Combined assessment of health hazard and odour impact of soils at a contaminated site: a case study on a defunct pharmaceuticals factory in China.

Surveys and assessments of contaminated sites primarily focus on hazardous pollutants in the soil with less attention paid to odorants. This makes the management of contaminated sites difficult. In this study, hazardous and odorous pollutants in the soil were assessed for a large site that was previously used for production of pharmaceuticals to determine the degree and characteristics of soil contamination at pharmaceutical production sites, for undertaking rational remediation measures. The main hazardous pollutants at the study site were triethylamine, n-butyric acid, benzo(a)pyrene (BaP), N-nitrosodimethylamine (NDMA), dibenzo(a,h)anthracene (DBA), total petroleum hydrocarbons (C10-C40) (TPH), and 1,2-dichloroethane; TEA, BA, and isovaleric acid (IC) were the main odorants. As the type and distribution of hazardous and odorous pollutants differ, it is necessary to separately assess the impact of these pollutants at a contaminated site. Soils in the surface layer pose significant non-carcinogenic (HI = 68.30) and carcinogenic risks (RT = 3.56E-5), whereas those in the lower layer only pose non-carcinogenic risks (HI > 7.43). Odorants were found at considerable concentrations both in the surface and lower layers, with the maximum concentrations being 29,309.91 and 41.27, respectively. The findings of this study should improve our understanding of soil contamination at former pharmaceutical production sites and should inform the assessment of the risks posed by contaminated sites, with problems associated with odour, and possible remediation strategies.

The complete chloroplast genome sequence of Urtica fissa.

Urtica fissa E. Pritz is not only an important medicinal plant for rheumatism and cough relief, but it is also an important forage plant. In this study, the complete chloroplast genome of U. fissa was assembled for the first time and reported to be 146,837 base pairs (bp) long with a typical tetragonal structure and including a large single-copy of 79,657 bp, a small single-copy of 17,712 bp, and two inverted repeats of 24,734 bp each. It harbors 115 unique genes, including 70 protein-coding genes, 38 transfer RNA genes, and 7 ribosomal RNA genes. Phylogenetic analysis showed that U. fissa is closely related to Urtica lobatifolia. This study contributes to the understanding of the origin and evolution of U. fissa, as well as its genetic relationships with other species.

Integrated Human and Murine Clinical Study Establishes Clinical Efficacy of Ruxolitinib in Chronic Myelomonocytic Leukemia.

PURPOSE: Chronic myelomonocytic leukemia (CMML) is a rare leukemia characterized by peripheral monocytosis with no disease-modifying therapies. CMML cells are uniquely hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) and robustly engraft in immunocompromised mice that secrete human cytokines. To leverage these unique biological features, we conducted an integrated human and murine study evaluating ruxolitinib, a JAK1/2 inhibitor that potently downregulates intracellular GM-CSF signaling. PATIENTS AND METHODS: A total of 50 patients with WHO-defined CMML were enrolled in this open-label, multi-institution phase I/II clinical study, with a ruxolitinib dose of 20 mg twice daily studied in phase II. In parallel, 49 patient-derived xenografts (PDX) derived from 13 study participants were generated and randomized to receive ruxolitinib or vehicle control. RESULTS: The most common grade 3/4 treatment-related toxicities observed were anemia (10%) and thrombocytopenia (6%). The clinical overall response rate was 38% by Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) International Working Group (IWG) criteria and 43% of patients with baseline splenomegaly achieved a spleen response. Profiling of cytokine levels and somatic mutations at baseline failed to identify predictive biomarkers. PDX models derived from screening samples of study participants recapitulated responses seen in humans, particularly spleen responses, and corroborated ruxolitinib's clinical efficacy in a randomized murine study not feasible in human trials. CONCLUSIONS: Ruxolitinib demonstrated clinical efficacy and an acceptable adverse event profile in patients with CMML, identifying a potential novel therapeutic in this rare malignancy. Furthermore, this study demonstrates proof of concept that PDX modeling can recapitulate responses of patients treated on clinical trial and represents a novel correlative study that corroborates clinical efficacy seen in humans.See related commentary by Shastri and Adrianzen-Herrera, p. 6069.

