Reversible, Covalent DNA Condensation Approach Using Chemical Linkers for Enhanced Gene Delivery.

Nonviral gene delivery has emerged as a promising technology for gene therapy. Nonetheless, these approaches often face challenges, primarily associated with lower efficiency, which can be attributed to the inefficient transportation of DNA into the nucleus. Here, we report a two-stage condensation approach to achieve efficient nuclear transport of DNA. First, we utilize chemical linkers to cross-link DNA plasmids via a reversible covalent bond to form smaller-sized bundled DNA (b-DNA). Then, we package the b-DNA into cationic vectors to further condense b-DNA and enable efficient gene delivery to the nucleus. We demonstrate clear improvements in the gene transfection efficiency in vitro, including with 11.6 kbp plasmids and in primary cultured neurons. Moreover, we also observed a remarkable improvement in lung-selective gene transfection efficiency in vivo by this two-stage condensation approach following intravenous administration. This reversible covalent assembly strategy demonstrates substantial value of nonviral gene delivery for clinical therapeutic applications.

Caffeic Acid O-Methyltransferase Gene Family in Mango (Mangifera indica L.) with Transcriptional Analysis under Biotic and Abiotic Stresses and the Role of MiCOMT1 in Salt Tolerance.

Caffeic acid O-methyltransferase (COMT) participates in various physiological activities in plants, such as positive responses to abiotic stresses and the signal transduction of phytohormones. In this study, 18 COMT genes were identified in the chromosome-level reference genome of mango, named MiCOMTs. A phylogenetic tree containing nine groups (I-IX) was constructed based on the amino acid sequences of the 71 COMT proteins from seven species. The phylogenetic tree indicated that the members of the MiCOMTs could be divided into four groups. Quantitative real-time PCR showed that all MiCOMT genes have particularly high expression levels during flowering. The expression levels of MiCOMTs were different under abiotic and biotic stresses, including salt and stimulated drought stresses, ABA and SA treatment, as well as Xanthomonas campestris pv. mangiferaeindicae and Colletotrichum gloeosporioides infection, respectively. Among them, the expression level of MiCOMT1 was significantly up-regulated at 6-72 h after salt and stimulated drought stresses. The results of gene function analysis via the transient overexpression of the MiCOMT1 gene in Nicotiana benthamiana showed that the MiCOMT1 gene can promote the accumulation of ABA and MeJA, and improve the salt tolerance of mango. These results are beneficial to future researchers aiming to understand the biological functions and molecular mechanisms of MiCOMT genes.

Progress of evapotranspiration research based on VOSviewer: A review.

Evapotranspiration (ET) is a key link between atmospheric processes and land surface hydrological processes. With the impact of global warming and human activities, research on ET has become a hot topic. Supported by a total of 1,222 Chinese and English literatures from China National Knowledge Infrastructure and the Web of Science Core Collection from 2013 to 2022, this paper adopts the bibliometric visualization method to review the current research progress and future trend of ET with respect to the time of publication, countries, institutions, journals, and research hotspots. The results show that the number of related research articles is increasing rapidly and the journals with high citations are Journal of Hydrology, Agricultural and Forest Meteorology and Agricultural Water Management. The research hotspots have been focused on prototype observation, remote sensing inversion, mechanism equation, model simulation, spatial-temporal analysis, and attribution identification. In the future, there is an urgent need to integrate algorithms such as machine learning and artificial intelligence, to develop higher resolution remote sensing products, to improve the mechanism equations based on precise observations, and to clarify the impact of synergistic effects on ET among the driving factors.

Ultrasound-Triggered In Situ Photon Emission for Noninvasive Optogenetics.

Optogenetics has revolutionized neuroscience understanding by allowing spatiotemporal control over cell-type specific neurons in neural circuits. However, the sluggish development of noninvasive photon delivery in the brain has limited the clinical application of optogenetics. Focused ultrasound (FUS)-derived mechanoluminescence has emerged as a promising tool for in situ photon emission, but there is not yet a biocompatible liquid-phase mechanoluminescence system for spatiotemporal optogenetics. To achieve noninvasive optogenetics with a high temporal resolution and desirable biocompatibility, we have developed liposome (Lipo@IR780/L012) nanoparticles for FUS-triggered mechanoluminescence in brain photon delivery. Synchronized and stable blue light emission was generated in solution under FUS irradiation due to the cascade reactions in liposomes. In vitro tests revealed that Lipo@IR780/L012 could be triggered by FUS for light emission at different stimulation frequencies, resulting in activation of opsin-expressing spiking HEK cells under the FUS irradiation. In vivo optogenetic stimulation further demonstrated that motor cortex neurons could be noninvasively and reversibly activated under the repetitive FUS irradiation after intravenous injection of lipid nanoparticles to achieve limb movements.

