Comparative analysis of biofilm characterization of probiotic Escherichia coli.

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

Modeling and optimizing through plenoptic function for the dual lenticular lens-based directional autostereoscopic display system.

We propose an autostereoscopic display system that ensures full resolution for multiple users by directional backlight and eye tracking technology. The steerable beam formed by directional backlight can be regarded as the result of sparsely sampling the light field in space. Therefore, we intuitively propose an optimization algorithm based on the characterization for the state of the steerable beams, which is computed in matrix form using the plenoptic function. This optimization algorithm aims to optimize the exit pupil quality and ultimately enhancing the viewing experience of stereoscopic display. Numerical simulations are conducted and the improvement in exit pupil quality achieved by the optimization scheme is verified. Furthermore, a prototype of the stereoscopic display that employs dual-lenticular lens sheets for the directional backlight has been constructed using the optimized optical parameters. It provides 9 independent exit pupils at the optimal viewing distance of 400 mm, with an exit pupil resolution of 1/30. The field of view is ±16.7°, the viewing distance range is 380 mm to 440 mm. At the optimal viewing distance 400 mm, the average crosstalk of the system is 3%, and the dynamic brightness uniformity across the entire viewing plane reaches 85%. The brightness uniformity of the display at each exit pupil is higher than 88%.

Physicochemical, Quality and Flavor Characteristics of Starch Noodles with Auricularia cornea var. Li. Powder.

Auricularia cornea var. Li., as an edible mushroom rich in various nutrients, could be widely used in noodle food. This study aimed to investigate the effect of Auricularia cornea var. Li. (AU) powder on the gel properties, structure and quality of starch noodles. Taking the sample without adding AU powder as a control, the addition of AU powder enhanced the peak viscosity, trough viscosity, final viscosity, breakdown, setback, peak time, gelatinization temperature, G' (storage modulus) and G'' (loss modulus). Meanwhile, the incorporation of AU powder significantly enhanced the stability of the starch gel structure and contributed to a more ordered microstructure also promoting the short-term aging of starch paste. In vitro digestion results displayed lower rapid digestibility (21.68%) but higher resistant starch content (26.58%) with the addition of AU powder and increased breaking rate, cooking loss, swelling index and a* and b* values. However, it decreased dry matter content and L*, particularly the reducing sugar content significantly increased to 4.01% (p < 0.05), and the total amino acid content rose to 349.91 mg/g. The GC-IMS library identified 51 VOCs, and the OPLS-DA model classified 18 VOCs (VIP > 1). Overall, the findings indicate that starch noodles with the addition of AU powder may provide greater nutritional quality, gel stability and starch antidigestibility.

Protopanaxadiol Targeting Membrane Induces HepG2 Cell Apoptosis Via Raft-like Formation and Tubulation Disruption.

Protopanaxadiol (PPD), which has a molecular structure similar to cholesterol, is a potent anticancer agent that has been proposed to target the lipid membrane for the pharmacological effects. However, the underlying mechanism by which PPD modulates the cell membrane leading to cancer cell death is not be fully understood. In this work, we used single cell infrared spectroscopy, scanning electron microscopy and confocal microscopy to investigate the effects of PPD on human hepatocellular carcinoma (HepG2) cells, focusing on the change in membrane structure. We found that PPD significantly reduced the number of membrane tubules over the course of treatment. Interestingly, the addition of PPD could promote the formation of lipid raft-like domains (PPD rafts) and even restore the domain disruption caused by methyl-beta-cyclodextrin depletion of membrane cholesterol. In addition, PPD pre-treatment may increase the induction effect of FasL, which impairs cell viability, although it does not appear to be beneficial for Fas clustering in the PPD rafts. Collectively, these results highlight a non-classical mechanism by which PPD induces HepG2 apoptosis by directly affecting the physical properties of the cell membrane, providing a novel insight into understanding membrane-targeted therapy.