Effect of glycosylation with sugar beet pectin on the interfacial behaviour and emulsifying ability of coconut protein.

The aim of the present study was to investigate the effect of glycosylation with sugar beet pectin (SBP) on the interfacial behaviour and emulsifying ability of coconut protein (CP). The physical stabilities of the emulsions were predicted by transmission variation, droplet distribution and zeta potentials. The results showed that SBP-CP-stabilized emulsions showed better stability during centrifugation than those stabilized by CP because SBP-CP reduced the degree of variation in the CP transmission profile. The adsorption kinetics of all emulsifiers at the oil-water interface were determined to investigate the relationship between the interfacial behaviour and emulsion stability. The presence of SBP considerably reduced the adsorption rate of CP (0.698 mN/m/s1/2) and hampered the development of a highly viscoelastic network at the oil-water interface. The values of the dilatational elastic modulus (Ed = 19.477 mN/m) and dilatational viscous modulus (E = 19.719 mN/m) were approximately equal, indicating that the adsorption process was mainly dominated by elastic behaviour. Additionally, the SBP-CP interaction enhanced the dilatational property of the CP-absorbed layer.

[Observation on therapeutic effect of electroacpuncture combined with penetrating moxibustion for postpartum pelvic organ prolapse].

OBJECTIVE: To compare the clinical therapeutic effect of electroacupuncture (EA) combined with penetrating moxibustion and biofeedback electrical stimulation on postpartum pelvic organ prolapsed (POP). METHODS: A total of 60 patients with POP who had delivery 6 weeks ago were randomized into an observation group and a control group, 30 cases in each one. In the observation group, EA was applied at Zigong (EX-CA 1), Ciliao (BL 32), Huiyang (BL 35), etc. while penetrating moxibustion was performed at acupoints of abdomen and lumbosacral region alternately every other day. In the control group, biofeedback electrical stimulation was provided. The treatment for 6 weeks was given once every other day, 3 times a week in both groups. Before treatment, after treatment and 6 months after delivery, pelvic floor muscle strength, pelvic organ prolapse quantification (POP-Q) evaluation and pelvic floor impact questionnaire short form-7 (PFIQ-7) were observed to assess the therapeutic effect. RESULTS: Compared before treatment, the sustained contraction and rapid contraction force of pelvic floor muscle after treatment and 6 months after delivery were increased in both of the two groups (P<0.05), and the changes in the observation group were larger than those in the control group (P<0.05). After treatment and 6 months after delivery, the POP degree in the observation group was alleviated to the control group (P<0.05). Compared before treatment, the scores of PFIQ-7 after treatment and 6 months after delivery were reduced in the two groups (P<0.05), and the changes in the observation group were larger than those in the control group (P<0.05). CONCLUSION: Electroacupuncture combined with penetrating moxibustion can strengthen the pelvic floor muscle contractility of patients with postpartum pelvic organ prolapse, and are superior to biofeedback electrical stimulation in improving the pelvic organ prolapse status and life quality.

Preparation and properties of ferulic acid-sugar beet pulp pectin ester and its application as a physical and antioxidative stabilizer in a fish oil-water emulsion.

