Catalytic Asymmetric Construction of Chiral Amines with Three Nonadjacent Stereocenters via Trifunctional Catalysis.

Pharmaceuticals and biologically active natural products usually contain multiple stereocenters. The development of catalytic asymmetric reactions for the direct construction of complex motifs containing three nonadjacent stereocenters is a particularly important and formidable challenge. In this paper, we report an unprecedented method for the direct asymmetric construction of complex chiral amines with 1,3,5- or 1,3,4-stereocenters from readily available achiral and racemic starting materials. The reaction was made possible by the development of highly efficient chiral ammonium catalysts that serve three distinct functions: promoting efficient kinetic resolution by chiral recognition of racemic electrophiles, promoting asymmetric C-C bond forming reactions by recognizing enantiotropic faces of achiral nucleophiles, and mediating a highly stereoselective protonation of carbanions. Using these trifunctional catalysts, the reaction of imines and tulipane derivatives proceeded in a highly regio-, chemo-, and stereoselective manner to produce synthetically useful yields of complex chiral amines. We believe that trifunctional catalysis can be applied in a variety of asymmetric transformations for the streamlined asymmetric synthesis of complex chiral molecules with multiple stereocenters.

Generating and screening de novo compounds against given targets using ultrafast deep learning models as core components.

Deep learning is an artificial intelligence technique in which models express geometric transformations over multiple levels. This method has shown great promise in various fields, including drug development. The availability of public structure databases prompted the researchers to use generative artificial intelligence models to narrow down their search of the chemical space, a novel approach to chemogenomics and de novo drug development. In this study, we developed a strategy that combined an accelerated LSTM_Chem (long short-term memory for de novo compounds generation), dense fully convolutional neural network (DFCNN), and docking to generate a large number of de novo small molecular chemical compounds for given targets. To demonstrate its efficacy and applicability, six important targets that account for various human disorders were used as test examples. Moreover, using the M protease as a proof-of-concept example, we find that iteratively training with previously selected candidates can significantly increase the chance of obtaining novel compounds with higher and higher predicted binding affinities. In addition, we also check the potential benefit of obtaining reliable final de novo compounds with the help of MD simulation and metadynamics simulation. The generation of de novo compounds and the discovery of binders against various targets proposed here would be a practical and effective approach. Assessing the efficacy of these top de novo compounds with biochemical studies is promising to promote related drug development.

Study on the Design and Performance of a Glove Based on the FBG Array for Hand Posture Sensing.

This study introduces a new wearable fiber-optic sensor glove. The glove utilizes a flexible material, polydimethylsiloxane (PDMS), and a silicone tube to encapsulate fiber Bragg gratings (FBGs). It is employed to enable the self-perception of hand posture, gesture recognition, and the prediction of grasping objects. The investigation employs the Support Vector Machine (SVM) approach for predicting grasping objects. The proposed fiber-optic sensor glove can concurrently monitor the motion of 14 hand joints comprising 5 metacarpophalangeal joints (MCP), 5 proximal interphalangeal joints (PIP), and 4 distal interphalangeal joints (DIP). To expand the measurement range of the sensors, a sinusoidal layout incorporates the FBG array into the glove. The experimental results indicate that the wearable sensing glove can track finger flexion within a range of 0° to 100°, with a modest minimum measurement error (Error) of 0.176° and a minimum standard deviation (SD) of 0.685°. Notably, the glove accurately detects hand gestures in real-time and even forecasts grasping actions. The fiber-optic smart glove technology proposed herein holds promising potential for industrial applications, including object grasping, 3D displays via virtual reality, and human-computer interaction.

Efficacy and safety of sodium oligomannate in the treatment of Alzheimer's disease.

To evaluate the efficacy and safety of sodium oligomannate in the treatment of Alzheimer's disease. Patients with mild-to-moderate AD were randomly divided into three groups, the scores of ADAS-Cog, ADL, CIBIC-plus, NPI and CSDD were evaluated at the 0th, 12th, 24th, 36th and 48th weeks of medication. Comparing the mean scores of each scale in each cycle of each group. Using SPSS21.0 software for measurement data using t test, Chi-square test was used for counting data. A total of 72 patients with AD were included. The difference of CIBIC-plus score at week 12(P=0.007) and 24(P=0.005), ADAS-Cog scores (P=0.01) at week 24 in GV-971 group was statistically significant compared with that in the control group. The CIBIC-plus score at week 24(P=0.01) and week 48 (P=0.04), CSDD scores at week 48(P=0.02) of GV-971 group was statistically significant compared with that of donepezil group. There were 2 cases of adverse reaction of increased stool frequency in GV-971 (5.67%), and 2 cases of adverse reaction of nausea in donepezil group (8.33%), the difference was statistically significant. GV-971 is as effective as donepezil in the treatment of Alzheimer's disease, and may even be better. It has good safety.

