Trapping of microplastics and other anthropogenic particles in seagrass beds: Ubiquity across a vertical and horizontal sampling gradient.

Seagrass beds can trap large amounts of marine debris leading to areas of accumulation, known as 'sinks', of anthropogenic particles. While the presence of vegetation can enhance accumulation, less is known about how the trapping effect changes from vegetated to less vegetated patches. To test this, vegetation and sediment were sampled along a vegetation percent cover gradient from the centre of seagrass beds to nearby less vegetated patches. To determine whether trapped particles can lead to increased accumulation in associated fauna, gastropods were also collected from the transects laid across this gradient. Extracted anthropogenic particles were counted and characterised. Particles were detected in all sample types and reached quantifiable limits in at least 50% of sediment and gastropod samples. There was no significant difference in the distribution of particles found in seagrass beds compared to less vegetated patches, suggesting other factors contribute to the trapping efficiency of biogenic habitats besides simply the presence or absence of vegetation.

Clinical application of middle descending colon-double lumen ostomy with distal stoma narrowing in the treatment of anorectal malformation.

BACKGROUND: Anorectal malformations (ARMs) are the most common congenital anomaly of the digestive tract. And colostomy should be performed as the first-stage procedure in neonates diagnosed with intermediate- or high-type ARMs. However, the most classic Pe˜na's colostomy still has some disadvantages such as complicated operation procedure, susceptibility to infection, a greater possibility of postoperative incision dehiscence, difficulty of nursing and large surgical trauma and incision scarring when closing the stoma. We aimed to explore the effectiveness of middle descending colon-double lumen ostomy (MDCDLO) in the treatment of high and intermediate types of anorectal malformations. METHODS: We retrospectively reviewed the data of patients who underwent MDCDLO for high or intermediate types of ARMs between June 2016 and December 2021 in our hospital. The basic characteristics were recorded. All patients were followed up monthly to determine if any complication happen. RESULTS: There were 17 boys and 6 girls diagnosed with high or intermediate types of ARMs in our hospital between June 2016 and December 2021. All 23 patients were cured without complications such as abdominal incision infection, stoma stenosis, incisional hernia, and urinary tract infection in the postoperative follow-up time of 6 months to 6 years except one case of proximal intestinal prolapse was restored under anesthesia. CONCLUSION: MDCDLO offers the advantages of simplicity, efficiency, safety, mild trauma, and small scarring in the treatment of high and intermediate types of anorectal malformations.

How to assess the long-term recovery outcomes of patients with cauda equina syndrome before surgery: a retrospective cohort study.

BACKGROUND: Factors influencing recovery after decompression surgery for cauda equina syndrome (CES) are not completely identified. We aimed to investigate the most valuable predictors (MVPs) of poor postoperative recovery (PPR) in patients with CES and construct a nomogram for discerning those who will experience PPR. METHODS: 356 patients with CES secondary to lumbar degenerative diseases treated at *** Hospital were randomly divided into training (N=238) and validation (N=118) cohorts at a 2:1 ratio. Moreover, 92 patients from the **** Hospital composed the testing cohort. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used for selecting MVPs. The nomogram was developed by integrating coefficients of MVPs in the logistic regression, and its discrimination, calibration, and clinical utility were validated in all three cohorts. RESULTS: After 3 to 5 years of follow-up, the residual rates of bladder dysfunction, bowel dysfunction, sexual dysfunction, and saddle anesthesia were 41.9%, 44.1%, 63.7%, and 29.0%, respectively. MVPs included stress urinary incontinence, overactive bladder, low stream, difficult defecation, fecal incontinence, and saddle anesthesia in order. The discriminatory ability of the nomogram was up to 0.896, 0.919, and 0.848 in the training, validation, and testing cohorts, respectively. Besides, the nomogram showed good calibration and clinical utility in all cohorts. Furthermore, the optimal cut-off value of the nomogram score for distinguishing those who will experience PPR was 148.02, above which postoperative outcomes tend to be poor. CONCLUSION: The first pre-treatment nomogram for discerning CES patients who will experience PPR was developed and validated, which will aid clinicians in clinical decision-making.