A ferulic acid-sugar beet pulp pectin complex (FA-SBPP) was prepared using an immobilized enzyme (Novozym 435®) as the catalyst at 60 °C in a vacuum-controlled system. The structure of FA-SBPP was characterized by FT-IR and NMR (1H and 13C). In addition, the antioxidant activity of FA-SBPP was evaluated according to the DPPH free radical scavenging ability and ORAC values. Moreover, the physical and oxidation stability of the emulsion was evaluated by particle size distribution, cream index (CI), peroxide value (POV), and 2-thiobarbituric acid reactive substance (TBARS) formation. The results showed that esterification between FA and SBPP was confirmed, and the reaction mainly occurred at the C-2, C-3, and C-6 positions. When the concentration was 1.0 mg/mL, the DPPH scavenging activity and total antioxidant activity of FA-SBPP-3 were 80.03% and 355.72 µmol TE/g, respectively. Compared with SBPP, FA-SBPP-stabilized emulsions exhibited significant smaller droplet sizes and lower CIs, POVs and TBARS amounts. Thus, the introduction of FA changed not only the chemical reactivity but also the polarity of SBPP, thereby improving its antioxidant ability and affinity for the oil-water interface. Thus, we provide a multifunctional stabilizer that can reduce the dose of antioxidants or even replace them in oil-in-water emulsions.

[Efficacy of electroacupuncture combined with penetrating moxibustion for postpartum stress urinary incontinence].

OBJECTIVE: To compare the clinical effect differences between electroacupuncture (EA) combined with penetrating moxibustion and the biological feedback training of pelvic floor muscle for postpartum stress urinary incontinence (SUI). METHODS: Sixty patients of SUI who had delivery 42 days ago were randomly divided into an observation group and a control group, 30 cases in each one. The observation group was treated with EA and penetrating moxibustion. EA was applied at Ciliao (BL 32) and Huiyang (BL 35), combined with acupuncture at Qihai (CV 6), Zhongji (CV 3), Zigong (EX-CA 1), Zusanli (ST 36) and Sanyinjiao (SP 6); penetrating moxibustion was performed on abdomen and lumbosacral area. The control group was treated with biological feedback training of pelvic floor muscle. Both the groups were treated once every other day, 3 times per week for continuous 6 weeks. The International Consultation on Incontinence Questionnaire-Short Form (ICI-Q-SF), 1 h urinal pad test and pelvic floor muscle strength were tested before and after treatment; the efficacy was evaluated after treatment and at 6-month follow-up visit. RESULTS: Compared before treatment, the ICI-Q-SF score and 1 h urine leakage were significantly reduced after treatment in the two groups (P<0.01), and the reduction in the observation group was superior to that in the control group (P<0.05). Compared before treatment, the pelvic muscle strength of muscle fibers Ⅰand Ⅱ were significantly increased after treatment in the two groups (P<0.01), and the differences between the two groups had no statistical significance (P>0.05). After treatment, the cured rate and total effective rate were 70.0% (21/30) and 96.7% (29/30) in the observation group, which were superior to 33.3% (10/30) and 70.0% (21/30) in the control group (P<0.01); in the 6-month postpartum period, the cured rate and total effective rate were 63.3% (19/30) and 93.3% (28/30) in the observation group, which were superior to 30.0% (9/30) and 66.7% (20/30) in the control group (P<0.05). CONCLUSION: EA combined with penetrating moxibustion could improve the urinary control ability, relieve the symptoms of urinary incontinence and have a better long-term effect in patients with postpartum SUI, which is superior to biological feedback training of pelvic floor muscle.

Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway.

