EGFR), H-RAS, p-RAF, p-MEK1/2, and p-extracellular signal-regulated protein kinase 1/2 (ERK1/2) in human thyroid carcinoma cells. EGCG inhibited the growth of human thyroid carcinoma xenografts by inducing apoptosis and down-regulating angiogenesis. CONCLUSIONS: EGCG could reduce the growth and increase the apoptosis of human thyroid carcinoma cells through suppressing the EGFR/RAS/RAF/MEK/ERK signaling pathway. EGCG can be developed as an effective therapeutic agent for the treatment of thyroid cancer.

Mangiferin enhances endochondral ossification-based bone repair in massive bone defect by inducing autophagy through activating AMP-activated protein kinase signaling pathway.

Endochondral ossification is crucial for bone formation in both adult bone repair process and embryo long-bone development. In endochondral ossification, bone marrow-derived mesenchymal stem cells (BMSCs) first differentiate to chondrocytes, then BMSC-derived chondrocytes endure a hypertrophic process to generate new bone. Endochondral ossification-based bone repair is a promising strategy to cure massive bone defect, which is a major clinical issue in orthopedics. However, challenges still remain for this novel strategy. One challenge is to ensure the sufficient hypertrophic differentiation. Another is to maintain the survival of the above hypertrophic chondrocytes under the hypoxic environment of massive bone defect. To solve this issue, mangiferin (MAG) was introduced to endochondral ossification-based bone repair. In this report, we proved MAG to be a novel autophagy inducer, which promoted BMSC-derived hypertrophic chondrocyte survival against hypoxia-induced injury through inducing autophagy. Furthermore, MAG enhances hypertrophic differentiation of BMSC-derived chondrocytes via upregulating key hypertrophic markers. Mechanistically, MAG induced autophagy in BMSC-derived chondrocytes by promoting AMPKα phosphorylation. Additionally, MAG balanced the expression of sex-determining region Y-box 9 and runt-related transcription factor 2 to facilitate hypertrophic differentiation. These results indicated that MAG was a potential drug to improve the efficacy of endochondral ossification-based bone repair in massive bone defects.-Bai, Y., Liu, C., Fu, L., Gong, X., Dou, C., Cao, Z., Quan, H., Li, J., Kang, F., Dai, J., Zhao, C., Dong, S. Mangiferin enhances endochondral ossification-based bone repair in massive bone defect by inducing autophagy through activating AMP-activated protein kinase signaling pathway.

Peptide P11 suppresses the growth of human thyroid carcinoma by inhibiting the PI3K/AKT/mTOR signaling pathway.

Thyroid carcinoma is the most common endocrine malignancy, and the incidence of thyroid carcinoma is increasing in recent decades. CYYGQSKYC (P6), a nonapeptide with anti-lymphangiogenic effect by its binding to VEGFR-3 and selectively inhibiting VEGF-C binding to VEGFR-3, could suppress the migration and invasion of cancer cells. LSPPRYP (P9) acts as an effective bFGF/FGFR antagonist and inhibits the growth of the murine melanoma B16-F10 cells. In order to increase the anti-tumor effects of P6 and P9, we connected P6 with P9 via a flexible linker Gly-Gly-Gly (GGG) to reconstruct a novel peptide P11, CYYGQSKYCGGGLSPPRYP. In the present study, the mechanism of action of peptide P11 on the growth of human thyroid carcinoma cells both in vitro and in vivo was determined. Our results showed that peptide P11 inhibited the proliferation, viability, migration, and invasion of human thyroid carcinoma cells. Peptide P11 increased the apoptosis and decreased the protein levels of p-PI3K, p-AKT, and p-mTOR in human thyroid carcinoma cells. In addition, P11 could effectively inhibit the growth of human thyroid carcinoma xenograft tumors in nude mice. In conclusion, peptide P11 could inhibit the growth of human thyroid carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway. Novel peptides can be designed and applied for the treatment of various types of cancer.

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells.

BACKGROUND/AIMS: In the process of bone development and remodeling, the vasculature is regarded as the communicative network between the bone and neighboring tissues. Recently, it has been reported that the processes of angiogenesis and osteogenesis are coupled temporally and spatially. However, few studies reported the relationship and relevant mechanism between osteoclastogenesis and vasculogenesis. METHODS: Arraystar Mouse lncRNA microarray V3.0 was firstly used to analyze the differentially expressed lncRNA genes in osteoclast different stages during osteoclastogenesis. Cell counting kit 8 (CCK-8) analysis, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, migration and tube formation assays were used to detect impact of osteoclast different stages on the proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs), respectively. Finally, transfection of AK131850 shRNA, miR-93-5p mimic and miR-93-5p inhibitor, qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA), fluorescence in situ hybridization (FISH) and luciferase reporter assay were carried out to dissect molecular mechanisms. RESULTS: In this study, we found that newborn OCs (N-OC) and mature OCs (M-OC) during osteoclastogenesis significantly promoted proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs). Through lncRNA microarray and GO&pathway analysis, we found that AK131850 and co-expressed gene, vascular endothelial growth factor a (VEGFa), were significantly up-regulated in N-OC and M-OC. After inhibition of AK131850 the promoting effect of N-OC and M-OC on EPCs was reversed. Furthermore, we found that AK131850 directly competed miR-93-5p in N-OC and M-OC through sponge, thereby increasing VEGFa transcription, expression and secretion through derepressing of miR-93-5p on VEGFa. CONCLUSION: Our results provided the first finding that lncRNA-AK131850 sponged miR-93-5p in N-OC and M-OC during osteoclastogenesis to enhance the secretion of VEGFa, thus promoting vasculogenesis of EPCs.