Lactiplantibacillus sp. G6 isolated from goose intestine as starter culture for degrading nitrite and improving quality in Chinese pickle fermentation.

Animal intestines is considered as a source of lactic acid bacteria (LAB) that have potential to decrease the nitrite level during fermentation of food such as pickles. It was hypothesized that optimized level of LAB has a high capacity to degrade nitrite during Chinese pickle fermentation and benefit a higher acceptability of the Chinese pickle product. This study aims to investigate the performance of a goose intestine-isolated LAB strain G6 under the species Lactiplantibacillus plantarum as a starter culture of Chinese pickles. The results showed that Lactiplantibacillus sp. G6 had a nitrite degradation rate close to 100% under the MRS broth condition of 25 °C, 2% inoculum volume and pH at 5. As a starter culture for Chinese pickle, this strain was able to achieve a higher LABs amount, lower nitrite residue after fermentation, compared with the group without the starter, which implicates its feasibility of applying on fermented food for reducing nitrite level. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01433-8.

Aflatoxin B1 exposure causes splenic pyroptosis by disturbing the gut microbiota-immune axis.

Aflatoxin B1 (AFB1) causes serious immunotoxicity and has attracted considerable attention owing to its high sensitivity and common chemical-viral interactions in living organisms. However, the sensitivity of different species to AFB1 widely varies, which cannot be explained by the different metabolism in species. The gut microbiota plays a crucial role in the immune system, but the interaction of the microbiota with AFB1-induced immunotoxicity still needs to be determined. Our results indicated that AFB1 exposure disrupted the structure of the gut microbiota and damaged the gut barrier, which caused translocation of microbiota metabolites, lipopolysaccharides, to the spleen. Subsequently, pyroptosis of the spleen was activated. Interestingly, AFB1 exposure had little effect on the splenic pyroptosis of pseudo-germfree mice (antibiotic mixtures eliminated their gut microbiota, ABX). Then, fecal microbiota transplant (FMT) and sterile fecal filtrate (SFF) were employed to validate the function of the gut microbiota and its metabolites in AFB1-induced splenic pyroptosis. The AFB1-disrupted microbiota and its metabolites significantly promoted splenic pyroptosis, which was worse than that in control mice. Overall, AFB1-induced splenic pyroptosis is associated with the gut microbiota and its metabolites, which was further demonstrated by FMT and SFF. The mechanism of AFB1-induced splenic pyroptosis was explored for the first time, which paves a new way for preventing and treating the immunotoxicity from mycotoxins by regulating the gut microbiota.

DPPA2/4 Promote the Pluripotency and Proliferation of Bovine Extended Pluripotent Stem Cells by Upregulating the PI3K/AKT/GSK3ß/ß-Catenin Signaling Pathway.

Developmental pluripotency-associated 2 (DPPA2) and DPPA4 are crucial transcription factors involved in maintaining pluripotency in humans and mice. However, the role of DPPA2/4 in bovine extended pluripotent stem cells (bEPSCs) has not been investigated. In this study, a subset of bEPSC-related differentially expressed genes (DEGs), including DPPA2 and DPPA4, was identified based on multiomics data (ATAC-seq and RNA-seq). Subsequent investigations revealed that double overexpression of DPPA2/4 facilitates the reprogramming of bovine fetal fibroblasts (BFFs) into bEPSCs, whereas knockout of DPPA2/4 in BFFs leads to inefficient reprogramming. DPPA2/4 overexpression and knockdown experiments revealed that the pluripotency and proliferation capability of bEPSCs were maintained by promoting the transition from the G1 phase to the S phase of the cell cycle. By activating the PI3K/AKT/GSK3ß/ß-catenin pathway in bEPSCs, DPPA2/4 can increase the nuclear accumulation of ß-catenin, which further upregulates lymphoid enhancer binding factor 1 (LEF1) transcription factor activity. Moreover, DPPA2/4 can also regulate the expression of LEF1 by directly binding to its promoter region. Overall, our results demonstrate that DPPA2/4 promote the reprogramming of BFFs into bEPSCs while also maintaining the pluripotency and proliferation capability of bEPSCs by regulating the PI3K/AKT/GSK3ß/ß-catenin pathway and subsequently activating LEF1. These findings expand our understanding of the gene regulatory network involved in bEPSC pluripotency.

