The Difference of Volatile Compounds in Female and Male Buds of Herpetospermum pedunculosum Based on HS-SPME-GC-MS and Multivariate Statistical Analysis.

Herpetospermum pedunculosum (Ser.) C. B. Clarke (Family Cucurbitaceae) is a dioecious plant and has been used as a traditional Tibetan medicine for the treatment of hepatobiliary diseases. The component, content, and difference in volatile compounds in the female and male buds of H. pedunculosum were explored by using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology and multivariate statistical analysis. The results showed that isoamyl alcohol was the main compound in both female and male buds and its content in males was higher than that in females; 18 compounds were identified in female buds including 6 unique compounds such as (E)-4-hexenol and isoamyl acetate, and 32 compounds were identified in male buds, including 20 unique compounds such as (Z)-3-methylbutyraldehyde oxime and benzyl alcohol. (Z)-3-methylbutyraldehyde oxime and (E)-3-methylbutyraldehyde oxime were found in male buds, which only occurred in night-flowering plants. In total, 9 differential volatile compounds between female and male buds were screened out, including isoamyl alcohol, (Z)-3-methylbutanal oxime, and 1-nitropentane based on multivariate statistical analysis such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). This is the first time to report the volatile components of H. pedunculosum, which not only find characteristic difference between female and male buds, but also point out the correlation between volatile compounds, floral odor, and plant physiology. This study enriches the basic theory of dioecious plants and has guiding significance for the production and development of H. pedunculosum germplasm resources.

1H NMR Combined with Multivariate Statistics for Discrimination of Female and Male Flower Buds of Populus tomentosa.

1H Nuclear Magnetic Resonance (1H NMR) combined with multivariate statistics was adopted to discriminate female and male flower buds of Populus tomentosa in the study. Samples of 11 female and 16 male flower buds of P. tomentosa were collected in Beijing, China. 1H NMR spectra were acquired on a 400 MHz spectrometer. In total, 30 chemical compounds were identified with standards and literature according to chemical shifts, peak areas, and multiplicity. Principal component analysis (PCA), hierarchical clustering analysis (HCA), and supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to discriminate female and male flower buds. An apparent grouping trend (R2X, 0.809; Q2, 0.903) between female and male groups was exhibited with PCA and HCA. The two groups were also well discriminated with OPLS-DA (R2X, 0.808; R2Y, 0.976; Q2, 0.960). Combined with variable importance in projection (VIP) > 1.0 and p < 0.05 of OPLS-DA, it was found that the content of daucosterol, ß-sitosterol, ursolic acid, and betulonic acid in male group was higher than that in female, which should be the key differences of chemical constituents in female and male flower buds of P. tomentosa. The study demonstrated that 1H NMR combined with multivariate statistics could be used to discriminate female and male plants and clarify differences, which provided a novel method to identify the gender of dioecious plants.

Epitaxial growth and characterization of high quality Bi2O2Se thin films on SrTiO3 substrates by pulsed laser deposition.

Recently, Bi2O2Se was revealed as a promising two-dimensional (2D) semiconductor for next generation electronics, due to its moderate bandgap size, high electron mobility and pronounced ambient stability. Meanwhile, it has been predicted that high-quality Bi2O2Se-related heterostructures may possess exotic physical phenomena, such as piezoelectricity and topological superconductivity. Herein, we report the first successful heteroepitaxial growth of Bi2O2Se films on SrTiO3 substrates via pulsed laser deposition (PLD) method. Films obtained under optimal conditions show an epitaxial growth with the c axis perpendicular to the film surface and the a and b axes parallel to the substrate. The growth mode transition to three-dimensional (3D) island from quasi-2D layer of the heteroepitaxial Bi2O2Se films on SrTiO3 (001) substrates is observed as prolonging deposition time of films. The maximum value of electron mobility reaches 160 cm2 V-1 s-1 at room temperature in a 70 nm thick film. The thickness dependent mobility provides evidence that interface-scattering is likely to be the limiting factor for the relatively low electron mobility at low temperature, implying that the interface engineering as an effective method to tune the low temperature electron mobility. Our work suggests the epitaxial Bi2O2Se films grown by PLD are promising for both fundamental study and practical applications.

Epitaxial Growth of 6 in. Single-Crystalline Graphene on a Cu/Ni (111) Film at 750 °C via Chemical Vapor Deposition.

