Targeting the Gut-Kidney Axis in Diarrhea with Kidney-Yang Deficiency Syndrome: The Role of Sishen Pills in Regulating TMAO-Mediated Inflammatory Response.

BACKGROUND Sishen Pills (SSPs) are commonly used to treat diarrhea with kidney-yang deficiency syndrome. Trimethylamine-N-oxide (TMAO) is produced through the metabolism of gut microbiota and can participate in diarrhea in kidney-yang deficiency syndrome by mediating the "gut-kidney axis" to transmit inflammatory factors. This study combined network pharmacology with animal experiments to explore whether SSPs can treat diarrhea with kidney-yang deficiency syndrome by affecting the interaction between TMAO and gut microbiota. MATERIAL AND METHODS A mouse model of diarrhea with kidney-yang deficiency syndrome was constructed by using adenine and Folium sennae decoction, and SSP decoction was used for treatment. This study utilized network pharmacology to predict the potential mechanisms of SSPs in treating diarrhea with kidney-yang deficiency syndrome. 16S rRNA high-throughput sequencing was used to analyze gut mucosal microbial characteristics. ELISA was used to measure TMAO, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), interleukin-1ß (IL-1ß), and transforming growth factor-ß1 (TGF-ß1) levels. We performed Masson and immunohistochemical (Occludin, ZO-1) staining of kidney and small intestinal tissues. The fluorescein diacetate (FDA) hydrolysis spectrophotometric method was used to assess the microbial activity in contents of the small intestine. RESULTS Network pharmacology analysis revealed that SSPs can modulate 108 target points involved in the development of diarrhea, including IL-1ß and TNF. The experimental results demonstrated that SSP decoction significantly improved the general behavioral profiles of the mice, and also reduced TMAO, NLRP3, IL-1ß, and TGF-ß1 levels (P<0.05). Correlation analysis revealed significant positive correlations between TMAO concentrations and NLRP3, IL-1ß and TGF-ß1 levels (P<0.05). Pathological analysis revealed improvements in renal fibrosis and increased expression of the Occludin and ZO-1 proteins in intestinal tissue. In the SSP group, there was a significant increase in microbial activity (P<0.001). According to the sequencing results, the characteristic bacteria of the SSP and NR groups included Succinatimonas hippei, uncultured Solirubrobacter sp., and Clostridium tyrobutyricum. Furthermore, TMAO, NLRP3, IL-1ß, and TGF-ß1 were significantly positively correlated (P<0.05) with Succinatimonas hippei and Clostridium tyrobutyricum. By modulating Firmicutes, Succinatimonas hippei, and Clostridium tyrobutyricum, SSP decoction lowers TMAO levels to alleviate diarrhea with kidney-yang deficiency syndrome. CONCLUSIONS TMAO likely plays a significant role in the "gut-kidney axis" of diarrhea with kidney-yang deficiency syndrome. By adjusting gut microbiota to reduce the inflammatory response that is transmitted through the "gut-kidney axis" as a result of elevated TMAO levels, SSP decoction can alleviate diarrhea with kidney-yang deficiency syndrome.

A fungal pathogen secretes a cell wall-associated ß-N-acetylhexosaminidase that is co-expressed with chitinases to contribute to infection of insects.

BACKGROUND: ß-N-acetylhexosaminidases (HEXs) are widely distributed in fungi and involved in cell wall chitin metabolism and utilization of chitin-containing substrates. However, details of the fungal pathogens-derived HEXs in the interaction with their hosts remain limited. RESULTS: An insect nutrients-induced ß-N-acetylhexosaminidase, BbHex1, was identified from the entomopathogenic fungus Beauveria bassiana, which was involved in cell wall modification and degradation of insect cuticle. BbHex1 was localized to cell wall and secreted, and displayed enzyme activity to degrade the chitinase-hydrolyzed product (GlcNAc)2. Disruption of BbHex1 resulted in a significant decrease in the level of cell wall chitin in the presence of insect nutrients and during infection of insects, with impaired ability to penetrate insect cuticle, accompanying downregulated cell wall metabolism-involved and cuticle-degrading chitinase genes. However, the opposite phenotypes were examined in the gene overexpression strain. Distinctly altered cell wall structures caused by BbHex1 mutation and overexpression led to the easy activation and evasion (respectively) of insect immune response during fungal infection. As a result, BbHex1 contributed to fungal virulence. Bioinformatics analysis revealed that promoters of some co-expressed chitinase genes with the BbHex1 promoter shared conserved transcription factors Skn7, Msn2 and Ste12, and CreA-binding motifs, implying co-regulation of those genes with BbHex1. CONCLUSION: These data support a mechanism that the fungal pathogen specifically expresses BbHex1, which is co-expressed with chitinases to modify cell wall for evasion of insect immune recognition and to degrade insect cuticle, and contributes to the fungal virulence against insects. © 2024 Society of Chemical Industry.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice.

