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The objective of this study was to investigate effects of anthocyanins (AC) and microbial transglutaminase (MTGase) on the physicochemical properties of surimi gels from silver carp. The addition of AC and MTGase significantly increased gel strength and water holding capacity (WHC) of surimi gels, but the effect of MTGase was much stronger (p<0.05). There were the highest gel strength, storage modulus (G') and WHC with 0.1 g/100 g AC and 0.4 g/100 g MTGase, while they were higher than that with AC or MTGase alone. AC promoted the cross-linking mainly by covalent and non-covalent bonds in surimi gels, while MTGase did mainly through covalent bonds. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) confirmed the results of gel strength, WHC, chemical interactions and G' of surimi gel or paste with AC and MTGase. In general, AC and MTGase could synergistically improve the physicochemical properties of surimi gels and potentially enhance the quality of surimi-based product from silver carp. This article is protected by copyright. All rights reserved.
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Background: Resectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them. Methods: A total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups. Results: The median size of sPAN was 6 (range, 2-9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p < 0.05). Conclusions: Standard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.
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The prevention and treatment of obesity have been one of the most difficult problems in the world. Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies have shown that IF could improve obesity and diabetes-related metabolic disorders. Here, we show that IF can change the composition and metabolic function of intestinal microbes, and reduce lipid absorption by inhibiting PI3K/AKT signaling pathway, with the participation of arginine. Arginine concentration in feces of fasted mice is inversely correlated with Akkermansia muciniphila abundance. Antibiotic-induced clearance of intestinal microbiota greatly inhibits the effect of IF. Furthermore, the colonization test of Akkermansia muciniphila again activates the browning of white adipose tissue and restores the improvement of metabolism to alleviate obesity. These phenomena indicate that every-other-day fasting regimen inhibits intestinal lipid absorption and promotes the browning of white adipose tissue in mice to ameliorate the risk of obesity and metabolic disorders through the microbial flora-metabolite-fat signaling axis. And the above results demonstrate new directions for the treatment of obesity and other metabolic disorders.
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Background/Aims: This study aimed to examine the independent and synergistic association of aerobic physical activity and resistance exercise with nonalcoholic fatty liver disease (NAFLD) using a nationwide representative database. Methods: This was a cross-sectional study using data from the Korea National Health and Nutritional Examination Survey between 2007 and 2010. Multiple logistic regression models were used to examine the independent and synergistic (additive interaction) associations of aerobic physical activity and resistance exercise with NAFLD after adjusting for multiple covariates. Results: The prevalence of NAFLD was 26.2% for men and 17.6% for women. In the fully adjusted multiple logistic regression model to examine the independent association of aerobic physical activity or resistance exercise with NAFLD, the odds ratios for NAFLD were significantly decreased in both men (p=0.03) and women (p<0.01) who had highly active aerobic physical activity. Regarding the frequency of resistance exercise, the odds ratio for NAFLD was decreased in men who did resistance exercise ≥5 days per week (p=0.04), but not in women (p=0.19). However, when investigating the synergistic associations of aerobic physical activity and resistance exercise, the odds ratios for NAFLD significantly decreased when the frequency of both exercises increased together in both men (p for interaction <0.01) and women (p for interaction<0.01). Conclusions: Combining aerobic physical activity and resistance exercise had a synergistic preventive association for NAFLD in Korean men and women.
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Background: Evidence from observational studies on the association of folate and vitamin B12 with autoimmune diseases are conflicting. Objective: We aimed to investigate the relationship of folate and vitamin B12 with autoimmune diseases using Mendelian randomization (MR). Materials and methods: We selected single-nucleotide polymorphisms associated with folate and vitamin B12 at the genome-wide significance level. Summary-level data for four common autoimmune diseases (vitiligo, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus) were obtained from large-scale genome-wide association studies, with a sample size of 44,266, 86,640, 58,284, and 23,210, respectively. MR analyses were conducted using the inverse variance weighted (IVW) approach, and sensitivity analyses were further performed to test the robustness. Results: We found that a higher genetically determined serum folate level per one standard deviation (SD) was associated with a decreased risk of vitiligo by the IVW method [odds ratios (OR) = 0.47; 95% confidence interval (CI): 0.32-0.69; P = 1.33 × 10-4]. Sensitivity analyses using alternative methods showed similar associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.919). In addition, we observed that vitamin B12 per one SD was positively associated with IBD (IVW: OR = 1.14, 95% CI: 1.03-1.26, P = 0.010; maximum likelihood: OR = 1.14, 95% CI: 1.01-1.29, P = 0.035; MR-PRESSO: OR = 1.14, 95% CI:1.01-1.28, P =0.037), while the association was not significant after Bonferroni correction. Conclusion: The study provides convincing evidence for an inverse association between serum folate level and risk of vitiligo. Further studies are warranted to elucidate the possible association between vitamin B12 and risk of IBD.