The future electronic application of graphene highly relies on the production of large-area high-quality single-crystal graphene. However, the growth of single-crystal graphene on different substrates via either single nucleation or seamless stitching is carried out at a temperature of 1000 °C or higher. The usage of this high temperature generates a variety of problems, including complexity of operation, higher contamination, metal evaporation, and wrinkles owing to the mismatch of thermal expansion coefficients between the substrate and graphene. Here, a new approach for the fabrication of ultraflat single-crystal graphene using Cu/Ni (111)/sapphire wafers at lower temperature is reported. It is found that the temperature of epitaxial growth of graphene using Cu/Ni (111) can be reduced to 750 °C, much lower than that of earlier reports on catalytic surfaces. Devices made of graphene grown at 750 °C have a carrier mobility up to ≈9700 cm2 V-1 s-1 at room temperature. This work shines light on a way toward a much lower temperature growth of high-quality graphene in single crystallinity, which could benefit future electronic applications.

Backstepping integral sliding mode control for pneumatic manipulators via adaptive extended state observers.

In this paper, a nonlinear control strategy is proposed for a pneumatic manipulator based on an adaptive extended state observer and a backstepping integral sliding mode controller. A single degree of freedom dynamic model is established for the pneumatic manipulator using an Euler-Lagrange dynamic equation. The adaptive extended state observer is designed by an adaptive law to estimate uncertainties and disturbances. The backstepping integral sliding mode controller is proposed using an integral sliding mode surface based on backstepping technique. Comparative experiments verify effectiveness of the proposed nonlinear control strategy for the pneumatic manipulator.

Accuracy of narrow-band imaging for diagnosing malignant transformation of vocal cord leukoplakia: A systematic review and meta-analysis.

Objective: To explore whether narrow-band imaging (NBI) endoscopy is accurate in the diagnosis of malignant transformation of vocal cord leukoplakia. Methods: The PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect data on studies reporting the use of NBI endoscopy as a diagnostic test for diagnosing vocal cord leukoplakia from January 2015 to December 2021. Study design, analysis method, and extraction results were performed according to the PRISMA guidelines. The sensitivity, specificity, pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) were used to summarize the performance metrics of the meta-analysis. Risk of bias data and the quality of the included studies was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). Results: Nine studies were finally included in the analysis. The results of the meta-analysis showed that the pooled sensitivity and specificity of NBI endoscopy for diagnosing leukoplakia lesions were 0.76 (95% CI: 0.72-0.8) and 0.93 (95% CI: 0.91-0.95), respectively. The PLR and NLR were 10.09 (95% CI: 6.53-15.59) and 0.22 (95% CI: 0.13-0.38), respectively. The comprehensive diagnostic odds ratio (DOR) was 54.96 (95% CI: 24.32-124.17), and the area under the curve was 0.9584. The eight articles had a low risk of bias risk and one article was unclear. Conclusion: NBI likely has good accuracy for diagnosing malignant transformation of vocal cord leukoplakia. However, multicenter studies and large samples are still needed.

Extensive identification of serum metabolites related to microbes in different gut locations and evaluating their associations with porcine fatness.

Gut microbiota plays important roles in host metabolism. Whether and how much the gut microbiota in different gut locations contributes to the variations of host serum metabolites are largely unknown, because it is difficult to obtain microbial samples from different gut locations on a large population scale. Here, we quantified the gut microbial compositions using 16S rRNA gene sequencing for 1070 samples collected from the ileum, cecum and faeces of 544 F6 pigs from a mosaic pig population. Untargeted metabolome measurements determined serum metabolome profiles. We found 1671, 12,985 and 103,250 significant correlations between circulating serum metabolites and bacterial ASVs in the ileum, cecum, and faeces samples. We detected nine serum metabolites showing significant correlations with gut bacteria in more than one gut location. However, most metabolite-microbiota pairwise associations were gut location-specific. Targeted metabolome analysis revealed that CDCA, taurine, L-leucine and N-acetyl-L-alanine can be used as biomarkers to predict porcine fatness. Enriched taxa in fat pigs, for example Prevotella and Lawsonia intracellularis were positively associated with L-leucine, while enriched taxa in lean pigs, such as Clostridium butyricum, were negatively associated with L-leucine and CDCA, but positively associated with taurine and N-acetyl-L-alanine. These results suggested that the contributions of gut microbiota in each gut location to the variations of serum metabolites showed spatial heterogeneity.

Signatures of the exciton gas phase and its condensation in monolayer 1T-ZrTe2.

