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Background: Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain.Methods: Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer.Results: Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free survival and 2.88 (2.07-4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total.Conclusions: Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To detect tumor angiogenesis in tumor-bearing mice using thiol-PEG-carboxyl-stabilized Fe2O3/Au nanoparticles targeted to CD105 on magnetic resonance imaging (MRI). Methods: Fe2O3/Au nanoparticles (hybrids) were prepared by reducing Au3+ on the surface of Fe2O3 nanoparticles. Hybrids were stabilized with thiol-PEG-carboxyl via the Au–S covalent bond, and further conjugated with anti-CD105 antibodies through amide linkages. Characteristics of the hybrid-PEG-CD105 nanoparticles were evaluated. Using these nanoparticles, the labeling specificity of human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. MRI T2*-weighted images were obtained at different time points after intravenous administration of the hybrid-PEG-CD105 nanoparticles in the tumor-bearing mice. After MR imaging, the breast cancer xenografts were immediately resected for immunohistochemistry staining and Prussian blue staining to measure the tumor microvessel density (MVD) and evaluate the labeling of blood microvessels by the hybrid-PEG-CD105 nanoparticles in vivo. Results: The mean diameter of the hybrid-PEG-CD105 nanoparticles was 56.6±8.0nm, as measured by transmission electron microscopy (TEM). Immune activity of the hybrid-PEG-CD105 nanoparticles was 53% of that of the anti-CD105 antibody, as detected by enzyme-linked immunosorbent assay (ELISA). The specific binding of HUVECs with the hybrid-PEG-CD105 nanoparticles was proved by immunostaining and Prussian blue staining in vitro. For breast cancer xenografts, the combination of the hybrid-PEG-CD105 nanoparticles with blood microvessels was detectable by MRI after 60min administration of the contrast agent. The T2* relative signal intensity (SIR) was positively correlated with the tumor MVD (R 2 =0.8972). Conclusion: Anti-CD105 antibody-coupled, thiol-PEG-carboxyl-stabilized core–shell Fe2O3/Au nanoparticles can efficiently target CD105 expressed by HUVECs. Furthermore, the hybrid-PEG-CD105 nanoparticles can be used to detect tumor angiogenesis in vivo. [Copyright &y& Elsevier]

Bimetallic core/shell Fe 2O 3/Au nanoparticles are promising candidate dual-mode contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) imaging. However, the gold coating on the hybrid nanoparticles (hybrids) affects the MRI and CT imaging quality. A thick gold nanoshell increases the X-ray attenuation effect but decreases the magnetic saturation of the hybrids. Therefore, we studied the effect of the Fe 2O 3 and Au composition on these properties to find a suitable hybrid for MRI and CT imaging. Water-soluble, Au-coated magnetic nanoparticles were synthesized by iteratively reducing Au 3+ onto the Fe 2O 3 surface via hydroxylamine seeding. The properties of the hybrids obtained after different numbers of Au seeding cycles were studied using transmission electron microscopy, UV–Vis spectrophotometry, a vibrating swatch gaussmeter, MRI, CT, and an MTT assay. The hybrids obtained after three Au seeding cycles had an Fe 2O 3:Au molar ratio of 7.2:26.8, a mean diameter of 48.3 nm, a UV–Vis absorbance peak of 550 nm, a saturation magnetization of 49.0 emu/g, and no cytotoxicity at a concentration of 500 μg/mL after incubation with RAW 264.7 cells for up to 72 h. The hybrids obtained after three Au seeding cycles are the preferred candidates for MRI and CT applications because of their relatively high R2 relaxivity (95 mM −1 s −1) and X-ray attenuation (1.87 times that of iodine) compared to those of the other hybrids investigated in this study. [ABSTRACT FROM AUTHOR]

