The effect of China's birth policy changes on birth defects-A large hospital-based cross-sectional study.

A retrospective analysis of birth data hospital-based obtained from 14 monitoring areas in the Huaihe River Basin from 2009 to 2019 was conducted. Trend in the total prevalence of birth defects (BDs) and subgroups were analyzed using the Joinpoint Regression model. The incidence of BDs increased gradually from 118.87 per 10,000 in 2009 to 241.18 per 10,000 in 2019 (AAPC = 5.91, P < 0.001). Congenital heart diseases were the most common subtype of BDs. The proportion of maternal age younger than 25 decreased but the age 25-40 years increased significantly (AAPC<20=-5.58; AAPC20-24=-6.38; AAPC25-29 = 5.15; AAPC30-35 = 7.07; AAPC35-40 = 8.27; All P < 0.05). Compared with the one-child policy period, the risk of BDs was greater for groups among maternal age younger than 40 years during the partial and universal two-child policy period (P < 0.001). The incidence of BDs and the proportion of women with advanced maternal age in Huaihe River Basin is increasing. There was an interaction between changes in birth policy and the mother's age on the risk of BDs.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

miR-1224 contributes to ischemic stroke-mediated natural killer cell dysfunction by targeting Sp1 signaling.

BACKGROUND: Brain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke. METHODS: Using a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion. Differential gene expression and function/pathway analysis were applied to investigate the main functions of predicted miRNA target genes. miR-1224 inhibitor/mimics transfection and passive transfer of NK cells were performed to confirm the impact of miR-1224 in NK cells after brain ischemia. RESULTS: We observed striking dysregulation of several miRNAs in response to ischemia. Among those miRNAs, miR-1224 markedly increased 3 days after ischemic stroke. Transfection of miR-1224 mimics into NK cells resulted in suppression of NK cell activity, while an miR-1224 inhibitor enhanced NK cell activity and cytotoxicity, especially in the periphery. Passive transfer of NK cells treated with an miR-1224 inhibitor prevented the accumulation of a bacterial burden in the lungs after ischemic stroke, suggesting an enhanced immune defense of NK cells. The transcription factor Sp1, which controls cytokine/chemokine release by NK cells at the transcriptional level, is a predicted target of miR-1224. The inhibitory effect of miR-1224 on NK cell activity was blocked in Sp1 knockout mice. CONCLUSIONS: These findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in an Sp1-dependent manner; this mechanism may be a novel target to prevent poststroke infection specifically in the periphery and preserve immune defense in the brain.

A Slug-dependent mechanism is responsible for tumor suppression of p53-stabilizing compound CP-31398 in p53-mutated endometrial carcinoma.

Mutation in the tumor suppressor gene p53 is the most frequent molecular defect in endometrial carcinoma (EC). Recently, CP-31398, a p53-stabilizing compound, has been indicated to possess the ability to alter the expression of non-p53 target genes in addition to p53 downstream genes in tumor cells. Herein, we explore the alternative mechanisms underlying the restoration of EC tumor suppressor function in mutant p53 by CP-31398. A p53-mutated EC cell was constructed in AN3CA cells with restored or partial loss of Slug using lentiviral vectors, followed by treatment with 25 µM CP-31398. A p53-independent mechanism of CP-31398 was confirmed by the interaction between mouse double minute 2 homolog (MDM2) and Slug AN3CA cells treated with IWR-1 (inhibitor of Wnt response 1). Furthermore, the AN3CA cells were treated with short hairpin RNA against Slug, Wnt-specific activators (LiCl) or inhibitors (XAV-939) followed by CP-31398 treatment. Moreover, AN3CA cell proliferation and apoptosis were examined. A tumorigenicity assay was conducted in nude mice. CP-31398 could promote the apoptosis of p53-mutated EC cells, while Slug reversed this effect. Slug ubiquitination was found to occur via binding of Slug to MDM2 in AN3CA cells. We found that CP-31398 increased the GSK-3ß, p-Slug, Puma, Wtp53, and Bax expressions whereas Wnt, Mtp-53, Slug, Bcl-2, and Ki-67 expressions were decreased. However, these findings were reversed following the activation of the Wnt pathway and overexpression of Slug. Finally, the in vivo experimental evidence confirmed that CP-31398 with depleted Slug suppressed tumor growth by downregulating the Slug. Collectively, CP-31398-regulated Slug downregulation represses the p53-mutated EC via the p53/Wnt/Puma pathway.

