Bifidobacterium Relieved Fluoride-Induced Hepatic and Ileal Toxicity via Inflammatory Response and Bile Acid Transporters in Mice.

Fluoride is a pervasive environmental contaminant. Prolonged excessive fluoride intake can inflict severe damage on the liver and intestines. Previous 16S rDNA sequencing revealed a decrease in ileal Bifidobacterium abundance during fluoride-induced hepatointestinal injury. Hence, this work aimed to investigate the possible mitigating function of Bifidobacterium on hepatointestinal injury caused by fluoride. Thirty-six 6-week-old C57BL/6J mice (equally divided between males and females) were allotted randomly to three groups: Ctrl group (distilled water), NaF group, and NaF + Ba group (100 mg/L NaF distilled water). After 10 weeks, the mice were given 1 × 109 CFU/mL Bifidobacterium solution (0.2 mL/day) intragastrically in the NaF + Ba group for 8 weeks, and the mice in other groups were given the same amount of distilled water. Dental damage, bone fluoride content, blood routine, liver and intestinal microstructure and function, inflammatory factors, and regulatory cholic acid transporters were examined. Our results showed that fluoride increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) activities, and the levels of lipopolysaccharide (LPS), IL-1ß, IL-6, TNF-α, and IL-10 levels in serum, liver, and ileum. However, Bifidobacterium intervention alleviated fluoride-induced changes in the above indicators. In addition, Bifidobacterium reduced the mRNA expression levels of bile acid transporters ASBT, IBABP, OST-α, and OST-ß in the ileum. In summary, Bifidobacterium supplementation relieved fluoride-induced hepatic and ileal toxicity via an inflammatory response and bile acid transporters in the liver and ileum of mice.

Fluoride induces pyroptosis via IL-17A-mediated caspase-1/11-dependent pathways and Bifidobacterium intervention in testis.

Fluoride, a ubiquitous environmental pollutant, poses a significant public health threat. Our previous study revealed a correlation between fluoride-induced testicular pyroptosis and male reproductive dysfunction. However, the underlying mechanism remains unclear. Wild-type and interleukin 17A knockout mice were exposed to sodium fluoride (100 mg/L) in deionized drinking water for 18 weeks. Bifidobacterium intervention (1 × 109 CFU/mL, 0.2 mL/day, administered via gavage) commenced in the 10th week. Sperm quality, testicular morphology, key pyroptosis markers, spermatogenesis key genes, IL-17A signaling pathway, and pyroptosis pathway related genes were determined. The results showed that fluoride reduced sperm quality, damaged testicular morphology, affected spermatogenesis, elevated IL-17A levels, and induced testicular pyroptosis. Bifidobacterium intervention alleviated adverse reproductive outcomes. Fluoride-activated testicular pyroptosis through both typical and atypical pathways, with IL-17A involvement. Bifidobacterium supplementation attenuated pyroptosis by downregulating IL-17A, inhibiting NLRP3 and PYRIN-mediated caspase-1 and caspase-11 dependent pathways in testis, thereby alleviating fluoride-induced male reproductive damage. In summary, this study uncovers the mechanism underlying fluorine-induced testicular pyroptosis and illustrates the novel protecting feature of Bifidobacterium against fluoride-induced harm to male reproduction, along with its potential regulatory mechanism. These results provide fresh perspectives on treating male reproductive dysfunction resulting from fluoride or other environmental toxins.

Experimental Study on the Interface Characteristics of Reinforced Crushed Rock Cushion Layer Based on Direct Shear Tests.

Through indoor large-scale direct shear tests, the interface characteristics of the crushed rock cushions layer reinforced with ParaLink geogrid were studied. The test results indicate that the shear strength of the crushed rock aggregate and the interface strength parameters have a non-linear relationship with the normal stress. The addition of the geogrid reduces the shear strength of the crushed rock aggregate and the interface strength parameters, which is mainly due to the relatively large size, small thickness, and high smoothness of the geogrid. The reinforced geogrid has a significant impact on the deformation and fragmentation characteristics of the crushed rock aggregate. It effectively suppresses the shear contraction and shear dilation effects of the crushed rock aggregate, reducing its peak compression and peak dilation angle. Furthermore, it inhibits the tendency of particle fragmentation in the crushed rock aggregate.