Reproductive toxicity of cadmium stress in male animals.

Cadmium (Cd) is a common heavy metal pollutant in the environment, and the widespread use of products containing Cd compounds in industry has led to excessive levels in the environment, which enter the animal body through the food chain, thus seriously affecting the reproductive development of animals. Related studies have reported that Cd severely affects spermatogonia development and spermatogenesis in animals. In contrast, the reproductive toxicity of Cd in males and its mechanism of action have not been clarified. Therefore, this paper reviewed the toxic effects of Cd on germ cells, spermatogonia somatic cells and hypothalamic-pituitary-gonadal axis (HPG axis) of male animals and its toxic action mechanisms of oxidative stress, apoptosis and autophagy from the perspectives of cytology, genetics and neuroendocrinology. The effects of Cd stress on epigenetic modification of reproductive development in male animals were also analyzed. We hope to provide a reference for the in-depth study of the toxicity of Cd on male animal reproduction.

The effect of coral colony morphology, coral surface condition, particle size, and seeding point on the trapping and deposition of microplastics.

Coral reefs are increasingly identified as microplastic sinks. Understanding the trapping and deposition effects on microplastics among coral colonies of different morphologies can help identify which corals and coral reefs are at higher risk of microplastic exposure. Here, we used a current-generating saltwater flume to explore microplastic trapping and deposition among branching coral, Pocillopora acuta, colonies with contrasting morphologies (open and compact), together with varying coral surface conditions (live, dead, and waxed), microplastic sizes (400 to 500 µm and 900 to 1000 µm), and seeding points (above-colony and mid-colony). Results revealed that more microplastics were trapped by, and deposited nearer to, compact colonies compared to those with a more open morphology-likely due to differences in flow dynamics. More of the larger microplastics were trapped, as were those introduced at the mid seeding point, but coral surface condition had no significant effect. These findings add to the growing evidence that corals are effective at trapping and facilitating deposition of microplastics. Branching corals with compact structures are potentially at high risk of microplastic pollution impact. We posit that coral composition, i.e. the relative abundance of compact branching colonies, will affect microplastic accumulation in natural reef environments. SYNOPSIS: This study demonstrates the effects of coral morphology on microplastic trapping and deposition, providing mechanistic insights into the factors that contribute to coral reefs acting as microplastic sinks.

Mechanistic Aspects of Photodegradation of Deoxynucleosides Induced by Triplet State of Effluent Organic Matter.

Excited triplet states of wastewater effluent organic matter (3EfOM*) are known as important photo-oxidants in the degradation of extracellular antibiotic resistance genes (eArGs) in sunlit waters. In this work, we further found that 3EfOM* showed highly selective reactivity toward 2'-deoxyguanosine (dG) sites within eArGs in irradiated EfOM solutions at pH 7.0, while it showed no photosensitizing capacity toward 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxycytidine (the basic structures of eArGs). The 3EfOM* contributed to the photooxidation of dG primarily via one-electron transfer mechanism, with second-order reaction rate constants of (1.58-1.74) × 108 M-1 s-1, forming the oxidation intermediates of dG (dG(-H)•). The formed dG(-H)• could play a significant role in hole hopping and damage throughout eArGs. Using the four deoxynucleosides as probes, the upper limit for the reduction potential of 3EfOM* is estimated to be between 1.47 and 1.94 VNHE. Compared to EfOM, the role of the triplet state of terrestrially natural organic matter (3NOM*) in dG photooxidation was minor (∼15%) mainly due to the rapid reverse reactions of dG(-H)• by the antioxidant moieties of NOM. This study advances our understanding of the difference in the photosensitizing capacity and electron donating capacity between NOM and EfOM and the photodegradation mechanism of eArGs induced by 3EfOM*.

CD4+ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors.

