Associations between new obesity indices and abnormal bone density in type 2 diabetes mellitus patients.

The clinical data analysis found that, compared with the traditional obesity index, the waist-weight ratio (WWR) has more advantages in predicting abnormal bone mineral density in subjects with type 2 diabetes. WWR may serve as a new predictive indicator for osteoporosis in T2DM patients. PURPOSE: This study was designed to explore the correlation between obesity-related indices and bone mineral density (BMD) and its influencing factors in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 528 patients with type 2 diabetes were recruited. Glucose tolerance, insulin stimulation, and blood biochemical tests were conducted on all participants. All subjects underwent dual-energy X-ray bone density testing and were grouped based on the bone density results. RESULTS: Compared with those in the normal BMD group, the waist-to-body weight ratio (WWR) and weight-adjusted-waist index (WWI) in the osteopenia and osteoporosis groups were significantly greater, while body mass index (BMI) was significantly lower (P < 0.05). The logistic regression results showed that the WWR, WWI, and BMI were independently correlated with abnormal BMD in T2DM patients (P < 0.05). WWR and the WWI were negatively correlated with the T-value of bone density in various parts of the body, while BMI was positively correlated with the T-value of bone density (P < 0.05). The area under the working characteristic curve (AUC) for T2DM patients with abnormal bone mass predicted by the WWR [0.806, 95% CI = (0.770-0.843), P < 0.001] was greater than that for patients with other obesity indicators, such as the WWI and BMI. CONCLUSION: We found a positive correlation between the WWR and bone density in T2DM patients. Compared with other obesity indicators, such as BMI and WWI, the WWR has a stronger discriminative ability for T2DM patients with abnormal bone density. Therefore, more attention should be given to the WWR in T2DM patients.

Insulin-Like Growth Factor-Binding Protein 5 Promotes the Cell Proliferation and Osteogenic Potential of Dental Pulp Stem Cells Dependent on Its Nuclear Localisation Sequence.

OBJECTIVES: Dental pulp stem cells (DPSCs) have been extensively used for tissue regeneration owing to their notable capabilities. Insulin-like growth factor-binding protein 5 (IGFBP5) regulates osteogenic differentiation of mesenchymal stem cells (MSCs); however, the underlying regulatory mechanisms require further investigation. MATERIALS AND METHODS: Carboxyfluorescein succinimidyl ester, an alkaline phosphatase (ALP) activity assay and Alizarin Red staining were used to reveal the role of IGFBP5 in DPSCs. Protein expression levels were determined using western blotting. Immunofluorescence was used to observe cell sub-localisation. Subcutaneous transplantation in nude mice was used to observe the osteogenesis of DPSCs in vivo. RESULTS: IGFBP5 enhanced the proliferation and osteogenic differentiation of DPSCs. Deletion of the nuclear localisation sequence (NLS) of IGFBP5 prevented its nuclear import and abolished all its promoting effects on DPSCs; ivermectin stimulation attenuated the enhancement of ALP activity by IGBFP5. Bone-like tissue formation promoted by IGFBP5 in vivo vanishes when the NLS is deleted. Inhibition of IGFBP5 nuclear import attenuated the IGFBP5-induced phosphorylation of JNK (p-JNK) and phosphorylated ERK (p-ERK) in DPSCs. CONCLUSION: Our findings suggest that cell proliferation and osteogenic differentiation effects exerted by IGFBP5 on DPSCs are closely associated with their entry into the nucleus, thereby providing a novel potential target for tissue regeneration.

Radiological assessment of immunotherapy effects and immune checkpoint-related pneumonitis for lung cancer.

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

Engineering single-atom catalysts toward biomedical applications.

