Multi-pathways-mediated mechanisms of selenite reduction and elemental selenium nanoparticles biogenesis in the yeast-like fungus Aureobasidium melanogenum I15.

Selenium (Se) plays a critical role in diverse biological processes and is widely used across manufacturing industries. However, the contamination of Se oxyanions also poses a major public health concern. Microbial transformation is a promising approach to detoxify Se oxyanions and produce elemental selenium nanoparticles (SeNPs) with versatile industrial potential. Yeast-like fungi are an important group of environmental microorganisms, but their mechanisms for Se oxyanions reduction remain unknown. In this study, we found that Aureobasidium melanogenum I15 can reduce 1.0 mM selenite by over 90% within 48 h and efficiently form intracellular or extracellular spherical SeNPs. Metabolomic and proteomic analyses disclosed that A. melanogenum I15 evolves a complicated selenite reduction mechanism involving multiple metabolic pathways, including the glutathione/glutathione reductase pathway, the thioredoxin/thioredoxin reductase pathway, the siderophore-mediated pathway, and multiple oxidoreductase-mediated pathways. This study provides the first report on the mechanism of selenite reduction and SeNPs biogenesis in yeast-like fungi and paves an alternative avenue for the bioremediation of selenite contamination and the production of functional organic selenium compounds.

Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

Insights into the differential molecular response of non-germinated and germinated spores of Ameson portunus in vitro by comparative transcriptome analysis.

Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.

Differential molecular responses of hemolymph and hepatopancreas of swimming crab, Portunus trituberculatus, infected with Ameson portunus (Microsporidia).

Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.

First Natural Yeast Strain Trichosporon asahii HZ10 with Robust Flavonoid Productivity and Its Potential Biosynthetic Pathway.

Flavonoids are generally thought to be essential plant natural products with diverse bioactivities and pharmacological effects. Conventional approaches for the industrial production of flavonoids through plant extraction and chemical synthesis face serious economic and environmental challenges. Searching for natural robust flavonoid-producing microorganisms satisfying green and sustainable development is one of the good alternatives. Here, a natural yeast, Trichosporon asahii HZ10, isolated from raw honeycombs, was found to accumulate 146.41 mg/L total flavonoids intracellularly. Also, T. asahii HZ10 represents a broad flavonoid metabolic profiling, covering 40 flavonoids, among which nearly half were silibinin, daidzein, and irigenin trimethyl ether, especially silibinin occupying 21.07% of the total flavonoids. This is the first flavonoid-producing natural yeast strain worldwide. Furthermore, T. asahii HZ10-derived flavonoids represent favorable antioxidant activities. Interestingly, genome mining and transcriptome analysis clearly showed that T. asahii HZ10 possibly evolves a novel flavonoid synthesis pathway for the most crucial step of flavonoid skeleton synthesis, which is different from that in plants and filamentous fungi. Therefore, our results not only enrich the diversity of the natural flavonoid biosynthesis pathway but also pave an alternative way to promote the development of a synthetic biology strategy for the microbial production of flavonoids.

Normal reference values for mitral annular plane systolic excursion by motion-mode and speckle tracking echocardiography: a prospective, multicentre, population-based study.

AIMS: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants. METHODS AND RESULTS: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography. CONCLUSION: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments.

Diversity investigation of cultivable yeasts associated with honeycombs and identification of a novel Rhodotorula toruloides strain with the robust concomitant production of lipid and carotenoid.

Oleaginous yeasts-derived microbial lipids provide a promising alternative feedstock for the biodiesel industry. However, hyperosmotic stress caused by high sugar concentration during fermentation significantly prevents high cell density and productivity. Isolation of new robust osmophilic oleaginous species from specific environment possibly resolves this issue to some extent. In this study, the cultivable yeast composition of honeycombs was investigated. Totally, 11 species of honeycomb-associated cultivable yeast were identified and characterized. Among them, an osmophilic yeast strain, designated as Rhodotorula toruloides C23 was featured with excellent lipogenic and carotenogenic capacity and remarkable cell growth using glucose, xylose or glycerol as feedstock, with simultaneous production of 24.41 g/L of lipids and 15.50 mg/L of carotenoids from 120 g/L glucose in 6.7-L fermentation. Comparative transcriptomic analysis showed that C23 had evolved a dedicated molecular regulation mechanism to maintain their high simultaneous accumulation of intracellular lipids and carotenoids and cell growth under high sugar concentration.

