It is desirable to obtain high levels of viable Lacticaseibacillus paracasei, a widely used food probiotic whose antibacterial activity and potential application in milk remain largely ...uninvestigated. Here, we isolated and purified the L. paracasei strain XLK 401 from food-grade blueberry ferments and found that it exhibited strong antibacterial activity against both gram-positive and gram-negative foodborne pathogens, including Staphylococcus aureus, Salmonella paratyphi B, Escherichia coli O157, and Shigella flexneri. Then, we applied alternating tangential flow (ATF) technology to produce viable L. paracasei XLK 401 cells and its cell-free supernatant (CFS). Compared with the conventional fed-batch method, 22 h of ATF-based processing markedly increased the number of viable cells of L. paracasei XLK 401 to 12.14 ± 0.13 log cfu/mL. Additionally, the CFS exhibited good thermal stability and pH tolerance, inhibiting biofilm formation in the abovementioned foodborne pathogens. According to liquid chromatography-mass spectrometry analysis, organic acids were the main antibacterial components of XLK 401 CFS, accounting for its inhibition activity. Moreover, the CFS of L. paracasei XLK 401 effectively inhibited the growth of multidrug-resistant gram-positive Staph. aureus and gram-negative E. coli O157 pathogens in milk, and caused a reduction in the pathogenic cell counts by 6 to 7 log cfu/mL compared with untreated control, thus considerably maintaining the safety of milk samples. For the first time to our knowledge, ATF-based technology was employed to obtain viable L. paracasei on a large scale, and its CFS could serve as a broad-spectrum biopreservative for potential application against foodborne pathogens in milk products.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as “combined (or mixed) hepatocellular‐cholangiocarcinoma.” These tumors, although described ...over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation. Conclusion: It is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113‐126).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Ferric uptake regulator (Fur) is a global regulator that controls bacterial iron homeostasis. In this study, a fur deletion mutant of the deep-sea bacterium Shewanella piezotolerans WP3 was ...constructed. Physiological studies revealed that the growth rate of this mutant under aerobic conditions was only slightly lower than that of wild type (WT), but severe growth defects were observed under anaerobic conditions when different electron acceptors (EAs) were provided. Comparative transcriptomic analysis demonstrated that Fur is involved not only in classical iron homeostasis but also in anaerobic respiration. Fur exerted pleiotropic effects on the regulation of anaerobic respiration by controlling anaerobic electron transport, the heme biosynthesis system, and the cytochrome c maturation system. Biochemical assays demonstrated that levels of c-type cytochromes were lower in the fur mutant, consistent with the transcriptional profiling. Transcriptomic analysis and electrophoretic mobility shift assays revealed a primary regulation network for Fur in WP3. These results suggest that Fur may act as a sensor for anoxic conditions to trigger and influence the anaerobic respiratory system.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chemical neurotransmission occurs at chemical synapses and endocrine glands, but up to now there was no means for direct monitoring of neurotransmitter exocytosis fluxes and their precise kinetics ...from inside an individual synapse. The fabrication of a novel finite conical nanoelectrode is reported perfectly suited in size and electrochemical properties for probing amperometrically inside what appears to be single synapses and monitoring individual vesicular exocytotic events in real time. This allowed obtaining direct and important physiological evidences which may yield important and new insights into the nature of synaptic communications.
Chemical neurotransmission occurs at chemical synapse, but up to now there was no means for direct monitoring of neurotransmitter exocytosis and its precise kinetics from inside individual infinitesimal synapse. A novel finite conical nanoelectrode is fabricated and used in a newly developed amperometric method (see picture) for probing inside what appears to be single synapses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•First review paper focused on transmissibility-based system identification.•Fundamental concepts of transmissibility and its basic properties are summarized.•The literature review categorizes ...transmissibility functions as local and global.•Application of transmissibility function in modal analysis, damage detection and model updating are reviewed.•Gaps requiring additional work and possible future trends are highlighted.