Due to inherent structural defects, common nanocatalysts always display limited catalytic activity and selectivity, making it practically difficult for them to replace natural enzymes in a broad scope of biologically important applications. By decreasing the size of the nanocatalysts, their catalytic activity and selectivity will be substantially improved. Guided by this concept, the advances of nanocatalysts now enter an era of atomic-level precise control. Single-atom catalysts (denoted as SACs), characterized by atomically dispersed active sites, strikingly show utmost atomic utilization, precisely located metal centers, unique metal-support interactions and identical coordination environments. Such advantages of SACs drastically boost the specific activity per metal atom, and thus provide great potential for achieving superior catalytic activity and selectivity to functionally mimic or even outperform natural enzymes of interest. Although the size of the catalysts does matter, it is not clear whether the guideline of "the smaller, the better" is still correct for developing catalysts at the single-atom scale. Thus, it is clearly a new, urgent issue to address before further extending SACs into biomedical applications, representing an important branch of nanomedicine. This review begins by providing an overview of recent advances of synthesis strategies of SACs, which serve as a basis for the discussion of emerging achievements in improving the enzyme-like catalytic properties at an atomic level. Then, we carefully compare the structures and functions of catalysts at various scales from nanoparticles, nanoclusters, and few-atom clusters to single atoms. Contrary to conventional wisdom, SACs are not the most catalytically active catalysts in specific reactions, especially those requiring multi-site auxiliary activities. After that, we highlight the unique roles of SACs toward biomedical applications. To appreciate these advances, the challenges and prospects in rapidly growing studies of SACs-related catalytic nanomedicine are also discussed in this review.

Functional diagnosis of placenta accreta by intravoxel incoherent motion model diffusion-weighted imaging.

OBJECTIVES: To investigate the diagnostic value of intravoxel incoherent motion (IVIM) DWI for placenta accreta by comparing diffusion and perfusion characteristics of placentas with accreta lesions (APs) with those of normal placentas (NPs). METHODS: Twenty-five pregnant women with AP and 24 with NP underwent 3-T magnetic resonance examinations with IVIM-DWI. The perfusion percentage (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) values were calculated from different ROIs: the entire-plane of the AP (AP-ROI) and NP (NP-ROI) and the implanted (IR-ROI) and non-implanted region (NIR-ROI) of the AP. The AP-ROIs and NP-ROIs were compared using covariance analysis; the IR-ROIs and NIR-ROIs were compared using the Wilcoxon signed-rank test. ROC curves were produced to evaluate the parameters for predicting placenta accreta. RESULTS: The f and D* values for the AP-ROIs ([45.0 ± 7.63]%, [11.64 ± 2.15]mm2/s) were significantly higher than those for the NP-ROIs ([31.85 ± 5.96]%, [9.04 ± 3.13]mm2/s) (both p < 0.05); the IR-ROIs (54.8%, 14.03 mm2/s) were also significantly higher than the NIR-ROIs (37.4%, 11.4 mm2/s) (both p < 0.05). No significant differences were found between the D values of the AP-ROIs and NP-ROIs (p > 0.05) or of the IR-ROIs and NIR-ROIs (p > 0.05). The areas under the curve for f and D* of the ROC curves were 0.93 and 0.79, respectively. CONCLUSIONS: These results suggest that the IVIM parameters f and D* can be used to quantitatively evaluate the higher perfusion of AP when compared with NP. Furthermore, IVIM may be a useful functional diagnostic technique to predict placenta accreta. KEY POINTS: • Intravoxel incoherent motion (IVIM) may be a useful diagnostic technique to quantitatively estimate the perfusion of the placenta. • The perfusion percentage (f) and pseudo-diffusion coefficient (D*) values differed significantly between placentas with accreta lesions and normal placentas. • ROC curves showed that perfusion percentage (f) and pseudo-diffusion coefficient (D*) values could accurately predict placenta accreta.

MR Virtual Endoscopy of the Fetal Limb Anomalies Using Three-Dimensional Fast Imaging Employing Steady-State Acquisition Sequence.

OBJECTIVE: To retrospectively investigate the feasibility of magnetic resonance virtual endoscopy (MRVE) to visualize the normal limbs and limb deformities Methods: MR sequences included two-dimensional (2D) single fast spin-echo sequence and 2D and 3D steady-state procession fast imaging sequences. MRVE reconstruction was retrospectively performed by 2 radiologists in 32 fetuses in 30 pregnant women. The correlation between the radiologists for the virtual endoscopy threshold of MRVE was determined. Image quality and limb segment visibility were independently rated. Area under the receiver operating characteristics curve (AUC) of 2D MRI and MRVE was calculated. RESULTS: The mean virtual endoscopy threshold required for the visualization of the limb was 991.93 ± 12.13 and 991.83 ± 12.26 for 2 radiologists, respectively. The correlation between the radiologists for virtual endoscopy threshold was excellent (r = 0.933). The weighted kappa statistic was 0.96 for the evaluation of image quality of limb segments, indicating excellent interobserver agreement. Compared to that of 2D MRI alone, a higher AUC of 2D MRI with MRVE was achieved in detection of both upper and lower limb deformities (0.91 vs. 0.69 and 0.83 vs. 0.71, respectively). CONCLUSION: MRVE may display normal and abnormal fetal limb orientation and structures from multiple perspectives and provide incremental information for obstetrics.

