Regulation of the Oxidase Mimetic Activity of Ceria Nanoparticles by Buffer Composition.

Ceria nanoparticles (CNPs) are important typical nanozymes with multiple enzyme mimetic activities, which could facilitate the oxidation of organic dyes in acidic conditions, because of the oxidase mimetic activity. Usually, the regulation of oxidase mimetic activity is focused on the adjustment of the structure, morphology, composition, surface, and other factors of nanozymes. However, the influence of the surrounding environment is not considered, which is very important during the reaction process. In this work, the oxidase mimetic activity of CNPs in buffer solutions including citric acid, acetic acid and glycine buffer solutions was investigated, with the results that carboxyl group in buffer solution could adsorb the CNPs on the surface to promote the oxidase mimetic activity. Due to the chelation with the cerium ion, the enhancement is more significant by molecules with polycarboxylic groups, and the enhancement is more efficient by carboxyl molecules in buffer solution, compared with the modification of the carboxyl groups on the surface, because of easier operation and smaller steric hindrance. From the viewpoint of increasing the oxidase mimetic activity of CNPs, the work is expected to provide references for the selection of the reaction systems to optimize the oxidase mimetic activity in bio-detection applications.

What Matters in Radiological Image Segmentation? Effect of Segmentation Errors on the Diagnostic Related Features.

Segmentation is a crucial step in extracting the medical image features for clinical diagnosis. Though multiple metrics have been proposed to evaluate the segmentation performance, there is no clear study on how or to what extent the segmentation errors will affect the diagnostic related features used in clinical practice. Therefore, we proposed a segmentation robustness plot (SRP) to build the link between segmentation errors and clinical acceptance, where relative area under the curve (R-AUC) was designed to help clinicians to identify the robust diagnostic related image features. In experiments, we first selected representative radiological series from time series (cardiac first-pass perfusion) and spatial series (T2 weighted images on brain tumors) of magnetic resonance images, respectively. Then, dice similarity coefficient (DSC) and Hausdorff distance (HD), as the widely used evaluation metrics, were used to systematically control the degree of the segmentation errors. Finally, the differences between diagnostic related image features extracted from the ground truth and the derived segmentation were analyzed, using the statistical method large sample size T-test to calculate the corresponding p values. The results are denoted in the SRP, where the x-axis indicates the segmentation performance using the aforementioned evaluation metric, and the y-axis shows the severity of the corresponding feature changes, which are expressed in either the p values for a single case or the proportion of patients without significant change. The experimental results in SRP show that when DSC is above 0.95 and HD is below 3 mm, the segmentation errors will not change the features significantly in most cases. However, when segmentation gets worse, additional metrics are required for further analysis. In this way, the proposed SRP indicates the impact of the segmentation errors on the severity of the corresponding feature changes. By using SRP, one could easily define the acceptable segmentation errors in a challenge. Additionally, the R-AUC calculated from SRP provides an objective reference to help the selection of reliable features in image analysis.

Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor-Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity.

Cancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor-targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)-targeting group (benzenesulfonamide) are synthesized. Phototherapy of tumor cells markedly amplifies ER stress and promotes tumor antigen release, as the ER is required for protein synthesis, secretion, and transport. More importantly, different electron-donating or -withdrawing substitutions are introduced into benzenesulfonamide to modulate the nonradiative decay pathways through intramolecular charge transfer, including singlet-triplet intersystem crossing (photodynamic effect) and internal thermal conversion (photothermal effect). Thus, a heptamethine cyanine photosensitizer containing a binitro-substituted benzenesulfonamide (ER-Cy-poNO2 ) is identified that preferentially accumulates in the ER of tumor cells. It significantly enhances the phototherapeutic effect by inducing excessive ER stress and robust ICD. Consequently, this small molecular photosensitizer triggers a sufficient antitumor immune response and effectively suppresses the growth of both primary and distant metastatic tumors, whereas no apparent toxicity is observed. This heptamethine cyanine photosensitizer has the potential to enhance cancer-targeted immunotherapy.

Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation.

