Targeting PNPO to suppress tumor growth via inhibiting autophagic flux and to reverse paclitaxel resistance in ovarian cancer.

Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC.

Photocatalytic Reduction of Perrhenate and Pertechnetate in a Strongly Acidic Aqueous Solution.

Pertechnetate (99TcO4-), a physiologically toxic radioactive anion, is of great concern due to its high mobility in environmental contamination remediation. Although the soluble oxyanion can be photoreduced to sparingly soluble TcO2·nH2O, its effective removal from a strongly acidic aqueous solution remains a challenge. Here, we found that low-crystalline nitrogen-doped titanium oxide (N-TiO2, 0.6 g L-1) could effectively uptake perrhenate (ReO4-, 10 mg L-1, a nonradioactive surrogate for TcO4-) with 50.8% during 360 min under simulated sunlight irradiation at pH 1.0, but P25 and anatase could not. The nitrogen active center formed by trace nitrogen doping in N-TiO2 can promote the separation and transfer of photogenerated carriers. The positive valence band value of N-TiO2 is slightly higher than those of P25 and anatase, which means that the photogenerated holes have a stronger oxidizability. These holes are involved in the formation of strong reducing •CO2- radicals from formic acid oxidation. The active radicals convert ReO4- to Re(VI), which is subsequently disproportionated to Re(IV) and Re(VII). Effective photocatalytic reduction/removal of Re(VII)/Tc(VII) is performed on the material, which may be considered a potential and convenient strategy for technetium decontamination and extraction in a strongly acidic aqueous solution.

Quantitative toxicological study of dose-dependent arsenic-induced cells via synchrotron-based STXM and FTIR measurement.

Inorganic arsenic (iAs) is a well-known naturally occurring metalloid with abundant hazards to our environment, especially being a human carcinogen through arsenic-contaminated drinking water. The iAs-related contamination is usually examined by a chemical assay system or fluorescence staining technique to investigate iAs accumulation and its deleterious effects. In this work, we present a dual-modality measurement and quantitative analysis methods for the overall evaluation of various dose-dependent iAs-related cytotoxicological manifestations by the combination of the synchrotron-radiation-based scanning transmission soft X-ray microscopy (SR-STXM) and Fourier transform infrared micro-spectroscopy (SR-FTIR) techniques. The gray level co-occurrence matrix (GLCM) based machine learning was employed on SR-STXM data to quantify the cytomorphological feature changes and the dose-dependent iAs-induced feature classifications with increasing doses. The infrared spectral absorption peaks and changes of dose-dependent iAs-induced cells were obtained by the SR-FTIR technique and classified by the multi-spectral-variate principle component analysis (PCA-LDA) method, showing the separated spatial distribution of dose-dependent groups. In addition, the quantitative comparisons of trivalent and pentavalent iAs under high dose conditions (iAsIII_H & iAsV_H) demonstrated that iAsIII_H and its compounds were more toxic than iAsV_H. This method has a potential in providing the morphological and spectral characteristics evolution of the iAs-related cells or particles, revealing the actual risk of arsenic contamination and metabolism.

High-resolution quantitative phase imaging based on a spatial light modulator and incremental binary random sampling.

We propose a single-beam high-resolution quantitative phase imaging method based on a spatial light modulator (SLM) and an incremental binary random sampling (IBRS) algorithm. In this method, the image of the test object presents on the image sensor through an optical microscopy system composed of an objective lens and a collimating lens. A transmittance SLM displaying a group of well-designed IBRS patterns is inserted in the optical microscopy system to modulate the object wavefront. The phase information of the object image can be quantitatively retrieved from the recorded intensities using the IBRS algorithm and the amplitude obtained directly from the diffraction intensity. The IBRS algorithm employed in our method has higher accuracy for phase retrieval compared with our previously proposed complementary random sampling algorithm, which is confirmed by simulations. Further, we demonstrate experimentally the feasibility of our method through several examples: phase imaging of immersion oil droplets with a diffraction-limited lateral resolution of 1.54 µm and a few microbiological specimens with 0.70 µm. Experimental results reveal that our proposed method provides a feasible single-beam technique for quantitative phase imaging with a high spatial resolution.

