Efficient Synthesis of Metastable Cyclodextrin-Based Polyrotaxanes with Tunable Threading Ratios.

Cyclodextrin-based polyrotaxanes (CD-PRs) are gaining attention for their dynamic sliding rings along the polymer axis, enabling various applications in molecular shuttles, drug delivery, and durable polymers with slidable cross-links. However, the conventional synthesis of CD-PRs with tunable threading ratios is typically laborious, time-consuming, and complicated, which limits their scalability and cost-effectiveness. Herein, we highlight the great potential of planetary centrifugal mixing, a process that significantly accelerates and simplifies the initial synthesis of polypseudorotaxanes (PPRs), followed by a thiol-ene click reaction as an efficient end-capping reaction for the synthesis of PRs. Notably, PRs synthesized with glutathione (GSH) as the end-capping reagent are in a metastable state, where GSH act as a molecular bumper that significantly prevent de-threading of α-CD rings at room temperature. Moreover, the rate of ring de-threading can be precisely controlled by heating, enabling the preparation of metastable PRs with tunable threading ratios over a wide range. The developed strategy is of great significance to the efficient synthesis of CD-PRs, thus marking a significant step towards their practical application in advanced functional materials and devices.

Organic ammonium salt assisted crystallization and defect passivation of a quasi-two-dimensional pure blue perovskite at the buried interface.

Quasi-two-dimensional (quasi-2D) perovskites exhibit excellent performance in light-emitting diodes (LEDs). However, the quality of perovskite films prepared via the solution method is significantly impacted by the enormous number of defects that unavoidably form at the grain boundaries and interfaces during the precursor to the crystal formation process. Here, we propose a strategy to assist perovskite crystallization and defect passivation at the buried interface through interfacial modification. The organic ammonium salt, ethylamine chloride (EACl), is added to the hole transport material and modifies the buried interface of the perovskite film. EACl introduces the nucleation sites for perovskite precursors, and promotes the crystallization process of the perovskite grains, contributing to the formation of high-quality perovskite films. At the same time, the presence of Lewis base (-NH2) groups in EACl and their lone electron pairs effectively inactivate unlocated Pb2+ ions at the buried interface, thereby reducing non-radiative recombination. In addition, chloride ions help to mitigate defects and to improve the morphology of perovskite films. Devices with this modification show a higher performance than control devices on all metrics. This work proposes a facile but efficient way for improving quasi-2D pure blue perovskite crystallization and growth.

Sishen Pill inhibits intestinal inflammation in diarrhea mice via regulating kidney-intestinal bacteria-metabolic pathway.

Background: Sishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been elucidated. Objective: This study investigated the mechanism of SSP in regulating intestinal microecology in diarrhea with DKYS. Methods: Adenine combined with Folium sennae was used to construct a mouse model of diarrhea with DKYS and administered with SSP. The behavioral changes and characteristics of gut content microbiota and short-chain fatty acids (SCFAs) of mice were analyzed to explore the potential association between the characteristic bacteria, SCFAs, intestinal inflammatory and kidney function-related indicators. Results: After SSP intervention, the body weight and anal temperature of diarrhea with DKYS gradually recovered and approached the normal level. Lactobacillus johnsonii was significantly enriched, and propionic, butyric, isobutyric and isovaleric acids were elevated. Serum creatinine (Cr), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels of the mice were reduced, while serum blood urea nitrogen (BUN) and secretory immunoglobulin A (sIgA) in the colonic tissues were increased. Moreover, there were correlations between L. johnsonii, SCFAs, intestinal inflammatory, and kidney function. Conclusion: SSP might suppress the intestinal inflammation by regulating the "L. johnsonii-propionic acid" pathway, thus achieving the effect of treating diarrhea with DKYS.

Alleviatory Role of Panax Notoginseng Saponins in Modulating Inflammation and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease: mechanisms and Implications.

