•Excessive addition or improper use of SPAs can produce possible harms.•BHT can induce apoptosis and promote tumorigenesis.•BHA metabolites are involved in carcinogenicity process.•TBHQ ...carcinogenicity is related to induction of TQ and CYP1A1.
Synthetic phenolic antioxidants can interact with peroxides produced by food. This paper reviews correlation between BHA, BHT and TBHQ metabolism and harms they cause and provides a theoretical basis for rational use of BHA, BHT and TBHQ in food, and also put some attention on the transformation and metabolic products of PG. We introduce BHA, BHT, TBHQ, PG and their possible metabolic pathways, and discuss possible harms and their specific mechanisms responsible. Excessive addition or incorrect use of synthetic phenolic antioxidants results in carcinogenicity, cytotoxicity, oxidative stress induction and endocrine disrupting effects, which warrant attention. BHA carcinogenicity is related to production of metabolites TBHQ and TQ, and cytotoxic effect of BHA is the main cause of apoptosis induction. BHT carcinogenicity depends on DNA damage degree, and tumour promotion is mainly related to production of quinone methylation metabolites. TBHQ carcinogenicity is related to induction of metabolite TQ and enzyme CYP1A1.
The pre-metastatic niche educated by primary tumor-derived elements contributes to cancer metastasis. However, the role of host stromal cells in metastatic niche formation and organ-specific ...metastatic tropism is not clearly defined. Here, we demonstrate that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis in the spontaneous metastatic models. Mechanistically, primary tumor-derived exosomal RNAs, which are enriched in small nuclear RNAs, activate TLR3 in lung epithelial cells, consequently inducing chemokine secretion in the lung and promoting neutrophil recruitment. Identification of metastatic axis of tumor exosomal RNAs and host lung epithelial cell TLR3 activation provides potential targets to control cancer metastasis to the lung.
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•TLR3 deficiency reduces lung metastasis in the spontaneous cancer metastatic models•Host TLR3 promotes lung pre-metastatic niche formation via neutrophil recruitment•Tumor exosomal RNAs activate alveolar epithelial TLR3 to induce chemokines•High TLR3 level and neutrophil infiltration in lung cancer predict poor prognosis
Liu et al. demonstrate that TLR3 in host alveolar epithelial cells is critical for neutrophil recruitment and lung pre-metastatic niche formation. Mechanistically, small nuclear RNAs from primary tumor-derived exosomes activate TLR3, which leads to chemokine secretion and neutrophil infiltration.
Curcumin exerts a suppressive effect in tumor growth by acting as a modulator of multiple molecular targets. Circular RNA hsa_circ_0007580 (circ-PRKCA) accelerates the tumorigenesis of non-small cell ...lung cancer (NSCLC). However, whether curcumin can regulate circ-PRKCA to inhibit NSCLC progression is unclear.
Cell viability, colony formation, apoptosis, migration, and invasion were analyzed using Cell Counting Kit-8 (CCK-8), plate clone, flow cytometry, or transwell assay. Expression of circ-PRKCA, microRNA (miR)-384, and ITGB1 mRNA (integrin subunit beta 1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Curcumin repressed NSCLC growth through regulating circ-PRKCA expression was validated by xenograft assay. The targeting relationship between circ-PRKCA or ITGB1 and miR-384 was verified by dual-luciferase reporter assay. The level of ITGB1 protein was measured by western blotting.
Circ-PRKCA and ITGB1 expression were elevated in NSCLC tissues and cells, but miR-384 had an opposing tendency. After curcumin treatment, the expression tendency of circ-PRKCA, miR-384, and ITGB1 in NSCLC cells was overturned. Furthermore, curcumin impeded viability, colony formation, migration, invasion, and accelerated apoptosis of NSCLC cells, but these impacts were partially reversed by circ-PRKCA elevation, miR-384 downregulation, or ITGB1 overexpression. Also, the inhibitory effect of curcumin on xenograft tumor was further enhanced after circ-PRKCA knockdown. Notably, circ-PRKCA regulated ITGB1 expression through sponging miR-384 in curcumin-treated NSCLC cells.