Central ischemic necrosis is one of the biggest obstacles in the clinical application of traditional tissue-engineered bone (TEB) in critical-sized bone defect regeneration. Because of its ability to promote vascular invasion, endochondral ossification-based TEB has been applied for bone defect regeneration. However, inadequate chondrocyte hypertrophy can hinder vascular invasion and matrix mineralization during endochondral ossification. In light of recent studies suggesting that ceria nanoparticles (CNPs) improve the blood vessel distribution within TEB, we modified TEB scaffold surfaces with CNPs and investigated the effect and mechanism of CNPs on endochondral ossification-based bone regeneration. The CNPs used in this study were synthesized by the microemulsion method and modified with alendronate-anchored polyethylene glycol 600. We showed that CNPs accelerated new bone formation and enhanced endochondral ossification-based bone regeneration in both a subcutaneous ectopic osteogenesis model and a mouse model of critical-sized bone defects. Mechanistically, CNPs significantly promoted endochondral ossification-based bone regeneration by ensuring sufficient hypertrophic differentiation via the activation of the RNA helicase, DEAH (Asp-Glu-Ala-His) box helicase 15, and its downstream target, p38 MAPK. These results suggested that CNPs could be applied as a biomaterial to improve the efficacy of endochondral ossification-based bone regeneration in critical-sized bone defects.-Li, J., Kang, F., Gong, X., Bai, Y., Dai, J., Zhao, C., Dou, C., Cao, Z., Liang, M., Dong, R., Jiang, H., Yang, X., Dong, S. Ceria nanoparticles enhance endochondral ossification-based critical-sized bone defect regeneration by promoting the hypertrophic differentiation of BMSCs via DHX15 activation.

Enantioselective synthesis of indanone spiro-isochromanone derivatives via a dinuclear zinc-catalyzed Michael/transesterification tandem reaction.

An enantioselective Michael/transesterification tandem reaction of α-hydroxy indanones with ortho-ester chalcones was realized using dinuclear zinc catalysts. A series of enantiomerically pure spiro[indanone-2,3'-isochromane-1-one] derivatives were obtained in good yields with excellent stereoselectivities (up to >20 : 1 dr, up to >99% ee). This protocol could be conducted on a gram scale without affecting its stereoselectivities. In addition, the absolute stereochemistry of the products was determined by X-ray crystallographic analysis of 3ac, and a positive nonlinear effect was observed. Finally, a possible catalytic cycle was proposed to explain the origin of the enantioselectivity.

Access to Chiral 2,5-Pyrrolidinyl Dispirooxindoles via Dinuclear Zinc-Catalyzed Asymmetric Cascade Reactions.

A series of new nonsymmetric semi-azacrown ether ligands were developed and applied to the asymmetric Michael/cyclic keto-imine formation/Friedel-Crafts alkylation reactions of 3-amino oxindole hydrochlorides and ß,γ-unsaturated α-keto amides. A diversity of 2,5-pyrrolidinyl dispirooxindoles containing two nonadjacent spiro-quaternary stereocenters were obtained in excellent diastereoselectivities and moderate to excellent enantioselectivities (up to 95% ee). A possible catalytic cycle was proposed to explain the origin of the asymmetric induction.

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells.

BACKGROUND/AIMS: In the process of bone development and remodeling, the vasculature is regarded as the communicative network between the bone and neighboring tissues. Recently, it has been reported that the processes of angiogenesis and osteogenesis are coupled temporally and spatially. However, few studies reported the relationship and relevant mechanism between osteoclastogenesis and vasculogenesis. METHODS: Arraystar Mouse lncRNA microarray V3.0 was firstly used to analyze the differentially expressed lncRNA genes in osteoclast different stages during osteoclastogenesis. Cell counting kit 8 (CCK-8) analysis, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, migration and tube formation assays were used to detect impact of osteoclast different stages on the proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs), respectively. Finally, transfection of AK131850 shRNA, miR-93-5p mimic and miR-93-5p inhibitor, qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA), fluorescence in situ hybridization (FISH) and luciferase reporter assay were carried out to dissect molecular mechanisms. RESULTS: In this study, we found that newborn OCs (N-OC) and mature OCs (M-OC) during osteoclastogenesis significantly promoted proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs). Through lncRNA microarray and GO&pathway analysis, we found that AK131850 and co-expressed gene, vascular endothelial growth factor a (VEGFa), were significantly up-regulated in N-OC and M-OC. After inhibition of AK131850 the promoting effect of N-OC and M-OC on EPCs was reversed. Furthermore, we found that AK131850 directly competed miR-93-5p in N-OC and M-OC through sponge, thereby increasing VEGFa transcription, expression and secretion through derepressing of miR-93-5p on VEGFa. CONCLUSION: Our results provided the first finding that lncRNA-AK131850 sponged miR-93-5p in N-OC and M-OC during osteoclastogenesis to enhance the secretion of VEGFa, thus promoting vasculogenesis of EPCs.

