BACKGROUND: Ionizing radiation (IR), including radiotherapy, can exert lasting harm on living organisms. While liposaccharide (LPS) offers resistance to radiation damage, it also induces toxic responses. Thankfully, an LPS analogue called N-formylmethionine-leucyl-phenylalanine (fMLP) holds the potential to mitigate this toxicity, offering hope for radiation protection.
METHODS: Survival of C57BL/6 mice exposed to IR after administration with fMLP/LPS/WR-2721 or saline was recorded. Cell viability and apoptosis assay of bone marrow (BMC), spleen and small intestinal epithelial (HIECs) cells were tested by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Tissue damage was evaluated by Hematoxilin and Eosin (H&E), Ki-67, and TUNEL staining. RNA sequencing was performed to reveal potential mechanisms of fMLP-mediated radiation protection. Flow cytometry and western blot were performed to verify the radiation protection mechanism of fMLP on the cell cycle.
RESULTS: The survival rates of C57BL/6 mice exposed to ionizing radiation after administering fMLP increased. fMLP demonstrated low toxicity in vitro and in vivo, maintaining cell viability and mitigating radiation-induced apoptosis. Moreover, it protected against tissue damage in the hematopoietic and intestinal system. RNA sequencing shed light on fMLP\'s potential mechanism, suggesting its role in modulating innate immunity and cell cycling. This was evidenced by its ability to reverse radiation-induced G2/M phase arrests in HIECs.
CONCLUSIONS: fMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR\'s detrimental effects.

Oxidative stress is a major pathogenic factor in many intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). The Nrf2 signaling pathway and mitophagy can reduce reactive oxygen species (ROS) and alleviate oxidative stress, but their relationship is unclear. Hydroxytyrosol (HT), a polyphenolic compound abundant in olive oil, has strong antioxidant activity and may help treat these diseases. We used pigs as a model to investigate HT\'s effect on intestinal oxidative damage and its mechanisms. Diquat (DQ) induced oxidative stress and impaired intestinal barrier function, which HT mitigated. Mechanistic studies in IPEC-J2 cells showed that HT protected against oxidative damage by activating the PI3K/Akt-Nrf2 signaling pathway and promoting mitophagy. Our study highlighted the synergistic relationship between Nrf2 and mitophagy in mediating HT\'s antioxidant effects. Inhibition studies confirmed that disrupting either pathway compromised HT\'s protective effects. Maintaining redox balance through Nrf2 and mitophagy is important for eliminating excess ROS. Nrf2 increases antioxidant enzymes to clear existing ROS, while mitophagy removes damaged mitochondria and reduces ROS generation. This study demonstrates that these pathways collaboratively modulate the antioxidant effects of HT, with neither being dispensable. Targeting Nrf2 and mitophagy could be a promising strategy for treating oxidative stress-related intestinal diseases, with HT as a potential treatment.

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage-CD90.2+NK1.1-NKp46-ST2-KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence.

Fecal incontinence (FI) referred to the inability to control the leakage of solid, liquid, or gaseous feces, the artificial anal sphincter (AAS) was the last resort for patients with FI except enterostomy. In order to the clinical application value of AAS was improved, the detection and analysis of intestinal pressure information was very necessary. Biaxial actuated artificial anal sphincter (BAAS) was a new type of AAS, which not only had a stable, long-term and safe energy supply, but also could provide real-time feedback of intestinal pressure information. In this paper, the BAAS was implanted into piglets for a long-term animal experiment. Piglets\' life habits, defecation habits and intestinal pressure were analyzed. The analysis results showed that the BAAS system had good feces control effect, when the actuator of the BAAS system was closed, there was basically no fecal leakage of piglets, and when the actuator of the BAAS system was opened, the piglets could defecate normally. Under the normal condition of the piglets\' health state and the BAAS\'s operating state, the accuracy of the defecation perception reached to 65.79%. This study realized the in-depth study of the mechanism of piglets\' defecation, and provided guidance for the development of a new generation of AAS.