Curcumin inhibited NSCLC growth through downregulating circ-PRKCA, which regulated ITGB1 expression by adsorbing miR-384. This study provided a new mechanism to understand how curcumin inhibited the progression of NSCLC.
The gut microbiota is the largest microbiota in the body, which is closely related to the immune state of the body. A number of studies have shown that gut microbiota and its metabolites are involved ...in host immune regulation. Immune checkpoint inhibitors have become an important drug for the treatment of many malignant tumors, which can significantly improve the prognosis of tumor patients. However, a considerable number of patients cannot benefit from immune checkpoint inhibitors. At present, the known treatment methods of microbiota manipulation mainly include fecal microbiota transplantation, dietary regulation, prebiotics and so on. Therefore, this paper will discuss the possibility of improving the anti-tumor efficacy of immunotherapy from the perspectives of the gut microbiota and immunotherapy.
The application of fiber-reinforced polymer (FRP) bars and ultra-high performance concrete (UHPC) in the field of civil engineering is promising. An innovative FRP bar-reinforced UHPC short-ribbed ...bridge deck slab, with low self-weight and high structural performance, was proposed in this study. The behavior of one-way basalt FRP (BFRP) bar-reinforced UHPC slabs under concentrated load was experimentally investigated, and compared with that of a steel bar-reinforced UHPC slab. The ultimate capacity of the one-way BFRP bar-reinforced UHPC slab was 0.59 times that of the steel bar-reinforced UHPC slab, while its ductility was better. Increasing the reinforcement ratio and loading area was beneficial to the ductility of one-way BFRP bar-reinforced UHPC slabs. Moreover, the model proposed by EI-Gamal et al. was found to be suitable for evaluating the punching shear capacities of one-way BFRP bar-reinforced UHPC slabs. However, the model failed to consider the unique strain-hardening characteristics of UHPC, which led to conservative prediction.
Field-cast ultra-high performance concrete (UHPC) connections are an innovative and prospective solution for combining full-depth precast concrete decks and steel girders. However, previous studies ...show that the slip capacity of stud shear connectors embedded in UHPC cannot meet the requirements for ductile connectors by Eurocode 4, which can reduce the resistance of steel and concrete composite members. In this study, the rubber-sleeved stud shear connector, which is a composite of ordinary stud and rubber sleeve, was adopted for the field-cast UHPC connections. Push-out tests were conducted to investigate the static and fatigue behavior of the rubber-sleeved stud shear connector as part of field-cast UHPC connections. Results of static tests showed that the rubber-sleeved stud shear connector has sufficient deformation capacity and its slip capacity is 1.5 times that of the ordinary stud shear connector. Compared to ordinary stud shear connectors, UHPC with high strength and stiffness has a relatively small effect on improving the shear strength and stiffness of rubber-sleeve stud shear connectors. Results of fatigue tests showed that the rubber-sleeved stud shear connector in UHPC has similar fatigue behavior to that in normal strength concrete. Though UHPC improves the restraint to the stud deformation, the influence of rubber sleeves is still decisive in determining the fatigue behavior of rubber-sleeve stud shear connectors. In addition, based on the results of strain gauges at stud roots, it was found that the crack initiation process consumes a small proportion of the fatigue life of rubber-sleeved stud shear connectors, which is about 5%.
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•RT-ddPCR demonstrated superior quantification accuracy for SARS-CoV-2 detection compared to RT-qPCR and was particularly advantageous at low viral levels with better precision and ...sensitivity.•RT-ddPCR outperformed RT-qPCR for viral RNA detection in the complex wastewater matrix and yielded a significantly higher detection rate in large-volume SARS-CoV-2 positive wastewater samples.•RT-ddPCR exhibited more robust SARS-CoV-2 detection with the presence of a mismatch in the probe binding region when consensus assay was used.•RT-ddPCR showed superiority over RT-qPCR for virus genotyping with higher accuracy and detection rate, especially at low levels of allele frequencies and concentrations.•By taking SARS-CoV-2 as a model system, this study suggested RT-ddPCR as a promising tool in wastewater surveillance scenarios and other relevant applications for future infectious disease outbreaks.
