LINC00662 promotes melanoma progression by competitively binding miR-107 and activating the ß-catenin signaling pathway.

Melanoma is a highly malignant tumor in the body. Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of various tumors. Emerging evidence demonstrates the critical role of lncRNAs in melanoma development. In this study, we aimed to investigate the expression, biological function and regulatory mechanism of LINC00662 in melanomas. First, we found that LINC00662 was up-regulated in melanoma tissues and cell lines. High expression of LINC00662 in melanomas was associated with a poor patient prognosis. Silencing of LINC00662 suppressed the proliferation, migration, and invasion of melanoma cells in vitro and in vivo, while overexpression of LINC00662 promoted melanoma cell proliferation in vitro. Bioinformatics analysis, dual-luciferase assay, and RIP assay confirmed that LINC00662 competitively regulated miR-107. Silencing of LINC00662 upregulated miR-107 expression in a melanoma cell line. Inhibition of miR-107 significantly reversed the inhibitory effect of LINC00662 silencing on cell proliferation and migration. Furthermore, POU3F2 was validated as a downstream target of LINC00662/miR107 and was downregulated when LINC00662 was silenced. Overexpressing POU3F2 attenuated the effect of si-LINC00662 on cellular functions. In addition, the results also showed that the ß-catenin pathway was involved in a si-LINC00662-induced function in melanoma. Overall, our results confirmed that LINC00662 promoted melanoma progression by sponging miR107 and inducing POU3F2, highlighting the mechanism of the LINC00662/miR-107/POU3F2 axis in melanoma cell proliferation and invasion.

Beam shifts controlled by orbital angular momentum in a guided-surface plasmon resonance structure with a four-level atomic medium.

We proposed a scheme to realize tunable giant Goos-Hänchen (GH) and Imbert Fedorov (IF) shifts of the Laguerre-Gauss (LG) beam on a guided-wave surface plasmon resonance (GWSPR) structure backed by a coherent atomic medium with the spontaneously generated coherence (SGC) effect. The orbital angular momentum carried by the incident LG beam can be applied to enhance and control IF shifts but is not beneficial to GH shifts. However, in the presence of SGC effect in the atomic medium, both GH and IF shifts can be simultaneously enhanced and well controlled. With the SGC effect, the linear absorption of the atomic medium vanishes, while the nonlinear absorption of that can be significantly enhanced and controlled by the trigger field, which contributes to controlling of the beam shifts. In particular, the direction of GH shifts can be switched by the Rabi frequency of the trigger field, which can be interpreted as the result of a competition between the inherent damping and the radiative damping corresponding to the nontrivial change in the loci of the reflection coefficients. This scheme provides an effective method to flexibly control and enhance the beam shifts, so it has potential applications in integrated optics, optical sensors, etc.

Evaluating the quantum Ziv-Zakai bound for phase estimation in noisy environments.

In the highly non-Gaussian regime, the quantum Ziv-Zakai bound (QZZB) provides a lower bound on the available precision, demonstrating the better performance compared with the quantum Cramér-Rao bound. However, evaluating the impact of a noisy environment on the QZZB without applying certain approximations proposed by Tsang [Phys. Rev. Lett.108, 230401 (2012)10.1103/PhysRevLett.108.230401] remains a difficult challenge. In this paper, we not only derive the asymptotically tight QZZB for phase estimation with the photon loss and the phase diffusion by invoking the variational method and the technique of integration within an ordered product of operators, but also show its estimation performance for several different Gaussian resources, such as a coherent state (CS), a single-mode squeezed vacuum state (SMSVS) and a two-mode squeezed vacuum state (TMSVS). In this asymptotically tight situation, our results indicate that compared with the SMSVS and the TMSVS, the QZZB for the CS always shows the better estimation performance under the photon-loss environment. More interestingly, for the phase-diffusion environment, the estimation performance of the QZZB for the TMSVS can be better than that for the CS throughout a wide range of phase-diffusion strength. Our findings will provide an useful guidance for investigating the noisy quantum parameter estimation.

Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression.

Background: Preeclampsia (PE) is an idiopathic hypertensive disorder of pregnancy, which is related to abnormal placental villi development. Our previous study has found that lncRNA NEAT1 promotes apoptosis of trophoblasts, but the role of NEAT1 in proliferation, migration, and invasion is still unclear. This study explores the role of NEAT1 in proliferation, migration, and invasion of trophoblasts.Methods: NEAT1 and miR-411-5p levels were detected by quantitative real-time PCR. Colony formation assay detected cell proliferation and transwell assay detected cell migration and invasion. Dual-luciferase reporter assay detected the binding between NEAT1 and miR-411-5p as well as the binding between miR-411-5p and PTEN. RNA pull-down assay detected the combination between NEAT1 and miR-411-5p.Result: NEAT1 was increased and miR-411-5p was reduced in PE patients and human trophoblasts (HTR8/SVneo cells) that were induced with H2O2. Interference with NEAT1 promoted cell proliferation, migration, and invasion, and the miR-411-5p inhibitor reversed the effect of siRNA-NEAT1. The expression of PTEN was promoted in PE patients and HTR8/SVneo cells that were induced with H2O2, while the miR-411-5p mimic inhibited PTEN expression, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic. Besides, under H2O2 induction, the miR-411-5p mimic promoted cell proliferation, migration, and invasion, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic.Conclusion: Interference with lncRNA NEAT1 promoted the proliferation, migration, and invasion of trophoblasts and alleviated the development of PE, which was partly mediated by upregulating miR-411-5p and inhibiting PTEN expression.

Dual cross-linked chitosan microspheres formulated with spray-drying technique for the sustained release of levofloxacin.

OBJECTIVE: This study was aimed to develop sustained drug release from levofloxacin (LF)-loaded chitosan (CS) microspheres for treating ophthalmic infections. SIGNIFICANCE: Dual cross-linked CS microspheres developed by the spray-drying technique displays significantly higher level of sustained drug release compared with non-cross-linked CS microspheres. METHODS: LF-loaded CS microspheres were prepared using the spray-drying technique, and then solidified with tripolyphosphate and glutaraldehyde as dual cross-linking agents. The microspheres were characterized by surface morphology, size distribution, zeta potential, encapsulation efficiency, and drug release profiles in vitro. The drug quantification was verified and analyzed by high-performance liquid chromatography (HPLC). The structural interactions of the CS with LF were studied with Fourier transform infrared spectroscopy. The effect of various influencing excipients in the formulation of the dual cross-linked CS microspheres on drug encapsulation efficiency and the drug release profiles were extensively investigated. RESULT: The microspheres demonstrated high encapsulation efficiency (72.4 ∼ 98.55%) and were uniformly spherical with wrinkled surface. The mean particle size was between 1020.7 ± 101.9 and 2381.2 ± 101.6 nm. All microspheres were positively charged (zeta potential ranged from 31.1 ± 1.32 to 42.81 ± 1.55 mV). The in vitro release profiles showed a sustained release of the drug and it was remarkably influenced by the cross-linking process. CONCLUSION: This novel spray-drying technique we have developed is suitable for manufacturing LF-loaded CS microspheres, and thus could serve as a potential platform for sustained drug release for effective therapeutic application in ocular infections.

Fabrication of chitosan based nanocomposite with legumain sensitive properties using charge driven self-assembly strategy.

