Jagged1在大鼠切割穹窿海马伞后海马内的表达变化

目的:探讨切割穹窿海马伞后不同时相点海马内Jagged1的动态表达变化。方法:切割SD大鼠双侧穹窿海马伞,于切割后第3、7、14、21 d分别提取海马组织总RNA和总蛋白,应用RT-PCR和Western Blot的方法分别检测Jagged1基因和蛋白的表达变化;切割SD大鼠右侧穹窿海马伞,7 d后通过免疫组织化学的方法检测海马齿状回颗粒下层和门区中Jagged1阳性细胞的数目和平均光密度值(MOD)。结果:Jagged1基因和蛋白在切割穹窿海马伞后的第3 d表达开始增高,第7 d时达到最高水平,第14 d后表达下降至正常水平;切割穹窿海马伞后的第7 d,切割侧海马齿状回颗粒下层和门区中Jagged1阳性细胞数为167.89±22.11,平均光密度值为0.11±0.02;正常侧阳性细胞数为140.45±22.63,平均光密度值为0.06±0.01;切割侧阳性细胞数和平均光密度值与正常侧均明显增高(P0.05)。结论:切割穹窿海马伞后Jagged1基因和蛋白的表达呈现出先增高后降低的变化趋势,提示Jagged1是切割穹窿海马伞后海马内微环境的重要组成分子。     

贵州地区汉族人群GDF5基因单核苷酸多态性与成人终身高的关系

目的 探讨生长分化因子5(GDF5)基因rs143383、rs143384、rs6060369和rs224331位点单核苷酸多态性(SNPs)与贵州地区汉族人群成人终身高的相关性.方法 对贵州地区1 069例汉族健康体检者进行体格检查及问卷调查,收集抗凝血标本并提取DNA.用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)方法检测GDF5基因的SNPs,并分析其与身高的相关性.结果 成年女性中,GDF5基因rs143383、rs143384、rs6060369和rs224331基因型分布可分别解释身高变异的1.4％、0.9％、1.1％和1.0％(P＜0.05);在GDF5基因rs143383和rs143384位点,携带GG基因型的个体平均身高均为最高,分别比AG和AA基因型个体高1.7 cm (P＜0.01)、2.3 cm (P＜0.05)和1.6 cm (P＜0.05)、2.1 cm(P＜0.01);在GDF5基因rs6060369位点,携带CC基因型的个体平均身高分别比CT和TT基因型个体高1.7 cm (P＜0.05)和2.2 cm (P＜0.01).但是在成年男性中未发现GDF5基因上述SNPs位点与身高的相关性.结论 GDF5基因单核苷酸多态性与贵州地区成年汉族女性身高有关,GDF5基因可能是影响中国汉族成人女性身高个体差异的基因.     

Voluntary exercise increases axonal regeneration from sensory neurons

Recent advances in understanding the role of neurotrophins on activity-dependent plasticity have provided insight into how behavior can affect specific aspects of neuronal biology. We present evidence that voluntary exercise can prime adult dorsal root ganglion neurons for increased axonal regeneration through a neurotrophin-dependent mechanism. Dorsal root ganglion neurons showed an increase in neurite outgrowth when cultured from animals that had undergone 3 or 7 days of exercise compared with sedentary animals. Neurite length over 18-22 h in culture correlated directly with the distance that animals ran. The exercise-conditioned animals also showed enhanced regrowth of axons after an in vivo nerve crush injury. Sensory ganglia from the 3- and 7-day-exercised animals contained higher brain-derived neurotrophic factor, neurotrophin 3, synapsin I, and GAP43 mRNA levels than those from sedentary animals. Consistent with the rise in brain-derived neurotrophic factor and neurotrophin 3 during exercise, the increased growth potential of the exercise-conditioned animals required activation of the neurotrophin signaling in vivo during the exercise period but did not require new mRNA synthesis in culture.     

Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated with endothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO). METHODS: Wistar rats were randomized into seven experimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 min followed by reperfusion. All experimental groups received different treatments 45 min before the laparotomy. For each group, half of the animals (six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanine aminotransferase (ALT) and TNF-α levels, liver tissue malondialdehyde (MDA) content, and severity of hepatic I/R injury. RESULTS: Basal serum NO levels in female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/L vs45.3μ10.1 μmol/L, P<0.01). Although serum NO levels decreased significantly after hepatic I/R (P<0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/L vs 23.8±4.7 μmol/L, P<0.01). Serum ALT and TNF-α levels, and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18μg/L and 0.86±0.11 μmol/g, respectively, P<0.01). I/R induced significant injury to the liver both in M and F groups (P<0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P<0.05 and P<0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P<0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β-estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P<0.01). The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P<0.01 and P<0.05). The NOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats. CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOS-derived NO.     

A Novel (SiO2/MgO/MgCl2)·TiClx Ziegler–Natta Catalyst for Ethylene and Ethylene/1‐Hexene Polymerization

A novel (SiO₂/MgO/MgCl₂)·TiCl_x Ziegler–Natta catalyst for ethylene and ethylene/1‐hexene polymerization is successfully developed through impregnation of aqueous solution of water‐soluble Mg‐compounds such as magnesium acetate on silica gel, and forming a supported thin layer of magnesium oxide on the surface of SiO₂ after high temperature calcination in dry air or oxygen, followed by further reacting with titanium tetrachloride to synthesize the magnesium dichloride carrier in situ and to support the titanium species simultaneously. The method is relatively simple and the resulting catalysts exhibit high activity, good hydrogen response, and copolymerization ability with high 1‐hexene incorporation. Unlike the traditional industrial Ti/Mg Ziegler–Natta catalysts using the relatively expensive, anhydrous and moisture‐sensitive MgCl₂, Mg(OEt)₂, MgR₂ or RMgCl as Mg‐sources, the most unique feature of this novel catalyst is its capability of utilization of any soluble Mg‐compounds and thus shows great potential for application in commercial gas‐phase polyolefin processes.

     

Renewable juglone nanowires with size-dependent charge storage properties

Inspired by the biological metabolic process, some biomolecules with reversible redox functional groups have been used as promising electrode materials for rechargeable batteries, supercapacitors and other charge-storage devices. Although these biomolecule-based electrode materials possess remarkable beneficial properties, their controllable synthesis and morphology-related properties have been rarely studied. Herein, one dimensional nanostructures based on juglone biomolecules have been successfully fabricated by an antisolvent crystallization and self-assembly method. Moreover, the size effect on their electrochemical charge-storage properties has been investigated. It reveals that the diameters of the one dimensional nanostructure determine their electron/ion transport properties, and the juglone nanowires achieve a higher specific capacitance and rate capability. This work will promote the development of environmentally friendly and high-efficiency energy storage electrode materials.

Renewable juglone nanowires have been successfully fabricated, and their size effect on electrochemical charge-storage properties has been investigated.