Quantitative analysis of analytical elements in Al-In-Sn-O thin film based on comprehensive calibration curves using picosecond laser-induced breakdown spectroscopy.

Al-In-Sn-O (AITO) thin film refers to a novel wide-bandgap transparent conductive material, which is formed by doping the aluminum element into In-Sn-O material. It is of promising application in deep ultraviolet optoelectronic devices. Al/Al+In+Sn and Sn/Al+In+Sn are capable of impacting the optical and electrical properties of AITO thin film. Three groups of AITO thin film samples with different sputtering powers, sputtering pressures, and sputtering times were prepared with magnetron sputtering. The concentration ratio of Al/Al+In+Sn and Sn/Al+In+Sn in AITO samples was quantitatively analyzed with laser-induced breakdown spectroscopy (LIBS) technology. A single calibration curve was drawn based on the sputtering parameters of each group, and the comprehensive calibration curves of two concentration ratios under any sputtering parameters were plotted. The accuracy of the comprehensive calibration curve was determined with samples prepared under random sputtering parameters, and the energy dispersive x-ray spectroscopy analysis results were compared with the LIBS technical analysis results. The relative error was less than 5%, so the LIBS technical analysis was demonstrated to be accurate. By building the comprehensive calibration curve, a novel method to conduct rapid online analysis of AITO thin films and timely determination of photoelectrical properties is presented, and the new application of LIBS technology is developed in thin film semiconductor materials.

Effect of Ni, W and Mo on the microstructure, phases and high-temperature sliding wear performance of CoCr matrix alloys.

CoCrNi, CoCrW and CoCrMo alloys were fabricated by powder metallurgy technology. The effect of nickel, tungsten and molybdenum, as alloying elements, on the microstructure, phase, mechanical and high-temperature tribological properties of CoCr matrix alloys were systematically studied. The wear and friction behaviors were investigated from room temperature (23 °C) to 1000 °C. The alloys were found to contain different ratios of γ(fcc) and ε(hcp) phases; Ni stabilized γ(fcc), while W and Mo stabilized ε(hcp). The hardness measurements showed that the strengthening effect increased with the addition of Ni, W, and Mo, respectively. Addition of Mo and W resulted in the lowest and highest friction coefficients with the addition of Ni resulting in a friction coefficient between the two. The wear and friction behaviors of the three alloys depended on the phase, alloying elements and oxidation from room temperature to 1000 °C. Coefficients of friction of the alloys were not directly correlated with the wear rates. CoCr matrix alloys reinforced with Mo showed the highest hardness and the best high-temperature tribological performance. It was attributed to the high hardness, stable oxide film, and in situ formed high-temperature solid lubricants. With an increase in temperature, the wear mechanism was found to change from abrasive wear to oxidative wear.

[Risk factors for minimally invasive surfactant administration failure in preterm infants with respiratory distress syndrome].

OBJECTIVE: To identify risk factors for minimally invasive surfactant administration (MISA) failure in the treatment of preterm infants with respiratory distress syndrome (RDS) and the influence of MISA failure on neonatal outcome. METHODS: A retrospective analysis was performed for the clinical data of 148 preterm infants with a gestational age of ≤32 weeks and a clinical diagnosis of RDS, who were admitted to the neonatal intensive care unit of eight tertiary hospitals in Beijing, Tianjin and Hebei Province from July 1, 2017 to December 31, 2018 and were treated with MISA (bovine pulmonary surfactant, PS). According to whether MISA failure (defined as the need for mechanical ventilation within 72 hours after MISA) was observed, the infants were divided into two groups: MISA failure group (n=16) and MISA success (n=132). A logistic regression analysis was used to investigate the risk factors for MISA failure and its influence on neonatal outcome. RESULTS: The MISA failure rate was 10.8% (16/148). The logistic regression analysis showed that a high incidence rate of grade >II RDS before PS administration, low mean arterial pressure and high pulse pressure before administration, a low dose of initial PS administration, and long injection time and operation time were the risk factors for MISA failure (OR=5.983, 1.210, 1.183, 1.055, 1.036, and 1.058 respectively, P<0.05). After the control for the above risk factors, the logistic regression analysis showed that the MISA failure group had a significantly higher incidence rate of bronchopulmonary dysplasia (BPD) (OR=8.537, P<0.05). CONCLUSIONS: A high grade of RDS, a low mean arterial pressure, and a high pulse pressure before administration are independent risk factors for MISA failure, and a low dose of initial PS administration, a long injection time, and a long operation time may increase the risk of MISA failure. MISA failure may increase the incidence rate of BPD in preterm infants.

