Predicting postinterventional rupture of intracranial aneurysms using arteriography-derived radiomic features after pipeline embolization.

Background and purpose: Postinterventional rupture of intracranial aneurysms (IAs) remains a severe complication after flow diverter treatment. However, potential hemodynamic mechanisms underlying independent predictors for postinterventional rupture of IAs remain unclear. In this study, we employed arteriography-derived radiomic features to predict this complication. Methods: We included 64 patients who underwent pipeline flow diversion for intracranial aneurysms, distinguishing between 16 patients who experienced postinterventional rupture and 48 who did not. We performed propensity score matching based on clinical and morphological factors to match these patients with 48 patients with postinterventional unruptured IAs at a 1:3 ratio. Postinterventional digital subtraction angiography were used to create five arteriography-derived perfusion parameter maps and then radiomics features were obtained from each map. Informative features were selected through the least absolute shrinkage and selection operator method with five-fold cross-validation. Subsequently, radiomics scores were formulated to predict the occurrence of postinterventional IA ruptures. Prediction performance was evaluated with the training and test datasets using area under the curve (AUC) and confusion matrix-derived metrics. Results: Overall, 1,459 radiomics features were obtained, and six were selected. The resulting radiomics scores had high efficacy in distinguishing the postinterventional rupture group. The AUC and Youden index were 0.912 (95% confidence interval: 0.767-1.000) and 0.847 for the training dataset, respectively, and 0.938 (95% confidence interval, 0.806-1.000) and 0.800 for the testing dataset, respectively. Conclusion: Radiomics scores generated using arteriography-derived radiomic features effectively predicted postinterventional IA ruptures and may aid in differentiating IAs at high risk of postinterventional rupture.

An MRI radiomics approach to discriminate hemorrhage prone intracranial tumors before stereotactic biopsy.

PURPOSE: To explore imaging biomarkers predictive of intratumoral hemorrhage for lesions intended for elective stereotactic biopsy. METHOD: This study included a retrospective cohort of 143 patients with 175 intracranial lesions intended for stereotactic biopsy. All the lesions were randomly split into a training dataset (n=121) and a test dataset (n=54) at a ratio of 7:3. 34 lesions were defined as "hemorrhage-prone tumors" as hemorrhage occurred between initial diagnostic MRI acquisition and the scheduled biopsy procedure. Radiomics features were extracted from the contrast-enhanced T1WI and T2WI images. Features informative of hemorrhage were then selected by the LASSO algorithm and an SVM model was built with selected features. The SVM model was further simplified by discarding features with low importance calculated using a "permutation importance" method. The model's performance was evaluated with confusion matrix-derived metrics and AUC value on the independent test dataset. RESULTS: Nine radiomics features were selected as hemorrhage related features of intracranial tumors by the LASSO algorithm. The simplified model's sensitivity, specificity, accuracy, and AUC reached 0.909, 0.930, 0.926, and 0.949 (95%CI: 0.865-1.000) on the test dataset in the discrimination of "hemorrhage-prone tumors". The permutation method rated feature "T2_gradient_firstorder_10Percentile" as the most important, the absence of which decreased the model's accuracy by 10.9%. CONCLUSION: Radiomics features extracted on contrast-enhanced T1WI and T2WI sequences were predictive of future hemorrhage of intracranial tumors with favorable accuracy. This model may assist in the arrangement of biopsy procedures and the selection of target lesions in patients with multiple lesions.

Rupture-Related Features of Cerebral Arteriovenous Malformations and Their Utility in Predicting Hemorrhage.