Extracellular protein coronas (exPCs), which have been identified in various biofluids, are recognized for their pivotal role in mediating the interaction between nanoparticles and the cytomembrane. However, it is still unclear whether various exPCs can induce different levels of intracellular proteostasis, which is of utmost importance in preserving cellular function, and eliciting distinct intracellular biological behaviors. To investigate this, two types of exPC-coated iron oxide nanoparticles (IONPs) are prepared and used to investigate the influence of exPCs on extracellular and intracellular biological outcomes. The results demonstrate that the formation of exPCs promotes the colloidal stability of IONPs, and the discrepancies in the components of the two exPCs, including opsonin, dysopsonin, and lipoprotein, are responsible for the disparities in cellular uptake and endocytic pathways. Moreover, the differential evolution of the two exPCs during cellular internalization leads to distinct autophagy and glycolysis activities, which can be attributed to the altered depletion of angiopoietin 1 during the formation of intracellular protein coronas, which ultimately impacts the PI3K/AKT-mTOR signaling. These findings offer valuable insights into the dynamic characteristics of exPCs during cellular internalization, and their consequential implications for cellular internalization and intracellular metabolism activity, which may facilitate the comprehension of PCs on biological effects of NPs and expedite the design and application of biomedical nanoparticles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Acute liver injury (AIL), a fatal clinical disease featured with a swift deterioration of hepatocyte functions in the short term, has emerged as a serious public health issues that warrants attention. However, the effectiveness of existing small molecular antioxidants and anti-inflammatory medications in alleviating AIL remains uncertain. The unique inherent structural characteristics of liver confer it a natural propensity for nanoparticle capture, which present an opportunity to exploit in the formulation of nanoscale therapeutic agents, enabling their selective accumulation in the liver and thereby facilitating targeted therapeutic interventions. Significantly increased reactive oxygen species (ROS) accumulation and inflammation response have been evidenced to play crucial roles in occurrence and development of AIL. Nanozymes with ROS-scavenging capacities have demonstrated considerable promise in ROS elimination and inflammation regulation, thereby offering an appealing therapeutic instrument for the management of acute liver injury. In this review, the mechanisms of different type of ALI were summarized. In addition, we provide a comprehensive summary and review of the available ROS-scavenging nanozymes, including transition metal-based nanozymes, noble metal nanozymes, carbon-based nanozymes, and some other nanozymes. Furthermore, the challenges still need to be solved in the field of ROS-scavenging nanozymes for ALI alleviation are also discussed., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Sun et al.)

Developing nanomedicines with superior reactive oxygen species (ROS) scavenging capability has emerged as a promising strategy in treating ROS-related diseases, for example, drug-induced liver injury. However, designing nanoscavengers with the self-propelling ability to scavenge ROS actively remains challenging. Here, a self-propelled silica-supported ultrasmall gold nanoparticles-tannic acid hybrid nanozyme (SAuPTB) is designed that can effectively alleviate acetaminophen (APAP)-induced liver injury by scavenging excessive ROS and regulating inflammation. SAuPTB exhibits multienzyme activity and displays significantly enhanced diffusion under hydrogen peroxide (H 2 O 2 ). This in vitro research shows that SAuPTB can effectively eliminate ROS, increasing the viability of H 2 O 2 -stimulated cells and reducing the cytotoxicity of APAP/H 2 O 2 -treated AML12 cells. The in vivo studies show that SAuPTB can accumulate at inflammatory sites in mouse liver, resulting in the decrease of alanine aminotransferase, aspartate aminotransferase, and ROS, reduction in pro-inflammatory cytokines and chemokines, hence reduced hepatocyte necrosis, liver injury, and mortality. Furthermore, SAuPTB activates the nuclear erythroid 2-related factor 2 pathway to upregulate antioxidative genes and reduce oxidative stress. Finally, the liver shows decreased high mobility group box 1 and F4/80 + macrophages, suggesting an anti-inflammatory response. This work provides a novel design strategy of nanozymes for ROS-related disease treatment., (© 2023 Wiley-VCH GmbH.)