The increased frequency of human infectious disease outbreaks caused by RNA viruses worldwide in recent years calls for enhanced public health surveillance for better future preparedness. Wastewater-based epidemiology (WBE) is emerging as a valuable epidemiological tool for providing timely population-wide surveillance for disease prevention and response complementary to the current clinical surveillance system. Here, we compared the analytical performance and practical applications between predominant molecular detection methods of RT-qPCR and RT-ddPCR on SARS-CoV-2 detection in wastewater surveillance. When pure viral RNA was tested, RT-ddPCR exhibited superior quantification accuracy at higher concentration levels and achieved more sensitive detection with reduced variation at low concentration levels. Furthermore, RT-ddPCR consistently demonstrated more robust and accurate measurement either in the background of the wastewater matrix or with the presence of mismatches in the target regions of the consensus assay. Additionally, by detecting mock variant RNA samples, we found that RT-ddPCR outperformed RT-qPCR in virus genotyping by targeting specific loci with signature mutations in allele-specific (AS) assays, especially at low levels of allele frequencies and concentrations, which increased the possibility for sensitive low-prevalence variant detection in the population. Our study provides insights for detection method selection in the WBE applications for future infectious disease outbreaks.
•We report major and trace element contents of plagioclase in meteoritic anorthosites.•Simple LMO crystallization cannot derive REE contents in anorthositic plagioclase.•Plagioclase and mafic ...minerals in lunar anorthosites may not be in equilibrium.•Anorthosites are primordial crust metasomatized by KREEP and mantle-derived melts.
The lunar magma ocean (LMO) model was proposed after the discovery of anorthosite in Apollo 11 samples. However, the chemical and isotopic compositions of lunar anorthosites are not fully consistent with its LMO origin. We have analyzed major and trace elements in anorthositic clasts from ten lunar feldspathic meteorites, which are related to the solidification of the LMO. The plagioclase rare earth element (REE) abundances and patterns are not correlated with the Mg# of coexisting mafic minerals in anorthosites, implying that mafic minerals and plagioclase may not be in chemical equilibrium, consistent with their textural differences. The REE abundances in plagioclase range approximately fortyfold, which cannot be produced by fractional crystallization of a single magma. Combining plagioclase trace element data from Apollo and meteoritic anorthosites, we propose that plagioclases derived from the LMO floated to the surface to form the primordial crust, which then may have been metasomatized by incompatible-element-rich KREEP (potassium, rare earth element, phosphorus) melts and mantle-derived partial melts. The lunar anorthosites may represent this metasomatized crust rather than solely a derivative from the LMO. Furthermore, silicate melts similar to the metasomatic agents may also have melted the crust to form the Mg-suite rocks. This hypothesis is consistent with overlapping ranges of age and initial εNd between lunar anorthosites and Mg-suite rocks. These events are consistent with an overturn event of the cumulate mantle very early after primordial crust formation to produce the partial melts that metasomatized the crust.
AIM2 and Psoriasis Zhang, Yuxi; Xu, Xiaoqing; Cheng, Hui ...
Frontiers in immunology,
01/2023, Letnik:
14
Journal Article
Recenzirano
Odprti dostop
Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The ...pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 (
), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.
Drosophila RhoGAP18B was identified as a negative regulator of small GTPase in the behavioral response to ethanol. However, the effect of RhoGAP18B on cell migration is unknown. Here, we report that ...RhoGAP18B regulates the migration of border cells in Drosophila ovary. The RhoGAP18B gene produces four transcripts and encodes three translation isoforms. We use different RNAi lines to knockdown each RhoGAP18B isoform, and find that knockdown of RhoGAP18B-PA, but not PC or PD isoform, blocks border cell migration. Knockdown of RhoGAP18B-PA disrupts the asymmetric distribution of F-actin in border cell cluster and increases F-actin level. Furthermore, RhoGAP18B-PA may act on Rac to regulate F-actin organization. Our data indicate that RhoGAP18B shows isoform-specific regulation of border cell migration.
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