Brain Development in Infants of Mothers With Gestational Diabetes Mellitus: A Diffusion Tensor Imaging Study.

OBJECTIVE: The objective of this study was to investigate clinical neurocognitive performance and microstructural white matter (WM) alterations in infants of mothers with gestational diabetes mellitus (GDM) using diffusion tensor imaging. MATERIALS AND METHODS: Infants (corrected gestational age, 33.42-36.00 weeks) of mothers with GDM (n = 31) and gestational age- and sex-matched unexposed controls (n = 31) accomplished 3-T diffusion tensor imaging scans and neurocognitive tests. Diffusion tensor imaging measures, mainly referring to fractional anisotropy (FA) values, were compared between 2 groups, and within-group analysis of correlation between FA values and neurocognitive testing outcomes in GDM-exposed infants was conducted subsequently. RESULTS: Fractional anisotropy was significantly decreased in the splenium of corpus callosum, posterior limb of internal capsule, thalamus in infants of mothers with GDM when compared with controls (P < 0.05), reflecting microstructural WM abnormalities in the GDM group. Decreased FA was associated with worse neurocognitive performance in the exposed group (P < 0.05). CONCLUSIONS: Individuals of mothers with GDM showed microstructural WM abnormalities in different brain regions, which were significantly related to worse neurocognitive performance. This might reveal that GDM directly insults the brain development of the offspring.

Effects of shRNA-mediated silencing of PSMA7 on cell proliferation and vascular endothelial growth factor expression via the ubiquitin-proteasome pathway in cervical cancer.

This study aims to evaluate the effects of PSMA7 silencing on cervical cancer (CC) cell proliferation and vascular endothelial growth factor (VEGF) expression through the ubiquitin-proteasome pathway. CC tissues (n = 43) and normal tissues (n = 27) were first collected from patients. Human CC cell line (SiHa) and human normal cervical epithelial cells (H8) were obtained and classified into the normal, blank, negative control (NC), PSMA7-shRNA1, and PSMA7-shRNA2 groups, respectively. In situ hybridization was used to detect the expressions of wild-type and mutant p53 proteins. Immunofluorescence assay was carried out to test the activity of 20S proteasomes. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were both performed to determine the expressions of PSMA7, ubiquitin, P27, P53, and VEGF in sample tissues and cells. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation rates, and flow cytometry was used to analyze the cell cycle and the apoptotic rate. Compared with normal tissues, CC tissues showed increased expression levels of PSMA7, ubiquitin, p53, VEGF as well as increased activity of 20S proteasomes but exhibited a decrease in p27 expression. Compared with the blank and NC groups, the PSMA7-shRNA1 and PSMA7-shRNA2 groups all had decreased expression levels of PSMA7, ubiquitin, p53, and VEGF as well as decreased cell proliferation, 20S proteasomes activity, and cell number in the S phase, increased p27 expression, cell apoptosis and cell number in the G0/G1 phase. Our study demonstrated that PSMA7 silencing can suppress CC cell proliferation and VEGF expression in addition to promoting cell apoptosis through inhibiting the UPP signaling pathway.

CP-31398 inhibits the progression of cervical cancer through reversing the epithelial mesenchymal transition via the downregulation of PAX2s.