COPD is an inflammatory lung disease that limits airflow and remodels the pulmonary vascular system. This study delves into the therapeutic potential and mechanistic underpinnings of Panax notoginseng Saponins (PNS) in alleviating inflammation and pulmonary vascular remodeling in a COPD rat model. Symmap and ETCM databases provided Panax notoginseng-related target genes, and the CTD and DisGeNET databases provided COPD-related genes. Intersection genes were subjected to protein-protein interaction analysis and pathway enrichment to identify downstream pathways. A COPD rat model was established, with groups receiving varying doses of PNS and a Roxithromycin control. The pathological changes in lung tissue and vasculature were examined using histological staining, while molecular alterations were explored through ELISA, RT-PCR, and Western blot. Network pharmacology research suggested PNS may affect the TLR4/NF-κB pathway linked to COPD development. The study revealed that, in contrast to the control group, the COPD model exhibited a significant increase in inflammatory markers and pathway components such as TLR4, NF-κB, HIF-1α, VEGF, ICAM-1, SELE mRNA, and serum TNF-α, IL-8, and IL-1ß. Treatment with PNS notably decreased these markers and mitigated inflammation around the bronchi and vessels. Taken together, the study underscores the potential of PNS in reducing lung inflammation and vascular remodeling in COPD rats, primarily via modulation of the TLR4/NF-κB/HIF-1α/VEGF pathway. This research offers valuable insights for developing new therapeutic strategies for managing and preventing COPD.

The Exosome-Mediated Bone Regeneration: An Advanced Horizon Toward the Isolation, Engineering, Carrying Modalities, and Mechanisms.

Exosomes, nanoparticles secreted by various cells, composed of a bilayer lipid membrane, and containing bioactive substances such as proteins, nucleic acids, metabolites, etc., have been intensively investigated in tissue engineering owing to their high biocompatibility and versatile biofunction. However, there is still a lack of a high-quality review on bone defect regeneration potentiated by exosomes. In this review, the biogenesis and isolation methods of exosomes are first introduced. More importantly, the engineered exosomes of the current state of knowledge are discussed intensively in this review. Afterward, the biomaterial carriers of exosomes and the mechanisms of bone repair elucidated by compelling evidence are presented. Thus, future perspectives and concerns are revealed to help devise advanced modalities based on exosomes to overcome the challenges of bone regeneration. It is totally believed this review will attract special attention from clinicians and provide promising ideas for their future works.

Effect of Methyl Hydro-Silicone Oil Content and Aging Time on Compression Modulus and Breakdown Strength of Additional Liquid Silicone Rubber Gel.

The performance of silicone rubber gel elastomers is affected by the composition and structure of the crosslinker. In this work, a two-component addition liquid silicone rubber gel material was developed, and the effects of the contents of two methyl hydro-silicone oils on the compression modulus and breakdown strength of the silicone rubber gel insulating material, as well as the performance change after hot air aging at different times (24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h), were studied. The results showed that the breakdown strength and compression modulus exhibited an upward trend with the increase in the hydrogen silicone oil content. The best performance was achieved in the silicone rubber gel with Si-H:Si-Vi = 1.4:1. Moreover, with the increase in aging time, the breakdown strength decreased and the compression modulus increased.

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1.

BACKGROUND: Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear. METHODS: The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells. RESULTS: POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance. CONCLUSION: Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.

Electrokinetic Analyses Uncover the Rate-Determining Step of Biomass-Derived Monosaccharide Electroreduction on Copper.

Electrochemical biomass conversion holds promise to upcycle carbon sources and produce valuable products while reducing greenhouse gas emissions. To this end, deep insight into the interfacial mechanism is essential for the rational design of an efficient electrocatalytic route, which is still an area of active research and development. Herein, we report the reduction of dihydroxyacetone (DHA)-the simplest monosaccharide derived from glycerol feedstock-to acetol, the vital chemical intermediate in industries, with faradaic efficiency of 85±5 % on a polycrystalline Cu electrode. DHA reduction follows preceding dehydration by coordination with the carbonyl and hydroxyl groups and the subsequent hydrogenation. The electrokinetic profile indicates that the rate-determining step (RDS) includes a proton-coupled electron transfer (PCET) to the dehydrated intermediate, revealed by coverage-dependent Tafel slope and isotopic labeling experiments. An approximate zero-order dependence of H+ suggests that water acts as the proton donor for the interfacial PCET process. Leveraging these insights, we formulate microkinetic models to illustrate its origin that Eley-Rideal (E-R) dominates over Langmuir-Hinshelwood (L-H) in governing Cu-mediated DHA reduction, offering rational guidance that increasing the concentration of the adsorbed reactant alone would be sufficient to promote the activity in designing practical catalysts.

Defects in lead halide perovskite light-emitting diodes under electric field: from behavior to passivation strategies.