BACKGROUND: Evaluating rupture risk in cerebral arteriovenous malformations currently lacks quantitative hemodynamic and angioarchitectural features necessary for predicting subsequent hemorrhage. We aimed to derive rupture-related hemodynamic and angioarchitectural features of arteriovenous malformations and construct an ensemble model for predicting subsequent hemorrhage. METHODS: This retrospective study included 3 data sets, as follows: training and test data sets comprising consecutive patients with untreated cerebral arteriovenous malformations who were admitted from January 2015 to June 2022 and a validation data set comprising patients with unruptured arteriovenous malformations who received conservative treatment between January 2009 and December 2014. We extracted rupture-related features and developed logistic regression (clinical features), decision tree (hemodynamic features), and support vector machine (angioarchitectural features) models. These 3 models were combined into an ensemble model using a weighted soft-voting strategy. The performance of the models in discriminating ruptured arteriovenous malformations and predicting subsequent hemorrhage was evaluated with confusion matrix-related metrics in the test and validation data sets. RESULTS: A total of 896 patients (mean±SD age, 28±14 years; 404 women) were evaluated, with 632, 158, and 106 patients in the training, test, and validation data sets, respectively. From the training set, 9 clinical, 10 hemodynamic, and 2912 pixel-based angioarchitectural features were extracted. A logistic regression model was built using 4 selected clinical features (age, nidus size, location, and venous aneurysm), whereas a decision-tree model was constructed from 4 hemodynamic features (outflow time, stasis index, cerebral blood flow, and outflow volume ratio). A support vector machine model was designed using 5 pixel-based angioarchitectural features. In the validation data set, the accuracy, sensitivity, specificity, and area under the curve of the ensemble model for predicting subsequent hemorrhages were 0.840, 0.889, 0.823, and 0.911, respectively. CONCLUSIONS: The ensemble model incorporating clinical, hemodynamic, and angioarchitectural features showed favorable performance in predicting subsequent hemorrhage of cerebral arteriovenous malformations.

Characterization of Two Gonadal Genes, zar1 and wt1b, in Hermaphroditic Fish Asian Seabass (Lates calcarifer).

Zygote arrest-1 (Zar1) and Wilms' tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, Lczar1 and Lcwt1b were identified in Asian seabass (Lates calcarifer), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of Lczar1 were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of Lcwt1b cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family. RT-qPCR analysis showed that Lczar1 mRNA was exclusively expressed in the ovary, while Lcwt1b mRNA was majorly expressed in the gonads in a higher amount in the testis than in the ovary. In situ hybridization results showed that Lczar1 mRNA was mainly concentrated in oogonia and oocytes at early stages in the ovary, but were undetectable in the testis. Lcwt1b mRNA was localized not only in gonadal somatic cells (the testis and ovary), but also in female and male germ cells in the early developmental stages, such as those of previtellogenic oocytes, spermatogonia, spermatocytes and spermatids. These results indicated that Lczar1 and Lcwt1b possibly play roles in gonadal development. Therefore, the findings of this study will provide a basis for clarifying the mechanism of Lczar1 and Lcwt1b in regulating germ cell development and the sex reversal of Asian seabass and even other hermaphroditic species.

Prediction of Venous Trans-Stenotic Pressure Gradient Using Shape Features Derived From Magnetic Resonance Venography in Idiopathic Intracranial Hypertension Patients.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology associated with venous sinus stenosis. This study aimed to develop a magnetic resonance venography (MRV)-based radiomics model for predicting a high trans-stenotic pressure gradient (TPG) in IIH patients diagnosed with venous sinus stenosis. MATERIALS AND METHODS: This retrospective study included 105 IIH patients (median age [interquartile range], 35 years [27-42 years]; female:male, 82:23) who underwent MRV and catheter venography complemented by venous manometry. Contrast enhanced-MRV was conducted under 1.5 Tesla system, and the images were reconstructed using a standard algorithm. Shape features were derived from MRV images via the PyRadiomics package and selected by utilizing the least absolute shrinkage and selection operator (LASSO) method. A radiomics score for predicting high TPG (≥ 8 mmHg) in IIH patients was formulated using multivariable logistic regression; its discrimination performance was assessed using the area under the receiver operating characteristic curve (AUROC). A nomogram was constructed by incorporating the radiomics scores and clinical features. RESULTS: Data from 105 patients were randomly divided into two distinct datasets for model training (n = 73; 50 and 23 with and without high TPG, respectively) and testing (n = 32; 22 and 10 with and without high TPG, respectively). Three informative shape features were identified in the training datasets: least axis length, sphericity, and maximum three-dimensional diameter. The radiomics score for predicting high TPG in IIH patients demonstrated an AUROC of 0.906 (95% confidence interval, 0.836-0.976) in the training dataset and 0.877 (95% confidence interval, 0.755-0.999) in the test dataset. The nomogram showed good calibration. CONCLUSION: Our study presents the feasibility of a novel model for predicting high TPG in IIH patients using radiomics analysis of noninvasive MRV-based shape features. This information may aid clinicians in identifying patients who may benefit from stenting.

