Wnt/ß-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer.

Wnt/ß-catenin signaling is a critical pathway that influences development and therapeutic response of non-small cell lung cancer (NSCLC). In recent years, many Wnt regulators, including proteins, miRNAs, lncRNAs, and circRNAs, have been found to promote or inhibit signaling by acting on Wnt proteins, receptors, signal transducers and transcriptional effectors. The identification of these regulators and their underlying molecular mechanisms provides important implications for how to target this pathway therapeutically. In this review, we summarize recent studies of Wnt regulators in the development and therapeutic response of NSCLC.

Cerebrovascular Dysregulation in Patients with Glioma Assessed with Time-shifted BOLD fMRI.

Background Microscopic vascular events, such as neovascularization and neurovascular uncoupling, are common in cerebral glioma. Mapping the cerebrovascular network remodeling at the macroscopic level may provide an alternative approach to assess hemodynamic dysregulation in patients with glioma. Purpose To investigate cerebrovascular dynamics and their relevance to tumor aggressiveness by using time-shift analysis (TSA) of the systemic low-frequency oscillation (sLFO) of the resting-state blood oxygenation level-dependent signal and a decision tree model. Materials and Methods In this retrospective study, 96 patients with histologically confirmed cerebral glioma were consecutively included (March 2012 to February 2017). TSA was performed to quantify the temporal properties of sLFO signals. Alteration in the time-shift properties was assessed in the tumor region and the contralesional hemisphere relative to the brains of healthy controls by using the Mann-Whitney U test. A decision tree model based on time-shift features was developed to predict the World Health Organization (WHO) glioma grade. Results A total of 88 patients with glioma (WHO grade II, 45; grade III, 21; grade IV, 22; mean age, 42 years; age range, 20-73 years; 51 men) and 40 healthy individuals from the 1000 Functional Connectomes Project (mean age, 32 years; age range, 24-49 years; 19 men) were included. The sLFO of the brain tissues was characterized by increased time shift in the tumor region and enhanced correlation with the global reference signal in the contralesional hemisphere compared with healthy brains. The proportion of tumor voxels with negative correlation to the reference signal significantly increased with the glioma malignancy grade. The decision tree model achieved an accuracy of 91% (80 of 88 patients) in predicting the glioma malignancy grade at the individual level (P = .004) based on the time-shift features. Conclusion Gliomas induced grade-specific cerebrovascular dysregulation in the entire brain, with altered time-shift features of systemic low-frequency oscillation signals. © RSNA, 2022 Online supplemental material is available for this article.

Roles of Infection in Psoriasis.

Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations. Genetic predisposition, environmental factors, and immune dysfunction all contribute to the pathogenesis of psoriasis with host-microbe interaction governing the progression of this disease. Emerging evidence has indicated that infection is an environmental trigger for psoriasis and plays multiple roles in its maintenance as evidenced by the frequent association between guttate psoriasis onset and acute streptococcal infection. Different infectious factors act on immune cells to produce inflammatory cytokines that can induce or aggravate psoriasis. In addition to bacterial infections, viral and fungal infections have also been shown to be strongly associated with the onset or exacerbation of psoriasis. Intervention of skin microbiota to treat psoriasis has become a hot research topic. In this review, we summarize the effects of different infectious factors (bacteria, viruses, and fungi) on psoriasis, thereby providing insights into the manipulation of pathogens to allow for the identification of improved therapeutic options for the treatment of this condition.

Functional characterization of T3SS C-ring component VscQ and evaluation of its mutant as a live attenuated vaccine in zebrafish (Danio rerio) model.

Vibrio alginolyticus, a Gram-negative bacterium, has been recognized as an opportunistic pathogen in marine animals as well as humans. Type III secretion system (T3SS) is critical for pathogen virulence and disease development. However, no more information is known about the C-ring component VscQ and its physiological role. In this study, gene vscQ was cloned from V. alginolyticus wild-type strain HY9901 and the mutant strain HY9901ΔvscQ was constructed by the in-frame deletion method. The HY9901ΔvscQ mutant showed an attenuated swarming phenotype and a closely 4.6-fold decrease in the virulence to Danio rerio. However, the HY9901ΔvscQ mutant showed no difference in growth, biofilm formation and ECPase activity. HY9901ΔvscQ reduces the release of LDH, NO and caspase-3 activity of infected FHM cell, which are involved in fish cell apoptosis. Deletion of gene vscQ downregulates the expression level of T3SS-related genes including vscL, vopB, hop, vscO, vscK, vopD, vcrV and vopS and flagellum-related genes (flaA and fliG). And Danio rerio vaccinated via i.m injection with HY9901ΔvscQ induced a relative percent survival (RPS) value of 71% after challenging with the wild-type HY9901. Real-time PCR assays showed that vaccination with HY9901ΔvscQ enhanced the expression of immune-related genes, including TNF-α, TLR5, IL-6R, IgM and c/ebpß in liver and spleen after vaccination, indicating that it is able to induce humoral and cell-mediated immune response in zebrafish. These results demonstrate that the HY9901ΔvscQ mutant could be used as an effective live vaccine to combat V. alginolyticus infection.