The excitonic insulator (EI) is a Bose-Einstein condensation (BEC) of excitons bound by electron-hole interaction in a solid, which could support high-temperature BEC transition. The material realization of EI has been challenged by the difficulty of distinguishing it from a conventional charge density wave (CDW) state. In the BEC limit, the preformed exciton gas phase is a hallmark to distinguish EI from conventional CDW, yet direct experimental evidence has been lacking. Here we report a distinct correlated phase beyond the 2×2 CDW ground state emerging in monolayer 1T-ZrTe2 and its investigation by angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy (STM). The results show novel band- and energy-dependent folding behavior in a two-step process, which is the signatures of an exciton gas phase prior to its condensation into the final CDW state. Our findings provide a versatile two-dimensional platform that allows tuning of the excitonic effect.

Untargeted Metabolomics Coupled with Chemometrics for Leaves and Stem Barks of Dioecious Morus alba L.

The differences in metabolites in male and female individuals of dioecious Morus alba L. (Moraceae) are usually ignored and lack study. In the present study, 58 leaves and 61 stem barks from male and female individuals were analyzed by untargeted metabolomics via headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) coupled with chemometrics, including principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). A total of 66 and 44 metabolites were identified from leaves and stem barks, respectively. Four and eight differential metabolites among candidate metabolites in leaves and stem barks from male and female individuals were identified. Moreover, females possessed stronger antioxidant activity than males. This is the first report where untargeted metabolomics coupled with chemometrics was used to analyze the different metabolites and to discriminate the gender of leaves and stem barks of dioecious M. alba. It provided the basis for further study of M. alba and reference value for researching dioecious plants.

Gender Discrimination of Flower Buds of Mature Populus tomentosa by HPLC Fingerprint Combined with Chemometrics.

A high performance liquid chromatography-diode array detector (HPLC-DAD) was used to establish the HPLC fingerprint. Chemometrics methods were used to discriminate against the gender of flower buds of Populus tomentosa based on areas of common peaks calibrated with the HPLC fingerprint. The score plot of principal component analysis (PCA) showed a clear grouping trend (R 2 X, 0.753; Q 2, 0.564) between female and male samples. Two groups were also well discriminated with orthogonal partial least squares-discriminant analysis (OPLS-DA) (R 2 X, 0.741; R 2 Y, 0.980; Q 2, 0.970). As the hierarchical clustering analysis (HCA) heatmap showed, all samples were separated into two groups. Four compounds were screened out by S-plot and variable importance in projection (VIP > 1.0). Two of them were identified as siebolside B and tremulacin. This study demonstrated that HPLC fingerprints combined with chemometrics can be applied to discriminate against dioecious plants and screen differences, providing a reference for identifying the gender of dioecious plants.

Lipoid Proteinosis of the Pharynx and Larynx: A Case Report.

Lipoid proteinosis (LP) is a rare inherited multisystem disease. Classical clinical features include beaded eyelid papules, laryngeal infiltration, and neurological symptoms. Here, we report the diagnosis and treatment of a female patient with LP in order to improve physician awareness and understanding of this disease.

Comprehensive Quality Evaluation for Medicinal and Edible Ziziphi Spinosae Semen before and after Rancidity Based on Traditional Sensory, Physicochemical Characteristics, and Volatile Compounds.

To comprehensively evaluate the quality of medicinal and edible Ziziphi Spinosae Semen (ZSS, the dried ripe seeds of Ziziphus jujuba var. spinosa) before and after rancidity during storage, some indicators including traditional sensory properties, physicochemical characteristics, and volatile compounds were analyzed. As a result, compared with the normal samples, the rancid samples of ZSS produced a darker color, a bitter taste, and an irritating odor, increased moisture content, electrical conductivity, fatty oil content, and acid value, and decreased water- and alcohol-soluble extract contents and pH value. Among them, the acid value had significant difference (p < 0.01) from 3.90 of normal ZSS to 18.68 mg/g of rancid ZSS. A total of 39 volatile compounds were identified in samples, including 20 in normal ZSS and 38 compounds in rancid ZSS. Nineteen common compounds were identified in normal and rancid samples. Among them, the content of 10 compounds such as δ-limonene, (R,R)-2,3-butanediol, and (R,S)-2,3-butanediol was decreased but that of nine compounds such as acetic acid, n-octanoic acid, and n-nonanoic acid was increased in rancid ZSS. Nineteen unique compounds such as ß-phellandrene, α-pinene, and 3-carene were detected and only one compound, δ-cadinene, was not detected in rancid ZSS. In addition, eight short-chain organic acids, acetic, propanoic, butanoic, pentanoic, hexanoic, heptanoic, octanoic, and nonanoic acids, were new products in rancid ZSS, and it was speculated that the production of a series of organic acids might be the material basis of irritating odor after normal ZSS became rancid. This is the first report that a series of short-chain organic acids have been found in a rancid substance. In conclusion, there was a significant difference between normal and rancid ZSS. These indicators could be used as an early warning for judging the rancidity phenomenon of medicinal and edible ZSS. In addition, this is the first comprehensive evaluation about the rancidity process of a medicinal and edible substance.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Gender discrimination of Populus tomentosa barks by HPLC fingerprint combined with multivariate statistics.

