SENP3 mediates the activation of the Wnt/ß-catenin signaling pathway to accelerate the growth and metastasis of oesophagal squamous cell carcinoma in mice.

As a common malignant tumor, esophageal squamous cell carcinoma (ESCC) is occasionally seen in clinical practice. This type of disease has low incidence rate and mortality. The post-translational modification of small ubiquitin like modifiers (SUMO) can play a crucial role in regulating protein function, and can significantly impact the occurrence and development of diseases. SUMO-specific peptidase (SENP) affects cell activity by regulating the biological function of SUMO. SENP3 belongs to the SENP family, and available data indicate that many malignancies are associated with SENPs, it is currently unclear its role in ESCC. This study indicates that there is a high level of SENP3 expression in ESCC tumor cells. If the expression level of this gene is high, it can have a significant impact on ESCC cell lines and affect physiological activities such as invasion of KYSE170 cells. If the gene is knocked out, this situation will not occur. There is also research data indicating that this gene can effectively activate related signaling pathways, thereby promoting the physiological activities of malignant tumor cells. In a nude mouse xenograft tumor model, KYSE170 cells with SENP3 expression knockdown induced a smaller volume and weight of tumor tissue. Therefore, it can be clearly stated that SENP3 can enable Wnt/ ß- The catenin signaling pathway is stimulated, which in turn affects the physiological activities of ESCC cells, including the invasion process. The results of this article lay the foundation for clinical staff to carry out clinical management.

Plaque Evolution and Vessel Wall Remodeling of Intracranial Arteries: A Prospective, Longitudinal Vessel Wall MRI Study.

BACKGROUND: Progression of intracranial atherosclerotic disease (ICAD) is associated with ischemic stroke events and can be quantified with three-dimensional (3D) intracranial vessel wall (IVW) MRI. However, longitudinal 3D IVW studies are limited and ICAD evolution remains relatively unknown. PURPOSE: To evaluate ICAD changes longitudinally and to characterize the imaging patterns of atherosclerotic plaque evolution. STUDY TYPE: Prospective. POPULATION: 37 patients (69 ± 12 years old, 12 females) with angiography confirmed ICAD. FIELD STRENGTH/SEQUENCE: 3.0T/3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each patient underwent baseline and 1-year follow-up IVW. Then, IVW data from both time points were jointly preprocessed using a multitime point, multicontrast, and multiplanar viewing workflow (known as MOCHA). Lumen and outer wall of plaques were traced and measured, and plaques were then categorized into progression, stable, and regression groups based on changes in plaque wall thickness. Patient demographic and clinical data were collected. Culprit plaques were identified based on cerebral ischemic infarcts. STATISTICAL TESTS: Generalized estimating equations-based linear and logistic regressions were used to assess associations between vascular risk factors, medications, luminal stenosis, IVW plaque imaging features, and longitudinal changes. A two-sided P-value<0.05 was considered statistically significant. RESULTS: Diabetes was significantly associated with ICAD progression, resulting in 6.6% decrease in lumen area and 6.7% increase in wall thickness at 1-year follow-up. After accounting for arterial segments, baseline contrast enhancement predicted plaque progression (odds ratio = 3.61). Culprit plaques experienced an average luminal expansion of 10.9% after 1 year. 74% of the plaques remained stable during follow-up. The regression group (18 plaques) showed significant increase in minimum lumen area (from 7.4 to 8.3 mm2), while the progression group (13 plaques) showed significant decrease in minimum lumen area (from 5.4 to 4.3 mm2). DATA CONCLUSION: Longitudinal 3D IVW showed ICAD remodeling on the lumen side. Culprit plaques demonstrated longitudinal luminal expansion compared with their non-culprit counterparts. Baseline plaque contrast enhancement and diabetes mellitus were found to be significantly associated with ICAD changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

When transfusion causes a splitting headache: A case report and rapid review of transfusion-associated reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare and understudied transfusion reaction most commonly seen in adult females after correction of chronic, severe anemia. Transfusion-associated RCVS (TA-RCVS) typically presents with thunderclap headaches and one or more systemic (hypertension, nausea/vomiting) or neurologic (seizure, stroke, visual changes) symptoms within a week after red blood cell transfusion. Treatment of RCVS is based on blood pressure control; a recent study suggested that early use of nimodipine could shorten the disease course.