In this work, we developed an ultrasensitive colorimetry for Salmonella typhimurium detection with multifunctional Au-Fe 3 O 4 dumbbell-like nanoparticles (DBNPs) which possessed easy bio-modifiability, excellent LSPR characteristics, superparamagnetic properties and super peroxidase-like activity. In the detection, the anti-S. typhimurium antibody modified DBNPs (IDBNPs) bound with S. typhimurium and aggregated on their surfaces in a large number, which showed much quicker magnetic response than free IDBNPs. By controlling appropriate separation conditions, IDBNPs@S. typhimurium composites were captured, while free IDBNPs were remained in the supernatant. Therefore, by detecting the absorbance of the supernatant, quantitative detection was achieved from 10 to 1000 CFU/mL. Moreover, utilizing the peroxidase-like activity of IDBNPs, we further realized semi-quantitative naked-eye detection. By adding ABTS into the above supernatant, which was oxidized to green chelate (OxABTS), colorimetric signal was amplified significantly, and meanwhile, the green chelates and the wine-red IDBNPs engendered mixed color, enhancing the range of color gradation and greatly improving the visual resolution. Finally, a detection limit (10 CFU/mL) comparable with that of above spectrum measurement was achieved. Besides, our method exhibited efficient capture capability (nearly 100% even for rare S. typhimurium), and had good stability and specificity, and acceptable anti-interference ability in fetal bovine serum and milk samples., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© The Author(s) 2022. Published by Oxford University Press.)

Purpose: To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 expression., Methods: The human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 gene overexpression lentivirus system (hTERT-AQP1) and cytomegalovirus (CMV) promoter-driven AQP1 gene overexpression lentivirus system (CMV-AQP1) were prepared, and transduced into telomerase-positive and -negative cells. The AQP1 expression and DWI signal intensity (SI) change in transduced cells were analyzed. Balb/C nude mice subcutaneous xenograft models derived from lentivirus-transduced telomerase-positive and -negative cells were used to evaluate AQP1 expression and DWI SI change in vivo. We further established another group of subcutaneous xenograft model using pristine telomerase-positive and -negative cells, followed by injecting the lentiviral vectors intratumorally or intravenously, to determine the malignant tumor-targeted imaging of hTERT-AQP1., Results: The hTERT-AQP1 and CMV-AQP1 were successfully prepared. After transduction, hTERT-AQP1 could induce the specific overexpression of AQP1 in telomerase-positive cells. Compared with untransduced cells, all CMV-AQP1-pretransduced cells and hTERT-AQP1-pretransduced telomerase-positive cells showed decreased SI and increased apparent diffusion coefficient (ADC) in DWI, while hTERT-AQP1-pretransduced telomerase-negative cells showed no obvious SI and ADC change. Correspondingly, hTERT-AQP1-transduced telomerase-positive tumors and CMV-AQP1-transduced telomerase-positive and -negative tumors showed decreased DWI SI and increased ADC, while hTERT-AQP1-transduced telomerase-negative tumor had no SI and ADC changes. After intratumoral or intravenous injection, CMV-AQP1 could upregulate AQP1 expression and induce DWI SI and ADC alteration in both telomerase-positive and -negative tumors, while hTERT-AQP1 worked in telomerase-positive tumors specifically., Conclusion: Cancers can be specifically visualized based on the DWI signal alteration which triggered by hTERT-AQP1 lentivirus system that combined AQP1 gene and hTERT promoter., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plasmonic nanomaterials with strong absorption at near-infrared frequencies are promising photothermal therapy agents (PTAs). The pursuit of high photothermal conversion efficiency has been the central focus of this research field. Here, we report the development of plasmonic nanoparticle clusters (PNCs) as highly efficient PTAs and provide a semiquantitative approach for calculating their resonant frequency and absorption efficiency by combining the effective medium approximation (EMA) theory and full-wave electrodynamic simulations. Guided by the theoretical prediction, we further develop a universal strategy of space-confined seeded growth to prepare various PNCs. Under optimized growth conditions, we achieve a record photothermal conversion efficiency of up to ∼84% for gold-based PNCs, which is attributed to the collective plasmon-coupling-induced near-unity absorption efficiency. We further demonstrate the extraordinary photothermal therapy performance of the optimized PNCs in in vivo application. Our work demonstrates the high feasibility and efficacy of PNCs as nanoscale PTAs.

