Gram-Scale Synthesis of Loganetin from S-(+)-Carvone.

Loganetin is the aglycone moiety of loganin that has a 5,6-fused bicyclic framework and exhibits a wide range of interesting biological activities. A gram-scale synthesis of loganetin has been accomplished from the readily accessible S-(+)-carvone. The key reactions of the synthesis are a Favorskii rearrangement to introduce four stereocenters and a sulfuric acid-meditated deprotection/cyclization reaction to assemble the sensitive dihydropyran ring with complete stereoselectivity. This work also enables us to synthesize C1 methoxy loganetin and the enantiomer of loganetin successfully.

Flocculation of combined contaminants of dye and heavy metal by nano-chitosan flocculants.

In this study, two multifunctional nano-chitosan flocculants (CPAM-NCS1 and CPAM-NCS2) were made through the graft modification of cationic monomer and carboxymethylchitosan (CMCTS) to remove combined contaminants. The effects of various factors (pH, flocculant dosage and hydraulic mixing conditions) on the flocculation performance under single and composite pollution conditions were systematically investigated, the optimal chemical oxygen demand (COD) and the chromaticity removal rates in the dye wastewater were 79.9% and 83.9% at wastewater pH 7, the fast stirring rate 300 rpm, the fast stirring time 8 min, and the dosage of CPAM-NCS1 80 mg/L, respectively. The optimal removal rates of Cu (II) obtained by CPAM-NCS1 and CPAM-NCS2 at were 80.3% and 75.2% at 60 mg/L and the wastewater pH 7, respectively. The optimal removal rates of Cu (II) and disperse orange were 85.3% and 89.4%, respectively, in a composite pollutant system in which Cu (II) and disperse orange coexisted when the pH of the composite system was 9 and the dosage of CPAM -NCS1 was 60 mg/L. This study proved that nanoflocculants made by modifying CMCTS with different structures can demonstrate ideal flocculation removal performance for dye and heavy metal wastewaters.

Heavy metal removal from aqueous solutions by chitosan-based magnetic composite flocculants.

In this study, three magnetic flocculants with different chelating groups, namely, carboxymethyl chitosan-modified Fe3O4 flocculant (MC), acrylamide-grafted magnetic carboxymethyl chitosan flocculant (MCM), and 2-acrylamide-2-methylpropanesulfonic acid copolyacrylamide-grafted magnetic carboxymethyl chitosan flocculant (MCAA) were prepared, synthesized, and characterized by photopolymerization technology. They were applied to the flocculation removal of Cr(III), Co(II), and Pb(II). The effect of flocculation condition on the removal performance of Cr(III), Co(II), and Pb(II) was studied. Characterization results show that the three magnetic carboxymethyl chitosan-based flocculants have been successfully prepared with good magnetic induction properties. Flocculation results show that the removal rates of MC, MCM, and MCAA on Cr(III) are 51.79%, 82.33%, and 91.42%, respectively, under the conditions of 80 mg/L flocculant, pH value of 6, reaction time of 1.5 hr, G value of 200 s-1, and precipitation magnetic field strength of 120 mT. The removal rates of Co(II) by MC, MCM, and MCAA are 54.33%, 84.99%, and 90.49%, respectively. The removal rates of Pb(II) by MC, MCM, and MCAA are 61.54%, 91.32%, and 95.74%, respectively. MCAA shows good flocculation performance in composite heavy metal-simulated wastewater. The magnetic carboxymethyl chitosan-based flocculant shows excellent flocculation performance in removing soluble heavy metals. This research provides guidance and ideas for the development of efficient and low-cost flocculation technology to remove heavy metals in wastewater.

Ligand fishing with cellular membrane-coated cellulose filter paper: a new method for screening of potential active compounds from natural products.