Integration of Cobalt Phthalocyanine, Acetylene Black and Cu2 O Nanocubes for Efficient Electroreduction of CO2 to C2 H4.

Suppressing side reactions and simultaneously enriching key intermediates during CO2 reduction reaction (CO2 RR) has been a challenge. Here, we propose a tandem catalyst (Cu2 O NCs-C-Copc) consisting of acetylene black, cobalt phthalocyanine (Copc) and cuprous oxide nanocubes (Cu2 O NCs) for efficient CO2 -to-ethylene conversion. Density-functional theory (DFT) calculation combined with experimental verification demonstrated that Copc can provide abundant CO to nearby copper sites while acetylene black successfully reduces the formation energies of key intermediates, leading to enhanced C2 H4 selectivity. X-ray photoelectron spectroscopy (XPS) and potentiostatic tests indicated that the catalytic stability of Cu2 O NCs-C-Copc was significantly enhanced compared with Cu2 O NCs. Finally, the industrial application prospect of the catalyst was evaluated using gas diffusion electrolyzers. The F E C 2 H 4 ${{\rm { F}}{{\rm { E}}}_{{{\rm { C}}}_{{\rm { 2}}}{{\rm { H}}}_{{\rm { 4}}}}}$ of Cu2 O NCs-C-Copc can reach to 58.4 % at -1.1 V vs. RHE in 0.1 M KHCO3 and 70.3 % at -0.76 V vs. RHE in 1.0 M KOH. This study sheds new light on the design and development of highly efficient CO2 RR tandem catalytic systems.

Cu2O Nanoparticles Wrapped by N-Doped Carbon Nanotubes for Efficient Electroreduction of CO2 to C2 Products.

Electroreduction of carbon dioxide (CO2) to C2 products (ethylene and ethanol) using efficient catalysts is a feasible approach to alleviate the climate crisis. Cuprous oxide nanoparticles (Cu2O NPs) are a promising catalyst for C2 production but suffer from inherent selectivity and durability. To address this challenge, a Cu2O NPs-nitrogen-doped carbon nanotube (Cu2O NPs-NCNT) composite was prepared with carbon nanotubes (CNTs), Cu2O NPs, and phthalocyanine (Pc). The results indicate that Cu2O NPs-NCNT has excellent Faradic efficiency of C2 products (77.61%) at -1.1 V vs RHE, which is 103.43% higher than that of Cu2O NPs. In the potentiostatic electrolysis combined with Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) measurements, Cu2O NPs-NCNT exhibited structural and catalytic current stability over 10 h. Finally, density functional theory calculations combined with XPS demonstrated that the NCNT in Cu2O NPs-NCNT can selectively absorb CO2 through specific N-CO2 interactions. Our work provides a unique strategy to promote the selectivity of Cu2O NPs for C2 production by introducing N-doped linear carbon materials to fabricate composite.

Global and Local Feature Reconstruction for Medical Image Segmentation.

Learning how to capture long-range dependencies and restore spatial information of down-sampled feature maps are the basis of the encoder-decoder structure networks in medical image segmentation. U-Net based methods use feature fusion to alleviate these two problems, but the global feature extraction ability and spatial information recovery ability of U-Net are still insufficient. In this paper, we propose a Global Feature Reconstruction (GFR) module to efficiently capture global context features and a Local Feature Reconstruction (LFR) module to dynamically up-sample features, respectively. For the GFR module, we first extract the global features with category representation from the feature map, then use the different level global features to reconstruct features at each location. The GFR module establishes a connection for each pair of feature elements in the entire space from a global perspective and transfers semantic information from the deep layers to the shallow layers. For the LFR module, we use low-level feature maps to guide the up-sampling process of high-level feature maps. Specifically, we use local neighborhoods to reconstruct features to achieve the transfer of spatial information. Based on the encoder-decoder architecture, we propose a Global and Local Feature Reconstruction Network (GLFRNet), in which the GFR modules are applied as skip connections and the LFR modules constitute the decoder path. The proposed GLFRNet is applied to four different medical image segmentation tasks and achieves state-of-the-art performance.