Syphilis susceptibility factors atlas: A wide-angled Mendelian randomization study.

OBJECTIVE: The pathogenic mechanisms of syphilis and the host defense mechanisms against syphilis remain poorly understood. Exploration of the susceptibility factors of syphilis may provide crucial clues for unraveling its underlying mechanisms. METHODS: A two-sample Mendelian Randomization framework was utilized, and the inverse-variance weighted method was used as the main analysis. All data was sourced from Genome-wide association studies datasets from 2015 to 2022 in Europe, and all participants were of European descent. Only summary-level statistics were used. Sensitivity analyses were conducted to evaluate the heterogeneity and pleiotropy of the datasets. RESULTS: Our study established 18 exposure factors (12 risk factors and 6 protective factors) for syphilis susceptibility. Twelve factors encompassing body mass index, waist circumference, darker natural skin, cooked vegetable intake, processed meat intake, diabetes mellitus, glucose regulation disorders, gout, autoimmune diseases, rheumatoid arthritis, diverticulitis, and longer menstrual cycles were found to increase susceptibility to syphilis. In contrast, 6 factors including easier skin tanning, blonde natural hair color, irritability, higher neuroticism scores, extended sleep duration, and delayed age at first sexual intercourse were connected to a reduced risk of syphilis infection (all P < 0.05). CONCLUSIONS: This study identified 18 influencing factors of syphilis susceptibility. These findings offered novel insights for further probing into the underlying pathogenic mechanisms of syphilis and underscored the importance of multifaceted prevention strategies against syphilis.

Synthesis of S(IV)-Stereogenic Chiral Thio-Oxazolidinones via Palladium-Catalyzed Asymmetric [3+2] Annulations.

Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed.

Using signal-to-cutoff ratios of HIV screening assay to predict HIV infection.

BACKGROUND: The sensitivity of HIV screening assays often leads to a high rate of false-positive results, requiring retests and confirmatory tests. This study aimed to analyze the capability of signal-to-cutoff (S/CO) ratios of HIV screening assay to predict HIV infection. METHODS: A retrospective study on the HIV screening-positive population was performed at Zhongshan Hospital, Xiamen University, the correlation between HIV screening assay S/CO ratios and HIV infection was assessed, and plotted Receiver Operating Characteristic (ROC) curves were generated to establish the optimal cutoff value for predicting HIV infection. RESULTS: Out of 396,679 patients, 836 were confirmed to be HIV-infected, with an HIV prevalence of 0.21%. The median S/CO ratios in HIV infection were significantly higher than that in non-HIV infection (296.9 vs. 2.41, P < 0.001). The rate of confirmed HIV infection was increased with higher S/CO ratios in the screening assay. The ROC curve based on the HIV screening assay S/CO ratio achieved a sensitivity of 93.78% and a specificity of 93.12% with an optimal cutoff value of 14.09. The area under the ROC curve was 0.9612. Further analysis of the ROC curve indicated that the S/CO ratio thresholds yielding positive predictive values of 99%, 99.5%, and 100% for HIV infection were 26.25, 285.7, and 354.5, respectively. CONCLUSION: Using HIV screening assay S/CO ratio to predict HIV infection can largely reduce necessitating retests and confirmatory tests. Incorporating the S/CO ratio into HIV testing algorithms can have significant implications for medical and public health practices.

Serum procalcitonin, C-reactive protein, and neutrophil gelatinase-associated lipocalin in early diagnosis of acute kidney injury after upper urinary tract calculi.

Objective: To investigate the value of serum procalcitonin(PCT), C-reactive protein(CRP), and neutrophil gelatinase-associated lipocalin(NGAL) in the early diagnosis of acute kidney injury(AKI) after upper urinary tract calculi(UUTC). Methods: The clinical data of 86 patients who underwent UUTC surgery in our hospital from March 2020 to April 2021 were analyzed retrospectively(Approval number: 20211205L, Date: 2021-12-21). Patients were divided into an AKI group (AKI≥7 days after the operation) and a Non-AKI group. PCT, CRP, and NGAL concentrations were compared before and two hours after the operation. Multivariate logistic regression analysis was used to identify risk factors affecting the early occurrence of AKI post-operation. The receiver operating characteristic curve evaluated PCT, CRP, and NGAL in the early AKI diagnosis. Results: A total of 86 patients (30 with AKI and 56 with Non-AKI) were included. Kidney injury molecule-1(KIM-1) and urinary microalbumin(mAlb) concentrations were significantly higher in the AKI group (P<0.05). PCT, CRP, and NGAL concentrations were significantly higher two hours after the operation than before the operation (P<0.05). KIM-1 levels and elevated PCT, CRP and NGAL concentrations affected the establishment of AKI after UUTC. The sensitivity of PCT, CRP, and NGAL in evaluating AKI after UUTC were 81.17%, 84.42%, and 79.02%; the specificity was 62.31%, 71.48%, and 73.32%; and the AUC was 0.812, 0.885 and 0.804 respectively. Conclusions: PCT, CRP, and NGAL concentrations in patients with AKI after UUTC were significantly increased two hours after the operation, which can be used for the early diagnosis of AKI after UUTC operation.