Urinary Endometriosis Misdiagnosed as Ureteral Malignant Tumor by PET/CT: A Case Study.

ABSTRACT: Endometriosis is a chronic inflammatory estrogen-dependent benign disease. It is defined as the endometrium growing outside the uterine cavity and the myometrium. It usually has low FDG uptake but rarely occurs in the ureters. We reported a case of a 47-year-old woman's left ureteral nodule originally misdiagnosed as a ureteral malignant tumor by PET/CT and finally pathologically confirmed as endometriosis.

Retrograde placement of flow diversion for the treatment of giant internal carotid artery aneurysm.

The use of flow diverters has been well-validated for the treatment of giant internal carotid artery aneurysms. However, in certain complex cases, the navigation of stent microcatheters across the neck may pose a relative challenge.1-3 In this technical video (video 1), we present the case of a patient in their 50s experiencing discomfort in the left eye. Angiography identified a giant aneurysm in the ophthalmic segment of the left internal carotid artery. Before seeking care at our institution, the patient had two interventional procedures, both unsuccessful due to difficulties in navigating the microcatheter past the aneurysm neck.4-5 In our management, after multiple unsuccessful anterograde attempts, we employed a retrograde strategy via the vertebral-basilar-posterior communicating artery route. This approach facilitated the successful deployment of the flow diverter and led to effective aneurysm embolization, underscoring the value of retrograde techniques for challenging cases.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Localized high-concentration electrolytes get more localized through micelle-like structures.

Liquid electrolytes in batteries are typically treated as macroscopically homogeneous ionic transport media despite having a complex chemical composition and atomistic solvation structures, leaving a knowledge gap of the microstructural characteristics. Here, we reveal a unique micelle-like structure in a localized high-concentration electrolyte, in which the solvent acts as a surfactant between an insoluble salt in a diluent. The miscibility of the solvent with the diluent and simultaneous solubility of the salt results in a micelle-like structure with a smeared interface and an increased salt concentration at the centre of the salt-solvent clusters that extends the salt solubility. These intermingling miscibility effects have temperature dependencies, wherein a typical localized high-concentration electrolyte peaks in localized cluster salt concentration near room temperature and is used to form a stable solid-electrolyte interphase on a Li metal anode. These findings serve as a guide to predicting a stable ternary phase diagram and connecting the electrolyte microstructure with electrolyte formulation and formation protocols of solid-electrolyte interphases for enhanced battery cyclability.

Quantitative evaluation of the subsequent hemorrhage with arteriography-derived hemodynamic features in patients with untreated cerebral arteriovenous malformation.

Background: Patients with untreated cerebral arteriovenous malformations (AVMs) are at risk of intracerebral hemorrhage. However, treatment to prevent AVM hemorrhage carries risks. Objective: This study aimed to analyze the AVM nidus-related hemodynamic features and identify the risk factors for subsequent hemorrhage. Methods: We retrospectively identified patients with untreated AVMs who were assessed at our institution between March 2010 and March 2021. Patients with ≥6 months of treatment-free and hemorrhage-free follow-up after diagnosed by digital subtraction angiography were included in subsequent examinations. The hemodynamic features were extracted from five contrast flow-related parameter maps. The Kaplan-Meier analyses and Cox proportional hazards regression models were used to find the potential risk factors for subsequent hemorrhage. Results: Overall, 104 patients with a mean follow-up duration of 3.37 years (median, 2.42 years; range, 6-117 months) were included in study, and the annual risk of rupture was 3.7%. Previous rupture (hazard ratio [HR], 4.89; 95% confidence interval [CI], 1.16-20.72), deep AVM location (HR, 4.02; 95% CI, 1.01-15.99), higher cerebral blood volume (HR, 3.35; 95% CI, 1.15-9.74) in the nidus, and higher stasis index (HR, 1.54; 95% CI, 1.06-2.24) in the nidus were associated with subsequent hemorrhage in untreated AVMs. Conclusion: Higher cerebral blood volume and stasis index in the nidus suggest increased blood inflow and stagnant blood drainage. The combination of these factors may cause subsequent hemorrhage of AVMs.

