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Radiation-induced intestinal injury (RIII) restricts the therapeutic efficacy of radiotherapy in abdominal or pelvic malignancies. Also, intestinal injury is a major cause of death following exposure to high doses of radiation in nuclear accidents. No safe and effective prophylactics or therapeutics for RIII are currently available. Here, we reported that the apigenin, a natural dietary flavone, prolonged the survival in c57 mice after lethal irradiation. Apigenin pretreatment brought about accelerated restoration of crypt-villus structure, including enhanced regenerated crypts, more differentiated epithelium cells, and increased villus length. In addition, intestinal crypt cells in the apigenin-treated group exhibited more proliferation and less apoptosis. Furthermore, apigenin increased the expression of Nrf2 and its downstream target gene HO-1, and decreased oxidative stress after irradiation. In conclusion, our findings demonstrate the radioprotective efficacy of apigenin. Apigenin has the potential to be used as a radioprotectant in cancer therapy and nuclear accidents.

[This corrects the article DOI: 10.3389/fimmu.2022.870679.].

Many immunological diseases can be treated by regulating neurobehavior, in which extracellular ATP is a vital member of endogenous danger-associated molecular pattern signaling molecule that plays a crucial part in innate neuro-related immunity. It is actively released through pannexin (Panx) and connexin (Cx) hemichannels from activated or stressed cells during inflammation, injury, or apoptosis. In addition to participating in ATP release, Panxs and Cxs also have crucial immune functions. In this study, pannexin1, three connexin32 isoforms and connexin43 were identified and characterized in spotted sea bass ( Lateolabrax maculatus ), which were named Lm Panx1, Lm Cx32.2, Lm Cx32.3, Lm Cx32.7, and Lm Cx43. Their similar topological structures were discovered by sequence analysis: a relatively unconserved C-terminal region and four highly conserved transmembrane (TM) domains, and so on. Each extracellular (ECL) region of Panx1 has two conserved cysteine residues. Unlike Panx1, each ECL region of Cx32 and Cx43 contains three conserved cysteine residues, forming two conserved motifs: CX 6 CX 3 C motif in ECL1 and CX 4 CX 5 C motif in ECL2. Furthermore, Panx1 and Cx43 share similar genomic organization and synteny with their counterparts in selected vertebrates. Cx32 and CX43 were located in the same locus in fish, but diverged into two loci from amphibian. Moreover, despite varying expression levels, the identified genes were constitutively expressed in all examined tissues. All genes were upregulated by PAMP [lipopolysaccharide and poly(I:C)] stimulation or bacterial infection in vivo and in vitro , but they were downregulated in the brain at 6 or 12 h after stimulation. Especially, the three Lm Cx32 isoforms and Lm Cx43 were upregulated by ATP stimulation in primary head kidney leukocytes; however, downregulation of Lm Cx32.3 and Lm Cx43 expression were noted at 12 h. Conversely, ATP treatment inhibited the expression of Lm Panx1. Importantly, we showed that the spotted sea bass Panx1, Cx43, and Cx32 were localized on the cellular membrane and involved in inflammation-induced ATP release. Taken together, our results demonstrated that Panx1, Cx32, and Cx43 are important neuro-related immune response genes involved in inflammation-induced ATP release.

P2X receptors, including seven subtypes, i.e., P2X1-7, are the ligand-gated ion channels activated by the extracellular ATP playing the critical roles in inflammation and immune response. Even though the immune functions of P2X receptors have been characterized extensively in mammals, their functions in fish remain largely unknown. In this study, four P2X receptor homologues were characterized in spotted sea bass ( Lateolabrax maculatus ), which were named LmP2X2, LmP2X4 , LmP2X5 , and LmP2X7 . Their tissue distributions and expression patterns were then investigated by real-time quantitative PCR (qPCR). Furthermore, their functions in regulating the expressions of inflammation-associated genes and possible signaling pathway were examined by qPCR and luciferase assay. The results showed that they share similar topological structures, conserved genomic organization, and gene synteny with their counterparts in other species previously investigated. And the four P2X receptors were expressed constitutively in the tested tissues. In addition, the expression of each of the four receptor genes was significantly induced by stimulation of Edwardsiella tarda and/or pathogen-associated molecular patterns (PAMPs) in vivo . Also, in primary head kidney leukocytes of spotted sea bass, LmP2X2 and LmP2X5 were induced by using PAMPs and/or ATP. Notably, the expressions of CCL2, IL-8, and TNF-α recognized as the pro-inflammatory cytokines, and of the four apoptosis-related genes, i.e., caspase3, caspase6, caspase7, and P53, were differentially upregulated in the HEK 293T cells with over-expressed LmP2X2 and/or LmP2X7 following ATP stimulation. Also, the over-expression of LmP2X4 can upregulate the expressions of IL-8, caspase6, caspase7, and P53, and LmP2X5 upregulates of IL-8, TNF-α, caspase7, and P53. Then in the present study it was demonstrated that the activation of any one of the four receptors significantly upregulated the activity of NF-κB promoter, suggesting that the activated LmP2Xs may regulate the expressions of pro-inflammatory cytokines via the NF-κB pathway. Taken together, the four P2X receptors were identified firstly from fish species in Perciformes, and they participate in innate immune response of spotted sea bass possibly by regulating the expressions of the inflammation-related genes. Our study provides the new evidences for the P2X receptors’ involvement in fish immunity.

Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family members are innate immune sensors involved in the recognition of highly conserved pathogen-associated molecular patterns (PAMPs). Apoptosis-associated speck-like protein (ASC) is a critical adaptor molecule in multiple inflammasome protein complexes, mediating inflammation and host defense. Caspase1, an inflammatory caspase, has been documented to play important roles in the innate immune system. In this study, we identified and characterized NLRC3-like, ASC, and Caspase1 (referred to as LmNLRC3L, LmASC, and LmCaspase1) from the spotted sea bass (Lateolabrax maculatus). A sequence analysis revealed that LmNLRC3L, LmASC, and LmCaspase1 shared similar features with their fish counterparts. LmNLRC3L contained a FISNA domain, a NACHT domain, and four LRR motifs, followed by a C-terminal fish-specific B30.2 domain. LmASC possessed a PYRIN domain for interacting with inflammasome sensor proteins, as well as a CARD domain. LmCaspase1 had a CARD domain at its N-terminus and a CASC domain at its C-terminus. These three genes were ubiquitously distributed in the liver, spleen, head kidney, gill, intestine, skin, muscle, and brain. They share similar expression patterns, and all demonstrate the highest level of expression in the gill. We analyzed the expression changes in genes in the spleen, gill, and head kidney after stimulation experiments in vivo. After lipopolysaccharide (LPS) stimulation, the expression levels of these three genes were significantly upregulated in the short term, followed by significant downregulation at 48 and 72 h in some examined tissues. Following Edwardsiella tarda infection, these three genes were upregulated in various tissues. However, the expressions of these three genes were not affected by polyinosinic-polycytidylic acid (poly (I:C)) stimulation. Overall, our results indicate that these three genes are involved in the immune response against bacterial infection in the spotted sea bass, providing the foothold for understanding the immune function and mechanism of the fish inflammasome.

Referring to the structure and parameters of the actual multi-way valve, the CAD software SOLIDWORKS was used to establish the three-dimensional geometric model of the internal flow passage of the hydraulic multi-way valve, and the model was calculated and analyzed by CFD software Star CCM+. By studying the flow field distribution in the valve chamber, the pressure distribution at each monitoring point in the chamber and the change of the overall flow rate were obtained, and the steady-state hydrodynamic force of the valve core was calculated. The effects of flow rate and the opening of the valve core on the pressure distribution and steady-state hydrodynamic force in the valve chamber were analyzed under various working conditions. The results show that the steady-state hydraulic force on the valve core increases with the increase of flow rate and decreases with the increase of valve opening. The pressure loss at the inlet and outlet of the slide valve is mainly caused by the throttling characteristics of the oil at the throttle port. The smaller the opening, the greater the inlet pressure and the greater the pressure at all points in the valve chamber.