Engineering a NO-Regulated Nanofluidic Sensor through the Cyclization Reaction Strategy.

Nitric oxide (NO) is known to be a secondary in vivo signaling agent, demonstrating various biological functions through regulating ion flux in channels. Considering the crucial role of NO in vivo, herein, a biomimetic NO-regulated nanofluidic sensor has been fabricated through a cyclization reaction strategy. This nanofluidic sensor exhibited a promising NO selectivity, sensitivity, and non-interference performance in complex matrices. Thus, such a NO-driven nanosensor will be meaningful for scientific researchers to grasp the in vivo functions of NO.

Network pharmacology-based study of the protective mechanism of conciliatory anti-allergic decoction on asthma.

BACKGROUND: This study aimed to explore the underlying anti-asthma pharmacological mechanisms of conciliatory anti-allergic decoction (CAD) with a network pharmacology approach. METHODS: Traditional Chinese medicine related databases were utilized to screen the active ingredients of CAD. Targets of CAD for asthma treatment were also identified based on related databases. The protein-protein interaction network, biological function and KEGG pathway enrichment analysis, and molecular docking of the targets were performed. Furthermore, an asthma mouse model experiment involving HE staining, AB-PAS staining, and ELISA was also performed to assess the anti-asthma effect of CAD. RESULTS: There were 77 active ingredients in CAD, including quercetin, kaempferol, stigmasterol, luteolin, cryptotanshinone, beta-sitosterol, acacetin, naringenin, baicalin, and 48 related targets for asthma treatment, mainly including TNF, IL4, IL5, IL10, IL13 and IFN-γ, were identified with ideal molecular docking binding scores by network pharmacology analysis. KEGG pathway analysis revealed that these targets were directly involved in the asthma pathway, Th1 and Th2 cell differentiation, and signaling pathways correlated with asthma (NF-κB, IL17, T cell receptor, TNF, JAK-STAT signaling pathways, etc.). Animal experiments also confirmed that CAD could attenuate inflammatory cell invasion, goblet cell hyperplasia and mucus secretion. The levels of the major targets TNF-α, IL4, IL5, and IL13 can also be regulated by CAD in an asthma mouse model. CONCLUSION: The anti-asthma mechanism of CAD possibly stemmed from the active ingredients targeting asthma-related targets, which are involved in the asthma pathway and signaling pathways to exhibit therapeutic effects.

Dual T1 and T2 weighted magnetic resonance imaging based on Gd3+ loaded bioinspired melanin dots.

In this report, a novel T1/T2 dual modal nanoprobe based on highly efficient and bioinspired melanin dots (M-dots) with directly loading gadolinium (Gd-M-dots) for magnetic resonance imaging (MRI) is described. In vitro and in vivo investigations have revealed that Gd-M-dots showed nontoxicity and good biocompatibilitity. Gd-M-dots relaxivity values on 3 T were determined to be r1 = 23.4 and r2 = 123.3 mM-1 s-1, which were much higher than both Gd-DTPA (r1 = 5.1, r2 = 6.2 mM-1 s-1) and Fe-M-dots (r1 = 1.2, r2 = 2.1 mM-1 s-1). For in vivo MRI, after injection of Gd-M-dots, simultaneous T1 and T2 contrast enhancement have been observed in the MRI of mice abdomen and mice bearing U87MG tumors. Furthermore, all the veins showed high signal intensity on T1-weighted MRI and remained for 2 h. Overall, in vitro and in vivo studies indicate that Gd-M-dot with high r1 relaxivity and r2 relaxivity has high potential to be a promising nanoprobe for MR venography and molecular imaging.

Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.

Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.

Speeding up PET/MR for cancer staging of children and young adults.

