Three stages in the variation of the depth of hypoxia in the California Current System 2003-2020 by satellite estimation.

The depth of hypoxia (DOH) is the shallowest depth at which the waters become hypoxic (oxygen concentration < 60 µmol kg-1), is a crucial indicator of the formation and expansion of oxygen minimum zones (OMZs). In this study, a nonlinear polynomial regression inversion model was developed to estimate the DOH in the California Current System (CCS), based on the dissolved oxygen profile detected by the Biogeochemical-Argo (BGC-Argo) float and remote sensing data. Satellite-derived net community production was used in the algorithm development, to denote the combined effect of phytoplankton photosynthesis and O2 consumption. Our model performs well, with a coefficient of determination of 0.82 and a root mean square error of 37.69 m (n = 80) from November 2012 to August 2016. Then, it was used to reconstruct the variation in satellite-derived DOH in the CCS from 2003 to 2020, and three stages of the DOH variation trend were identified. From 2003 to 2013, the DOH showed a significant shallowing trend due to the intense subsurface O2 consumption caused by strong phytoplankton production in the CCS coastal region. The trend was interrupted by two successive strong climate oscillation events from 2014 to 2016, which led to a significant deepening of the DOH and a slowing, or even reversal, of the variations in other environmental parameters. After 2017, the effects of climate oscillation events gradually disappeared, and the shallowing pattern in the DOH recovered slightly. However, by 2020, the DOH had not returned to the pre-2014 shallowing characteristic, which would lead to continuing complex ecosystem responses in the context of global warming. Based on the satellite inversion model of DOH in the CCS, we provide a new insight on the high-resolution spatiotemporal OMZ variations during an 18-year period in the CCS, which will aid in the evaluation and prediction of local ecosystems variation.

Hydrophobically Modified Cellulose Nanofibers-Enveloped Solid Lipid Microparticles for Improved Antioxidant Cargo Retention.

This study introduces a cellulose nanofiber surfactant system, in which the surface is hydrophobically modified with different alkyl chain structures for the effective envelopment of solid lipid microparticles (SLMs). To endow bacterial cellulose nanofibers (BCNFs) with excellent ability to assemble at the lipid-water interface, alkyl chains with designated molecular structures, such as decane, didecane, and eicosane, are covalently grafted onto the BCNF surface. Interfacial tension and interfacial rheology measurements indicate that dialkyl chain-grafted BCNFs (diC10 BCNF) exhibit strong interfibrillar association at the interface. The formation of a dense and tough fibrillary membrane contributes significantly to the enveloping of the SLMs, regardless of the lipid type. Because the diC10 BCNF-enveloped SLMs exhibit a core molecular crystalline phase at the microscale, they can immobilize an oil-soluble antioxidant while maintaining its long-term storage stability. These findings show that the cellulose-surfactant-based SLM technology is applicable to the stabilization and formulation of readily denatured active ingredients.

Microfluidic macroemulsion stabilization through in situ interfacial coacervation of associative nanoplatelets and polyelectrolytes.

HYPOTHESIS: Since macroemulsions tend to break down to lower free energy, they hardly retain their initial drop state. Therefore, studies are being conducted to overcome this based on advanced interface engineering techniques, but it is still challenging. Herein we hypothesize that the stability of giant droplets can be secured without chemical bonding through the interfacial coacervation of polyelectrolyte and associative nanoplatelets. EXPERIMENTS: We synthesized associative silica nanoplates (ASNPs) via polypeptide-templated silicification and consecutive wettability adjustment. To produce monodisperse macrodroplets, the inner fluid containing partially positively charged ASNPs and the outer fluid dissolving negatively charged polyacrylic acid (PAA) were coflowed through a capillary-based microfluidic channel. FINDINGS: Dynamic interfacial tension and interfacial rheology measurements revealed that the migration of ASNPs and PAA from each phase to the interface led to the formation of a complex bilayered thin membrane with an enhanced interfacial modulus. In addition, we demonstrated that adjusting the surface properties of ASNPs by coupling a fluorochemical enabled the production of monodisperse fluorocarbon-in-oil-in-water double macroemulsions. These results highlighted the applicability of our microfluidics-based interfacial coacervation technology in the development of complex fluid products with visual differentiation and drug encapsulation.

Biomarkers for early diagnosis of type 2 diabetic nephropathy: a study based on an integrated biomarker system.