Ligand fishing is a widely used approach for screening active compounds from natural products. Recently, cell membrane (CM) as affinity ligand has been applied in ligand fishing, including cell membrane chromatography (CMC) and CM-coated magnetic bead. However, these methods possess many weaknesses, including complicated preparation processes and time-consuming operation. In this study, cheap and easily available cellulose filter paper (CFP) was selected as carrier of CM and used to fabricate a novel CM-coated CFP (CMCFP) for the first time. The type of CFP was optimized according to the amount of immobilized protein, and the immobilization of CM onto CFP by the insertion and self-fusion process was verified by confocal imaging. The CMCFP exhibited good selectivity and stability and was used for fishing potentially active compounds from extracts of Angelica dahurica. Three potentially active compounds, including bergapten, pabulenol, and imperatorin, were fished out and identified. The traditional Chinese medicine systems pharmacology database and analysis platform was used to build an active compound-target protein network, and accordingly, the gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) was deduced as potential target of CM for the active compounds of Angelica dahurica. Molecular docking was performed to evaluate the interaction between active compounds and GABRA1, and bergapten was speculated as a new potentially active compound. Compared with other methods, the fishing assay based on CMCFP was more effective, simpler, and cheaper.

Application of a sensitive and specific LC-ESI-MS/MS method for the simultaneous quantification of twelve bioactive components in dog plasma for an intravenous pharmacokinetic study of Yiqifumai Injection in beagle dogs.

Yiqifumai Injection is a lyophilized powder preparation widely used to treat coronary heart disease. However, its in vivo bioactive components and pharmacokinetic behavior remain unknown. Therefore a sensitive and specific LC-MS/MS was developed and validated for the simultaneous quantification of eight saponins and four lignans in beagle dog plasma. The plasma samples were pretreated by protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation of all the 12 analytes and estazolam (internal standard, IS) was successfully accomplished on an Ultimate® XB-C8 column (100 × 2.1 mm, 3 µm) with a gradient elution system. The total running time was 8 min with a flow rate of 0.40 mL/min. Acquisition of mass spectrometric data was performed via positive electrospray ionization in multiple reaction monitoring mode. The assay was fully validated in terms of selectivity, linear range, lower limit of quantitation, precision, accuracy, matrix effect, recovery and stability. This validated method was successfully applied to the pharmacokinetics of 12 bioactive components after intravenous administration of Yiqifumai Injection to beagle dogs at a dose of 0.541 g/kg.

Preparation and characterization of micro-cell membrane chromatographic column with silica-based porous layer open tubular capillary as cellular membrane carrier.

Cell membrane chromatography (CMC) is a powerful tool to study membrane protein interactions and to screen active compounds extracted from natural products. Unfortunately, a large amount of cells are typically required for column preparation in order to carry out analyses in an efficient manner. Micro-CMC (mCMC) has recently been developed by using a silica capillary as a membrane carrier. However, a reduced retention of analytes is generally associated with mCMC mostly due to a low ligand (cellular membrane) capacity. To solve this common problem, in this work a silica-based porous layer open tubular (PLOT) capillary was fabricated and, to the best of our knowledge, for the first time applied to mCMC. The mCMC column was prepared by physical adsorption of rabbit red blood cell (rRBC) membranes onto the inner surface of the PLOT capillary. The effects of the PLOT capillaries fabricated by different feed compositions, on the immobilization amount of cellular membranes (represented by the fluorescence intensity of the capillary immobilized with fluorescein isothiocyanate isomer-labeled cellular membranes) and on the dynamic binding capacity (DBC) of verapamil (VP, a widely used calcium antagonist which specific interacts with L-type calcium channel proteins located on cellular membrane of rRBC) have been systematically investigated. The fluorescence intensity of the mCMC column when combined with the PLOT capillary was found to be more than five times higher than the intensity using a bare capillary. This intriguing result indicates that the PLOT capillary exhibits a higher cellular membrane capacity. The DBC of VP in the PLOT column was found to be more than nine times higher than that in the bare capillary. An rRBC/CMC column was also prepared for comparative studies. As a result, mCMC provides similar chromatographic retention factors and stability with common CMC; however, the cellular membrane consumption for mCMC was found to be more than 460 times lower than that for CMC. Graphical Abstract Comparision of mCMC chromatograms and SEM images between bare capillary and PLOT capillary.

Thermosensitive in situ nanogel as ophthalmic delivery system of curcumin: development, characterization, in vitro permeation and in vivo pharmacokinetic studies.