[A clinical analysis of late-onset sepsis in very low birth weight and extremely low birth weight infants].

OBJECTIVE: To study the clinical features and pathogenic bacteria of late-onset sepsis (LOS) in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. METHODS: Among the VLBW/ELBW infants with a gestational age of <32 weeks who were admitted to the hospital between January 2012 and December 2016, those with LOS were enrolled as the LOS group, and those without sepsis were matched for the infant with LOS in gestational age were enrolled as the control group. According to the presence or absence of in-hospital death, the LOS group was further divided into a death subgroup and a survival subgroup. Risk factors for LOS, clinical features, distribution of pathogenic bacteria, drug resistance, and high-risk factors for LOS-related death were analyzed. RESULTS: A total of 513 VLBW/ELBW infants were enrolled, and there were 65 infants in the LOS group and 130 in the control group. The incidence rate of LOS was 12.7%. In the LOS group, 6 infants died and 59 survived. Compared with the control group, the LOS group had a significantly lower birth weight (P<0.05) and significantly longer indwelling time of peripherally inserted central catheter (PICC), duration of mechanical ventilation, and length of hospital stay (P<0.05). Compared with the control group, the LOS group had a significantly higher proportion of small-for-gestational-age infants, infants undergoing mechanical ventilation, infants with neonatal necrotizing enterocolitis, or infants who died (P<0.05). Low birth weight, small-for-gestational-age infant, and long indwelling time of PICC were independent risk factors for LOS in VLBW/ELBW infants (OR=1.396, 2.550, and 1.068 respectively, P<0.05). Purulent meningitis was an independent risk factor for LOS-related death in VLBW/ELBWIs infants (OR=13.443, P<0.05). A total of 65 strains of pathogenic bacteria were cultured in the LOS group, among which there were 39 strains (60%) of Gram-negative bacteria, including 15 strains producing extended spectrum beta-lactamases (ESBLs), and antibiotics were applied for 67% (10/15) of the ESBL strains within 2 weeks before the onset of LOS. The rate of antibiotic use for ESBL strains was significantly higher than that for non-resistant strains [67% (10/15) vs 29% (7/24); P<0.05]. CONCLUSIONS: Low birth weight, SGA infant, and long indwelling time of PICC are independent risk factors for LOS in VLBW/ELBW infants, and death tends to occur in LOS infants with purulent meningitis. Most pathogenic bacteria of LOS are Gram-negative bacteria, and use of antibiotics within 2 weeks before disease onset may increase the risk of ESBL strain infection.

Controllable Synthesis of [11-2-2] Faceted InN Nanopyramids on ZnO for Photoelectrochemical Water Splitting.

Indium nitride (InN) is one of the promising narrow band gap semiconductors for utilizing solar energy in photoelectrochemical (PEC) water splitting. However, its widespread application is still hindered by the difficulties in growing high-quality InN samples. Here, high-quality InN nanopyramid arrays are synthesized via epitaxial growth on ZnO single-crystals. The as-prepared InN nanopyramids have well-defined exposed facets of [0001], [11-2-2], [1-212], and [-2112], which provide a possible routine for understanding water oxidation processes on the different facets of nanostructures in nanoscale. First-principles density functional calculations reveal that the nonpolar [11-2-2] face has the highest catalytic activity for water oxidation. PEC investigations demonstrate that the band positions of the InN nanopyramids are strongly altered by the ZnO substrate and a heterogeneous n-n junction is naturally formed at the InN/ZnO interface. The formation of the n-n junction and the built-in electric field is ascribed to the efficient separation of the photogenerated electron-hole pairs and the good PEC performance of the InN/ZnO. The InN/ZnO shows good photostability and the hydrogen evolution is about 0.56 µmol cm-2 h-1 , which is about 30 times higher than that of the ZnO substrate. This study demonstrates the potential application of the InN/ZnO photoanodes for PEC water splitting.