Growing evidence has demonstrated that cold and humid environmental stress triggers gastrointestinal (GI) disorders. In this study, we explored the effects of intestinal microbiota homeostasis on the intestinal mucus barrier and GI disorders by cold and humid environmental stress. Moreover, the inner link between the intestinal mucosal microbiota and metabolites in mice with cold and humid environmental stress was interpreted by integrative analysis of PacBio HiFi sequencing microbial genomics and targeted metabolomics. In the current study, we found (1) after the cold and wet cold and humid environmental stress intervened in the intestinal microbiota disorder and homeostasis mice respectively, the bacterial culturing and fluorescein diacetate (FDA) microbial activity detection of intestinal microbiota including feces, intestinal contents, and intestinal mucosa suggested that the cold and humid environmental stress decreased the colony of culturable bacteria and microbial activity, in which intestinal microbiota disorder aggravated the injury of the intestinal mucus barrier and the GI symptoms related to cold and humid environmental stress; (2) the serum amino acid transferases such as glutamate pyruvic transa (GPT), and glutamic oxaloacetic transaminase (GOT) in cold and humid environmental stressed mice increased significantly, indicating that the intestinal microbiota adapted to cold and humid environmental stress by regulating the host's amino acid metabolism; (3) the integrative analysis of multi-omics illustrated a prediction model based on the microbiota Lactobacillus reuteri abundance and host amino acid level that can predict intestinal mucoprotein Muc2 with an adjusted R2 of 75.0%. In conclusion, the cold and humid environmental stress regulates the neurotransmitter amino acids metabolic function both in intestinal mucosal microbiota and host serum by adjusting the composition of the dominant bacterial population Lactobacillus reuteri, which contributes to the intestinal mucus barrier injury and GI disorders caused by cold and humid environmental stress.

Zhishi Daozhi decoction alleviates constipation induced by a high-fat and high-protein diet via regulating intestinal mucosal microbiota and oxidative stress.

Background: A growing body of evidence has demonstrated that a high-fat and high-protein diet (HFHPD) causes constipation. This study focuses on understanding how the use of Zhishi Daozhi decoction (ZDD) affects the intricate balance of intestinal microorganisms. The insights gained from this investigation hold the potential to offer practical clinical approaches to mitigate the constipation-related issues associated with HFHPD. Materials and methods: Mice were randomly divided into five groups: the normal (MN) group, the natural recovery (MR) group, the low-dose ZDD (MLD) group, the medium-dose ZDD (MMD) group, and the high-dose ZDD (MHD) group. After the constipation model was established by HFHPD combined with loperamide hydrochloride (LOP), different doses of ZDD were used for intervention. Subsequently, the contents of cholecystokinin (CCK) and calcitonin gene-related peptide (CGRP) in serum, superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver were determined. The DNA of intestinal mucosa was extracted, and 16S rRNA amplicon sequencing was used to analyze the changes in intestinal mucosal microbiota. Results: After ZDD treatment, CCK content in MR group decreased and CGRP content increased, but the changes were not significant. In addition, the SOD content in MR group was significantly lower than in MLD, MMD, and MHD groups, and the MDA content in MR group was significantly higher than in MN, MLD, and MHD groups. Constipation modeling and the intervention of ZDD changed the structure of the intestinal mucosal microbiota. In the constipation induced by HFHPD, the relative abundance of pathogenic bacteria such as Aerococcus, Staphylococcus, Corynebacterium, Desulfovibrio, Clostridium, and Prevotella increased. After the intervention of ZDD, the relative abundance of these pathogenic bacteria decreased, and the relative abundance of Candidatus Arthromitus and the abundance of Tropane, piperidine, and pyridine alkaloid biosynthesis pathways increased in MHD group. Conclusion: Constipation induced by HFHPD can increase pathogenic bacteria in the intestinal mucosa, while ZDD can effectively relieve constipation, reduce the relative abundance of pathogenic bacteria, and alleviate oxidative stress injury. In addition, high-dose ZDD can increase the abundance of beneficial bacteria, which is more conducive to the treatment of constipation.