Potential Protective Effect of Riboflavin Against Pathological Changes in the Main Organs of Male Mice Induced by Fluoride Exposure.

Long-term exposure to excessive fluorine could cause damage to various tissues and organs in human and animals. However, there is no effective antidote to prevent and cure fluorosis except for avoiding fluoride intake. As an essential nutrient, riboflavin (VB2) has been identified to relieve oxidative stress and inflammation in animal tissues caused by other toxic substances, whether it can alleviate the damage caused by fluoride is unknown. For this, 32 ICR male mice were allocated to four groups of eight each. They were treated with 0 (distilled water), 100 mg/L sodium fluoride (NaF), 40 mg/L VB2, and their combination (100 mg/L NaF plus 40 mg/L VB2) via the drinking water for 90 consecutive days, respectively. The content of bone fluoride and the histomorphology of the main organs including liver, kidney, cerebral cortex, epididymis, small intestine, and colon were evaluated and pathologically scored. The results found that fluoride caused the pathological changes in liver, kidney, cerebral cortex, epididymis, small intestine, and colon at varying degrees, while riboflavin supplementation reduced significantly the accumulation of fluoride in bone, alleviated the morphological damage to cerebral cortex, epididymis, ileum, and colon. This study provides new clues for deeply exploring the mechanism of riboflavin intervention in fluorosis.

GDCSeg-Net: general optic disc and cup segmentation network for multi-device fundus images.

Accurate segmentation of optic disc (OD) and optic cup (OC) in fundus images is crucial for the analysis of many retinal diseases, such as the screening and diagnosis of glaucoma and atrophy segmentation. Due to domain shift between different datasets caused by different acquisition devices and modes and inadequate training caused by small sample dataset, the existing deep-learning-based OD and OC segmentation networks have poor generalization ability for different fundus image datasets. In this paper, adopting the mixed training strategy based on different datasets for the first time, we propose an encoder-decoder based general OD and OC segmentation network (named as GDCSeg-Net) with the newly designed multi-scale weight-shared attention (MSA) module and densely connected depthwise separable convolution (DSC) module, to effectively overcome these two problems. Experimental results show that our proposed GDCSeg-Net is competitive with other state-of-the-art methods on five different public fundus image datasets, including REFUGE, MESSIDOR, RIM-ONE-R3, Drishti-GS and IDRiD.

Synthesis and characterization of a flexible fluorescent magnetic Fe3O4@SiO2/CdTe-NH2 nanoprobe.

In this study, we designed and synthesized two novel fluorescent magnetic nanoparticles. Fe3O4@SiO2-NH-GSH-CdTe (FSGC) (GSH = glutathione) nanoparticles were synthesized using amino-functionalized Fe3O4@SiO2 nanoparticles and GSH-stabilized CdTe quantum dots (CdTe QDs), while flexible Fe3O4@SiO2-NH-GSH-CdTe-NH-NH2 (FSGCN) nanoparticles were synthesized using the FSGC precursor and 1,6-hexamethylenediamine. These two kinds of nanoprobes exhibited excellent magnetic and fluorescent properties. By comparing the fluorescence quenching effect of folic acid (FA) on FSGC and FSGCN, we found that the quenching effect of FA on FSGC was acute and the process was too fast to determine the FA content. However, the quenching effect of FA on flexible FSGCN was mild and hence it could be used as a nanoprobe to determine FA concentration. At physiological pH, the fluorescence quenching effect of FA on the FSGCN nanoprobes was fitted according to the Stern-Volmer equation with a linear response in the concentration range of 0.14 to 4.20 µg mL-1 with a detection limit of 15.1 × 10-9 g mL-1 (S/N = 3) under optimized experimental conditions. The proposed flexible nanoprobe was successfully used to determine the content of FA in folic acid tablets. Recovery was found to be in the range of 92.7%-105.6% with a relative standard deviation of 1.12%-3.84%. Owing to their good stability, environment-friendly characteristics, high selectivity, and good optical properties and biocompatibility, these nanoprobes have potential for usage in practical applications.

