Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Environmental characteristics in three seamount areas of the Tropical Western Pacific Ocean: Focusing on nutrients.

Nutrients distribution and influencing factors in three seamount areas named Y3, M2 and C4 of the Tropical Western Pacific Ocean (TWPO) were investigated. Nutrients showed obvious uplifts around the three seamounts, consistent with the uplifts of isotherms and isohalines, indicating the existence of a bottom-up process of nutrients. Meanwhile, compared with the stations away from seamount and the reference stations in the TWPO, nutrients concentrations around seamount were much higher. Among the three seamounts, the average nutrients concentrations were highest in Y3, while they were lowest in C4. Moreover, compared with the obvious nitrogen limitation in Y3 and M2, the N:P (13.5:1) and Si:N (6.1:1) were closed to the Redfield ratio. The current-seamount interaction was the determining influencing factor on nutrients distribution, causing the hydrology dynamic changes such as uplifts and Taylor column. Meanwhile, T and S also affected nutrients distribution, especially nutrients and T showed significant negative correlations.

Occurrence and origins of biomarker aliphatic hydrocarbons and their indications in surface sediments of the East China Sea.

The composition, distribution, indexes and budget of saturated lipid biomarker aliphatic hydrocarbons (AHs) in sediments of the East China Sea (ESC) were analyzed to identify their indications and sources. The resolved n-alkane (R) contents were 0.70-2.89 µg/g, with long-chain n-alkanes as the dominant composition in the ECS. The high R values mainly appeared at south inner shelf and north outer upwelling area, corresponding to the high mud, total organic carbon (TOC) and Chl a contents there. The composition, distribution pattern, combined with indexes of AHs, suggested no petroleum contamination and predominant biogenic sources in the ECS. The biogenic sources mainly were the mixed terrestrial higher plant, marine plankton and bacteria and aquatic macrophyte origins. Biotic source apportionment suggested that terrestrial higher plants were the dominant source of AHs, followed by marine planktons, with the lowest of submerged/floating macrophytes. Quantitative evaluation of R sources suggested that the Changjiang River input was the primary terrestrial contributor, accounting for 67.9% of total terrestrial input. The burial flux of R was 1.11 × 103 t/yr, with inner shelf and estuary as main accumulation areas. Although there was a huge amount of R influx from terrestrial and marine sources, only 9.8% could be preserved in sediments.

[Release and supplement of carbon, nitrogen and phosphorus from jellyfish (Nemopilema nomurai) decomposition in seawater].

Abstract: Jellyfish bloom has been increasing in Chinese seas and decomposition after jellyfish bloom has great influences on marine ecological environment. We conducted the incubation of Nemopilema nomurai decomposing to evaluate its effect on carbon, nitrogen and phosphorus recycling of water column by simulated experiments. The results showed that the processes of jellyfish decomposing represented a fast release of biogenic elements, and the release of carbon, nitrogen and phosphorus reached the maximum at the beginning of jellyfish decomposing. The release of biogenic elements from jellyfish decomposition was dominated by dissolved matter, which had a much higher level than particulate matter. The highest net release rates of dissolved organic carbon and particulate organic carbon reached (103.77 ± 12.60) and (1.52 ± 0.37) mg · kg⁻¹ · h⁻¹, respectively. The dissolved nitrogen was dominated by NH4⁺-N during the whole incubation time, accounting for 69.6%-91.6% of total dissolved nitrogen, whereas the dissolved phosphorus was dominated by dissolved organic phosphorus during the initial stage of decomposition, being 63.9%-86.7% of total dissolved phosphorus and dominated by PO4³â»-P during the late stage of decomposition, being 50.4%-60.2%. On the contrary, the particulate nitrogen was mainly in particulate organic nitrogen, accounting for (88.6 ± 6.9) % of total particulate nitrogen, whereas the particulate phosphorus was mainly in particulate. inorganic phosphorus, accounting for (73.9 ±10.5) % of total particulate phosphorus. In addition, jellyfish decomposition decreased the C/N and increased the N/P of water column. These indicated that jellyfish decomposition could result in relative high carbon and nitrogen loads.

Jellyfish (Cyanea nozakii) decomposition and its potential influence on marine environments studied via simulation experiments.

A growing body of evidence suggests that the jellyfish population in Chinese seas is increasing, and decomposition of jellyfish strongly influences the marine ecosystem. This study investigated the change in water quality during Cyanea nozakii decomposition using simulation experiments. The results demonstrated that the amount of dissolved nutrients released by jellyfish was greater than the amount of particulate nutrients. NH4(+) was predominant in the dissolved matter, whereas the particulate matter was dominated by organic nitrogen and inorganic phosphorus. The high N/P ratios demonstrated that jellyfish decomposition may result in high nitrogen loads. The inorganic nutrients released by C. nozakii decomposition were important for primary production. Jellyfish decomposition caused decreases in the pH and oxygen consumption associated with acidification and hypoxia or anoxia; however, sediments partially mitigated the changes in the pH and oxygen. These results imply that jellyfish decomposition can result in potentially detrimental effects on marine environments.

Environmental significance of biogenic elements in surface sediments of the Changjiang Estuary and its adjacent areas.

Biogenic elements and six phosphorus (P) fractions in surface sediments from the Changjiang Estuary and adjacent waters were determined to investigate the governing factors of these elements, and further to discuss their potential uses as paleo-environment proxies and risks of P release from sediment. Total organic carbon (TOC) and leachable organic P (Lea-OP) showed high concentrations in the estuary, Zhejiang coast and offshore upwelling area. They came from both the Changjiang River and marine biological input. Biogenic silicon (BSi) exhibited a high concentration band between 123 and 124 degree E. BSi mainly came from diatom production and its concentration in the inshore area was diluted by river sediment. Total nitrogen (TN) was primarily of marine biogenic origin. Seaward decreasing trends of Fe-bound P and Al-bound P revealed their terrestrial origins. Influenced by old Huanghe sediment delivered by the Jiangsu coastal current, the maximum concentration of detrital P (Det-P) was observed in the area north of the estuary. Similar high concentrations of carbonate fluorapatite (CFA-P) and CaCO3in the southern study area suggested marine calcium-organism sources of CFA-P. TOC, TN and non-apatite P were enriched in fine sediment, and Det-P partially exhibited coarse-grain enrichment, but BSi had no correlation with sediment grain size. Different sources and governing factors made biogenic elements and P species have distinct potential uses in indicating environmental conditions. Transferable P accounted for 14%-46% of total P. In an aerobic environment, there was low risk of P release from sediment, attributed to excess Fe oxides in sediments.

Petroleum hydrocarbons and their effects on fishery species in the Bohai Sea, North China.

Systematic studies on the changes in concentrations of petroleum hydrocarbons (PHs) and their effects on fishery species in the Bohai Sea during 1974-2004 are presented. Changes in PHs concentrations were closely related to Yellow River runoff. Concentrations of PHs accumulated in fish and shrimp increased by about 0.712 mg/kg dry weight when trophic level of fish and shrimps increased by 1. Attention should also be paid to the high PHs concentrations in mollusks along the coastal waters of the Bohai Sea. Average concentration of PHs in the adjacent coastal waters of Tianjin City during 1996-2005 decreased the population growth rates of fish, crustaceans and mollusks in the Bohai Sea by 2.58%, 6.59% and 2.33%, respectively. Therefore, PHs have significantly contributed to the decline in fisheries in the Bohai Sea, and they must be reduced to realize the sustainable fisheries.