Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice.

OBJECTIVE: To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS). METHODS: The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively. RESULTS: LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups. CONCLUSION: HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.

Mechanisms of Epichloë bromicola to Promote Plant Growth and Its Potential Application for Coix lacryma-jobi L. Cultivation.

Endophytic fungi play important roles in regulating plant growth and development and usually used as a promising strategy to enhance the biosynthesis of host valuable secondary metabolite, but the underlying growth-promoting mechanisms are only partly understood. In this study, the wild-type Arabidopsis thaliana seedlings co-cultured with fungal endophyte Epichloë bromicola showed auxin (IAA)-stimulated phenotypes, and the growth-promoting effects caused by E. bromicola were further verified by the experiments of spatially separated co-culture and fungal extract treatment. IAA was detected and identified in the extract of E. bromicola culture by LC-HRMS/MS, whereas 2,3-butanediol was confirmed to be the predominant volatile active compound in the diethyl ether and ethyl acetate extracts by GC-MS. Further study observed that IAA-related genes including synthesis key enzyme genes (CYP79B2, CYP79B3, NIT1, TAA1 and YUCCA1) and controlling polar transport genes (AUX1, BIG, EIR1, AXR3 and ARF1), were highly expressed at different periods after E. bromicola inoculation. More importantly, the introduction of fungal endophyte E. bromicola could effectively promote the growth and accumulation of coixol in Coix under soil conditions. Our study showed that endophytic fungus E. bromicola might be considered as a potential inoculant for improving medicinal plant growth.

[Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification].

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12ß-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Protective Effect of the Eluting Fraction of Da-Yuan-Yin Decoction on Acute Lung Injury.

Context: The Da-yuan-yin (DYY) decoction is a classical prescription of traditional Chinese medicine that has antipyretic and anti-inflammatory effects. Network Pharmacology (NP) is an emerging discipline based on system-biology theory and biosystem network analysis that researchers can use to predict drug-action targets and mechanisms. Objective: The study intended to use NP evaluate the protective effects of the fifth eluting fraction of the supernatant of the DYY decoction (DYY-5) for mice induced with acute lung injury (ALI) using lipopolysaccharide (LPS) and to explore DYY-5's mechanisms. Design: The research team performed an animal study. Setting: The study took place at the College of Pharmaceutical Science at Soochow University in Suzhou, China. Animals: The animals were 42 male Balb/c mice, about 20 to 25 g in weight. Intervention: The research team: instilled 2 mg/kg of LPS intratracheally (i.t.) to induce ALI. The team divided the mice into seven groups of six mice: (1) a control group; (2) a negative control group-the DYY-5 group with mice treated only with a high dosage, 60 mg/kg, of DYY-5 to investigate the effects of DYY-5 on normal mice; (3) the positive control group, the LPS group, with induced ALI but no treatments; (4) the LPS+60 mg/kg-DYY-5 group with induced ALI treated with a high dosage of DYY-5; (5) the LPS+30 mg/kg-DYY-5 group with induced ALI treated with a medium dosage of DYY-5; (6) the LPS+15 mg/kg-DYY-5 group with induced ALI treated with a low dosage of DYY-5; and (7) a reference drug control group, the LPS+DXM group, with induced ALI treated with 5 mg/kg of dexamethasone (DXM). Outcome Measures: The research team: (1) determined the chemical components of DYY; (2) identified the anticomplementary activities of DYY-5; (3) took lung specimens, serum, and bronchoalveolar lavage fluid (BALF) from the mice for histopathological examination, Western blot, and biochemical analysis; (4) measured total protein concentrations and lung W/D ratios; (5) measured the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) using quantitative real-time polymerase chain reaction (PCR); (6) measured the levels of pro-inflammatory and anti-inflammatory factors, the activity of myeloperoxidase (MPO) and superoxide dismutase (SOD), and the levels of complements, including complements 3 (C3), C3c, C5a, C5aR1, and C5b-9, using kits; (7) analyzed the levels of nuclear factor-kappa B (NF-κB) and IkB kinase (IKK) using Western blot; and (8) used network pharmacology (NP) to predict DYY-5's mechanisms and potential targets. Results: The study's results were consistent with the NP analysis, which reflected the multitarget and multipathway characteristics of DYY-5 in alleviating ALI. The LPS+30 mg/kg-DYY-5 group had significantly lower lung wet-to-dry (W/D) ratios and total protein concentrations in BALF than the LPS group did, with P < .01 and P < .0001, respectively as did the LPS+60 mg/kg-DYY-5 group (both P < .0001). The 60 mg/kg of DYY-5 compared to the LPS group: (1) regulated the levels tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin-1 beta (IL-1ß), with all P < .0001, anti-inflammatory factors-IL-4 (P < .05), IL-10 (P < .001), and IL-13 (P < .001); (2) increased the activity of SOD (P < .0001) and decreased the activity of MPO (P < .0001) and the expressions of iNOS and COX-2 mRNA (both P < .01); (3) blocked the activation of NF-κB and IKK; and (4) alleviated the pathological changes in the lung tissue, by reducing the depositions of C3c and decreasing the levels of C3, C5a and C5aR1 (all P < .0001), C5b-9 (P < .001) and C3c (P < .01) in serum. Conclusions: The protective effects of DYY-5 on ALI were related to antioxidation, anti-complementary activities, and regulation of inflammatory factors through the IKK/NF-κB signal pathway. DYY-5 may be useful as a potential therapeutic agent for treating ALI in clinics.

[Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis].

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1ß, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1ß, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1ß, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1ß, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

Chemoproteomic profiling to identify activity changes and functional inhibitors of DNA-binding proteins.

DNA-binding proteins are promising therapeutic targets but are notoriously difficult to drug. Here, we evaluate a chemoproteomic DNA interaction platform as a complementary strategy for parallelized compound profiling. To enable this approach, we determined the proteomic binding landscape of 92 immobilized DNA sequences. Perturbation-induced activity changes of captured transcription factors in disease-relevant settings demonstrated functional relevance of the enriched subproteome. Chemoproteomic profiling of >300 cysteine-directed compounds against a coverage optimized bead mixture, which specifically captures >150 DNA binders, revealed competition of several DNA-binding proteins, including the transcription factors ELF1 and ELF2. We also discovered the first compound that displaces the DNA-repair complex MSH2-MSH3 from DNA. Compound binding to cysteine 252 on MSH3 was confirmed using chemoproteomic reactive cysteine profiling. Overall, these results suggested that chemoproteomic DNA bead pull-downs enable the specific readout of transcription factor activity and can identify functional "hotspots" on DNA binders toward expanding the druggable proteome.

Effects of electroacupuncture on angiogenesis and cortical VEGF and BDNF expression inrats with focal cerebral ischemia / 针灸推拿医学（英文版）

Objective: To observe the effect of electroacupuncture (EA) of "concurrent treatment of the brain and heart" on angiogenesis and cortical vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in rats with focal cerebral ischemia, and to explore the mechanism of EA in cerebral ischemia treatment. Methods: A total of 108 Sprague-Dawley rats, 27 rats were randomly selected as the sham-operation group, and the rest rats received the right middle cerebral artery occlusion operation for model preparation firstly, and then were divided into a model group, a traditional acupoint group, and a concurrent treatment of the brain and heart group, with 27 rats in each group. In the sham-operation group, only the carotid artery was isolated. EA at Shuigou (CV26), Quchi (LI11), Hegu (LI4), and Zusanli (ST36) in the traditional acupoint group, and EA at Fengfu (GV16), Baihui (GV20), Xinshu (BL15), and Neiguan (PC6) in the concurrent treatment of the brain and heart group were performed 4 h after the operation, once a day, for 14 consecutive days. Rats in the sham-operation group and the model group were identically fixed without any treatment. Before and after treatment, the modified neurological severity score (mNSS), regional cerebral blood flow (rCBF), and CD34 positive expression by immunohistochemistry were measured. The positive protein expression levels of VEGF and BDNF were detected by immunofluorescence, and the mRNA expression levels of VEGF and BDNF were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: Compared with the sham-operation group, the mNSS, rCBF, and ischemic side cortical micro-vessel density (MVD) decreased, and the protein and mRNA expression levels of VEGF and BDNF increased in the model group (P<0.01). Compared with the model group, the mNSS of the two EA groups decreased, and the mNSS of the concurrent treatment of the brain and heart group was lower than that of the traditional acupoint group on the 14th day (P<0.05). Compared with the model group, the rCBF in the two EA groups increased, and the rCBF reached the highest on the 14th day (P<0.05 or P<0.01), and the rCBF in the concurrent treatment of the brain and heart group was higher than that in the traditional acupoint group (P<0.05); the MVD of the two EA groups was higher than that of the model group, and the MVD of the concurrent treatment of the brain and heart group was higher than that of the traditional acupoint group on the 7th and 14th days (P<0.05 or P<0.01). Compared with the model group, the protein and mRNA expression levels of VEGF and BDNF in the two EA groups increased (P<0.01). The VEGF expression level was the highest on the 7th day in the concurrent treatment of the brain and heart group (P<0.05), and the BDNF expression level was higher on the 7th and 14th days than on the 3rd day (P<0.05). The mRNA expression levels of VEGF and BDNF in both EA groups reached the highest on the 7th day (P<0.05 or P<0.01). Conclusion: EA therapy can up-regulate the VEGF and BDNF expression levels and increase the rCBF in the cortex of rats with focal cerebral ischemia, which may be one mechanism of EA in the cerebral ischemia treatment. The therapeutic effect is accumulated with the effective time, and the concurrent treatment of the brain and heart group is superior to the traditional acupoint group in promoting angiogenesis.