Equivalent modeling of PMSG-based wind power plants considering LVRT capabilities: electromechanical transients in power systems.

Hardware protection and control action are two kinds of low voltage ride-through technical proposals widely used in a permanent magnet synchronous generator (PMSG). This paper proposes an innovative clustering concept for the equivalent modeling of a PMSG-based wind power plant (WPP), in which the impacts of both the chopper protection and the coordinated control of active and reactive powers are taken into account. First, the post-fault DC link voltage is selected as a concentrated expression of unit parameters, incoming wind and electrical distance to a fault point to reflect the transient characteristics of PMSGs. Next, we provide an effective method for calculating the post-fault DC link voltage based on the pre-fault wind energy and the terminal voltage dip. Third, PMSGs are divided into groups by analyzing the calculated DC link voltages without any clustering algorithm. Finally, PMSGs of the same group are equivalent as one rescaled PMSG to realize the transient equivalent modeling of the PMSG-based WPP. Using the DIgSILENT PowerFactory simulation platform, the efficiency and accuracy of the proposed equivalent model are tested against the traditional equivalent WPP and the detailed WPP. The simulation results show the proposed equivalent model can be used to analyze the offline electromechanical transients in power systems.

Respiratory muscle pacing with chronically implanted intramuscular Permaloc electrodes: A feasibility study.

We tested the feasibility of stimulating upper-intercostal and abdominal muscles plus the diaphragm by using chronically implanted intramuscular electrodes.During two survival surgeries with six dogs, intramuscular electrodes were implanted bilaterally in the three respiratory muscles. Standard stimulation of the diaphragm was conducted. The dorsolateral and ventrolateral abdominal wall areas were stimulated with a 25 mA current. The second to fourth intercostal spaces were stimulated to elicit the largest tidal volume associated with the least coactivation of the serratus and latissimus muscles. Lone diaphragm and upper-intercostal muscle pacing produced inhaled tidal volumes (mean +/- standard error of the mean) of 293 +/- 36 mL and 59 +/- 17 mL, respectively. Lone abdominal muscle pacing produced an exhaled volume of 55 +/- 17 mL. Combined pacing of diaphragm and intercostal muscles increased the inhaled volume to 389 +/- 39 mL. The addition of abdominal pacing following the combined stimulation of diaphragm and intercostals increased the exhaled volume to 472 +/- 54 mL. During autopsy, dislodgement of the electrodes overlying the ribs was a concern and probably resulted from loose animal jackets. Chronic intramuscular Permaloc electrodes can be implanted in several respiratory muscles and increase tidal volumes more than diaphragm stimulation alone.

Stimulating multiple respiratory muscles with intramuscular Permaloc electrodes.

OBJECTIVE: To test the feasibility of implanting intramuscular electrodes (Permaloc, Synapse Biomedical Inc, Oberlin OH) with self-securing polypropylene anchors to stimulate upper-intercostal and abdominal muscles plus the diaphragm. METHODS/RESULTS: In 6 anesthetized dogs, 12 Permaloc electrodes were implanted in the 3 respiratory muscles (4 in each muscle group). Tidal volume with diaphragmatic stimulation was 310 +/- 38 mL (mean +/- SE); with upper intercostal stimulation, it was 68 +/- 18 mL; and with combined diaphragm intercostal stimulation, it was 438 +/- 78 mL. By study design, stimulation in the upper intercostal muscles was limited to not more than slight/moderate contraction of the serratus and latissimus muscles overlying the ribs. Abdominal muscle stimulation produced exhaled volumes of 38 +/- 20 mL (this stimulation was limited by the maximal output of the stimulator of 25 milliamperes). Combined diaphragm intercostal stimulation followed by abdominal muscle stimulation increased exhaled volumes from 312 +/- 31 mL to 486 +/- 58 mL (P = 0.024). CONCLUSIONS: Permaloc electrodes can be successfully implanted in upper intercostal and abdominal muscles in addition to the diaphragm. Combined diaphragm intercostal stimulation followed by abdominal muscle stimulation increased the exhaled volumes recorded with diaphragmatic stimulation alone.