Correction: Voltammetric pH sensor based on electrochemically modified pseudo-graphite.

Correction for 'Voltammetric pH sensor based on electrochemically modified pseudo-graphite' by Haoyu Zhu et al., Analyst, 2020, 145, 7252-7259, https://doi.org/10.1039/D0AN01405B.

[Biochar or Straw Substituting Chemical Fertilizer Increase the Risk of Phosphorus Loss in Subsurface Runoff in Sloping Farmland].

The purple soil slope farmland is an important agricultural land in southwest China but is also one of the main sources of agricultural non-point source pollution in the Three Gorges Reservoir area. Taking reasonable measures to control the loss of soil nutrients is of great significance to the treatment of non-point source pollution in the region. Here, a three-year (2018-2020) field runoff experiment was conducted to monitor and evaluate the phosphorus (P) loss in sloping farmland via surface runoff (i.e., surface flow, 0-20 cm) and subsurface runoff (i.e., subsurface flow, 20-60 cm), with five treatments including no fertilization (CK), conventional fertilization (CF), optimal fertilization (OF), biochar combined with 85% of OF (BF), and straw combined with 85% of OF (SF). The results showed that fertilization application reduced the sediment yields and surface runoff flux but increased the subsurface runoff flux. The total loss flux of phosphate (PO3-4-P), total phosphorus (TP), and particulate phosphorus (PP) in surface flow were the highest in the BF treatment and the lowest in the SF treatment. All fertilization applications increased the P loss fluxes in subsurface flow relative to that in CK. The highest PO3-4-P and TP loss flux in subsurface flow was found in the BF (213.88 g·hm-2 and 694.54 g·hm-2, respectively) treatment, followed by that in the OF and SF treatments. Redundancy analysis (RDA) results showed that surface runoff flux and biochar application were the main factors contributing to increased P loss in surface flow, and subsurface runoff flux was the main factor contributing to increased P loss in subsurface flow. In summary, the SF treatment reduced the amount of sediment yield and surface runoff flux in sloping farmland of purple soil and was the most effective for controlling P loss, whereas the risk of subsurface runoff flux requires further attention.

Research Progress and Molecular Mechanisms of Endothelial Cells Inflammation in Vascular-Related Diseases.

Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between the bloodstream and the walls of blood vessels. These versatile cells serve myriad functions, including the regulation of vascular tension and the management of hemostasis and thrombosis. Inflammation constitutes a cascade of biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently a protective mechanism, dysregulated inflammation can precipitate a host of vascular pathologies. ECs play a critical role in the genesis and progression of vascular inflammation, which has been implicated in the etiology of numerous vascular disorders, such as atherosclerosis, cardiovascular diseases, respiratory diseases, diabetes mellitus, and sepsis. Upon activation, ECs secrete potent inflammatory mediators that elicit both innate and adaptive immune reactions, culminating in inflammation. To date, no comprehensive and nuanced account of the research progress concerning ECs and inflammation in vascular-related maladies exists. Consequently, this review endeavors to synthesize the contributions of ECs to inflammatory processes, delineate the molecular signaling pathways involved in regulation, and categorize and consolidate the various models and treatment strategies for vascular-related diseases. It is our aspiration that this review furnishes cogent experimental evidence supporting the established link between endothelial inflammation and vascular-related pathologies, offers a theoretical foundation for clinical investigations, and imparts valuable insights for the development of therapeutic agents targeting these diseases.

Portable and integrated microfluidic flow control system using off-the-shelf components towards organs-on-chip applications.