Extracellular recording is often used in whole nerve recordings. However, it has proven difficult to obtain stable recordings from multiple units simultaneously in peripheral nerves. Breathing and other movements can easily disrupt the delicate contact between the electrodes and cells, such that even bonded or fabricated integrate electrode array are not reliable in in vivo experiments. Extracellular recordings may also suffer from poor spatial resolution. A \"sieve electrode\", consisting of multiple separate electrical channels, was introduced by Mensinger, et al [1] for the purpose of recording the electrical activity of multiple separate neurons in a chronic in vivo preparation. However, this design had few channels, and many that had axons growing through them provided no signals. To improve the success rate of regeneration through the device, recording stability, and increase the number of channels, two 3-D MEMS device design are introduced here. The first one is based on multi-layer silicon substrate. The substrate is processed by photolithography and etching to form channels, which have comparable parameters with small bundles of axons. Then the substrates was stacked and bonded together with biocompatible epoxy based photoresist at 45°C. The second device is built on polyimide flexible film substrate, and both conductive and isolated lines are patterned by photolithography. The film is rolled up to form a cylindrical structure. By elongating the channel dimensions (i.e., creating a 3-D structure rather than the 2-D sieve) to internodal lengths, the probability for signal detection will theoretically be greatly increased. Also, a 3D structure provides a larger substrate for axon regeneration than sieve electrodes. After six weeks regeneration time, confocal microscopy examination revealed that lipophilic fluorescent tracer was observed all through the devices and nuclei of supporting cells were also be observed. Although axon specific fluorescent labeling is still necessary, the current result suggests that the device is biocompatible and allows regeneration.

This study investigates how English learning burnout (ELB), academic buoyancy (AB), and foreign language enjoyment (FLE) jointly and independently influence the English academic achievement of Chinese senior high school students. Drawing on the Control-Value Theory of Achievement Emotions, data from 640 students were analyzed using both regression and fuzzy-set Qualitative Comparative Analysis (fsQCA). Regression results indicated that intrinsic enjoyment of language learning was the strongest positive predictor of achievement, whereas exhaustion exerted a notable negative effect. The fsQCA results revealed five pathways to high achievement, such as the combination of high enjoyment and buoyancy with low burnout, which predicted success even without strong teacher support. Conversely, low buoyancy and enjoyment coupled with high burnout characterized underachievement. These findings enrich Control-Value Theory by highlighting asymmetry between the causes of success and failure, and they emphasize the importance of fostering both intrinsic enjoyment and resilience in exam-driven educational contexts. Practical strategies are suggested to help educators reduce negative states and promote sustainable learning engagement.

Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes. Male sex is a risk factor for impaired glucose metabolism and type 2 diabetes. Here the authors identify that androgen modulates the gut microbiome, which drives insulin resistance and contributes to sexual dimorphism in glucose metabolism in mice.

Purpose This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer (CRC). Methods Sixty-two CRC patients who underwent total-body PET/CT (uEXPLORER, United Imaging Healthcare, Shanghai, China) with an ultra-low dose (0.37 MBq/kg) of [18F]-FDG were enrolled in this retrospective study. The PET images were reconstructed with the entire 15-min dataset first and then split into 13-, 8-, 5-, 4-, 3-, 2-, and 1-min duration groups to simulate fast scanning images. For simplicity, the images reconstructed with the data from 15 to 1 min were referred to as G15, G13, and so on until G1. Subjective image quality was assessed with 5-point Likert scales. The objective image quality parameters included the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver and blood pool and the SUVmax and tumor-to-background ratio (TBR) of the lesions. G15 served as the control to evaluate lesion detectability. Results A total of 62 patients (43 men, 19 women; age 41–88, mean ± SD 64.0 ± 10.9 years) with 64 CRC primary tumor lesions and 10 low-grade intraepithelial neoplasia (LGIN) lesions were enrolled in this study. The subjective scores were highest for G15 (4.5 ± 0.5) and then decreased from G13 (4.3 ± 0.4) to G8 (3.7 ± 0.5). The liver SNR increased with the extension of acquisition time from G8 (17.2 ± 2.8) to G13 (20.6 ± 3.4) and G15 (21.9 ± 3.4). The liver SNR of G8 was not significantly different from that of G13 ( p  = 0.15) and was significantly different from that of G15 ( p  = 0.001). All 64 CRC lesions could be identified in all image groups, even on G1. One of ten LGINs was missed on G1, G2, and G3, and one LGIN was missed on G1, G2, G3, and G4. G15 served as the control, and 100% (48/48) lymph nodes could be found on G13 and G8 compared to 93.8% (45/48) lymph nodes on G5 and G4, 85.4% (41/48) lymph nodes on G3, 81.3% (39/48) lymph nodes on G2, and 77.1% (37/48) lymph nodes on G1. For liver metastases, there were no missed liver lesions on G13 and G8 and 3, 4, 6, 7, and 9 missed liver lesions on G5, G4, G3, G2, and G1, respectively. For other areas of metastasis, including the lung, peritoneum, and ovaries, there were no missed lesions in any group. Conclusions Total-body PET/CT with an ultra-low dose of [18F]-FDG can maintain satisfactory image quality and lesion detectability in CRC.