Synthesis and Characterization of PEGylated Trityl Radicals: Effect of PEGylation on Physicochemical Properties.

Tetrathiatriarylmethyl (TAM, trityl) radicals have attracted considerable attention as spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging owing to their sharp EPR singlet signals and high biostability. However, their in vivo applications were limited by the short blood circulation lifetimes and strong binding with albumins. Our previous results showed that PEGylation is a feasible method to overcome the issues facing in vivo applications of TAM radicals. In the present study, we synthesized a series of new PEGylated TAM radicals (TTP1, TPP2, TNP1, TNP2, d-TNP1, and d-TNP3) containing various lengths and numbers of mPEG chains. Our results found that the pattern of PEGylation exerts an important effect on physicochemical properties of the resulting TAM radicals. Dendritic PEGylated TAM radicals, TNP1 and TNP2, have higher water solubility and lower susceptibility for self-aggregation than their linear analogues TPP1 and TPP2. Furthermore, dendritic PEGylated TAM radicals exhibit extremely high stability toward various biological oxidoreductants as well as in rat whole blood, liver homogenate, and following in vivo intravenous administration in mice. Importantly, the deuterated derivatives, especially d-TNP3, exhibit excellent properties including the sharp and O2-sensitive EPR singlet signal, good biocompatibility, and prolonged kinetics with half-life time of ≥10 h in mice. These PEGylated TAM radicals should be suitable for a wide range of applications in in vivo EPR spectroscopy and imaging.

Large-area snow-like MoSe2 monolayers: synthesis, growth mechanism, and efficient electrocatalyst application.

This study explores the large-area synthesis of controllable morphology, uniform, and high-quality monolayer. MoSe2 is essential for its potential application in optoelectronics, photocatalysis, and renewable energy sources. In this study, we successfully synthesized snow-like MoSe2 monolayers using a simple chemical vapor deposition method. Results reveal that snow-like MoSe2 is a single crystal with a hexagonal structure, a thickness of ∼0.9 nm, and a lateral dimension of up to 20 µm. The peak position of the photoluminescence spectra is ∼1.52 eV corresponding to MoSe2 monolayer. The growth mechanism of the snow-like MoSe2 monolayer was investigated and comprised a four-step process during growth. Finally, we demonstrate that the snow-like MoSe2 monolayers are ideal electrocatalysts for hydrogen evolution reactions (HERs), reflected by a low Tafel slope of ∼68 mV/decade. Compared with the triangular-shaped MoSe2 monolayer, the hexangular snow-like shape with plentiful edges is superior for perfect electrocatalysts for HERs or transmission devices of optoelectronic signals.

Supramolecular host-guest interaction of trityl-nitroxide biradicals with cyclodextrins: modulation of spin-spin interaction and redox sensitivity.

Supramolecular host-guest interactions of trityl-nitroxide (TN) biradicals CT02-VT, CT02-AT and CT02-GT with methyl-ß-cyclodextrin (M-ß-CD), hydroxypropyl-ß-cyclodextrin (H-ß-CD) and γ-cyclodextrin (γ-CD) were investigated by EPR spectroscopy. In the presence of cyclodextrins (i.e., γ-CD, M-ß-CD and H-ß-CD), host-guest complexes of CT02-VT are formed where the nitroxide and linker parts possibly interact with the cyclodextrins' cavities. Complexation with cyclodextrins leads to suppression of the intramolecular through-space spin-spin exchange coupling in CT02-VT, thus allowing the determination of the through-bond spin-spin exchange coupling which was calculated to be 1.6 G using EPR simulations. Different types of cyclodextrins have different binding affinities with CT02-VT in the order of γ-CD (95 M(-1)) > M-ß-CD (70 M(-1)) > H-ß-CD (32 M(-1)). In addition, the effect of the linkers in TN biradicals on the host-guest interactions was also investigated. Among the three TN biradicals studied, CT02-VT has the highest association constant with one designated cyclodextrin derivative. On the other hand, the complexes of CT02-GT (∼ 22 G) and CT02-AT (7.7-9.0 G) with cyclodextrins have much higher through-bond spin-spin exchange couplings than those of CT02-VT (1.6 G) due to the shorter linkers than those of CT02-VT. Furthermore, the stability of TN biradicals towards ascorbate was significantly enhanced after the complexation with CDs, with an almost 2-fold attenuation of the second-order rate constants for all the biradicals. Therefore, the supramolecular host-guest interactions with cyclodextrins will be an alternative method to modulate the magnitude of the spin-spin interactions and redox sensitivity of TN biradicals, and the resulting complexes are promising as highly efficient DNP polarizing agents as well as EPR redox probes.