Protective Effect of Selenomethionine on T-2 Toxin-Induced Rabbit Immunotoxicity.

T-2 toxin is a trichothecene mycotoxin produced by fusarium species, which is mainly prevalent in grain and livestock feed. One of the main effects of this toxin is immunodepression. Previous studies have shown that T-2 toxin can cause damage to immune organs and impaired immune function in animals. However, selenomethionine (SeMet) as an organic selenium source can not only promote the growth and development of the body but also effectively improve the body's immune function. In this study, rabbits were exposed to 0.4-mg/kg T-2 toxin, and abnormal blood routine indicators were found in the rabbits. HE staining also showed obvious lesions in the spleen and thymus tissue structures, accompanied by a large number of bleeding points. In addition, rabbits showed strong oxidative stress and inflammatory response after T-2 toxin action. 0.2 mg/kg, 0.4 mg/kg, and 0.6 mg/kg organic selenium were added to the feed. However, it was found that 0.2 mg/kg selenium can effectively improve the abnormal changes of blood routine and spleen and thymus tissue of rabbits. On the other hand, it can significantly increase the expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the spleen and thymus, and downregulate the expression of reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, inflammatory factors interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood were also significantly inhibited; the expression of proliferating cell nuclear antigen (PCNA) in the spleen and thymus was also significantly increased after low-dose selenium treatment. Surprisingly, 0.4 mg/kg and 0.6 mg/kg of selenium did not effectively alleviate the immunotoxic effects caused by T-2 toxin, and cause damage to a certain extent. In summary, our results show that 0.2 mg/kg of SeMet can effectively alleviate the immunotoxicity caused by T-2 toxin. Selenium may protect rabbits from T-2 toxin by improving its antioxidant and anti-inflammatory capabilities.

Dietary Omega-3 Fatty Acid Intake and Mortality in CKD Population: A 1999-2014 NHANES Analysis.

INTRODUCTION: High risk of early death, especially contributed to cardiovascular disease, exists in patients who have chronic kidney disease (CKD). And the burden of cardiovascular disease is able to be lightened by an increase in omega-3 polyunsaturated fatty acid (omega-3 PUFA). A diet high in omega-3 PUFA in the general population is protective, although it is inconclusive about its beneficial role in the CKD population. METHODS: From the 1999 to 2014 National Health and Nutrition Examination Surveys (NHANES), we can collect 2,990 participants who suffered from CKD, who were classified into 4 groups: <0.86, 0.87-1.30, 1.31-1.92, and 1.93-9.65 g/day based on NHANES 24-h dietary recall questionnaire dietary omega-3 PUFA. Moreover, their mortality details were available to be obtained by linking NHANES to the National Death Index. The associations between dietary omega-3 PUFA and mortality were evaluated by constructing multivariable Cox proportional hazards models. RESULTS: Over 8 years of a median follow-up, 864 deaths were recorded. The adjusted hazard ratios (95% confidence interval) for all-cause mortality of the diseased people with CKD in the 2nd (0.87-1.30 g/day), 3rd (0.87-1.30 g/day), and 4th (1.93-9.65 g/day) quartiles of dietary omega-3 PUFA were 0.94 (0.72, 1.23), 0.74 (0.54, 1.02), and 0.67 (0.48, 0.93), respectively, versus those with the lowest quartile of dietary omega-3 PUFA intake (<0.86 g/day) (p for trend = 0.011). CONCLUSION: There may be a inverse relation of dietary omega-3 PUFA intake and all-cause mortality in patients with CKD. Therefore, an increase of dietary omega-3 PUFA may be encouraged to be used clinically in patients with CKD.

