Supported Cu3 cluster on N-doped graphene: An efficient triatom catalyst for CO electroreduction to propanol at low potential.

Electroreduction of carbon monoxide into high-energy fuel is an excellent energy strategy for sustainable development, but the high yield of multi-carbon products remains a difficult challenge. Inspired by the successful synthesis of various trimer metal clusters and studies on electrocatalysis of CO to C3 products by Cu-based catalysts, Cu3 supported on N-doped graphene structures (Cu3@NG) are investigated as electrocatalysts for CORR toward propanol in this paper. Due to the appropriate Cu-Cu bond length, the moderate charge of the Cu site, mild CO adsorption energy, and 100 % CO coverage, the absorbed 3*CO substance can form the critical *CO-CO-CO intermediate with a rather low kinetic barrier of 0.25 eV. The limiting potential of the whole process for the formation of propanol is just -0.15 V. Our work not only showed that Cu3@NG is an excellent catalyst for the formation of propanol with high selectivity at low potential but also indicated that the *CO coverage can greatly reduce the CO hydrogenation potential and bonding of some intermediates such as *CH2O. This research will provide a new idea for the material design of products tending to multi-carbon.

HDR syndrome presented with nephrotic syndrome in a Chinese boy: A case report.

BACKGROUND: HDR syndrome is a rare genetic disease caused by variants in the GATA3 gene and is phenotypically defined by the triad of hypoparathyroidism (H), deafness (D), and renal disease (R). Renal disorders of HDR are mainly developmental abnormalities, although renal functional abnormalities can also be observed. Nephrotic syndrome or nephrotic-level proteinuria is rare in HDR syndrome. Here, we report a Chinese infant with HDR syndrome who presented with early-onset nephrotic syndrome. We suggest that variants in the GATA3 gene might be associated with nephrotic syndrome. CASE SUMMARY: A 9-month-old boy was hospitalized with a complaint of diarrhea. Proteinuria was detected in the patient by routine testing for 3 days. No edema, oliguria, fever or abnormal urine color were observed. Routine urinary tests at a local hospital revealed proteinuria (protein 3 +) and microscopic hematuria (red blood cells 5-10/HP). The patient was born by cesarean delivery due to placental abruption at 35 weeks + 4 days of gestation. Intrauterine growth retardation was detected beginning at 6 months of gestation. His birth weight was 1.47 kg (< P3th), length was 39 cm (< P3th), and head circumference was 28 cm (< P3th). His motor developmental milestones were obviously delayed. Clinical data were analyzed, and genetic analysis for hereditary nephrotic syndrome was performed by next-generation sequencing. The clinical data showed that the boy exhibited growth retardation, early-onset nephrotic syndrome, microscopic hematuria, sensorineural deafness, T-cell immunodeficiency and congenital heart disease. Genetic tests revealed that the boy carried a de novo hemizygous variant, c.704C>T (p.Pro235 Leu), in exon 3 of the GATA3 gene. CONCLUSION: We report an infant with HDR syndrome who presented with early-onset nephrotic syndrome in China. We suggest that variants in the GATA3 gene might be associated with infant-onset nephrotic syndrome.

Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial ß-glucuronidases from the Tibetan medicine Rhodiola crenulata.

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.

Epidemiologic changes of a longitudinal surveillance study spanning 51 years of scrub typhus in mainland China.

Scrub typhus may be one of the world's most prevalent, neglected and serious, but easily treatable, febrile diseases. It has become a significant potential threat to public health in China. In this study we used national disease surveillance data to analyze the incidence and spatial-temporal distribution of scrub typhus in mainland China during 1952-1989 and 2006-2018. Descriptive epidemiological methods and spatial-temporal epidemiological methods were used to investigate the epidemiological trends and identify high-risk regions of scrub typhus infection. Over the 51-year period, a total of 182,991 cases and 186 deaths were notified. The average annual incidence was 0.13 cases/100,000 population during 1952-1989. The incidence increased sharply from 0.09/100,000 population in 2006 to 1.93/100,000 population in 2018 and then exponentially increased after 2006. The incidence was significantly higher in females than males (χ2 = 426.32, P < 0.001). Farmers had a higher incidence of scrub typhus than non-farmers (χ2 = 684.58, P < 0.001). The majority of cases each year were reported between July and November with peak incidence occurring during October each year. The trend surface analysis showed that the incidence of scrub typhus increased gradually from north to south, and from east and west to the central area. The spatial autocorrelation analysis showed that a spatial positive correlation existed in the prevalence of scrub typhus on a national scale, which had the characteristic of aggregated distribution (I = 0.533, P < 0.05). LISA analysis showed hotspots (High-High) were primarily located in the southern and southwestern provinces of China with the geographical area expanding annually. These findings provide scientific evidence for the surveillance and control of scrub typhus which may contribute to targeted strategies and measures for the government.

