Enhanced ocean oxygenation during Cenozoic warm periods.

Dissolved oxygen (O2) is essential for most ocean ecosystems, fuelling organisms' respiration and facilitating the cycling of carbon and nutrients. Oxygen measurements have been interpreted to indicate that the ocean's oxygen-deficient zones (ODZs) are expanding under global warming1,2. However, models provide an unclear picture of future ODZ change in both the near term and the long term3-6. The paleoclimate record can help explore the possible range of ODZ changes in warmer-than-modern periods. Here we use foraminifera-bound nitrogen (N) isotopes to show that water-column denitrification in the eastern tropical North Pacific was greatly reduced during the Middle Miocene Climatic Optimum (MMCO) and the Early Eocene Climatic Optimum (EECO). Because denitrification is restricted to oxygen-poor waters, our results indicate that, in these two Cenozoic periods of sustained warmth, ODZs were contracted, not expanded. ODZ contraction may have arisen from a decrease in upwelling-fuelled biological productivity in the tropical Pacific, which would have reduced oxygen demand in the subsurface. Alternatively, invigoration of deep-water ventilation by the Southern Ocean may have weakened the ocean's 'biological carbon pump', which would have increased deep-ocean oxygen. The mechanism at play would have determined whether the ODZ contractions occurred in step with the warming or took centuries or millennia to develop. Thus, although our results from the Cenozoic do not necessarily apply to the near-term future, they might imply that global warming may eventually cause ODZ contraction.

Oceanic nutrient rise and the late Miocene inception of Pacific oxygen-deficient zones.

The modern Pacific Ocean hosts the largest oxygen-deficient zones (ODZs), where oxygen concentrations are so low that nitrate is used to respire organic matter. The history of the ODZs may offer key insights into ocean deoxygenation under future global warming. In a 12-My record from the southeastern Pacific, we observe a >10‰ increase in foraminifera-bound nitrogen isotopes (15N/14N) since the late Miocene (8 to 9 Mya), indicating large ODZs expansion. Coinciding with this change, we find a major increase in the nutrient content of the ocean, reconstructed from phosphorus and iron measurements of hydrothermal sediments at the same site. Whereas global warming studies cast seawater oxygen concentrations as mainly dependent on climate and ocean circulation, our findings indicate that modern ODZs are underpinned by historically high concentrations of seawater phosphate.

Study on the immune-enhancing and inhabiting transmissible gastroenteritis virus effects of polysaccharides from Cimicifuga rhizoma.

Cimicifugae rhizoma is a traditional Chinese herbal medicine in China, and modern pharmacological research showed that it has obvious antiviral activity. Many polysaccharides have been proved to have immune enhancement and antiviral activity, but there are few studies on the biological activity of Cimicifuga rhizoma polysaccharide (CRP). The aim was to explore the character of CRP and its effects on improving immune activity and inhibiting transmissible gastroenteritis virus (TGEV). The monosaccharide composition, molecular weight, fourier transform infrared spectra and electron microscopy analysis of CRP was measured. The effect of CRP on immune activity in lymphocytes and RAW264.7 cells were studied by colorimetry, FITC-OVA fluorescent staining and ELISA. The effect of CRP on TGEV-infected PK-15 cells was determined using Real-time PCR, Hoechst fluorescence staining, trypan blue staining, acridine orange staining, Annexin V-FITC/PI fluorescent staining, DCFH-DA loading probe, and JC-1 staining. Network pharmacology was used to predict the targets of CRP in enhancing immunity and anti-TGEV, and molecular docking was used to further analyze the binding mode between CPR and core targets. The results showed that CRP was mainly composed of glucose and galactose, and its molecular weight was 64.28 kDa. The content of iNOS and NO in CRP group were significantly higher than the control group. CRP (125 and 62.5 µg/mL) could significantly enhance the phagocytic capacity of RAW264.7 cells, and imprive the content of IL-1ß content compared with control group. 250 µg/mL of CRP possessed the significant inhibitory effect on TGEV, which could significantly reduce the apoptosis compared to TGVE group and inhibit the decrease in mitochondrial membrane potential compared to TGVE group. The mRNA expression of TGEV N gene in CRP groups was significantly lower than TGEV group. PPI showed that the core targets of immune-enhancing were AKT1, MMP9, HSP90AA1, etc., and the core targets of TGE were CASP3, MMP9, EGFR, etc. Molecular docking show that CRP has binding potential with target. These results indicated that CRP possessed the better immune enhancement effect and anti-TGEV activity.

Apigenin analogs as α-glucosidase inhibitors with antidiabetic activity.

This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a Ki value of 2.61 µM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health.

Coal fly ash is a major carbon flux in the Chang Jiang (Yangtze River) basin.