Dietary seaweed (Enteromorpha) polysaccharides improves growth performance involved in regulation of immune responses, intestinal morphology and microbial community in banana shrimp Fenneropenaeus merguiensis.

The present study was conducted to evaluate the effects of marine polysaccharides from seaweed Enteromorpha on growth performance, immune responses, intestinal morphology and microbial community in the banana shrimp Fenneropenaeus merguiensis. Two thousand and four hundred juvenile shrimps with an average body weight of 2.18 ± 0.06 g were fed for 42 d with diets containing different levels of Enteromorpha polysaccharides (EPS): 0 (control), 1, 2 and 3 g/kg as treatment groups, each of group was replicated three times with two hundred shrimps per replicate. Dietary supplementation of 1 g/kg EPS showed a consistent improvement in the final weight, weight gain, average daily gain rate (ADGR) and specific growth rate (SGR) (P < 0.05), while showed a decrease in the feed conversion ratio (FCR) of shrimp (P < 0.05). Besides, the total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), lysozyme (Lyz), alkaline phosphatase (ALP), and phenoloxidase (PO) activities in hemolymph were enhanced by dietary supplementation of 1 g/kg EPS (P < 0.05), while it reduced the hemolymph MDA content (P < 0.05). Shrimp fed 1 g/kg EPS supplemented diets up-regulated FmLyz, FmSOD5 and FmCLAP gene expression level of hepatopancreas and gill (P < 0.05), and also improved the intestinal FmLC2, FmLyz, FmSOD5 and FmCLAP gene expression levels (P < 0.05). In addition, shrimp fed diets containing 1 g/kg EPS increased the villus width (P < 0.05) and resulted in a higher villus surface area (P < 0.05). According to 16S rRNA sequencing results, dietary supplementation of 1 g/kg EPS tended to increase the relative abundance of Firmicutes at phylum level (P = 0.07) and decrease the relative abundance of Vibrio at genus level (P = 0.08). There was a significant positive correlation between the relative abundance of Firmicutes and mRNA expression of intestinal immune-related genes (P < 0.05). These findings revealed that dietary 1 g/kg EPS could improve growth performance, enhance nonspecific immunity and modulate intestinal function of banana shrimp F. merguiensis.

Atomic Mechanism in Layer-by-Layer Growth via Surface Reconstruction.

Layer-by-layer growth played a critical role in the fine design of novel materials and devices. Although it has been widely studied during materials synthesis, the atomic mechanism of the growth remains unclear due to the lack of direct observation at the atomic scale. Here, we report a new mode in layer-by-layer growth via surface reconstruction on MoO2 (011) by environmental transmission electron microscopy and density functional theory calculations. Our in situ environmental transmission electron microscopy results demonstrate that the layer-by-layer growth of MoO2 experiences two steps that occur in an oscillatory manner: (1) the formation of an atomic ledge by transforming a section of the reconstructed layer to the intrinsic surface layer and then (2) the spontaneous reconstruction of the newly formed intrinsic surface section. Thus, the surface reconstruction can be considered as an intermediated phase during the layer-by-layer growth of MoO2. A similar phenomenon was also observed in the MoO2 dissolution procedure.

Survival and immune response of white shrimp Litopenaeus vannamei following single and concurrent infections with WSSV and Vibrio parahaemolyticus.