Background: The aging process and declining estradiol levels are two important factors that cause structural brain alterations. Many prior studies have investigated these two elements and revealed controversial results in menopausal women. Here, a cross-sectional study was designed to individually evaluate estradiol-related structural changes in the brain. Methods: A total of 45 early menopausal women and 54 age-matched premenopausal controls were enrolled and subjected to magnetic resonance imaging (MRI) scans, blood biochemistry tests, and neuropsychological tests. MRI structural images were analyzed using FreeSurfer to detect changes in subcortical and cortical volumes as well as cortical thickness. Finally, structural brain data as well as clinical and neuropsychological data were used for Pearson's correlation analyses to individually determine estradiol-related structural and functional changes in the brains of early menopausal women. Results: Compared with the premenopausal controls, the early menopausal women showed significant subcortical volumetric loss in the left amygdala and right amygdala, higher serum follicle-stimulating hormone (FSH) levels, more recognizable climacteric and depressive symptoms, decreased quality of sleep, and decreased working memory and executive functions. Simultaneously, FSH levels were related to lower working memory accuracy and longer working memory reaction time. Decreased subcortical volume in the bilateral amygdala was also related to lower working memory accuracy and longer executive reaction time in early menopausal women. Conclusion: The data suggest that estradiol deficiency in early menopausal women can lead to subcortical volume and functional brain changes, which may contribute to further understanding the neurobiological role of declined estradiol levels in early menopausal women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Fan, Hu, Wen, Gong, Liu, Hu, Li and Zhang.)

Background: Satisfactory prognosis of breast cancer (BC) is limited by difficulty in early diagnosis and insufficient treatment. The combination of molecular imaging and photothermal therapy (PTT) may provide a solution., Methods: Fe 3 O 4 -Au shell nanoparticles (NPs) were prepared by thermal decomposition, seeded growth and galvanic replacement and were comprehensively characterized. After conjugated to PEG, NPs were used as MRI and PTT agents in vitro and in vivo., Results: Fe 3 O 4 -Au shell NPs which had uniform Janus-like morphology were successfully synthesized. The Fe 3 O 4 had a size of 18 ± 2.2 nm, and the Au shell had an outer diameter of 25 ± 3.3 nm and an inner diameter of 20 ± 2.9 nm. The NPs showed superparamagnetism, a saturation magnetization of 36 emu/g, and an optical absorption plateau from 700 to 808 nm. The Fe 3 O 4 -Au shell NPs were determined to possess good biocompatibility. After PEG coating, the zeta potential of NPs was changed from -23.75 ± 1.37 mV to -13.93 ± 0.55 mV, and the FTIR showed the characteristic C-O stretching vibration at 1113 cm -1 . The NPs' MR imaging implied that the T 2 can be shortened by Fe 3 O 4 -Au shell NPs in a concentration-dependent manner, and the Fe 3 O 4 -Au shell NPs coated with PEG at the molar ratio of 160 (PEG: NPs) showed the highest transverse relaxivity ( r 2 ) of 216 mM -1 s -1 . After irradiation at 0.65 W/cm 2 for 5 min, all cells incubated with the Fe 3 O 4 -Au shell -PEG160 NPs (Fe: 30 ppm, Au: 70 ppm) died. After administrated intratumorally, Fe 3 O 4 -Au shell -PEG160 notably decreased the signal intensity of tumor in T 2 WI images. Under the same irradiation, the temperature of tumors injected with Fe 3 O 4 -Au shell -PEG160 quickly rose to 54.6°C, and the tumors shrank rapidly and were ablated in 6 days., Conclusion: Fe 3 O 4 -Au shell -PEG NPs show good r 2 and PTT performance and are promising synergistic theranostic agents of MRI and PTT for BC., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Kang et al.)

Herein, we developed a novel strategy for the shape-controlled synthesis of iron oxide nanostructures with superior r2 values through the introduction of fluoride ions as a morphology controlling agent and dopant. The selective adsorption of fluoride ions onto the specified crystal planes of iron oxide nanocrystals leads to the formation of octapod nanoparticles (ONPs) and cubic nanocrystal clusters (CNCs). Both ONPs and CNCs present high r2 values (526.5 and 462.2 mM-1 s-1, respectively) due to the synergistic effect of a larger effective radius, clustering and fluorine doping. The in vivo MRI results show significant enhancement in T2-weighted images of the liver after the intravenous injection of ONPs and CNCs, suggesting their great potential as efficient T2-weighted MRI contrast agents. This new approach of achieving anisotropic fluorine-doped iron oxide nanostructures with high r2 relaxivity provides an alternative strategy for the development of highly sensitive T2 contrast agents for MRI.