CP-31398, a styrylquinazoline, emerges from a screen for therapeutic agents that restore the wild-type DNA-binding conformation of mutant p53 to suppress tumors in vivo, but its effects on cervical cancer (CC) remain unknown. Hence, this study aimed to explore the effects CP-31398 has on the CC cells and to investigate whether it is associated with paired box 2 (PAX2) expression. CC cells were treated with different concentrations of CP-31398 (1, 2, 4, 6, 8, and 10 µg/ml) to determine the optimum concentration using fluorometric microculture cytotoxicity assay. After constructing the sh-PAX2 vector, CC cells were transfected with sh-PAX2 or treated with CP-31398. The effects of CP-31398 or PAX2 silencing on CC cell proliferation, apoptosis, invasion, and migration were evaluated. Epithelial mesenchymal transition (EMT)-related genes such as E-cadherin, vimentin, N-cadherin, snail, and twist in CC cells were detected. Tumor formation experiment in nude mice was performed to observe tumor growth. The optimum concentration of CP-31398 was 2 µg/ml. PAX2 was overexpressed in CC cells. CC cells treated with CP-31398 or treated with sh-PAX2 inhibited proliferation, invasion, and migration but promoted apoptosis with decreased PAX2 expression. The EMT process in CC cells was also reversed after treatment with CP-31398 or sh-PAX2. Moreover, the tumor formation experiment in nude mice revealed the inhibitory activity of CP-31398 in CC tumor in nude mice by suppressing PAX2. Our results provide evidence that CP-31398 could inhibit EMT and promote apoptosis of CC cells to curb CC tumor growth by downregulating PAX2.

Determination of multipool contributions to endogenous amide proton transfer effects in global ischemia with high spectral resolution in vivo chemical exchange saturation transfer MRI.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI has been used for quantitative assessment of dilute metabolites and/or pH in disorders such as acute stroke and tumor. However, routine asymmetry analysis (MTRasym ) may be confounded by concomitant effects such as semisolid macromolecular magnetization transfer (MT) and nuclear Overhauser enhancement. Resolving multiple contributions is essential for elucidating the origins of in vivo CEST contrast. METHODS: Here we used a newly proposed image downsampling expedited adaptive least-squares fitting on densely sampled Z-spectrum to quantify multipool contribution from water, nuclear Overhauser enhancement, MT, guanidinium, amine, and amide protons in adult male Wistar rats before and after global ischemia. RESULTS: Our results revealed the major contributors to in vivo T1 -normalized MTRasym (3.5 ppm) contrast between white and gray matter (WM/GM) in normal brain (-1.96%/second) are pH-insensitive macromolecular MT (-0.89%/second) and nuclear Overhauser enhancement (-1.04%/second). Additionally, global ischemia resulted in significant changes of MTRasym , being -2.05%/second and -1.56%/second in WM and GM, which are dominated by changes in amide (-1.05%/second, -1.14%/second) and MT (-0.88%/second, -0.62%/second). Notably, the pH-sensitive amine and amide effects account for nearly 60% and 80% of the MTRasym changes seen in WM and GM, respectively, after global ischemia, indicating that MTRasym is predominantly pH-sensitive. CONCLUSION: Combined amide and amine effects dominated the MTRasym changes after global ischemia, indicating that MTRasym is predominantly pH-sensitive and suitable for detecting tissue acidosis following acute stroke.

SHH gene silencing suppresses epithelial-mesenchymal transition, proliferation, invasion, and migration of cervical cancer cells by repressing the hedgehog signaling pathway.

The study aimed to investigate the mechanism by which the sonic Hedgehog (SHH) gene silencing acts upon epithelial-mesenchymal transition (EMT), proliferation, invasion, and migration of cervical cancer (CC) cells via the Hedgehog signaling pathway. RT-qPCR and Western blotting were all employed to detect the SHH mRNA and protein expressions. HeLa and CasKi cells were cultured and subsequently divided into the blank, negative control (NC), and SHH-RNAi groups. A cell counting kit-8 (CCK-8) assay was utilized for cell proliferation. Cell migration and invasion ability were evaluated through scratching test and Transwell assay. The mRNA and protein expressions of the Hedgehog signaling pathway-related factors were detected using RT-qPCR and Western blotting, respectively. After tumor xenograft in nude mice, tumor growth was subsequently observed. SHH mRNA and protein expressions were greater in the SHH-RNAi group than in the blank and NC groups. Compared with the blank group and NC groups, the SHH-RNAi group displayed inhibited levels of proliferation, migration, invasion abilities, as well as a decreased in the Hh signaling pathway-related factors, as well as a reduction in the mRNA and protein expressions of N-cadherin and Vimentin, however, on the contrary increased expressions of E-cadherin were observed. Following tumor xenograft in nude mice, tumor growth was exhibited vast levels of inhibition, particularly in the SHH-RNAi group in comparison to the blank and the NC groups. During the study it was well established that SHH gene silencing suppresses EMT, proliferation, invasion, and migration of CC cells through the repression of the Hedgehog signaling pathway.