Diabetic nephropathy is a devastating disease that affects a growing number of diabetic patients. A complete cure is very hard to achieve once the disease has been diagnosed, therefore the diagnosis of early stages in diabetic nephropathy has become a hot area. Numbers of molecules have been proposed to be potential biomarkers for this purpose. However, some problems still remain, such as discovering effective biomarkers to diagnose the disease before obvious clinical evidence appears. Thus, the main purpose of this study was to find plasma biomarkers for early diagnosis of type 2 diabetic nephropathy stage 1 and stage 2, as well as separating them from diabetes. 182 subjects (Chinese) were recruited for this study, including 50 healthy controls, 33 type 2 diabetic patients and 99 type 2 diabetic nephropathy patients (33 of these were stage 3). Important clinical indicators including proteinuria, serum creatinine, and urea nitrogen were measured and the glomerular filtration rate was estimated to assess kidney function; fasting blood glucose, postprandial blood glucose and glycated hemoglobin were measured to assess the blood glucose control. Key metabolites and genes in plasma samples were identified and determined using -omic and quantitative techniques. The potential biomarkers were then combined and carefully screened to determine the most informative ones for early diagnosis of type 2 diabetic nephropathy. An integrated biomarker system (IBS) incorporating 6 clinical indicators, 40 metabolites and 5 genes was established. Correlation analysis results revealed that most of the potential biomarkers significantly correlated with the 6 clinical indicators. Discriminant analysis results showed that the developed IBS gave the highest total predictive accuracy (98.9%). Significant test and receiver operating characteristic analysis results indicated that inosine had the highest sensitivity (0.889), specificity (1.000), positive predictive rate (1.000) and negative predictive rate (0.900) amongst the 48 potential biomarkers when separating patients with diabetes from patients with diabetic nephropathy stage 3. Finally, inosine with a cutoff of 0.086 mg L(-1) was combined with estimated GFR to differentiate between diabetic nephropathy stages 1 and 2 from diabetes. The results demonstrate that IBS combined with a proper statistical analysis technique is a powerful tool for biomarker screening.

A metabonomic approach to the effect evaluation of treatment in patients infected with influenza A (H1N1).

UNLABELLED: The pandemic influenza A virus (H1N1) was transmitted to the human population since 2009, resulting in some consequences of viral pneumonia, respiratory failure, multiple organ failure and, most severely, death. In clinical practice, Chinese medicine possessed extensive experience for prevention and treatment of influenza, but its mechanism still remain unclear. In addition, the efficacy of combination therapy of Chinese and Western medicine was attractive, but not yet clear. In the present study, 131 patients from Guangzhou China referred for H1N1 virus mRNA testing for the evaluation of possible influenza A-infected were eligible for participation. A metabonomics study was carried out to explore the difference between before and after treatment in patients with H1N1 through Chinese and/or Western medicine. Results from metabolic profiling and biochemical detection indicated significant metabolic change in the arachidonic acid metabolic pathway. In the group of combination therapy of Chinese and western medicine, its efficacy was best and the potential biomarkers were significantly changed compared with untreated state. Those results indicated that the potential metabolic biomarker could be supplemented with biochemical detection to obtain more precise diagnosis for H1N1 infection. CLINICAL TRIALS REGISTRATION: Clinical Trials. Gov No. 2008GL-50.

A simple way to configure on-line two-dimensional liquid chromatography for complex sample analysis: acquisition of four-dimensional data.

An on-line comprehensive two-dimensional liquid chromatography (HPLC×UPLC-TOF MS) was set up just using the injection valve of the ultra performance liquid chromatography (UPLC) as the interface through which the effluent of high performance liquid chromatography (HPLC) was injected automatically to UPLC coupled to time-of-flight mass spectrometry (TOF MS). As a demonstrative application, a complex sample of Traditional Chinese Medicine, Qingkailing was analyzed. As a result, a four-dimensional (4D) data containing 2D retention times, peak intensity and m/z ratios was plotted, where 398 peaks were counted and low concentration components were distinguished from the high concentration ones with a total peak capacity of 1090. Comparing with traditional 3D data acquired by HPLC×HPLC, the 4D data generated by HPLC×UPLC-TOF MS can increase the number of recognized components by three times, reduce the analysis time by 75%. Such a configuration of HPLC×UPLC-TOF MS can realize easily upon commercial chromatographs while exhibited enhanced separation efficiency, high sensitivity, huge peak capacity and great potential in complex sample analysis.

