This experiment was conducted to investigate the effects of serotonin or 5-hydroxytryptamine (5-HT) and homocysteine (Hcy) levels on the incidence and severity of autism in children. For this aim,120 ...autistic children were selected as the study group, and 120 children who took early psychological intervention were included in the study group I, and 120 children who took late psychological intervention were included in study group II. 120 non-autistic children hospitalized in the same period were selected as the control group. The levels of serotonin and Hcy were compared between the two groups. At the same time, the effects of different levels of serotonin and Hcy on the severity of autism in children were compared. Results showed that there were significant differences in 5-HT level, Hcy level, cesarean section, breast milk mode, premature delivery, vitamin B12 level, birth weight and early illness between study group I and control group, and between study group II and control group (all P < 0.01). The ASD score growth rate, ASD score change rate, 5-HT change rate and complications of study group I were lower than those of study group II, but the cure rate was significantly higher than that of study group II (P < 0.01). 5-HT, breast feeding, Hcy, vitamin B12 level, febrile convulsion and traumatic brain injury were the main risk factors for children with autism, while the psychological intervention was the main protective factor, which had a significant positive impact on the severity of children with autism (p < 0.05). 5-HT and Hcy levels have significant predictive effects on the development of children with autism and can be used as predictive indicators for the development of autism. In conclusion, 5-HT, feeding mode, Hcy, vitamin B12 level and febrile convulsion are the main risk factors for autism in children, and there are significant correlations.
Animals require complex metabolic and physiological adaptations to maintain the function of vital organs in response to environmental stresses and infection. Here, we found that infection or injury ...in Drosophila induced the excretion of hemolymphatic lipids by Malpighian tubules, the insect kidney. This lipid purge was mediated by a stress-induced lipid-binding protein, Materazzi, which was enriched in Malpighian tubules. Flies lacking materazzi had higher hemolymph concentrations of reactive oxygen species (ROS) and increased lipid peroxidation. These flies also displayed Malpighian tubule dysfunction and were susceptible to infections and environmental stress. Feeding flies with antioxidants rescued the materazzi phenotype, indicating that the main role of Materazzi is to protect the organism from damage caused by stress-induced ROS. Our findings suggest that purging hemolymphatic lipids presents a physiological adaptation to protect host tissues from excessive ROS during immune and stress responses, a process that is likely to apply to other organisms.
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•Hemolymphatic lipids are removed by Malpighian tubules after infection and injury•The lipid-binding protein Materazzi removes lipids from the hemolymph•Materazzi prevents hemolymphatic lipid peroxidation and tubule dysfunction•Lipid removal is a stress response that adjusts ROS level and promotes survival
Li et al. show that infection or injury in Drosophila induced the excretion of hemolymphatic lipids by Malpighian tubules, the insect kidney, via a mechanism centered on the stress-induced lipid-binding protein, Materazzi. Thus, lipid removal presents a physiological adaptation to protect host tissues from excessive ROS during immune and stress responses, a process that is likely to apply to other organisms.
In this paper, we use the analytic method and the properties of classical Gauss sums to study the computational problems of one kind hybrid power mean of quartic Gauss sums and two-term exponential ...sums, and give an interesting fourth-order linear recurrence formula for it.
RNA interference (RNAi) is a powerful method to inhibit gene expression in a sequence specific manner. Recently silencing the target gene through feeding has been successfully carried out in many ...insect species.
Escherichia coli strain HT115 was genetically engineered to express dsRNA targeting genes that encode ribosomal protein Rpl19, V type ATPase D subunit, the fatty acid elongase Noa and a small GTPase Rab11. qRT-PCR showed that mRNA level of four target genes was reduced compared to ds-egfp control by feeding either engineered bacteria or dsRNAs. The maximum down-regulation of each gene varied from 35% to 100%. Tissue specific examination indicated that RNAi could be observed not only in midgut but also in other tissues like the ovary, nervous system and fat body. Silencing of rab11 through ingestion of dsRNA killed 20% of adult flies. Egg production was affected through feeding ds-noa and ds-rab11 compared to ds-egfp group. Adult flies were continuously fed with dsRNA and bacteria expressing dsRNA for 14 days and up-regulations of target genes were observed during this process. The transcripts of noa showed up-regulation compared to ds-egfp control group in four tissues on day 7 after continuous feeding either dsRNA or engineered bacteria. The maximum over-expression is 21 times compared to ds-egfp control group. Up-regulation of rab11 mRNA level could be observed in testes on day 7 after continuous bacteria treatment and in midgut on day 2 after ds-rab11 treatment. This phenomenon could also be observed in rpl19 groups.
Our results suggested that it is feasible to silence genes by feeding dsRNA and bacteria expressing dsRNA in Bactrocera dorsalis. Additionally the over-expression of the target gene after continuously feeding dsRNA or bacteria was observed.
On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma ...proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The approval was based on CodeBreaK 100 (Study 20170543), a dose-escalation and dose-expansion trial in patients with an advanced, KRAS G12C-mutated, solid tumor. The overall response rate (ORR) observed in patients with KRAS G12C-mutated NSCLC treated with sotorasib (n = 124) was 36% 95% confidence interval (CI), 28-45. The median duration of response was 10.0 months (95% CI, 6.9-not estimable). The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. This is the first approval of a targeted therapy for KRAS G12C-mutated NSCLC. Because of pharmacokinetic data and ORRs of patient cohorts who took sotorasib at lower doses in the dose-escalation portion of CodeBreaK 100, a dose comparison study is being conducted as a post-marketing requirement.