HOXC6 gene silencing inhibits epithelial-mesenchymal transition and cell viability through the TGF-ß/smad signaling pathway in cervical carcinoma cells.

BACKGROUND: Homeobox C6 (HOXC6) plays a part in malignant progression of some tumors. However, the expression of HOXC6 and its clinical significance remains unclear in cervical carcinoma (CC). The purpose of this study is to verify the effects of HOXC6 gene silencing on CC through the TGF-ß/smad signaling pathway. METHODS: CC tissues and corresponding paracancerous tissues were collected from CC patients with involvement of a series of HOXC6-siRNA, HA-HOXC6 and the TGF-ß/smad pathway antagonist. HOXC6 expression was analyzed in six CC cell lines (C-33A, HeLa, CaSki, SiHa, ME-180, and HCC-94) by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The mRNA and protein expression of HOXC6, TGF-ß1, TGF-ß RII, smad4, smad7, E-cadherin, N-cadherin, Vimentin, ki-67, proliferating cell nuclear antigen (PCNA), p27, and Cyclin D1 were determined by RT-qPCR and western blot analysis. Cell proliferation, apoptosis and cell cycle were detected by MTT assay and flow cytometry, respectively. RESULTS: Higher positive expression rate of HOXC6 protein was observed in CC tissues and HOXC6 was related to TNM stage, lymphatic metastasis, cancer types, primary lesion diameter, and histological grade of CC. Silencing HOXC6 inhibited epithelial-mesenchymal transition (EMT) (shown as decreased N-cadherin and Vimentin, and increased E-cadherin) through the inactivation of the TGF-ß/smad signaling pathway. HOXC6 gene silencing hindered cell proliferation and accelerated cell apoptosis of CC cells. Furthermore, the effect of HOXC6 silencing was enhanced when the TGF-ß/smad signaling pathway was suppressed. CONCLUSION: The results reveal that HOXC6 gene silencing may inhibit EMT event and cell viability in CC through the inhibition of the activation of TGF-ß/smad signaling pathway.

Positive-contrast cellular MRI of embryonic stem cells for tissue regeneration using a highly efficient T1 MRI contrast agent.

PURPOSE: To investigate the feasibility of high-sensitivity cellular MRI of embryonic stem (ES) cells using a novel cell permeable and cell retentive T1 contrast agent. MATERIALS AND METHODS: Mouse ES cells were labeled with a novel manganese porphyrin contrast agent, MnAMP, at 0.1 mM over 2 to 24 h and retained in contrast-free medium for up to 24 h postlabeling. MRI was performed on a 3 Tesla clinical scanner; T1 and T2 relaxation times were measured. Quantification of manganese content was performed using atomic absorption spectroscopy. Viability and proliferation assays were done for the longest labeling interval. Differentiation capacity was assessed using the hanging drop method to direct differentiation toward cardiomyocytes. RESULTS: MnAMP-labeled ES cells exhibited over a fourfold decrease in T1 compared with unlabeled cells, and maintained up to a threefold decrease 24 h postlabeling. Viability and proliferation were not affected. Most importantly, labeled ES cells differentiated into functional cardiomyocytes that exhibited normal contractility patterns. CONCLUSION: MnAMP-based cellular MRI is a very high sensitivity T1 approach for cellular imaging. It has the potential for noninvasive in vivo monitoring of stem cell therapy in cardiac regeneration and other tissue engineering and regenerative medicine applications. J. Magn. Reson. Imaging 2016;44:1456-1463.