Highly Enantioselective O-H Bond Insertion Reaction of α-Alkyl- and α-Alkenyl-α-diazoacetates with Water.

Catalytic asymmetric reactions in which water is a substrate are rare. Enantioselective transition-metal-catalyzed insertion of carbenes into the O-H bond of water can be used to incorporate water into the stereogenic center, but the reported chiral catalysts give good results only when α-aryl-α-diazoesters are used as the carbene precursors. Herein we report the first highly enantioselective O-H bond insertion reactions between water and α-alkyl- and α-alkenyl-α-diazoesters as carbene precursors, with catalysis by a combination of achiral dirhodium complexes and chiral phosphoric acids or chiral phosphoramides. Participation of the phosphoric acids or phosphoramides in the carbene transfer reaction markedly suppressed competing side reactions, such as ß-H migration, carbene dimerization, and olefin isomerization, and thus ensured good yields of the desired products. Fine-tuning of the ester moiety facilitated enantiocontrol of the proton transfer reactions of the enol intermediates and resulted in excellent enantioselectivity. This protocol represents an efficient new method for preparation of multifunctionalized chiral α-alkyl and α-alkenyl hydroxyl esters, which readily undergo various transformations and can thus be used for the synthesis of bioactive compounds. Mechanistic studies revealed that the phosphoric acids and phosphoramides promoted highly enantioselective [1,2]- and [1,3]-proton transfer reactions of the enol intermediates. Maximization of molecular orbital overlap in the transition states of the proton transfer reactions was the original driving force to involve the proton shuttle catalysts in this process.

Highly Enantioselective Copper- and Iron-Catalyzed Intramolecular Cyclopropanation of Indoles.

We report the first intramolecular enantioselective cyclopropanation of indoles, which was accomplished in good to high yield (up to 94%) with excellent enantioselectivity (up to >99.9% ee) by using copper or iron complexes of chiral spiro bisoxazolines as catalysts. This reaction is a straightforward, efficient method for constructing polycyclic compounds with an all-carbon quaternary stereogenic center at the 3-position of the indole skeleton, a core structure shared by numerous natural products and bioactive compounds.

The role of HMGB1-RAGE axis in migration and invasion of hepatocellular carcinoma cell lines.

High mobility group protein box1 (HMGB1) and its receptor-receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells. Furthermore, our data show that rhHMGB1 promotes cellular proliferation, migration, and invasion, and increases the level of nuclear factor kappa B (NF-κB), while administrations of HMGB1-siRNA, RAGE-siRNA, anti-HMGB1 neutralizing antibody, anti-RAGE neutralizing antibody, and sRAGE inhibit cellular proliferation, migration, and invasion. Moreover, we also demonstrate that the expression of NF-кB is inhibited by knockdown of HMGB1 or RAGE. Collectively, these data demonstrate that HMGB1 activates RAGE signaling pathways and induces NF-кB activation to promote cellular proliferation, invasion, and metastasis, in HCC cell lines. Taken together, HMGB1-RAGE axis may become a potential target in HCC therapy.

Rapid detection and quantification of apolipoprotein L1 genetic variants and total levels in plasma by ultra-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Human genetics studies in African Americans have shown a strong correlation between polymorphisms in the ApoL1 gene and chronic kidney disease (CKD). To gain further insight into the etiology of ApoL1-associated kidney diseases, the determination of circulating levels of both wild type as well as ApoL1 variants could be of significant use. To date, antibodies that discriminate between all three ApoL1 variant forms (wild type, G1 and G2) are not available. We aimed to develop a rapid method for detecting and quantifying ApoL1 variants and total levels in plasma. METHODS: Ultra-performance liquid chromatography (UPLC) and tandem mass spectrometry (MS/MS) in multiple-reaction monitoring acquisition mode was used to quantify ApoL1. RESULTS: We demonstrated that it is feasible to detect and quantify ApoL1 variants (wild type, G1 and G2), and total ApoL1 concentrations in plasma. ApoL1 genotypes determined by LC/MS agreed perfectly with the traditional method DNA sequencing for 74 human subjects. The method exhibited at least three orders of linearity with a lower limit of quantification of 10 nM. Moreover, the method can readily be multiplexed for the quantification of a panel of protein markers in a single sample. CONCLUSIONS: The method reported herein obviates the need to perform DNA genotyping of ApoL1 variants, which is of significant value in cases where stored samples are unsuitable for DNA analysis. More importantly, the method could potentially be of use in the early identification of individuals at risk of developing CKD, and for the stratification of patients for treatment with future ApoL1-modifying therapies.