Vitamin E prevents ethanol-induced inflammatory, hormonal, and cytotoxic changes in reproductive tissues.

Ethanol causes decreased function of the hypothalamic-pituitary-gonadal (HPG) axis. Ethanol resulted in inflammatory changes in HPG manifested by increased concentrations of pro-inflammatory cytokines. Since, such cytokines have deleterious effects on functions of HPG, it seemed possible that ethanol's suppressive action could be due, at least in part, to this inflammation. Since oxidative stress can cause inflammation, we have used the antioxidant vitamin E to test, whether reducing inflammation might protect reproductive functions from ethanol. Rats were fed an ethanol diet or pair fed identically without ethanol for a 3-week period. For the last 10 days, animals were given 30 IU/kg or 90 IU/kg or vehicle. Ethanol significantly increased hypothalamic, pituitary and testicular TNF-alpha and IL-6, all changes prevented by the higher dose of vitamin E. Also, ethanol induced changes in LHRH, LH, testosterone, and testicular germ cell apoptosis were similarly prevented by vitamin E. These data strikingly show that vitamin E protects the HPG from deleterious effects of ethanol and suggests that the mechanism of this protection might be both anti-inflammatory and antioxidant.

Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction.

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) content, and decreased or inappropriately normal serum LH and FSH levels, suggesting impaired secretory release of gonadotropins. The molecular mechanisms behind this disorder are undefined, but a disruption of vesicle-mediated secretory processes is possible because intracellular protein trafficking pathways are involved in secretion of glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab family have been implicated as key regulators of membrane and protein trafficking in mammalian cells, this study was designed to test if ethanol-impaired pituitary FSH and LH secretion is associated with changes in Rab proteins, particularly Rab1B, Rab3B, Rab6, and Rab11. Male Sprague-Dawley rats 35 days old were pair-fed a Lieber-DeCarli diet with ethanol or without ethanol for 5 to 60 days. After ethanol exposure, serum testosterone levels decreased while LH and FSH were inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B, Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected by ethanol exposure. We concluded that reductions in key Rab proteins may lead to altered vesicle trafficking and may play a role in disruption of pituitary FSH and LH secretion caused by ethanol.

Exposure to ethanol induces oxidative damage in the pituitary gland.

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone and decreased or inappropriately normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels suggesting a functional defect in the pituitary. The molecular mechanisms behind this disorder are undefined. A role for ethanol-induced oxidative damage in the pathophysiology is supported by studies in liver, muscle, and heart of experimental animals, but there is limited evidence in the pituitary. We examined markers of oxidative damage to lipids and proteins in pituitaries from rats consuming ethanol for 5, 10, 20, 30, and 60 days in addition to markers of damage to nucleic acids in pituitaries after 60 days of ethanol exposure. There were increases in 8-oxo-deoxyguanosine immunoreactivity, a marker of oxidative damage to nucleic acids, and an overall increase in malondialdehyde and 4-hydroxynonenal, markers of lipid peroxidation. Protein carbonylation and protein nitrotyrosination, markers of protein oxidation, were significantly increased after 30 days and 60 days of ethanol consumption, respectively. After 60 days of ethanol exposure, TUNEL assay revealed that cell death in the ethanol-treated pituitaries was not significantly different from that in the pair-fed controls at the time of examination. We also measured serum testosterone, FSH, and LH after ethanol consumption for 5, 10, 20, 30, and 60 days. Through 5 to 60 days of ethanol exposure, testosterone levels were consistently lower whereas LH and FSH were inappropriately unchanged, suggesting pituitary malfunction. These results provide evidence for ethanol-induced oxidative damage at the pituitary level, which may contribute to pituitary dysfunction.

Calponin is expressed by Sertoli cells within rat testes and is associated with actin-enriched cytoskeleton.