Research Progress on Machine Learning Assisted Non-Targeted Screening Strategy for Identification of Fentanyl Analogs.

In recent years, the types and quantities of fentanyl analogs have increased rapidly. It has become a hotspot in the illicit drug control field of how to quickly identify novel fentanyl analogs and to shorten the blank regulatory period. At present, the identification methods of fentanyl analogs that have been developed mostly rely on reference materials to target fentanyl analogs or their metabolites with known chemical structures, but these methods face challenges when analyzing new compounds with unknown structures. In recent years, emerging machine learning technology can quickly and automatically extract valuable features from massive data, which provides inspiration for the non-targeted screening of fentanyl analogs. For example, the wide application of instruments like Raman spectroscopy, nuclear magnetic resonance spectroscopy, high resolution mass spectrometry, and other instruments can maximize the mining of the characteristic data related to fentanyl analogs in samples. Combining this data with an appropriate machine learning model, researchers may create a variety of high-performance non-targeted fentanyl identification methods. This paper reviews the recent research on the application of machine learning assisted non-targeted screening strategy for the identification of fentanyl analogs, and looks forward to the future development trend in this field.

Structural Analysis and Characterization of 4-F-α-PVP Analog 4-F-3-Methyl-α- PVP Hydrochloride.

OBJECTIVES: To identify 1-(4-fluorophenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-α-PVP) analog 1-(4-fluoro-3-methyl phenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-3-Methyl-α-PVP) hydrochloride without reference substance. METHODS: The direct-injection electron ionization-mass spectrometry (EI-MS), GC-MS, electrospray ionization-high resolution mass spectrometry (ESI-HRMS), ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UPLC-HRMS/MS), nuclear magnetic resonance (NMR), ion chromatography and Fourier transform infrared spectroscopy (FTIR) were integrated utilized to achieve the structural analysis and characterization of the unknown compound in the sample, and the cleavage mechanism of the fragment ions was deduced by EI-MS and UPLC-HRMS/MS. RESULTS: By analyzing the direct-injection EI-MS, GC-MS, ESI-HRMS and UPLC-HRMS/MS of the compound in the samples, it was concluded that the unknown compound was a structural analog of 4-F-α-PVP, possibly with one more methyl group in the benzene ring. According to the analysis results of 1H-NMR and 13C-NMR, it was further proved that the methyl group is located at the 3-position of the benzene ring. Since the actual number of hydrogen in 1H-NMR analysis was one more than 4-F-3-Methyl-α-PVP neutral molecule, it was inferred that the compound existed in the form of salt. Ion chromatography analysis results showed that the compound contained chlorine anion (content 11.14%-11.16%), with the structural analysis of main functional group information by FTIR, the unknown compound was finally determined to be 4-F-3-Methyl-α-PVP hydrochloride. CONCLUSIONS: A comprehensive method using EI-MS, GC-MS, ESI-HRMS, UPLC-HRMS/MS, NMR, ion chromatography and FTIR to identify 4-F-3-Methyl-α-PVP hydrochloride in samples is established, which will be helpful for the forensic science laboratory to identify this compound or other analog compounds.

Chloramine-T-Enabled Mass Spectrometric Analysis of C═C Isomers of Unsaturated Fatty Acids and Phosphatidylcholines in Human Thyroids.

