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Background: Prostate cancer recognized as a “cold” tumor has an immunosuppressive microenvironment in which regulatory T-cells (Tregs) usually represent a major role. Therefore, identifying a prognostic signature of Tregs has promising benefits of improving survival of prostate cancer patients. However, the prognostic signature based on Tregs-specific mRNAs for prostate cancer is lacking. Methods: We systematicly analyzed transcriptional profiles of Tregs and 19 other immune cell types using 42 purified immune cell datasets from GEO to identify Tregs-specific mRNAs, and develop and validate a prognostic signature of Tregs (named “TILTregSig”) for monitoring prognosis of prostate cancer using TCGA and ICGC datasets. We also applied the signature to five immunotherapy response datasets and GSCALite to analyze the potential of the TILTregSig for predicting CIT response and cancer therapeutic resistance.Results: We develop the TILTregSig comprising five mRNAs (SOCS2, EGR1, RRM2, TPP1 and C11orf54) for prostate cancer patients. We find that the TILTregSig is a stronger predictor for tumor immunity compared with tumor mutation burden (TMB) and glycolytic activity which have been reported as immune predictors. Further analyses indicate that the TILTregSig may influence tumor immunity mainly by mediating tumor-infiltrating Tregs. Moreover, the TILTregSig also shows promising potential for predicting cancer immunotherapy (CIT) response and therapeutic resistance in multiple cancers.Conclusions: Our study has highlighted the value of the TILTregSig as a prognostic biomarker of prostate cancer from a tumor-infiltrating Tregs perspective, and strengthened its potential application as predictor of CIT response and cancer therapeutic resistance, which warrants further.

We synthesized an ultrasensitive probe TP-Golgi for the two-photon ratiometric fluorescence imaging of Golgi polarity. Probe TP-Golgi possesses a large Stokes shift, excellent sensitivity and good selectivity to quantitatively detect environmental polarity. By application of TP-Golgi, we found that the Golgi polarity increased obviously in the kidneys of mice with AKI.

Abnormal expression of proteins, including catalytic and expression dysfunction, is directly related to the development of various diseases in living organisms. Reactive oxygen species (ROS) could regulate protein expression by redox modification or cellular signal pathway and thus influence the development of disease. Determining the expression level and activity of these ROS-associated proteins is of considerable importance in early-stage disease diagnosis and the identification of new drug targets. Fluorescence imaging technology has emerged as a powerful tool for specific in situ imaging of target proteins by virtue of its non-invasiveness, high sensitivity and good spatiotemporal resolution. In this review, we summarize advances made in the past decade for the design of fluorescent probes that have contributed to tracking ROS-associated proteins in disease. We envision that this review will attract significant attention from a wide range of researchers in their utilization of fluorescent probes for in situ investigation of pathological processes synergistically regulated by both ROS and proteins., Abnormal proteins, influenced by reactive oxygen species (ROS), are directly related to the development of various diseases.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can cause extreme joint pain. However, current therapies cannot provide symptomatic relief for a large proportion of patients with RA. Thus, the development of novel therapeutic drugs constitutes a major challenge for RA treatment. Endoplasmic reticulum (ER) stress is reportedly involved in RA pathogenesis. Notably, abnormal ER pH is often closely related to ER stress. Therefore, ER pH has the potential to become a new evaluation parameter for RA. In this study, we demonstrated that a novel ratiometric fluorescence probe, herein called pH-ER, could be used in imaging ER pH in cells in situ within the range of 6.02–9.57. This probe was successfully applied in the evaluation of the joints of mice with RA of different severity. The novel probe developed herein can be used to evaluate the efficacy of drugs for RA treatment.

Arthritis is an inflammatory and autoimmune disease seriously affecting the quality of a patient’s life, and its pathogenesis remains obscure. Mitochondrial oxidative stress is involved in the patho-physiology of arthritis. Cystein (Cys) plays a crucial role as a free radical scavenger in oxidative stress, and thus decreased mitochondrial Cys might be observed in mice with arthritis. To verify this inference, we report a two-photon imaging probe for fluorescence measurement of mitochondrial Cys with high selectivity and good sensitivity. InCYS can track Cys in situ through one-photon and two-photon fluorescence imaging in vivo. By using InCYS, we successfully revealed decreases in the levels of mitochondrial Cys in the ankles of mice with arthritis. This work provides an effective bio-target for the development of novel therapeutic approaches for arthritis, and a practical tool for revealing the connections between mitochondrial oxidative stress and severe diseases.