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BACKGROUND AND AIMS: Out-of-hospital cardiac arrest exerts a large disease burden, which may be mitigated by bystander cardiopulmonary resuscitation and automated external defibrillation. We aimed to estimate the global prevalence and distribution of bystander training among laypersons, which are poorly understood, and to identify their determinants. METHODS: We searched electronic databases for cross-sectional studies reporting the prevalence of bystander training from representative population samples. Pooled prevalence was calculated using random-effects models. Key outcome was cardiopulmonary resuscitation training (training within two-years and those who were ever trained). We explored determinants of interest using subgroup analysis and meta-regression. RESULTS: 28 studies were included, representing 53,397 laypersons. Among national studies, the prevalence of cardiopulmonary resuscitation training within two-years and among those who were ever trained, and automated external defibrillator training was 10.02% (95% CI 6.60-14.05) and 39.64% (95%CI 29.11-50.67), and 15.70% (95% CI 10.17-22.18) respectively. Subgroup analyses by continent revealed pooled prevalence estimates of 31.58% (95%CI 18.70-46.09), 52.62% (95%CI 38.40-66.63), 18.93 (95%CI 0.00-62.94), 64.97% (95%CI 64.00-65.93), and 50.56% (95%CI 47.57-53.54) in Asia, Europe, Middle East, North America, and Oceania respectively, with significant subgroup differences (p<0.01). A country's income and cardiopulmonary resuscitation training (ever trained) (p=0.033) were positively correlated. Similarly, this prevalence was higher among the employed (p<0.00001) and highly educated (p<0.00001). CONCLUSIONS: Large regional variation exists in data availability and bystander training prevalence. Socioeconomic status correlated with prevalence of bystander training, and regional disparities were apparent between continents. Bystander training should be promoted, particularly in Asia, Middle East, and low-income regions. Data availability should be encouraged from under-represented regions.
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Mine wastewater treatment using bio-sulfate reduction technology forms sulfur-containing wastewater that comprises sulfides (HS- and S2-) and metal ions. Biosulfur generated by sulfur-oxidizing bacteria in such wastewater is usually negatively charged hydrocolloidal particles. However, biosulfur and metal resource recovery are difficult using traditional methods. In this study, the sulfide biological oxidation-alkali flocculation (SBO-AF) method was investigated to recover the above resources, and to provide a technical reference for mine wastewater resource recovery and heavy metal pollution control. Specifically, the performance of SBO in forming biosulfur and the key parameters of SBO-AF were explored and then applied in a pilot-scale process to recover resources from wastewater. Results show that partial sulfide oxidation was achieved under a sulfide loading rate of 5.08 ± 0.39 kg/m3·d, dissolved oxygen of 2.9-3.5 mg/L and temperature of 27-30 °C. The average sulfide oxidation rate and sulfur selectivity ratio were 92.86 % and 90.22 %, respectively. At pH 10, metal hydroxide and biosulfur colloids co-precipitated through the precipitation catching and adsorption charge neutralization effect. The average manganese, magnesium and aluminum concentrations and turbidity in the wastewater were 53.93 mg/L, 522.97 mg/L, 34.20 mg/L and 505 NTU, respectively, and decreased to 0.49 mg/L, 80.65 mg/L, 1.00 mg/L and 23.33 NTU, respectively, after treatment. The recovered precipitate mainly contained sulfur, along with metal hydroxides. The average sulfur, manganese, magnesium and aluminum contents were 45.6 %, 29.5 %, 15.1 % and 6.5 %, respectively. Economic feasibility analysis and the above results show that SBO-AF has obvious technical and economic advantages in the recovery resources from mine wastewater.
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The role of peptidoglycan-associated lipoprotein (Pal) in A. baumannii pathogenesis remains unclear. Here, we illustrated its role by constructing a pal deficient A. baumannii mutant and its complementary strain.Transcriptome analysis of the WT and pal mutant revealed a total of 596 differentially expressed genes. Gene Ontology analysis revealed that pal deficiency caused the downregulation of genes related to material transport and metabolic processes. The pal mutant showed a slower growth and was sensitive to detergent and serum killing compared to WT strain, whereas, the complemented pal mutant showed rescued phenotype. The pal mutant caused decreased mortality in mice pneumonia infection compared to WT strain, while the complemented pal mutant showed increased mortality. Mice immunized with recombinant Pal showed 40% protection against A. baumannii-mediated pneumonia. Collectively, these data indicate Pal is a virulence factor of A. baumannii and may serve as a potential target for preventive or therapeutic interventions.