Organ-on-a-chip (OoC) devices require the precise control of various media. This is mostly done using several fluid control components, which are much larger than the typical OoC device and connected through fluidic tubing, i.e., the fluidic system is not integrated, which inhibits the system's portability. Here, we explore the limits of fluidic system integration using off-the-shelf fluidic control components. A flow control configuration is proposed that uses a vacuum to generate a fluctuation-free flow and minimizes the number of components used in the system. 3D printing is used to fabricate a custom-designed platform box for mounting the chosen smallest footprint components. It provides flexibility in arranging the various components to create experiment-specific systems. A demonstrator system is realized for lung-on-a-chip experiments. The 3D-printed platform box is 290 mm long, 240 mm wide and 37 mm tall. After integrating all the components, it weighs 4.8 kg. The system comprises of a switch valve, flow and pressure controllers, and a vacuum pump to control the diverse media flows. The system generates liquid flow rates ranging from 1.5 [Formula: see text]Lmin[Formula: see text] to 68 [Formula: see text]Lmin[Formula: see text] in the cell chambers, and a cyclic vacuum of 280 mbar below atmospheric pressure with 0.5 Hz frequency in the side channels to induce mechanical strain on the cells-substrate. The components are modular for easy exchange. The battery operated platform box can be mounted on either upright or inverted microscopes and fits in a standard incubator. Overall, it is shown that a compact integrated and portable fluidic system for OoC experiments can be constructed using off-the-shelf components. For further down-scaling, the fluidic control components, like the pump, switch valves, and flow controllers, require significant miniaturization while having a wide flow rate range with high resolution.

Pipeline embolization devices for the treatment of nonsaccular aneurysms in pediatric patients.

Objective: Pediatric nonsaccular aneurysms are rare but challenging lesions; pipeline embolization devices (PEDs) are their potential treatment option. In this study, we aimed to evaluate the safety and efficacy of PEDs for treatment of these aneurysms. Methods: We retrospectively selected pediatric patients with nonsaccular aneurysms treated using PEDs between June 2015 and July 2021 from our prospectively maintained database. For each patient, demographics, aneurysm characteristics, procedure details, and clinical and angiographic follow-up data were collected and summarized. Results: This study included 16 pediatric patients with 16 nonsaccular aneurysms treated with PEDs. A median clinical follow-up time of 1,376 days was achieved in 93.75% of the patients. The complication rate of the included patients was 25%, with two patients developing mass effect, one patient undergoing major ischemic stroke, and one patient experiencing stent foreshortening after the procedure. The complete occlusion rate of aneurysms without any neurologic sequelae was 93.33%, with a median angiographic follow-up period of 246 days. The mortality rate was 6.25%. Conclusions: The use of PEDs to treat pediatric nonsaccular aneurysms is feasible, with a high rate of complete occlusion of the aneurysm and favorable follow-up outcomes.

Gap junction is essential for the antidepressant effects of fluoxetine.

OBJECTIVES: Fluoxetine has been used as the first line for the therapy of depression. However, lack of therapeutic efficacy and time lag still limit the application of fluoxetine. Gap junction dysfunction is a potentially novel pathogenic mechanism for depression. To clarify the mechanism underlying these limitations, we investigated whether gap junction was related to the antidepressant effects of fluoxetine. METHODS AND KEY FINDINGS: After chronic unpredictable stress (CUS), animals showed decreases in gap junction intracellular communication (GJIC). Treatment with fluoxetine 10 mg/kg significantly improved GJIC and anhedonia of rats until six days. These results indicated that fluoxetine improved gap junction indirectly. Furthermore, to test the role of gap junction on antidepressant effects of fluoxetine, we blocked gap junction using carbenoxolone (CBX) infusion in the prefrontal cortex. CBX dampened fluoxetine-induced decrease in immobility time of mice in tail suspension test (TST). CONCLUSIONS: Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.

A multi-target protective effect of Danggui-Shaoyao-San on the vascular endothelium of atherosclerotic mice.

BACKGROUND: Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years. METHODS: ApoE-/- atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin-eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5ß1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. RESULTS: DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5ß1/ c-Abl/YAP in the aortic vessels. CONCLUSIONS: Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY.

The Application of Cinnamon Twig Extract as an Inhibitor of Listeriolysin O against Listeria monocytogenes Infection.