Owing to the localized surface plasmon resonance (LSPR), dynamic manipulation of optical properties through the structure evolution of plasmonic nanoparticles has been intensively studied for practical applications. This paper describes a novel method for direct reversible self-assembly and dis-assembly of Au nanoparticles (AuNPs) in water driven by pH stimuli. Using 3-aminopropyltriethoxysilane (APTES) as the capping ligand and pH-responsive agent, the APTES hydrolyzes rapidly in response to acid and then condenses into silicon. On the contrary, the condensed silicon can be broken down into silicate by base, which subsequently deprotonates the APTES on AuNPs. By controlling condensation and decomposition of APTES, the plasmonic coupling among adjacent AuNPs could be reversible tuned to display the plasmonic color switching. This study provides a facile and distinctive strategy to regulate the reversible self-assembly of AuNPs, and it also offers a new avenue for other plasmonic nanoparticles to adjust plasmonic properties via reversible self-assembly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Fu, Xu, Zhang, Sun, Du, Kang, Xiao, Zhou, Gong and Zhang.)

Background: Manganese Ferrite Nanoparticles (Mn-IONPs) are widely used in biomedical field and their cytotoxicity has been initially explored, but the mechanism remains obscure. The nano-bio interactions are believed to be crucial for cytotoxicity mechanism, while little data have been acquired., Methods: Mn-IONPs were synthesized by thermal decomposition of acetylacetonate precursor. After physicochemical characterization, we analyzed the metabolic conversion and removal of Mn-IONPs in RAW264.7 cells by Prussian blue staining, TEM, HRTEM and elemental quantitative analysis, followed by gene expression evaluation using quantitative RT-PCR., Results: Mn-IONPs were successfully synthesized. Both the uptake and cytotoxicity of Mn-IONPs on RAW264.7 cells were time- and dose-dependent. After internalized, Mn-IONPs were passed to daughter cells with passages on. Meanwhile, Mn-IONPs were exocytosed and digested to metal ions and further excreted out, resulted in the labeling rate and ions contents decreased gradually. As ion influx related genes, the expressions of ZIP14, IRP2, FtH and DMT1 were suppressed within 24 hours but overexpressed to a plateau at the 48th hour in a dose-dependent manner. At the 72nd hour, ZIP14 and DMT1 mRNA levels decreased toward normal, while IRP2 and FtH kept up-regulated. As efflux related genes, FPN, SLC30A10 and Hamp2 genes were up-regulated within 24-72 hours; SPCA1 was suppressed at the 24th and 72nd hour, while overexpressed at the 48th hour. All the efflux related genes' mRNA had a dose-dependent increasing manner at the corresponding time points., Conclusion: Mn-IONPs showed time- and dose-dependent cytotoxicity and cell labeling rate in RAW264.7 cells. Accompanying with the intracellular catabolic breakdown and exocytosis of Mn-IONPs, RAW264.7 cells also secreted and re-uptook manganese and iron ions to maintain intracellular homeostasis in the succeeding passages. And the metabolic conversion of Mn-IONPs in RAW264.7 cells can affect the expression of ZIP14, DMT1, FPN, SLC30A10, IRP2, FtH, Hamp2 and SPCA1 genes., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Zhang et al.)

Objective: We aimed to explore differences in the educational impact of the mini-Clinical Evaluation Exercise (mini-CEX) on resident (RE) and professional degree postgraduate (PDPG) trainees, as well as influencing factors, to provide suggestions for hospital managers, trainers, and trainees., Methods: We performed a retrospective analysis of all scores among first-year resident standardization training trainees registered during 2017 to 2019 at Xinqiao Hospital of Army Medical University, to identify differences in mini-CEX outcomes between REs and PDPGs., Results: We collected data of 154 registered trainees for retrospective analysis, including 57 PDPG trainees and 97 RE trainees. The mean (standard deviation) overall performance score of PDPGs was 84.18 (4.25), which was higher than that of REs (81.48 (3.35)). In terms of domain analysis, PDPG trainees performed significantly better than REs in history taking, physical examination, clinical diagnosis/treatment regimen, and the knowledge examination; communication skills/humanistic care were comparable between the groups., Conclusions: PDPGs performed better than REs in overall competency, history taking, physical examination, clinical diagnosis/treatment regimen, and the knowledge examination. A better knowledge base, supervisor-dominated one-to-one teaching mode, higher self-esteem and learning goals, and more sophisticated responses to feedback were potential contributors to a superior educational impact of the mini-CEX.