Currently, the development of high-performance electrochemical energy-storage materials and devices is attracting intensive interest. Conventional electrode materials involving transition metal compounds,^1–4 elementary substances,^5–8 and conductive polymers,^9–12 with superior charge storage properties have been widely investigated. However, the poor biocompatibility, rising prices and depletion issues limit their sustainable applications due to their intrinsic material properties.¹³ Thus, exploring naturally abundant and renewable charge-storage materials with promising electrochemical performance is of great significance.In the biological system, its metabolic process mainly relies on ions transport and energy exchanges of redox-active biomolecules with special functional groups such as carbonyl groups, carboxyl groups, and pteridine centres.¹⁴ Due to their abundance, sustainability, environmental benignity, these renewable and nature-derivable biomolecules with well-defined charge-storage behaviors are ideal alternatives to conventional electrode materials for the next-generation green energy-storage devices.^15–17 For instance, biomolecules such as lignin,¹⁸ melanin,¹⁹ riboflavin,²⁰ juglone²¹ and humic acid²² have been demonstrated as promising electrode materials for the rechargeable batteries, supercapacitors and other charge-storage devices. Although these biomolecule-based electrode materials possess remarkable beneficial properties, they are still confronted with several serious problems of poor conductivity and high electrochemical reaction impedance.²³ For some conventional inorganic and organic active electrode materials, decreasing their size has been demonstrated to be effective strategies to enhance the electrochemical reaction kinetics by exposing more active sites to electrolytes and conductive agent.^8,24,25 These results have strongly motivated us to develop biomolecule-based nanostructures, and investigated their size-correlative charge storage behavior.^26,27Herein, one dimensional (1D) nanostructures based on juglone, a renewable redox-active biomolecule which can be derived from matured fruits of black walnut and the green peel of juglandaceae, have been successfully fabricated by an antisolvent crystallization and self-assembly method.^28–30 The size effect on the electrochemical charge-storage properties of these biomolecule-based 1D nanostructures have been investigated. It reveals that the electronic/ionic transport properties and charge-storage performance can be modulated by the size of self-assembled 1D nanostructures, and the samples with smaller diameter realize the higher specific capacitance and rate capability. Our work will provide insights for the development of high-performance biomolecule-based green energy-storage materials and devices.Juglone, also called 5-hydroxy-1,4-naphthalenedione, is a nature-derivable biomolecule, and displays a well-defined redox behavior in acetonitrile due to its quinone groups (Fig. 1a and b).³¹ As organic molecule inherently, it is soluble in organic solvent and difficult to dissolve in water, so its nano-architectures could be condonably fabricated by an antisolvent crystallization strategy (Fig. 1c) and would carry out stably for charge storage in an aqueous electrolyte.^29,30 Firstly, the juglone-biomolecule-based 1D nanostructures with different size were synthesized. The juglone micropillars with a mean diameter around 12 μm were prepared by directly recrystallizing a water/acetonitrile mixed solution of juglone at room temperature (Fig. 2a and d). Compared to commercially available raw juglone materials (Fig. S1^†), the juglone micropillars could increase its charge storage performance, but its relative large size would still confine its contact with electrolyte, and thus remarkably reduce the reaction kinetics.³² To further improve the potential reaction kinetics, the juglone microwires with an average diameter about 1 μm (Fig. 2b and e) and juglone nanowires with a mean diameter about 550 nm (Fig. 2c and f) were fabricated at room temperature using the reprecipitation method.³³ In the specific synthesis process, a high-concentration juglone acetonitrile solution is injected into water, which is a poor solvent for juglone molecules. Under stirring, juglone started to crystallize within a few seconds owing to its poor solubility in the water/acetonitrile mixture solvent and self-assembled into 1D nanostructures, and this procedure could be resulted from the π–π interaction.²⁹ It can be found that the diameter of 1D juglone materials is adjustable by tuning the concentration of juglone in acetonitrile, and the higher concentration of juglone acetonitrile solution yields the smaller size of 1D juglone materials. The insert panels show the percentage of juglone micropillar, microwire, nanowire with different diameter coverage (Fig. 2d–f).Open in a separate windowFig. 1(a) Chemical structural formula of juglone biomolecules which can be derived from the bark of black walnuts. (b) Juglone redox activity verified in a mixed solution of acetonitrile/deionized water by a three-electrode system using Pt foils as both the counter and working electrodes, Ag/AgCl as the reference electrode, and 2.3 M H₂SO₄ as the electrolyte. (c) Schematically illustration of the fabrication of the juglone nanowire/microwire.Open in a separate windowFig. 2SEM images of juglone 1D nanostructures at different magnification. (a and d) Juglone micropillar, (b and e) juglone microwire, (c and f) juglone nanowire. The insert images in panels (d–f) are corresponding mathematical statistic results of juglone samples with different diameter.Generally, the covalent bond, hydrogen bond, van der Waals forces, electrostatic forces, surface tension forces/dewetting, and π–π stacking interactions are considered as the effective factors in the self-assembly procedure of organic compounds.^34–36 The juglone biomolecule has a α-naphthol backbone with two carbonyl groups, which may induce the molecules self-assembly by the π–π interactions.^29,37–39 Fourier Transform Infrared Spectroscopy (FTIR) of such samples was utilized to examine the ingredient of these samples. As shown in Fig. S2,^† all the samples show similar characteristic peaks, the peak at 1640 cm⁻¹ is attributed to the stretching vibration of carbonyl groups, which is the main reversible redox center presented in juglone molecules. Meanwhile, Raman spectra also corroborated the results (Fig. S4^†). The crystal structures of these samples are further characterized by X-ray diffraction (XRD) as shown in Fig. S3.