Specific locations of carbon-carbon double bonds (C═C) in lipids often play an essential role in biological processes, and there has been a booming development in C═C composition analysis by mass spectrometry. However, a universal derivatization and fragmentation pattern for the annotation of C═C positions in lipids is still challenging and attractive. To expand this field in lipidomics, a flexible and convenient N-tosylaziridination method was developed, with high derivatization efficiency, sensitivity, and specificity. The derivatization was very fast (15 s), and C═C numbers as well as locations could be pinpointed specifically in tandem mass spectra. By qualitative and quantitative studies of paratumor and tumor thyroid tissues of human beings, the total content of unsaturated fatty acids was suggested to be increased in tumor tissues, and good correlations in and between lysophosphatidylcholines and phosphatidylcholines were revealed by Spearman analysis. Further studies of C═C isomers showed that n-6/n-3 ratios were closely associated with human thyroid tumorigenesis, and high ratios of n-6/n-3 isomers seemed to suffer a high risk of carcinogenesis. Other isomers were not very representative; however, C═C in n-9/n-7 could also be significant for oncology research. Generally, it is supposed that both total amounts and C═C isomer ratios were related to cancer, and N-tosylaziridine derivatization could provide an alternative strategy for the C═C isomer study of disease models.

Analysis of the Amine Submetabolome Using Novel Isotope-Coded Pyrylium Salt Derivatization and LC-MS: Herbs and Cancer Tissues as Cases.

The amine submetabolome, including amino acids (AAs) and biogenic amines (BAs), is a class of small molecular compounds exhibiting important physiological activities. Here, a new pyrylium salt named 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate ([d0]-DMMIC) with stable isotope-labeled reagents ([d3]-/[d6]-DMMIC) was designed and synthesized for amino compounds. [d0]-/[d3]-/[d6]-DMMIC-derivatized had a charged tag and formed a set of molecular ions with an increase of 3.02 m/z and the characteristic fragment ions of m/z 204.1:207.1:210.1. When DMMIC coupled with liquid chromatography-mass spectrometry (LC-MS), a systematic methodology evaluation for quantitation proved to have good linearity (R2 between 0.9904 and 0.9998), precision (interday: 2.2-21.9%; intraday: 1.0-19.7%), and accuracy (recovery: 71.8-108.8%) through the test AAs. Finally, the methods based on DMMIC and LC-MS demonstrated the advantaged application by the nontargeted screening of BAs in a common medicinal herb Senecio scandens and an analysis of metabolic differences among the amine submetabolomes between the carcinoma and paracarcinoma tissues of esophageal squamous cell carcinoma (ESCC). A total of 20 BA candidates were discovered in S. scandens as well as the finding of 13 amine metabolites might be the highest-potential differential metabolites in ESCC. The results showed the ability of DMMIC coupled with LC-MS to analyze the amine submetabolome in herbs and clinical tissues.

Built-In Stable Lithiophilic Sites in 3D Current Collectors for Dendrite Free Li Metal Electrode.

Stable lithiophilic sites in 3D current collectors are the key to guiding the uniform Li deposition and thus suppressing the Li dendrite growth, but such sites created by the conventional surface decoration method are easy to be consumed along with cycling. In this work, carbon fiber (CF)-based 3D porous networks with built-in lithiophilic sites that are stable upon cycling are demonstrated. Such heterostructured architecture is constructed by the introduction of zeolitic imidazolate framework-8-based nanoparticles during the formation of the 3D fibrous carbonaceous network and the following annealing. The introduced Zn species are found to be re-distributed along the entire individual CF in the 3D network, and function as lithiophilic sites that favor the homogenous lithium nucleation and growth. The 3D network also presents a multi-scale porous structure that improves the space utilization of the host. The corresponding symmetric cells adopting such 3D anode demonstrate excellent cycling performance, especially at a high rate (300 cycles at 10 mA cm-2 with a capacity of 5 mA h cm-2 ). A full cell with LiFePO4 cathode shows a capacity retention of 98% after cycling at 1C for 300 cycles. This method provides an effective design strategy for 3D hosting electrodes in dendrite-free alkali metal anode applications.

ESR1 mediates estrogen-induced feminization of genetic male Chinese soft-shelled turtle†.