Dinuclear zinc complex catalyzed asymmetric methylation and alkynylation of aromatic aldehydes.

A general AzePhenol dinuclear zinc catalytic system has been successfully developed and introduced into the asymmetric addition of dimethylzinc and alkynylzinc to aromatic aldehydes. In this system, an azetidine derived chiral ligand has proven to be an effective enantioselective promoter. Under the optimal reaction conditions, a series of chiral 1-hydroxyethyl (up to 99% ee) and secondary propargylic alcohols (up to 96% ee) were generated with good yields and enantioselectivities. Additionally, this novel catalytic system showed good functional group compatibility. Remarkably, the substituent's electronic nature alone is not sufficient to allow for exclusive enantioselectivity, an additional substituent's location also had an effect. We proposed that the formation of a stable and structural rigid transition state by the chelation of ortho substituted benzaldehydes to the zinc atom was responsible for the observed higher enantioselectivity. The possible catalytic cycles of both transformations accounting for the stereoselectivity were described accordingly.

Azetidine-derived dinuclear zinc catalyzed asymmetric phospha-Michael addition of dialkyl phosphite to α,ß-unsaturated carbonyl compounds.

The asymmetric phospha-Michael addition of dialkyl phosphite to α,ß-unsaturated carbonyl compounds by using an azetidine-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad spectrum of enones and α,ß-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using additives. The products were obtained with more than 95% ee for 23 examples of α,ß-unsaturated carbonyl compounds. A positive nonlinear effect was observed and the possible mechanism was proposed.

Preparation of magnetic imprinted graphene oxide composite for catalytic degradation of Congo red under dark ambient conditions.

Magnetic imprinted N-doped P25/Fe3O4-graphene oxide (MIGNT) was prepared with methyl orange as the dummy template and pyrrole as functional monomer for catalytic degradation of Congo red (CR). Hummers method and the hydrothermal method were used to synthesize Fe3O4-GO and N-doped P25, respectively. The results of adsorption and degradation experiments showed that the adsorption capacity and catalytic degradation ability of the imprinted composite for CR were obviously higher than those of a non-imprinted one. Moreover, the effect factors on degradation efficiency of CR, such as the initial concentration of CR, catalysis time, pH of the solution and temperature, were investigated. The MIGNT was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, a physical property measurement system and a thermal gravimetric analyzer. The degradation products of CR were detected with high performance liquid chromatography and a mass spectrometer. The MIGNT was a brand-new imprinted composite and had high degradation efficiency for CR under dark ambient conditions. The MIGNT could be recycled conveniently, due to its magnetic property, and could be used as an effective, environmentally friendly and low-cost catalytic degradation material for the treatment of water contaminated by CR.

HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis.

The bone-resorbing osteoclast (OC) is essential for bone homeostasis, yet deregulation of OCs contributes to diseases such as osteoporosis, osteopetrosis, and rheumatoid arthritis. Here we show that histone deacetylase 2 (HDAC2) is a key positive regulator during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Bone marrow macrophages (BMMs) showed increased HDAC2 expression during osteoclastogenesis. HDAC2 overexpression enhanced, whereas HDAC2 deletion suppressed osteoclastogenesis and bone resorption using lentivirus infection. Mechanistically, upon RANKL activation, HDAC2 activated Akt; Akt directly phosphorylates and abrogates Forkhead box protein O1 (FoxO1), which is a negative regulator during osteoclastogenesis through reducing reactive oxygen species. HDAC2 deletion in BMMs resulted in decreased Akt activation and increased FoxO1 activity during osteoclastogenesis. In conclusion, HDAC2 activates Akt thus suppresses FoxO1 transcription results in enhanced osteoclastogenesis. Our data imply the potential value of HDAC2 as a new target in regulating osteoclast differentiation and function.

Dual Effect of Cyanidin on RANKL-Induced Differentiation and Fusion of Osteoclasts.