Lead halide perovskites (LHPs) are emerging semiconductor materials for light-emitting diodes (LEDs) owing to their unique structure and superior optoelectronic properties. However, defects that initiate degradation of LHPs through external stimuli and prompt internal ion migration at the interfaces remain a significant challenge. The electric field (EF), which is a fundamental driving force in LED operation, complicates the role of these defects in the physical and chemical properties of LHPs. A deeper understanding of EF-induced defect behavior is crucial for optimizing the LED performance. In this review, the origins and characterization of defects are explored, indicating the influence of EF-induced defect dynamics on LED performance and stability. A comprehensive overview of recent defect passivation approaches for LHP bulk films and nanocrystals (NCs) is also provided. Given the ubiquity of EF, a summary of the EF-induced defect behavior can enhance the performance of perovskite LEDs and related optoelectronic devices.

Post-infarction ventricular septal rupture complicated with cardiogenic shock and multiple organ hemorrhage: An autopsy case report.

Ventricular septal rupture (VSR) is a catastrophic mechanical complication of acute myocardial infarction (AMI) that can result in acute heart failure. Delaying operative intervention frequently leads to cardiogenic shock and multi-organ failure. Here we report a case of massive anterior MI complicated with VSR that was discovered through cardiac Doppler ultrasound and suspected multiple organ hemorrhage. The patient showed signs of rapid cardiogenic shock and eventually died. The morphological changes of VSR and MI were identified during necropsy, and microscopic examinations of the heart, brain, and kidney revealed multiple organ hemorrhage. This autopsy case suggested that the complication of VSR caused by AMI results in a reduction of oxygen and nutrient content of the circulating blood throughout the body and, eventually, functional failure of multiple organs. We provide clinical and pathological evidence elucidating changes in multiple organs under the severe condition of post-infarction VSR and demonstrate the consequences of a lack of immediate surgery and sufficient medical intervention for a patient suffering from AMI with VSR.

Modulating the polarization phenotype of microglia - A valuable strategy for central nervous system diseases.

Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.

Evaluation of toxicological effects of chemical substances by gut microbiota: The example of adenine damage to the kidney and gut.

This study explored the effects of different doses of adenine intake on mice in terms of kidney function, oxidative stress and gut content microbiota to elucidate interactions between adenine-induced kidney function impairment and gut content microbiota disorder. Mice were gavaged with low-dosage adenine suspension (NML), middle-dosage adenine suspension (NMM), high-dosage adenine suspension (NMH) and sterile water (NC). Behaviour, kidney structure and function, colonic structure, oxidative stress and gut content microbiota were detected. Mice in NML, NMM, and NMH groups had significantly lower body weight, anal temperature and food intake, increased water intake, the mice had loose and deformed feces with obvious water stains through the paper. NMM mice presented significantly structural damage to kidney and colonic tissues, considerably higher BUN and Cr, MDA and lower SOD. MDA and SOD levels in NMM and NMH groups were closely associated with Cr and BUN. Moreover, different doses of adenine intake effected the mice gut content microbiota, and enriched the different characteristic bacteria. Characteristic bacteria Lactobacillus and Bifidobacterium presented significant correlations with MDA. Eventually, Lactobacillus and Bifidobacterium mediated oxidative stress pathway involved in the process of adenine-induced kidney injure in mice.

Adipocyte-derived exosomal miR-22-3p modulated by circadian rhythm disruption regulates insulin sensitivity in skeletal muscle cells.

Circadian rhythm disruption leads to dysregulation of lipid metabolism, which further drive the occurrence of insulin resistance (IR). Exosomes are natural carrier systems that advantageous for cell communication. In the present study, we aimed to explore whether and how the exosomal microRNAs (miRNAs) in circulation participate in modulating skeletal muscle IR induced by circadian rhythm disruption. In the present study, 24-h constant light (12-h light/12-h light, LL) was used to establish the mouse model of circadian rhythm disruption. Bmal1 interference was used to establish the cell model of circadian rhythm disruption. And in clinical experiments, we chose a relatively large group of rhythm disturbance-shift nurses. We showed that LL-induced circadian rhythm disruption led to increased body weight and visceral fat volume, as well as occurrence of IR in vivo. Furthermore, exosomal miR-22-3p derived from adipocytes in the context of circadian rhythm disruption induced by Bmal1 interference could be uptaken by skeletal muscle cells to promote IR occurrence in vitro. Moreover, miR-22-3p in circulation was positively correlated with the clinical IR-associated factors. Collectively, these data showed that exosomal miR-22-3p in circulation may act as potential biomarker and therapeutic target for skeletal muscle IR, contributing to the prevention of diabetes in the context of rhythm disturbance.

Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway: Network Pharmacology Analysis and Experimental Validation.

OBJECTIVE: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis. METHODS: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). RESULTS: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002. CONCLUSION: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.

Predicting cervical lymph node metastasis in OSCC based on computed tomography imaging genomics.

BACKGROUND: To investigate the correlation between computed tomography (CT) radiomic characteristics and key genes for cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC). METHODS: The region of interest was annotated at the edge of the primary tumor on enhanced CT images from 140 patients with OSCC and obtained radiomic features. Ribonucleic acid (RNA) sequencing was performed on pathological sections from 20 patients. the DESeq software package was used to compare differential gene expression between groups. Weighted gene co-expression network analysis was used to construct co-expressed gene modules, and the KEGG and GO databases were used for pathway enrichment analysis of key gene modules. Finally, Pearson correlation coefficients were calculated between key genes of enriched pathways and radiomic features. RESULTS: Four hundred and eighty radiomic features were extracted from enhanced CT images of 140 patients; seven of these correlated significantly with cervical LNM in OSCC (p < 0.01). A total of 3527 differentially expressed RNAs were screened from RNA sequencing data of 20 cases. original_glrlm_RunVariance showed significant positive correlation with most long noncoding RNAs. CONCLUSIONS: OSCC cervical LNM is related to the salivary hair bump signaling pathway and biological process. Original_glrlm_RunVariance correlated with LNM and most differentially expressed long noncoding RNAs.

Association of Short-Chain Fatty Acids with Gut Microbiota and Lipid Metabolism in Mice with Diarrhea Induced by High-Fat Diet in a Fatigued State.

SCOPE: Preliminary research finds that a high-fat diet (HFD) in a fatigued state triggers diarrhea, but the exact mechanism has not been clarified. To address concerns about the pathogenesis of diarrhea, the study evaluates the composition and metabolomics of the gut microbiota. METHODS AND RESULTS: The study uses the multiple platform apparatus device to induce fatigue in mice, combined with intragastric administration of lard-caused diarrhea. Subsequently, the characteristics and interaction relationship of gut microbiota, short-chain fatty acids (SCFAs), inflammatory biomarkers, brain-gut peptides, and lipid metabolism are analyzed at the end of the experiment. HFD in a fatigued state results in a significant increase in interleukin-17, interleukin-6, cholecystokinin, somatostatin, and malondialdehyde content in mice (p < 0.05), along with a substantial decrease in high-density lipoprotein (p < 0.05). Additionally, an HFD in a fatigued state causes changes in the structure and composition of the gut microbiota, with Lactobacillus murinus as its characteristic bacteria, and reduces the production of SCFAs. CONCLUSIONS: An HFD in a fatigued state triggers diarrhea, possibly associated with gut content microbiota dysbiosis, SCFAs deprivation, increased inflammation, and dysregulated lipid metabolism.

Modulation Phase Distribution of Ruddlesden-Popper Quasi-2D Perovskites with a Similarly Spaced Dion-Jacobson Phase.

Quasi-two-dimensional (quasi-2D) perovskites exhibit excellent performance when applied to light-emitting diodes (LEDs). However, quasi-2D perovskite films generally have nonuniform n phases and irregular internal crystal structures, which degrade the device's performance. Here, we propose using a Dion-Jacobson (DJ)-type organic spacer to modulate the phase distribution of the Ruddlesden-Popper (RP) quasi-2D perovskite. A DJ-type organic spacer cation, 1.6-hexamethylenediamine (HDABr2), was introduced into the perovskite as the second spacer cation with propylamine hydrobromide (PABr). As DJ-type and RP-type perovskites have similar spacings, RP-DJ style does not cause a chaotic crystalline structure; instead, it modulates the perovskite crystallization and narrows the phase distribution. In parallel, there is a substantial improvement in the maximum luminance, current efficiency, external quantum efficiency, and device stability of the quasi-2D perovskite LEDs. This work provides a novel concept for combining the organic spacer cations for quasi-2D perovskites.

Stability and Degradation in Lead Halide Perovskite Nanocrystals via Regulation of Lattice Strain.

