Revealing the hidden burden for lake management: the sediment phosphorus storage pools in Eastern Plain Lake Zone, China.

As one of the essential components in ecosystems, lakes play a major role in the global phosphorus (P) cycle. It is helpful for further understanding of the inside lake P geochemical cycle to research P pollution and storage in lakes, which is of positive significance for lake eutrophication restoration. In this study, we investigated the total phosphorus concentrations (TPC) of water and sediments from 37 lakes in the Eastern Plain Lake Zone (EPL) of China, evaluated the P pollution degree of lakes, and estimated P storage in lake sediments with quantitative data of lake area and number. The results indicate that the total phosphorus concentrations of water (TPCW) and total phosphorus concentrations of the surface sediments (0-1 cm, TPCSS) in EPL were high, the mean values were 0.11 mg·L-1 and 869.85 mg·kg-1 respectively, with obvious differences between urban and rural areas, as well as between different river basins. Over half (56.76% and 70.27% respectively) of the lakes reached severe pollution levels in water and surface sediments. There were 16224 lakes (> 0.01 km2) with a total area of 21662.37 km2 in the EPL, and the P storage in the lake sediments (0-30 cm) was about 4.87 ± 2.08 Tg (1 Tg = 1 × 1012 g), accounting for about 2.74% of the basin soil. TPCW and TPCSS of lakes in the EPL were significantly positively correlated, may suggest a close nutrient cycling relationship between the lake water and the sediment. During periods of high winds and waves, the stored P in the top sediments in the EPL may continue to participate in the internal P geochemical cycle and migrate to the overlying water, posing a potential pollution hazard. Therefore, it is crucial to take into account the sediment P pools when formulating effective lake phosphorus management strategies.

Effect of tandem repeats of antimicrobial peptide CC34 on production of target proteins and activity of Pichia pastoris.

Antimicrobial peptides (AMPs) are attracting attention in the fields of medicine, food, and agriculture because of their broad-spectrum antibacterial properties, low resistance, and low-residue in the body. However, the low yield and instability of the prepared AMP drugs limit their application. In this study, we designed a tetramer of the AMP CC34, constructed and transfected two recombinant expression vectors with pGAPZαA containing a haploid CC34 and tetraploid CC34 (CC34-4js) into Pichia pastoris to explore the effect of biosynthesized peptides. The results showed that CC34 and CC34-4js expression levels were 648.2 and 1105.3 mg/L, respectively, in the fermentation supernatant of P. pastoris. The CC34-4js tetramer showed no antibacterial activity, could be cleaved to the monomer using formic acid, and the hemolytic rate of the polyploid was slightly lower than that of monomeric CC34. The average daily gain, average daily feed intake, feed conversion ratio and immune organ index of rats fed CC34 and CC34-4js showed no differences. In conclusion, CC34-4js exhibited a higher yield and lower hemolysis in P. pastoris than those of CC34. Finally, CC34 and CC34-4js enterokinase lysates showed similar antibacterial activity and both expressed peptides potentially improved the growth performance and organ indices of rats.

In situ and in vitro evaluation of the bioavailability of rumen-protected methionine with coating prototypes.

Rumen protected amino acids are supplements that can enhance ruminal performance, yet the coating designed to protect the amino acids might also lead to different effects. Methionine is an essential methyl donor to synthesize protein, and little data exists on the effects of coating materials on its bioavailability. The purpose of this study was to estimate the effect of rumen-protected methionine (RPM) coatings with different ratios of acrylic resin IV (AR), ethyl cellulose (EC), and a mixture of AR and EC (AREC). Fifteen RPMs were prepared according to a single factor design, with 5 proportions each of AR, EC, and AREC to DL-methionine (DL-Met). Twelve hybrid small-tailed Han sheep with rumen fistula were utilized to evaluate in situ escape of RPMs, followed by in vitro abomasum-intestinal release of the RPMs. The results showed a regular variation in both ruminal disappearance and gastrointestinal release of RPMs with different coating prototypes and retention time. The RPMs that were EC and AREC coated presented high bioavailability compared to those with AR. Bioavailability of RPMs was optimal with the 2:20 AREC: DL-Met ratio, when the proportion of AR:EC is 1:1. Additionally, RPMs with a 1:3 ratio of AR:EC confirmed the optimum effect for the RPM of 2:20 AREC: DL-Met. In conclusion, an RPM with a lower AREC ratio coating can achieve better bioavailability and is synergistic to those with EC and AR.