Ultrasensitive anion detection by NMR spectroscopy: a supramolecular strategy based on modulation of chemical exchange rate.

NMR spectroscopy is a powerful tool for monitoring molecular interactions and is widely used to characterize supramolecular systems at the atomic level. NMR is limited for sensing purposes, however, due to low sensitivity. Dynamic processes such as conformational changes or binding events can induce drastic effects on NMR spectra in response to variations in chemical exchange (CE) rate, which can lead to new strategies in the design of supramolecular sensors through the control and monitoring of CE rate. Here, we present an indirect NMR anion sensing technique in which increased CE rate, due to anion-induced conformational flexibility of a relatively rigid structure of a novel sensor, allows ultrasensitive anion detection as low as 120 nM.

Gadolinium-free extracellular MR contrast agent for tumor imaging.

PURPOSE: To evaluate a new formulation of manganese porphyrin as a potential gadolinium (Gd)-free extracellular magnetic resonance imaging (MRI) contrast agent for dynamic contrast-enhanced (DCE) MRI of tumors. MATERIALS AND METHODS: A previously reported new contrast agent, MnTCP, was evaluated in six female tumor-bearing nude rats. MRI was performed on a 3 T clinical scanner 3 to 4 weeks after inoculation of breast tumor cells in the mammary fat pads. Gd-DTPA was injected intravenously, followed by injection of MnTCP at least 2 hours later (both at 0.05 mmol/kg). T1 relaxation time measurements and DCE-MRI were performed. RESULTS: Enhancement and clearance patterns were visually similar between MnTCP and Gd-DTPA. However, relative R1 increases in all 11 tumors were larger for MnTCP over 60 minutes postcontrast, the difference being significant as late as 20 minutes (R1post /R1pre = 1.42 ± 0.15 for MnTCP vs. 1.20 ± 0.08 for Gd-DTPA, P < 0.05). R1 -related effects for MnTCP were largely reduced after 60 minutes (R1post /R1pre = 1.13 ± 0.07) and completely gone within 24 hours (R1post /R1pre = 0.97 ± 0.06). DCE-MRI revealed a consistently larger (1.5 to over 2-fold) peak enhancement and higher values of the steepest slope, time-to-peak, and AUC60 in all tumors with MnTCP (P < 0.01). CONCLUSION: MnTCP is an alternative to extracellular Gd agents for tumor imaging, offering sensitive detection and rapid renal clearance.

Ultrashort echo time magnetic resonance imaging of the lung using a high-relaxivity t1 blood-pool contrast agent.

The lung remains one of the most challenging organs to image using magnetic resonance imaging (MRI) due to intrinsic rapid signal decay. However, unlike conventional modalities such as computed tomography, MRI does not involve radiation and can provide functional and morphologic information on a regional basis. Here we demonstrate proof of concept for a new MRI approach to achieve substantial gains in a signal to noise ratio (SNR) in the lung parenchyma: contrast-enhanced ultrashort echo time (UTE) imaging following intravenous injection of a high-relaxivity blood-pool manganese porphyrin T1 contrast agent. The new contrast agent increased relative enhancement of the lung parenchyma by over 10-fold compared to gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), and the use of UTE boosted the SNR by a factor of 4 over conventional T1-weighted gradient echo acquisitions. The new agent also maintains steady enhancement over at least 60 minutes, thus providing a long time window for obtaining high-resolution, high-quality images and the ability to measure a number of physiologic parameters.

Binding of a dimeric manganese porphyrin to serum albumin: towards a gadolinium-free blood-pool T1 MRI contrast agent.