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.

Modulating the Microenvironment of Silanols in Pure-Silicon Zeolites for Boosting Vapor-phase Beckmann Rearrangement of Cyclohexanone Oxime.

Vapor-phase Beckmann rearrangement of cyclohexanone oxime (CHO) to ε-caprolactam (CPL) is still difficult to commercialize at the industrial scale due to its relatively low catalytic activity and poor lifetime. Herein, we synthesized a series of pure-silicon zeolites (including MFI, MEL, and -SVR) with three-dimensional 10-member-ring topolgies, diverse silanol status, and hierarchical porosity to investigate the synergistic effects of inner diffusivity and reactivity. S-1 zeolite of MFI-type topology with plentiful silanol nests exhibits a more preferable catalytic performance in terms of CHO conversion (99.7%) and CPL selectivity (89.7%), much higher than those of MEL- and -SVR-type zeolites mainly due to their diverse silanol distribution. With the construction of hierarchical porosity, S-1-P shows improved CPL selectivity of 94.1% owing to the enhanced diffusivity to shorten the retention time of the reactant and product molecules. The reaction mechanism and network have been further revealed by density functional theory (DFT) calculations and experimental designs, which indicate that silanol nests are major active sites due to their suitable interaction with CHO rather than terminal silanols. Particularly, the microenvironments of silanols can be modulated by alcohol solvents, ascribed to their different charge transfer and steric hindrance. Consequently, S-1-P shows superior CPL selectivity of 97.3% in ethonal solvents, which have higher adsorb energy of -0.627 eV with silanol nests than other alcohols. The present study not only provides a fundamental guide for the design of zeolite catalysts but also provides a reference for modulating the microenvironment of active sites according to the catalytic mechanism.

Gallium Triggers Ferroptosis through a Synergistic Mechanism.

The gallium ion (Ga3+ ) has long been believed to disrupt ferric homeostasis in the body by competing with iron cofactors in metalloproteins, ultimately leading to cell death. This study revealed that through an indirect pathway, gallium can trigger ferroptosis, a type of non-apoptotic cell death regulated by iron. This is exemplified by the gallium complex of the salen ligand (Ga-1); we found that Ga-1 acts as an effective anion transporter that can affect the pH gradient and change membrane permeability, leading to mitochondrial dysfunction and the release of ferrous iron from the electron transfer chain (ETC). In addition, Ga-1 also targeted protein disulfide isomerases (PDIs) located in the endoplasmic reticulum (ER) membrane, preventing the repair of the antioxidant glutathione (GSH) system and thus enforcing ferroptosis. Finally, a combination treatment of Ga-1 and dietary polyunsaturated fatty acids (PUFAs), which enhances lipid peroxidation during ferroptosis, showed a synergistic therapeutic effect both in vitro and in vivo. This study provided us with a strategy to synergistically induce Ferroptosis in tumor cells, thereby enhancing the anti-neoplastic effect.

Brain-bacteria-gut axis and oxidative stress mediated by intestinal mucosal microbiota might be an important mechanism for constipation in mice.

Intestinal microbiota disorder was associated with constipation. This study investigated the microbiota-gut-brain axis and oxidative stress mediated by intestinal mucosal microbiota in mice with spleen deficiency constipation. The Kunming mice were randomly divided into the control (MC) group and the constipation (MM) group. The spleen deficiency constipation model was established by gavage with Folium sennae decoction and controlled diet and water intake. The body weight, spleen and thymus index, 5-Hydroxytryptamine (5-HT) and Superoxide Dismutase (SOD) content were significantly lower in the MM group than the MC group, the content of vasoactive intestinal peptide (VIP) and malondialdehyde (MDA) content were significantly higher than the MC group. The Alpha diversity of intestinal mucosal bacteria was not changed but beta diversity was changed in mice with spleen deficiency constipation. Compared to the MC group, the relative abundance of Proteobacteria was an upward trend and the Firmicutes/Bacteroidota (F/B) value was a downward trend in the MM group. There was a significant difference in the characteristic microbiota between the two groups. In the MM group, Brevinema, Akkermansia, Parasutterella, Faecalibaculum, Aeromonas, Sphingobium, Actinobacillus, and other pathogenic bacteria were enriched. Meanwhile, there was a certain relationship between the microbiota and gastrointestinal neuropeptide and oxidative stress indicators. The community structure of intestinal mucosal bacteria in mice with spleen deficiency constipation was changed, which was characterized by the reduction of F/B value and enrichment of Proteobacteria. Microbiota-gut-brain axis may be important for spleen deficiency constipation.