Discovery of plant chemical defence mediated by a two-component system involving ß-glucosidase in Panax species.

Plants usually produce defence metabolites in non-active forms to minimize the risk of harm to themselves and spatiotemporally activate these defence metabolites upon pathogen attack. This so-called two-component system plays a decisive role in the chemical defence of various plants. Here, we discovered that Panax notoginseng, a valuable medicinal plant, has evolved a two-component chemical defence system composed of a chloroplast-localized ß-glucosidase, denominated PnGH1, and its substrates 20(S)-protopanaxadiol ginsenosides. The ß-glucosidase and its substrates are spatially separated in cells under physiological conditions, and ginsenoside hydrolysis is therefore activated only upon chloroplast disruption, which is caused by the induced exoenzymes of pathogenic fungi upon exposure to plant leaves. This activation of PnGH1-mediated hydrolysis results in the production of a series of less-polar ginsenosides by selective hydrolysis of an outer glucose at the C-3 site, with a broader spectrum and more potent antifungal activity in vitro and in vivo than the precursor molecules. Furthermore, such ß-glucosidase-mediated hydrolysis upon fungal infection was also found in the congeneric species P. quinquefolium and P. ginseng. Our findings reveal a two-component chemical defence system in Panax species and offer insights for developing botanical pesticides for disease management in Panax species.

Exon junction complex modulates the formation of the m6A epitranscriptome.

N6-methyladenosine (m6A) is one of the most abundant chemical modifications in mRNA and plays essential roles in diverse physiological and pathological processes. m6A is highly enriched near stop codons and in long internal exons of mRNA, but the mechanism leading to this specific distribution has been unclear. Recently, three papers have solved this major problem by revealing that exon junction complexes (EJCs) act as m6A suppressors and shape the formation of the m6A epitranscriptome. Here, we briefly introduce the m6A pathway, elaborate the roles of EJC on the formation of m6A modification based on these results, and describe the effect of exon-intron structure on mRNA stability via m6A, which will help us better understand the latest progress in the m6A RNA modification field.

Immobilized triatomic CuB2 clusters on 2D carbon nitride: highly selective conversion of CO to ethanol at low potentials.

A promising pathway for carbon usage and energy storage is electrocatalytic reduction of CO to form high-value multi-carbon products. Herein, the d-p coupled triatomic catalyst CuB2@g-C3N4 with significant activity and selectivity for ethanol is presented for the first time. Density functional theory calculations elucidate that these spatially confined triatomic centers are capable of immobilizing multiple CO molecules, providing an exclusive reaction channel for direct C-C coupling. The CuB2@g-C3N4 catalyst can effectively reduce the energy barrier of CO dimerization to 0.46 eV. The limiting potential is only -0.19 V, which is much smaller than that of other Cu-based catalysts. Additionally, the CuB2@g-C3N4 catalyst can effectively inhibit the generation of competing C1 products and hydrogen evolution reactions. Excitingly, CuB2 loading makes g-C3N4 more optically active in visible and even infrared light. This work provides important ideas for the atomically precise design of novel d-p coupled catalysts for the direct conversion of CO2/CO into energetic fuels and high-value chemicals.

Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-protein interaction.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall has been used in Chinese Medicine for thousands of years, especially having anti-inflammatory, sedative, analgesic and other ethnic pharmacological effects. Moreover, Paeoniflorin is the main active ingredient of the Paeonia lactiflora Pall, and most are used in the treatment of inflammation-related autoimmune diseases. In recent years, studies have found that Paeoniflorin has a therapeutic effect on a variety of kidney diseases. AIM OF THE STUDY: Cisplatin (CIS) is limited in clinical use due to its serious side effects, such as renal toxicity, and there is no effective method for prevention. Paeoniflorin (Pae) is a natural polyphenol which has a protective effect against many kidney diseases. Therefore, our study is to explore the effect of Pae on CIS-induced AKI and the specific mechanism. MATERIALS AND METHODS: Firstly, CIS induced acute renal injury model was constructed in vivo and in vitro, and Pae was continuously injected intraperitoneally three days in advance, and then Cr, BUN and renal tissue PAS staining were detected to comprehensively evaluate the protective effect of Pae on CIS-induced AKI. We then combined Network Pharmacology with RNA-seq to investigate potential targets and signaling pathways. Finally, affinity between Pae and core targets was detected by molecular docking, CESTA and SPR, and related indicators were detected in vitro and in vivo. RESULTS: In this study, we first found that Pae significantly alleviated CIS-AKI in vivo and in vitro. Through network pharmacological analysis, molecular docking, CESTA and SPR experiments, we found that the target of Pae was Heat Shock Protein 90 Alpha Family Class A Member 1 (Hsp90AA1) which performs a crucial function in the stability of many client proteins including Akt. RNA-seq found that the KEGG enriched pathway was PI3K-Akt pathway with the most associated with the protective effect of Pae which is consistent with Network Pharmacology. GO analysis showed that the main biological processes of Pae against CIS-AKI include cellular regulation of inflammation and apoptosis. Immunoprecipitation further showed that pretreatment with Pae promoted the Hsp90AA1-Akt protein-protein Interactions (PPIs). Thereby, Pae accelerates the Hsp90AA1-Akt complex formation and leads to a significant activate in Akt, which in turn reduces apoptosis and inflammation. In addition, when Hsp90AA1 was knocked down, the protective effect of Pae did not continue. CONCLUSION: In summary, our study suggests that Pae attenuates cell apoptosis and inflammation in CIS-AKI by promoting Hsp90AA1-Akt PPIs. These data provide a scientific basis for the clinical search for drugs to prevent CIS-AKI.

Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation, chemical profiling and biochemical assay.

Although herbal medicines (HMs) are widely used in the prevention and treatment of obesity and obesity-associated disorders, the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood. Recently, we assessed the inhibitory potentials of several HMs against human pancreatic lipase (hPL, a key therapeutic target for human obesity), among which the root-extract of Rhodiola crenulata (ERC) showed the most potent anti-hPL activity. In this study, we adopted an integrated strategy, involving bioactivity-guided fractionation techniques, chemical profiling, and biochemical assays, to identify the key anti-hPL constituents in ERC. Nine ERC fractions (retention time = 12.5-35 min), obtained using reverse-phase liquid chromatography, showed strong anti-hPL activity, while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS/MS). Among the identified ERC constituents, 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) and catechin gallate (CG) showed the most potent anti-hPL activity, with pIC50 values of 7.59 ± 0.03 and 7.68 ± 0.23, respectively. Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner, with inhibition constant (K i) values of 0.012 and 0.082 µM, respectively. Collectively, our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC, as well as to elucidate their anti-hPL mechanisms. These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Increasing angiotensin-converting enzyme 1 regulated by histone 3 lysine 27 hyperacetylation in high-fat diet-induced hypertensive rat kidney.

BACKGROUND: Obesity is a key risk factor of hypertension. Angiotensin-converting enzyme 1 (ACE1) is a key enzyme involved in the renin-angiotensin-aldosterone system (RAAS), which contributes to obesity-related hypertension (OrHTN). Emerging evidence has shown that histone acetylation is also involved in OrHTN. As kidney is an effector organ that activates the RAAS by secreting renin after hypertension occurs, this study aimed to explore the regulatory role of histone acetylation on renal RAAS expression. METHODS: Nineteen male Wistar rats were randomly divided into a control group ( n  = 9, fed normal chow) and a high-fat diet (HFD) group ( n  = 10, fed HFD for 16 weeks). The renal transcriptome and histone acetylation spectrum was analyzed by RNA sequencing and tandem mass spectrometry and was further confirmed by RT-qPCR, western blot, and immunohistochemistry. Then, chromatin immunoprecipitation (ChIP)-qPCR analysis was performed for the detection of DNA-protein interaction. RESULTS: After 16-week HFD, the rats became obese with increased plasma triglyceride and high blood pressure. Increased ACE1 and histone 3 lysine 27 acetylation (H3K27ac) expression levels were found in OrHTN rat kidneys. The following ChIP-qPCR analysis illustrated that the upregulation of ACE1 transcription was mediated by increased H3K27ac. CONCLUSION: H3K27ac could be an important histone acetylation site that activates renal ACE1 in HFD-induced hypertensive rats.