Flavor Characteristics, Antioxidant Activity and In Vitro Digestion Properties of Bread with Large-Leaf Yellow Tea Powder.

Foods containing tea could be widely utilized due to the addition of good tea ingredients, especially large-leaf yellow tea, which is rich with a good flavor. Applying this change to bread containing tea would improve its product quality. In this research, large-leaf yellow tea bread (LYB), possessing a special flavor, was developed using ultrafine large-leaf yellow tea powder and flour as the main raw materials. The amount of ultrafine large-leaf yellow tea powder added to bread was optimized using texture, sensation, and specific volume as comprehensive evaluation indicators. At the optimal dosage, the free amino acids, volatile flavor compounds, antioxidant activity, and in vitro starch digestibility of LYB were measured. Response surface optimization experimental results showed that the comprehensive score of bread was highest when the added amount of ultrafine large-leaf yellow tea powder was 3%. In particular, compared to blank bread (BB), adding ultrafine large-leaf yellow tea powder into bread could effectively increase its amino acid composition, enhance its volatile flavor compounds, improve the antioxidant capacity, and reduce the digestibility of starch.

Vibrational phenomics decoding of the stem cell stepwise aging process at single-cell resolution.

We introduce vibrational spectroscopy to quantitatively measure the phenotypic heterogeneity of senescent stem cells in the aging process at the single cell level. Using an aging model of serially passaged human mesenchymal stem cells (MSCs), we characterized the phenotypic changes of MSCs during different aged stages and discovered a stepwise aging process with several distinct subtypes.

The effects of Salvia miltiorrhiza and ligustrazine injection combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review and meta-analysis are necessary to assess the efficacy and safety of SML injection for the treatment of DKD. METHODS: We searched 6 electronic literature databases comparing randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), SML injection in combination with ACEIs/ARBs that were conducted from inception until September 5, 2023. Two reviewers extracted data and independently assessed the risk of bias. Using the Cochrane Risk of Bias Tool for Risk Assessment. Mean differences (MD) were combined with random-effects models and the corresponding 95% confidence intervals (CI) were reported. Review Manager 5.4 software was used for meta-analysis. Stata 17.0 software was used for sensitivity analysis and Egger test. RESULTS: The combined results show that the use of SML injection along with ACEI/ARB led to better outcomes than the use of controls in terms of enhancing recovery: renal function: Serum creatinine (MD = -14.69, 95% CI (-19.38, -10.00)), Blood urea nitrogen (MD = -1.23, 95% CI (-1.72, -0.74)), Urinary ß2-microglobulin (MD = -4.58, 95% CI (-7.72, -1.44)); urinary protein: Urinary albumin excretion rate (MD = -45.74, 95% CI (-58.92, -32.56)), Urine albumin-creatinine ratio (MD = -11.93, 95% CI (-13.89, -9.96)), 24-h urine proteinuria (MD = -0.59, 95% CI (-0.86, -0.32)), Urine microalbumin (MD = -13.50, 95% CI (-20.18, -6.83)). Additionally, adjuvant therapy with SML injection enhanced results in blood glucose, blood pressure, lipids, and inflammatory responses, and no significant variations in adverse events were discovered between the 2 groups. CONCLUSIONS: In patients with DKD, combining SML injection with ACEI/ARB improves renal function, renal proteinuria, hyperglycemia, blood pressure, dyslipidemia, and inflammatory response.

Additive renal protective effects between arctigenin and puerarin in diabetic kidney disease.