MAL31, a sugar transporter involved in pullulan biosynthesis in Aureobasidium pullulans.

To investigate the role of the sugar transporter MAL31 on pullulan biosynthesis, the coding gene mal31 was respectively disrupted and overexpressed in the parental strain A. pullulans CCTCC M 2012259 to construct mutants of A. pullulans Δmal31 and A. pullulans Mal31. Batch pullulan production significantly decreased by 69.1 % in A. pullulans Δmal31 but increased by 15.9 % in A. pullulans Mal31, as compared to the parental strain. We performed kinetics analysis, assays of key enzymes, determination of intracellular UDPG, NADH, and ATP contents, and measurement of transcriptional levels of genes associated with pullulan biosynthesis and excretion. The results confirmed that the mal31 disruption decreased the glucose consumption rate, decreased the formation rate and titer of pullulan, but increased the intracellular UDPG supply for ß-glucan accumulation. In contrast, the mal31 overexpression increased the transcriptional levels of genes associated with pullulan biosynthesis, and accelerated the rates of glucose consumption and pullulan formation, thereby increased pullulan production. Our findings revealed that MAL31 is involved in the transport of precursors for pullulan biosynthesis. This study provides an accurate operating site for genetic modification of A. pullulans for improving pullulan production and also presents a feasible technique route for the overproduction of other polysaccharides.

Association Between Serum Lactate Dehydrogenase Level and Hematoma Expansion in Patients with Primary Intracerebral Hemorrhage: A Propensity-Matched Analysis.

OBJECTIVE: The present study aimed to explore whether a higher serum lactate dehydrogenase (sLDH) level on admission is associated with hematoma expansion (HE) in patients with primary intracerebral hemorrhage (ICH). METHODS: This single-center prospective observational study of patients with primary ICH aged 19 years or older was conducted at the Dehua County Hospital from January 2018 to May 2021. Clinical data and demographic information and outcomes were collected and analyzed. The association between increased sLDH levels and HE was assessed in univariate and multivariate analyses. Propensity-score matching (PSM) analysis was implemented to reduce baseline differences between the groups. RESULTS: Of 609 patients with ICH screened, 360 who met all eligibility criteria were enrolled in the study (mean age, 59.83 ± 12.64 years; 60.28% female patients), of whom 69 (19.17%) developed early HE. sLDH levels were statistically higher in the HE group compared with the non-HE group (236.0 [222.30-275.50] U/L vs. 209.6 [179.30-253.8] U/L; P < 0.001). Multivariable analysis showed that higher sLDH levels were still statistically associated with HE (odds ratio [OR], 0.08; 95% confidence interval, 0.03-0.210; P < 0.001). After PSM, the matched HE group had a significantly higher sLDH level than did the matched non-HE group (236.0 [222.0-279.10] vs. 216.30 [173.0-278.7] U/L; P = 0.003). The area under the curve of 0.704 (95% confidence interval, 0.654-0.751; P < 0.0001) (sensitivity, 92.75%; specificity, 52.58%), and the optimal cutoff value for sLDH level as a predictor for HE in patients with primary ICH was determined as 211.0U/L. The area under the curve of the logistic regression model based on these predictors (the TsL (time from onset to initial computed tomography,sLDH) modelbased on these predictors: sLDH, time from onset to initial computed tomography) was 0.817, with a sensitivity of 84.06% and specificity of 72.51% for HE. The TsL model produced the best ability to predict HE compared with single sLDH. sLDH levels were statistically correlated with poor outcome. CONCLUSIONS: The current PSM analysis study shows that increased serum LDH level is statistically associated with HE. Our findings indicate that the TsL model constructed by sLDH and time from onset to initial computed tomography markedly enhances the prediction of HE after ICH.

Structure-activity relationship and biological evaluation of 12 N-substituted aloperine derivatives as PD-L1 down-regulatory agents through proteasome pathway.