CD4+ T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8+ cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4+ T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4+ T cells in humans. Activated CD4+ T cells produce IFNß via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses. In cooperation with CD40 ligand (L), IFNß also optimizes the costimulatory and other functions of cDC1s required for CTL response induction. IFN-I-producing CD4+ T cells are present in diverse T-cell-infiltrated cancers and likely deliver "help" signals to CTLs locally, according to their transcriptomic profile and colocalization with "helped/licensed" cDCs and tumor-reactive CD8+ T cells. In agreement with this scenario, the presence of IFN-I-producing CD4+ T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

Surface Lattice Modulation Enables Stable Cycling of High-Loading All-solid-state Batteries at High Voltages.

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

Location matters: spatial dynamics of tumor-infiltrating T cell subsets is prognostic in colon cancer.

Background: Colon cancer is a heterogeneous disease and consists of various molecular subtypes. Despite advances in high-throughput expression profiling, limitations remain in predicting clinical outcome and assigning specific treatment to individual cases. Tumor-immune interactions play a critical role, with tumors that activate the immune system having better outcome for the patient. The localization of T cells within tumor epithelium, to enable direct contact, is essential for antitumor function, but bulk DNA/RNA sequencing data lacks spatial distribution information. In this study, we provide spatial T cell tumor distribution and connect these data with previously determined genomic data in the AC-ICAM colon cancer patient cohort. Methods: Colon cancer patients (n=90) with transcriptome data available were selected. We used a custom multiplex immunofluorescence assay on colon tumor tissue sections for quantifying T cell subsets spatial distribution in the tumor microenvironment, in terms of cell number, location, mutual distance, and distance to tumor cells. Statistical analyses included the previously determined Immunologic Constant of Rejection (ICR) transcriptome correlation and patient survival, revealing potential prognostic value in T cell spatial distribution. Results: T cell phenotypes were characterized and CD3+CD8-FoxP3- T cells were found to be the predominant tumor-infiltrating subtype while CD3+FoxP3+ T cells and CD3+CD8+ T cells showed similar densities. Spatial distribution analysis elucidated that proliferative T cells, characterized by Ki67 expression, and Granzyme B-expressing T cells were predominantly located within the tumor epithelium. We demonstrated an increase in immune cell density and a decrease in the distance of CD3+CD8+ T cells to the nearest tumor cell, in the immune active, ICR High, immune subtypes. Higher densities of stromal CD3+FoxP3+ T cells showed enhanced survival outcomes, and patients exhibited superior clinical benefits when greater spatial distances were observed between CD3+CD8-FoxP3- or CD3+CD8+ T cells and CD3+FoxP3+ T cells. Conclusion: Our study's in-depth analysis of the spatial distribution and densities of major T cell subtypes within the tumor microenvironment has provided valuable information that paves the way for further research into the intricate relationships between immune cells and colon cancer development.

Optical Variation and Molecular Transformation of Brown Carbon During Oxidation by NO3• in the Aqueous Phase.

The NO3•-driven nighttime aging of brown carbon (BrC) is known to greatly impact its atmospheric radiative forcing. However, the impact of oxidation by NO3• on the optical properties of BrC in atmospheric waters as well as the associated reaction mechanism remain unclear. In this work, we found that the optical variation of BrC proxies under environmentally relevant NO3• exposure depends strongly on their sources, with enhanced light absorptivity for biomass-burning BrC but bleaching for urban aerosols and humic substances. High-resolution mass spectrometry using FT-ICR MS shows that oxidation by NO3• leads to the formation of light-absorbing species (e.g., nitrated organics) for biomass-burning BrC while destroying electron donors (e.g., phenols) within charge transfer complexes in urban aerosols and humic substances, as evidenced by transient absorption spectroscopy and NaBH4 reduction experiments as well. Moreover, we found that the measured rate constants between NO3• with real BrCs (k = (1.8 ± 0.6) × 107 MC-1s-1, expressed as moles of carbon) are much higher than those of individual model organic carbon (OC), suggesting the reaction with OCs may be a previously ill-quantified important sink of NO3• in atmospheric waters. This work provides insights into the kinetics and molecular transformation of BrC during the oxidation by NO3•, facilitating further evaluation of BrC's climatic effects and atmospheric NO3• levels.

HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis.

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance. Schematic depicting that HMGA1 maintains intracellular redox homeostasis against ferroptosis by assisting ATF4 to activate SLC7A11 transcription, resulting in ESCC resistance to chemotherapy.

Terricoxanthones A-E, unprecedented dihydropyran-containing dimeric xanthones from the endophytic fungus Neurospora terricola HDF-Br-2 associated with the vulnerable conifer Pseudotsuga gaussenii.

An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 µg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 µg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 µg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics.

Immune checkpoints targeting dendritic cells for antibody-based modulation in cancer.

Dendritic cells (DC) are professional antigen-presenting cells which link innate to adaptive immunity. DC play a central role in regulating antitumor T-cell responses in both tumor-draining lymph nodes (TDLN) and the tumor microenvironment (TME). They modulate effector T-cell responses via immune checkpoint proteins (ICPs) that can be either stimulatory or inhibitory. Functions of DC are often impaired by the suppressive TME leading to tumor immune escape. Therefore, better understanding of the mechanisms of action of ICPs expressed by (tumor-infiltrating) DC will lead to potential new treatment strategies. Genetic manipulation and high-dimensional analyses have provided insight in the interactions between DC and T-cells in TDLN and the TME upon ICP targeting. In this review, we discuss (tumor-infiltrating) DC lineage cells and tumor tissue specific "mature" DC states and their gene signatures in relation to anti-tumor immunity. We also review a number of ICPs expressed by DC regarding their functions in phagocytosis, DC activation, or inhibition and outline position in, or promise for clinical trials in cancer immunotherapy. Collectively, we highlight the critical role of DC and their exact status in the TME for the induction and propagation of T-cell immunity to cancer.

Oxygen vacancy induction strategy to regulate the evolution of valence- and free-electrons for boosting visible photodegradation of tetracycline hydrochloride.

The generation, migration and reaction paths of electrons are the key steps for photodegradation of pollutants. However, efficient operation of the above pathways is still challenging. Herein, by strong coordination and slow pyrolysis, we constructed a narrow band Zn-Mn bimetallic photoactive core-shell material (Mn@Zn-N-C, Eg = 3.38 eV) with abundant oxygen vacancies for enhancing the above electronic paths. The photodegradation experiments of tetracycline hydrochloride (TCH) showed that the formation and transfer of vacancy-induced free electrons in the synthesized Mn@Zn-N-C was the key to improve the photocatalytic activity. The DFT calculation results revealed that the photogenerated electrons can transfer along the Mn-O-Zn bridge in Mn@Zn-N-C, and promote the formation of MnIV, which directly capture the free electrons and reset itself to MnII site. In this case, the introduction of Mn would enhance the separation of h+ and e-. The adjacent vacancies and defects then also trapped the above free electrons and hinder the recombination of photogenerated carriers. Simultaneously, the localized valence electron transfer between the above redox pairs (Mn4+/Mn2+ and Zn2+/Zn0) also promoted the long-term stability of the photocatalytic process. In summary, using vacancy induction strategy to regulate the evolution of valence- and free-electrons is a promising method to improve the production-transfer-utilization efficiency of photogenerated carriers.

Enhancement of the viability of T cells electroporated with DNA via osmotic dampening of the DNA-sensing cGAS-STING pathway.

Viral delivery of DNA for the targeted reprogramming of human T cells can lead to random genomic integration, and electroporation is inefficient and can be toxic. Here we show that electroporation-induced toxicity in primary human T cells is mediated by the cytosolic pathway cGAS-STING (cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase-stimulator of interferon genes). We also show that an isotonic buffer, identified by screening electroporation conditions, that reduces cGAS-STING surveillance allowed for the production of chimaeric antigen receptor (CAR) T cells with up to 20-fold higher CAR T cell numbers than standard electroporation and with higher antitumour activity in vivo than lentivirally generated CAR T cells. The osmotic pressure of the electroporation buffer dampened cGAS-DNA interactions, affecting the production of the STING activator 2'3'-cGAMP. The buffer also led to superior efficiencies in the transfection of therapeutically relevant primary T cells and human haematopoietic stem cells. Our findings may facilitate the optimization of electroporation-mediated DNA delivery for the production of genome-engineered T cells.