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Acinetobacter baumannii , Pneumonia , Vacinas , Animais , Camundongos , Virulência/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Peptidoglicano/genética , Peptidoglicano/metabolismo , Vacinas/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismoRESUMO
Dicer1 plays a vital role in the formation of mature miRNA and regulates the growth, development, and reproduction of insects. However, it remains to be clarified whether Dicer1 is involved in regulating the biological processes underlying molting and reproduction of Sogatella furcifera (Horváth). Herein, SfDicer1 expression fluctuated in all the developmental stages of S. furcifera and increased as molting progressed. SfDicer1 exhibited high expression in the integument, head, fat body, and ovary of the insects. SfDicer1 dsRNA injection into 1-day-old fourth instar nymphs of S. furcifera substantially decreased the survival rate and expression of the lethal phenotypes of wing malformation and molting defects and significantly inhibited the expression of four conserved miRNAs associated with molting development. Subsequently, following the knockdown of SfDicer1 in the newly emerged (1-12 h) females of S. furcifera, SfVg and SfVgR expression levels were decreased, thereby delaying ovarian development, decreasing the number of eggs, and considerably reducing the hatching rate compared with those of the control. Finally, after silencing SfDicer1 for 48 h, the comparative transcriptome analysis of differentially expressed genes revealed considerable enrichment of the Gene Ontology terms structural constituent of cuticle, structural molecule activity, chitin metabolic process, amino sugar metabolic process, and intracellular anatomical structure, indicating that SfDicer1 inhibition affects the transcription of genes associated with growth and development. Thus, our results suggest that SfDicer1 is essential in the molting, survival, ovarian development, and fecundity of S. furcifera and is a suitable target gene for developing an RNAi-based strategy targeting the most destructive rice insect pest.
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Integrated clinicopathological and molecular analyses of Richter transformation of diffuse large B-cell lymphoma subtype (RT-DLBCL) cases remain limited. This study group included 142 patients with RT-DLBCL. Morphological evaluation and immunophenotyping, using immunohistochemistry and/or multicolour flow cytometry, were performed. The results of conventional karyotyping, fluorescence in situ hybridisation analysis and mutation profiling performed using next generation sequencing were reviewed. Patients included 91 (64.1%) men and 51 (35.9%) women with a median age of 65.4 years (range 25.4-84.9 years) at the time of RT-DLBCL diagnosis. Patients had CLL for a median of 49.5 months (range 0-330 months) before onset of RT-DLBCL. Most cases (97.2%) of RT-DLBCL had immunoblastic (IB) morphology, the remainder had a high grade morphology. The most commonly expressed markers included: CD19 (100%), PAX5 (100%), BCL2 (97.5%), LEF1 (94.7%), CD22 (90.2%), CD5 (88.6%), CD20 (85.7%), CD38 (83.5%), MUM1 (83.3%), CD23 (77%) and MYC (46.3%). Most (51/65, 78.4%) cases had a non-germinal centre B-cell immunophenotype. MYC rearrangement was detected in 9/47 (19.1%) cases, BCL2 rearrangement was detected in 5/22 (22.7%) cases, and BCL6 rearrangement was detected in 2/15 (13.3%) cases. In comparison to CLL, RT-DLBCL had higher numbers of alterations involving chromosomes 6, 17, 21, and 22. The most common mutations detected in RT-DLBCL involved TP53 (9/14, 64.3%), NOTCH1 (4/14, 28.6%) and ATM (3/14, 21.4%). Among RT-DLBCL cases with mutant TP53, 5/8 (62.5%) had TP53 copy number loss, and among those, such loss was detected in the CLL phase of the disease in 4/8 (50%) cases. There was no significant difference in overall survival (OS) between patients with germinal centre B-cell (GCB) and non-GCB RT-DLBCL. Only CD5 expression correlated significantly with OS (HR=2.732; 95% CI 1.397-5.345; p=0.0374). RT-DLBCL has distinctive morphological and immunophenotypic features, characterised by IB morphology and common expression of CD5, MUM1 and LEF1. Cell-of-origin does not seem to have prognostic implications in RT-DLBCL.