BACKGROUND: Several studies have recently found that oxidative stress plays a pivotal role in the pathogenesis of traumatic brain injury (TBI) and may represent a target in TBI treatment. Hydrogen-rich water was recently shown to exert neuroprotective effects in various neurological diseases through its antioxidant properties. However, the mechanisms underlying its effects in TBI are not clearly understood. The purpose of our study was to evaluate the neuroprotective role of hydrogen-rich water in rats with TBI and to elucidate the possible mechanisms underlying its effects. MATERIALS AND METHODS: The TBI model was constructed according to the modified Feeney weight-drop method. In part 1 of the experiment, we measured oxidative stress levels by observing the changes in catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) expressions. We also evaluated nuclear factor erythroid 2-related factor 2 (Nrf2) levels to determine the role of the protein in the neuroprotective effects against TBI. In part 2, we verified the neuroprotective effects of hydrogen-rich water in TBI and observed its effects on Nrf2. All the experimental rats were divided into sham group, TBI group, and TBI + hydrogen-rich water-treated (TBI + HW) group. We randomly chose 20 rats from each group and recorded their 7-d survival rates. Modified neurological severity scores were recorded from an additional six rats per group, which were then sacrificed 24 h after testing. Spectrophotometry was used to measure GPx, CAT, and MDA levels, whereas western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry were used to measure the expression of Nrf2 and downstream factors like heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). RESULTS: GPx and CAT activity was significantly decreased, and MDA content was increased in the TBI group compared with the sham group at 6 h after TBI. MDA content peaked at 24 h after TBI. Nrf2 nucleoprotein levels were upregulated in the TBI group compared with the sham group and peaked at 24 h after TBI; however, no significant changes in Nrf2 mRNA levels were noted after TBI. Hydrogen-rich water administration significantly increased 7-d survival rates, reduced neurologic deficits, and lowered intracellular oxidative stress levels. Moreover, hydrogen-rich water caused Nrf2 to enter the cell nucleus, which resulted in increases in the expression of downstream factors such as HO-1 and NQO1. CONCLUSIONS: Our results indicate that hydrogen-rich water has neuroprotective effects against TBI by reducing oxidative stress and activating the Nrf2 pathway.

Calcium effect on the metabolic pathway of phosphorus accumulating organisms in enhanced biological phosphorus removal systems.

Phosphorus accumulating organisms (PAOs) have been found to act as glycogen-accumulating organisms (GAOs) under certain conditions, thus, the deterioration in the performance of enhanced biological phosphorus removal systems is not always attributed to the proliferation of GAOs. In this work, the effects of calcium on the metabolic pathway of PAOs were explored. It was found that when the influent Ca(2+) concentration was elevated, the tendency and extent of extracellular calcium phosphate precipitation increased, and the intracellular inert Ca-bound polyphosphate was synthesized, while the microbial population remained almost unchanged. The changes in the ratios of phosphorus released/acetate uptaken, the glycogen degraded/acetate uptaken and the poly-ß-hydroxyalkanoates synthesized/acetate uptaken during the anaerobic period confirm that, as the influent Ca(2+) concentration was increased, the polyphosphate-accumulating metabolism was partially shifted to the glycogen-accumulating metabolism. At an influent Ca(2+) around 50 mg/L, in addition to the extracellular calcium phosphate precipitation, the intracellular inert Ca-bound polyphosphate synthesis might also be involved in the metabolic change of PAOs. The results of the present work would be beneficial to better understand the biochemical metabolism of PAOs in enhanced biological phosphorus removal systems.

Roles of extracellular polymeric substances in enhanced biological phosphorus removal process.

Enhanced biological phosphorus removal (EBPR) process is known to mainly rely on the ability of phosphorus-accumulating organisms to take up, transform and store excess amount of phosphorus (P) inside the cells. However, recent studies have revealed considerable accumulation of P also in the extracellular polymeric substances (EPS) of sludge, implying a non-negligible role of EPS in P removal by EBPR sludge. However, the contribution of EPS to P uptake and the forms of accumulated extracellular P vary substantially in different studies, and the underlying mechanism of P transformation and transportation in EPS remains poorly understood. This review provides a new recognition into the P removal process in EBPR system by incorporating the role of EPS. It overviews on the characteristics of P accumulation in EPS, explores the mechanism of P transformation and transportation in EBPR sludge and EPS, summarizes the main influential factors for the P-accumulation properties of EPS, and discusses the remaining knowledge gaps and needed future efforts that may lead to better understanding and use of such an EPS role for maximizing P recovery from wastewater.

[Effect of retinociacdi combined extracts from testudinis carapacis et plastri on proliferating in MSCs and its mechanism].