Comprehensive investigation of pharmacodyamic material basis of Wikstroemia indica (L.) C. A. Mey. by serum pharmacochemistry and bivariate correlation analysis.

In this study, the theory of serum pharmacochemistry of traditional Chinese medicine was used to analyze the constituents absorbed into serum after oral administration of Wikstroemia indica (L.) C. A. Mey. by ultra high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The micro-liquid dilution method was used to determine the minimum inhibitory concentration of the serum containing Wikstroemia indica. The bivariate correlation analysis method was used to study the spectral-efficiency relationship between the drug-containing serum and the antibacterial activity, and find the main antibacterial active components in serum containing Wikstroemia indica. A total of 26 serum migration components were identified or speculated in the samples, including 11 prototype components and 15 metabolites. Of which, syringic acid, caffeic acid, dihydrocaffeic acid, 4-hydroxybenzoic acid, hippuric acid, 3-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propanoic acid, triumbelletin, (7R)-3-hydroxy-1-methyl-2-oxo-7-(prop-1-en-2-yl)-2,3,5,6,7,8- hexahydroazulene-4- carbaldehyde and (1S,3aS,8aS)-1,3,5-trihydroxy-1,4-dimethyl-7-(propan-2- ylidene) octahydroazulen-6(1H)-one were bacteriostatic active substances. It is the first time to study the constituents in serum containing Wikstroemia indica and reveal its antibacterial pharmacodyamic material basis. The above works provide scientific reference for the in-depth study of Wikstroemia indica.

[Research progress and analysis on mechanism of polysaccharides against type 2 diabetes mellitus].

Polysaccharides are macromolecular compounds formed by more than 10 monosaccharide molecules linked by glycosidic bonds. Polysaccharides have a wide range of sources, high safety and low toxicity, with a variety of biological activities, such as anti-tumor, anti-virus, immune regulation, lowering blood glucose, and lowering blood lipids. Type 2 diabetes mellitus(T2 DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance and low inflammation. In recent years, the treatment of T2 DM with polysaccharide has become a research hotspot. Polysaccharides can not only make up for the side effects such as hypoglycemia, weight gain, gastrointestinal injury caused by long-term treatment of acarbose, biguanidine and sulfonylurea, but also play an effective role in reducing glucose by regulating glucose metabolism, oxidative stress, inflammatory response, intestinal flora, etc. In this paper, the research progress of polysaccharides in the treatment of T2 DM was reviewed. In addition, the hot spots such as the hypoglycemic activity of polysaccharides with structural modifications were summarized, providing theoretical guidance for the development of active polysaccharide hypoglycemic medicines and the further study of action mechanism.

Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Post-last glacial maximum expansion of Y-chromosome haplogroup C2a-L1373 in northern Asia and its implications for the origin of Native Americans.

OBJECTIVES: Subbranches of Y-chromosome haplogroup C2a-L1373 are founding paternal lineages in northern Asia and Native American populations. Our objective was to investigate C2a-L1373 differentiation in northern Asia and its implications for Native American origins. MATERIALS AND METHODS: Sequences of rare subbranches (n = 43) and ancient individuals (n = 37) of C2a-L1373 (including P39 and MPB373), were used to construct phylogenetic trees with age estimation by BEAST software. RESULTS: C2a-L1373 expanded rapidly approximately 17.7,000-14.3,000 years ago (kya) after the last glacial maximum (LGM), generating numerous sublineages which became founding paternal lineages of modern northern Asian and Native American populations (C2a-P39 and C2a-MPB373). The divergence pattern supports possible initiation of differentiation in low latitude regions of northern Asia and northward diffusion after the LGM. There is a substantial gap between the divergence times of C2a-MPB373 (approximately 22.4 or 17.7 kya) and C2a-P39 (approximately 14.3 kya), indicating two possible migration waves. DISCUSSION: We discussed the decreasing time interval of "Beringian standstill" (2.5 ky or smaller) and its reduced significance. We also discussed the multiple possibilities for the peopling of the Americas: the "Long-term Beringian standstill model," the "Short-term Beringian standstill model," and the "Multiple waves of migration model." Our results support the argument from ancient DNA analyses that the direct ancestor group of Native Americans is an admixture of "Ancient Northern Siberians" and Paleolithic communities from the Amur region, which appeared during the post-LGM era, rather than ancient populations in greater Beringia, or an adjacent region, before the LGM.