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells derived from hematopoietic stem cells (HSCs) or monocyte/macrophage progenitor cells and formed by osteoclasts precursors (OCPs) fusion. Cyanidin is an anthocyanin widely distributed in food diet with novel antioxidant activity. However, the effect of cyanidin on osteoclasts is still unknown. We investigated the effect of cyanidin on RANKL-induced osteoclasts differentiation and cell fusion. The results showed that cyanidin had a dual effect on RANKL-induced osteoclastogenesis. Lower dosage of cyanidin (< 1 µg/ml) has a promoting effect on osteoclastogenesis while higher dosage of cyanidin (> 10 µg/ml) has an inhibitory effect. Fusogenic genes like CD9, ATP6v0d2, DC-STAMP, OC-STAMP, and osteoclasts related genes like NFATc1, mitf, and c-fos were all regulated by cyanidin consistent to its dual effect. Further exploration showed that low concentration of cyanidin could increase osteoclasts fusion whereas higher dosage of cyanidin lead to the increase of LXR-ß expression and activation which is suppressive to osteoclasts differentiaton. All these results showed that cyanidin exhibits therapeutic potential in prevention of osteoclasts related bone disorders.

Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1.

The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated osteoclast-mediated bone resorption. It is reported that monocytes/macrophage progenitor cells or either hematopoietic stem cells (HSCs) gave rise to multinucleated osteoclasts. Thus, inhibition of osteoclastic bone resorption generally seems to be a predominant therapy for treating osteoporosis. Recently, more and more natural compounds have been discovered, which have the ability of inhibiting osteoclast differentiation and fusion. Alliin (S-allyl-l-cysteine sulfoxides, SACSO) is the major component of aged garlic extract (AGE), bearing broad-spectrum natural antioxidant properties. However, its effects on bone health have not yet been explored. Hence, we designed the current study to explore its effects and role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast fusion and differentiation. It was revealed that alliin had an inhibitory effect in osteoclasteogenesis with a dose-dependent manner via blocking the c-Fos-NFATc1 signaling pathway. In addition, alliin decreased the generation of reactive oxygen species (ROS) and down-regulated the expression of NADPH oxidase 1 (Nox1). The overall results revealed that alliin could be a potential therapeutic agent in the treatment of osteoporosis.

MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation.

DC-STAMP is a key regulating molecule of osteoclastogenesis and osteoclast precursor (OCP) fusion. Emerging lines of evidence showed that microRNAs play crucial roles in bone metabolism and osteoclast differentiation, but no microRNA has yet been reported to be directly related to OCPs fusion. Through a microarray, we found that the expression of miR-7b in RAW264.7 cells was significantly decreased after induction with M-CSF and RANKL. The overexpression of miR-7b in RAW264.7 cells attenuated the number of TRAP-positive cells number and the formation of multinucleated cells, whereas the inhibition of miR-7b enhanced osteoclastogenesis. Through a dual luciferase reporter assay, we confirmed that miR-7b directly targets DC-STAMP. Other fusogenic molecules, such as CD47, ATP6v0d2, and OC-STAMP, were detected to be down-regulated in accordance with the inhibition of DC-STAMP. Because DC-STAMP also participates in osteoclast differentiation through the ITAM-ITIM network, multiple osteoclast-specific genes in the ITAM-ITIM network were detected to identify how DC-STAMP is involved in this process. The results showed that molecules associated with the ITAM-ITIM network, such as NFATc1 and OSCAR, which are crucial in osteoclastogenesis, were consistently altered due to DC-STAMP inhibition. These findings suggest that miR-7b inhibits osteoclastogenesis and cell-cell fusion by directly targeting DC-STAMP. In addition, the inhibition of DC-STAMP and its downstream signals changed the expression of other fusogenic genes and key regulating genes, such as Nfatc1, c-fos, Akt, Irf8, Mapk1, and Traf6. In conclusion, our findings indicate that miR-7b may be a potential therapeutic target for the treatment of osteoclast-related bone disorders.

Enantioselective Friedel-Crafts alkylation of pyrrole with chalcones catalyzed by a dinuclear zinc catalyst.

A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of ß-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions. The absolute stereochemistry of the products was determined to be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a weak negative nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible mechanism was proposed to explain the origin of the asymmetric induction.

Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea.

Each approach for artificial cornea design is toward the same goal: to develop a material that best mimics the important properties of natural cornea. Accordingly, the selection and optimization of corneal substitute should be based on their physicochemical properties. In this study, three types of polyvinyl alcohol (PVA) hydrogels with different polymerization degree (PVA1799, PVA2499 and PVA2699) were prepared by freeze-thawing techniques. After characterization in terms of transparency, water content, water contact angle, mechanical property, root-mean-square roughness and protein adsorption behavior, the optimized PVA2499 hydrogel with similar properties of natural cornea was selected as a matrix material for artificial cornea. Based on this, a biomimetic artificial cornea was fabricated with core-and-skirt structure: a transparent PVA hydrogel core, surrounding by a ringed PVA-matrix composite skirt that composed of graphite, Fe-doped nano hydroxyapatite (n-Fe-HA) and PVA hydrogel. Different ratio of graphite/n-Fe-HA can tune the skirt color from dark brown to light brown, which well simulates the iris color of Oriental eyes. Moreover, morphologic and mechanical examination showed that an integrated core-and-skirt artificial cornea was formed from an interpenetrating polymer network, no phase separation appeared on the interface between the core and the skirt.