^† No impurity peak is observed in these patterns, demonstrating that these samples have the same crystal structure. And the peak intensity of juglone nanowire is stronger than juglone microwire and micropillar, suggesting that juglone nanowires have high crystallinity and relatively uniform crystal size.³⁰To investigate the redox behavior of 1D juglone micro/nanostructures, the cyclic voltammetry (CV) measurements were firstly performed (Fig. 3a), and the result reveals that these samples show a superior reversible redox performance, implying a potential application as energy storage materials. Meanwhile, compared with the CV curves of raw juglone, juglone micropillar and juglone microwire, the juglone nanowire exhibits the strongest redox peak, suggesting that the juglone nanowire-based electrode has a better charge storage behavior. To further evaluate the electrochemical performance of these samples, galvanostatic charge–discharge (GCD) measurements were carried out (Fig. 3b). First, juglone nanowire shows a higher specific capacity than that of microwire and micropillar. Besides, the plot of juglone 1D-based electrodes exhibit symmetric triangular shape with one pair of charge–discharge voltage plateau, and the voltage plateau of juglone micropillar, microwire and nanowire appears at 0.28 V, 0.26 V, 0.22 V, which is roughly consistent with the results of CV curves. Furthermore, it further reveals that the 1D nanostructure with smaller size exhibits higher specific capacity during the scan rates increasing from 10 to 200 mV s⁻¹ (Fig. 3c). In detail, at a low scan rate of 10 mV s⁻¹, the specific capacity delivered by juglone nanowire, juglone microwire, juglone micropillar are 389 F g⁻¹, 375 F g⁻¹, 116 F g⁻¹, respectively, and these samples possess the specific capacities of 232 F g⁻¹, 205 F g⁻¹, 80 F g⁻¹, when the scan rate are enhanced to 200 mV s⁻¹. The general perception is that nanomaterials with higher specific surface areas usually possess better electrochemical performance.⁴⁰ Obviously, the higher specific capacitance and superior rate capability are achieved by juglone nanowire electrode.Open in a separate windowFig. 3Electrochemical performance of the juglone samples with different diameter. (a) CV curves of juglone micropillar, microwire, nanowire electrodes in the potential range of −0.1 to 0.7 V (vs. Ag/AgCl) with a scan of 50 mV s⁻¹, (b) galvanostatic charge–discharge curves of juglone electrodes with different diameter at 2 A g⁻¹. (c) Statistical study of the rate performance conducted at each scan rate based on the cyclic voltammetry capacity of five electrodes as one batch. (d) Impedance phase angle as a function of frequency for juglone micropillar, microwire, nanowire electrodes. Inset is the Nyquist plot of them. (e) Correlation between the diameter and the specific capacity of the juglone samples at various scan rates.Then, the reaction kinetics of juglone with different sizes were investigated by electrochemical impedance spectroscopy (EIS) (Fig. 3d and S5^†). The crooked curve at high frequency denotes the interface resistance, involving contact and charge transfer resistances, while the low-frequency line represents ion diffusion resistance. The interface resistances of juglone nanowire, microwire, micropillar, raw material electrodes are 3.45 Ω, 3.80 Ω, 3.95 Ω, 4.02 Ω. The plot of the phase angle against the frequency reveals the characteristic frequency f₀ at the phase angle of −45° is 7.46 Hz for juglone nanowire-based electrode, and it is relatively higher than that for juglone microwire (7.36 Hz), micropillar (7.25 Hz) and raw material (6.48 Hz). Accordingly, the time constant t₀ (t₀ = 1/f₀) that represents the minimum time to discharge ≥50% of all the energy from the electrode was 0.134 s for juglone nanowire, whereas 0.136 s, 0.138 s, 0.154 s were required for juglone microwire, micropillar and raw material. The low charge transfer resistance, and short time constant validated the excellent charge and discharge capability of the juglone nanowire-based electrode.⁴¹In addition, for solid-state diffusion of H⁺ in electrode materials, the mean diffusion time is proportional to the square of the diffusion path length according to the following equation:t ≈ L²/D_H⁺1where L is the diffusion length and D_H⁺ the diffusion constant.^42,43 It has been found that the diffusion pathway will be shortening by nanostructuring of electrode materials when the diffusion constant D is same,⁴⁴ indicating that the smaller size nanostructures of juglone facilitate rapid ion/electron transport. Thus, 1D juglone nanowires possess higher specific capacitance and show slower capacity decay during the increased scan rates (Fig. 3e).Furthermore, the CV and GCD for juglone nanowire-based electrodes were tested under various scan rates and current densities. The CV profiles show that the redox activity can be maintained very well when increasing the scan rate from 10 to 100 mV s⁻¹ (Fig. 4a). Moreover, the GCD curves collected at different current densities exhibit symmetric triangular shape with one pair of charge–discharge voltage plateau, which is similar to the results of CV test (Fig. 4b and c). And the specific capacity is 342 F g⁻¹ at a current density of 2 A g⁻¹, it is approximately equivalent to the 345 F g⁻¹ at a scan rate of 20 mV s⁻¹. Next, the specific capacitance of our juglone nanowire is further compared to those of the reported conventional electrode materials.^45–51 As shown in Fig. 4d, the capacity of N/rGO (reduced graphene oxide doping with nitrogen) is 138 F g⁻¹, and our juglone nanowire have about 2-fold higher specific capacity than N/rGO, 1.5-fold higher than Fe₃O₄/rGO (154 F g⁻¹).Open in a separate windowFig. 4(a) CV curves of the juglone nanowire electrode at different scan rates from 10 mV s⁻¹ to 100 mV s⁻¹. (b) Charge and discharge curves in the current density range from 2 A g⁻¹ to 10 A g⁻¹. (c) Various specific capacity of the juglone nanowire electrode when increasing the scan rate from 10 mV s⁻¹ to 200 mV s⁻¹. (d) Specific capacity of juglone nanowire in comparison with different materials.     