Exogenous estrogen have shown their feminization abilities during the specific sex differentiation period in several reptiles. However, the specific regulatory mechanism and downstream regulatory genes of estrogen remain elusive. In the present study, 17ß-estradiol (E2), as well as drugs of specific antagonists and/or agonists of estrogen receptors, were employed to figure out the molecular pathway involved in the E2-induced feminization in Chinese soft-shelled turtles, an important aquaculture species in China. E2 treatment led to typical female characteristics in the gonads of ZZ individuals, including thickened outer cortex containing a number of germ cells and degenerated medullary cords, as well as the disappearance of male marker SOX9, and the ectopic expression of ovarian regulator FOXL2 at the embryonic developmental stage 27 and 1 month after hatching. The specific ESR1 antagonist or a combination of three estrogen receptor antagonists could block the sex reversal of ZZ individuals induced by estrogen. In addition, specific activation of ESR1 by agonist also led to the feminization of ZZ gonads, which was similar to the effect of estrogen treatment. Furthermore, transcriptome data showed that the expression level of FOXL2 was significantly upregulated, whereas mRNA levels of DMRT1, SOX9, and AMH were downregulated after estrogen treatment. Taken together, our results indicated that E2 induced the feminization of ZZ Chinese soft-shelled turtles via ESR1, and decrease of male genes DMRT1, SOX9, and AMH and increase of ovarian development regulator FOXL2 might be responsible for the initiation of E2-induced feminization.

Multi-Planar, Multi-Contrast and Multi-Time Point Analysis Tool (MOCHA) for Intracranial Vessel Wall Characterization.

BACKGROUND: Three-dimensional (3D) intracranial vessel wall (IVW) magnetic resonance imaging can reliably image intracranial atherosclerotic disease (ICAD). However, an integrated, streamlined, and optimized workflow for IVW analysis to provide qualitative and quantitative measurements is lacking. PURPOSE: To propose and evaluate an image analysis pipeline (MOCHA) that can register multicontrast and multitime point 3D IVW for multiplanar review and quantitative plaque characterization. STUDY TYPE: Retrospective. POPULATION: A total of 11 subjects with ICAD (68 ± 10 years old, 6 males). FIELD STRENGTH/SEQUENCE: A 3.0 T, 3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each participant underwent two IVW sessions within 2 weeks. Scan and rescan IVW images were preprocessed using MOCHA. The presence of atherosclerotic lesions was identified in different intracranial arterial segments by two readers (GC and JS, 12 years of vascular MR imaging experience each) following an established review protocol to reach consensus on each of the reviews. For all locations with identified plaques, plaque length, lumen and vessel wall areas, maximum and mean wall thickness values, normalized wall index and contrast enhancement ratio were measured. STATISTICAL TESTS: Percent agreement and Cohen's κ were used to test scan-rescan reproducibility of detecting plaques using MOCHA. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate scan-rescan reproducibility for plaque morphologic and enhancement measurements. RESULTS: In 150 paired intracranial vessel segments, the overall agreement in plaque detection was 92.7% (κ = 0.822). The ICCs (all ICCs > 0.90) and Bland-Altman plots (no bias observed) indicated excellent scan-rescan reproducibility for all morphologic and enhancement measurements. DATA CONCLUSION: Findings from this study demonstrate that MOCHA provides high scan-rescan reproducibility for identification and quantification of atherosclerosis along multiple intracranial arterial segments and highlight its potential use in characterizing plaque composition and monitoring plaque development. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants.

Androgen receptor (AR) serves as a main therapeutic target for prostate cancer (PCa). However, resistance to anti-androgen therapy (SAT) inevitably occurs. Indomethacin is a nonsteroidal anti-inflammatory drug that exhibits activity against prostate cancer. Recently, we designed and synthesized a series of new indomethacin derivatives (CZ compounds) via Pd (II)-catalyzed synthesis of substituted N-benzoylindole. In this study, we evaluated the antitumor effect of these novel indomethacin derivatives in castration-resistant prostate cancer (CRPC). Upon employing CCK-8 cell viability assays and colony formation assays, we found that these derivatives had high efficacy against CRPC tumor growth in vitro. Among these derivatives, CZ-212-3 exhibited the most potent efficacy against CRPC cell survival and on apoptosis induction. Mechanistically, CZ-212-3 significantly suppressed the expression of AR target gene networks by degrading AR and its variants. Consistently, CZ-212-3 significantly inhibited tumor growth in CRPC cell line-based xenograft and PDX models in vivo. Taken together, the data show that the indomethacin derivative CZ-212-3 significantly inhibited CRPC tumor growth by degrading AR and its variants and could be a promising agent for CRPC therapy.