Exposure to the space microenvironment has been found to disrupt the homeostasis of intestinal epithelial cells and alter the composition of the microbiota. To investigate this in more detail and to examine the impact of ginsenoside Rb1, we utilized a mouse model of hindlimb unloading (HU) for four weeks to simulate the effects of microgravity. Our findings revealed that HU mice had ileum epithelial injury with a decrease in the number of intestinal stem cells (ISCs) and the level of cell proliferation. The niche functions for ISCs were also impaired in HU mice, including a reduction in Paneth cells and Wnt signaling, along with an increase in oxidative stress. The administration of Rb1 during the entire duration of HU alleviated the observed intestinal defects, suggesting its beneficial influence on epithelial cell homeostasis. Hindlimb unloading also resulted in gut dysbiosis. The supplementation of Rb1 in the HU mice or the addition of Rb1 derivative compound K in bacterial culture in vitro promoted the growth of beneficial probiotic species such as Akkermansia. The co-housing experiment further showed that Rb1 treatment in ground control mice alone could alleviate the defects in HU mice that were co-housed with Rb1-treated ground mice. Together, these results underscore a close relationship between dysbiosis and impaired ISC functions in the HU mouse model. It also highlights the beneficial effects of Rb1 in mitigating HU-induced epithelial injury by promoting the expansion of intestinal probiotics. These animal-based insights provide valuable knowledge for the development of improved approaches to maintaining ISC homeostasis in astronauts.

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Deoxynivalenol (DON) is a mycotoxin produced by Fusarium fungi widespread in wheat, corn, barley and other grain crops, posing the potential for being toxic to human and animal health, especially in the small intestine, which is the primary target organ for defense against the invasion of toxins. This study firstly investigated DON contamination in a local area of a wheat production district in China. Subsequently, the mechanism of DON toxicity was analyzed through cellular molecular biology combining with intestinal flora and gene transcription analysis; the results indicated that DON exposure can decrease IPEC-J2 cell viability and antioxidant capacity, stimulate the secretion and expression of proinflammatory factors, destroy the gut microbiota and affect normal functions of the body. It is illustrated that DON could induce intestinal damage through structural damage, functional injury and even intestinal internal environment disturbance, and, also, these intestinal toxicity effects are intrinsically interrelated. This study may provide multifaceted information for the treatment of intestinal injury induced by DON.

The objective of this study is to assess the prevalence of antibiotic-resistant genes (ARGs) in the intestines of infants and the factors affecting their distribution. Breast milk and infant stool samples were collected from nine full-term, healthy mother-infant pairs. The bacterial distribution and various types of ARGs present in the samples were analyzed using metagenomic next-generation sequencing. Over a period spanning from 2 to 240 d after birth, a total of 273 types of ARGs were identified in both infant feces and breast milk, exhibiting a trend of increasing prevalence over time. High concentrations of representative ARG populations were identified in the intestines of infants, especially at 12-15 d after birth. These populations included APH3-Ib, tetW/N/W, mphA, and Haemophilus influenzae PBP3, and multiple ARG Escherichia coli soxS that were resistant to common clinically used aminoglycoside, tetracycline, macrolide, and beta-lactam antibiotics. Gammaproteobacteria and Bacilli, especially Enterococcus, Staphylococcus, Acinetobacter, Streptococcus, and Escherichia were among the identified ARG carriers. Maternal age and body mass index (present and before pregnancy), infant sex, maternal consumption of probiotic yogurt during pregnancy, and lactation might be substantial factors influencing the occurrence of ARG-carrying bacteria and ARG distribution in the infant feces. These results indicate that environmental factors may influence the distribution of ARG-carrying bacteria and ARGs themselves in infants during early life. Providing appropriate recommendations regarding maternal age, body mass index during pregnancy, and use of probiotic products could potentially mitigate the transmission of antibiotic-resistant microbiota and ARGs, thereby diminishing the risk of antibiotic-resistant infections and safeguarding children\'s health.