A high-performance liquid chromatography (HPLC) fingerprint method with multivariate statistical analyses was applied to discriminate the male and female barks of Populus tomentosa for the first time. The samples of 11 male and 13 female barks of mature P. tomentosa were collected in Beijing. The chemical fingerprint of methanol extract was established by HPLC method with diode array detector (DAD). The principal component analysis (PCA), hierarchical clustering analysis (HCA), and supervised orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to discriminate male and female barks based on the area of common peaks identified in HPLC fingerprints. A clear grouping trend (R 2 X, 0.83; Q 2, 0.595) among the male and female samples was exhibited by PCA score plot. Two groups were clearly divided into male and female samples by HCA. Both male and female samples were well discriminated with OPLS-DA (R 2 X, 0.775; Q 2, 0.795). Seven potential chemical markers were screened by variable importance in projection (VIP values >1.0) of OPLS-DA model and four of them were identified as micranthoside, siebolside B, sakuranin, and isosakuranin. The HPLC fingerprint combined with multivariate statistical analyses could be used to discriminate the gender of barks of P. tomentosa and revealed the differences in chemical components, which enriched the basic studies on dioecious plant.

Quantum spin Hall state in monolayer 1T'-TMDCs.

Although the 1T' phase is rare in the transition metal dichalcogenides (TMDCs) family, it has attracted rapid growing research interest due to the coexistence of superconductivity, unsaturated magneto-resistance, topological phases etc. Among them, the quantum spin Hall (QSH) state in monolayer 1T'-TMDCs is especially interesting because of its unique van der Waals crystal structure, bringing advantages in the fundamental research and application. For example, the van der Waals two-dimensional (2D) layer is vital in building novel functional vertical heterostructure. The monolayer 1T'-TMDCs has become one of the widely studied QSH insulator. In this review, we review the recent progress in fabrications of monolayer 1T'-TMDCs and evidence that establishes it as QSH insulator.

Explaining the interactions between metaldehyde and acidic surface groups of activated carbon under different pH conditions.

Metaldehyde (MA) is an organic compound widely used in agriculture all around the world as molluscicide. There are growing concerns that relatively high levels of MA have been detected in surface water, which could be ascribed to the fact that it is transparent to common wastewater treatment processes. A theoretical study of the influence of activated carbon (AC) surface groups (SGs) on MA adsorption is done in order to help to understand the process and to evaluate the influence of the acid SGs over the adsorption in AC filters. Multiple Minima Hypersurface methodology was employed in order to study the interactions of the MA with acid SGs (hydroxyl and carboxyl) at acidic and neutral pH, and at different hydration conditions explicitly taking into account the solvent influence. Selected structures were re-optimized using Density Functional Theory and posteriorly refined to achieve a well-defined electron density to characterize the interactions by the Quantum Theory of Atoms in Molecules approach. The obtained results showed that the presence of SGs enhances the adsorption process. The deprotonated carboxyl and hydroxyl SGs of AC models show the strongest interactions, suggesting greater adsorption at neutral pH which is in concordance with experimental data. The main interactions are of a dispersive nature between the pesticide and the π-cloud of the AC and hydrogen bonds between the MA and the acid SGs suggesting that the adsorption process is driven by a physisorption mechanism. Water acts as an intermediary between the AC and MA and competing with it for the adsorption sites.

The impact of humic acid on metaldehyde adsorption onto powdered activated carbon in aqueous solution.

Metaldehyde has been detected in surface water and drinking water in the UK, exceeding the EU and UK standard of 0.1 µg L-1. The presence of natural organic matter (NOM) is considered to affect the removal efficiency of metaldehyde using traditional treatment methods such as adsorption by granular activated carbon. This paper selected humic acid (HA) to represent NOM and investigated the single and binary adsorption systems of metaldehyde and HA by powdered activated carbon (PAC). Metaldehyde was effectively removed by PAC in both systems. Since the percentage removal of metaldehyde was only 3% lower in the binary adsorption system, HA was therefore not considered as a significant compound competing with metaldehyde for adsorption sites on PAC. An adsorption equilibrium study and kinetic study for metaldehyde in a single system suggested that the Langmuir isotherm and the pseudo-second order kinetic model were more suitable in this case than the Freundlich isotherm and the pseudo-first order kinetic model. The two models revealed that the maximum adsorption capacity (q m) of metaldehyde by PAC was 28.3 mg g-1 and the adsorption rate (k 2) was 0.16 g mg-1 min-1. The effect of pH of metaldehyde solution was also investigated in a single system. Higher percentage removal of metaldehyde was found under alkaline conditions. In contrast to metaldehyde, HA was not effectively and efficiently removed by PAC in both systems, even with higher PAC dosages and longer contact times. Hence, the microporous and mesoporous PAC was suitable for removing metaldehyde even in the binary system.