OBJECTIVE: Combining 18F-FDG PET with whole-body MR for paediatric cancer staging is practically feasible if imaging protocols can be streamlined. We compared 18F-FDG PET/STIR with accelerated 18F-FDG PET/FSPGR for whole-body tumour imaging in children and young adults. METHODS: Thirty-three children and young adults (17.5 ± 5.5 years, range 10-30) with malignant lymphoma or sarcoma underwent a 18F-FDG PET staging examination, followed by ferumoxytol-enhanced STIR and FSPGR whole-body MR. 18F-FDG PET scans were fused with MR data and the number and location of tumours on each integrated examination were determined. Histopathology and follow-up imaging served as standard of reference. The agreement of each MR sequence with the reference and whole-body imaging times were compared using Cohen's kappa coefficient and Student's t-test, respectively. RESULTS: Comparing 18F-FDG PET/FSPGR to 18F-FDG PET/STIR, sensitivities were 99.3 % for both, specificities were statistically equivalent, 99.8 versus 99.9 %, and the agreement with the reference based on Cohen's kappa coefficient was also statistically equivalent, 0.989 versus 0.992. However, the total scan-time for accelerated FSPGR of 19.8 ± 5.3 minutes was significantly shorter compared to 29.0 ± 7.6 minutes for STIR (p = 0.001). CONCLUSION: F-FDG PET/FSPGR demonstrated equivalent sensitivities and specificities for cancer staging compared to 18F-FDG PET/STIR, but could be acquired with shorter acquisition time. KEY POINTS: • Breath-hold FSPGR sequences shorten the data acquisition time for whole-body MR and PET/MR. • Ferumoxytol provides long-lasting vascular contrast for whole-body MR and PET/MR. • 18 F-FDG PET/FSPGR data provided equal sensitivity and specificity for cancer staging compared to 18 F-FDG PET/STIR.

Assessment of apparent diffusion coefficient of normal fetal brain development from gestational age week 24 up to term age: a preliminary study.

OBJECTIVES: This study was designed to investigate the feasibility of apparent diffusion coefficient (ADC) values in evaluating normal fetal brain development from gestational week 24 up to term age. METHODS: Diffusion-weighted imaging (DWI) was performed on 40 normal fetuses (with normal results on sonography and normal fetal MRI results), with two b-values of 0 and 600 s/mm² in the three (x, y, z) orthogonal axes. Ten regions of interest (ROIs) were manually placed symmetrically in the bilateral frontal white matter (FWM), occipital white matter (OWM), thalamus (THAL), basal ganglia (BG), and cerebellar hemispheres (CH). ADC values of the ten ROIs in all subjects were measured by two radiologists independently. One-way ANOVA was used to calculate the differences among the five regions in the fetal brain and linear regression analysis was used to evaluate the correlation between ADC values and gestational age (GA). p < 0.05 was considered significantly different. RESULTS: Mean GA was 31.3 ± 3.9 (range 24-41) weeks. The overall mean ADC values (× 10⁻6 mm²/s) of the fetuses were 1,800 ± 214 (FWM), 1,400 ± 100 (BG), 1,300 ± 126 (THAL), 1,700 ± 133 (OWM) and 1,400 ± 155 (CH), respectively. The ADC value of BG was not significantly different from those of THAL and CH, while the other four ROIs had significant differences with each other. The ADC values of BG, THAL, OWM and CH had strong negative correlations with increasing GA (R were -0.568, -0.716, -0.830 and -0.700, respectively, all p < 0.01), OWM declined fastest with GA, followed by CH and THAL, the slowest being BG. The ADC value of FWM had no significant change with GA (p = 0.366). CONCLUSIONS: The measurement of ADC values is feasible to evaluate fetal brain development with high reliability and reproducibility.

Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism.

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

Response of food waste anaerobic digestion to the dimensions of micron-biochar under 30 g VS/L organic loading rate: Focus on gas production and microbial community structure.

Biochar modification is an effective approach to enhance its ability to promote anaerobic digestion (AD). Focusing on the physical properties of biochar, the impact of different particle sizes of biochar on AD of food waste (FW) at high organic loading rate (OLR) was investigated. Four biochar with different sizes (40-200 mesh) were prepared and used in AD systems at OLR 30 g VS/L. The research results found that biochar with a volume particle size of 102 µm (RBC-P140) had top-performance in promoting cumulative methane production, increasing by 13.20% compared to the control group. The analysis results of the variety in volatile acids and alkalinity in the system did not show a correlation with the size of biochar, but small size has the potential to improve the environmental tolerance of the system to high acidity. Microbial community analysis showed that the abundance of aceticlastic methanogen and the composition of zoogloea were optimized through relatively small-sized biochar. Through revealing the effect of biochar particle size on AD system at high OLR, this work provided theoretical guidance for regulating fermentation systems using biochar.