Nanoplastics (NPs) and 2,4-di-tert-butylphenol (2,4-DTBP) are ubiquitous emerging environmental contaminants detected in aquatic environment. While the intestinal toxicity of 2,4-DTBP alone has been studied, its combined effects with NPs remain unclear. Herein, adult zebrafish were exposed to 80 nm polystyrene nanoplastics (PS-NPs) or/ and 2,4-DTBP for 28 days. With co-exposure of PS-NPs, impact of 2,4-DTBP on feeding capacity and intestinal histopathology was enhanced in males while attenuated in females. Addition of PS-NPs significantly decreased the uptake of 2,4-DTBP in females, while the intestinal concentrations of 2,4-DTBP were not different between the sexes in co-exposure groups. Furthermore, lower intestinal pH and higher contents of digestive enzymes were detected in male fish, while bile acid was significantly increased in co-exposed females. In addition, co-exposure of PS-NPs stimulated female fish to remodel microbial composition to potentially enhance xenobiotics degradation, while negative Aeromonas aggravated inflammation in males. These results indicated that in the presence of PS-NPs, the gut microenvironment in females can facilitate the detoxification of 2,4-DTBP, while exaggerating toxiciy in males. Overall, this study demonstrates that toxicological outcomes of NPs-chemical mixtures may be modified by sex-specific physiology and microbiota composition, furthering understanding for environmental risk assessment and management of aquatic environments.

UNASSIGNED: To explore the bacterial blocking effect of oriented multilayer MXene/polyvinyl alcohol (PVA) nanocomposite hydrogels and their effect on the repair of intestinal defects.
UNASSIGNED: MXene/PVA nanocomposite hydrogels were prepared using the traditional freezing method and the bidirectional freezing ice template method. The structures of the different hydrogels were observed using scanning electron microscopy (SEM) and micro-CT reconstruction. The rheological properties of the hydrogels were measured using a dynamic rheometer, and their mechanical properties were assessed using a universal testing machine. The burst pressure of the hydrogels was determined through burst experiments, and bacterial colony growth was observed by the osmosis method to assess the bacteria blocking ability of the hydrogels in vitro. A rat model of cecal perforation was established, and the hydrogels were used for intestinal repair. Gram staining was performed to observe in vivo the bacterial blocking ability of the hydrogels, HE staining was performed to observe the intestinal inflammation, and CD31 and CD68 immunofluorescence staining and proliferating cell nuclear antigen (PCNA) staining were performed to observe the repair effect of the hydrogels on intestinal defects.
UNASSIGNED: SEM and micro-CT reconstruction revealed that the hydrogel prepared by the traditional freezing method exhibited a random porous structure, while the hydrogel prepared by the bidirectional freezing method showed an oriented multilayer structure. Rheological and tensile tests indicated that the oriented hydrogel had superior mechanical properties, and the burst pressure of the oriented multilayer hydrogel was as high as 27 kPa, significantly higher than that of the non-oriented hydrogel (P<0.001). Bacterial colony growth was observed by the osmosis method and it was found that, compared with the non-oriented hydrogel, the oriented multilayer hydrogel could effectively prevent the infiltration of Escherichia coli and Staphylococcus aureus in vitro. Gram staining results showed that the oriented multilayer hydrogel could effectively block intestinal bacteria from entering the abdominal cavity in vivo. HE staining results showed that the oriented multilayer hydrogel could effectively reduce intestinal inflammation in vivo. CD31 and CD68 immunofluorescence staining and PCNA staining results showed that the oriented multilayer hydrogel had a repairing effect on intestinal defects in vivo.
UNASSIGNED: The oriented multilayer hydrogel prepared by bidirectional freezing effectively prevents bacterial infiltration and reduces intestinal inflammation.