Ferroptosis, a newly identified form of regulated cell death, is characterized by overwhelming iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Preventing cellular iron ...overload by reducing iron uptake and increasing iron storage may contribute to inhibit ferroptosis. Mitochondrial ferritin (FtMt) is an iron-storage protein that is located in the mitochondria, which has a significant role in modulating cellular iron metabolism. Recent studies showed that FtMt played inhibitory effects on oxidative stress-dependent neuronal cell damage. However, the potential role of FtMt in the progress of ferroptosis in neuronal cells has not been studied. To explore this, we established ferroptosis models of cell and drosophila by erastin treatment. We found that overexpression of FtMt in neuroblastoma SH-SY5Y cells significantly inhibited erastin-induced ferroptosis, which very likely was achieved by regulation of iron homeostasis. Upon erastin treatment, significant increases of cellular labile iron pool (LIP) and cytosolic ROS were observed in wild-type SH-SY5Y cells, but not in the FtMt-overexpressed cells. Consistent with that, the alterations of iron-related proteins in FtMt-overexpressed cells were different from that of the control cells. We further investigated the role of FtMt in erastin-induced ferroptosis in transgenic drosophila. We found that the wild-type drosophilas fed an erastin-containing diet didn't survive more than 3 weeks. In contrast, the FtMt overexpressing drosophilas fed the same diet were survival very well. These results indicated that FtMt played a protective role in erastin-induced ferroptosis.
Electrolyte additive is an effective strategy to inhibit the uncontrolled growth of Li dendrites for lithium metal batteries (LMBs). However, most of the additives are complex synthesis and prone to ...decompose in cycling. Herein, in order to guide the homogeneous deposition of Li+, carbonized polymer dots (CPDs) as electrolyte additives are successfully designed and synthesized by microwave (M‐CPDs) and hydrothermal (H‐CPDs) approaches. The controllable functional groups containing N or O (especially pyridinic‐N, pyrrolic‐N, and carboxyl group) enable CPDs to keep stable in electrolytes for at least 3 months. Meanwhile, the clusters formed between CPDs and Li+ through electrostatic interaction effectively guide the uniform Li dispersion and limit the “tip effect” and dendrite formation. Moreover, as lithiophilic groups increase, the strong electrostatic interference for the solvation effect of Li+ in the electrolyte is formed, which induces faster Li+ diffusion/transfer. As expected, H‐CPDs achieve the ultra‐even Li+ transfer. The corresponding Li//LiFePO4 full cell delivers a high capacity retention rate of 93.8% after 200 cycles, which is much higher than that of the cells without additives (61.2%) and with M‐CPDs (83.7%) as additives. The strategy in this work provides a theoretical direction for CPDs as electrolyte additives used in energy storage devices.
Two kinds of carbonized polymer dots (CPDs) (M‐CPDs and H‐CPDs) as electrolyte additives are successfully designed and synthesized. H‐CPDs with more pyridinic‐N, pyrrolic‐N, and COOH deliver more even Li+ flux through abundant H‐CPDs‐Li clusters bound by strong electrostatic interaction. The symmetrical cell exhibits enhanced cycling stability of 3700 h.
High‐risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost‐effective HCV testing strategies for high‐risk ...populations to identify potential undiagnosed HCV‐infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high‐risk populations. Among the 2093 samples from high‐risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV‐positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high‐risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti‐HCV screening, followed by HCV RNA testing on reactive samples.
This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC).
The relationship between HOXB7 expression ...and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways.
HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G(0)-G(1) to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G(1)-S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity.
Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.
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•An improved sharp interface model for subsurface LNAPL extraction was developed.•Shark-fin LNAPL saturation distribution and constant-head boundary are considered.•The model improved ...20% accuracy in predicting field LNAPL extraction.•Pump should locate in the middle of LNAPL layer in well with single-pump extraction.•LNAPL pump should gradually approach the air-oil interface with dual-pump extraction.