Amyloid-β (Aβ40/Aβ42) peptide with a length of 40 or 42 residues is naturally secreted as cleavage product of the amyloid precursor protein, and formation of Aβ aggregates in a patient’s brain is a hallmark of Alzheimer’s disease (AD). Therefore, disaggregation and disruption provide potential therapeutic approaches to reduce, inhibit, and even reverse Aβ aggregation. The disaggregation/inhibition effect of the inhibitors applies generally to both Aβ40 and Aβ42 aggregations. Here we capture the atomic-level details of the interaction between Aβ40/Aβ42 and either natural tanshinone compound TS1 or its derivative TS0, and observe novel results by using molecular dynamics simulations. We observe that the natural TS1 indeed inhibits the monomolecular Aβ42 (mAβ42) aggregation and disaggregates Aβ42 amyloid fibrils, being in good agreement with the experimental results. TS1 is favorable to stabilize mAβ40 and even Aβ40 fibril, playing an opposite role to that in the Aβ42 counterpart, however. TS0 can inhibit th...

The aggregation of amyloid-β (Aβ) peptide induced by Cu(2+) is a key factor in development of Alzheimer's disease (AD), and metal ion chelation therapy enables treatment of AD. Three CQi (i = 1, 2, and 3 with R = H, Cl, and NO2, respectively) drugs had been verified experimentally to be much stronger inhibitors than the pioneer clioquinol (CQ) in both disaggregation of Aβ40 aggregate and reduction of toxicity induced by Cu(2+) binding at low pH. Due to the multiple morphologies of Cu(2+)-Aβ40 complexes produced at different pH states, we performed a series of molecular dynamics simulations to explain the structural changes and morphology characteristics as well as intrinsic disaggregation mechanisms of three Cu(2+)-Aβ40 models in the presence of any of the three CQi drugs at both low and high pH states. Three inhibition mechanisms for CQi were proposed as "insertion", "semi-insertion", and "surface" mechanisms, based on the morphologies of CQi-model x (CQi-x, x = 1, 2, and 3) and the strengths of binding between CQi and the corresponding model x. The insertion mechanism was characterized by the morphology with binding strength of more than 100 kJ/mol and by CQi being inserted or embedded into the hydrophobic cavity of model x. In those CQi-x morphologies with lower binding strength, CQi only attaches on the surface or inserts partly into Aβ peptide. Given the evidence that the binding strength is correlated positively with the effectiveness of drug to inhibit Aβ aggregation and thus to reduce toxicity, the data of binding strength presented here can provide a reference for one to screen drugs. From the point of view of binding strength, CQ2 is the best drug. Because of the special role of Asp23 in both Aβ aggregation and stabilizing the Aβ fibril, the generation of a H-bond between CQ3 and Asp23 of the Aβ40 peptide is believed to be responsible for CQ3 having the strongest disaggregation capacity. Therefore, besides strong binding, stronger propensity to H-bond with Asp23 would be another key factor to be taken seriously into account in drug screens. Meanwhile, the structural characteristics of drug CQi itself are also worthy of attention. First, the increasing polarity from CQ1 and CQ2 to CQ3 in turn results in increasing probability and strength of the interaction between the drug and the N-terminal (NT) region of Aβ40, which obviously inhibits Aβ peptide aggregation induced by Cu(2+) binding. Second, both the benzothiazole ring and phenol ring of CQi can overcome the activation energy barrier (∼16 kJ/mol) to rotate flexibly around the intramolecular C7-N14 bond to achieve the maximum match and interaction with the ambient Aβ40 residues. Such a structural feature of CQi paves the new way for ones in selection and modification of a drug.

In this study, structural and mechanical properties of a series of models of Aβ42 (one- and two-fold) and Aβ40 (two- and three-fold) fibrils have been computed by using all-atom molecular dynamics simulations. Based on calculations of the twist angle (θ) and periodicity (v=360d/θ), oligomers formed by 20, 11, and 13 monomers were found to be the smallest realistic models of three-fold Aβ40 , one-fold Aβ42 , and two-fold Aβ42 fibrils, respectively. Our results predict that the Aβ40 fibrils initially exist in two staggered conformations [STAG(+2) and STAG(+1)] and then undergo a [STAG(+2)→STAG(+1)] transformation in a size-dependent manner. The length of the loop region consisting of the residues 23-29 shrinks with the elongation of both Aβ40 and Aβ42 fibrils. A comparison of the computed potential energy suggests that a two-fold Aβ40 aggregate is more stable than its three-fold counterpart, and that Aβ42 oligomers can exist only in one-fold conformation for aggregates of more than 11 monomers in length. The computed Young's modulus and yield strengths of 50 GPa and 0.95 GPa, respectively, show that these aggregates possess excellent material properties.