Two Secretory T2 RNases Act as Cytotoxic Factors Contributing to the Virulence of an Insect Fungal Pathogen.

RNase T2 members are secreted by several pathogens or parasites during infection, playing various roles in pathogen-host interaction. However, functions of those members in biocontrol microbes targeting their hosts are still unknown. Here, we report that an insect fungal pathogen, Beauveria bassiana, produces two secretory RNase T2 members that act as cytotoxic factors, which were examined by insect bioassays using the targeted gene(s) disruption and overexpression strains. Overexpression strains displayed dramatically increased virulence, which was concurrent with few fungal cells and hemocytes in hemocoel, suggesting a cytotoxicity of the overexpressed gene products. In vitro assays using yeast-expressed proteins verified the cytotoxicity of the two members against insect cells, to which the cytotoxic effect was dependent on their RNases enzyme activities and glycosylation modification. Moreover, the excessive humoral immune responses triggered by the two ribonucleases were examined. These results suggested prospects of these two T2 ribonucleases for improvement of biocontrol agents.

Smoking Bans and Circulatory System Disease Mortality Reduction in Macao (China): Using GRA Models.

This study evaluates the association between smoking rates and mortality from circulatory system diseases (CSD) after implementing a series of smoking bans in Macao (China). (1) Background: Macao phased in strict total smoking bans since 2012. During the past decade, smoking rates among Macao women have dropped by half. CSD mortalities in Macao also show a declining trend. (2) Method: Grey relational analysis (GRA) models were adopted to rank the importance of some key factors, such as income per capita, physician density, and smoking rates. Additionally, regressions were performed with the bootstrapping method. (3) Results: Overall, smoking rate was ranked as the most important factor affecting CSD mortality among the Macao population. It consistently remains the primary factor among Macao's female population. Each year, on average 5 CSD-caused deaths were avoided among every 100,000 women, equivalent to about 11.45% of the mean annual CSD mortality. (4) Conclusions: After the implementation of smoking bans in Macao, the decrease in smoking rate among women plays a primary role in the reduction in CSD mortality. To avoid excess CSD mortality due to smoking, Macao needs to continue to promote smoking cessation among the male population.

Biofilter-constructed wetland-trophic pond system: A new strategy for effective sewage treatment and agricultural irrigation in rural area.

Artificial ecosystems with high biological complexity are generally considered to be efficient in metabolizing substances and resistant to temperature shock. In this study, a novel near-natural system (BCT system), which consisted of simple biofilter, constructed wetland and trophic biology pond, was conducted to treat rural sewage in situ for irrigation into farmland. Water quality related to carbon and nutrients and microbial community were analyzed along the system to reveal the effect of each unit. The annual average removals of BCT system for TN, NH4+-N, TP and COD could reach 46.53%, 52.18%, 41.48%, and 53.21%, respectively. There was no significant decrease for removal efficiencies from high temperature period (HTP, ≥15 °C) to low temperature period (LTP, <15 °C). In LTP, the trophic pond (TRP) removed 34.85% of TN, 33.93% of NH4+-N, 13.71% of TP and 18.77% of COD, while the removal efficiencies of constructed wetland fluctuated greatly. The TRP facilitated the BCT system to maintain the removal capability during low temperature period. The relative abundance of denitrification functional genes in TRP increased nearly tenfold from HTP to LTP. The effluent quality from the system can meet the agricultural irrigation standards, demonstrating the effect of BCT system on sewage treatment and agricultural irrigation in rural area.

Simo decoction curing spleen deficiency constipation was associated with brain-bacteria-gut axis by intestinal mucosal microbiota.