Twenty-nine 12 N-substituted aloperine derivatives were synthesized and screened for suppression on PD-L1 expression in H460 cells, as a continuation of our work. Systematic structural modifications led to the identification of compound 6b as the most active PD-L1 modulator. Compound 6b could significantly down-regulate both constitutive and inductive PD-L1 expression in NSCLC cells, and successively enhance the cytotoxicity of co-cultured T cells against tumor cells at the concentration of 20 µM. Also, it exhibited a moderate in vivo anticancer efficacy against Lewis tumor xenograft with a stable PK and safety profile. The mechanism study indicated that 6b mediated the degradation of PD-L1 through a proteasome pathway, rather than a lysosome route. These results provided the powerful information for cancer immunotherapy of aloperine derivatives with unique endocyclic skeleton by targeting PD-L1 to activate immune cells to kill cancer cells.

Molecular mechanism and therapeutic targeting of necrosis, apoptosis, pyroptosis, and autophagy in cardiovascular disease.

ABSTRACT: Cell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis.

[Spatial Distribution Characteristics of the Spectrum, Source Analysis, and Nitrogen Response of Dissolved Organic Matter in Summer Rainfall in the Hebei Province].

Dissolved organic matter(DOM) is an important component of the organic matter in the environment. This study explored the characteristics of DOM. The components and spectral characteristics of rainwater DOM were measured using Ultraviolet-visible absorption spectrum(UV-vis) and three-dimensional fluorescence spectrum in the Hebei province. The results showed significant differences for DOM molecular weight in the northern, central, and southern region; the DOM of the northern region exhibited the lowest molecular weight. Two humic-like(C1 and C4), one protein-like(C2) and one fulvic-like(C3) components were identified by parallel factor(PARAFAC) analysis. Component C2 had a significant positive correlation with components C3 and C4(P<0.001), which may have similar sources. The C2(protein-like substances) accounted for the major proportion of DOM with the average abundance 40.59%. The DOM components based on PARAFAC exhibited significantly difference between city and country regions without spatial difference, which was consistent with the result of fluorescence regional integration(FRI). The protein-like substances based on FRI were the main components, which accounted for 61.59%-89.01%. Redundancy analysis(RDA) showed that total nitrogen, nitrate, and ammonia were the main environmental factors determining the distribution of DOM. Spectral indices presented a significant difference between city and country regions. High fluorescence(FI) and biological(BIX) and low humification(HIX) values showed that summer rain exhibited the strong autochthonous and low humification characteristics, and country region have stronger autochthonous characteristics than city region. The regression analysis demonstrates that the prediction accuracy of rainwater quality parameters in city region is high. From all the results, rainwater DOM, showing strong autogenous characteristics, exhibited significant differences between city and country regions without spatial difference in Hebei. Meanwhile, it can also provide technical support for rainwater nitrogen concentration prediction based on DOM components.

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex.

BACKGROUND: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration. METHODS: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. RESULTS: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and -15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. CONCLUSION: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.

Analysis of the Status Quo and Influencing Factors of Community Residents' Awareness of Basic Life Support and Willingness to Attempt Rescue.

OBJECTIVE: This study aimed to investigate community residents' awareness of basic life support (BLS) and their willingness to attempt rescue. METHODS: From October to December 2020, in the communities of Nantong City, a stratified three-stage random sampling method was adopted to select residents from 12 neighborhood committees over the age of 18 with whom to conduct a cross-sectional questionnaire survey. A self-designed questionnaire was adopted, the contents of which included the general situation of the respondent, knowledge, attitude, and behavior in relation to BLS; the Cronbach's α coefficient of the questionnaire was 0.719. RESULTS: A total of 3000 questionnaires were distributed, of which 2812 were valid, with a valid response rate of 93.73%. Of the 2812 respondents, 41.18% had seen an automatic external defibrillator (AED), 48.83% had experience of' cardiopulmonary resuscitation (CPR), and 25.07% of the respondents had experience of' AEDs. When an accident occurred, 50.50% of residents were willing to attempt rescue, 70.80% were willing to attempt rescue under professional guidance, and 71.23% were willing to attempt rescue after learning BLS techniques. Of the residents who were unwilling to attempt rescue, 32.75% were worried about their lack of ability, 27.91% were concerned about legal issues, 14.01% feared infectious diseases, and 10.35% were unwilling to perform mouth-to-mouth artificial respiration. Age, occupation, education level, and whether they had participated in first aid training were the influencing factors. CONCLUSION: Residents in Nantong have less knowledge of BLS, and their knowledge of CPR is better than that of AEDs. Residents have a strong willingness to learn BLS. Measures need to be taken to improve their understanding of BLS and their application skills. Residents have high levels of willingness to attempt rescue, but a certain percentage of residents have concerns. Interventions can be made to target the different reasons.