CONTEXT: The nanogel combining cationic nanostructured lipid carriers (CNLC) and thermosensitive gelling agent could enhance preocular retention and ocular permeation capacity of curcumin (CUR). OBJECTIVE: The purpose of the study was to develop and characterize a thermosensitive ophthalmic in situ nanogel of CUR-CNLC (CUR-CNLC-GEL) and evaluate in vitro and in vivo properties of the formulations. MATERIALS AND METHODS: The physicochemical properties, in vitro release and corneal permeation, were evaluated. Ocular irritation and preocular retention capacity were also conducted. Finally, pharmacokinetic study in the aqueous humor was investigated by microdialysis technique. RESULTS: The solution-gel transition temperature of the optimized formulation diluted by simulated tear fluid was 34 ± 1.0 °C. The CUR-CNLC-GEL displayed zero-order release kinetics. The apparent permeability coefficient (Papp) and the area under the curve (AUC0→∞) of CUR-CNLC-GEL were 1.56-fold and 9.24-fold, respectively, than those of curcumin solution (CUR-SOL, p < 0.01). The maximal concentration (Cmax) was significantly improved (p < 0.01). The prolonged mean residence time (p < 0.01) indicated that CUR-CNLC-GEL is a controlled release formulation. DISCUSSION AND CONCLUSION: Those results demonstrated that CUR-CNLC-GEL could become a potential formulation for increasing the bioavailability of CUR in the aqueous humor by enhancing corneal permeation and retention capacity.

[Effects of seed priming on physiology of seed germination and seeding growth of Marsdenia tenacissima under NaCl stress].

To offer the reference and method for salt damage in the cultivation of Marsdenia tenacissima, the seeds of M. tenacissima collected from Maguan city ( Yunnan province) were taken as the test materials to study the effects of different priming materials on improving germination and growth under high-level salt stress condition. Four different treatments, which were GA3, KNO3-KH2PO4, PEG-6000, NaCl, combined with ANOVA were applied to test the performance of germination energy, germination percentage, germination index, MDA, SOD, and CAT. The results showed that the seed germination was obviously inhibited under salt stress and the soaked seeds with different priming materials could alleviate the damage of salt stress. Under these treatments, the activities of SOD, CAT the content of soluble protein significantly increased. While the content of MDA significantly decreased. The maximum index was obtained when treated with 1.20% KNO3-KH2PO4, the germination percentage increased from 52.67% to 87.33% and the activity of SOD increased from 138.01 to 219.44 respectively. Comparing with the treatment of 1.20% KNO3-KH2PO4, the germination percentage of treating with 300 mg x L(-1) GA3 increased from 52.67% to 80.67%, while the activity of SOD increased from 138.01 to 444.61.

[FTIR fingerprint spectrograms of traditional Chinese medicine Marsdenia tenacissima].

In this paper, Fourier transform infrared spectroscopy fingerprint analysis of Marsdenia tenacissima samples was used to develop a reliable method of tracing the geographical origins. Forty-eight samples from four provinces of China were analyzed by FTIR. We analyzed and characterized the fingerprints in both the full spectrum peaks and characteristic peaks, then the principal component analysis and the cluster analysis were carried out. The results of fingerprint analysis, correlation analysis, principal component analysis and cluster analysis can identify the geographic origins correctly, which verified and supplemented each other; the identification results and the actual location showed a high degree of consistency, namely the lower the space distance, the greater the similarity of different samples. These results revealed the obvious superiority and practical value in comparison to the more tedious and time-consuming wet chemistry method normally used. Using appropriate metrology methods can trace the geographical source correctly. The M. tenacissima materials from the region of Maguan should be considered as genuine medicinal materials taking into account the good quality.

Network pharmacology and experimental verification to explore the anti-superficial thrombophlebitis mechanism of Mailuo shutong pill.