HLA-DR genetic polymorphisms and hepatitis B virus mutations affect the risk of hepatocellular carcinoma in Han Chinese population.

BACKGROUND: Human leucocyte antigen (HLA)-DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate the associations of HLA-DR single nucleotide polymorphisms (SNPs) with the generation of hepatocellular carcinoma (HCC)-related HBV mutations. The effects of HLA-DR SNPs and their interactions with HBV mutations on HCC risks were also determined. METHODS: Five HLA-DR SNPs (rs3135363, rs9268644, rs35445101, rs24755213, and rs984778) were genotyped in 792 healthy controls, 586 chronic hepatitis B (CHB) patients, 536 liver cirrhosis (LC) patients, and 1500 HCC patients using quantitative PCR. Sanger sequencing was used to identify the HBV mutations. Logistic regression model was performed to evaluate the association of HLA-DR SNPs with HCC risk and the frequencies of HCC-related HBV mutations. RESULTS: The variant genotypes at rs3135363, rs9268644, rs35445101, rs24755213, and rs984778 were associated with decreased HCC risks. In genotype C HBV-infected subjects, variant genotypes of these SNPs were associated with decreased frequencies of HCC-related HBV mutations such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, and preS deletion. AG genotype at rs3135363, CA genotype at rs9268644, and AG genotype at rs24755213 reduced the generation of T1753A/C and G1896A in genotype B HBV-infected subjects, respectively. In addition, the interactions of rs3135363, rs9268644, rs24755213 with C1653T, T1753A/C, A1846T, and G1896A decreased the risks of HCC. CONCLUSIONS: HLA-DR genetic polymorphisms might predispose the host to immunoselection of HCC-related HBV mutations and affect the HCC risks possibly through interacting with HBV mutations.

Pyrazine as a More Efficient Luminophore than Benzene for Producing Red-Shifted and Enhanced Photoluminescence.

The development of organic photoluminescent (PL) materials with red-shifted and enhanced emissions is beneficial to promoting their applications. Luminescent materials based on aromatic heterocycles (e.g., pyrazine) usually have red-shifted and enhanced photoluminescence compared with phenyl-based luminescent materials. In this work, the photoluminescence behaviors of pyrazine and its derivatives (o-dichloro-, o-dicyano-, and dichlorodicyano-substituted) are compared with those of benzene and its derivatives. All compounds exhibit fluorescence emissions ranging from blue to yellow, and the fluorescence emissions of pyrazinyl compounds are more red-shifted than those of phenyl compounds. Except for the o-dicyano-substituted compound, pyrazinyl compounds exhibit stronger fluorescence emissions than corresponding phenyl compounds in both pure substances and ethanol solutions. In addition, both 5,6-dichloro-2,3-dicyanopyrazine (P4) and 4,5-dichloro-1,2-dicyanobenzene (B4) exhibit room temperature phosphorescence, and the maximum delayed emission wavelength is red-shifted from 575 nm of B4 to 637 nm of P4. The energy gaps between the highest occupied molecular orbital and the lowest unoccupied molecular orbital of the monomers of pyrazinyl compounds are reduced by 0.07-1.37 eV compared with the monomers of phenyl compounds, which is the fundamental reason for the red-shifted emissions of the pyrazinyl compounds. Moreover, compared to B4, the smaller molecular spacing in the P4 crystal structure facilitates interlayer electron transfer and hence the formation of more extended through-space conjugation, resulting in the red-shifted emission of P4. This work proves that pyrazine is a more efficient luminophore than benzene for constructing PL compounds with longer emission wavelengths and higher quantum yields, which are important in guiding the design and preparation of organic PL materials.

The application of integrating comprehensive evaluation and clustering algorithms weighted by maximal information coefficient for urban flood susceptibility.