The Effect of Early Time-Restricted Eating vs Later Time-Restricted Eating on Weight Loss and Metabolic Health.

CONTEXT: It remains controversial whether the choice of the daily eating window early or later in time-restricted eating (TRE) intervention (early or later TRE) has different effects on weight loss and metabolic health. OBJECTIVE: A network meta-analysis was performed to evaluate the efficacy between early and later TRE in adults with obesity or overweight. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published until October 16, 2022. We conducted a network meta-analysis to evaluate the efficacy of early and later TRE on body weight and metabolic parameters, including glycemic metabolism, blood pressure, and lipid profiles. RESULTS: Twelve RCTs with 730 obese or overweight adults were included in this meta-analysis. Early TRE and later TRE both elicited moderate reductions in body weight and insulin resistance (IR) (homeostasis model assessment of IR) when compared to non-TRE. Interestingly, early TRE showed more effectiveness than later TRE in improving IR (early vs later TRE: -0.44; 95% CI, -0.86 to -0.02; P < .05), whereas no statistically significant difference was detected in weight loss (early vs later TRE: -0.31 kg; 95% CI, -1.15 to 0.53 kg; P >.05). In addition, early TRE rather than later TRE showed significant benefits in glycemic metabolism and blood pressure when compared to non-TRE. No significant differences between early and later TRE were observed for fasting blood glucose, blood pressure, and lipid profiles. CONCLUSION: This meta-analysis suggests that people may choose early TRE for more effective weight management and metabolic benefits. Nevertheless, further large-scale RCTs are warranted to verify our findings.

Atrial high-rate episodes intensify R2CHA2DS2-VASc score for prognostic stratification in pacemaker patients.

Patients with device detected atrial high-rate episodes (AHRE) have an increased risk of MACE. The R2CHA2DS2-VASc, CHADS2, R2CHADS2 and CHA2DS2-VASc score have been investigated for predicting major adverse cardiovascular events (MACE) in different groups of patients. We aimed to evaluate the R2CHA2DS2-VASc score in combination with AHRE ≥ 6 min for predicting MACE in patients with dual-chamber PPM but no prior atrial fibrillation (AF). We retrospectively enrolled 376 consecutive patients undergoing dual-chamber PPM implantation and no prior AF. The primary endpoint was subsequent MACE. For all patients in the cohort, CHADS2, R2CHADS2, CHA2DS2-VASc, R2CHA2DS2-VASc scores and AHRE ≥ or < 6 min were determined. AHRE was recorded as a heart rate > 175 bpm (Medtronic) or > 200 bpm (Biotronik) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine the independent predictors of MACE. ROC-AUC analysis was performed for CHADS2, R2CHADS2, CHA2DS2-VASc, and R2CHA2DS2-VASc scores and then adding AHRE ≥ 6 min to the four scores. The median age was 77 years, and 107 patients (28.5%) developed AHRE ≥ 6 min. After a median follow-up of 32 months, 46 (12.2%) MACE occurred. Multivariate Cox regression analysis showed that R2CHA2DS2-VASc score (HR, 1.485; 95% CI, 1.212-1.818; p < 0.001) and AHRE ≥ 6 min (HR, 2.125; 95% CI, 1.162-3.887; p = 0.014) were independent predictors for MACE. The optimal R2CHA2DS2-VASc score cutoff value was 4.5 (set at ≥ 5), with the highest Youden index (AUC, 0.770; 95% CI, 0.709-0.831; p < 0.001). ROC-AUC analysis of the four risk scores separately combined with AHRE ≥ 6 min all showed better discriminatory power than the four scores alone (All Z-statistic p < 0.05). In patients with PPM who develop AHRE ≥ 6 min, it is crucial to perform risk assessment with either four scores to further stratify risk for MACE.