ETHNOPHARMACOLOGICAL RELEVANCE: Mailuo shutong pill (MLST) has been widely used in clinical treatment of superficial thrombotic phlebitis (STP). Nevertheless, the major active components of MLST and the mechanism of synergistic action have not been reported. AIM OF THE STUDY: The present study aimed to evaluate the improving effects and the underlying mechanism of MLST on mannitol-induced STP in rabbits. MATERIAL AND METHODS: In this study, Ultrahigh-performance liquid chromatography electrospray ionization quadrupole-exactive orbitrap mass spectrometry (UHPLC-ESI-Q-Exactive-Orbitrap-MS) was used to analyze and identify the chemical composition of MLST and the prototype components absorbed into the blood. Then, according to the prototype components in serum, the targets and mechanisms of MLST were explored by applying network pharmacology. The rabbit model of STP was established by injecting 20% mannitol into bilateral auricular vein. The pathological changes of rabbit ear tissues, inflammatory factors, coagulation function and hemorheology were detected. In addition, molecular docking verified the interaction between the main active ingredient and the key target. Finally, the PI3K/AKT pathway and its regulated downstream pathways were verified by Western blot. RESULTS: A total of 96 MLST components and 53 prototypical components absorbed into the blood were successfully identified. Based on network pharmacology, PI3K/AKT pathway and 10 chemical components closely related to this pathway were obtained. Hematoxylin-eosin (HE) staining results indicated that MLST effectively improved of the pathological damage of ear tissues. MLST decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and C-reactive protein (CRP). The expression of platelets (PLT) and fibrinogen concentration (FIB) was decreased, while prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. In addition, the plasma viscosity and whole blood viscosity in the MLST groups were significantly decreased. The more important discovery was that the expressions of P-PI3K, VEGF, P-AKT, P-IκB-α, P-NF-κB, NLRP3, ASC, Cleaved IL-1ß and Cleaved Caspase-1 were effectively reversed after treatment with MLST. CONCLUSIONS: This study comprehensively analyzed and characterized the chemical composition of MLST and the prototypical components absorbed into the blood. This study strongly confirmed the pharmacodynamic effect of MLST on STP. More importantly, this pharmacodynamic effect was achieved through inhibition of the PI3K/AKT pathway and its regulated NF-κB and NLRP3 pathways.

Compositional effects on structural, electronic, elastic, piezoelectric and dielectric properties of GaInN alloys: a first-principles study.

We conduct a comprehensive theoretical analysis of wurtzite GaxIn1-xN ternary alloys, focusing on their structural, electronic, elastic, piezoelectric, and dielectric properties through rigorous first-principles calculations. Our investigation systematically explores the influence of varying Ga composition (x = 0%, 25%, 50%, 75%, 100%) on the alloy properties. Remarkably, we observe a distinctive non-linear correlation between the band gap and Ga concentration, attributable to unique slopes in the absolute positions of the valence band maximum and conduction band minimum with respect to Ga concentration. Our effective band structure analysis reveals the meticulous preservation of Bloch characters near band extrema, minimizing charge carrier scattering. Furthermore, we scrutinize deviations from linear Vegard-like dependence in elastic, piezoelectric, and dielectric constants. Additionally, our calculations encompass various optical properties, including absorption coefficient, reflectivity, refractive index, energy loss function, and extinction coefficient. We analyze their trends with photon energy, providing valuable insights into the optical behavior of GaxIn1-xN alloys. Our results, in excellent agreement with available experimental data, significantly contribute to a deeper understanding of the alloys' electronic properties. This study offers valuable insights that may illuminate potential applications of GaxIn1-xN alloys in diverse technological fields.

Rhizobacterial compositions and their relationships with soil properties and medicinal bioactive ingredients in Cinnamomum migao.