Identification of Genes Reveals the Mechanism of Cell Ferroptosis in Diabetic Nephropathy.

Aims/Introduction: Diabetic nephropathy (DN) is one of the main complications of diabetes. Genomics may reveal the essential pathogenesis of DN. We analyzed datasets to search for key genes to explore pathological mechanisms of DN. Materials and Methods: In this study, weighted gene co-expression network analysis (WGCNA) was used to divide the differential expression genes (DEGs) from GSE142025 into different modules, and enrichment pathway analysis was conducted for each module to find key genes related to cell death pathway. Then, verification was carried out through network and histopathology. Finally, the regulatory mechanisms of key gene expression, including transcription factors (TFs), miRNA and E3 ligases related to ubiquitination, were predicted through website prediction and then miRNA results were validated using GSE51674 dataset. Results: The results of WGCNA and enrichment pathway analysis indicated that ferroptosis had significantly occurred in advanced DN (AND) group. Analysis of DEGs indicated that the occurrence and development of ferroptosis are mainly through ALOX15-mediated lipid metabolism pathway, which was found in all intrinsic cells of the glomerulus detected by IHC and IF staining. Moreover, network predictions were used for searching ALOX15-related TFs and ubiquitination. Meanwhile, the network predictions combining with other dataset furtherly discovered miRNAs which regulated ALOX15 expression. This study showed that the levels of mmu-miR-142-3p increased in DN mice kidney tissues, compared with the NC group. Conclusion: Ferroptosis existed in glomerular intrinsic cells of ADN group and its potential key candidate gene was ALOX15 which may be regulated by miR-142 and miRNA-650, TFs (CREBBP, EP300, HDAC1, MTA1, SPI1, STAT6) and E3 ligases related to ubiquitination (PML, ZMIZ1, MARCHF1, MARCHF3, MARCHF8, MARCHF11).

Characterizing the influence of different drying methods on chemical components of Panax notoginseng leaves by heart-cutting two-dimensional liquid chromatography coupled to orbitrap high-resolution mass spectrometry.

Panax notoginseng leaves (PNL) was considered as a promising functional food ingredient with abundant protopanaxdiol ginsenosides. In this study, the influence of different drying methods on chemical components in PNL was characterized by a newly developed heart-cutting 2D-LC-HRMS. Our data indicates that vigorous ginsenoside transformation occurs in PNL processed by sun-air drying and hot-air drying (HAD) at 50 °C, but not shade-air drying (SAD), HAD at 25 °C and steaming prior to drying (SD). Specifically, the main components of PNL, ginsenosides Rb3, Rc, Rb2, Rb1 and Rd, can be transformed into notoginsenosides Fd and Fe, ginsenoside Rd2, Gypenoside XVII and ginsenoside F2, respectively, by highly selective cleavage of ß-1,2-glucosidic linkage at the C-3 position. Only SD can inactivate the proteins that mediate this transformation. Different drying methods also greatly affect the quality of PNL products extracted by the conventional decoction method. These findings offer the scientific basis to design industrial drying methods for ensuring the quality of PNL.

Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay / 药物分析学报

Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Protective Immunity Induced by TgMIC5 and TgMIC16 DNA Vaccines Against Toxoplasmosis.