The survival and immune responses of Litopenaeus vannamei were evaluated during white spot syndrome virus (WSSV) or Vibrio parahaemolyticus single and concurrent infections. The mortality, WSSV load, activities of 4 immune enzymes: acid phosphatase (ACP), alkaline phosphatase (AKP), peroxidase (POD) and superoxide dismutase (SOD), and the transcription of Evolutionarily Conserved Signaling Intermediate in Toll pathways of L.vannamei (LvECSIT) were quantified at 0, 3, 6, 12, 24, 48, 72 and 96 h post-infection (pi). The results showed: (i) the cumulative mortality of the co-infection group (WSSV and V. Parahaemolyticus 83%) was significantly lower than the WSSV infection group (97%) (P < 0.05) at 96 hpi; (ii) copies of WSSV in the co-infection group were significantly lower than that of the single infection group from 24 to 96 hpi (P < 0.05); (iii) ACP, AKP,POD and SOD activity in the gills of the co-infection group was higher than that of the WSSV group at12, 48 and 96 hpi (P < 0.05).The expression of LvECSIT mRNA in the co-infection group was significantly higher than in the WSSV infection group from 12 to 72 hpi (P < 0.05).The results indicate that proliferation of WSSV is inhibited by V.parahaemolyticus infection. In addition, infection with WSSV alone causes a significant reduction in some immune responses of shrimp than co-infection with WSSV and V.parahaemolyticus occurs at 26 °C. Third, LvECSIT, an essential member of TLR signaling pathway might play a crucial role in shrimp defense against WSSV - Vibrio co-infection.

Study of a position-sensitive scintillator neutron detector prototype based on 6LiF/ZnS scintillator and silicon photomultiplier arrays readout.

Due to the shortage of the 3He gas and its rapidly increasing price, scintillator detectors, the advantages of which are high spatial resolution and capability of detection in real time, become widely used in many neutron instruments. In this work, a position-sensitive neutron detector consisting of a 6LiF/ZnS scintillation screen and a silicon photomultiplier array linked to a capacitive network to detect the positions of incident neutrons, is constructed and tested. To evaluate the detector performance, a series of neutron beam experiments with the detector prototype were performed in the BL20 at the China Spallation Neutron Source. The spatial resolution was measured, and the energy-selective neutron imaging and Bragg edge measurements of a 316L stainless steel sample were performed. A sub-millimeter spatial resolution could be obtained for the detector prototype under study. The detector with such a high spatial resolution is promising for applications in neutron scattering experimental installations, especially for neutron single-crystal diffractometers.

The Role of the Pentose Phosphate Pathway in Diabetes and Cancer.

The pentose phosphate pathway (PPP) branches from glucose 6-phosphate (G6P), produces NADPH and ribose 5-phosphate (R5P), and shunts carbons back to the glycolytic or gluconeogenic pathway. The PPP has been demonstrated to be a major regulator for cellular reduction-oxidation (redox) homeostasis and biosynthesis. Enzymes in the PPP are reported to play important roles in many human diseases. In this review, we will discuss the role of the PPP in type 2 diabetes and cancer.

Acetylome profiling of Vibrio alginolyticus reveals its role in bacterial virulence.

It is well known that lysine acetylation (Kace) modification is a common post-translational modification (PTM) that plays an important role in multiple biological and pathological functions in bacteria. However, few studies have focused on lysine acetylation modification in aquatic pathogens to date. In this study, the acetylome profiling of fish pathogen, Vibrio alginolyticus was investigated by combining affinity enrichment with LC MS/MS. A total of 2883 acetylation modification sites on 1178 proteins in this pathogen were identified. The Kace modification of several selected proteins were further validated by Co-immunocoprecipitation combined with Western blotting. Bioinformatics analysis showed that seven conserved motifs can be enriched among Kace peptides, and many of them were significantly enriched in metabolic processes such as biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and biosynthesis of amino acids, which was similar to data previously published for V. parahaemolyticus. Moreover, we found at least 102 acetylation modified proteins predicted as virulence factors, which indicate the important role of PTM on bacterial virulence. In general, our results provide a promising starting point for further investigations of the biological role of lysine acetylation on bacterial virulence in V. alginolyticus. BIOLOGICAL SIGNIFICANCE: Lysine acetylation (Kace) modification, is well known to play important roles on diverse biological functions in prokaryotic cell, whereas few studies focused on aquatic pathogens to date. In this study, the acetylome profiling of fish pathogen, Vibrio alginolyticus was investigated by combining affinity enrichment with LC MS/MS. A total of 2883 acetylation modification sites on 1178 proteins in this pathogen were identified. The further bioinformatics analysis showed that seven conserved motifs can be enriched among Kace peptides, and many of them were significantly enriched in metabolic processes, which was similar to data previously published for V. parahemolyticus. Moreover, we found at least 102 acetylation modified proteins predicted as virulence factors, which indicate the important role of PTM on bacterial virulence. In general, our results provide a promising starting point for further investigations of the biological role of lysine acetylation on bacterial virulence in V. alginolyticus.