OBJECTIVE: To explore the effect of retinociacdi (RA) combined extracts from Testudinis Carapacis et Plastri(PTE) on proliferating in MSCs and its mechanism. METHODS: Transfected PGL3-ID1 using the calcium phosphate co-precipitation method in rat MSCs. PTE combined with RA and retinociacdi receptor inhibitor(Ro41) acted on transfected MSCs with respective concentrations of 10(-6), 10(-7) and 10(-8) mol/L. Luciferase activity measurement was used to detect the activity of RAR and IDI 36 h later. PTE acted on MSCs 36 h,3 d and 7 d for respective concentrations of 1, 3, 30 and 100 microg/mL,then collected cells to detect RAR with RT-PCR. PTE combined with RA for 10(-7) mol/L and Ro41 for 10(-6) mol/L respectively on MSCs for 36 h,and then collected cells to detect RAR and ID1 with RT-PCR. RESULTS: PTE promoted expression of ID1 on MSCs. When combined with RA, the promotion effect became greater and it promoted expression of RAR at the same time; When inhibited RA using Ro41, the promotion of IDI was weaken by PTE. CONCLUSION: RA promotes expression of IDI on MSCs, PTE regulates proliferation and differentiation of MSCs by expression of nuclear receptor RAR.

Sulfated modification can enhance antiglycation abilities of polysaccharides from Dendrobium huoshanense.

Dendrobium huoshanense is an important edible-medicinal plant with high nutritional values and health functions. A homogenous polysaccharide (DHPD1) with molecular weight of 3.2 × 10(3)Da was extracted from D. huoshanense, which was mainly composed of glucose, arabinose, galactose, mannose and xylose. Chlorosulfonic acid-pyridine (CSA-Pyr) method was performed to modify the structure of DHPD1. In order to get a high degree of substitution (DS), sulfated modification conditions were optimized by response surface methodology. The maximum DS of 1.473 was obtained when the reaction condition was fixed at reaction temperature 60°C, reaction time 160 min and volume ratio of Pyr to CSA 2:1. NMR spectra revealed that this sulfation occurred to C-2 and C-6 of glycosyl residues in DHPD1. After 28 days of incubation, the sulfated DHPD1 at 1.0mg/mL showed the inhibitory ability of 58.5%, which increased by 16.2% and 52.5% than that of aminoguanidine and DHPD1 at the same dosage.

Phosphorus removal in an enhanced biological phosphorus removal process: roles of extracellular polymeric substances.

Phosphorus-accumulating organisms are considered to be the key microorganisms in the enhanced biological phosphorus removal (EBPR) process. A large amount of phosphorus is found in the extracellular polymeric substances (EPS) matrix of these microorganisms. However, the roles of EPS in phosphorus removal have not been fully understood. In this study, the phosphorus in the EBPR sludge was fractionated and further analyzed using quantitative (31)P nuclear magnetic resonance spectroscopy. The amounts and forms of phosphorus in EPS as well as their changes in an anaerobic-aerobic process were also investigated. EPS could act as a reservoir for phosphorus in the anaerobic-aerobic process. About 5-9% of phosphorus in sludge was reserved in the EPS at the end of the aerobic phase and might further contribute to the phosphorus removal. The chain length of the intracellular long-chain polyphosphate (polyP) decreased in the anaerobic phase and then recovered under aerobic conditions. However, the polyP in the EPS had a much shorter chain length than the intracellular polyP in the whole cycle. The migration and transformation of various forms of phosphorus among microbial cells, EPS, and bulk liquid were also explored. On the basis of these results, a model with a consideration of the roles of EPS was proposed, which is beneficial to elucidate the mechanism of phosphorus removal in the EBPR system.

Species of phosphorus in the extracellular polymeric substances of EBPR sludge.

In this study, the species of extracellular phosphorus and their transformation during extracellular polymeric substances (EPS) extraction were explored by using (31)P nuclear magnetic resonance spectroscopy. Results show that the extraction methods had a substantial influence on the phosphorus species in the extracted EPS. Cation exchange resin method was more appropriate for extracting EPS from the enhanced biological phosphorus removal (EBPR) sludge. Orthophosphate, pyrophosphate and polyphosphate were the main species of phosphorus found to be present in the EPS, which together accounted for about 6.6-10.5% of the total phosphorus in the EBPR sludge. The high percentage of extracellular phosphorus and their diverse species might reveal a new insight into the characteristics of the phosphorus in EPS in EBPR system.