Multiphase extraction (MPE) is widely used as an in situ method for the remediation of groundwater contaminated by light non-aqueous liquid (LNAPL). For the purpose of achieving the best performance of MPE remediation, it is critical to accurately characterize the LNAPL transport processes above the groundwater table with an easy-to-use model. In this study, we developed an improved sharp interface model considering constant head at the well screen and shark-fin distribution of LNAPL saturation above groundwater table. The model was successfully validated using the test data of Lari et al. (2018). The results indicate, the LNAPL extraction rate is most sensitive to the properties of fluid and media. Also, this improved model was used to analyze the effects of technical parameters such as submersible position of oil pump and water extraction rate on remediation performance, we observed that in the case of a single-pump MPE, even after changing the hydraulic conductivity and porosity of the media, the optimized location of the submersible LNAPL pump is halfway inside the well. Similarly, in the case of dual-pump MPE, an increasing pump rate of water (Qw) promotes the LNAPL extraction rate, and an empirical relationship between the optimized LNAPL pump position (ms) varies with the Qw exhibiting a certain pattern. Overall, the improved sharp interface model better interprets the field MPE data compared to the interphase mass-transport model proposed by Lari et al. (2018). Therefore, the proposed model characterizes LANPL transport during LNAPL extraction better and can also be utilized to optimize the MPE more comprehensively.
Plants have evolved sophisticated genetic networks to regulate iron (Fe) homeostasis for their survival. Several classes of plant hormones including jasmonic acid (JA) have been shown to be involved ...in regulating the expression of iron uptake and/or deficiency-responsive genes in plants. However, the molecular mechanisms by which JA regulates iron uptake remain unclear. In this study, we found that JA negatively modulates iron uptake by downregulating the expression of FIT (bHLH29), bHLH38, bHLH39, bHLH100, and bHLH101 and promoting the degradation of FIT protein, a key regulator of iron uptake in Arabidopsis. We further demonstrated that the subgroup IVa bHLH proteins, bHLH18, bHLH19, bHLH20, and bHLH25, are novel interactors of FIT, which promote JA-induced FIT protein degradation. These four IVa bHLHs function redundantly to antagonize the activity of the Ib bHLHs (such as bHLH38) in regulating FIT protein stability under iron deficiency. The four IVa bHLH genes are primarily expressed in roots, and are inducible by JA treatment. Moreover, we found that MYC2 and JAR1, two critical components of the JA signaling pathway, play critical roles in mediating JA suppression of the expression of FIT and Ib bHLH genes, whereas they differentially modulate the expression of bHLH18, bHLH19, bHLH20, and bHLH25 to regulate FIT accumulation under iron deficiency. Taken together, these results indicate that by transcriptionally regulating the expression of different sets of bHLH genes JA signaling promotes FIT degradation, resulting in reduced expression of iron-uptake genes, IRT1 and FRO2, and increased sensitivity to iron deficiency. Our data suggest that there is a multilayered inhibition of iron-deficiency response in the presence JA in Arabidopsis.
This study show that JA, an important integrator balancing plant growth and defense responses, inhibits iron uptake by repressing the expression of FIT and four Ib bHLH genes and modulating the degradation of FIT. The tight regulation of iron acquisition during JA-mediated defense processes may be beneficial for plant survival in an ever-changing environment.
Background
Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (pneumococcus) and influenza vaccines are administered in children to prevent infections caused by these pathogens. The ...benefits of vaccination for asthma control in children and the elicited immune response are not fully understood. This study aimed to investigate the impact of these vaccinations on respiratory infections, asthma symptoms, asthma severity and control status, pathogen colonization and in vitro immune responses to different stimulants mimicking infections in asthmatic children.
Methods
Children aged 4–6 years were recruited into the multicentre prospective PreDicta study conducted across five European countries. Information about vaccination history, infections, antibiotic use, inhaled corticosteroid (ICS) use and asthma symptoms in the last 12 months were obtained from questionnaires of the study. Nasopharyngeal samples were collected at the first visit to assess bacterial and viral colonization, and venous blood for isolation of peripheral blood mononuclear cells (PBMCs). The PBMCs were stimulated with phytohemagglutinin, R848, Poly I:C and zymosan. The levels of 22 cytokines and chemokines were measured in cell culture supernatants using a luminometric multiplex assay.