On the basis of the present development of the book evaluation research, the article develop an informative and comprehensive evaluation system by combining with the feature of real data, such as the traditional paper books, e-books and network book reviews, so as to evaluate the academic influence of the books in the medical field. The empirical analysis showed that Sci-Tech books present the long-tailed distribution, and that foreign language translated books are highly influential. The results also showed the effectiveness of evaluation system.

Erythropoietin-producing hepatoma-amplified sequence (Eph) receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, function as a unique signaling system triggered by cell to cell interaction and have been shown to mediate neurodevelopmental processes. However, the role of Eph in spinal cord injury (SCI) was unclear. Here, the lentiviral expressing vectors, pGCSIL-green fluorescent protein (GFP) vectors expressing an active small interfering RNA (siRNA) targeting EphB3 sequence were used to determine the effect of RNAi knockdown of EphB3 on function recovery of limb in adult rats by Basso-Beattie-Bresnahan (BBB) scores. Four weeks after intraparenchymal administration of the siRNA into the right lumbar, EphB3 mRNA and protein levels in siRNA group were significantly reduced (P < 0.01) in the spine when compared with the negative group animals. BBB locomotor scores were significantly increased (P < 0.05) in siRNA animals when compared with the control animals. These results indicate that vector-derived siRNAs can effectively produce spatial knockdown of EphB3 gene expression, and this knockdown selectively increased BBB scores of the rats. This preclinical study demonstrates the use of RNAi to target the expression of genes mediating SCI and the therapeutic potential of this approach. Key word: Spinal cord injury, erythropoietin-producing hepatoma-amplified sequence (Eph) B3 receptors, quantitative reverse transcription polymerase chain reaction (qRT-PCR), EphB3, western-blot, Basso-Beattie-Bresnahan (BBB) scale.

Cerium molybdate (Ce–Mo) hierarchical architectures (such as the flowerlike, microspheric, and bundlelike structure) are successfully synthesized via a facile route with the assistance of amino acid (lysine, Lys). The influences of reaction parameters on the crystal structure and morphology of Ce–Mo hierarchical architectures are investigated. Samples obtained are characterized using X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), and thermogravimetric analysis (TGA). Furthermore, the photocatalytic and adsorption performances of samples obtained are investigated using different dyes, such as Cationic red X-GTL, Congo red, Methylene blue, Acid blue 80, and Methyl orange, as the model. The results show that Ce–Mo hierarchical architectures exhibit remarkably high efficiency to photocatalytically decompose Congo red under visible light irradiation, and significant adsorption performance on Catio...

Ephrin (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) and their membrane bound ligands, The Eph plays an important role in formation of spines with normal morpholog and synaptic plasticity. However, the Eph receptors expression in spinal tissue with spinal cord injury (SCI) was unclear to have little regarding molecular studies; thus, the present study aims to investigate changes from EphB3 receptors in spinal tissue of rats with injured spinal cord on mRNA level and protein level by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. It was found that EphB3 receptors were significantly up-regulated in SCI group in comparison to the control group on mRNA level. On protein level, EphB3 receptors were also highly increased in SCI group compared with control group. These results suggested that decreased EphB3 expression might also become a potential target in the treatment of SCI in future. Key word: Spinal cord injury, Ephrin B3 (EphB3) receptors, qRT-PCR, Ephrin B (EphB), western blot.