Chitosan (CS) based nanoparticles (NPs) have several advantages in delivering drugs. They are usually prepared in a micro-emulsion solvent system but this route can leave significant levels of potentially harmful organic solvent residue in the NPs. In this study, we prepared CS based nanocomposites using charge driven self-assembly in an aqueous buffer, thus avoiding the use of organic solvents. Doxorubicin (DOX) was covalently attached to positive charged CS with a legumain substrate peptide to confer targeted drug release property, since legumain is often overexpressed in tumors or tumor associated micro environments. This DOX prodrug solution interacted with negative charged methoxyl poly (ethylene glycol)-block-poly (glutamic acid) copolymer (PEG-PGA) in an aqueous buffer forming nanocomposite with a regular morphology. The particle size and zeta potential of these NPs was regulated by the addition of different PEG-PGA concentrations into the DOX prodrug solution. Due to its potential for legumain triggered release, this DOX NP exhibited enhanced cytotoxicity against choroidal melanoma cell line (Mum-2C) and reduced cytotoxicity on normal human corneal epithelial cells (HCEC), suggesting a good potential for enhanced targeted delivery of chemotherapeutic agents. A chitosan based nanocomposite with legumain sensitive properties are rapidly controllable prepared in aqueous buffer by charge driven self-assembly strategy, without using micro-emulsion solvent system and cross-linking agents.

A prediction model for neonatal necrotizing enterocolitis in preterm and very low birth weight infants.

Objectives: Neonatal necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that primarily affects preterm and very low birth weight infants, with high morbidity and mortality. We aim to build a reliable prediction model to predict the risk of NEC in preterm and very low birth weight infants. Methods: We conducted a retrospective analysis of medical data from infants (gestational age <32 weeks, birth weight <1,500 g) admitted to Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. We collected clinical data, randomly dividing it into an 8:2 ratio for training and testing. Multivariate logistic regression was employed to identify significant predictors for NEC. Principal component analysis was used for dimensionality reduction of numerical variables. The prediction model was constructed through logistic regression, incorporating all relevant variables. Subsequently, we calculated performance evaluation metrics, including Receiver Operating Characteristic (ROC) curves and confusion matrices. Additionally, we conducted model performance comparisons with common machine learning models to establish its superiority. Results: A total of 292 infants were included, with 20% (n = 58) randomly selected for external validation. Multivariate logistic regression revealed the significance of four predictors for NEC in preterm and very low birth weight infants: temperature (P = 0.003), Apgar score at 5 min (P = 0.004), formula feeding (P = 0.007), and gestational diabetes mellitus (GDM, P = 0.033). The model achieved an accuracy of 82.46% in the test set with an F1 score of 0.90, outperforming other machine learning models (support vector machine, random forest). Conclusions: Our logistic regression model effectively predicts NEC risk in preterm and very low birth weight infants, as confirmed by external validation. Key predictors include temperature, Apgar score at 5 min, formula feeding, and GDM. This study provides a vital tool for NEC risk assessment in this population, potentially improving early interventions and child survival. However, clinical validation and further research are necessary for practical application.

A prediction model for short-term neurodevelopmental impairment in preterm infants with gestational age less than 32 weeks.

Introduction: Early identification and intervention of neurodevelopmental impairment in preterm infants may significantly improve their outcomes. This study aimed to build a prediction model for short-term neurodevelopmental impairment in preterm infants using machine learning method. Methods: Preterm infants with gestational age < 32 weeks who were hospitalized in The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, and were followed-up to 18 months corrected age were included to build the prediction model. The training set and test set are divided according to 8:2 randomly by Microsoft Excel. We firstly established a logistic regression model to screen out the indicators that have a significant effect on predicting neurodevelopmental impairment. The normalized weights of each indicator were obtained by building a Support Vector Machine, in order to measure the importance of each predictor, then the dimension of the indicators was further reduced by principal component analysis methods. Both discrimination and calibration were assessed with a bootstrap of 505 resamples. Results: In total, 387 eligible cases were collected, 78 were randomly selected for external validation. Multivariate logistic regression demonstrated that gestational age(p = 0.0004), extrauterine growth restriction (p = 0.0367), vaginal delivery (p = 0.0009), and hyperbilirubinemia (0.0015) were more important to predict the occurrence of neurodevelopmental impairment in preterm infants. The Support Vector Machine had an area under the curve of 0.9800 on the training set. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the curve on the test set is 0.70. The external validation proves the reliability of the prediction model. Conclusion: A support vector machine based on perinatal factors was developed to predict the occurrence of neurodevelopmental impairment in preterm infants with gestational age < 32 weeks. The prediction model provides clinicians with an accurate and effective tool for the prevention and early intervention of neurodevelopmental impairment in this population.

Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury.

Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation.

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In vitro, we found that stevioside could suppress RANKL-induced osteoclastogenesis and titanium particle-induced inflammatory response in a dose-dependent manner. Mechanistically, stevioside achieved these effects by disrupting the phosphorylation of TAK1 and subsequent activation of NF-κB/MAPKs signaling pathways. Collectively, our data suggest that stevioside effectively suppresses osteoclastogenesis and inflammatory response both in vitro and in vivo, and it might be a potential therapy for particle-induced osteolysis and other osteolytic diseases.

The comparison of chemical liquid deposition and acid dealumination modified ZSM-5 for catalytic pyrolysis of pinewood using pyrolysis-gas chromatography/mass spectrometry.

Catalyst deactivation is the main reason for low petrochemical yield in catalytic fast pyrolysis (CFP) of biomass. ZSM-5 catalysts modified by chemical liquid deposition (CLD) and acid dealumination (AD) were prepared to improve petrochemical yields for CFP of pinewood. The results showed that CLD by SiO2 led to the coverage of strong acid sites, while AD favored the removal of superficial acid sites. CFP of pinewood showed that the relative area ratio of BTX was boosted by 37.2% and 30.4% over modified ZSM-5 catalysts by CLD and AD, respectively. The yield of indenes and naphthalenes which were important precursors of heavy coke decreased sharply. Considering environmental cost and catalytic performance, CLD seems to be a preferable modification method over ZSM-5 in the catalytic pyrolysis of biomass for petrochemicals.

G-patch domain containing 2, a gene highly expressed in testes, inhibits nuclear factor-κB and cell proliferation.

G-patch domain containing 2 (GPATC2), a human gene that is highly expressed in the testes, was implicated as a novel cancer/testis antigen. The present study investigated GPATC2 expression in a number of human cell lines and rat tissues, and its potential biological function in 293T cells. Semi­quantitative reverse transcription-polymerase chain reaction analysis showed that GPATC2 was widely expressed in 15 human cell lines (representing different lineages) and in 11 different rat tissues, and that the GPATC2 mRNA relative expression level was significantly higher in the testis than it was in other tissues. 293T cells were transiently transfected with GPATC2-p enhanced green fluorescent protein (EGFP)­N1 or GPATC2-pEGFP-C3 and the nuclei were stained with 4',6'­diamidino­2­phenylindole. The results showed that GPATC2 is predominantly expressed in the nucleus of 293T cells. Overexpression of GPATC2 may inhibit transcription of the NF-κB reporter gene. The role of GPATC2 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that over­expression of GPATC2 in 293T cells significantly inhibited cell proliferation by decreasing the number of cells in S phase. By contrast, GPATC2 knockdown by RNA interference exhibited the opposite effect, suggesting that GPATC2 may be involved in inhibiting G1-S phase transition in 293T cells. In conclusion, these results provide novel insight into the breadth of expression of GPATC2 and its role in cell proliferation.

MicroRNA profiles and potential regulatory pattern during the early stage of spermatogenesis in mice.

Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, microRNAs (miRNAs) are involved in multiple developmental processes as critical regulators of transcriptional and post-transcriptional gene silencing. This study investigated the expression pattern of miRNAs in type B spermatogonia cells (BSc) and primary spermatocytes (PSc) of mice, using a high-throughput small RNA sequencing system. The results revealed that the expression levels of Let-7 family miRNAs were remarkably high in both cell types. Furthermore, the expression levels of miR-21, miR-140-3p, miR-103, miR-30a, miR-101b and miR-99b were decreased during the transformation from BSc to PSc. These miRNAs target vital genes that participate in apoptosis, cell proliferation and differentiation, junction assembly and cell cycle regulation. These results highlight the indispensable role of miRNAs in spermatogenesis.