Different sub-regions of Zhengzhou city have various levels of sensitivity to flood due to the impact of urbanization. Thus, an accurate flood sensitivities assessment is a key tool for flood prevention and urban planning and development. To successfully link the urban flood sensitivity assessment with the real flood situation, a method combining clustering algorithm with comprehensive evaluation is presented. The proposed method is not affected by the classification standard of sensitivities levels and has a small and undemanding demand for flood data. First, Maximal Information Coefficient between conditional factors and flood is employed to determine the weight. Then, the different results are obtained by three clustering algorithms. Finally, a four-layer evaluation structure weighted by analytic hierarchy process is established to select the best flood susceptibility map. A case study in the Zhengzhou city, China shows that the positive scale amplification strategy is relatively best and the flood sensitivity of sub-regions in Zhengzhou city should be divided into four levels obtained by K-Means clustering. Hence, it supplies the valuable insights for the urban planning and flood mitigation.

Hydrogen-Bonding-Driven Nontraditional Photoluminescence of a ß-Enamino Ester.

Nontraditional luminogens (NTLs) do not contain any conventional chromophores (large π-conjugated structures), but they do show intrinsic photoluminescence. To achieve photoluminescence from NTLs, it is necessary to increase the extent of through-space conjugation (TSC) and suppress nonradiative decay. Incorporating strong physical interactions such as hydrogen bonding is an effective strategy to achieve this. In this work, we carried out comparative studies on the photoluminescence behaviors of two ß-enamino esters with similar chemical structures, namely methyl 3-aminocrotonate (MAC) and methyl (E)-3-(1-pyrrolidinyl)-2-butenoate (MPB). MAC crystal emits blue fluorescence under UV irradiation. The critical cluster concentration of MAC in ethanol solutions was determined by studying the relationship between the photoluminescence intensity (UV-visible absorbance) and concentration. Furthermore, MAC exhibits solvatochromism, and its emission wavelength redshifts as the solvent polarity increases. On the contrary, MPB is non-emissive in both solid state and solutions. Crystal structures and theoretical calculation prove that strong inter- and intramolecular hydrogen bonds lead to the formation of large amounts of TSC of MAC molecules in aggregated states. No hydrogen bonds and thus no effective TSC can be formed between or within MPB molecules, and this is the reason for its non-emissive nature. This work provides a deeper understanding of how hydrogen bonding contributes to the luminescence of NTLs.

Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics.

Optogenetics, which uses visible light to control the cells genetically modified with light-gated ion channels, is a powerful tool for precise deconstruction of neural circuitry with neuron-subtype specificity. However, due to limited tissue penetration of visible light, invasive craniotomy and intracranial implantation of tethered optical fibers are usually required for in vivo optogenetic modulation. Here we report mechanoluminescent nanoparticles that can act as local light sources in the brain when triggered by brain-penetrant focused ultrasound (FUS) through intact scalp and skull. Mechanoluminescent nanoparticles can be delivered into the blood circulation via i.v. injection, recharged by 400-nm photoexcitation light in superficial blood vessels during circulation, and turned on by FUS to emit 470-nm light repetitively in the intact brain for optogenetic stimulation. Unlike the conventional "outside-in" approaches of optogenetics with fiber implantation, our method provides an "inside-out" approach to deliver nanoscopic light emitters via the intrinsic circulatory system and switch them on and off at any time and location of interest in the brain without extravasation through a minimally invasive ultrasound interface.

Effects of Through-Bond and Through-Space Conjugations on the Photoluminescence of Small Aromatic and Aliphatic Aldimines.

Through-bond conjugation (TBC) and/or through-space conjugation (TSC) determine the photophysical properties of organic luminescent compounds. No systematic studies have been carried out to understand the transition from aromatic TBC to non-aromatic TSC on the photoluminescence of organic luminescent compounds. In this work, a series of small aromatic and aliphatic aldimines were synthesized. For the aromatic imines, surprisingly, N,1-diphenylmethanimine with the highest TBC is non-emissive, while N-benzyl-1-phenylmethanimine and N-cyclohexyl-1-phenylmethanimine emit bright fluorescence in aggregate states. The aliphatic imines are all emissive, and their maximum emission wavelength decreases while the quantum yield increases with a decrease in steric hindrance. The imines show concentration-dependent and excitation-dependent emissions. Theoretical calculations show that the TBC extents in the aromatic imines are not strong enough to induce photoluminescence in a single molecule state, while the intermolecular TSC becomes dominant for the fluorescence emissions of both aromatic and aliphatic imines in aggregate states, and the configurations and spatial conformations of the molecules in aggregate states play a key role in the formation of effective TSC. This study provides an understanding of how chemical and spatial structures affect the formation of TBC and TSC and their functions on the photoluminescence of organic luminescent materials.