This study investigated the aberrant connectivity of the salience network (SN) and default mode network (DMN) and the relevance between these abnormalities and symptom improvement in hyperthyroid patients using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based functional connectivity (FC) analyses were performed on state fMRI data to reveal possible differences in critical node connectivity in the SN and DMN between 41 new-onset, untreated hyperthyroid patients and 41 healthy controls. Subsequently, follow-up data were available for 25 patients treated with methimazole for one month. Compared with the healthy controls, the patients exhibited abnormal internetwork FC from the SN to the DMN and the executive control network (ECN) and decreased intra-network FC within the SN. Relative to the hyperthyroid state, the antithyroid therapy induced reversible connectivity of the left insula to the dorsal anterior cingulate cortex(dACC)and ECN, and persistently increased connectivity between the SN and DMN in patients with improved thyroid function. Finally, Pearson's correlation analyses were performed among the abnormal FC, neuropsychological assessment and serum free triiodothyronine(FT3)level data. The results indicated that aberrant intra- and internetwork FC in the SN and DMN might underlie the pathogenesis of hyperthyroidism, and antithyroid treatment could regulate the FC of certain key brain regions within the SN and DMN in hyperthyroid patients.

Background: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T 1 /T 2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T 1 /T 2 dual-contrast CA, and evaluated its feasibility of T 1 /T 2 dual-contrast MRI in vitro and in vivo., Methods: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo., Results: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity ( r 1 = 7.1 mM -1 s -1 ) and transversal relaxivity ( r 2 = 120.9 mM -1 s -1 ), making it a better candidate for T 1 /T 2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T 1 -weighted and T 2 -weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T 1 and T 2 enhancement were optimum at that time., Conclusion: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T 1 /T 2 dual-contrast mMRI., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Xiao et al.)

Considering the situation that environmental issues become more serious day by day, research on practical applications of semiconductor photocatalysis for environmental purification has attracted broad attention, including the remediation of water pollution, air contaminant treatment, photocatalytic sterilization etc. , among which the application of semiconductor photocatalytic properties for the disinfection of soil surfaces, air and water, such as TiO 2 , is of great interest. In this paper, we give an overview of the photocatalytic antibacterial ability of TiO 2 and other novel carbon material semiconductors. We have introduced the background information of photocatalytic disinfection and the disinfection mechanism of pure TiO 2 . Furthermore, other modified TiO 2 sterilization materials are listed, such as those with doping modification. In addition, some novel carbon based nanomaterials are discussed as well in this review, for instance, g-C 3 N 4 , carbon nanotubes and graphene nanosheets. Finally, we present an outlook over two dimensional (2D) materials and coupling techniques based on the combination of photocatalysis and other sterilization technologies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Magnetic/plasmonic hybrid nanoparticles are highly desirable for multimodal bioimaging and biosensing. Although the synthesis of heterodimeric nanoparticles has been reported, the products are usually hydrophobic so that post-treatment procedures are required to transfer them into water which are often difficult to perform and cause damages to the structures. Direct synthesis of hydrophilic hybrid nanostructures has remained a grand challenge albeit its immediate advantage of biocompatibility. Herein we report a general seed-mediated approach to the synthesis of hydrophilic and biocompatible M-Fe 3 O 4 (M = Au, Ag, and Pd) heterodimers, in which the size of metals and Fe 3 O 4 can be independently regulated in a wide range. Benefiting from the aqueous synthesis, this approach can be further extended to design more complex heterodimeric structures such as AgPt alloy -Fe 3 O 4 , Au core @Pd shell -Fe 3 O 4 , and Au shell -Fe 3 O 4 . The hydrophilic nature of our heterodimers makes them readily useful for biomedical applications without the need of additional ligand exchange processes in contrast to those prepared in nonpolar solvents. These nanoscale magnetic/plasmonic heterostructures were shown to be ideally suited for integrated biomedical diagnoses, such as magnetic resonance imaging, photoacoustic imaging, optical coherence tomography, and computed tomography, in virtue of their biocompatibility and combined tunable magnetic and plasmonic properties.