Recent studies have shown that the combined use of renin angiotensin system inhibitor, SGLT2 inhibitors and/or mineralocorticoid receptor antagonist provides additional renal protection for patients with diabetic kidney disease (DKD). Similarly, in traditional Chinese medicine, the synergistic application of multiple herbs often brings more significant therapeutic effects. However, the synergistic or additive mechanisms of traditional Chinese medicine in combination therapy are not fully understood. In our previous studies, we show that arctigenin (ATG), a major component of Fructus Arctii, attenuates proteinuria and renal injury in diabetic mice by activating PP2A, and puerarin (a class of known isoflavones) can also reduce proteinuria and renal injury in diabetic mice via activation of Sirt1. Here, we further explored the potential additive renal protection of these two compounds in diabetic mice. Research has found that ATG and puerarin have a synergistic effect in reducing albuminuria in db/db mice. Mechanistically, we found that ATG reduced NF-κB p65 phosphorylation likely through activation of PP2A while puerarin reduced p65 acetylation via Sirt1 activation. Therefore, ATG and puerarin have additive inhibitory effects on the NF-κB activation, which is a key inflammatory pathway in DKD. RNA-sequencing analysis revealed distinct pathways activated by ATG and puerarin in the diabetic kidney, which may provide an additional mechanism for their additive effects in DKD. Our study suggests that ATG and puerarin could be a new combination therapy for DKD and reveals its underlined mechanisms.

Characterization of Cell Type Abundance and Gene Expression Timeline from Burned Skin Bulk Transcriptomics by Deconvolution.

Currently, no timeline of cell heterogeneity in thermally injured skin has been reported. In this study, we proposed an approach to deconvoluting cell type abundance and expression from skin bulk transcriptomics with cell type signature matrix constructed by combining independent normal skin and peripheral blood scRNA-seq datasets. Using CIBERSORTx group mode deconvolution, we identified perturbed cell type fractions and cell type-specific gene expression in three stages postthermal injury. We found an increase in cell proportions and cell type-specific gene expression perturbation of neutrophils, macrophages, and endothelial cells and a decrease in CD4+ T cells, keratinocytes, melanocyte, and fibroblast cells, and cell type-specific gene expression perturbation postburn injury. Keratinocyte, fibroblast, and macrophage up regulated genes were dynamically enriched in overlapping and distinct Gene Ontology biological processes including acute phase response, leukocyte migration, metabolic, morphogenesis, and development process. Down-regulated genes were enriched in Wnt signaling, mesenchymal cell differentiation, gland and axon development, epidermal morphogenesis, and fatty acid and glucose metabolic process. We noticed an increase in the expression of CCL7, CCL2, CCL20, CCR1, CCR5, CCXL8, CXCL2, CXCL3, MMP1, MMP8, MMP3, IL24, IL6, IL1B, IL18R1, and TGFBR1 and a decrease in expression of CCL27, CCR10, CCR6, CCR8, CXCL9, IL37, IL17, IL7, IL11R, IL17R, TGFBR3, FGFR1-4, and IGFR1 in keratinocytes and/or fibroblasts. The inferred timeline of wound healing and CC and CXC genes in keratinocyte was validated on independent dataset GSE174661 of purified keratinocytes. The timeline of different cell types postburn may facilitate therapeutic timing.

Peptide composition analysis, structural characterization, and prediction of iron binding modes of small molecular weight peptides from mung bean.

Iron supplementation is a proactive approach to limit instances of iron deficiency anemia. This study is based on the enzymatic hydrolysis and fractionation of mung bean proteins (MBPs) followed by the determination of the Fe2+ chelating activities of these peptide-containing fractions. MBP-Fe complex was generated using a chemical chelation method and subsequently characterized. Following Sephadex G15 separation of MBPs, one of the fractions containing 10 different peptides, demonstrated maximum Fe2+ chelating activity of 39.97 ± 0.07 µg/mg. The sequences of these peptides were determined using liquid chromatography-tandem mass spectrometry. The Fe2+ ion content of the MBP-Fe complex was determined using X-ray photoelectron spectroscopy and 80% of the iron was found to be in Fe2+ oxidation state. After iron chelation, there was an increase in the peptide's particle size, with an average value of 550.67 ± 0.70 nm. This increase in size was attributed to the contributions of the amino proline and glycine, which extended the peptides to form the MBP-Fe complex. Finally, molecular docking studies revealed that Fe2+ mainly bound to carboxy-oxygen of glutamate and aspartate residues of mung bean peptides to form MBP-Fe complex. This research could serve as a scientific foundation for the development of dietary iron supplements using plant-derived peptides.

CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e+ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e- cells. CD66e+CD34+CD90+CD45RA- cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e-CD34+CD90+CD45RA-cells. CD66e expression also identified almost all repopulating HSCs within the CD34+CD90+CD45RA- population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Derivation of Arbas Cashmere Goat Induced Pluripotent Stem Cells in LCDM with Trophectoderm Lineage Differentiation and Interspecies Chimeric Abilities.

The Arbas cashmere goat is a unique biological resource that plays a vital role in livestock husbandry in China. LCDM is a medium with special small molecules (consisting of human LIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride) for generation pluripotent stem cells (PSCs) with bidirectional developmental potential in mice, humans, pigs, and bovines. However, there is no report on whether LCDM can support for generation of PSCs with the same ability in Arbas cashmere goats. In this study, we applied LCDM to generate goat induced PSCs (giPSCs) from goat fetal fibroblasts (GFFs) by reprogramming. The derived giPSCs exhibited stem cell morphology, expressing pluripotent markers, and could differentiate into three germ layers. Moreover, the giPSCs differentiated into the trophectoderm lineage by spontaneous and directed differentiation in vitro. The giPSCs contributed to embryonic and extraembryonic tissue in preimplantation blastocysts and postimplantation chimeric embryos. RNA-sequencing analysis showed that the giPSCs were very close to goat embryos at the blastocyst stage and giPSCs have similar properties to typical extended PSCs (EPSCs). The establishment of giPSCs with LCDM provides a new way to generate PSCs from domestic animals and lays the foundation for basic and applied research in biology and agriculture.

Predicting response to CCRT for esophageal squamous carcinoma by a radiomics-clinical SHAP model.

BACKGROUND: Radical concurrent chemoradiotherapy (CCRT) is frequently used as the first-line treatment for patients with locally advanced esophageal cancer. Unfortunately, some patients respond poorly. To predict response to radical concurrent chemoradiotherapy in pre-treatment patients with esophageal squamous carcinoma (ESCC), and compare the predicting efficacies of radiomics features of primary tumor with or without regional lymph nodes, we developed a radiomics-clinical model based on the positioning CT images. Finally, SHapley Additive exPlanation (SHAP) was used to explain the models. METHODS: This retrospective study enrolled 105 patients with medically inoperable and/or unresectable ESCC who underwent radical concurrent chemoradiotherapy (CCRT) between October 2018 and May 2023. Patients were classified into responder and non-responder groups with RECIST standards. The 11 recently admitted patients were chosen as the validation set, previously admitted patients were randomly split into the training set (n = 70) and the testing set (n = 24). Primary tumor site (GTV), the primary tumor and the uninvolved lymph nodes at risk of microscopic disease (CTV) were identified as Regions of Interests (ROIs). 1762 radiomics features from GTV and CTV were respectively extracted and then filtered by statistical differential analysis and Least Absolute Shrinkage and Selection Operator (LASSO). The filtered radiomics features combined with 13 clinical features were further filtered with Mutual Information (MI) algorithm. Based on the filtered features, we developed five models (Clinical Model, GTV Model, GTV-Clinical Model, CTV Model, and CTV-Clinical Model) using the random forest algorithm and evaluated for their accuracy, precision, recall, F1-Score and AUC. Finally, SHAP algorithm was adopted for model interpretation to achieve transparency and utilizability. RESULTS: The GTV-Clinical model achieves an AUC of 0.82 with a 95% confidence interval (CI) of 0.76-0.99 on testing set and an AUC of 0.97 with a 95% confidence interval (CI) of 0.84-1.0 on validation set, which are significantly higher than those of other models in predicting ESCC response to CCRT. The SHAP force map provides an integrated view of the impact of each feature on individual patients, while the SHAP summary plots indicate that radiomics features have a greater influence on model prediction than clinical factors in our model. CONCLUSION: GTV-Clinical model based on texture features and the maximum diameter of lesion (MDL) may assist clinicians in pre-treatment predicting ESCC response to CCRT.