Introduction: Rhizobacterial communities and their metabolites can affect plant growth, development, and stress resistance, as well as the biosynthesis and accumulation of bioactive compounds in medicinal plants. This relationship has been well-characterized in many medicinal herbs, although much less commonly in medicinal trees. Methods: Here, we analyzed the composition and structure of Cinnamomum migao rhizobacterial communities across nine growing regions in Yunnan, Guizhou and Guangxi, China, as well as differences in soil properties and fruit bioactive compounds. Results: Results showed that the C. migao rhizobacterial communities exhibited high species richness, but location-specific differences in structure. Site-specific differences in soil properties and bioactive compounds were also observed. Furthermore, rhizobacterial community compositions were correlated with both soil properties and fruit bioactive compounds, metabolism-related functions were most common in C. migao rhizobacteria. Discussion: Several bacterial genera, including Acidothermus, Acidibacter, Bryobacter, Candidatus_Solibacter, and Acidimicrobiales, potentially promote the biosynthesis and accumulation of 1,8-cineole, cypressene, limonene, and α-terpineol, Nitrospira and Alphaproteobacteria may play an inhibitory role. Finally, our results emphasized the critical role that soil pH and nitrogen levels play in driving rhizobacterial community structure, and specific functional bacteria can also counteract with soil properties, Acidibacter and Nitrospira can affect soil pH and nitrogen effectiveness. Overall, this study provides additional insight into the complex correlation of rhizosphere microorganisms with bioactive ingredients and soil properties of medicinal plants.

Pharmacokinetics, tissue distribution and excretion of six bioactive components from total glucosides picrorhizae rhizoma, as simultaneous determined by a UHPLC-MS/MS method.

Total glucosides picrorhizae rhizome (TGPR) is an innovative traditional Chinese medicine, which is a candidate drug for the treatment of nonalcoholic steatohepatitis (NASH). However, there is still lack of deep research on the behaviors of TGPR in vivo. In this study, a reliable, specific, and sensitive liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been constructed for simultaneous determination of picroside I, picroside II, vanillic acid, androsin, cinnamic acid and picroside IV, the major active constituents of TGPR, in rat various biological matrices (plasma, tissue, bile, urine and feces) using diphenhydramine hydrochloride and paeoniflorin as the internal standard. All biosamples were prepared using a simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a waters UHPLC® HSS T3 (100×2.1 mm, 1.8 µm) column. The mobile phase consisted of methanol: acetonitrile1(1:1, V/V) and 0.5 mM ammonium formate in water, was employed to separate six components from endogenous interferences. The components were detected with a triple quadrupole mass spectrometer using positive and negative ion multiple reaction monitoring (MRM) mode. The newly developed method was successfully applied to investigate the pharmacokinetics, tissue distribution and excretion of six components in rats. The pharmacokinetic results indicated that the six components in TGPR could be quickly absorbed and slowly eliminated and their bioavailability were less than 12.37%, which implied the poor absorption after intragastric dosing. For tissue distribution, the six components in TGPR were detected in liver and only androsin could penetrate the blood-brain barrier. Meanwhile, the excretion study demonstrated that vanillic acid was mostly excreted as prototype drugs and the remaining five components might be widely metabolized in vivo as the metabolites, the unconverted form was excreted mainly by feces route. The pharmacokinetics, tissue distribution and excretion characteristics of six bioactive components in TGPR were firstly revealed, which will provide references for further clinical application of TGPR as an anti-NASH drug.

Arbuscular Mycorrhizal Fungi Improve the Growth, Water Status, and Nutrient Uptake of Cinnamomum migao and the Soil Nutrient Stoichiometry under Drought Stress and Recovery.

Drought greatly influences the growth and ecological stoichiometry of plants in arid and semi-arid regions such as karst areas, where Cinnamomum migao (C. migao) is an endemic tree species that is used as a bioenergy resource. Arbuscular mycorrhizal fungi (AMF) play a key role in nutrient uptake in the soil-plant continuum, increasing plant tolerance to drought. However, few studies have examined the contribution of AMF in improving the growth of C. migao seedlings and the soil nutrient stoichiometry under drought-stress conditions. A pot experiment was conducted under natural light in a plastic greenhouse to investigate the effects of individual inoculation and Co-inoculation of AMF [Funneliformis mosseae (F. mosseae) and Claroideoglomus etunicatum (C. etunicatum)] on the growth, water status, and nutrient uptake of C. migao as well as the soil nutrient stoichiometry under well-watered (WW) and drought-stress (DS) conditions. The results showed that compared with non-AMF control (CK), AM symbiosis significantly stimulated plant growth and had higher dry mass. Mycorrhizal plants had better water status than corresponding CK plants. AMF colonization notably increased the total nitrogen and phosphorus content of C. migao seedlings compared with CK. Mycorrhizal plants had higher leaf and stem total carbon concentrations than CK. The results indicated that AM symbiosis protects C. migao seedlings against drought stress by improving growth, water status, and nutrient uptake. In general, the C. migao seedlings that formed with C. etunicatum showed the most beneficial effect on plant growth, water status, and nutrient uptake among all treatments. In the future, we should study more about the biological characteristics of each AMF in the field study to understand more ecological responses of AMF under drought stress, which can better provide meaningful guidance for afforestation projects in karst regions.