The Traumatic Experience of Clinical Nurses During the COVID-19 Pandemic: Which Factors are Related to Post-Traumatic Growth?

OBJECTIVE: Post-traumatic growth (PTG) is a positive result of fighting against traumatic events. This study aimed to investigate the current status of PTG of clinical nurses and analyze its influencing factors. METHODS: A total of 1790 nurses participated in the study and completed the questionnaire. Demographic data and related scales of PTG, post-traumatic stress disorder, coping style, social support, and self-efficacy were collected online. Through univariate analysis and multiple linear regression analysis, the related influencing factors were studied. RESULTS: The total score of PTG of 1790 nurses was 67.17 ± 14.79. The analysis revealed that good social support and self-efficacy were important factors to improve the level of PTG of clinical nurses, while bad psychological state and working for many years were the negative factors of PTG. CONCLUSION: Good social support and self-efficacy can help clinical nurses cope with the novel coronavirus disease 2019 pandemic and accept the disease's challenges. If these factors can be considered in clinical practice, this will help promote clinical nurses' mental health.

Omipalisib Inhibits Esophageal Squamous Cell Carcinoma Growth Through Inactivation of Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK Signaling.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a life-threatening digestive tract malignancy with no known curative treatment. This study aimed to investigate the antineoplastic effects of omipalisib and its underlying molecular mechanisms in ESCC using a high throughput screen. MATERIAL AND METHODS MTT assay and clone formation were used to determine cell viability and proliferation. Flow cytometry was conducted to detect cell cycle distribution and apoptosis. Global gene expression and mRNA expression levels were determined by RNA sequencing and real-time PCR, respectively. Protein expression was evaluated in the 4 ESCC cell lines by Western blot analysis. Finally, a xenograft nude mouse model was used to evaluate the effect of omipalisib on tumor growth in vivo. RESULTS In the pilot screening of a 1404-compound library, we demonstrated that omipalisib markedly inhibited cell proliferation in a panel of ESCC cell lines. Mechanistically, omipalisib induced G0/G1 cell cycle arrest and apoptosis. RNA-seq, KEGG, and GSEA analyses revealed that the PI3K/AKT/mTOR pathway is the prominent target of omipalisib in ESCC cells. Treatment with omipalisib decreased expression of p-AKT, p-4EBP1, p-p70S6K, p-S6, and p-ERK, therefore disrupting the activation of PI3K/AKT/mTOR and ERK signaling. In the nude mouse xenograft model, omipalisib significantly suppressed the tumor growth in ESCC tumor-bearing mice without obvious adverse effects. CONCLUSIONS Omipalisib inhibited the proliferation and growth of ESCC by disrupting PI3K/AKT/mTOR and ERK signaling. The present study supports the rationale for using omipalisib as a therapeutic approach in ESCC patients. Further clinical studies are needed.

Admission Neutrophil-Lymphocyte Ratio Predicts Rebleeding Following Aneurismal Subarachnoid Hemorrhage.

OBJECTIVE: The relationship between neutrophil-lymphocyte ratio (NLR) and the occurrence of rebleeding in aneurysmal subarachnoid hemorrhage (aSAH) is poorly understood. Our study aimed to investigate the association between NLR on admission and rebleeding following aSAH. METHODS: Clinical and laboratorial data from patients with aSAH were retrospectively collected, including leukocyte, neutrophil, lymphocyte, and NLR. Univariate and multivariate analyses were performed to assess for the association of NLR with rebleeding. We performed propensity-score matching analyses to correct imbalances in patient characteristics between the rebleeding group and nonrebleeding group. RESULTS: Rebleeding occurred in 30 of 716 (4.19%) patients with aSAH in this cohort. Patients with rebleeding had significantly higher NLR comparing with patients without rebleeding (11.27 vs. 5.5; P < 0.05) in the univariate analysis. In the multivariate analysis, NLR was considered as a risk factor of rebleeding (odds ratio, 0.283; 95% confidence interval, 0.130-0.620; P = 0.002), as well as Fisher grade (odds ratio, 0.353, 95% confidence interval, 0.151-0.824; P = 0.016). The area under the curve of the NLR and combined NLR-Fisher grade model was 0.702 and 0.744 (sensitivity was 39.94%, and specificity was 100%) for predicting rebleeding, respectively. After propensity-score matching, the optimal cutoff value for NLR as a predictor for rebleeding following aSAH was determined as 5.4 (sensitivity was 83.33%, and the specificity was 63.33%). CONCLUSIONS: Higher NLR predicts the occurrence of rebleeding and poor outcome, and NLR combined with Fisher grade significantly improves the prediction of rebleeding following aSAH.