Reversibly Photoswitching Upconversion Nanoparticles for Super-Sensitive Photoacoustic Molecular Imaging.

Photoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle-based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice. Such a nanoprobe is built with upconverting nanocrystals and photoswitchable small molecules and can be switched on by NIR light through upconversion to UV energy. Reversibly photoswitching of the nanoprobe reliably removed strong tissue background, increased the contrast-to-noise ratio, and thus improved imaging sensitivity. We have shown that PAPSI can image 0.05 nM of the nanoprobe in hemoglobin solutions and 104 labeled cancer cells after implantation in living mice using a commercial PA imager.

Human health risk assessment of groundwater nitrate at a two geomorphic units transition zone in northern China.

To assess groundwater nitrate contamination and its human health risks, 489 unconfined groundwater samples were collected and analyzed from Zhangjiakou, northern China. The spatial distribution of principle hydrogeochemical results showed that the average concentrations of ions in descend order was HCO3-, SO42-, Na+, Ca2+, Cl-, NO3-, Mg2+ and K+, among which the NO3- concentrations were between 0.25 and 536.73 mg/L with an average of 29.72 mg/L. In total, 167 out of 489 samples (~ 34%) exceeded the recommended concentration of 20 mg/L in Quality Standard for Groundwater of China. The high NO3- concentration groundwater mainly located in the northern part and near the boundary of the two geomorphic units. As revealed by statistical analysis, the groundwater chemistry was more significantly affected by anthropogenic sources than by the geogenic sources. Moreover, human health risks of groundwater nitrate through oral and dermal exposure pathways were assessed by model, the results showed that about 60%, 50%, 32% and 26% of the area exceeded the acceptable level (total health index>1) for infants, children, adult males and females, respectively. The health risks for different groups of people varied significantly, ranked: infants> children> adult males>adult females, suggesting that younger people are more susceptible to nitrate contamination, while females are more resistant to nitrate contamination than males. To ensure the drinking water safety in Zhangjiakou and its downstream areas, proper management and treatment of groundwater will be necessary to avoid the health risks associated with nitrate contamination.

Strong adhesion of poly(vinyl alcohol)-glycerol hydrogels onto metal substrates for marine antifouling applications.

Hydrogels can be used as an alternative coating material for ships against marine biofouling. However, the adhesion of wet and soft hydrogels onto solid metals remains a challenging problem. Here we report the adhesion of a typical hydrogel material, poly(vinyl alcohol) (PVA)-glycerol hydrogel, onto stainless steel substrates and the antifouling potency of the adhered PVA-glycerol hydrogels. Poly(allylamine hydrochloride) (PAH) hydrogel and ethyl α-cyanoacrylate (ECA) are used as the binders, and they are found to be able to firmly bond the PVA-glycerol hydrogels onto the stainless steel substrates. The PAH hydrogel does not affect the mechanical properties of the PVA-glycerol hydrogel during use, but it tends to lose the adhesive ability in a dehydrating environment. In contrast, the ECA adhesive can maintain strong bonding between PVA-glycerol hydrogels and substrates upon several water losing/water absorbing cycles, despite some negative effects on the strength of the PVA-glycerol hydrogel. Biological experiments show that the PVA-glycerol hydrogel has a strong settlement-inhibiting effect on the barnacle Balanus albicostatus, suggesting that combining the PVA-glycerol hydrogel with ECA adhesive may have promising applications in marine antifouling.

Tough, Stimuli-Responsive, and Biocompatible Hydrogels with Very High Water Content.

Some marine creatures like jellyfish have gel-like bodies consisting mostly of water (above 95 wt%). Yet, their gel-like bodies still show quite good mechanical properties and can respond to external stimuli. Artificial hydrogels with very high water content are generally extremely weak, and hence their practical applications are strongly limited. Inspired by jellyfish, tough and biocompatible poly(vinyl alcohol)/sodium polyacrylate (PVA/PAANa) hydrogels with very high equilibrium water content (98.23-99.58 wt%) are developed. The equilibrium swollen PVA/PAANa hydrogels show good mechanical properties, with elastic modulus, tensile strength, and elongation up to 0.046 MPa, 0.14 MPa, and 206%, respectively, very close to those of jellyfish mesoglea. Moreover, the PVA/PAANa hydrogels can respond to external multi-stimuli distinctly, such as metal cations, pH, and salts. Very impressively, the PVA/PAANa hydrogel can easily distinguish tap water from deionized water, and its detection limit of metal cations can be as low as 10-4  mol L-1 . Cell cytotoxicity tests and in vivo biocompatibility tests prove that the PVA/PAANa hydrogels have excellent biocompatibility. The tough, stimuli-responsive, and biocompatible hydrogels with very high water content may find a variety of practical applications in load-bearing biomaterials, detection, sensors, and agricultural fields.