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma.

Background: T cell exhaustion (TEX) heterogeneity leads to unfavorable immunotherapeutic responses in patients with cancer. Classification of TEX molecular phenotypes is pivotal to overcoming TEX and improving immunotherapies in the clinical setting. Cuproptosis is a novel form of programmed cell death associated with tumor progression. However, the relation between cuproptosis-related genes (CuRGs) and the different TEX phenotypes has not been investigated in lung adenocarcinoma (LUAD). Methods: Unsupervised hierarchical clustering and principal component analysis (PCA) algorithm were performed to determine CuRGs-related molecular subtypes and scores for patients with LUAD. The tumor immune microenvironment (TIME) landscape in these molecular subtypes and scores was estimated using ESTIMATE and ssGSEA algorithms. Furthermore, TEX characteristics and phenotypes were evaluated in distinct molecular subtypes and scores through GSVA and Spearman correlation analysis. Finally, TIDE scores, immunophenoscore, pRRophetic, GSE78220, and IMvigor210 datasets were employed to appraise the distinguishing capacity of CuRGscore in immunotherapy and pharmacotherapy effectiveness. Results: We identified three CuRGclusters, three geneClusters, and CuRGscore based on 1012 LUAD transcriptional profiles from five datasets. Compared with other molecular subtypes, CuRGcluster B, geneCluster C, and low-CuRGscore group with good prognosis presented fewer TEX characteristics, including immunosuppressive cells infiltration and TEX-associated gene signatures, signal pathways, checkpoint genes, transcription and inflammatory factors. These molecular subtypes were also responsive in distinguishing TEX phenotype in the terminal, GZMK+, and OXPHOS- TEX subtypes, but not the TCF7+ TEX subtype. Notably, copper importer and exporter, SLC31A1 and ATP7B, were remarkably associated with four TEX phenotypes and nine checkpoint genes such as PDCD1, CTLA4, HAVCR2, TIGIT, LAG3, IDO1, SIGLEC7, CD274, PDCD1LG2, indicating that cuproptosis was involved in the development of TEX and immunosuppressive environment in patients with LUAD. Moreover, CuRGscore was significantly related to the TIDE score, immunophenoscore, and terminal TEX score (Spearman R = 0.62, p < 0.001) to effectively predict immunotherapy and drug sensitivity in both training and external validation cohorts. Conclusion: Our study demonstrated the extensive effect of cuproptosis on TEX. CuRGs-related molecular subtypes and scores could illuminate the heterogeneity of TEX phenotype as reliable tools in predicting prognosis and directing more effective immunotherapeutic and chemotherapeutic strategies for patients with LUAD.

Three new constituents from the Tujia ethnomedicine Swertia punicea Hemsl.

Three new constituents: 1,5R-dihydroxy-3,8S-dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3S,4R,16S,17R)-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3-O-ß-D-glucopyranoside (2), and new natural product (S)-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea. Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7, 9 and 14 showed antioxidant activities with IC50 values of 68.9, 50.8 and 48.2 µM, respectively.

Proposed strategies to overcome venous occlusion in the implantation of a cardiac implantable electronic device: A case report and literature review.

This case report describes a successful balloon venoplasty to overcome a total occlusion from the brachiocephalic vein to the superior vena cava in a patient undergoing cardiac resynchronization therapy. It is crucial for implanting physicians to be familiar with strategies to overcome venous occlusion in lead implantation, especially balloon venoplasty, which is an effective and safe approach.

Droplet Manipulation under a Magnetic Field: A Review.

The magnetic manipulation of droplets is one of the emerging magnetofluidic technologies that integrate multiple disciplines, such as electromagnetics, fluid mechanics and so on. The directly driven droplets are mainly composed of ferrofluid or liquid metal. This kind of magnetically induced droplet manipulation provides a remote, wireless and programmable approach beneficial for research and engineering applications, such as drug synthesis, biochemistry, sample preparation in life sciences, biomedicine, tissue engineering, etc. Based on the significant growth in the study of magneto droplet handling achieved over the past decades, further and more profound explorations in this field gained impetus, raising concentrations on the construction of a comprehensive working mechanism and the commercialization of this technology. Current challenges faced are not limited to the design and fabrication of the magnetic field, the material, the acquisition of precise and stable droplet performance, other constraints in processing speed and so on. The rotational devices or systems could give rise to additional issues on bulky appearance, high cost, low reliability, etc. Various magnetically introduced droplet behaviors, such as deformation, displacement, rotation, levitation, splitting and fusion, are mainly introduced in this work, involving the basic theory, functions and working principles.