Melittin and phospholipase A2: Promising anti-cancer candidates from bee venom.

As the research on cancer-related treatment deepens, integrating traditional therapies with emerging interventions reveals new therapeutic possibilities. Melittin and phospholipase A2, the primary anti-cancer components of bee venom, are currently gaining increasing attention. This article reviews the various formulations of melittin in cancer therapy and its potential applications in clinical treatments. The reviewed formulations include melittin analogs, hydrogels, adenoviruses, fusion toxins, fusion peptides/proteins, conjugates, liposomes, and nanoparticles. The article also explored the collaborative therapeutic effects of melittin with natural products, synthetic drugs, radiotherapy, and gene expression regulatory strategies. Phospholipase A2 plays a key role in bee venom anti-cancer strategy due to its unique biological activity. Using an extensive literature review and the latest scientific results, this paper explores the current state and challenges of this field, with the aim to provide new perspectives that guide future research and potential clinical applications. This will further promote the application of bee venom in cancer therapy.

Porcine TLR8 signaling and its anti-infection function are disturbed by immune checkpoint receptor TIM-3 via inhibition of P13K-AKT pathway.

Toll-like receptor 8 (TLR8), an important innate immune receptor recognizing single stranded RNA and the antiviral imidazoquinoline compounds, can activate intracellular signaling pathway and produce an inflammatory response to kill and eliminate pathogens. However, the molecular regulation mechanisms of TLR8 signaling and its anti-infection activity are not fully elucidated. Our previous transcriptome analysis of porcine TLR8 (pTLR8) signaling suggested the immune checkpoint receptor TIM-3 as the potential regulator for pTLR8. Here we investigated TIM-3 in the regulation of pTLR8 signaling and its anti-infection activity. Our results showed that porcine TIM-3 is upregulated by pTLR8 signaling and TIM-3 inhibits pTLR8 signaling activity in a negative feedback way. Accordingly, TIM-3 disturbs pTLR8 mediated anti-bacterial and anti-viral activity. Mechanistically, TIM-3 suppresses PI3K-AKT pathway by inhibiting the TLR8-PI3K p85 interaction and subsequent AKT phosphorylation which is essential for TLR8 signaling and anti-infection activity. Therefore, our study reveals new insights into innate immune TLR8 signaling and its anti-infection function.

Pectic polysaccharides from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects in vitro.

Two pectic polysaccharides (WLBP-A3-c and WPOP-A-c) were isolated from traditional Chinese medicines Lilium brownii and Polygonatum odoratum, respectively. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicated that both WLBP-A3-c (59 kDa) and WPOP-A-c (33 kDa) contained homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains, with mass ratios of 76.0: 17.2:6.8 and 76.8:10.6:12.6, respectively. Two RG-I domains WLBP-A3-c-DE1 and WPOP-A-c-DE1, correspondingly obtained from WLBP-A3-c and WPOP-A-c by enzymatic hydrolysis, were composed of repeating units of [→2)-α-L-Rhap-(1 â†’ 4)-α-D-GalpA-(1→] with highly branched neutral sugar side chains at the O-4 position of Rhap, which contained arabinan, galactan, arabinogalactan I and II (AG-I and AG-II) side chains in different proportions. By comparison, WPOP-A-c exhibited higher scavenging effects against DPPH, ABTS and hydroxy radicals than WLBP-A3-c, probably because WPOP-A-c had higher contents of GalA residues and HG domains and lower molecular weight. Among three domains of WPOP-A-c, HG domain possessed the strongest activity in decreasing ROS production and promoting SOD activity, resulting in the effective protection of HepG2 cells against H2O2-induced oxidative stress. Our study provides evidence that pectins rich in HG domains from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects, which hold potential for the application in the field of healthcare products.

A novel urokinase plasminogen activator receptor-targeted peptide-based probe for in-vivo molecular imaging of glioblastoma.