(+)-Cholesten-3-one induces differentiation of neural stem cells into dopaminergic neurons through BMP signaling.

To identify small molecules that induce dopaminergic neurons from neural stem cells (NSCs) is promising for therapy of Parkinson's disease. Here we report the results of analyzing structurally related steroids in traditional Chinese medicine to identify agents that enhance dopaminergic differentiation of NSCs. Using P19 cells transfected by tyrosine hydroxylase (TH) promoter reporter construct, (+)-Cholesten-3-one with carbonyl, but not cholesterol and cholesterol myristate can effectively promote the activity of TH promoter. This effect depends on bone morphogenetic protein (BMP) signaling. Phenotypic cellular analysis indicated that (+)-Cholesten-3-one induces differentiation of NSCs to dopaminergic neurons with increased expression of specific dopaminergic markers including TH, dopamine transporter, dopa decarboxylase and higher level of dopamine secretion. (+)-Cholesten-3-one significantly increases the expression of BMPR IB, but not BMPR IA or BMPR II; p-Smad1/5/8 positive nuclei and expression of p-Smad1/5/8 were detected in NSCs treated with (+)-Cholesten-3-one, indicating that (+)-Cholesten-3-one may activate the BMP signaling. Moreover, overexpression of BMP4 or inhibition of BMP affects the effect of (+)-Cholesten-3-one on the dopaminergic phenotype. These findings may contribute to efficient production of dopaminergic neurons from NSCs culture for many applications and raise interesting questions about the role of (+)-Cholesten-3-one in neurogenesis.

Autocrine BMP4 signaling involves effect of cholesterol myristate on proliferation of mesenchymal stem cells.

We recently identified that cholesterol myristate in traditional Chinese medicine (TCM) is the active compound that increases proliferation of mesenchymal stem cell (MSCs). The present study is further to determine what signal pathway involves in effect of cholesterol myristate. Reverse transcription-PCR, Western blot and ELISA analysis show that cholesterol myristate increases the release of bone morphogenetic protein 4 (BMP4) from MSCs and the expression in the intracellular levels of BMP4 in a time- and dose dependent manner. However, structurally related steroids such as cholesterol and cholesten presented in TCM, both lack of the myristate, did not affect the secretion and expression of BMP4 on MSCs. These finds suggest that myristate is essential for the effects of cholesterol myristate. Furthermore, cholesterol myristate significantly increase BMPRIB levels of MSCs and the number of BMPRIB positive cells in a time- and dose dependent manner, but not BMPR IA or BMPR II. Our results indicate that action of cholesterol myristate may activate the BMP4-BMPRIB autocrine. Moreover, a blocking antibody against BMP4 or the BMP4 antagonist, noggin, partially reduced the effects of cholesterol myristate on MSCs proliferation. Thus, this study is to provide evidence that autocrine BMP4 signaling involves effect of cholesterol myristate on MSCs proliferation.

[Studies on chemical constituents of Uvaria macrophylia].

AIM: To study the chemical constituents from Uvaria macrophylla Roxb. (Annonaceae). METHODS: Various chromatography techniques were used to separate and purify the constituents. Their structures were elucidated by UV, IR, MS, 1HNMR, 13CNMR, 1H-1H COSY, HMQC and HMBC spectral analysis. RESULTS: Seven compounds have been isolated from the CHCl3 extract of the roots of the U. macrophylla. They were identified as macrophyllin (1), onysilin (2), taraxerol (3), 3,5-dimethoxy benzyl benzoic acid ester (4), benzoic acid (5), beta-sitosterol (6) and daucosterol (7). CONCLUSION: Compound 1 is a new compound. Compounds 2-7 were obtained from this plant for the first time.