Extensive crystal fractionation of high-silica magmas revealed by K isotopes.

Fractional crystallization plays a critical role in generating the differentiated continental crust on Earth. However, whether efficient crystal-melt separation can occur in viscous felsic magmas remains a long-standing debate because of the difficulty in discriminating between differentiated melts and complementary cumulates. Here, we found large (~1 per mil) potassium isotopic variation in 54 strongly peraluminous high-silica (silicon dioxide >70 weight %) leucogranites from the Himalayan orogen, with potassium isotopes correlated with trace elemental proxies (e.g., strontium, rubidium/strontium, and europium anomaly) for plagioclase crystallization. Quantitative modeling requires up to ~60 to 90% fractional crystallization to account for the progressively light potassium isotopic composition of the fractionated leucogranites, while plagioclase accumulation results in enrichment of heavy potassium isotopes in cumulate leucogranites. Our findings strongly support fractional crystallization of high-silica magmas and highlight the great potential of potassium isotopes in studying felsic magma differentiation.

Efficacy and safety of Zicuiyin decoction on diabetic kidney disease: A multicenter, randomized controlled trial.

BACKGROUD: Zicuiyin (ZCY) decoction created by Xichun Zhang in the Qing dynasty has been used on diabetes mellitus and complications for more than two centuries in China. Huangkui capsule (HKC) is a listed Chinese patent medicine to treat diabetic kidney disease (DKD). To determine whether ZCY is non-inferior to HKC in the treatment of DKD, a multicenter, parallel-control, open-label, randomized clinical trial was conducted. METHODS: In this clinical trial, 88 DKD patients were recruited at three centers in Tianjin from January 2018 to December 2019. They were randomized to receive HKC (2.5 g, TID) or ZCY (crude drug amount 75 g, 150 ml, BID) for eight weeks based on routine treatment. The primary outcome was the change of estimated glomerular filtration rate (eGFR). The secondary outcomes included change of serum creatinine (SCr), urinary albumin excretion rate, 24 h urinary protein, urinary albumin-creatinine ratio, glycosylated hemoglobin A1c, symptom scores, and microbiota compositions profiles. RESULTS: The change of eGFR in HKC and ZCY groups were -7.08 ± 24.65 and 2.57 ± 18.49 ml/min/1.73 m2, respectively (p < 0.05). The 95% lower confidence limit for the difference between the estimated means was 1.93 ml/min/1.73 m2, establishing the superiority of ZCY. Compared to HKC, ZCY could significantly decrease SCr and symptom scores (p < 0.05). There were no significant differences in other outcomes between the two groups (p > 0.05). ZCY ameliorated gut microbiota dysbiosis, including increased Prevotellaceae and Lactobacillaceae and decreased Enterobacteriales, Clostridiaceae and Micrococcaceae. No severe adverse events were reported in any group. CONCLUSIONS: ZCY had better efficacy in improving and protecting kidney function. It would be an alternative option to treat DKD, especially those who decline eGFR and gut microbiota dysbiosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OON-17012076. Registered July 21, 2017.

[Efficacy of Yishen Huoxue Tongluo() medicated serum on apoptosis of nucleus pulposus cells of human intervertebral disc under overload static pressure].