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Microplastics (MPs) and nanoplastics (NPs) are novel environmental pollutants that are ubiquitous in the environment and everyday life. NPs can easily enter the tissues and have more significant potential health risks due to their smaller diameter. Previous studies have shown that NPs can induce male reproductive toxicity, but the detailed mechanisms remain uncertain. In this study, intragastric administration treated mice with polystyrene NPs (PS-NPs, 50, and 90 nm) at 3 and 15 mg/mL/day doses for 30 days. Then, the fresh fecal samples were collected from those mice that the exposure doses of 50 nm PS-NPs at 3 mg/mL/day and 90 nm at 15 mg/mL/day for subsequent investigations of 16S rRNA and metabolomics according to significant toxicological effects (Sperm number, viability, abnormality, and testosterone level). The conjoint analysis findings indicated that PS-NPs disrupted the homeostasis of the gut microbiota, metabolism, and male reproduction, suggesting that abnormal gut microbiota-metabolite pathways may be important in PS-NPs-induced male reproductive toxicity. Meanwhile, the common differential metabolites such as 4-deoxy-Erythronic acid, 8-iso-15-keto-PGE2, apo-10'-violaxanthin, beta-D-glucosamine, isokobusone, oleamide, oxoadipic acid, sphingosine induced by 50 and 90 nm PS-NPs might be used as biomarkers to explore PS-NPs-induced male reproductive toxicity. In addition, this study systematically demonstrated that nano-scale PS-NPs induced male reproductive toxicity via the crosstalk of gut microbiota and metabolites. It also provided valuable insights into the toxicity of PS-NPs, which was conducive to reproductive health risk assessment for public health prevention and treatment.
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Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.
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The flagellum is an important organelle for the survival of bacteria and consists of a basal body, hook, and filament. The FlgE protein is the subunit of the hook that connects the basal body and the filament and determines the motility of bacteria. Also, flgE gene plays an essential role in flagellar biosynthesis, swimming ability and biofilm formation. Although the intact flagella and the major component filament have been extensively studied, so far, little is known about the comprehensive understanding of flagellar hook and FlgE. Here in this review, we summarize the structures of flagellar hook and its subunit FlgE in various species and physiological functions of FlgE, including the hook assembly, the structural characteristics of flagellar hook, the mechanical properties of hook, and the similarities and differences between FlgE (hook) and FlgG (distal rod), with special attention on the interaction of FlgE with other molecules, the antigenicity and pro-inflammatory effect of FlgE, and cross-linking of FlgE in spirochetes. We hope our summary of this review could provide a better understanding of the FlgE protein and provide some useful information for developing new effective antibacterial drugs in the future work.
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Proteínas de Bactérias , Flagelos , Proteínas de Bactérias/metabolismo , Flagelos/genéticaRESUMO
κ-Opioid receptors (κ-OR) are widely used to regulate the activity of the cardiovascular system. To explore the effect and mechanism of κ-OR on salt-sensitive hypertensive endothelial dysfunction, we used Dah1 rats to construct a rat model of salt-sensitive hypertension on a high-salt (HS) diet. Then, the rats were treated with κ-OR activators U50,488H (1.25 mg/kg) and inhibitor nor-BNI (2.0 mg/kg) for 4 weeks, respectively. The rat aortas were collected to detect the contents of NO, ET-1, AngII, NOS, T-AOC, SO, and NT. Protein expression was determined for NOS, Akt, and Caveolin-1. In addition, the vascular endothelial cells were extracted, and the levels of NO, TNF-α, IL-1, IL-6, IL-8, IL-10, p-Akt, and p-eNOS in cell supernatants were detected. In vivo results showed that compared with the HS group, treated with U50,488H promoted rats' vasodilation by increasing the NO content and decreasing ET-1 and AngII contents. U50,488H reduced endothelial cell apoptosis and attenuated vascular, smooth muscle cell and endothelial cell injury. U50,488H also enhanced the rats' response to oxidative stress by increasing the NOS and T-AOC contents. Moreover, U50,488H increased the eNOS, p-eNOS, Akt, and p-AKT expression and decreased the iNOS and Caveolin-1 expression. In vitro results showed that U50,488H promoted NO, IL-10, p-Akt, and p-eNOS levels in endothelial cell supernatants versus the HS group. And U50,488H reduced the adhesion of peripheral blood mononuclear cells and polymorphonuclear neutrophils to endothelial cells and the migration function of polymorphonuclear neutrophils. Our study suggested that κ-OR activation may improve vascular endothelial dysfunction in salt-sensitive hypertensive rats through the PI3K/Akt/eNOS signaling pathway. This may be a potential therapeutic approach in the treatment of hypertension.