Transfer and transformation characteristics of Zn and Cd in soil-rotation plant (Brassica napus L and Oryza sativa L) system and its influencing factors.

Rice-rape rotation is a widely practiced cropping system in China. However, changes in soil properties and management could change the bioavailability of Cd, In order to explore the occurrence state, transportation and transformation characteristics of heavy metals Cd and Zn in rice-rape rotation system in Guizhou karst area with high background value of Cd. In the karst rice-rape rotation area, the physical and chemical properties of soil, chemical specifications and activities of Cd and Zn at different soil depths and during various crop growth stages, and the bioaccumulation of Cd and Zn in different tissues of rice and rape were studied by field experiment and laboratory analysis. The bioaccumulation of Cd and Zn and the effects of physical and chemical soil properties on the activities and bioavailabilities of Cd and Zn during rice-rape rotation were explored. The findings revealed that soil particle size, composition, pH, redox potential, soil organic matter, and Cd and Zn contents varied dramatically, especially in deep soils. The physical and chemical properties of the deep and surface soils were significantly related to the bioaccumulation of Cd and Zn. Cd and Zn are activated during crop rotation. Cd was easier to be enriched in rice, while Zn was easier to be enriched in rape. The correlation between Cd and Zn contents in Brassica campestris L and their enrichment abilities were not significant, but that in Oryza sativa L were significant. During rice-rape rotation, the chemical speciations and activities of Cd and Zn changed with the changes of soil properties and waterlogging environment. This study had important basic guiding significance for the evaluation, prevention and control of heavy metal pollution, and improving soil quality in different rotation systems in karst areas, and was conducive to promoting the safe production of rape and rice.

Intestinal flora, intestinal metabolism, and intestinal immunity changes in complete Freud's adjuvant-rheumatoid arthritis C57BL/6 mice.

Rheumatoid arthritis (RA) is an inflammatory-mediated autoimmune disease characterized by persistent joint enlargement, synovial cartilage damage, and inflammatory infiltrates. Although the pathogenesis and treatment of RA are still currently insufficient, the importance of the intestine flora, metabolism and immunity for RA has been gradually recognized, and many intestine regulatory strategies have been used to treat RA. However, the relationship between RA and intestine flora, metabolism and immunity has not been fully expounded. In this study, Complete Freund's Adjuvant (CFA) was used to establish RA model, CyTOF technology was used to study the changes of intestinal immune cell types, 16S rRNA technology was used to analyze the differences of intestinal flora, and LC-MS technology was used to explain the effects of metabolites produced by the changed intestinal flora on RA. Moreover, we systematically explored how the imbalance of intestinal flora changed the intestinal immune status through its metabolites in RA mice. Our results showed that the intestinal flora of RA mice changed significantly, and the bacteria producing short-chain fatty acids (SCFAs), indole classes and secondary bile acids were significantly reduced. The abundance of SCFAs, indole classes and secondary bile acids in the intestine were significantly decreased. The balance of immune cells in the intestine of RA mice was significantly disrupted, with an overall decrease in immune cells. This work reveals the possible relationship between intestinal flora, metabolism and immunity and RA in mice, which will provide new therapeutic strategies for RA.

Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.

Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.

Jingfang granules ameliorate inflammation and immune disorders in mice exposed to low temperature and high humidity by restoring the dysregulation of gut microbiota and fecal metabolites.