Hydrogen-Bonded Polymer-Small Molecule Complexes with Tunable Mechanical Properties.

A novel type of polymeric material with tunable mechanical properties is fabricated from polymers and small molecules that can form hydrogen-bonded intermolecular complexes (IMCs). In this work, poly(vinyl alcohol) (PVA)-glycerol hydrogels are first prepared, and then they are dried to form IMCs. The tensile strengths and moduli of IMCs decrease dramatically with increasing glycerol content, while the elongations increase gradually. The mechanical properties are comparable with or even superior to those of common engineering plastics and rubbers. The IMCs with high glycerol content also show excellent flexibility and cold-resistance at subzero temperatures. Cyclic tensile and stress relaxation tests prove that there is an effective energy dissipation mechanism in IMCs and dynamic mechanical analysis confirms their physical crosslinking nature. FTIR and NMR characterizations prove the existence of hydrogen bonding between glycerol and PVA chains, which suppresses the crystallization of PVA from X-ray diffraction measurement. These PVA-glycerol IMCs may find potential applications in barrier films, biomedical packaging, etc., in the future.

Tuning the threshold voltage of carbon nanotube transistors by n-type molecular doping for robust and flexible complementary circuits.

Tuning the threshold voltage of a transistor is crucial for realizing robust digital circuits. For silicon transistors, the threshold voltage can be accurately controlled by doping. However, it remains challenging to tune the threshold voltage of single-wall nanotube (SWNT) thin-film transistors. Here, we report a facile method to controllably n-dope SWNTs using 1H-benzoimidazole derivatives processed via either solution coating or vacuum deposition. The threshold voltages of our polythiophene-sorted SWNT thin-film transistors can be tuned accurately and continuously over a wide range. Photoelectron spectroscopy measurements confirmed that the SWNT Fermi level shifted to the conduction band edge with increasing doping concentration. Using this doping approach, we proceeded to fabricate SWNT complementary inverters by inkjet printing of the dopants. We observed an unprecedented noise margin of 28 V at V(DD) = 80 V (70% of 1/2V(DD)) and a gain of 85. Additionally, robust SWNT complementary metal-oxide-semiconductor inverter (noise margin 72% of 1/2VDD) and logic gates with rail-to-rail output voltage swing and subnanowatt power consumption were fabricated onto a highly flexible substrate.

Molecular genetics of blood-fleshed peach reveals activation of anthocyanin biosynthesis by NAC transcription factors.

Anthocyanin pigmentation is an important consumer trait in peach (Prunus persica). In this study, the genetic basis of the blood-flesh trait was investigated using the cultivar Dahongpao, which shows high levels of cyanidin-3-glucoside in the mesocarp. Elevation of anthocyanin levels in the flesh was correlated with the expression of an R2R3 MYB transcription factor, PpMYB10.1. However, PpMYB10.1 did not co-segregate with the blood-flesh trait. The blood-flesh trait was mapped to a 200-kb interval on peach linkage group (LG) 5. Within this interval, a gene encoding a NAC domain transcription factor (TF) was found to be highly up-regulated in blood-fleshed peaches when compared with non-red-fleshed peaches. This NAC TF, designated blood (BL), acts as a heterodimer with PpNAC1 which shows high levels of expression in fruit at late developmental stages. We show that the heterodimer of BL and PpNAC1 can activate the transcription of PpMYB10.1, resulting in anthocyanin pigmentation in tobacco. Furthermore, silencing the BL gene reduces anthocyanin pigmentation in blood-fleshed peaches. The transactivation activity of the BL-PpNAC1 heterodimer is repressed by a SQUAMOSA promoter-binding protein-like TF, PpSPL1. Low levels of PpMYB10.1 expression in fruit at early developmental stages is probably attributable to lower levels of expression of PpNAC1 plus the presence of high levels of repressors such as PpSPL1. We present a mechanism whereby BL is the key gene for the blood-flesh trait in peach via its activation of PpMYB10.1 in maturing fruit. Partner TFs such as basic helix-loop-helix proteins and NAC1 are required, as is the removal of transcriptional repressors.