Growth and structural characterisation of Sr-doped Bi2Se3 thin films.

We grew Sr-doped Bi2Se3 thin films using molecular beam epitaxy, and their high quality was verified using transmission electron microscopy. The thin films exhibited weak antilocalisation behaviours in magneto-resistance measurements, a typical transport signature of topological insulators, but were not superconducting. In addition, the carrier densities of the non-superconducting thin-film samples were similar to those of their superconducting bulk counterparts. Atom-by-atom energy-dispersive X-ray mapping also revealed similar Sr doping structures in the bulk and thin-film samples. Because no qualitative distinction between non-superconducting thin-film and superconducting bulk samples had been found, we turned to a quantitative statistical analysis, which uncovered a key structural difference between the bulk and thin-film samples. The separation between Bi layers in the same quintuple layer was compressed whereas that between the closest Bi layers in two neighbouring quintuple layers was expanded in the thin-film samples compared with the separations in pristine bulk Bi2Se3. In marked contrast, the corresponding changes in the bulk doped samples showed opposite trends. These differences may provide insight into the absence of superconductivity in doped topological insulator thin films.

Degradation of metaldehyde in water by nanoparticle catalysts and powdered activated carbon.

Metaldehyde, an organic pesticide widely used in the UK, has been detected in drinking water in the UK with a low concentration (<1 µg L-1) which is still above the European and UK standard requirements. This paper investigates the efficiency of four materials: powdered activated carbon (PAC) and carbon-doped titanium dioxide nanocatalyst with different concentrations of carbon (C-1.5, C-40, and C-80) for metaldehyde removal from aqueous solutions by adsorption and oxidation via photocatalysis. PAC was found to be the most effective material which showed almost over 90% removal. Adsorption data were well fitted to the Langmuir isotherm model, giving a q m (maximum/saturation adsorption capacity) value of 32.258 mg g-1 and a K L (Langmuir constant) value of 2.013 L mg-1. In terms of kinetic study, adsorption of metaldehyde by PAC fitted well with a pseudo-second-order equation, giving the adsorption rate constant k 2 value of 0.023 g mg-1 min-1, implying rapid adsorption. The nanocatalysts were much less effective in oxidising metaldehyde than PAC with the same metaldehyde concentration and 0.2 g L-1 loading concentration of materials under UV light; the maximum removal achieved by carbon-doped titanium dioxide (C-1.5) nanocatalyst was around 15% for a 7.5 ppm metaldehyde solution. Graphical abstract ᅟ.

Targeting eIF4E inhibits growth, survival and angiogenesis in retinoblastoma and enhances efficacy of chemotherapy.

Although the eukaryotic translation initiation factor 4E (eIF4E) has been shown to be critically involved in the transformation and progression of various tumors, little is known about the role of eIF4E in retinoblastoma. In this work, we report that ribavirin, a pharmacologic inhibitor of eIF4E function, effectively targets retinoblastoma and angiogenesis. Ribavirin treatment dose-dependently blocked the growth and stimulated apoptosis in various retinoblastoma cell lines, with IC50 values that are within the clinically achievable range. Ribavirin also significantly inhibited angiogenesis via disrupting capillary network formation and suppressing VEGF-induced migration, proliferation and survival of human retinal endothelial cells. In addition, ribavirin significantly augments chemotherapy agent's inhibitory effects in retinoblastoma in vitro and in vivo. Mechanistically, ribavirin inhibited eIF4E function in retinoblastoma cells as shown by the decreased protein levels of Cyclin D1, c-Myc and VEGF without affecting their mRNA expression. Overexpression of the wildtype and phosphormimetic but not the nonphosphorylatable form of eIF4E significantly abolished the inhibitory effects of ribavirin, further demonstrating eIF4E as the target of ribavirin. Genetic knockdown of eIF4E using two independent siRNAs mirrored ribavirin's effects, confirming the role of eIF4E in retinoblastoma growth, survival and response to chemotherapy. Our findings provide a preclinical rationale to explore ribavirin as a strategy to treat retinoblastoma and highlight the therapeutic value of targeting eIF4E in retinoblastoma.