P16INK4A and survivin: Diagnostic and prognostic markers in cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

OBJECTIVE: To explore the the correlations of p16INK4A (p16) and survivin expressions with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. METHODS: The p16 and survivin expressions were detected in 50 cervical squamous cell carcinoma tissues, 150 various grades of CIN tissues and 30 normal cervical tissues using immunohistochemistry. All data were analyzed applying SPSS 17.0 software. RESULTS: The p16 and survivin expressions showed the presence of statistical significance in cervical cancer, CINI, CINII, CINIII and normal cervical tissues (P<0.05), and the comparison also revealed statistical significance among groups (all P<0.05); the p16 and survivin expressions were positively correlated with the grade of cervical diseases (both P<0.05). Moreover, p16 protein was associated with CIN grade and lymph node metastases in cervical cancer (all P<0.05); survivin protein was also related with clinical stages, CIN grade and lymph node metastases (all P<0.05); the p16 and survivin expressions were positively correlated with cervical cancer (r=0.854, P<0.001), and associated with poor prognosis of cervical cancer. CONCLUSION: Briefly, p16 and survivin expression may be correlated with the clinico-pathological and prognosis of cervical cancer.

Optimization of reconstructed quality of hard x-ray phase microtomography.

For applications of hard x-ray propagation-based phase-contrast computed microtomography (PPCT) in high-resolution biological research, high spatial resolution and high contrast-to-noise ratio are simultaneously required for tiny structural discrimination and characterization. Most existing micro-CT techniques to improve image quality are limited by high cost, physical limitations, and complexity of the experimental hardware and setup. In this work, a novel PPCT technique, which combines a wavelet-transform-based modulation transform function compensation algorithm and a generalized phase-retrieval algorithm, is proposed to optimize the reconstruction quality of tomographic slices. Our experimental results, which compared the spatial resolutions and contrast-to-noise ratios of reconstructed images, demonstrated the validity of the proposed generalized PPCT technique. The experimental results showed that the proposed generalized PPCT technique is superior to the direct PPCT and the linearized phase-retrieval PPCT techniques. This novel PPCT technique demonstrates great potential for biological imaging, especially for applications that require high spatial resolution and limit radiation exposure.

Predictive Value of Free ß-hCG Multiple of the Median for Women with Preeclampsia.

BACKGROUND: Preeclampsia (PE) is relatively common and is unpredictable in its onset and progression. AIMS: We investigated the clinical value of using the multiple of the median (MoM) of free ß-human chorionic gonadotropin (ß-hCG) concentrations in women with normal pregnancy and PE. METHODS: This study was based on a dataset available from published studies, and the relevant studies were retrieved from multiple electronic databases. Data were extracted from case-control studies; a random-effects model was employed, and standardized mean difference and 95% confidence intervals were calculated. Twelve case-control studies (eleven English-based articles and one Chinese-based article) were analyzed in the current meta-analysis and included 702 patients with PE and 8,233 women with normal pregnancies. RESULTS: Statistical analysis revealed a higher MoM of ß-hCG serum levels in patients with PE. Ethnicity subgroup analysis showed that the MoM of serum ß-hCG levels was significantly higher in women with PE in both Asian and Caucasian populations. CONCLUSION: The MoM of ß-hCG serum levels was significantly increased in women with PE compared to women with normal pregnancies. Screening for serum ß-hCG MoM levels will be helpful in the early identification of pregnancies at risk of developing PE. © 2015 S. Karger AG, Basel.