Comparison of methods of isolating extracellular vesicle microRNA from HepG2 cells for High-throughput sequencing.

Background: Extracellular vesicles (EVs) were reported to participate in various cellular processes based on the biomolecules, particularly microRNAs. Numerous commercial EVs isolation reagents are available. However, whether these reagents are suitable for separating EVs from the culture medium supernatant supernatant of model cell lines, such as HepG2, and whether the isolated products are suitable for High-throughput sequencing remains unclear. Methods: We examined three commonly used EVs isolation kits: the ExoQuick-TC exosome precipitation solution (EQ), Total Exosome Isolation from cell culture medium (EI), and exoEasy Maxi Kit (EM), to isolate EVs from HepG2 cell culture medium supernatants. EVs were identified based on marker proteins, particle size measurements, and electron microscopy analysis. The total amounts of microRNA and microRNA High-throughput sequencing data quality from EVs isolated by each kit were compared. Results: The total amount of EVs' microRNA isolated from the EI and EM groups were higher than that obtained from the EQ group (EQ/EI: p = 0.036, EI/EM: p = 0.024). High-throughput sequencing data quality evaluation showed that the EI group possessed higher quality than those in the EM group. Conclusion: For the cell culture medium from HepG2, EVs' microRNA isolated by EI reagents might be more suitable for High-throughput sequencing applications.

MCP-1 facilitates VEGF production by removing miR-374b-5p blocking of VEGF mRNA translation.

Monocyte chemotactic protein-1 (MCP-1) is known to be able to facilitate vascular endothelial growth factor (VEGF) gene expression, hence promoting vascular hyperpermeability and neovascularization. We show here that a microRNA molecule, miR-374b-5p can target the 3'-untranslated region of the VEGF mRNA, thus preventing VEGF production. Additionally, MCP-1 promotes the acetylation of transcription factor stat3 at Lys685, which facilitates the formation of an ac-stat3-DNA methyltransferase-histone methyltransferase complex (ac-stat3/DNMT1/EZH2) that binds to the promoter of the miR-374b-5p gene. This results in diminished miR-374b-5p expression and enhanced VEGF production. Moreover, treatment of appropriate animal models either with a miR-374b-5p mimicry or with inhibitors of either stat3 acetylation, DNMT1, or EZH2, leads to marked inhibition of MCP-1-promoted neovascularization and tumor growth. These findings indicate that MCP-1 facilitated inhibition of miR-374b-5p gene expression leads to the removal of a block of VEGF mRNA translation by miR-374b-5p. This mechanism could be of importance in the modulation of inflammatory conditions.

Effect of lipoxin A4 on lipopolysaccharide-induced endothelial hyperpermeability.

Excessive oxidative stress, decreased antioxidant capacity, and enhanced cellular calcium levels are initial factors that cause endothelial cell (EC) hyperpermeability, which represents a crucial event in the pathogenesis of pre-eclampsia. Lipoxin A4 (LXA4) strongly attenuated lipopolysaccharide (LPS)-induced hyperpermeability through maintaining the normal expression of VE-cadherin and â-catenin. This effect was mainly mediated by a specific LXA4 receptor. LXA4 could also obviously inhibit LPS-induced elevation of the cellular calcium level and up-regulation of the transient receptor potential protein family C 1, an important calcium channel in ECs. At the same time, LXA4 strongly blocked LPS-triggered reactive oxidative species production, while it promoted the expression of the NF-E2 related factor 2 (Nrf2) protein. Our findings demonstrate that LXA4 could prevent the EC hyperpermeability induced by LPS in human umbilical vein endothelial cells (HUVECs), under which the possible mechanism is through Nrf2 as well as Ca2+-sensitive pathways.

[Effect of lipoxin A(4) on lipopolysaccharide-induced endothelial hyperpermeability in human umbilical vein endothelial cell].