AIM: The urokinase plasminogen activator receptor (uPAR) is a promising biomarker for cancer diagnosis and therapy. We herein fabricated a new type of uPAR-targeted imaging probe Al18F-NOTA-VC and preliminarily evaluated its potential application in PET imaging of the glioma model in vivo. METHODS: Peptide VC was synthesized and identified by MALDI-TOF-MS. The IC50 between VC/precursor NOTA-VC and uPAR was then determined before the synthesis and purification of Al18F-NOTA-VC, followed by further studies of in-vitro properties of Al18F-NOTA-VC. Meanwhile, the AE105-based probe followed a similar procedure in-vitro test. Finally, the PET imaging properties, including uPAR-targeting ability and the metabolism of Al18F-NOTA-VC, were investigated. RESULTS: The VC and NOTA-VC were obtained successfully and demonstrated a good affinity with uPAR. Followed by Al18F labeling successfully, excellent properties, including the serum stability, water solubility, and specificity of Al18F-NOTA-VC, were obtained in-vitro test compared with AE105 based probe. An excellent tumor uptake and renal excretion data of Al18F-NOTA-VC were acquired from in-vivo U87MG tumor model PET imaging, consistent with the subsequent biodistribution study. CONCLUSION: In addition to the excellent specificity and high tumor/normal tissue contrast for uPAR-targeted PET imaging of U87MG tumor, Al18F-NOTA-VC possessed promising clearance ability by renal system route. These excellent properties facilitated Al18F-NOTA-VC to be a promising imaging agent for uPAR high-expressing tumors and, thus, provided a paradigm for developing peptide-based probes for uPAR-associated disease diagnosis.

Determination of Paraquat in Arabidopsis Tissues and Protoplasts by UHPLC-MS/MS.

Paraquat is a cost-effective herbicide, widely used in many countries, that can induce severe oxidative stress in photosynthetic tissues. Studying plant herbicide resistance or antioxidant stress mechanisms requires determining the cellular paraquat level when plants are treated by paraquat. The traditional isotopic labeling method has the potential risk to cause problems to both human health and the environment. For radioisotope manipulation, special operation spaces and strict environmental inspection are also required. In addition, the radiolabeled paraquat is increasingly hard to buy due to the extended production cycle. Here, we describe a nonradioactive method to determine the paraquat level in a small number of Arabidopsis tissues or protoplasts, using a high resolution ultra-high-performance liquid chromatography (UHPLC)-mass spectrometry (MS)/MS method. This method is highly selective and sensitive, and more environmentally compatible and technically feasible than the isotope detection method.

Accelerated three-dimensional susceptibility weighted imaging of the whole spine of fetus at 3T.

OBJECTIVES: To investigate the image quality and capability of generalized auto-calibrating partially parallel acquisition (GRAPPA) accelerated Three-dimensional (3D) susceptibility weighted imaging (SWI) of the whole spine at 3T. METHODS: A total of 37 pregnant women (gestation age 22 to 39 weeks, average 29 ± 3 weeks) with suspected fetal vertebral anomalies by ultrasound (US) screening underwent 3.0T MR imaging with 3D SWI, conventional two-dimensional (2D) half-flourier acquisition single-shot turbo spin-echo (HASTE) and 3D true fast imaging with steady-state precession (True FISP). The acquisition time of each protocol was recorded. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were determined in representative interest regions of fetal thoracic vertebrae and compared among three pulse sequences. Two radiologists rated image quality independently in random order on a 5-point scale. Kappa coefficients were computed to assess inter-observer reliability. Receiver operating characteristic curves were generated, and the area under the curve (AUC) was used to compare the diagnostic performance of each protocol in vertebral deformities. RESULTS: The acquisition time was 15 s for 3D-SWI and 17 s for 3D True FISP, significantly shorter than conventional HASTE (37 s; both P < 0.01). Of the three protocols, The SNR was highest on 3D True FISP, while the CNR was highest on 3D SWI. Visualization of all segments of the whole spine by 3D SWI was comparable with 3D True FISP. In contrast, 3D SWI and 3D True FISP depicted cervical and sacrococcygeal vertebrae better than HASTE. The weighted kappa statistic was 0.70-0.89 to evaluate the image quality of all segments of the whole spine, indicating good to excellent interobserver agreement. 3D SWI had the highest diagnostic performance for detecting fetal vertebral anomalies (AUC = 0.92). CONCLUSIONS: 3D-SWI is feasible for improved visualization of the whole fetal vertebral column and its congenital malformations with adequate image quality and high accuracy, thereby providing a supplementary method to conventional MR imaging.