High and low molecular weight hyaluronic acid-coated gold nanobipyramids for photothermal therapy

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is known that hyaluronic acid (HA) binds CD44 receptors, which are overexpressed on the surface of TNBC cells. To optimize the targeting ability of HA, in this study we coated gold nanobipyramids (GBPs) with high and low molecular weight HA (380 kDa and 102 kDa), named GBPs@h-HA and GBPs@l-HA, respectively. GBPs@l-HA and GBPs@h-HA had excellent stability when dispersed in water and PBS (pH 7.4) for seven days. The HA density was calculated by the ratio of HA to GBPs@l-HA and GBPs@h-HA, which was 13.22 and 4.77, respectively. The two nanoparticles displayed good photostability, which was evaluated by their photothermal performance and similar biocompatibility. Inductively coupled plasma atomic emission spectrometry (ICP-AES) revealed superior cellular uptake of GBPs@h-HA over GBPs@l-HA. Upon 808 nm laser irradiation, the GBPs@h-HA also showed higher therapeutic efficacy than GBPs@l-HA both in vitro and in vivo. Overall, our study demonstrates that the molecular weight of HA plays an important role in the targeting ability and thus photothermal therapeutic efficacy of HA-coated gold nanobipyramids.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Hyaluronic acid (HA) could bind CD44 receptors, which are overexpressed on the surface of TNBC cells. Upon 808 nm laser irradiation, the GBPs@HA showed high therapeutic efficacy in vivo.     

Analysis of anomalous origin of coronary arteries by coronary angiography in Chinese patients with coronary artery disease

With the development of coronary angiography for the diagnosis of coronary artery disease, its clinical significance in detecting coronary artery anomalies and evaluating the seriousness is attracting more attention. In the study we aimed to assess the prevalence of anomalous origin of coronary arteries in a Chinese population who underwent coronary angiography for coronary artery disease, and explore any patterns in the common variants and typical anomalies, especially the potentially serious ones. Patients who underwent coronary angiography from January 2013 to December 2016 in Fuwai Hospital were included. Baseline characteristics and angiographic data were collected, the incidence of anomalous origin of coronary arteries was calculated, and the typical patterns were analyzed. Comparisons between the present results and those of existing reports were also conducted. A total of 110,158 patients were included in the study, among which 0.76% (835 cases) had anomalous origin of coronary arteries. Among the anomalies, the incidences of anomalous origin of the right coronary artery (RCA), the left coronary artery (LCA), both the RCA and LCA, single coronary artery (SCA) and dextrocardia were 76.76% (641 cases), 14.61% (122 cases), 1.80% (15 cases), 4.67% (39 cases) and 2.16% (18 cases), respectively. Moreover, 47.54% (397 cases) of the anomalies were shown to be potentially serious, and an RCA arising from the left sinus of Valsalva (LSV) was the most common subtype (39.28%, 328 cases). Although anomalous origin of coronary arteries is not quite common, more clinical attention should be paid to this condition due to the potential risk of serious sequelae.     