[Study on the correlation between Chinese medicine syndrome types in influenza A (H1N1) virus and potential biomarkers].

OBJECTIVE: To investigate the contents changes of potential biomarkers of patients infected with influenza A (H1N1) virus of different Chinese medicine (CM) syndrome types. METHODS: Eighty-two patients with influenza A (H1N1) virus were differentiated as three syndrome types, i. e., wind-heat invading weifen syndrome (51 cases), heat-toxicity attacking Fei syndrome (22 cases), and superficies tightened by wind cold syndrome (9 cases) according to Chinese medicine syndrome typing. According to patients' willingness and clinical conditions, they were treated by three therapeutic schedules, i. e., herbal therapy, symptomatic treatment, and antiviral therapy. The changes of potential biomarkers contents were detected in the serum of patients of various syndrome types before and after treatment. Results There was no statistical difference in the potential biomarkers contents correlated to symptoms of fever, inflammation and cough, such as PGG2, 20-COOH-LTB4, homocystein, and so on in the serum of patients of various syndrome types before treatment (P > 0.05). There was statistical difference in the potential biomarkers such as 20-OH-LTE4, LTA4, and linolenic acid, etc. between superficies tightened by wind cold syndrome and wind-heat invading weifen syndrome (P < 0.05, P < 0.01). There was statistical difference in the potential biomarkers such as PGF1alpha, prostanoic acid, and etc. between superficies tightened by wind cold syndrome and heat-toxicity attacking Fei syndrome (P < 0.05, P < 0.01). Statistical difference existed in other indices other than dUTP; 5,10-methylene-THF and PGF1alpha in wind-heat invading weifen syndrome and superficies tightened by wind cold syndrome; prostanoic acid, homocysteine, and glucose in superficies tightened by wind cold syndrome when compared with before treatment in the same group (P < 0.05, P < 0.01). The changing tendency of potential biomarkers among different syndrome types was identical. Of them, the change of 6-keto-PGF1alpha content was the most obviously of all indices. CONCLUSION: There was difference in the contents of potential biomarkers of patients infected with influenza A (H1N1) virus of different syndrome types, and our study provided experimental data support for the objectiveness of CM syndrome differentiation from the perspective of metabolic substances.

[Effects of tangshen recipe on the homocysteine metabolism of patients with diabetic nephropathy].

OBJECTIVE: To observe the effects of Tangshen Recipe (TR) on the homocysteine (Hcy) metabolism of patients with diabetic nephropathy. METHODS: 64 patients with diabetic nephropathy were randomly assigned to two groups, 32 in each. Those in the Western medicine treatment group (Group A) received insulin and orally took anti-diabetic drugs, while those in the TR group (Group B) received insulin and orally took TR (consisting of astragalus, raw rehmannia root, sanchi root, euonymus branchlet, rhubarb, bitter orange, and dogwood fruit, etc. 4 g/package). Six months was taken as one therapeutic course. Another 48 healthy volunteers were recruited as the control group. Eight intermediate metabolites of the homocysteine metabolism in plasma were quantitated before treatment, three months and six months after treatment. The in vivo changes of each metabolite after treatment were analyzed. RESULTS: Compared with the healthy control group, contents of cysteine (Cys), Hcy, s-adenosylmethionine (SAM), and SAH significantly increased in Group A and B before treatment. Contents of methionine (Met), glutathione (GSH), and Cys-gly decreased significantly, showing statistical difference (P<0.05). Patients' in vivo contents of Cys, Hcy, SAM, and SAH significantly decreased, while contents of Met, GSH, and Cys-gly significantly increased after three and six months of treatment when compared with before treatment in the same group (all P<0.05). No statistical difference existed in contents of SAH, SAM, and GSH of Group A and B after six months of treatment when compared with the healthy control group (P>0.05). No adverse reaction occurred in Group A and B. CONCLUSIONS: Treatment of insulin and TR showed similar favorable effect to Western medicine in treatment of diabetic nephropathy. It could improve in vivo hypomethylation and oxidative stress.

A metabonomic approach applied to predict patients with cerebral infarction.