GnRH antagonist protocol versus progestin-primed ovarian stimulation in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was comparing the efficacy of GnRH antagonist (GnRH-ant) protocol and progestin-primed ovarian stimulation (PPOS) in polycystic ovarian syndrome (PCOS) women. METHODS: A search was conducted from PubMed, Embase, The Cochrane library, Web of Science, and Scopus databases to collect clinical papers regarding GnRH-ant protocol and PPOS protocol from inception to September 2023. Subsequently, the retrieved documents were screened, and the content of the documents that conformed to the requirements was extracted. Moreover, statistical meta-analyses were conducted using the RevMan 5.4 software. Furthermore, with the use of a star-based system and the Cochrane handbook, the methodological quality of the covered papers was evaluated on the Ottawa-Newcastle scale. RESULTS: A total of eight papers were covered in the meta-analysis, with 2156 PCOS women enrolled (i.e., 1085 patients in the GnRH-ant protocol group and 1071 patients in the PPOS group). As indicated by the meta-analysis results, the PPOS group was correlated with a lower risk of ovarian hyperstimulation syndrome (OHSS) (SMD = 9.24, [95% CI: (2.50, 34.21)], P = 0.0009), more gonadotropin (Gn) dose (SMD = - 0.34, [95% CI: (- 0.56, - 0.13)], P = 0.002) compared with GnRH-ant group. No statistical difference was identified on the oocytes condition and pregnancy outcomes. CONCLUSIONS: As revealed by the data of this study, the progesterone protocol is comparable with the GnRH-ant protocol in oocytes condition and clinical outcomes. The progestin-primed ovarian stimulation could serve as an alternative for polycystic ovarian syndrome women who have failed in GnRH antagonist protocol. The above-described conclusions should be verified by more high-quality papers due to the limitation of the number and quality of included papers. TRIAL REGISTRATION: PROSPERO registration: CRD42023411284.

One-electron oxidant-induced transformation of dissolved organic matter: Optical and antioxidation properties and molecules.

Dissolved organic matter (DOM) is a major sink of radicals in advanced oxidation processes (AOPs) and the radical-induced DOM transformation influences the subsequent water treatment processes or receiving waters. In this study, we quantified and compared DOM transformation by tracking the changes of dissolved organic carbon (DOC), UVA254, and electron donating capacity (EDC) as functions of four one-electron oxidants (SO4•-, Cl2•-, Br2•-, and CO3•-) exposures as well as the changes of functional groups and molecule distribution. SO4•- had the highest DOC reduction while Cl2•- had the highest EDC reduction, which could be due to their preferential reaction pathways of decarboxylation and converting phenols to quinones, respectively. Br2•- and CO3•- induced less changes in DOC, UVA254, and EDC than SO4•- and Cl2•-. Additionally, DOM enriched with high aromatic contents tended to have higher DOC, UVA254, and EDC reductions. Decreases in hydroxyl and carboxyl groups and increases in carbonyl groups were observed in these four types of radicals treated DOM using Fourier transform infrared spectroscopy. High resolution mass spectrometry using FTICR-MS showed that one-electron oxidants preferred to attack unsaturated carbon skeletons and transformed into molecules featuring high saturation and low aromaticity. Moreover, SO4•- was inclined to decrease oxidation state of carbon and O/C of DOM due to its strong decarboxylation capacity. This study highlights the distinct DOM transformation by four one-electron oxidants and provides comprehensive insights into the reactions of one-electron oxidants with DOM.

Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters.

BACKGROUND: There is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. OBJECTIVES: This study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. METHODS: In experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. RESULTS: In experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2-0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. CONCLUSIONS: The optimal dietary Se dose for reproductive health of breeder roosters is 0.25-0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.