Fly ash-the residuum of coal burning-contains a considerable amount of fossilized particulate organic carbon (FOCash) that remains after high-temperature combustion. Fly ash leaks into natural environments and participates in the contemporary carbon cycle, but its reactivity and flux remained poorly understood. We characterized FOCash in the Chang Jiang (Yangtze River) basin, China, and quantified the riverine FOCash fluxes. Using Raman spectral analysis, ramped pyrolysis oxidation, and chemical oxidation, we found that FOCash is highly recalcitrant and unreactive, whereas shale-derived FOC (FOCrock) was much more labile and easily oxidized. By combining mass balance calculations and other estimates of fly ash input to rivers, we estimated that the flux of FOCash carried by the Chang Jiang was 0.21 to 0.42 Mt C⋅y-1 in 2007 to 2008-an amount equivalent to 37 to 72% of the total riverine FOC export. We attributed such high flux to the combination of increasing coal combustion that enhances FOCash production and the massive construction of dams in the basin that reduces the flux of FOCrock eroded from upstream mountainous areas. Using global ash data, a first-order estimate suggests that FOCash makes up to 16% of the present-day global riverine FOC flux to the oceans. This reflects a substantial impact of anthropogenic activities on the fluxes and burial of fossil organic carbon that has been made less reactive than the rocks from which it was derived.

Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.

Relationship between caffeine intake and thyroid function: results from NHANES 2007-2012.

BACKGROUND: Moderate caffeine intake decreases the risk of metabolic disorders and all-cause mortality, and the mechanism may be related to its ergogenic actions. Thyroid hormones are vital in metabolic homeostasis; however, their association with caffeine intake has rarely been explored. OBJECTIVE: To investigate the association between caffeine intake and thyroid function. METHODS: We collected data on demographic background, medical conditions, dietary intake, and thyroid function from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Subgroups were classified using two-step cluster analysis, with sex, age, body mass index (BMI), hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD) being used for clustering. Restrictive cubic spline analysis was employed to investigate potential nonlinear correlations, and multivariable linear regression was used to evaluate the association between caffeine consumption and thyroid function. RESULTS: A total of 2,582 participants were included, and three subgroups with different metabolic features were clustered. In the most metabolically unhealthy group, with the oldest age, highest BMI, and more cases of hypertension, hyperglycemia, and CVD, there was a nonlinear relationship between caffeine intake and serum thyroid stimulating hormone (TSH) level. After adjusting for age, sex, race, drinking, smoking, medical conditions, and micronutrient and macronutrient intake, caffeine intake of less than 9.97 mg/d was positively associated with serum TSH (p = 0.035, standardized ß = 0.155); however, moderate caffeine consumption (9.97-264.97 mg/d) indicated a negative association (p = 0.001, standardized ß = - 0.152). CONCLUSIONS: Caffeine consumption had a nonlinear relationship with serum TSH in people with metabolic disorders, and moderate caffeine intake (9.97 ~ 264.97 mg/d) was positively associated with serum TSH.

PP2A regulates metastasis and vasculogenic mimicry formation via PI3K/AKT/ZEB1 axis in non-small cell lung cancers.

Studies have shown that inhibition of PI3K/AKT signaling is a key strategy for the treatment of tyrosine kinase inhibitor resistance in non-small cell lung cancer (NSCLC). Vasculogenic mimicry (VM) not only accelerates tumor progression but also increases drug-induced resistance. As a tumor suppressor, protein phosphatase 2A (PP2A) is a ubiquitous conserved serine/threonine phosphatase. While its effects and mechanisms on VM formation and invasion in NSCLC remain unclear. The present study aimed to investigate the role of PP2A in VM formation and elucidate the underlying mechanisms. Results showed that PP2A could significantly inhibit VM formation and VM-dependent behavior, including invasion and migration both in vitro and in vivo. Activation of PP2A with FTY720 or Ad-PP2A reduced phosphorylated AKT and inhibited ZEB1 transcription, thereby further downregulating the expression of MMP-2, VE-cadherin, and VEGFR-2, whereas inhibition of PP2A with okadaic acid (OA) or Ad-dn-PP2A exerted the opposite effect. Furthermore, PP2A inhibited tumor growth and VM formation in the xenograft tumor model. PI3K inhibitor BENC-511 could potentiate activation of PP2A, leading to inhibition of p-AKT/ZEB1 and VM formation in vitro and in vivo. This study indicated that PP2A could regulate VM formation in NSCLC through the PI3K/AKT/ZEB1 axis. PP2A reactivation or combination with PI3K inhibitor might be a more effective treatment against advanced NSCLC by inhibiting VM formation.

The roles of IDH1 in tumor metabolism and immunity.