Toxoplasma gondii is an obligate intracellular parasite, which is responsible for a widely distributed zoonosis. Effective vaccines against toxoplasmosis are necessary to protect the public health. The aim of this study is to evaluate the immune efficacy of DNA vaccines encoding TgMIC5 and TgMIC16 genes against T. gondii infection. The recombinant plasmid pVAX-MIC5 and pVAX-MIC16 were constructed and injected intramuscularly in mice. The specific immune responses and protection against challenge with T. gondii RH tachyzoites were evaluated by measuring the cytokine levels, serum antibody concentrations, lymphocyte proliferation, lymphocyte populations, and the survival time. The protection against challenge with the T. gondii RH tchyzoites and PRU cysts was examined by evaluation of the reduction in the brain cyst burden. The results indicated that immunized mice showed significantly increased levels of IgG, IFN-γ, IL-2, IL-12p70, and IL-12p40 and percentages of CD4+ and CD8+ T cells. Additionally, vaccination prolonged the mouse survival time and reduced brain cysts compared with controls. Mouse groups immunized with a two-gene cocktail of pVAX-MIC5 + pVAX-MIC16 were more protected than mouse groups immunized with a single gene of pVAX-MIC5 or pVAX-MIC16. These results demonstrate that TgMIC5 and TgMIC16 induce effective immunity against toxoplasmosis and may serve as a good vaccine candidate against T. gondii infection.

Preparative separation of gypenoside XVII, ginsenoside Rd2, and notoginsenosides Fe and Fd from Panax notoginseng leaves by countercurrent chromatography and orthogonality evaluation for their separation.

The minor ginsenosides with less polarity may have more potent biological activities. Four minor saponins, i.e., gypenoside XVII, ginsenoside Rd2, notoginsenoside Fe, and notoginsenoside Fd, were successfully separated from Panax notoginseng leaves (PNL) after biotransformation by one-step countercurrent chromatography using the biphasic solvent system consisting of n-butanol-ethyl acetate-water (1:4:5, v/v/v). 30 mg of the refined extract of PNL produced 1 mg of gypenoside XVII, 4 mg of notoginsenoside Fe, 2.5 mg of ginsenoside Rd2, and 8.4 mg of notoginsenoside Fd, with purity of 74.9, 95.2, 87.3, and 97.6%, respectively. Besides, orthogonality evaluation for the separation of the four saponins using countercurrent chromatography and liquid chromatography was discussed. Four minor saponins were successfully separated from each other on a preparative scale by countercurrent chromatography from PNL, which will facilitate to provide ample of these minor saponins for further pharmacological studies.

Ginsenoside distribution in different architectural components of Panax notoginseng inflorescence and infructescence.

The roots of Panax notoginseng (Burk) F. H. Chen are used as a highly valuable Chinese herbal medicine in the prevention and treatment of cardiovascular and hematological diseases. Several aerial parts of plant are usually abandoned as the wastes. Panax notoginseng inflorescence (IFO) is commonly used as a folk medicine and dietary ingredient, its fruiting stage is referred as infructescence (IFU). Owing to high chemical complexity and structural similarity of ginsenosides, the co-eluting phenomenon, especially for the isomers, is inevitable in the chromatogram, resulting in the inaccurate quantitation. A novel LCMS method using hybrid positive full scan and multiple reaction monitoring (MRM) modes was developed to characterize ginsenoside distribution in different architectural components of IFO and IFU. MRM was performed for the quantification of G-Ra2 and NG-Fp2, a pair of co-eluting isomers with identical negative MS and MS/MS characteristics, and full scan was conducted to quantify other investigated saponins. Our data indicate that flower buds have the highest abundance of the summed saponins, fruit pedicel and fruit pericarp, commonly considered as the useless by-products of seed processing, contain the abundant saponins. Additionally, the contents of the detected ginsenosides in these architectural components significantly increased along with their growth years. Our findings will facilitate comprehensive utilization and exploitation of P. notoginseng inflorescence and infructescence.

Effects of acid ionization on the formation mechanism of bimodal mesoporous Al-MCM-41s from coal gasification fine residue and evaluation of adsorption capabilities.