Magnetic Fe3O4 nanoparticle catalyzed chemiluminescence for detection of nitric oxide in living cells.

Direct and real-time measurement of nitric oxide (NO) in biological media is very difficult due to its transient nature. Fe3O4 nanoparticles (nanoFe3O4) because of their unique catalytic activities have attracted much attention as catalysts in a variety of organic and inorganic reactions. In this work, we have developed a magnetic Fe3O4 nanoparticle-based rapid-capture system for real-time detection of cellular NO. The basic principle is that the nanoFe3O4 can catalyze the decomposition of H2O2 in the system to generate superoxide anion (O2 (·-)) and the O2 (·-) can serve as an effective NO(·) trapping agent yielding peroxynitrite oxide anion, ONOO(-). Then the concentration of NO in cells can be facilely determined via peroxynitrite-induced luminol chemiluminescence. The linear range of the method is from 10(-4) to 10(-8) mol/L, and the detection of limit (3σ, n = 11) is as low as 3.16 × 10(-9) mol/L. By using this method, the NO concentration in 0.1 and 0.5 mg/L LPS-stimulated BV2 cells was measured as 4.9 and 11.3 µM, respectively. Surface measurements by synchrotron X-ray photoelectron spectroscopy (SRXPS) and scanning transmission X-ray microscopy (STXM) demonstrate the catalytic mechanism of the nanoFe3O4-based system is that the significantly excess Fe(II) exists on the surface of nanoFe3O4 and mediates the rapid heterogeneous electron transfer, thus presenting a new Fe2O3 phase on the surface.

Radical Chain Polymerization Catalyzed by Graphene Oxide and Cooperative Hydrogen Bonding.

Graphene oxide (GO) is effective in catalyzing a wide variety of organic reactions and a few types of polymerization reactions. No radical chain polymerizations catalyzed by GO have been reported. In this article, we probe the catalytic role and acceleration effect of GO for self-initiated radical chain polymerizations of acrylic acid (AA) in the presence of GO and a pre-existing polymer, poly(N-vinylpyrrolidone) (PVP), from a calorimetric perspective. Gelation experiments and DSC studies show that GO can function as a catalyst to accelerate the radical chain polymerization of AA. Isothermal polymerization kinetic data shows that the addition of GO diminishes the induction periods and increases the polymerization rates, as indicated by the much enhanced overall kinetic rate constants and lowered activation energies. The catalytic effect of GO for the polymerization of AA is attributed to the acidity of GO and the hydrogen bonding interactions between GO and monomer molecules and/or polymers.

Size-Dependent Translocation Pattern, Chemical and Biological Transformation of Nano- and Submicron-Sized Ferric Oxide Particles in the Central Nervous System.

The present study investigated the size-dependent translocation pattern and biological fate of intranasally instilled nano- and submicron-sized Fe2O3 particles (40 nm and 280 nm) in the CNS. The particle translocation in different parts of brain at 4 h, 12 h, 24 h, 3 d, 7 d, and 30 d after intranasal instillation were quantified using ICP-MS method. A biexponential model (correlation coefficient r = 0.98-0.99) was satisfactory to describe the particokinetic translocation behavior of Fe2O3 nanoparticles in brain. We found a size-dependent translocation pattern and a time-dependent translocation mode for nano- and submicron-sized Fe2O3 nanoparticles in the olfactory bulb, which are most significant in toxic concerns of nanoparticles in the CNS. The TEM images showed particle-like substances of approximately 35-50 nm were located in the axons of olfactory neurons and in the mitochondria and lysosomes of hippocampus cells in the 40 nm-Fe2O3 exposed mice. The synchrotron-based near-edge X-ray absorption spectroscopy (XANES) was used to identify the chemical forms of the nanoparticles in brain. The XANES results indicate that the presence of chemical speciation of the Fe2O3 nanoparticle (-17%) and protein-complex like apotransferrin-Fe2O3 (-16%) in the olfactory bulb, implying that self-coating of Fe2O3 nanoparticles with transferrin occurred in brain. All the findings suggest size-sensitive manners of nano- and submicron-sized Fe2O3 particles in the brain; the smaller one possesses evident detention properties in the CNS versus the larger one.