Analysis of TMEM174 gene expression in various renal cancer types by RNA in situ hybridization.

Transmembrane protein 174 (TMEM174) mRNA is easily detectable in human kidney tissues and activates AP-1 and promotes 293T cell proliferation. In the present study, RNA in situ hybridization was used to detect TMEM174 gene expression in various malignant renal cancer and normal renal tissues. The results showed that TMEM174 exhibits differential expression in renal tissues, with a high positive rate of expression in squamous cell carcinoma with necrosis, papillary renal cell carcinoma and transitional cell carcinoma, and a low positive rate of expression in clear cell carcinoma, interstitial nephritis, undifferentiated carcinoma, retroperitoneal metastatic clear cell carcinoma, adrenal gland metastatic clear cell carcinoma, pelvic cavity metastatic chromophobe carcinoma, severe atypical hyperplasia of transitional epithelium and hyperplasia. Extremely weak expression was exhibited in collecting duct carcinoma, Wilms' tumor, chronic pyelonephritis, acute pyelonephritis, cancer adjacent normal renal tissue and normal renal tissue. In conclusion, the TMEM174 gene exhibited high expression levels in certain renal carcinomas, which may indicate that TMEM174 may have a significant role in the development and progression of these renal carcinomas.

δEF1 upregulates CDK4 transcription via the E2-box element on the CDK4 promoter.

The zinc finger-homeodomain transcription factor, δ-crystallin enhancer factor 1 (δEF1) has been identified as a regulatory factor involved in the promotion of breast cancer cell proliferation via the downregulation of p21 and the upregulation of cyclin-dependent kinase-2 (CDK2) and CDK4 expression. However, the molecular mechanisms underlying the regulation of CDK4 expression by δEF1 have not yet been elucidated. The present study demonstrated that the ectopic expression of δEF1 in MDA-MB-231 breast cancer cells significantly increased the activity of the CDK4 promoter. Deletion of the E2-box (CACGTG), which is located at position -197/-191 on the human CDK4 promoter, significantly attenuated the activation of CDK4 transcription by δEF1. In addition, a CDK4 promoter-M construct was generated via site-directed mutagenesis of the E2-box on the human CDK4 promoter. Luciferase assay showed that the activation of CDK4 promoter-M activity by δEF1 was markedly decreased compared with the CDK4-promoter-0.4k promoter. Knockdown of δEF1 using RNA interference resulted in the inhibition of CDK4 promoter activity. These observations suggest that δEF1 upregulates CDK4 transcription via the E2-box element on the CDK4 promoter.

Catalytic conversion of biomass pyrolysis-derived compounds with chemical liquid deposition (CLD) modified ZSM-5.

Chemical liquid deposition (CLD) with KH550, TEOS and methyl silicone oil as the modifiers was used to modify ZSM-5 and deposit its external acid sites. The characteristics of modified catalysts were tested by catalytic conversion of biomass pyrolysis-derived compounds. The effects of different modifying conditions (deposited amount, temperature, and time) on the product yields and selectivities were investigated. The results show KH550 modified ZSM-5 (deposited amount of 4%, temperature of 20°C and time of 6h) produced the maximum yields of aromatics (24.5%) and olefins (16.5%), which are much higher than that obtained with original ZSM-5 catalyst (18.8% aromatics and 9.8% olefins). The coke yield decreased from 44.1% with original ZSM-5 to 26.7% with KH550 modified ZSM-5. The selectivities of low-molecule-weight hydrocarbons (ethylene and benzene) decreased, while that of higher molecule-weight hydrocarbons (propylene, butylene, toluene, and naphthalene) increased comparing with original ZSM-5.