A T3SS Regulator Mutant of Vibrio alginolyticus Affects Antibiotic Susceptibilities and Provides Significant Protection to Danio rerio as a Live Attenuated Vaccine.

Vibrio alginolyticus is a major cause of Vibriosis in farmed marine aquatic animals and has caused large economic losses to the Asian aquaculture industry in recent years. Therefore, it is necessary to control V. alginolyticus effectively. The virulence mechanism of V. alginolyticus, the Type III secretion system (T3SS), is closely related to its pathogenicity. In this study, the T3SS gene tyeA was cloned from V. alginolyticus wild-type strain HY9901 and the results showed that the deduced amino acid sequence of V. alginolyticus tyeA shared 75-83% homology with other Vibrio spp. The mutant strain HY9901ΔtyeA was constructed by Overlap-PCR and homologous recombination techniques. The HY9901ΔtyeA mutant exhibited an attenuated swarming phenotype and an ~40-fold reduction in virulence to zebrafish. However, the HY9901ΔtyeA mutant showed no difference in growth, biofilm formation and ECPase activity. Antibiotic susceptibility test was observed that wild and mutant strains were extremely susceptible to Amikacin, Minocycline, Gentamicin, Cefperazone; and resistant to oxacillin, clindamycin, ceftazidime. In contrast wild strains are sensitive to tetracycline, chloramphenicol, kanamycin, doxycycline, while mutant strains are resistant to them. qRT-PCR was employed to analyze the transcription levels of T3SS-related genes, the results showed that compared with HY9901 wild type, ΔtyeA had increased expression of vscL, vscK, vscO, vopS, vopN, vscN, and hop. Following vaccination with the mutant strain, zebrafish had significantly higher survival than controls following infection with the wild-type HY9901 (71.2% relative percent survival; RPS). Analysis of immune gene expression by qPCR showed that vaccination with HY9901ΔtyeA increased the expression of IgM, IL-1ß, IL-6, and TNF-α in zebrafish. This study provides evidence of protective efficacy of a live attenuated vaccine targeting the T3SS of V. alginolyticus which may be facilitated by up-regulated pro-inflammatory and immunoglobulin-related genes.

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats.

BACKGROUND: Hyperbaric oxygen (HBO) is an effective adjuvant therapy for ischemia- reperfusion (I/R) injury of the brain, small intestine and testis in addition to crushing injury. Studies have shown that HBO increases the activity of villi of the ileum 30 minutes after I/R injury. The present study aimed to observe the effect of HBO on apoptosis of epithelial cells in the small intestine during different periods of I/R and to elucidate the potential mechanisms. METHODS: Rats were subjected to 60-minute ischemia by clamping the superior mesenteric artery and 60-minute reperfusion by removal of clamping. The rats were randomly divided into four groups: I/R group, HBO precondition or HBO treatment before ischemia (HBO-P), HBO treatment during ischemia period (HBO-I), and HBO treatment during reperfusion (HBO-R). After 60-minute reperfusion, samples of the small intestine were prepared to measure the level of ATP by using the colorimetric method and immunochemical expression of caspase-3. The levels of TNF-α in intestinal tissue were measured using the enzyme-linked immunosorbent assay method (Elisa). RESULTS: TNF-α levels were significantly lower in the HBO-I group than in the HBO-P (P<0.05), HBO-R and I/R groups; there was no significant difference between the HBO-R and I/R groups (P>0.05). The expression of caspas-3 was significantly lower in the HBO-I group than in the HBO-P group (P<0.05); it was also significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). ATP level was significantly lower in the HBO-I group than in the HBO-P group (P<0.05), and also it was significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). CONCLUSIONS: There is an association between HBO, small intestinal I/R injury, and mucosa apoptosis. HBO maintains ATP and aerobic metabolism, inhibites TNF-α production, and thus prevents intestinal mucosa from apoptosis. Best results can be obtained when HBO is administered to patients in the period of ischemia, and no side effects are produced when HBO is given during the period of reperfusion.