[Sedimentary Diatom Records Reveal the Succession of Ecosystem in Lake Xihu, Dali over the Past 50 Years].

In recent decades, intense human activities have caused a decline in many lake ecosystems in Yunnan Province, rendering the transformation of the lake from a clear macrophyte-dominated state to a turbid phytoplankton-dominated state. Improved understanding of the ecological changes in lake ecosystem has significant implications for management. In this study, a small lake in Dali Prefecture of Yunnan Province, i.e., Lake Xihu, was selected. Combined with diatom records and physicochemical proxies from the lake sediments, this paper focuses on the long-term ecological changes in Lake Xihu, Dali since the mid-1960s. The results show that the Lake Xihu, Dali has undergone a significant shift in stable states over the past 50 years. Prior to 2000, the benthic-epiphytic species (i.e., Cocconeis placentula, Staurosira construens, Gomphonema angustum, and Achnanthidium minutissimum) dominated in diatom assemblages, indicating oligotrophic conditions; since 2000, benthic-epiphytic species (i.e., Encyonopsis microcephala and Navicula cryptocephala) and planktonic species (i.e., Cyclotella atomus, Cyclotella meneghiniana, Stephanodiscus hantzschii, and Aulacoseira granulata) dominated successively, indicating mesotrophic to eutrophic conditions. Principal component analysis based on the diatom assemblages in temporal scale showed the response of diatoms succession to nutrients. Redundancy analysis also confirmed that nutrient enrichment was the main driving force for the succession of diatom assemblages in Lake Xihu, Dali. In the past 50 years, climate change and human activities (i.e., agricultural reclamation, fertilization, animal husbandry, and fishery) have enhanced the accumulation of nutrients in the lake. The continuous loading of nutrients promoted the propagation of planktonic algae, and also the productivity of the lake, rendering the transformation to a turbid phytoplankton-dominated state.

Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is an acute and serious diabetic complication characterized by renal hypertrophy and renal fibrosis with the expansion of extracellular matrices. Diabetic nephropathy has become a major cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound prescription which has been widely applied in clinical medicine for the prevention and treatment of diabetic nephropathy as well as for acute and chronic kidney injuries. However, the mechanism of protective effects of SZGB in DN remains unclear. MATERIALS AND METHODS: In this research, we investigated the effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by performing a right uninephrectomy along with a single intraperitoneal injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D, SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage for 12 weeks. Samples from urine, blood and kidneys were collected for biochemical, histological, immunohistochemical and western blot analyses. RESULTS: We found that rats treated with SZGB showed reduced 24-h urinary protein excretion along with reduced serum total cholesterol (TC) and triglyceride (TG) levels. SZGB was also shown to prevent the disruption of catalase activity and reduce serum urea, creatinine, and renal malondialdehyde while increasing glutathione levels. Moreover, SZGB administration markedly improved the expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased the expression levels of Vimentin, α-SMA and Cleaved caspase-3 in the kidneys of diabetic rats. The renoprotective effects of SZGB was believed to be mediated by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. CONCLUSIONS: Therefore, it is suggested that SZGB can restrain epithelial-mesenchymal transition (EMT) through stimulating the Nrf2 pathway, which improves renal interstitial fibrosis in DN.

Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h-1) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch-1) seeds (P < 0.05), presumably explaining viability loss during fast cooling when temperature approaches -20 °C. Total soluble sugars increase in low temperature environment, but did not differ significantly between two cooling rates (P > 0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

Serum pharmacochemistry for tracking bioactive components by UPLC-Q-TOF-MS/MS combined chromatographic fingerprint for quality assessment of Sanziguben Granule.

To more reasonably and effectively control the quality of Sanziguben Granule, chromatographic fingerprinting and serum pharmacochemistry of this traditional Chinese medicine compound were performed. A comprehensive comparison and evaluation of 15 batches of Sanziguben Granule was successfully conducted by using high performance liquid chromatography (HPLC) fingerprint analysis. After administering a set amount of Sanziguben Granule orally to rats, blood samples were collected and tested 4 times at intervals of 30min, 1h, 2h, and 4h using UPLC-Q-TOF-MS/MS. The blood showed presence of gallic acid and corilagin indicating the pharmacological significance of these two chemical compounds. According to the result, above mentional chemical compounds were designated biomarkers for quality control of Sanziguben Granule. Therefore, a purposeful and efficient method for quality control of Sanziguben Granule was established in the present study.

Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada.

BACKGROUND: To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective. METHODS: A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings. CONCLUSION: Based on the willingness-to-pay threshold for end-of-life cancer drugs, ceritinib may be considered as a cost-effective option compared with other alternatives in patients who have progressed or are intolerant to crizotinib in Canada.

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime.

Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting from its long-term usage has hampered its prolonged therapeutic usage. Schisandra chinensis extracts (SCE) have previously been used in traditional Chinese medicine and more recently coadministered with Western medicine for the treatment of CsA-induced side effects in the People's Republic of China. This study aimed to investigate the possible effects of SCE on the pharmacokinetics of CsA in rats and elucidate the potential mechanisms by which it hinders the development of CsA-induced nephrotoxicity. A liquid chromatography/tandem mass spectrometry method was developed and validated for determining the effect of SCE on the pharmacokinetics of CsA. Male Sprague Dawley rats, which were administered with CsA (25 mg/kg/d) alone or in combination with SCE (54 mg/kg/d and 108 mg/kg/d) for 28 days, were used to evaluate the nephroprotective effects of SCE. Our study showed that SCE increased the mean blood concentration of CsA. Furthermore, we found that the concomitant administration of SCE alongside CsA prevented the disruption of catalase activity and reduction in creatinine, urea, renal malondialdehyde, and glutathione peroxidase levels that would have otherwise occurred in the absence of SCE administration. SCE treatment markedly suppressed the expression of 4-hydroxynonenal, Bcl-2-associated X protein, cleaved caspase 3, and autophagy-related protein LC3 A/B. On the other hand, the expression of heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf2), and P-glycoprotein was enhanced by the very same addition of SCE. SCE was also able to increase the systemic exposure of CsA in rats. The renoprotective effects of SCE were thought to be mediated by its antiapoptotic and antioxidant abilities, which caused the attenuation of CsA-induced autophagic cell death. All in all, these findings suggest the prospective use of SCE as an effective adjunct in a CsA-based immunosuppressive regimen.

An LC/MS quantitative and microdialysis method for cyclovirobuxine D pharmacokinetics in rat plasma and brain: The pharmacokinetic comparison of three different drug delivery routes.

To explore the brain-targeting of cyclovirobuxine D(CVB-D) after administered intranasally, the pharmacokinetics of CVB-D via three different drug delivery routes: intragastric (i.g.), intranasal (i.n.), and intravenous (i.v.) in rat brain and blood was compared. Firstly, an in vivo microdialysis method for sampling CVB-D in both plasma and brain of the rat was established. Secondly, a liquid chromatography-tandem mass spectrometry method has been developed and validated for determination of CVB-D in microdialysis samples. For plasma and brain microdialysis samples, liquid-liquid extraction was used and donepezil was chosen as internal standard. Both were followed by HPLC separation and positive electrospray ionization tandem mass spectrometry detection (ESI-MS/MS). Chromatographic separation was achieved on a agilent C18 column with a mobile phase of methanol-water (50:50, v/v) (pH 3.2) containing 0.1% formic acid and 5mM ammonium acetate. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (MRM) of the transitions at m/z 403.4→372.3 for CVB-D and m/z 380.2→243.1 for donepezil (IS). Good linearities were obtained in the range of 10-4000ng/mL in rat microdialysates for CVB-D. The lowest limit of quantitation was 5ng/mL, with an extraction recovery >75%, and no significant matrix effects. Intra- and inter-day precisions were all <15% with accuracies of 97.26-116.20%. All of which proved that the established method was successfully applied to the pharmacokinetic study of CVB-D. Simultaneously, brain uptake and pharmacokinetic studies were performed by determination of CVB-D concentration in blood and brain respectively for CVB-D i.g., i.n. and i.v.. Results showed that the intranasal CVB-D could improve brain targeting and had advantages for direct nose to brain transport of CVB-D when compared with injection and oral delivery routes, which indicates that intranasal administration of CVB-D could be a promising approach for the treatment of cerebrovascular disease.