Study on chitosan/gelatin hydrogels containing ceria nanoparticles for promoting the healing of diabetic wound.

Chronic inflammation at diabetic wound sites results in the uncontrolled accumulation of pro-inflammatory factors and reactive oxygen species (ROS), which impedes cell proliferation and delays wound healing. To promote the healing of diabetic wounds, chitosan/gelatin hydrogels containing ceria nanoparticles (CNPs) of various sizes were created in the current study. CNPs' efficacy in removing O 2 • - , •OH, and H2O2 was demonstrated, and the scavenging ability of CNPs of varying sizes was compared. The in vitro experiments demonstrated that hydrogels containing CNPs could effectively protect cells from ROS-induced damage and facilitate mouse fibroblast migration. Furthermore, during the treatment of diabetic wounds in vivo, hydrogels containing CNPs exhibited anti-inflammatory activity and could reduce the expression of the pro-inflammatory factors TNF-α (above 30%), IL-6 (above 90%), and IL-1ß (above 80%), and effectively promote wound closure (above 80%) by inducing re-epithelialization, collagen deposition, and angiogenesis. In addition, the biological properties and therapeutic effects of hydrogels containing CNPs of various sizes were compared and discussed. The finding revealed that hydrogels with 4 nm CNPs exhibited more significant biological properties and had implications for diabetic wound treatment.

Small Ceria Nanoclusters with High ROS Scavenging Activity and Favorable Pharmacokinetic Parameters for the Amelioration of Chronic Kidney Disease.

The over production of reactive oxygen species (ROS) plays a critical role in the progression of chronic kidney disease (CKD). Organic ROS scavengers currently used for CKD treatment do not satisfy low dosage and high efficiency requirements. Ceria nanomaterials featured with renewable ROS scavenging activity are potential candidates for CKD treatment. Herein, a method for the synthesis of ceria nanoclusters (NCs) featured with small size of ≈1.2 nm is reported. The synthesized NCs are modified by three hydrophilic ligands with different molecular weights, including succinic acid (SA), polyethylene glycol diacid 600 (PEG600), and polyethylene glycol diacid 2000 (PEG2000). The surface modified NCs exhibit excellent ROS scavenging activity due to the high Ce3+ /Ce4+ ratio in their crystal structures. Compared with bigger-sized ceria nanoparticles (NPs) (≈45 nm), NCs demonstrate smoother blood concentration-time curve, lower organ accumulation, and faster metabolic rate superiorities. The administration of NCs to CKD mice, especially PEG600 and PEG2000 modified NCs, can effectively inhibit oxidative stress, inflammation, renal fibrosis, and apoptosis in their kidneys. Due to these benefits, the constructed NCs can ameliorate the progression of CKD. These findings suggest that NCs is a potential redox nanomedicine for future clinical treatment of CKD.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Central nervous system injury meets nanoceria: opportunities and challenges.

Central nervous system (CNS) injury, induced by ischemic/hemorrhagic or traumatic damage, is one of the most common causes of death and long-term disability worldwide. Reactive oxygen and nitrogen species (RONS) resulting in oxidative/nitrosative stress play a critical role in the pathological cascade of molecular events after CNS injury. Therefore, by targeting RONS, antioxidant therapies have been intensively explored in previous studies. However, traditional antioxidants have achieved limited success thus far, and the development of new antioxidants to achieve highly effective RONS modulation in CNS injury still remains a great challenge. With the rapid development of nanotechnology, novel nanomaterials provided promising opportunities to address this challenge. Within these, nanoceria has gained much attention due to its regenerative and excellent RONS elimination capability. To promote its practical application, it is important to know what has been done and what has yet to be done. This review aims to present the opportunities and challenges of nanoceria in treating CNS injury. The physicochemical properties of nanoceria and its interaction with RONS are described. The applications of nanoceria for stroke and neurotrauma treatment are summarized. The possible directions for future application of nanoceria in CNS injury treatment are proposed.