Cerebral infarction is always of sudden onset, and usually leading to serious consequence. It is of therapeutic significance to develop fast and accurate diagnosis methods for cerebral infarction so that patients can be treated timely and properly. A metabonomic approach was then proposed to investigate the potential biomarkers and metabolic pathways associated with cerebral infarction and also establish a prediction model of cerebral infarction for the fast diagnosis. Serum metabolic profiling of sixty-seven cerebral infarction patients and sixty-two controls was obtained using UPLC-TOF MS. The resulting data were then processed by multivariate statistical analysis to graphically demonstrate metabolic variations. The PLS-DA model was validated with cross validation and permutation tests to assure the model's reliability, and significant difference was obtained between the original and hypothetical models (p<0.0001). A series of endogenous metabolites in the one-carbon cycle, such as folic acid, cysteine, S-adenosyl homocysteine and oxidized glutathione, were determined as potential biomarkers of cerebral infarction. A prediction model developed using PLS-KNN algorithm was established to differentiate cerebral infarction patients from controls, and an average accuracy of 100% was obtained. In conclusion, metabonomic approach is a powerful tool to investigate the pathogenesis of stroke and is expected to be developed as a useful method for the fast diagnosis.

Metabonomic study on women of reproductive age treated with nutritional intervention: screening potential biomarkers related to neural tube defects occurrence.

Nutritional intervention is effective in reducing the risk of neural tube defects (NTDs). To determine the effects of nutritional supplementation on human metabolism, a metabonomic study was carried out on 96 women of reproductive age. Subjects with nutritional intervention were given fortified wheat flour (containing folic acid, vitamin B1, vitamin B2, ferric sodium edetate and zinc oxide) for 8 months. Serum metabolic fingerprinting was detected via ultraperformance liquid chromatography in tandem with time-of-flight mass spectrometry (UPLC-TOF MS), and data acquired was processed by multivariate statistical analysis. The result revealed a significant difference between the control and intervention group. Twenty potential biomarkers, including fructose 6-phosphate, sphingosine 1-phosphate, docosahexaenoic acid and hexadecanoic acid, were located and identified by the accurate mass measurement of TOF MS. These compounds are believed to be functionally related to anti-oxidative competence in vivo. In conclusion, metabonomics study is a valuable approach in exploring the effect mechanism of nutritional intervention on NTD prevention.

HPLC-electrospray tandem mass spectrometry for simultaneous quantitation of eight plasma aminothiols: application to studies of diabetic nephropathy.

It was reported that Hcy was related to the development of kidney disease, but it remains unknown whether Hcy is an independent biomarker for diabetic nephropathy. Analytical method for simultaneous determination of aminothiols among the Hcy metabolic cycle is desirable to discover other potential biomarkers. A high-performance liquid chromatography-electrospray tandem mass spectrometric (HPLC-ESI-MS/MS) method was established for simultaneous quantitation of Cysteine (Cys), total homocysteine (tHcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), cystathionine (Cysta), methionine (Met), glutathione (GSH) and cysteinylglycine (Cys-gly) in plasma with N-(2-mercaptopropionyl)-glycine (MPG) as internal standard. The method had simple pretreatment without derivatization and the chromatograms show better separation of the eight aminothiols and the analytic time was 20 min. The results demonstrated that it provided an excellent linearity for all analytes over their respective concentration ranges and illustrated excellent precision and plasma recovery as well. Then, the method was applied in the case-control study of patients with diabetes mellitus (DM) and diabetic nephropathy (DN). In conclusion, it is an effective method to quantitate the concentrations of aminothiols in the human plasma. SAH and SAM were suggested as better potential biomarkers of DM and DN.

HPLC determination of anethole trithione and its application to pharmacokinetics in rabbits.

To evaluate the relative bioavailability of anethole trithione (ATT) from self-microemulsifying drug delivery system (SMEDDS) and tablet, a sensitive, accurate and reliable liquid chromatography method was developed and validated to determine ATT in rabbit plasma. Chromatographic separation was performed on a Diamonsil C18 column by using a mixture of methanol-water (90:10, v/v) delivered at a flow rate of 1.0 ml/min. The wavelength was set at 348 nm and mifepristone was used as the internal standard. A linear relationship for ATT was found in the range of 0.5-32 ng/ml. The mean extraction recoveries of ATT determined over three concentrations were 84.7+/-5.8, 92.3+/-3.4 and 89.9+/-5.1%. After administration of SMEDDS and tablets to rabbits, significant differences were found in main pharmacokinetic parameters of Tmax, Cmax and AUC(0-infinity) between these two formulations, and a 2.5-fold enhancement of relative bioavailability of ATT was observed from the SMEDDS compared with tablets.