Background: Simo decoction (SMD) is a traditional prescription for treating gastrointestinal diseases. More and more evidences prove that SMD can treat constipation by regulating intestinal microbiota and related oxidative stress indicators, but the specific mechanism is still unclear. Methods: A network pharmacological analysis was used to predict the medicinal substances and potential targets of SMD to alleviate constipation. Then, 15 male mice were randomly divided into normal group (MN group), natural recovery group (MR group), and SMD treatment group (MT group). Constipation model mice were constructed by gavage of Folium sennae decoction and control of diet and drinking water, and SMD was used for intervention after successful modeling. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), superoxide dismutase (SOD), malondialdehyde (MDA), and fecal microbial activities were measured, and the intestinal mucosal microbiota was sequenced. Result: Network pharmacology analysis showed that a total of 24 potential active components were obtained from SMD, and 226 target proteins were obtained after conversion. Meanwhile, we obtained 1,273 and 424 disease-related targets in the GeneCards database and the DisGeNET database, respectively. After combination and deduplication, the disease targets shared 101 targets with the potential active components of SMD. When the mice were intervened with SMD, the 5-HT, VIP, MDA, SOD content, and microbial activity in MT group were close to MN group, and Chao 1 and ACE in MT group were significantly higher than that in MR group. In the Linear discriminant analysis Effect Size (LEfSe) analysis, the abundance of beneficial bacteria such as Bacteroides, Faecalibacterium, Alistipes, Subdoligranulum, Lactiplantibacillus, and Phascolarctobacterium in MT group increased. At the same time, there were some associations between microbiota and brain-gut peptides and oxidative stress indicators. Conclusion: SMD can promote intestinal health and relieve constipation through brain-bacteria-gut axis associating with intestinal mucosal microbiota and alleviate oxidative stress.

Carbon Reduction and Pollutant Abatement by a Bio-Ecological Combined Process for Rural Sewage.

In order to explore the treatment effect of a bio-ecological combined process on pollution reduction and carbon abatement of rural domestic wastewater under seasonal changes, the rural area of Lingui District, Guilin City, Guangxi Province, China was selected to construct a combined process of regulating a pond, biological filter, subsurface flow constructed wetland, and ecological purification pond. The influent water, effluent water, and the characteristics of pollutant treatment in each unit were investigated. The results showed that the average removal rates of COD, TN, and NH3-N in summer were 87.57, 72.18, and 80.98%, respectively, while they were 77.46, 57.52, and 64.48% in winter. There were significant seasonal differences in wastewater treatment results in Guilin. Meanwhile, in view of the low carbon:nitrogen ratio in the influent and the poor decontamination effect, the method of adding additional carbon sources such as sludge fermentation and rice straw is proposed to strengthen resource utilization and achieve carbon reduction and emission reduction. The treatment effect of ecological units, especially constructed wetland units, had a high contribution rate of TN treatment, but it was greatly impacted by seasons. The analysis of the relative abundance of the microbial community at the phylum level in constructed wetlands revealed that Proteobacteria, Acidobacteria, Chloroflexi, Firmicutes, Bacteroidetes, Planctomycetota, and Actinobacteria were the dominant phyla. The relative abundance of microbial communities of Proteobacteria, Chloroflexi, and Acidobacteria decreased to a large extent from summer to winter, while Firmicutes, Bacteroidetes, and Planctomycetota increased to varying degrees. These dominant bacteria played an important role in the degradation of pollutants such as COD, NH3-N, and TN in wetland systems.

A novel MOFs-induced strategy for preparing anatase-free hierarchical TS-1 zeolite:synthesis routes, growth mechanisms and enhanced catalytic performance.

Titanosilicate-1 zeolites (TS-1) as one of the most commonly used catalysts for alkene epoxidation, construction of hierarchical pores as well as elimination of anatase to promote mass transportation and avoid invalid decomposition of hydrogen peroxide are always desirable yet challenging goals. Here, a novel and unique Ti-based metal organic frameworks (MOFs)-induced synthetic strategy for fabricating anatase-free hierarchical TS-1 was first proposed. All the components of MOFs perform different functions: the uniformly distributed Ti nodes replace conventional tetrabutyl titanate (TBOT) to serve as sole Ti source for constructing zeolite crystal; the separated ligands can be embedded in the zeolite framework and act as template to in situ build hierarchical pore structure; the coordination interaction between Ti nodes and ligands can efficiently avoid the anatase generation by balancing the forming rates of Ti-OH and Si-OH. This synthetic strategy is of general applicability, and two different synthetic routes including traditional hydrothermal process and steam assisted crystallization (SAC) procedure are successfully adopted. The obtained hydrothermal TS-1 and SAC anatase-free samples all possess abundant intercrystalline mesopores of 20-50 nm and even macropores between 50 and 150 nm, improving the conversion over 25 % for 1­hexene epoxidation than TS-1 sample prepared by conventional route. The influences of the amount of Ti MOFs precursor and the crystallization process are studied in detail, and possible synthesis mechanisms are proposed. This MOFs-induced strategy might open up an avenue for the rational design of ideal and hierarchical zeolite to boost the catalytic efficiency.