The development of synthetic methods to obtain high value-added mesoporous Al-MCM-41 from a low-cost silicon-aluminum source with low toxicity is an active research topic in solid waste resource utilization. In particular, the controlled synthesis of MCM-41 with a two-level pore distribution is a challenging task. In this work, the synthesis of unimodal and bimodal mesoporous Al-MCM-41s was achieved using acids with different degrees of ionization from coal gasification fine residue (CGFR) as bulk solid waste generated by the coal gasification process. We determined that the degree of acid ionization affected the self-assembly of inorganic/organic species as well as condensation processes, resulting in some changes of the hexagonal mesoscopic structure. The unimodal mesoporous Al-MCM-41 with acetic acid HAc and bimodal mesoporous Al-MCM-41s with an inorganic acid environment (HCl, HNO3 or H2SO4) could be effectively prepared in a controllable manner by the silicon and aluminum source obtained at alkali dissolution time 6 h and crystallization conditions at pH 10.5 and 383 K in 72 h. Moreover, the synthesis of Al-MCM-41-HAc with different SiO2/Al2O3 molar ratios (18-89) could also be realized by different alkali dissolution times. And alkali dissolution time (2-24 h) and the crystallization conditions (pH 4.5-11.5, temperatures 373-393 K, and time 48-96 h) also affected the formation of unimodal and bimodal mesoporous Al-MCM-41-HAc. In addition, the maximum adsorption amount onto bimodal mesoporous Al-MCM-41-H2SO4 (476.19 mg g-1 at 308 K) was larger than that onto unimodal mesoporous Al-MCM-41-HAc (243.90 mg g-1 at 303 K). The mesoporous Al-MCM-41s showed good stability.

Ginsenosides Rb2 and Rd2 isolated from Panax notoginseng flowers attenuate platelet function through P2Y12-mediated cAMP/PKA and PI3K/Akt/Erk1/2 signaling.

Saponins derived from Panax notoginseng root are widely used as herbal medicines and dietary supplements due to their wide range of health benefits. However, the effects of those from Panax notoginseng flowers (PNF) on platelet function and thrombus formation remain largely unknown. Using a series of platelet function assays, we found that G-Rb2 and G-Rd2, among the ten PNF saponin monomers, significantly inhibited human platelet aggregation and activation induced by adenosine diphosphate (ADP) in vitro. The 50% inhibitory concentration (IC50) of G-Rb2 and G-Rd2 against ADP-induced platelet aggregation was 85.5 ± 4.5 µg mL-1 and 51.4 ± 4.6 µg mL-1, respectively. Mechanistically, G-Rb2 and G-Rd2 could effectively modulate platelet P2Y12-mediated signaling by up-regulating cAMP/PKA signaling and down-regulating PI3K/Akt/Erk1/2 signaling pathways. Co-incubation of the P2Y12 antagonist cangrelor with either G-Rb2 or G-Rd2 did not show significant additive inhibitory effects. G-Rb2 and G-Rd2 also substantially suppressed thrombus growth in a FeCl3-induced murine arteriole thrombosis model in vivo. Interestingly, G-Rd2 generally exhibited more potent inhibitory effects on platelet function and thrombus formation than G-Rb2. Thus, our data suggest that PNF-derived G-Rb2 and G-Rd2 effectively attenuate platelet hyperactivity through modulating signaling pathways downstream of P2Y12, which indicates G-Rb2 and G-Rd2 may play important preventive roles in thrombotic diseases.

[Critical quality attribute assessment of big brand traditional Chinese medicine: visualization of blending process for rare medicines in Tongren Niuhuang Qingxin Pills based on spatial distribution uniformity].

The spatial distribution uniformity of valuable medicines is the critical quality attribute in the process control of Tongren Niuhuang Qingxin Pills. With the real world sample of the mixed end-point powder of Tongren Niuhuang Qingxin Pills as the research object, hyperspectral imaging technology was used to collect a total of 32 400 data points with a size of 180 pix×180 pix. Spectral angle matching(SAM), classical least squares and mixed tuned matched filtering(MTMF) were used to identify the spatial distribution of rare medicines. MTMF model showed higher identification accuracy, therefore the spatial distribution of the blended intermediates was identified based on the MTMF model. The histogram method was also used to evaluate the spatial distribution uniformity of rare medicines. The results showed that the standard deviation was 4.78, 6.5, 3.48, 1.96, and 3.00 respectively for artificial bezoar, artificial musk, Borneol, Antelope horn and Buffalo horn; the variance was 22.8, 42.3, 12.1, 3.82, and 9.00, and the skewness was 1.26, 1.71, 0.06,-0.86, and 1.04, respectively. The final results showed that the most even blending was achieved in concentrated powder of Borneol, Antelope horn and Buffalo horn, followed by artificial bezoar, and last artificial musk. A visualization method was established for quality attributes of distribution uniformity in blending process of Tongren Niuhuang Qingxin Pills. It could provide evidences of quality control methods in the mixing process of big brand traditional Chinese medicine.