Haiming Sun,1,* Xiaohui Chen,2,* Dan Chen,1 Mingyan Dong,1 Xinning Fu,1 Qian Li,1 Xi Liu,1 Qingzhi Wu,1 Tong Qiu,1 Tao Wan,1 Shipu Li11State Key Laboratory of Advanced Technology for Materials Synthesis and Processing and Biomedical Materials and Engineering Center, Wuhan University of Technology, Wuhan, China; 2Department of Prosthetics, School of Stomatology, Wuhan University, Wuhan, China*Both authors contributed equally to this workAbstract: Malignant gliomas are primary brain tumors with high rates of morbidity and mortality; they are the fourth most common cause of cancer death. Novel diagnostic and therapeutic techniques based on nanomaterials provide promising options in the treatment of malignant gliomas. In order to evaluate the potential of FePt nanoparticles (NPs) for malignant glioma therapy, FePt NPs with different surface coatings and components were tunably synthesized using oleic acid/oleylamine (OA/OA) and cysteines (Cys) as the capping agents, respectively. The samples were characterized using X-ray diffraction, transmission electron microscopy (TEM), X-ray photon spectroscopy, Fourier transform infrared spectroscopy, atomic absorption spectrum, and zeta potential. The influence of the surface coatings and components of the FePt NPs on the proliferation of glioma cells was assessed through MTT assay and TEM observation using three typical glioma cell lines (glioma U251 cells, astrocytoma U87 cells, and neuroglioma H4 cells) as in vitro models. The results showed that the proliferation of glioma cells was significantly suppressed by lipophilic FePt-OA/OA NPs in a time- and/or dose-dependent manner, while no or low cytotoxic effects were detected in the case of hydrophilic FePt-Cys NPs. The IC50 value of FePt-OA/OA NPs on the three glioma cell lines was approximately 5–10 µg mL-1 after 24 hours’ incubation. Although the cellular uptake of FePt NPs was confirmed regardless of the surface coatings and components of the FePt NPs, the suppression of FePt NPs on glioma cell proliferation was dominantly determined by their surface coatings rather than their components. Therefore, these results demonstrate that, through engineering of the surface coating, FePt NPs can potentially be developed as novel therapeutic agents for malignant gliomas.Keywords: FePt nanoparticles, surface coatings, compositions, glioma cells, proliferation

We report a facile synthesis of superparamagnetic CoFe2O4 nanostructures with the assistance of an amino acid (lysine). Monodisperse CoFe2O4 nanospheres and nanoparticles were obtained by adjusting the synthesis parameters (such as the molar ratio of reactants and the solvent). The samples were characterized through scanning electron microscopy, transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, and Fourier-transform infrared spectroscopy. The magnetic property and measured zeta potential shows that both CoFe2O4 nanostructures were superparamagnetic and positively charged. The adsorption performance of the CoFe2O4 nanostructures was evaluated using different dyes, namely, methylene blue, Congo red, Acid Blue 80, methyl orange, rhodamine B, and Cationic red X-GTL, as models. The results show that CoFe2O4 nanospheres consisting of nanoparticles display high adsorption performance on methylene blue, methyl orange, and Congo red, whereas CoFe2O4 nanoparticles prefer adsorbing rhodamine B and Congo red. Therefore, the tunable synthesis of superparamagnetic CoFe2O4 nanostructures provides promising applications for the selective and highly efficient removal of various organic contaminants from industrial effluents.

Layered double hydroxides (LDHs) are characterised by the two-dimensional lamellar-stacking structure through weak interactions and have attracted great interest because of their extensive applications as ion-exchanging carriers, adsorbents, precursors of metal oxide catalysts etc. In this work, a facile hydrothermal route has been developed to synthesise novel pyroaurite-type Co–Fe LDHs, with a formula of CoII5.84FeIII2.16(OH)16(CO3)1.08 · 0.32H2O, using lysine (Lys) molecules as the directing reagent. Co–Fe LDH nanostructures obtained were characterised by means of a scanning electron microscope, transmission electron microscopy, X-ray diffraction, fourier transform infrared and thermogravimetric analysis. Furthermore, the adsorption performance of Co–Fe LDH nanostructures, both the flower-like and octahedral structure, was assessed using different dyes as the model. The results demonstrate that pyroaurite-type Co–Fe LDHs exhibit excellent adsorption performance on anionic dyes (such as Methyl orange, Congo red and Acid blue 80) in aqueous solution, indicating great potential for the removal of anionic organic contaminants from the industrial effluents.

Cobalt hydroxide is considered one of the promising materials for the fabrication of various electrodes and electrochemical devices. However, detailed information on the structural transformation of cobalt hydroxide remains scarce. In this study, cobalt hydroxide intercalated with carbonate anions was synthesised in different phase structures and morphologies, including non-crystal nanosheets and single-crystal nanorods and nanosheets, using amino acid (glycine) molecules. The transformation of phases and morphologies was time dependent and directed by glycine molecules, accompanied by the formation of rodlike-embryo intermediates. The samples were characterised by X-ray diffraction, transmission electron microscopy and high resolution transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. Furthermore, the electrochemical property of cobalt hydroxide carbonate nanostructures was characterised by cyclic voltammetry measurement, suggesting their preferential application as supercapacitor materials.