Uniparental Genetic Analyses Reveal the Major Origin of Fujian Tanka from Ancient Indigenous Daic Populations.

The Fujian Tanka people are officially classified as a southern Han ethnic group, whereas they have customs similar to Daic and Austronesion people. Whether they originated in Han or Daic people, there is no consensus. Three hypotheses have been proposed to explain the origin of this group: (1) the Han Chinese origin, (2) the ancient Daic origin, (3) and the admixture between Daic and Han. This study addressed this issue by analyzing the paternal Y chromosome and maternal mtDNA variation of 62 Fujian Tanka and 25 neighboring Han in Fujian. The southern East Asian predominant haplogroups (e.g., Y-chromosome O1a1a-P203 and O1b1a1a-M95, and mtDNA F2a, M7c1, and F1a1) had relatively high frequencies in Tanka. The interpopulation comparison revealed that the Tanka have a closer affinity with Daic populations than with Han Chinese in paternal lineages but are closely clustered with southern Han populations such as Hakka and Chaoshanese in maternal lineages. Network and haplotype-sharing analyses also support the admixture hypothesis. The Fujian Tanka mainly originate from the ancient indigenous Daic people and have only limited gene flows from Han Chinese populations. Notably, the divergence time inferred by the Tanka-specific haplotypes indicates that the formation of Fujian Tanka was a least 1033.8-1050.6 years before present (the early Northern Song dynasty), indicating that they are an indigenous population, not late Daic migrants from southwestern China.

Exploring the additive bio-agent impacts upon ectoine production by Halomonas salina DSM5928T using corn steep liquor and soybean hydrolysate as nutrient supplement.

Ectoine production using inexpensive and renewable biomass resources has attracted great interest among the researchers due to the low yields of ectoine in current fermentation approaches that complicate the large-scale production of ectoine. In this study, ectoine was produced from corn steep liquor (CSL) and soybean hydrolysate (SH) in replacement to yeast extract as the nitrogen sources for the fermentation process. To enhance the bacterial growth and ectoine production, biotin was added to the Halomonas salina fermentation media. In addition, the effects addition of surfactants such as Tween 80 and saponin on the ectoine production were also investigated. Results showed that both the CSL and SH can be used as the nitrogen source substitutes in the fermentation media. Higher amount of ectoine (1781.9 mg L-1) was produced in shake flask culture with SH-containing media as compared to CSL-containing media. A total of 2537.0 mg L-1 of ectoine was produced at pH 7 when SH-containing media was applied in the 2 L batch fermentation. Moreover, highest amount of ectoine (1802.0 mg L-1) was recorded in the SH-containing shake flask culture with addition of 0.2 µm mL-1 biotin. This study demonstrated the efficacy of industrial waste as the nutrient supplement for the fermentation of ectoine production.

Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.

The ratio of H/C is a useful parameter to predict adsorption of the herbicide metolachlor to biochars.

Biochar adsorbent was produced by pyrolyzing traditional Chinese medicinal herb residue at 300, 500 and 750 °C (referred to as biochar-300, biochar-500 and biochar-750). Basic physical and chemical analyses, Fourier transform infrared spectroscopy (FT-IR), and thermodynamic analyses were performed to elucidate adsorption and properties of biochar. Biochar adsorption capacity of herbicide metolochlor, as measured by batch-type adsorption experiments by Freundlich constant Kf (mg1-n Ln kg-1), followed the order: biochar-750 > biochar-300 > biochar-500. Thermodynamic analysis suggested that adsorption of metolachlor on biochar was a spontaneous process. The adsorption isotherm for the biochar produced at the highest pyrolysis temperature was characteristic for adsorption process driven by a high surface area of biochar (85.30 m2 g-1), while the adsorption process for the biochar produced at the lowest temperature was controlled by its higher content of organic matter (39.06%) and abundant functional groups. The FT-IR spectra also showed that the biochar prepared at the lowest temperature had the highest number of surface groups. In general, pore-filling induced by the large surface area of the biochar was the dominant adsorption mechanism. When the H/C value was >0.5, the adsorption mechanism of biochar was dominated by surface chemical bond, while pore-filling played a major role when the H/C value was <0.5.