Results
One‐hundred and forty asthmatic preschool children (5.3 ± 0.7 years) and 53 healthy children (5.0 ± 0.8 years) from the PreDicta cohort were included in the current study. Asthmatic children were associated with more frequent upper and lower respiratory infections, and more frequent and longer duration of antibiotic use compared with healthy children. In asthmatic children, sufficient H. influenzae vaccination was associated with a shorter duration of upper respiratory infection (URI) and overall use and average dose of ICS. The airway colonization was characterized by less pneumococcus and more rhinovirus. Pneumococcal vaccination was associated with a reduction in the use rate and average dose of ICS, improved asthma control, and less human enterovirus and more H. influenzae and rhinovirus (RV) airway colonization. Influenza vaccination in the last 12 months was associated with a longer duration of URI, but with a decrease in the occurrence of lower respiratory infection (LRI) and the duration of gastrointestinal (GI) infection and antibiotic use. Asthmatic preschoolers vaccinated with H. influenzae, pneumococcus or influenza presented higher levels of Th1‐, Th2‐, Th17‐ and regulatory T cells (Treg)‐related cytokines in unstimulated PBMCs. Under stimulation, PBMCs from asthmatic preschoolers with pneumococcal vaccination displayed a predominant anti‐inflammatory immune response, whereas PBMCs from asthmatic children with sufficient H. influenzae or influenza vaccination were associated with both pro‐ and anti‐inflammatory immune responses.
Conclusion
In asthmatic preschoolers, the standard childhood vaccinations to common respiratory pathogens have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis.
In the PreDicta cohort, we found that pneumococcal vaccination was associated with a reduced ICS use and better asthma control. Haemophilus influenzae vaccination was associated with reduced ICS use and influenza vaccination was associated with reduced LRI and antibiotic use in asthmatic preschool children. Pneumococcal vaccination was associated with a predominant anti‐inflammatory immune response, whereas H. influenzae or influenza vaccinations were associated with both pro‐ and anti‐inflammatory responses. Our results indicate that common vaccinations in asthmatic children benefit to asthma control and modulate immune responses relevant to improving asthma pathogenesis.Abbreviations: CCL, chemokine (C‐C motif) ligand; CXCL, chemokine (C‐X‐C motif) ligand; ICS, inhaled corticosteroid; CCL, chemokine (C‐C motif) ligand; CXCL, chemokine (C‐X‐C motif) ligand; PBMCs, peripheral blood mononuclear cells; PreDicta, post‐infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases; RI, respiratory infection; TNF‐α, tumor necrosis factor alpha
Apoptosis plays a key role in keloids. Growth arrest and DNA damage‐inducible gene 153 (GADD153) is regulated by apoptosis. Botulinum toxin type A (BTXA) can induce apoptosis in keloid fibroblasts. ...This research aimed to explore the hypothesis that GADD153 mediates apoptosis in keloid fibroblasts exposed to BTXA. BTXA significantly induced GADD153 protein and mRNA expression in keloid fibroblasts. Treatment with c‐Jun N‐terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and tumour necrosis factor‐alpha (TNF‐α) antibodies reversed the BTXA‐induced GADD153 expression. BTXA enhanced the transcriptional activity of GADD153, whereas the GADD153 mutant plasmid, JNK siRNA and anti‐TNF‐α antibody treatment abolished the BTXA‐induced transcriptional activity of GADD153. The addition of TNF‐α to keloid fibroblasts markedly increased GADD153 protein expression. The addition of GADD153 siRNA, SP600125 and anti‐TNF‐α antibodies reversed cell death and caspase 3 and 9 activity induced by BTXA.
The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since ...2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China.
Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS.
A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates.
This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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