IDH1 is a key metabolic enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle that can convert isocitrate into α-ketoglutarate (α-KG) and generate NADPH. The reduction of IDH1 may affect dioxygenase activity and damage the body's detoxification mechanism. Many studies have shown that IDH1 is closely related to the occurrence and development of tumors, and the changes in IDH1 expression levels or gene mutations have appeared in many tumor tissues and produced a series of metabolic and immunity changes at the same time. To better understand the relationship between IDH1 and tumor development, this article reviews the latest advances in IDH1 and tumor metabolism, tumor immunity, IDH1 regulatory mechanisms and IDH1 target inhibitors.

IDH1 is a key metabolic enzyme for cellular respiration. The changes in IDH1 expression or gene mutations may affect enzyme activity and damage the body's detoxification mechanism. Studies have shown that IDH1 is closely related to the occurrence and development of tumors, and the changes in IDH1 also produced a series of metabolic and immunity changes. To better understand the relationship between IDH1 and tumor development, this article reviews the latest advances in IDH1 and tumor metabolism, tumor immunity, IDH1 regulatory mechanisms and IDH1 target inhibitors.

Combining network pharmacology with chromatographic fingerprinting and multicomponent quantitative analysis for the quality evaluation of Moutan Cortex.

In this study, we combined network pharmacology, chromatographic fingerprinting and multicomponent quantitative analysis to evaluate the quality of Moutan Cortex (MC). Specifically, through network pharmacology, we obtained a comprehensive understanding of the active components and pharmacological activities of MC. In addition, the method of establishing fingerprint and multicomponent quantification by ultra high-performance liquid chromatography is convenient and comprehensive, and can more fully reflect the overall distribution of various chemical components. Principal component analysis and discriminant least square analysis were used. The results show that MC plays a synergistic role through multiple targets and pathways. The contents of chemical components in MC from different sources were significantly different. Combining network pharmacology and multicomponent quantitative results, gallic acid, benzoyl paeonol, paeonol, methyl gallate, benzoic acid and paeonol can be used as quality markers for MC quality control. This study provides a comprehensive and reliable strategy for the quality evaluation of MC and determines its quality indicators to ensure the quality of Chinese herbal medicine.

Effects of photoperiod on morphology and function in testis and epididymis of Cricetulus barabensis.

Photoperiod regulates the seasonal reproductive rhythms of mammals by influencing the development and function of sexual organs; however, the underlying mechanism remains unclear. We examined the morphology and functioning of the main sex organs of striped dwarf hamsters (Cricetulus barabensis) under different photoperiods (short daylight [SD], moderate daylight [MD], and long daylight [LD]) and further investigated the underlying molecular mechanisms. There was an inverse correlation between blood melatonin levels and photoperiod in the order SD > MD > LD. Decreases in body and tissue weights were observed under SD, whereas testis and epididymis weights between MD and LD were comparable. The diameters of the spermatogenic tubules, thickness of the spermatogenic epithelium, and the number of spermatogonia and Sertoli cells decreased under SD, whereas the serum-luteinizing hormone, follicle-stimulating hormone, and fecal testosterone concentrations decreased under LD. In SD, bax/bcl2 protein expression increased in the testes and decreased in the epididymides, whereas LC3II/LC3I remained unchanged in the testes and increased in the epididymides compared with the MD group. In LD, bax/bcl2 and LC3II/LC3I protein expression levels were unchanged in the testes but were decreased in the epididymides. In SD and LD, adenosine triphosphate synthase and citrate synthase protein expression levels were unchanged in the testes but were decreased in the epididymides. Drp1 and Mff protein expression increased in the testes and decreased in the epididymides. Overall, different regulatory mechanisms in the testis and epididymis led to degeneration under SD and maintenance under LD, preferentially protecting mitochondrial function in the testis by regulating mitochondrial fission.

Exploring the Potential of Electrospray-Orbitrap for Stable Isotope Analysis Using Nitrate as a Model.

Widely used isotope ratio mass spectrometers have limited capabilities to measure metabolites, drugs, or small polyatomic ions without the loss of structural isotopic information. A new approach has recently been introduced that uses electrospray ionization Orbitrap to measure multidimensional isotope signatures of intact polar compounds. Using nitrate as a model compound, this study aims to establish performance metrics for comparisons with conventional IRMS at the natural abundance level. We present a framework on how to convert isotopolog intensities to δ values that are commonly used in the isotope geochemistry community. The quantification of seven nitrate isotopologs provides multiple pathways for obtaining the primary N and O δ values including non-mass-dependent O isotope variations, as well as opportunities to explore nonrandom isotopic distributions (i.e., clumping effects) within molecular nitrate. Using automation and the adaptation of measurement principles that are specific to isotope ratio analysis, nitrate δ15NAIR, δ18OVSMOW, and δ17OVSMOW were measured with a long-term precision of 0.4‰ or better for isotopic reference materials and purified nitrate from environmental samples. In addition, we demonstrate promising results for unpurified environmental samples in liquid form. With these new developments, this study connects the two largely disparate mass spectrometry fields of bioanalytical MS and isotope ratio MS, thus providing a route to measure new isotopic signatures in diverse organic and inorganic solutes.