The gut must perform a dual role of protecting the host against toxins and pathogens while harboring mutualistic microbiota. Previous studies suggested that the NADPH oxidase Duox contributes to ...intestinal homeostasis in Drosophila by producing reactive oxygen species (ROS) in the gut that stimulate epithelial renewal. We find instead that the ROS generated by Duox in the Malpighian tubules leads to the production of Upd3, which enters the gut and stimulates stem cell proliferation. We describe in Drosophila the existence of a countercurrent flow system, which pushes tubule-derived Upd3 to the anterior part of the gut and stimulates epithelial renewal at a distance. Thus, our paper clarifies the role of Duox in gut homeostasis and describes the existence of retrograde fluid flow in the gut, collectively revealing a fascinating example of inter-organ communication.
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•ROS-mediated gut cell renewal during oral infection does not require Duox in the gut•Oral infection activated Duox-dependent ROS production in the Malpighian tubules•ROS produced in Malpighian tubules leads to the production of cytokine Upd3•The tubules illicit a gut retro-flow bringing Upd3 to the gut
Liu et al. show that Malpighian tubule-produced Duox reactive oxygen species (ROSs) are required for gut homeostasis after oral infection in Drosophila melanogaster. They show that infection activates a renal-gut countercurrent flow, which could bring renal-derived cytokines to the gut, regulating gut stem cell proliferation.
Port-wine stains (PWSs) are congenital vascular malformations that involve the skin and mucosa. To date, the mechanisms underlying the pathogenesis and progression of PWSs are yet to be clearly ...elucidated. The potential reasons for dilated vessels are as follows: (1) somatic GNAQ (R183Q) mutations that form enlarged capillary malformation-like vessels through angiopoietin-2, (2) decreased perivascular nerve elements, (3) the coexistence of Eph receptor B1 and ephrin B2, and (4) the deficiency of αSMA expression in pericytes. In addition, ERK, c-JNK, P70S6K, AKT, PI3K, and PKC are assumed to be involved in PWS development. Although pulsed-dye laser (PDL) remains the gold standard for treating PWSs, the recurrence rate is high. Topical drugs, including imiquimod, axitinib, and rapamycin, combined with PDL treatments, are expected to alter the recurrence rate and reduce the number of PDL sessions for PWSs. For the deep vascular plexus, photosensitizers or photothermal transduction agents encapsulated by nanocarriers conjugated to surface markers (CD133/CD166/VEGFR-2) possess a promising therapeutic potential in photodynamic therapy or photothermal therapy for PWSs. The pathogenesis, progression, and treatment of PWSs should be extensively investigated.
The main purpose of this paper is using the analytic method and the properties of the classical Gauss sums to study the computational problem of one kind fourth hybrid power mean of the quartic Gauss ...sums and Kloosterman sums, and give an exact computational formula for it.
To improve the accuracy of shallow neural networks in processing complex signals and cable fault diagnosis, and to overcome the shortage of manual dependency and cable fault feature extraction, a ...deep learning method is introduced, and a time-frequency domain joint impedance spectrum is proposed for cable fault identification and localization based on a deep belief network (DBN). Firstly, based on the distribution parameter model of power cables, we model and analyze the cables under normal operation and different fault types, and we obtain the headend input impedance spectrum and the headend input time-frequency domain impedance spectrum of cables under various operating conditions. The headend input impedance amplitude and phase of normal operation and different fault cables are extracted as the original input samples of the cable fault type identification model; the real part of the headend input time-frequency domain impedance of the fault cables is extracted as the original input samples of the cable fault location model. Then, the unsupervised pre-training and supervised inverse fine-tuning methods are used for automatically learning, training, and extracting the cable fault state features from the original input samples, and the DBN-based cable fault type recognition model and location model are constructed and used to realize the type recognition and location of cable faults. Finally, the proposed method is validated by simulation, and the results show that the method has good fault feature extraction capability and high fault type recognition and localization accuracy.
The JAK/STAT pathway is a key signaling pathway in the regulation of development and immunity in metazoans. In contrast to the multiple combinatorial JAK/STAT pathways in mammals, only one canonical ...JAK/STAT pathway exists in Drosophila. It is activated by three secreted proteins of the Unpaired family (Upd): Upd1, Upd2 and Upd3. Although many studies have established a link between JAK/STAT activation and tissue damage, the mode of activation and the precise function of this pathway in the Drosophila systemic immune response remain unclear. In this study, we used mutations in upd2 and upd3 to investigate the role of the JAK/STAT pathway in the systemic immune response. Our study shows that haemocytes express the three upd genes and that injury markedly induces the expression of upd3 by the JNK pathway in haemocytes, which in turn activates the JAK/STAT pathway in the fat body and the gut. Surprisingly, release of Upd3 from haemocytes upon injury can remotely stimulate stem cell proliferation and the expression of Drosomycin-like genes in the intestine. Our results also suggest that a certain level of intestinal epithelium renewal is required for optimal survival to septic injury. While haemocyte-derived Upd promotes intestinal stem cell activation and survival upon septic injury, haemocytes are dispensable for epithelium renewal upon oral bacterial infection. Our study also indicates that intestinal epithelium renewal is sensitive to insults from both the lumen and the haemocoel. It also reveals that release of Upds by haemocytes coordinates the wound-healing program in multiple tissues, including the gut, an organ whose integrity is critical to fly survival.