Celastrol ameliorates lupus by promoting apoptosis of autoimmune T cells and preventing autoimmune response in MRL/lpr mice.

OBJECTIVE: Celastrol is a bioactive constituent extracted from Tripterygium wilfordii (thunder god vine). It has been demonstrated to have a therapeutic effect on experimental disease models for chronic inflammatory and immune disorders. In the present study, we investigated whether and how celastrol exerts a regulatory effect on the autoimmune response in MRL/lpr mice. METHODS: We performed an in vivo study to determine the therapeutic effects of celastrol in MRL/lpr mice and then further investigated the underlying mechanism of celastrol in the regulation of the autoimmune response in MRL/lpr mice. RESULTS: Celastrol showed a therapeutic effect in MRL/lpr mice by preventing the enlargement of the spleen and lymph nodes, alleviating renal injury, and reducing the levels of ANA and anti-double-stranded DNA antibodies. Furthermore, celastrol suppressed the in vivo inflammatory response in MRL/lpr mice by reducing the serum levels of multiple cytokines, including interleukin (IL)-6, tumour necrosis factor (TNF) and interferon (IFN)-γ, and the production of multiple antibody subsets, including total IgG, IgG1 and IgG2b. In vitro, celastrol reduced anti-CD3 antibody stimulation-induced T helper 1 and TNF-producing cells in CD4+ T cells of MRL/lpr mice. In addition, celastrol significantly affected B cell differentiation and prevented the generation of plasma cells from B cells in MRL/lpr mice by reducing the frequency of activated and germinal centre B cells. Celastrol treatment also affected T cell differentiation and significantly reduced central memory T cell frequencies in MRL/lpr mice. Importantly, celastrol treatment specifically promoted apoptosis of CD138+ but not CD138- T cells to suppress autoimmune T cell accumulation in MRL/lpr mice. CONCLUSIONS: Celastrol exerted therapeutic effects on lupus by specifically promoting apoptosis of autoimmune T cells and preventing the progression of autoimmune response.

Prediction Model for Therapeutic Responses in Ovarian Cancer Patients Using Paclitaxel-Resistant Immune-Related lncRNAs.

BACKGROUND: Ovarian cancer (OC) is the deadliest malignant tumor in women with a poor prognosis due to drug resistance and lack of prediction tools for therapeutic responses to anti- cancer drugs. OBJECTIVE: The objective of this study was to launch a prediction model for therapeutic responses in OC patients. METHODS: The RNA-seq technique was used to identify differentially expressed paclitaxel (PTX)- resistant lncRNAs (DE-lncRNAs). The Cancer Genome Atlas (TCGA)-OV and ImmPort database were used to obtain immune-related lncRNAs (ir-lncRNAs). Univariate, multivariate, and LASSO Cox regression analyses were performed to construct the prediction model. Kaplan- Meier plotter, Principal Component Analysis (PCA), nomogram, immune function analysis, and therapeutic response were applied with Genomics of Drug Sensitivity in Cancer (GDSC), CIBERSORT, and TCGA databases. The biological functions were evaluated in the CCLE database and OC cells. RESULTS: The RNA-seq defined 186 DE-lncRNAs between PTX-resistant A2780-PTX and PTXsensitive A2780 cells. Through the analysis of the TCGA-OV database, 225 ir-lncRNAs were identified. Analyzing 186 DE-lncRNAs and 225 ir-lncRNAs using univariate, multivariate, and LASSO Cox regression analyses, 9 PTX-resistant immune-related lncRNAs (DEir-lncRNAs) acted as biomarkers were discovered as potential biomarkers in the prediction model. Single-cell RNA sequencing (scRNA-seq) data of OC confirmed the relevance of DEir-lncRNAs in immune responsiveness. Patients with a low prediction score had a promising prognosis, whereas patients with a high prediction score were more prone to evade immunotherapy and chemotherapy and had poor prognosis. CONCLUSION: The novel prediction model with 9 DEir-lncRNAs is a valuable tool for predicting immunotherapeutic and chemotherapeutic responses and prognosis of patients with OC.