OBJECTIVE: To explore whether lipoxin A(4) (LXA(4))could prevent lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVEC) monolayer hyperpermeability and its possible mechanism. METHODS: Human umbilical cords were obtained from women with normal pregnancy immediately after delivery from Tongji Hospital Affiliated of Tongji Medical College. Primary HUVEC were isolated from umbilical veins and subcultured, then, HUVEC were divided into four groups:control group; LPS group (10 mg/L of LPS); LPS + LXA(4) group(10 mg/L of LPS and 100 nmol/L of LXA(4)); LPS + LXA(4) + BOC-2 group [10 µmol/L of BOC-2, an effective antagonist of formyl peptide receptor like 1 (FPRL-1)]. All expriments were performed after cells were treated for 24 hours. Endothelial permeability was measured by fluorescein isothiocyan-ate labelled bovine serum albumin (FITC-BSA) clearance across the monolayer; tumor necrosis factor α (TNF-α) mRNA and secretion were detected by reverse transcriplase (RT)-PCR and ELISA assay respectively, and nuclear factor κB (NF-κB) protein change was determined by western blot. RESULTS: (1) LPS induced a significant increase in the permeability [Pa value of LPS group was (183.1 ± 1.7)%], while co-administrating with LXA(4) obviously attenuated this LPS-induced hyperpermeability, Pa value of LPS + LXA(4) group was (103.1 ± 2.2)%, LPS + LXA(4) + BOC-2 group was (162.2 ± 2.8)%, control group was 100%, the permeability of HUVEC monolayer was significantly increased by LPS which was (83.1 ± 1.7)% of control (P < 0.01), however, it was notably inhibited by LXA(4) (P < 0.05); the blockade of FPRL-1 could attenuate the effect of LXA(4), that is, there was no difference between the LPS + LXA(4) + BOC-2 group and the LPS group. (2) After treatment with different concentration of LPS(0, 0.1, 1, 10 mg/L), the mRNA expressions of TNF-α were increased (1.11 ± 0.11, 1.27 ± 0.03, 1.60 ± 0.06, 1.82 ± 0.04, respectively), compared with the control group, at the concentration of 1, 10 mg/L LPS, the difference was statistically significant (P < 0.05). (3) The increased levels of NF-κB and inflammatory mediator TNF-α in the LPS group were both inhibited by LXA(4). Levels of NF-κB protein and TNF-α mRNA secretion in LPS treated group (0.53 ± 0.06 and 0.81 ± 0.09, respectively) were both inhibited by LXA(4)(0.19 ± 0.05 and 0.41 ± 0.07, respectively, and both had significant difference, P < 0.05). (4) Levels of TNF-α in HUVEC culture medium of LPS group [(31.94 ± 0.01) ng/L] was significantly higher than the control group [(18.17 ± 0.03) ng/L, P < 0.05], LPS + LXA(4) group [(15.72 ± 0.07) ng/L] was significantly lower than the LPS group (P < 0.05). CONCLUSION: Our findings demonstrated that LXA(4) could prevent the endothelial cell hyperpermeability induced by LPS in HUVEC under which the possible mechanism was through inhibiting the expression of NF-κB and its related cytokines through receptor-dependent.

Eliminating vascular interference from the Spot Sign contributes to predicting hematoma expansion in individuals with spontaneous cerebral hemorrhages.

The computed tomography angiography (CTA) Spot Sign is an effective means of predicting hematoma expansion (HE) in the context of spontaneous intracerebral hemorrhage (ICH). We investigated whether continuous CTA source images could differentiate the Spot Sign and blood vessels in the hematoma, and whether it would improve Spot Sign accuracy as an HE predictor. We screened for the presence of CTA Spot Sign in individuals affected by spontaneous ICH within 24 h of symptom development. Based on our findings, we determined the sensitivity, specificity, and positive/negative predictive values of this sign as a predictor of HE both on its own and following the exclusion of blood vessels. In addition, a receiver-operating characteristic approach was used to assess the accuracy of Spot Sign with and without elimination of vascular interference. A total of 265 patients were included in this study. The Spot Sign was observed in 100 patients, including in 29 patients wherein it was confirmed to be blood vessels as determined based upon continuous CTA source images. With respect to predicting HE, Spot Sign sensitivity, specificity, positive predictive values, and negative predictive values were 57%, 71%, 48% and 78%, respectively. Following the exclusion of blood vessels, these values were 57%, 87%, 68% and 81%, respectively. Spot Sign area under the curve after excluding blood vessels was 0.718, which was higher than that of the Spot Sign (0.638). After continuous CTA, source images are used to exclude blood vessels in the hematoma, the Spot Sign is thus more accurate in predicting HE.