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Caveolina 1 , Endotélio Vascular , Hipertensão , Receptores Opioides kappa , Animais , Ratos , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/uso terapêutico , Células Endoteliais , Hipertensão/tratamento farmacológico , Interleucina-10 , Leucócitos Mononucleares , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Cloreto de Sódio na Dieta , Receptores Opioides kappa/metabolismo , Endotélio Vascular/fisiopatologiaRESUMO
This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.
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Etologia , Transtornos de Estresse Pós-Traumáticos , Animais , Ratos , Fluoxetina , Hipocampo , Aprendizagem em LabirintoRESUMO
Trehalose is a substrate for the chitin synthesis pathway in insects. Thus, it directly affects chitin synthesis and metabolism. Trehalose-6-phosphate synthase (TPS) is a crucial enzyme in the trehalose synthesis pathway in insects, but its functions in Mythimna separata remain unclear. In this study, a TPS-encoding sequence in M. separata (MsTPS) was cloned and characterized. Its expression patterns at different developmental stages and in diverse tissues were investigated. The results indicated that MsTPS was expressed at all analyzed developmental stages, with peak expression levels in the pupal stage. Moreover, MsTPS was expressed in the foregut, midgut, hindgut, fat body, salivary gland, Malpighian tubules, and integument, with the highest expression levels in the fat body. The inhibition of MsTPS expression via RNA interference (RNAi) resulted in significant decreases in the trehalose content and TPS activity. It also resulted in significant changes in Chitin synthase (MsCHSA and MsCHSB) expression, and significantly decrease the chitin content in the midgut and integument of M. separata. Additionally, the silencing of MsTPS was associated with a significant decrease in M. separata weight, larval feed intake, and ability to utilize food. It also induced abnormal phenotypic changes and increased the M. separata mortality and malformation rates. Hence, MsTPS is important for M. separata chitin synthesis. The results of this study also suggest RNAi technology may be useful for enhancing the methods used to control M. separata infestations.
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Immune checkpoint inhibitors (PD-1 inhibitors) have shown clinical activity in Richter transformation-diffuse large B-cell lymphoma variant (RT-DLBCL), thus providing for a novel therapeutic approach. The study group consists of 64 patients with RT-DLBCL. Expression of PD-1, PD-L1, CD30, and microsatellite instability (MSI) status (hMLH1, hMSH2, hMSH6, PMS1) was assessed using immunohistochemistry. EBV-encoded RNA (EBER) was evaluated using colorimetric in situ hybridization. PD-1 and PD-L1 expression levels were categorized on the basis of tumor cell expression as follows: negative (< 5%), positive to low-positive (5-50%), or high-positive (> 50%). An "immune evasion phenotype" (IEP) was defined as RT-DLBCL cases having high-positive expression of PD-1 and/or PD-L1 on tumor cells. The level of PD1-positive tumor-infiltrating lymphocytes (TILs) was estimated as a fraction of total lymphocytes and categorized as negative/low vs. brisk (> 20%). 28/64 (43.7%) patients were characterized as IEP+ RT-DLBCL. A brisk level of PD1+ TILs was significantly more common in IEP1+ compared with IEP- tumors (17/28, 60.7% vs. 5/34, 14.7%; p = 0.001). In addition, CD30 expression was significantly more common in IEP+ compared with IEP- RT-DLBCL (6/20, 30% vs. 1/27, 3.7%; p = 0.0320). Two (2/36; 5.5%) cases were positive for EBER, both IEP+. There was no significant difference between the two groups in terms of age, sex, or time to transformation. Assessment of mismatch repair proteins demonstrated absence of microsatellite instability (MSI) in all cases (18/18; 100%). Notably, patients with brisk PD1+ TILs had a significantly better OS compared to those with a negative/low infiltrate (p = 0.0285).
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Three unreported ent-abietane-type norditerpene lactones, euphohelides A-C (1-3), and 11 known analogs (4-14) were isolated from the whole plants of Euphorbia helioscopia L. Euphohelide A (1) is an unprecedented 2-nor-ent-abietane lactone bearing a unique 5/6/6/5 tetracyclic system. Euphohelides B (2) and C (3) possess 2-nor-6/6/6/5 and 2,3-dinor-5/6/6/5 dilactone tetracyclic moieties, respectively. Their structures were established by spectroscopic methods, computational ECD, and X-ray crystallographic analyses. A biomimetic synthesis of 1 was achieved from precursor 4 based on the speculative biogenetic pathway. Compounds 1 and 5 significantly alleviated the release of LPS-induced NO with IC50 values of 32.98 ± 1.13 and 33.82 ± 3.25 µM, which might be related to the regulation of the NF-κB signaling pathway.
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[This corrects the article DOI: 10.1016/j.apjon.2021.12.017.].