Isolated metastasis of hepatocellular carcinoma in the right ventricle.

BACKGROUND: Hepatocellular carcinoma (HCC) with right ventricle metastasis without inferior vena cava and right atrium involvement is very rare and the prognosis of HCC with RV metastasis is generally poor. The mass in the cardiac chamber may lead to lethal instability of hemodynamics, however, the initial symptom is probably non-specific, which means that diagnosis timely becomes even harder. CASE PRESENTATION: We present a 63-year-old male with isolated metastasis of HCC in the right ventricle which caused inflow obstruction. Moreover, we reviewed a series of studies of isolated metastasis of hepatocellular carcinoma between 1980 and 2018, and summarized the relative outcomes. CONCLUSIONS: Isolated metastasis of hepatocellular carcinoma in the right ventricle is extraordinarily rare. It may damage cardiac structure and broke hemodynamic balance. Multimodality imaging plays an important in accurate pre-operation assessment. Nowadays, palliative treatments could relieve fatal symptoms to some degree, however, standard treatment has not been well established.

Infantile hepatic hemangiomas associated with high-output cardiac failure and pulmonary hypertension.

BACKGROUND: Infantile hepatic hemangioma (IHH) is a rare endothelial cell neoplasm, which may be concurrent with severe complications and result in poor outcomes. Moreover, the coexistence of IHH and congenial heart disease is even rarer. CASE PRESENTATION: We present a 10-day-old male born with IHH associated with patent ductus arteriosus (PDA), atrial septal defect (ASD) and pulmonary hypertension. Moreover, we reviewed a series of studies of IHH-associated high-output cardiac failure between 1974 and 2018, and summarized the treatment outcomes. CONCLUSIONS: Infantile hepatic hemangioma (IHH) has been known to induce high-output heart failure. There is no literature to summarize the severity of its impact on heart, which can lead to a high mortality rate. When IHH is detected by ultrasound, the heart should be evaluated to facilitate treatment. The outcomes of IHH associated with heart failure are good.

A Comparative Study on High Selectivities of Human Telomeric Dimeric G-Quadruplexes by Dimeric G-Quadruplex Binders.

Three new polyether-tethered bisquinolinium dimers (3 a-c) were synthesized, and their binding affinities, selectivities, and thermal stabilization towards dimeric G-quadruplex DNA (G2T1) in human telomeric regions were studied. The bisquinolinium dimer with a medium-length polyether linker (3 b) showed 30-425-fold higher binding affinity and selectivity towards antiparallel G2T1 than towards monomeric quadruplexes, which included human telomeric monomeric G-quadruplexes (G1), c-kit 1, c-kit 2, and c-myc. In addition, compound 3 b induced the formation of quadruplexes and displayed the highest level of thermal stabilization (ΔTm >28.1 °C) among all reported multimeric G-quadruplex binders. Compound 3 b also displayed a higher selectivity towards antiparallel G2T1 than monomer 360 A and bisquinolinium dimers 3 a and c. In contrast with our recent research on the analogous berberine dimer 1 b and dinickel-salphen complex 2 c, polyether linkers and their monomeric G-quadruplex binders in these dimeric G-quadruplex binders play a crucial role in regulating the binding affinities, selectivities, and thermal stabilization towards G2T1. More interestingly, these dimeric G-quadruplex compounds bind through end-stacking with the two adjacent G-quadruplex units in G2T1, and they showed high selectivity towards antiparallel G2T1 rather than mixed-type G2T1. In addition, compound 3 b, which displayed high selectivity towards antiparallel G2T1, showed strong telomerase inhibition and potent anticancer activities against HeLa and MCF-7 cells.