Selective SERS Detection of TATB Explosives Based on Hydroxy-Terminal Nanodiamond-Multilayer Graphene Substrate.

Selective surface-enhanced Raman scattering (SERS) detection of target explosives with good reproducibility is very important for monitoring soldiers' health and ecological environment. Here, the specific charge transfer pathway was constructed between a stable nanodiamond-multilayer graphene (MGD) film substrate and the target explosives. Two-step wet chemical oxidation methods of H2O2 (30%) and HNO3 (65%) solutions were used to regulate the terminal structure of MGD films. The experimental results showed that the hydroxyl (-OH) functional groups are successfully modified on the surface of MGD thin films, and the MGD-OH substrates having good selectivity for 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) explosive in mixed solutions of the TATB, 2,2-dinitroethene-1,1-diamine, 2,4,6-trinitrotoluene, and 1,3,5-trinitroperhydro-1,3,5-triazine explosives compared with MGD substrates were demonstrated. Finally, first-principles density functional theory simulations revealed that the SERS enhancement of the MGD-OH substrate is mainly attributed to the transferred electrons between the -NO2 groups of TATB and the -OH groups of the MGD-OH substrate.

Deletion of toll-like receptor 4 ameliorates diabetic retinopathy in mice.

BACKGROUND: Diabetic retinopathy is a common and specific microvascular complication of diabetes, which is also the leading cause of preventable blindness. Therefore, we aimed to find a promising therapeutic strategy for diabetic retinopathy. METHODS: To investigate the role of toll-like receptor 4 (TLR4) in the diabetic retinopathy, we injected streptozotocin (STZ) into wild-type (wt) and TLR4 knock-out mice to induce diabetes. RESULTS: While STZ induced diabetes both in wt and TLR4-/- mice, deletion of TLR4 in diabetic mice significantly improved diabetic retinopathy compared to diabetic wt mice, as judged by the enhanced thickness of retinal tissue. Furthermore, TLR4-dependent NF-κB pathway, inflammatory cytokine release and the expressions of vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP), which were all remarkably stimulated in STZ-injected wt mice, were inhibited in STZ-injected TLR4-/- mice. CONCLUSION: TLR4 could serve as an independent target for treating diabetic retinopathy.

RBM15­mediating MDR1 mRNA m6A methylation regulated by the TGF­ß signaling pathway in paclitaxel­resistant ovarian cancer.

Ovarian cancer (OC) lacks effective biomarkers for diagnosis at an early stage and often develops chemoresistance after the initial treatment at an advanced stage. RNA­binding motif protein 15 (RBM15) is an RNA m6A methylation mediator that serves an oncogenic role in some cancers. However, the function and molecular mechanisms of RBM15 in ovarian tumorigenesis and chemoresistance remain to be elucidated. The present study identified the overexpression of RBM15 in OC tissues and paclitaxel (PTX)­resistant cells using reverse transcription­quantitative (q)PCR, western blotting and immunohistochemistry. Clinical data analyses showed that high expression of RBM15 was associated with poor prognosis in patients with OC. Overexpression of RBM15 led to an increase in cell viability and colony formation and a decrease in cell sensitivity to PTX and apoptosis, whereas the knockdown of RBM15 resulted in the inhibition of cell viability and colony formation in vitro and tumor formation in vivo and increased cell apoptosis and sensitivity to PTX in a time­ and dose­dependent manner. Furthermore, RBM15 knockdown reduced the spheroid formation of PTX­resistant OC cells. Silencing of RBM15 decreased multidrug resistance 1 (MDR1) mRNA m6A methylation detected by the methylated RNA immunoprecipitation­qPCR assay and downregulated the expression of a chemo­drug efflux pump MDR1 at the mRNA and protein levels. Finally, RBM15 expression was suppressed by the activation of the TGF­ß signaling pathway. Thus, the findings revealed a TGF­ß/RBM15/MDR1 regulatory mechanism. Targeting RBM15 may provide a novel therapeutic strategy for the treatment of PTX­resistant OC.