It is still quite challenging to achieve high-performance and stable blue perovskite materials due to their instability and degradation. The lattice strain provides an important pathway to investigate the degradation process. In this article, the lattice strain in perovskite nanocrystals was regulated by the ratio of Cs+, EA+, and Rb+ cations with different sizes. Their electrical structure, formation energy, and ion migration activation energy were calculated with the density functional theory (DFT) method. The luminescence properties and stability of blue lead bromide perovskite nanocrystals were analyzed with spectra regulation from 516 to 472 nm. It was demonstrated that the lattice strain plays an important role in the luminescence performance and degradation process of perovskite materials. The study provides the positive correlation between lattice strain and degradation as well as luminescence properties in lead halide perovskite materials, which is of great importance in uncovering their degradation mechanism and developing stable and high-performance blue perovskite materials.

Lipophilic statins inhibit YAP coactivator transcriptional activity in HCC cells through Rho-mediated modulation of actin cytoskeleton.

Hepatocellular carcinoma (HCC) is the third leading cause of liver-related death. Lipophilic statins have been associated with a decrease in HCC incidence, raising the possibility of their use as chemoprevention agents. The Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) have emerged as an important pro-oncogenic mechanism in HCC. Statins modulate YAP/TAZ in other solid tumors, but few studies have assessed their mechanisms in HCC. We aimed to delineate how lipophilic statins regulate YAP protein localization by interrogating the mevalonate pathway in a stepwise manner using pharmacological and genetical approaches in HCC cells. Huh7 and Hep3B HCC cells were treated with the lipophilic statins cerivastatin and atorvastatin. YAP protein localization was determined using quantitative immunofluorescence (IF) imaging. The gene expression of CTGF and CYR61, known YAP/TEA-domain DNA-binding factor (TEAD)-regulated genes, was measured using quantitative real-time PCR. Rescue experiments were conducted using metabolites of the mevalonate pathway including mevalonic acid and geranylgeranyl pyrophosphate (GG-PP). The cellular cytoskeleton was assessed using F-actin IF staining. YAP protein was extruded from the nucleus to the cytoplasm with statin treatment. Consistently, CTGF and CYR61 mRNA expression significantly decreased with statins. Cytoskeletal structure was also compromised with statins. Gene expression, YAP protein localization, and cytoskeletal structure were all restored to baseline with exogenous GG-PP but not with other metabolites of the mevalonate pathway. Direct Rho GTPase inhibitor treatment mirrored the statin effects on YAP. YAP protein localization is regulated by lipophilic statins via Rho GTPases, causing cytoskeletal structural changes and is independent of cholesterol metabolites.NEW & NOTEWORTHY Statins are widely used for the treatment of cardiovascular diseases. Recently, their use has been associated with a decrease in the incidence of hepatocellular carcinoma (HCC); however, their mechanism(s) has remained elusive. In this study, we delineate the mechanism by which statins affect the Yes-associated protein (YAP), which has emerged as a key oncogenic pathway in HCC. We investigate each step of the mevalonate pathway and demonstrate that statins regulate YAP via Rho GTPases.

Intestinal mucosal flora of the intestine-kidney remediation process of diarrhea with deficiency kidney-yang syndrome in Sishen Pill treatment: Association with interactions between Lactobacillus johnsonii, Ca2+-Mg2+-ATP-ase, and Na+-K+-ATP-ase.

This study aims to investigate the effect of Sishen Pill on the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Fifteen Kunming male mice were randomly divided into Normal control group (C), Model self-healing group (X) and Sishen Pill group (S), with 5 mice/cages. Hematoxylin eosin (HE) staining was used to observe the kidney structure. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA), Analysis of intestinal mucosal flora using third-generation high-throughput sequencing. The relative abundance results in the three groups revealed that the dominant bacterial genera: Lactobacillus, Muribaculum and Candidatus-Arthromitus; bacterial species: Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus murinus, and Lactobacillus intestinalis, and differences in the presence of major microbiota between the X and S groups. A positive correlation between Lactobacillus johnsonii and both Ca2+-Mg2+-ATP-ase and Na+-K+-ATP-ase was found via correlation analysis. Sishen Pill also changed the manufacture of other secondary metabolites, as well as the metabolism of carbohydrates, glycans, energy, lipids, and other amino acids, and xenobiotics biodegradation and metabolism. In conclusion, Sishen Pill improved kidney structure, energy metabolism and the diversity and structure of intestinal mucosal flora. In addition, Lactobacillus johnsonii may be a characteristic species of Sishen Pill in treating diarrhea with kidney-yang deficiency syndrome.