As the first clinically approved gadolinium-based blood-pool MRI contrast agent, gadofosveset was designed to bind to human serum albumin (HSA) reversibly, extending the circulation time in the bloodstream. This valuable pharmacokinetic property required for vasculature imaging, however, raises the risk of release and accumulation of gadolinium in vivo. The binding of gadofosveset to HSA significantly increases the relaxivity at low field, which decreases drastically when the magnetic field increases, limiting the applications of gadofosveset at fields of 3 T and higher. To address those challenges, we evaluated a novel dimeric manganese(III) porphyrin (MnP2) in vitro and in vivo as a potential gadolinium-free blood-pool agent. Through multiple spectroscopic studies, we demonstrated that MnP2 binds to HSA tightly. MnP2 exhibits a moderate relaxivity decrease on HSA binding. Nevertheless, owing to the unique field-dependent relaxation behaviors and the dimeric construct (two Mn(III) ions per complex), MnP2-HSA has a molar relaxivity twice that of the gadofosveset-HSA complex at 3 T. Through intravenous injection in rats, MnP2 exhibits long retention and significant contrast enhancement in the vascular compartment, as tested in a 3-T high-field clinical MRI scanner. Taken together, these data demonstrate that MnP2 represents a new class of gadolinium-free blood-pool agents suitable for both regular and high-field applications.

Gadolinium-free T1 contrast agents for MRI: tunable pharmacokinetics of a new class of manganese porphyrins.

PURPOSE: To evaluate a new class of manganese porphyrins with tunable pharmacokinetics as potential gadolinium (Gd)-free T1 agents for contrast-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Two new contrast agents, MnTCP and MnP2, were evaluated in four female rats. MRI was performed daily up to 3 days postinjection (0.05 mmol/kg) on a 3 T clinical scanner. T1 relaxation times and dynamic contrast-enhanced MRI were performed to assess contrast enhancement and clearance in blood, heart, liver, kidney, and muscle. RESULTS: Relative T1 decreases were similar for MnTCP and Gd-DTPA in all tissues but were significantly larger (P < 0.05) for MnP2 in blood, heart, kidney, and liver (2-6-fold larger). Clearance of MnTCP was similar to Gd-DTPA, with T1 returning to baseline by 40 minutes and complete elimination in 1 day. MnP2 was cleared from blood after 2 days and sustained a lowered T1 in other tissues for at least 1 hour (P < 0.05). The maximum enhancement, slope, and time-to-peak were similar between contrast agents. Only the parameter AUC60 differed, with MnP2 yielding the largest AUC60 values primarily through longer retention in tissue. CONCLUSION: MnTCP and MnP2 offer distinct applications as Gd-free T1 contrast agents. MnTCP behaves like a Gd-DTPA analog, while MnP2 provides significantly greater and longer positive signal enhancement.

Gadolinium-free Magnetic Resonance Imaging of the Liver via an Oatp1-Targeted Manganese(III) Porphyrin.

Controversy surrounding gadolinium-based contrast agents (GBCAs) has rendered their continued utility highly contentious, but the liver-specific GBCA Gd(III) ethoxybenzyl-diethylene triamine pentaacetic acid (Gd(III)-EOB-DTPA) remains in use because it provides unique diagnostic information that could not be obtained by any other means. To address the need for an alternate liver-specific MRI probe, we synthesized Mn(III) 20-(4-ethoxyphenyl) porphyrin-5,10,15-tricarboxylate (Mn(III)TriCP-PhOEt), which exhibited significantly higher r1 relaxivity than Gd(III)-EOB-DTPA in vitro, while also targeting hepatocyte-specific organic anion-transporting polypeptide 1 (Oatp1) channels as a marker of viability. In mice, Mn(III)TriCP-PhOEt resulted in significant and specific increases in liver signal intensity on T1-weighted images and significant decreases in liver T1 time relative to pre-contrast measurements. Our findings suggest that Mn(III)TriCP-PhOEt operates as a specific and sensitive MR probe for Oatp1-targeted imaging in vivo.

Diagnostic Value of Diffusion Tensor Imaging for Infants' Brain Development Retardation Caused by Pre-Eclampsia.

