Mechanical Bistability in Kerr-modified Cavity Magnomechanics.

Bistable mechanical vibration is observed in a cavity magnomechanical system, which consists of a microwave cavity mode, a magnon mode, and a mechanical vibration mode of a ferrimagnetic yttrium-iron-garnet sphere. The bistability manifests itself in both the mechanical frequency and linewidth under a strong microwave drive field, which simultaneously activates three different kinds of nonlinearities, namely, magnetostriction, magnon self-Kerr, and magnon-phonon cross-Kerr nonlinearities. The magnon-phonon cross-Kerr nonlinearity is first predicted and measured in magnomechanics. The system enters a regime where Kerr-type nonlinearities strongly modify the conventional cavity magnomechanics that possesses only a radiation-pressure-like magnomechanical coupling. Three different kinds of nonlinearities are identified and distinguished in the experiment. Our Letter demonstrates a new mechanism for achieving mechanical bistability by combining magnetostriction and Kerr-type nonlinearities, and indicates that such Kerr-modified cavity magnomechanics provides a unique platform for studying many distinct nonlinearities in a single experiment.

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. METHODS: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. RESULTS: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). CONCLUSIONS: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.

Luteolin suppresses gastric cancer progression by reversing epithelial-mesenchymal transition via suppression of the Notch signaling pathway.

BACKGROUND: Gastric cancer (GC) is one of the most malignant tumors and the second leading cause of cancer-related deaths in the world. Luteolin, a flavonoid present in many fruits and green plants, suppresses cancer progression. The effects of luteolin on GC cells and their underlying mechanisms remain unclear. METHODS: Effects of luteolin on cell proliferation, migration, invasion, and apoptosis were examined in vitro and in vivo by cell counting kit-8 (CCK-8), transwell assays, and flow cytometry, respectively. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blots were performed to evaluate Notch1 signaling and activation of epithelial-mesenchymal transition (EMT) in GC cells treated with or without luteolin. Immunohistochemistry was performed to examine proliferation and Notch1 expression in xenograft tumors. RESULTS: Luteolin significantly inhibited cell proliferation, invasion, and migration in a dose-dependent and time-dependent manner and promoted cell apoptosis. Luteolin reversed EMT by shrinking the cytoskeleton and by inducing the expression of epithelial biomarker E-cadherin and downregulating the mesenchymal biomarkers N-cadherin, vimentin and Snail. Furthermore, Notch1 signaling was inhibited by luteolin, and downregulation of Notch1 had similar effects as luteolin treatment on cell proliferation, migration, and apoptosis. In addition, luteolin suppressed tumor growth in vivo. A higher expression of Notch1 correlated with a poor overall survival and a poor time to first progression. Furthermore, co-immunoprecipitation analysis revealed that activated Notch1 and ß-catenin formed a complex and regulated cell proliferation, migration, and invasion. CONCLUSIONS: In this study, GC progression was inhibited by luteolin through suppressing Notch1 signaling and reversing EMT, suggesting that luteolin may serve as an effective anti-tumor drug in GC treatment.

Identification of a five-lncRNA signature for the diagnosis and prognosis of gastric cancer.

Gastric cancer (GC) is one of the most aggressive malignancies and has a poor prognosis. Identifying novel diagnostic and prognostic markers is of great importance for the management and treatment of GC. Long non-coding RNAs (lncRNAs), which are involved in multiple processes during the development and progression of cancer, may act as potential biomarkers of GC. Here, by performing data mining using four microarray data sets of GC downloaded from the Gene Expression Omnibus (GEO) database with different classifiers and risk score analyses, we identified a five-lncRNA signature (AK001094, AK024171, AK093735, BC003519 and NR_003573) displaying both diagnostic and prognostic values for GC. The results of the Kaplan-Meier survival analysis and log-rank test showed that the risk score based on this five-lncRNA signature was closely associated with overall survival time (p = 0.0001). Further analysis revealed that the risk score is an independent predictor of prognosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of 30 pairs of GC tissue samples confirmed that the five lncRNAs were dysregulated in GC, and receiver operating characteristic (ROC) curves showed the high diagnostic ability of combining the five lncRNAs, with an area under the curve (AUC) of 0.95 ± 0.025. The five lncRNAs involved in several cancer-related pathways were identified using gene set enrichment analysis (GSEA). These findings indicate that the five-lncRNA signature may have a good clinical applicability for determining the diagnosis and predicting the prognosis of GC.

Biomechanical evaluation of compression buttress screw and medial plate fixation for the treatment of vertical femoral neck fractures.