As a major virulence factor of Listeria monocytogenes (L. monocytogenes), listeriolysin O (LLO) can assist in the immune escape of L. monocytogenes, which is critical for the pathogen to evade host immune recognition, leading to various infectious diseases. Cinnamon twig (CT), as a traditional medicine, has been widely used in clinics for multiple functions and it has exhibited excellent safety, efficacy and stability. There are few reports on the effects of the extracts of traditional medicine on bacterial virulence factors. CT has not been reported to be effective in the treatment of L. monocytogenes infection. Therefore, this study aims to explore the preventive effect of CT against L. monocytogenes infection in vivo and in vitro by targeting LLO. Firstly, a hemolysis assay and a cell viability determination are used to detect the effect of CT extract on the inhibition of the cytolytic activity of LLO. The potential mechanism through which CT extract inhibits LLO activity is predicted through network pharmacology, molecular docking assay, real-time polymerase chain reaction (RT-PCR), Western blotting and circular dichroism (CD) analysis. The experimental therapeutic effect of CT extract is examined in a mouse model infected with L. monocytogenes. Then, the ingredients are identified through a high-performance liquid chromatography (HPLC) and thin layer chromatography (TLC) analysis. Here we find that CT extract, containing mainly cinnamic acid, cinnamaldehyde, ß-sitosterol, taxifolin, catechin and epicatechin, shows a potential inhibition of LLO-mediated hemolysis without any antimicrobial activity. The results of the mechanism research show that CT extract treatment can simultaneously inhibit LLO expression and oligomerization. Furthermore, the addition of CT extract led to a remarkable alleviation of LLO-induced cytotoxicity. After treatment with CT extract, the mortality, bacterial load, pathological damage and inflammatory responses of infected mice are significantly reduced when compared with the untreated group. This study suggests that CT extract can be a novel and multicomponent inhibitor of LLO with multiple strategies against L. monocytogenes infection, which could be further developed into a novel treatment for infections caused by L. monocytogenes.

Fungal Biomarkers in Traditional Starter Determine the Chemical Characteristics of Turbid Rice Wine from the Rim of the Sichuan Basin, China.

The fungal community in Qu plays a key role in the formation of turbid rice wine (TRW) style. The Sichuan Basin and its surrounding areas have become one of the main TRW production regions in China; however, the fungal community in Qu and how they affect the characteristics of TRW remain unknown. Therefore, this study provided insight into the fungal biomarkers in Qu from Guang'an (GQ), Dazhou (DQ), Aba (AQ), and Liangshan (LQ), as well as their relationships with compounds in TRW. The main biomarkers in GQ were Rhizopus arrhizus, Candida glabrata, Rhizomucor pusillus, Thermomyces lanuginosus and Wallemia sebi. However, they changed to Saccharomycopsis fibuligera and Mucor indicus in DQ, Lichtheimia ramose in AQ, and Rhizopus microsporus and Saccharomyces cerevisiae in LQ. As a response to fungal biomarkers, the reducing sugar, ethanol, organic acids, and volatile compounds were also changed markedly in TRWs. Among important volatile compounds (VIP > 1.00), phenethyl alcohol (14.1-29.4%) was dominant in TRWs. Meanwhile, 3-methyl-1-butanol (20.6-56.5%) was dominant in all TRWs except that fermented by GQ (GW). Acetic acid (29.4%) and ethyl palmitate (10.1%) were dominant in GW and LW, respectively. Moreover, GQ biomarkers were positively correlated with acetic acid and all unique important volatile compounds in GW. DQ biomarkers had positive correlations with unique compounds of acetoin and ethyl 5-chloro-1,3,4-thiadiazole-2-carboxylate in DW. Meanwhile, the AQ biomarkers were positively correlated with all AW unique, important, and volatile compounds. Although there were not any unique volatile compounds in LW, 16 important volatile compounds in LW were positively related to LQ biomarkers. Obviously, biomarkers in different geographic Qu played vital roles in the formation of important volatile compounds, which could contribute specific flavor to TRWs. This study provided a scientific understanding for future efforts to promote the excellent characteristics of TRW by regulating beneficial fungal communities.