Intravascular ultrasound-guided drug-eluting stent implantation is associated with improved clinical outcomes in patients with unstable angina and complex coronary artery true bifurcation lesions

Stenting coronary artery bifurcation lesion is associated with suboptimal clinical results. Clinical improvement by intravascular ultrasound (IVUS) guided bifurcation stenting is controversial because small-side-branch (SB), low-risk patients and false bifurcations were included in previous studies that had no exact IVUS criteria for optimal stent expansion. We sought determine whether IVUS guidance is superior to angiography guidance for patients with true and complex bifurcation lesions. Between July 2006 and July 2012, 1465 patients with unstable angina and Medina 1,1,1 or 0,1,1 coronary bifurcation lesions were prospectively studied. 310 patients in the IVUS guidance (defined as stent symmetry index?>?0.7, stent expansion index?>?0.9, well apposition, and no Type B/C dissection) group were paired with 620 patients in the angiography group by propensity score-matching. The primary endpoint was the rate of composite major adverse cardiac events (MACE) (cardiac death, myocardial infarction (MI), or clinically-driven target vessel revascularization) at 1-year and at the end of study after indexed procedure. Use of IVUS guidance was mainly driven by stenting technique selection and identification of lesions’ specificities. IVUS criteria for optimal stent expansion were achieved in 82.9% of patients which contribute to IVUS group data assessment and the rest did not meet optimal criteria. MACE occurred in 10.0% of patients at 1-year follow-up and 15.2% at the 7-year follow-up in the IVUS group, significantly different from 15.0% (p?=?0.036) and 22.4% (p?=?0.01) in the angiography group, respectively. Compared to angiography guidance, IVUS guidance also resulted in a lower 7-year cardiac death rate (6.5 versus 1.3%, p?=?0.002) and MI (8.4 versus 2.3%, P?<?0.001). Any revascularization was also statistically lower in the IVUS group through whole study period, compared to the angiography group. Lower MACE rates were observed in IVUS guidance group in a 7-year follow-up compared with angiography guidance alone.     

Fluorescence Molecular Imaging and Tomography of Matrix Metalloproteinase-Activatable Near-Infrared Fluorescence Probe and Image-Guided Orthotopic Glioma Resection

Purpose

Malignant gliomas are major causes of cancer-related mortality and morbidity. Traditional surgery usually leads to incomplete resection of gliomas resulting in the high incidence of tumor recurrence. Advanced medical imaging technology, such as fluorescence imaging-guided surgery, combined with tumor-specific imaging probes allows the identification of tumor margins and improved surgery. However, there are two pressing issues that need to be addressed: first, few fluorescence imaging probes can specifically target gliomas; second, fluorescence molecular imaging (FMI) cannot get the in-depth information of deep-seated gliomas; both of which affect the complete removal of the gliomas.

Procedures

In this study, the biodistribution of smart matrix metalloproteinase (MMP) targeting near-infrared (NIR) fluorescent probe MMPSense 750 FAST (MMP-750) was examined in both U87MG-GFP-fLuc glioma xenograft and orthotopic mouse models using FMI. Then, CT and FMI images of orthotopic gliomas were acquired for the reconstruction of fluorescence molecular tomography (FMT) using a randomly enhanced adaptive subspace pursuit (REASP) algorithm. Furthermore, the resection of orthotopic glioma was performed using the fluorescence surgical navigation system after the injection of the MMP-750 probe. After surgery, bioluminescence imaging (BLI) and hematoxylin and eosin staining were carried out to confirm the precision resection of the tumor.

Results

FMI results showed that the MMP-750 probe can specifically target U87MG glioma in vivo. FMT presented the spatial information of the orthotopic glioma using the REASP reconstruction algorithm. Furthermore, MMP-750 could effectively delineate the tumor margin during glioma surgery leading to a complete resection of the tumors.

Conclusions

The smart MMP-750 specifically targets the glioma and FMT of MMP-750 provides 3D information for the spatial localization of the glioma. MMP-750 can work as an ideal fluorescence probe for guiding the intraoperative surgical resection of the glioma, possessing clinical translation.