Within seminiferous tubules, Sertoli cells form three types of actin-filament-containing cell junctions, viz., tight junctions, ectoplasmic specializations, and tubulobulbar complexes. These Sertoli cell junctions are involved in the formation of the blood-testis barrier, germ cell translocation, and the release of spermatozoa. Actin and actin-binding proteins are important for these functions. In the present study, a monoclonal antibody against human smooth-muscle-cell calponin detected a 38-kDa protein in a total protein extract of rat testis. The protein has a molecular weight identical to that of aorta calponin and binds calmodulin. Calponin mRNA was detected in the testis and cultured rat Sertoli cells by the reverse transcription/polymerase chain reaction method. Thus, the 38-kDa protein present in the testes is a basic isoform of calponin. In adult rats (70 days of age or older), calponin was detected within seminiferous tubules at sites of Sertoli cell junctions. Cultured Sertoli cells express calponin, whereas cultured spermatogonia do not. When rat testicular tissue was fractionated into cytosol, membrane, and cytoskeleton fractions, calponin was detected in all three fractions. Calcium, potassium, and okadaic acid reduced the amount of calponin associated with the cytoskeleton. These data suggest that Sertoli cells express calponin. The function of calponin within the testis is as yet unknown.

Antiphospholipid antibodies before and after liver transplantation.

OBJECTIVE: The aim of this study was to determine whether liver transplantation of patients with antiphospholipid antibodies (APA) is 1) adversely affected with vascular thrombosis and 2) whether such antibodies persist post transplantation. METHODS: Twelve patients with APA awaiting transplant were identified and characterized biochemically and immunologically. Each had the level of APA determined using commercially available enzyme-linked immunoassay kits before, during, and after liver transplantation. RESULTS: No patient in this series experienced a transplant-related vascular thrombosis. The titer of APA fell to levels at or below those present in normals and remained low in two of 12 or undetectable in 10 of 12 patients 1 yr after liver transplantation. CONCLUSIONS: We reached the following conclusions: 1) Antiphospholipid positivity does not identify patients at high risk for post-transplant vascular thrombosis. 2) The levels of antiphospholipid present in sera pretransplant fell during transplantation and remained low or undetectable 1 month and 1 yr post transplantation.

Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells.

Soybean consumption may be beneficial to prevention of certain human cancers. Low incidence of colon cancer in Asian countries is associated with consumption of soybean products. A limited number of human and animal studies suggested that soybean consumption might prevent colon cancer; other studies did not support this conclusion. Therefore, it is important to understand the biological effects of soybeans on colon cells. In the present study, cultures of Caco-2, SW620, and HT-29 cells were treated with soybean extract, the soluble fraction of a soybean product. The crude extract contains proteins and many soluble components of soybeans. After incubation with soybean extract (1-6%, vol/vol) for 24 h, most Caco-2 cells were found to contain numerous vacuoles within the cytoplasm and to become very flat. Exposure to > 6% soybean extract resulted in cell death and giant vacuoles. Soybean extract (0.25-2%) induced small vacuoles within the cytoplasm of SW620 cells. SW620 cells detached from culture dishes at > 2% soybean extract. Exposure to 0.5-2% soybean extract produced vacuoles within HT-29 cells similar to those observed in SW620 cells. Soybean extract significantly reduced density of Caco-2, SW620, and HT-29 cells. Reducing protein content of soybean extract reduced but did not abolish its effects on colon cells. Purified genistein (12.5 micrograms/ml) was capable of producing morphological changes similar to those observed after treatment of colon cells with soybean extract. Assays using annexin V-propidium iodide demonstrated that treatment of Caco-2 and SW620 cells with soybean extract increased cell death. Membranes of vacuoles in soybean-treated Caco-2 and SW620 cells were labeled with Texas red-conjugated wheat germ agglutinin, a cytological marker for the Golgi apparatus. Exposure to soybean extract enhanced protein levels of Rab6, a small GTP-binding protein that is involved in regulation of membrane traffic of the Golgi apparatus. Data from this study suggest that exposure to soybean extract or isoflavones affects morphology and survival of colon cancer cells and that the response to soybean extract varies depending on the cell lines examined.