OBJECTIVE: To explore the efficacy of Yishen Huoxue Tongluo() decoction containing serum on the apoptosis of human disc nucleus pulposus cells under the overload static pressure stress and its related mechanism. METHODS: Human nucleus pulposus cells were divided into three groups. The blank group had no intervention. The model group and traditional Chinese medicine serum intervention group were treated with 3 MPa compressive stress in vitro for 2, 4 and 6 hours. The changes and differences of morphology, growth status and ultrastructure of intervertebral disc nucleus pulposus cells were observed. The apoptosis rate of nucleus pulposus cells and nuclear factor kappa-B p65 (NF-κB p65), SRY-related high mobility group box 9 (SOX9), C/EBP-homologous protein (CHOP), matrix metalloprotein-13 (MMP-13) and corresponding gene expression were detected. RESULTS: At the same time, compared with the blank group, the nucleus pulposus cells in the model group were smaller in volume, less in cytoplasm and worse in growth; the nucleus pulposus cells in the traditional Chinese medicine serum intervention group were slightly larger in volume, more complete in morphology, richer in cytoplasm and better in growth. Under the same action time, the ultrastructure of nucleus pulposus cells in blank group was complete, and the structures of primary and secondary processes were not broken;and the ultrastructure of model group and traditional Chinese medicine serum intervention group were damaged, the main and secondary processes were broken to varying degrees, and there was no significant difference between the two groups. At the same time, the apoptosis rate of nucleus pulposus cells in model group was higher than that in blank group, while the apoptosis rate of nucleus pulposus cells in the traditional Chinese medicine serum intervention group was lower than that inmodel group, the difference was statistically significant (P<0.05); with the increase of action time, there was no significant difference in the apoptosis rate of nucleus pulposus cells between blank group and traditional Chinese medicine serum intervention group, and the apoptosis rate of nucleus pulposus cells in model group was increased. Compared with model group, the expression of NF-κB p65, CHOP, MMP-13 were decreased and SOX9 was increased in traditional Chinese medicine serum intervention group at the same time (P<0.05);with the increase of action time, the expression of NF-κB p65, CHOP and MMP-13 were increased, and the expression of SOX9 was decreased in blank group and model group(P<0.05), and the expression level of model group was higher than that of blank group(P<0.05). Overall observation by gene expression, under the same action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 in traditional Chinese medicine serum intervention group were lower than that in model group, while SOX9 was increased (P<0.05);compared with model group, the relative quantifications of NF-κB p65, CHOP and MMP-13 in blank group were decreased(P<0.05), and the relative quantification of SOX9 was increased(P<0.05);with the increase of action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 of nucleus pulposus cells in blank group and model group were increased and SOX9 was decreased(P<0.05). CONCLUSION: Yishen Huoxue Tongluo() decoction can reduce the apoptosis of nucleus pulposus cells under overload and static pressure, and has the effect of delaying the degeneration of nucleus pulposus cells. Its mechanism may be related to the decrease of CHOP, MMP-13 expression and the increase of SOX9 expression by inhibiting NF-κB p65 signal pathway of nucleus pulposus cells.

Acute hepatotoxicity and nephrotoxicity risk assessment of the Tibetan medicine 25 flavors of the turquoise pill based on 1H-NMR metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Therapeutic assessment of fractions of Gastrodiae Rhizoma on chronic atrophic gastritis by 1H NMR-based metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics.

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

[Distribution of Nitrogen and Phosphorus in the Tidal Reach and Estuary of the Daliao River and Analysis of Potential Eutrophication].

Based on the monitoring data in the tidal reach and estuary of the Daliao river in August and November, 2013, the seasonal and spatial distribution of the nitrogen and phosphorus forms were studied, and the degree of eutrophication was evaluated. The results showed that nitrate nitrogen was the main chemical species and occupied about fifty-five percent of inorganic nitrogen, and the particulate phosphorus was the main chemical species and occupied about fifty percent of total phosphorus in the tidal reach and estuary of the Daliao river in wet and dry seasons, 2013. The concentrations of nitrogen and phosphorus nutrients decreased in the direction from tidal reach to estuary of the Daliao river. Correlation analysis showed that there was a significant negative correlation between the nitrogen and phosphorus forms and salinity in most of the water body, which illustrated that physical dilution of seawater played a major role in the spatial distribution of nitrogen and phosphorus forms. The concentrations of nitrogen and phosphorus nutrients in the dry season were higher than those in the wet season, this was mainly related to the seasonal terrestrial input of the tidal reach. The concentration of the dissolved inorganic nitrogen was higher than 0.30 mg · L⁻¹, and the value of N/P was higher than 60, which indicated that PO4³â»-P was the nutrient limiting phytoplankton growth in the tidal reach and estuary of the Daliao river in August and November, 2013.