Application of virtual technology to maximize esthetics and function in the restoration of anterior traumatic dental injuries.

The restoration of multiple teeth with traumatic injury in the esthetic zone is complex. For the present patient, an intraoral scanner, a facial scanner, a jaw motion analyzer, and cone beam computed tomography were applied to collect patient data and establish a virtual dental patient. The virtual technology increased the accuracy of tooth- and implant-supported crowns in both appearance and occlusion.

Photodynamic Cationic Ultrasmall Copper Oxide Nanoparticles-Loaded Liposomes for Alleviation of MRSA Biofilms.

Introduction: As we enter the post-antibiotic era, the rise of antibiotic-resistant pathogenic bacteria is becoming a serious threat to public health. This problem is further complicated by antibiotic-resistant biofilms, for which current treatment options are limited. Methods: To tackle this challenge, we propose a novel approach that involves the use of photodynamic cationic pH-sensitive liposomes loaded with ultra-small copper oxide (Ce6@Lipo/UCONs) to effectively eliminate drug-resistant bacteria and eradicate biofilms while minimizing safety concerns and the risk of resistance development. Results: Our study demonstrates that Ce6@Lipo/UCONs have minimal toxicity to mammalian cells and can significantly enhance the association affinity with methicillin-resistant Staphylococcus aureus (MRSA) as confirmed by fluorescent microscope and flow cytometry, thereby greatly improving the bactericidal effect against planktonic MRSA. The cationic nature of Ce6@Lipo/UCONs also enables them to penetrate MRSA biofilms and respond to the acidic microenvironment within the biofilm, effectively releasing the loaded UCONs. Our results indicate that Ce6@Lipo/UCONs could effectively eliminate biofilms under light irradiation conditions, as evidenced by both biomass analysis and scanning electron microscopy observations. In addition, significant antibacterial effects and abscess healing were observed in MRSA-infected mice treated with Ce6@Lipo/UCONs upon light irradiation, while good biocompatibility was achieved in vivo. Conclusion: Taken together, our findings suggest that photodynamic cationic ultrasmall copper oxide nanoparticles-loaded liposomes are a highly promising nano platform for combating antibiotic-resistant microbial pathogens and biofilms. The effective biofilm penetration and synergistic effect between photodynamic inactivation and metal sterilization make them a valuable tool for overcoming the challenges posed by antibiotic resistance.

Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism.

Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.

Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters.

Mixed-lineage leukemia 1 (MLL1) introduces 1-, 2- and 3-methylation into histone H3K4 through the evolutionarily conserved set domain. In this study, bovine embryonic stem cells (bESCs, known as bESCs-F7) were established from in vitro-fertilized (IVF) embryos via Wnt signaling inhibition; however, their contribution to the endoderm in vivo is limited. To improve the quality of bESCs, MM-102, an inhibitor of MLL1, was applied to the culture. The results showed that MLL1 inhibition along with GSK3 and MAP2K inhibition (3i) at the embryonic stage did not affect bESCs' establishment and pluripotency. MLL1 inhibition improved the pluripotency and differentiation potential of bESCs via the up-regulation of stem cell signaling pathways such as PI3K-Akt and WNT. MLL1 inhibition decreased H3K4me1 modification at the promoters and altered the distribution of DNA methylation in bESCs. In summary, MLL1 inhibition gives bESCs better pluripotency, and its application may provide high-quality pluripotent stem cells for domestic animals.