Inhibition of oocyte maturation by nitric oxide synthase 1 (NOS1) in zebrafish.

It is well-documented that nitric oxide (NO) is an important regulator of oocyte maturation in mammals. Conversely, the function of NO during oocyte maturation has received little attention in nonmammalian vertebrates. NO is produced from L-arginine through the action of the enzyme NO synthase (NOS). Herein, we examined the expression, hormonal regulation, and involvement of NOS in meiotic signaling in zebrafish oocyte maturation. Three types of nos genes, nos1, nos2a, and nos2b, have been identified in zebrafish. We found that the expression of nos1 was highest in the ovary among the three nos genes, with maximal expression in full-grown (FG)-stage follicles during folliculogenesis. In addition, the concentration of NO was reduced during oocyte maturation and this corresponded with the decreased expression of nos1 in the follicular cell layers, suggesting that NOS1-derived NO may be one of the inhibitors of oocyte maturation in zebrafish. This is the first description of nos1 involvement in oocyte maturation in vertebrates. Moreover, the NO donor SNAP (S-nitroso-l-acetyl penicillamine) partially attenuates human chorionic gonadotropin (hCG)- and 17,20ß-P-induced GVBD (germinal vesicle breakdown), perhaps by increasing cGMP levels during oocyte maturation. Finally, our results showed that SNAP and the cGMP analog 8-Br-cGMP inhibited hCG-induced mitogen-activated protein kinase (MAPK) activation, further indicating that NO and cGMP block oocyte maturation in zebrafish.

Characterization of non-stenotic plaques in intracranial arteries with multi-contrast, multi-planar vessel wall image analysis.

OBJECTIVES: Non-stenotic plaques have been observed in intracranial arteries but are less understood compared to those in coronary and carotid arteries. We sought to compare plaque distribution and morphology between stenotic and non-stenotic intracranial plaques with MR vessel wall imaging (VWI) and quantitative image analysis. MATERIALS AND METHODS: Twenty-four patients with intracranial arterial stenosis or luminal irregularity on clinical imaging were scanned with a multi-contrast VWI protocol. Plaques were detected as focal wall thickening on co-registered multiplanar reformats of multi-contrast VWI, with assessment of the location and morphology. TOF-MRA was independently reviewed for any appreciable stenosis using the WAISD criteria. RESULTS: Across 504 arterial segments, a total of 80 plaques were detected, including 23 (29%) with stenosis on TOF-MRA, 56 (70%) without, and 1 (1%) not covered by TOF-MRA. Plaques involving the ICA were more likely to be non-stenotic than those involving other segments (80% versus 55%, p = 0.030) whereas the basilar artery (40%) and PCA (33%) had the lowest proportions of non-stenotic plaques. Maximum wall thickness, indicative of plaque burden, correlated poorly with degree of stenosis (p = 0.10) and overlapped substantially between stenotic and non-stenotic plaques (1.9 [1.5, 2.4] versus 2.0 [1.5, 2.2] mm, p = 0.074). CONCLUSIONS: Intracranial plaques without appreciable stenosis on TOF-MRA represent a large proportion of lesions throughout arterial segments but disproportionately affect the ICA. Morphological characterization of plaques with and without stenosis shows that luminal stenosis is a poor indicator of the underlying burden of intracranial atherosclerosis.

[Regulation of vascular endothelial cell activator expression by tanshinone â ¡_A based on PI3K/Akt signaling pathway].