Objective: Pre-eclampsia (PE) can cause brain development delay in infants. This work aims to characterize the pattern differences of brain white matter development in premature infants under PE conditions and those without. Methods: Eighty preterm infants delivered by women with PE were selected as the PE group, and ninety-six preterm infants of the same period born to women without high-risk perinatal factors were used as control. All infants underwent diffusion tensor imaging (DTI) examination. The fractional anisotropy (FA) was measured in five regions of interests (ROIs), including posterior limbs of internal capsule (PLIC), splenium of the corpus callosum (SCC), superior frontal gyrus (SFG), superior parietal lobule (SPL), and superior occipital gyrus (SOG). The relationship between the FA values and postmenstrual age (PMA) was analyzed. Results: After adjusting for the birth weight and gestational ages, in the SCC and PLIC, the PMA and FA values showed a low-to-medium intensity positive correlation in the control group (r = 0.30, p=0.003; r = 0.53, p < 0.0001), while no positive relevance was detected in the PE group (r = 0.08, p=0.47; r = 0.19, p < 0.08). In the PE and control groups, in the SPL and SOG, the PMA and FA values showed a near-consistent positive correlation (r = 0.57, r = 0.55 vs. r = 0.31, r = 0.55; all p < 0.05). In the control group, in SFG, the PMA and FA values had a medium intensity positive correlation (r = 0.47, p < 0.0001), but there was no statistical difference in correlation in PE (r = 0.10, p=0.39). Conclusion: PE may cause lagging brain development in the SCC, PLIC, and SFG during infancy. DTI may be an effective and sensitive detection tool.

MRI sensing based on the displacement of paramagnetic ions from chelated complexes.

We introduce a mechanism for ion sensing by MRI in which analytes compete with paramagnetic ions for binding to polydentate chelating agents. Displacement of the paramagnetic ions results in alteration of solvent interaction parameters and consequent changes in relaxivity and MRI contrast. The MRI changes can be tuned by the choice of chelator. As an example, we show that calcium-dependent displacement of Mn(2+) ions bound to EGTA and BAPTA results in a T(1)-weighted MRI signal increase, whereas displacement from calmodulin results in a signal decrease. The changes are ion selective and can be explained using relaxivity theory. The ratio of T(2) to T(1) relaxivity is also calcium-dependent, indicating the feasibility of "ratiometric" analyte detection, independent of the probe concentration. Measurement of paramagnetic ion displacement effects could be used to determine analyte ion concentrations with spatial resolution in opaque specimens.

Water-soluble porphyrins as a dual-function molecular imaging platform for MRI and fluorescence zinc sensing.

We report a molecular platform for dual-function fluorescence/MRI sensing of mobile zinc. Zinc-selective binding units were strategically attached to a water-soluble porphyrin template. The synthetic strategy for achieving the designed target ligand is flexible and convenient, and the key intermediates can be applied as general building blocks for the construction of other metal sensors based on a similar mechanism. The metal-free form, (DPA-C(2))(2)-TPPS(3) (1), where DPA is dipicolylamine and TPPS(3) is 5-phenyl-10,15,20-tris(4-sulfonatophenyl)porphine, is an excellent fluorescent sensor for zinc. It has certain superior physical properties compared with earlier-generation zinc sensors including emission in the red and near-IR regions [lambda(em) = 645 nm (s) and 715 nm (m)], with a large Stokes shift of >230 nm. The fluorescence intensity of 1 increases by >10-fold upon zinc binding. The fluorescence "turn-on" is highly selective for zinc versus other divalent metal ions and is relatively pH-insensitive within the biologically relevant pH window. The manganese derivative, [(DPA-C(2))(2)-TPPS(3)Mn(III)] (2), switches the function of the molecule to generate an MRI contrast agent. In the presence of zinc, the relaxivity of 2 in aqueous solution is significantly altered, which makes it a promising zinc MRI sensor. Both metal-free and Mn(III)-inserted forms are efficiently taken up by live cells, and the intracellular zinc can be imaged by either fluorescence or MR, respectively. We anticipate that in vivo applications of the probes will facilitate a deeper understanding of the physiological roles of zinc and allow detection of abnormal zinc homeostasis for pathological diagnoses.