Background : Patients with ulcerative colitis (UC) usually display cognitive impairments, such as memory loss, attention deficits, and declining executive functions, particularly during the active stage of the disease. However, the potential neurological mechanisms of these symptoms remain unclear. Method : Forty-one patients with mildly to moderately active UC, as well as 42 matched healthy controls, were recruited for an examination using psychological scales, cognitive function tests and resting-state functional magnetic resonance imaging (rs-fMRI). Seed points were identified via analysis of amplitude of low-frequency fluctuation (ALFF), and functional connectivity (FC) was calculated between these seed regions and other voxels in the whole brain. Correlation analyses were performed among clinical indexes, neuropsychological assessments and neuroimaging data. Result : Compared with the healthy controls, patients with UC exhibited lower ALFF values in the bilateral hippocampal/parahippocampal (HIPP/ParaHIPP) region and higher ALFF values in the left posterior cingulate cortex (PCC.L) and left middle frontal gyrus (MFG.L). With HIPP/ParaHIPP as the seed point, the strengths of the FC in the bilateral middle frontal gyri (MFG), anterior cingulate cortex (ACC), and left caudate nucleus (CAU.L) increased; using the PCC.L as the seed point, the strengths of the FC in the middle cingulate cortex (MCC) and the left angular gyrus (AUG.L) increased. These abnormal brain regions were mainly located in the limbic system. By analyzing the correlations between these brain regions and behavioral data, we observed a close correlation between decreased HIPP/ParaHIPP activity and memory loss; increased PCC activity and strength of FC with the AUG.L were related to dysfunction of executive function and attention network in patients with UC. Conclusion : Based on these results, the limbic lobe might be the core of the brain-gut axis (BGA) and play an important role in cognitive impairments, suggesting potential mechanisms for cognitive impairment in patients with UC in the active stage of the disease.

Background : Early postmenopausal women frequently suffer from cognitive impairments and emotional disorders, such as lack of attention, poor memory, deficits in executive function and depression. However, the underlying mechanisms of these impairments remain unclear. Method : Forty-three early postmenopausal women and forty-four age-matched premenopausal controls underwent serum sex hormone analysis, neuropsychological testing and resting-state functional magnetic resonance imaging (rs-fMRI). Degree centrality (DC) analysis was performed to confirm the peak points of the functionally abnormal brain areas as the centers of the seeds. Subsequently, the functional connectivity (FC) between these abnormal seeds and other voxels across the whole brain was calculated. Finally, the sex hormone levels, neuroimaging indices and neuropsychological data were combined to detect potential correlations. Results : Compared with the premenopausal controls, the early postmenopausal women exhibited significantly higher serum follicle-stimulating hormone (FSH) levels, more severe climacteric and depressive symptoms, worse sleep quality and more extensive cognitive impairments. Concurrently, the neuroimaging results showed elevated DC values in the left amygdala (AMYG.L), reduced DC values in the left middle occipital gyrus (MOG.L) and right middle occipital gyrus (MOG.R). When we used the AMYG.L as the seed point, FC with the left insula (INS.L), bilateral prefrontal cortex (PFC) and right superior frontal gyrus (SFG.R) was increased; these regions are related to depressive states, poor sleep quality and decreased executive function. When bilateral MOG were used as the seed points, FC with left inferior parietal gyrus (IPG.L), this area closely associated with impaired memory, was decreased. Conclusion : These results illuminated the regional and network-level brain dysfunction in early postmenopausal women, which might provide information on the underlying mechanisms of the different cognitive impairments and emotional alterations observed in this group.

Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM(-1) s(-1), which was much higher than that of MnFe2O4 nanoparticles (67.5 mM 1 s(-1)). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn(2+) ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.