The dramatic changes in global climate on human health have been extremely severe. The immune disorder caused by low temperature and high humidity (LTHH) have become a severe public health issue. Clinically, Jingfang granule (JF) has the effect of dispelling cold and eliminating dampness, and is widely used in the treatment of cold caused by wind and cold, autoimmune diseases, and COVID-19 with cold-dampness stagnating in the lung pattern. Our study aims to elucidate the effect of JF on LTHH-induced immune disorders in mice as well as the underlying mechanisms. In this study, JF increased the spleen index, improved fecal character, repaired the intestinal barrier and alleviated intestinal inflammatory responses. Most importantly, JF ameliorated immune disorder in LTHH mice, which was manifested primarily by the significant increase in gdT, CD8+ Tcm, and CD8+ Tem cells, as well as the decrease in TH1, TH17, CD4+ Tem1, CD4+ Tem2, immature NK, mature NK cells, and M1-like macrophages. Interestingly, the JF treatment not only regulated the gut microbiota by decreasing the abundance of harmful bacteria, as well as up-regulating the abundance of beneficial bacteria, but also ameliorated the metabolic disorders by reversing the levels of fecal metabolites to normality. The results of the correlation analysis demonstrated a significant association among gut microbiota, fecal metabolites and immune cells. In addition, JF inhibited the TLR4/NF-κB/NLRP3 pathway in LTHH mice. In conclusion, our results suggested that JF alleviated inflammation and immune disorders in LTHH mice by restoring gut microbiota and fecal metabolism.

Research progress of signaling pathways of the natural substances intervene dyslipidemia (Review).

Dyslipidemia is an umbrella term for a range of lipid metabolic disorders in the body. This condition has been widely reported to greatly increase the risk of cardiovascular diseases, threatening human health. In recent years, advances in molecular biology have deepened understanding of the dyslipidemia-related signaling pathways and specific mechanisms underlying dyslipidemia. Signaling pathways possess the ability to transmit an extracellular signal to the inside of the cell, leading to specific biological effects. Lipid metabolism disorders and lipid levels in the blood are frequently affected by aberrant alterations in the dyslipidemia-related signaling pathways. Therefore, further investigations into these pathways are required for the prevention and treatment of dyslipidemia. The present review summarizes the characteristics of six dyslipidemia-associated signaling pathways: Peroxisome proliferator-activated receptor, adenosine monophosphate-activated protein kinase, farnesoid X receptor, forkhead box O, adipocytokine and cyclic adenosine monophosphate signaling pathways. In particular, specific focus was placed on previous experimental studies and reports on the intervention effects of natural substances (compounds from animals, plants, marine organisms and microorganisms) on dyslipidemia.

Preparation and defect structure analysis of near-stoichiometric lithium tantalate wafers.

A vapour transfer equilibrium (VTE) method has been used to prepare near-stoichiometric lithium tantalate (NSLT) crystals with different Li contents. The NSLT crystals were tested and analyzed by differential thermal analysis (DTA) and X-ray photoelectron spectroscopy (XPS) to investigate the effect of Li content on the Curie temperature and internal defects of NSLT crystals. This study found that when the Li content increased in the NSLT wafer, the binding energy corresponding to the peak of the Ta4f electron layer in the XPS spectrum first decreased and then increased, indicating that the proportion of Ta valence states was different in wafers with different Li contents. From XPS energy spectrum analysis, it can be seen that the lithium tantalate crystal contains Ta5+, Ta4+, Ta3+ and lower-valence Ta. As the Li content increases in the NSLT wafer, Ta4+ disappears and the proportion of Ta5+ decreases initially, follows by a later increase and then subsequent further decrease. However, the change in proportion of Ta3+ and lower-price Ta is completely opposite to that of Ta5+, showing a trend of first rising, then falling and then finally rising again. Moreover, when the Li content is 49.751% in the NSLT wafer, the proportion of Ta5+ reaches a maximum, showing that at this Li concentration the NSLT crystal has a more perfect lattice structure. In this study, we propose a mixed defect model in which polarons coexist with Li vacancies and Ta inversion, explaining the change in Ta valence state in lithium tantalate crystals. This model is more in line with the observed results in this work. The new hybrid defect model and the variation law of Ta valence state with Li concentration proposed in this paper provide a new direction and experimental proof for the defect study of NSLT crystals, and also provide a theoretical basis to explore the Li content at the best physical properties of NSLT crystals.