Sex hormones influence the intestinal microbiota composition in mice.

Sex hormone secretion difference is one of the main reasons for sexually dimorphic traits in animals, which affects the dimorphism of the intestinal microbiota; however, their interaction is still unknown. Intestinal mucosa-associated microbiota (MAM) and intestinal luminal content microbiota (LM) belong to two different habitats according to the difference in interactions between bacteria and host intestinal epithelium/nutrients. To clarify the sexually dimorphic characteristics of MAM and LM and their correlation with sex hormones, 12 specific pathogen-free (SPF) Kunming mice from the same nest were fed separately according to sex. After 8 weeks, samples from the male intestinal mucosa group (MM group), the female intestinal mucosa group (FM group), the male intestinal content group (MC group), and the female intestinal content group (FC group) were collected and then, the next-generation sequencing of 16S ribosomal ribonucleic acid (rRNA) gene was performed. Our results showed that the sexual dimorphism of MAM was more obvious than that of LM and the relative abundance of Muribaculaceae, Turicibacter, and Parasutterella was significantly higher in the FM group than in the MM group (p < 0.001, p < 0.05, p < 0.05). Next, we measured the level of serum sex hormones in mice and calculated the correlation coefficient between major bacteria and sex hormones. The results showed that the correlation between MAM and sex hormones was more prominent, and finally, three bacterial genera (Muribaculaceae, Turicibacter, and Parasutterella) were obtained, which could better represent the relationship between sexual dimorphism and sex hormones. The abundance of Parasutterella is positively and negatively correlated with estradiol and testosterone (T), respectively, which may be related to the differences in the metabolism of bile acid and glucose. A decrease in the abundance of Turicibacter is closely related to autism. Our results show that the abundance of Turicibacter is negatively and positively correlated with T and estradiol, respectively, which can provide a hint for the prevalence of male autism. In conclusion, it is proposed in our study that intestinal microbiota is probably the biological basis of physiological and pathological differences due to sex, and intestinal MAM can better represent the sexual dimorphism of mice.

Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

Gut-Kidney Impairment Process of Adenine Combined with Folium sennae-Induced Diarrhea: Association with Interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and Acetic Acid, Inflammation, and Kidney Function.

BACKGROUND: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. METHODS: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. RESULTS: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. CONCLUSIONS: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Diarrhea with deficiency kidney-yang syndrome caused by adenine combined with Folium senna was associated with gut mucosal microbiota.

The present study aims to study and analyze the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Ten male mice were randomly divided into the control group and the model group. Diarrhea mice model with deficiency kidney-yang syndrome was established by adenine combined with Folium sennae. The kidney structure was observed by hematoxylin-eosin (HE) staining. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA). The characteristics of gut mucosal microbiota were analyzed by performing third-generation high-throughput sequencing. The results showed that the model mice exhibit obvious structural damage to the kidney. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels showed a decreased trend in the model group. The diversity and community structure of the gut mucosal microbiota improved in the model group. Dominant bacteria like Candidatus Arthromitus, Muribaculum, and Lactobacillus reuteri varied significantly at different taxonomic levels. The characteristic bacteria like Bacteroides, Erysipelatoclostridium, Anaerotignum, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii were enriched in the model group. A correlation analysis described that Erysipelatoclostridium was positively correlated with Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels, while Anaerotignum exhibited an opposite trend. Together, adenine combined with Folium sennae damaged the structure of the kidney, affected energy metabolism, and caused disorders of gut mucosal microbiota in mice. Bacteroides, Erysipelatoclostridium, and Anaerotignum showed significant inhibition or promotion effects on energy metabolism. Besides, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii might be the characteristic species of gut mucosal microbiota responsible for causing diarrhea with deficiency kidney-yang syndrome.