The present study investigated the regulatory effect of tanshinone Ⅱ_A(TAⅡ_A) on activator expression in human umbilical vein endothelial cells(HUVECs) and the effect on the phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt) signaling pathway in patients with antiphospholipid syndrome(APS). HUVECs cultured in vitro were divided into a medium group, a blank control group, an APS model group, an APS+LY5 group, an APS+LY10 group, an APS+LY20 group, an APS+TAⅡ_A5 group, an APS+TAⅡ_A10 group, an APS+TAⅡ_A20 group, and an APS+TAⅡ_A10+LY10 group. The effects of LY294002 and TAⅡ_A at different concentrations on the secretion of interleukin-6(IL-6), interleukin-8(IL-8), and monocyte chemoattractant protein-1(MCP-1) by HUVECs were investigated. The effects on the mRNA expression of annexin A2(ANXA2), PI3 K, Akt, and E-cadherin(E-cad) were detected by quantitative polymerase chain reaction(qPCR), and Western blot was used to determine the effects on the protein expression of ANXA2, p-PI3 K/PI3 K, p-Akt/Akt, and E-cad. The results revealed that compared with the APS model group, the APS+TAⅡ_A10 group showed statistically reduced IL-6 and MCP-1 and increased IL-8 in a concentration-dependent manner with the increase in TAⅡ_A dose, while the APS+TAⅡ_A10 group showed increased mRNA and protein expression of ANXA2, PI3 K, Akt, and E-cad(P<0.05 or P<0.01) in a concentration-dependent manner with the increase in TAⅡ_A dose. The findings indicated that the serum of APS patients could lead to the decreased mRNA and protein expression levels of ANXA2, PI3 K, Akt, and E-cad in HUVECs, increased secretion of IL-6 and MCP-1, and reduced secretion of IL-8, and activate vascular endothelial cells. In contrast, once the PI3 K/Akt signaling pathway was blocked, the mRNA and protein expression of ANXA2 and E-cad significantly decreased, IL-6 and MCP-1 secretion significantly increased, and IL-8 secretion was significantly reduced. It suggests that TAⅡ_A regulates the activation of vascular endothelial cells in APS patients by activating the PI3 K/Akt signaling pathway.

Chiral Analysis of Lactate during Direct Contact Coculture by Single-Cell On-Probe Enzymatic Dehydrogenation Derivatization: Unraveling Metabolic Changes Caused by d-Lactate.

In vitro noncontact cell-based coculture models are frequently employed to study cell-to-cell communication. However, these models cannot accurately represent the complexity of in vivo signaling. d-Lactate is an unusual metabolite produced and released by cancer cells. The characterization of d-lactate is challenging as it shares the same mass but has much lower amounts compared with l-lactate. Herein, d-α-hydroxy acids were specifically recognized and dehydrogenated by d-α-hydroxy acid dehydrogenase. The dehydrogenation products were rapidly quaternized for enhancement of mass signals. An on-probe enzymatic dehydrogenation-derivatization method was proposed for chiral analysis of α-hydroxy acids at the single-cell level. It is a promising amplification methodology and affords over 3 orders of magnitude signal enhancement. Furthermore, direct contact coculture models were used to precisely mimic the tumor microenvironment and explore the communication between cancer and normal cells. Single-cell mass spectrometry (SCMS) was further applied to easily sample cell extracts and study the differences of the aspects of small molecule metabolism in cocultured cells. On the basis of direct contact coculture SCMS, several differential small molecule metabolites and differences of oxidative stress between cocultured and monocultured normal cells were successfully detected. Additionally, d-lactate was discovered as a valuable differential metabolite with application of the two developed methods. It may account for the cancer-associated metabolic behavior of normal cells. These changes could be relieved after d-lactate metabolism-related drug treatment. This discovery may promote the investigation of d-lactate metabolism, which may provide a novel direction for cancer therapy.

Rapid Characterization of Polymer Materials Using Arc Plasma-Based Dissociation-Mass Spectrometry.

Fingerprinting spectra of polymer materials containing information of monomers' molecular weight and detailed structure, constituents, and sequences were obtained by a direct analytical process using arc plasma-based dissociation (APD)-mass spectrometry. The thermal arc plasma generated using a simple arc discharge device induces the dissociation of the polymeric backbone, producing mass spectra with strong regularity within seconds. The molecular weight of the repeating unit was revealed by equal intervals between peak series and protonated monomer ions in the mass spectra. Meanwhile, lots of secondary fragment ions were produced to provide abundant structural information. For polyethers, it is even possible to decipher (read) the "sequence" directly from their spectra. Polymers composed of isomers or only differing in their initiator moieties were easily distinguished with their characteristic APD mass spectra. The spectra were highly reproducible according to the results of similarity calculation. Unlike pyrolysis mass spectrometry, in the APD device, polymers in liquid, solid, powder, and crude samples can be analyzed directly without any pretreatment, and the regular spectra are easier to interpret. Compared with other direct analytical methods, more structural informative spectra can be acquired owing to the high energy, high temperature, and unique chemical reactivity of arc plasma. Thus, this technique is promising to be a valuable tool in rapid elucidation of polymer materials.