OBJECTIVE: To compare the biomechanical properties of compression buttress screw (CBS) fixation with three plate fixation methods for the treatment of vertical femoral neck fractures (FNFs). METHODS: A total of forty synthetic femoral models with simulated Pauwels type III fractures (angle of 70°) were equally assigned to one of four fixation groups: CBS fixation, anteromedial plate fixation (AMP), medial buttress plate fixation (MBP) and medial buttress plate fixation without proximal screw (MBPw). Within each group, half of the specimens were randomly assigned to two loading settings, an axial compression loading test and a hip-flexion torsion test. RESULTS: There were no significant differences in axial load to failure, axial stiffness, torsional strength, or torsional stiffness when comparing CBS with MBP (p>0.05). In the axial compression loading test, both CBS and MBP showed higher load to failure and axial stiffness than MBPw (p<0.05). In torsional testing, AMP exhibited superior torsional strength and torsional stiffness than both MBPw and MBP (all p<0.05) and a higher torsional strength than CBS fixation (p<0.05). There were no significant differences in torsional stiffness between the CBS and AMP fixation groups (p>0.05). CONCLUSION: The biomechanical parameters of CBS fixation are comparable to that of AMP and MBP, and demonstrate superior axial stiffness than MBPw fixation. Although the CBS method for surgical fixation of vertical FNF holds promise as a less invasive surgical technique than plate fixation with similar biomechanical assessments, further clinical evaluation is warranted.

Metabolomics Signatures in Type 2 Diabetes: A Systematic Review and Integrative Analysis.

OBJECTIVE: Metabolic signatures have emerged as valuable signaling molecules in the biochemical process of type 2 diabetes (T2D). To summarize and identify metabolic biomarkers in T2D, we performed a systematic review and meta-analysis of the associations between metabolites and T2D using high-throughput metabolomics techniques. METHODS: We searched relevant studies from MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library as well as Chinese databases (Wanfang, Vip, and CNKI) inception through 31 December 2018. Meta-analysis was conducted using STATA 14.0 under random effect. Besides, bioinformatic analysis was performed to explore molecule mechanism by MetaboAnalyst and R 3.5.2. RESULTS: Finally, 46 articles were included in this review on metabolites involved amino acids, acylcarnitines, lipids, carbohydrates, organic acids, and others. Results of meta-analysis in prospective studies indicated that isoleucine, leucine, valine, tyrosine, phenylalanine, glutamate, alanine, valerylcarnitine (C5), palmitoylcarnitine (C16), palmitic acid, and linoleic acid were associated with higher T2D risk. Conversely, serine, glutamine, and lysophosphatidylcholine C18:2 decreased risk of T2D. Arginine and glycine increased risk of T2D in the Western countries subgroup, and betaine was negatively correlated with T2D in nested case-control subgroup. In addition, slight improvements in T2D prediction beyond traditional risk factors were observed when adding these metabolites in predictive analysis. Pathway analysis identified 17 metabolic pathways may alter in the process of T2D and metabolite-related genes were also enriched in functions and pathways associated with T2D. CONCLUSIONS: Several metabolites and metabolic pathways associated with T2D have been identified, which provide valuable biomarkers and novel targets for prevention and drug therapy.

Use of a locking intramedullary nail for the treatment of initial varus proximal humeral fracture: a prospective pilot study.

OBJECTIVE: To evaluate the feasibility of locked intramedullary nailing, rather than locking plate fixation combined with fibular allograft augmentation, for initial varus proximal humeral fractures. METHODS: This prospective pilot study enrolled patients with initial varus proximal humeral fractures that were treated with a locking intramedullary nail. Radiography was performed to evaluate fracture healing. Data about the visual analogue scale (VAS) pain score, Constant Shoulder Score (CSS), Disabilities of the Arm, Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score and shoulder range of motion (ROM) were recorded. RESULTS: Twenty patients, including eight with Neer two-part and 12 with three-part fractures, were followed-up, with a mean time of 12.3 months. All patients sustained fractures that healed without re-varus. During the last follow-up, the shoulder function of the patients had recovered well, with a mean VAS pain score of 1.4, a mean CSS of 83.1, a mean DASH score of 80.8, a mean ASES score of 84.0 and a satisfactory ROM. In one patient, the proximal locking screw came out and was removed via a second surgery. CONCLUSIONS: The use of a locking intramedullary nail alone for initial varus proximal humeral two-/three-part fractures was feasible. This treatment has advantages, such as preventing re-varus and causing milder surgical trauma, than that seen with a locking plate.

G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.

Androgen receptor promotes gastric cancer cell migration and invasion via AKT-phosphorylation dependent upregulation of matrix metalloproteinase 9.

Androgen receptor (AR) plays an important role in many kinds of cancers. However, the molecular mechanisms of AR in gastric cancer (GC) are poorly characterized. Here, we investigated the role of AR in GC cell migration, invasion and metastatic potential. Our data showed that AR expression was positively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by activation of AKT and upregulation of matrix metalloproteinase 9 (MMP9). AR overexpression induced increases in GC cell migration, invasion and proliferation in vitro and in vivo. These effects were attenuated by inhibition of AKT, AR and MMP9. AR overexpression upregulated MMP9 protein levels, whereas this effect was counteracted by AR siRNA. Inhibition of AKT by siRNA or an inhibitor (MK-2206 2HC) decreased AR protein expression in both stably transfected and parental SGC-7901 cells. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that AR bound to the AR-binding sites of the MMP9 promoter. In summary, AR overexpression induced by AKT phosphorylation upregulated MMP9 by binding to its promoter region to promote gastric carcinogenesis. The AKT/AR/MMP9 pathway plays an important role in GC metastasis and may be a novel therapeutic target for GC treatment.