[Preparation and Dissolution Evaluation of Breviscapine Self-microemulsion].

OBJECTIVE: To study the prescription and preparation technology of breviscapine self-microemulsion for oral administration, and to evaluate the quality, stability and in vitro dissolution. METHODS: The prescription and preparation technology were selected and optimized through the solubility experiment, compatibility test, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter and stability as indexes. The droplet morphous, drug content, stability and dissolution were evaluated. Results:The prescription composition of breviscapine self-microemulsion was caprylic/capric triglyceride(GTCC,40%), Cremophor RH-40(50%), and PEG-400 (10%), with the drug loading of 7. 0 mg/g. The breviscapine self-microemulsion exhibited uniform and transparent,with the particle size of 38. 57 nm,Zeta potential of - 8. 80 mV. The results of dissolution indicated that the accumulative dissolution in 0. 1 mol/L hydrochloric acid was able to reach 90. 30% after 90 min, being 5. 9 times to that of the raw material medicine. The stability result showed that the content of breviscapine self-microemulsion was affected by high temperature, indicating it should be stored at low temperature. CONCLUSION: The preparation of breviscapine self-microemulsion is simple, which can increase the solubility of breviscapine in water and the absorption of breviscapine in the stomach and intestine, and conform to the main indexes of oral drug delivery system. It offers the basis for further research of breviscapine.

[Input Characteristics and Pollution Assessment of Nutrients Pollution in the Primary Pollution Source of the Daliao River].

A total of 13 surface water samples were collected from sewage outfalls and 3 main tributaries ( Hunhe River, Taizi River and Haicheng River) of the Daliao River to clarify the pollution characteristics of various species of nitrogen and phosphorus in July 2013, respectively. The results showed that the concentrations of DON in the Hunhe River, NO3(-)-N in the Taizi River, NH4(+) -N, PO4(3-) -P and DOP in the Haicheng River were higher than others. In water samples from the 3 main tributaries of the Daliao River, the TN and TP contents were above the national environmental quality standards for surface water (GB 3838-2002, grade V) except for the TP that was classified as grade IV in the Taizi River. The percentages of various N species showed that NO3(-) -N was the major N species in the Taizi River and Haicheng River, meanwhile DON was the major N species in the Hunhe River. The percentages of various P species showed that TPP was the major P species in the Hunhe River and Taizi River, and DOP was the major P species in the Haicheng River. TN content was above the national environmental quality standards for surface water (GB 3838-2002, grade V) in sewage outfalls. But TP content was classified as grade IV to above grade V. And the concentrations of NH4(+) -N, TN and TP in sewage outfalls of Shachang and Gangjian were higher than those in other sewage outfalls. The percentages of various N species in sewage outfalls showed that DIN was the major N species in sewage outfalls. There were higher level of TN and TP content in the Daliao River than those of tribtaries, and NO3(-) -N and TPP were the major N and P species, respectively. In general, the nutrients analysis of tributaries, sewage outfalls and the Daliao River showed that nutrients of the Daliao River were affected by sewage outfalls. And the effect was significant and non-ignorable.

[Fluorescence resonance energy transfer quenching method for determination of arsenic with acridine orange-rhodamine B].

A new method for the determination of trace arsenic was developed by using fluorescence resonance energy transfer from acridine orange (AO) to rhodamine B (RB). It was found that under the condition of lambda(ex)/lambda(em) = 470/580 nm, effective energy transfer could occur between AO and RB in the dodecyl benzene sodium sulfonate solution. The fluorescence intensity of RB was diminished by molybdoarsenide which was formed by the reaction of arsenic (V) with molybdate in sulfuric acid medium. The detection limit of this method was 2. 56 microg x L(-1). This method was used for the determination of trace arsenic in tea. The range of determination for arsenic was 0.01-0.25 mg x L(-1). The relative standard deviation for the determination of arsenic was 0.48%-0.64%. The recoveries for the addition of 0.01-0.03 mg x L(-1) arsenic were 98%-103%. The method has been applied to the determination of arsenic with satisfactory results.