The difficulty of achieving controlled input has led to the development of new output-only structural health monitoring (SHM) approaches. Without measuring the input or assuming a specific input model, a transmissibility function (TF) as a mathematical representation of the output-to-output relationship has proven to be an attractive tool in SHM. The state of the art and challenges to TF analysis that cast SHM in the context of a system identification (SI) paradigm are reviewed and discussed in this study. This review starts with an overview of the fundamentals of TFs by illustrating its categories, connections with frequency response functions (FRFs), and basic properties. By categorizing TFs as local and global, this literature review limits the practice of various methodologies to the following key aspects: modal analysis, damage detection, and model updating. A brief treatment of the basic ideas is presented while a comprehensive and critical explanation of their contents is not attempted. Based on the review, existing studies are discussed, highlighting gaps requiring additional work and possible future trends for TF-based system identification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intrahepatic cholangiocarcinoma (iCCA) has over the last 10‐20 years become the focus of increasing concern, largely due to its rising incidence and high mortality rates worldwide. The significant ...increase in mortality rates from this primary hepatobiliary cancer, particularly over the past decade, has coincided with a rapidly growing interest among clinicians, investigators, and patient advocates to seek greater mechanistic insights and more effective biomarker‐driven targeted approaches for managing and/or preventing this challenging liver cancer. In addition to discussing challenges posed by this aggressive cancer, this review will emphasize recent epidemiological, basic, and translational research findings for iCCA. In particular, we will highlight emerging demographic changes and evolving risk factors, the critical role of the tumor microenvironment, extracellular vesicle biomarkers and therapeutics, intertumoral and intratumoral heterogeneity, and current and emerging targeted therapies regarding iCCA. Specifically, recent evidence linking non–bile duct medical conditions, such as nonalcoholic fatty liver disease and nonspecific cirrhosis, to intrahepatic cholangiocarcinogenesis together with geographic and ethnic variation will be assessed. Recent developments concerning the roles played by transforming growth factor‐β and platelet‐derived growth factor D in driving the recruitment and expansion of cancer‐associated myofibroblasts within cholangiocarcinoma (CCA) stroma as well as their therapeutic implications will also be discussed. In addition, the potential significance of extracellular vesicles as bile and serum biomarkers and therapeutic delivery systems for iCCA will be described. An integrated systems approach to classifying heterogeneous iCCA subtypes will be further highlighted, and recent clinical trials and emerging targeted therapies will be reviewed, along with recommendations for future translational research opportunities. Established international CCA networks are now facilitating collaborations aimed at advancing iCCA translational and clinical research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Solid tumors are thought to contain cancer stem cells (CSCs) as a distinct population responsible for tumor relapse and metastasis due to their abilities to self-renew, differentiate, and give rise ...to a new tumor in local or distant organs. CSCs have been identified in many tumor types, including hepatocellular carcinoma (HCC), the fifth most common and third most deadly malignancy with observable heterogeneity. Numerous studies have shown that hepatic CSCs could be enriched via different cell surface markers, eg, CD13, CD24, CD44, CD90, CD133, EpCAM (CD326), and OV6. They also could be identified through functional assays such as isolating the side population cells by Hoechst dye staining or screening cells with a high activity of aldehyde dehydrogenase. Functional characterization of hepatic CSCs has revealed several deregulated signaling pathways, such as Wnt/β-catenin, AKT, transforming growth factor-beta (TGF-β), interleukin (IL)-6/STAT3 pathways to be critical in inducing "stemness" of HCC and in promoting self-renewal, tumorigenicity, and chemoresistance. An increased understanding of hepatic CSC biology facilitated the development of new diagnostic, prognostic, and therapeutic strategies for improving HCC clinical management. In this review, we summarize recent evidence including the identification of the hepatic CSC and its underlying biological mechanisms, and discuss the potential clinical implications in HCC.
Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce their immune-mediated clearance to prevent tumor initiation, a process termed “senescence surveillance.” However, ...senescent hepatocytes give rise to hepatocellular carcinomas (HCCs), if the senescence program is bypassed or if senescent cells are not cleared. Here, we show context-specific roles for CCR2+ myeloid cells in liver cancer. Senescence surveillance requires the recruitment and maturation of CCR2+ myeloid cells, and CCR2 ablation caused outgrowth of HCC. In contrast, HCC cells block the maturation of recruited myeloid precursors, which, through NK cell inhibition, promote growth of murine HCC and worsen the prognosis and survival of human HCC patients. Thus, while senescent hepatocyte-secreted chemokines suppress liver cancer initiation, they may accelerate the growth of fully established HCC.
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•The CCL2-CCR2 axis is necessary for clearance of pre-cancerous senescent hepatocytes•Absence of the CCL2-CCR2 axis leads to HCC outgrowth from senescent hepatocytes•Peritumoral tissue senescence accelerates growth of HCC in mice and humans•Senescence-recruited CCR2+ myeloid cells enhance HCC growth by NK cell inhibition
Eggert et al. show that CCL2 is secreted from oncogene-induced senescent hepatocytes to recruit CCR2+ immature myeloid cells (iMC). These iMC differentiate into macrophages that clear pre-malignant senescent cells, but iMC promote growth of established hepatocellular carcinoma through NK cell inhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Micro/nanoprocessing of graphene surfaces has attracted significant interest for both science and applications due to its effective modulation of material properties, which, however, is usually ...restricted by the disadvantages of the current fabrication methods. Here, by exploiting cylindrical focusing of a femtosecond laser on graphene oxide (GO) films, we successfully produce uniform subwavelength grating structures at high speed along with a simultaneous in situ photoreduction process. Strikingly, the well-defined structures feature orientations parallel to the laser polarization and significant robustness against distinct perturbations. The proposed model and simulations reveal that the structure formation is based on the transverse electric (TE) surface plasmons triggered by the gradient reduction of the GO film from its surface to the interior, which eventually results in interference intensity fringes and spatially periodic interactions. Further experiments prove that such a regular structured surface can cause enhanced optical absorption (>20%) and an anisotropic photoresponse (~0.46 ratio) for the reduced GO film. Our work not only provides new insights into understanding the laser-GO interaction but also lays a solid foundation for practical usage of femtosecond laser plasmonic lithography, with the prospect of expansion to other two-dimensional materials for novel device applications.
Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under ...medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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