Herbal Textual Research and Modern Analysis of Pheretima / 中国实验方剂学杂志

Pheretima has a long history of medication, its original name was earthworm, and it was first recorded in Shennong Bencaojing, which was listed as inferior product. In the 2015 edition of Chinese Pharmacopoeia, two varieties of Pheretima were included. However, due to the variety of Pheretima, there are mixed non-pharmacopoeia collection of Pheretima family status. Based on the systematic review of ancient and modern literature, this paper conducts herbal textual research on Pheretima in terms of name, origin, distribution of origin, genuine production area, harvesting time, processing methods, etc. Based on the analysis of various ancient books and modern research documents of herbal medicine and their accompanying drawings, it is found that the Pheretima and white-necked Pheretima mentioned in ancient books are the general names of the genus Pheretima. The ancient people thought that white-necked Pheretima was a good medicinal material, which was the same as the opinion that Guangdilong was better in quality than Tudilong in modern research. In ancient and modern literature, the origin of earthworm is relatively consistent, but due to the change of environment, the output of wild Pheretima is reduced, and now the output of Pheretima is mainly artificial breeding. In ancient times, harvesting should be as far as possible in spring, summer and autumn. However, in modern times, the best harvest time is autumn. Different processing methods of earthworm in different ages and regions are different. Attention should be paid to following and inheriting the ancient processing methods, combining with modern research techniques, the quantitative standard of processing of Pheretima should be formulated, so that Pheretima medicinal materials can be applied comprehensively and effectively. This research provides the basis for the original source, resource development, correct use, genuine producing area and processing method determination of Pheretima.

Identification of curcumin content in raw and vinegar-processed rhizomes of Curcuma kwangsiensis based on electronic nose combined with back propagation neural network / 中国中药杂志

This study aimed to establish a rapid and accurate method for identification of raw and vinegar-processed rhizomes of Curcuma kwangsiensis, in order to predict the content of curcumin compounds for scientific evaluation. A complete set of bionics recognition mode was adopted. The digital odor signal of raw and vinegar-processed rhizomes of Curcuma kwangsiensis were obtained by e-nose, and analyzed by back propagation(BP) neural network algorithm, with the accuracy, the sensitivity and specificity in discriminant model, correlation coefficient as well as the mean square error in regression model as the evaluation indexes. The experimental results showed that the three indexes of the e-nose signal discrimination model established by the neural network algorithm were 100% in training set, correction set and prediction set, which were obviously better than the traditional decision tree, naive bayes, support vector machine, K nearest neighbor and boost classification, and could accurately differentiate the raw and vinegar products. Correlation coefficient and mean square error of the regression model in prediction set were 0.974 8 and 0.117 5 respectively, and could well predict curcumin compounds content in Curcuma kwangsiensis, and demonstrate the superiority of the simulation biometrics model in the analysis of traditional Chinese medicine. By BP neural network algorithm, e-nose odor fingerprint could quickly, conveniently and accurately realize the discrimination and regression, which suggested that more bionics information acquisition and identification patterns could be combined in the field of traditional Chinese medicine, so as to provide ideas and methods for the rapid evaluation and stan-dardization of the quality of traditional Chinese medicine.

[Chemical profiling from water extract of Wikstroemia indica by UPLC-Q-TOF-MS/MS].

In this study,a method using ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) was established to identify complicated chemical constituents of Wikstroemia indica. Chromatographic separation was performed on an AcclaimTMRSLC 120-C18 column( 2. 1 mm×100 mm,2. 2 µm) using gradient elution with 0. 2% ammonium formate buffer salt solution( A)-0. 2% ammonium formate buffer salt solution methanol( B) as mobile phase. The column temperature was maintained at 30 ℃. The analytes were determined by positive and negative ion modes with electro-spray ionization source. A total of 52 compounds( including eleven coumarins,thirteen flavonoids,ten lignans,two amides,four phenolic acids,six sesquiterpenes and six other compounds) were identified or tentatively characterized from the water extract of W. indica by comparing their retention times and MS spectra with those of authentic standards or literature datas. Three compounds were found for the first time from W.indica namely isomer of indicanone,ß-hydroxypropiovanillone and epiprocurcumenol. Furthermore,the fragmentation rules of some compounds were speculated and summarized. In addition,the cleavage pathways of guaiane sesquiterpenes were described for the first time,which can provide reference for studying the fragmentation pathways of similar compounds. This study provides an easy way to identify chemical constituents of traditional Chinese medicine and a basis for the further study on chemical fundamentals of W. indica.