Natural forcing of the North Atlantic nitrogen cycle in the Anthropocene.

Human alteration of the global nitrogen cycle intensified over the 1900s. Model simulations suggest that large swaths of the open ocean, including the North Atlantic and the western Pacific, have already been affected by anthropogenic nitrogen through atmospheric transport and deposition. Here we report an ∼130-year-long record of the 15N/14N of skeleton-bound organic matter in a coral from the outer reef of Bermuda, which provides a test of the hypothesis that anthropogenic atmospheric nitrogen has significantly augmented the nitrogen supply to the open North Atlantic surface ocean. The Bermuda 15N/14N record does not show a long-term decline in the Anthropocene of the amplitude predicted by model simulations or observed in a western Pacific coral 15N/14N record. Rather, the decadal variations in the Bermuda 15N/14N record appear to be driven by the North Atlantic Oscillation, most likely through changes in the formation rate of Subtropical Mode Water. Given that anthropogenic nitrogen emissions have been decreasing in North America since the 1990s, this study suggests that in the coming decades, the open North Atlantic will remain minimally affected by anthropogenic nitrogen deposition.

Emissive Platinum(II) Cages with Reverse Fluorescence Resonance Energy Transfer for Multiple Sensing.

It is quite challenging to realize fluorescence resonance energy transfer (FRET) between two chromophores with specific positions and directions. Herein, through the self-assembly of two carefully selected fluorescent ligands via metal-coordination interactions, we prepared two tetragonal prismatic platinum(II) cages with a reverse FRET process between their faces and pillars. Bearing different responses to external stimuli, these two emissive ligands are able to tune the FRET process, thus making the cages sensitive to solvents, pressure, and temperature. First, these cages could distinguish structurally similar alcohols such as n-butanol, t-butanol, and i-butanol. Furthermore, they showed decreased emission with bathochromic shifts under high pressure. Finally, they exhibited a remarkable ratiometric response to temperature over a wide range (223-353 K) with high sensitivity. For example, by plotting the ratio of the maximum emission (I600/I480) of metallacage 4b against the temperature, the slope reaches 0.072, which is among the highest values for ratiometric fluorescent thermometers reported so far. This work not only offers a strategy to manipulate the FRET efficiency in emissive supramolecular coordination complexes but also paves the way for the future design and preparation of smart emissive materials with external stimuli responsiveness.

Stable Isotope Analysis of Intact Oxyanions Using Electrospray Quadrupole-Orbitrap Mass Spectrometry.

The stable isotopes of sulfate, nitrate, and phosphate are frequently used to study geobiological processes of the atmosphere, ocean, as well as land. Conventionally, the isotopes of these and other oxyanions are measured by isotope-ratio sector mass spectrometers after conversion into gases. Such methods are prone to various limitations on sensitivity, sample throughput, or precision. In addition, there is no general tool that can analyze several oxyanions or all the chemical elements they contain. Here, we describe a new approach that can potentially overcome some of these limitations based on electrospray hyphenated with Quadrupole Orbitrap mass spectrometry. This technique yields an average accuracy of 1-2‰ for sulfate δ34S and δ18O and nitrate δ15N and δ18O, based on in-house and international standards. Less abundant variants such as δ17O, δ33S, and δ36S, and the 34S-18O "clumped" sulfate can be quantified simultaneously. The observed precision of isotope ratios is limited by the number of ions counted. The counting of rare ions can be accelerated by removing abundant ions with the quadrupole mass filter. Electrospray mass spectrometry (ESMS) exhibits high-throughput and sufficient sensitivity. For example, less than 1 nmol sulfate is required to determine 18O/34S ratios with 0.2‰ precision within minutes. A purification step is recommended for environmental samples as our proposed technique is susceptible to matrix effects. Building upon these initial provisions, new features of the isotopic anatomy of mineral ions can now be explored with ESMS instruments that are increasingly available to bioanalytical laboratories.

Molecular typing and genomic characteristic of human adenoviruses in Datong, Northern China.

The molecular prevalence of human adenoviruses (HAdVs) in Datong city and molecular evolution of HAdV-C species is still obscure. Here, we explored the molecular prevalence of HAdVs by simultaneous sequencing of hexon and fiber. Then, the penton gene fragments of HAdV-C species were determined by sequencing. Finally, genomic and proteotyping analysis were performed for exploration of molecular evolution of unique HAdV-6. Our results showed that dominant molecular types of HAdVs were HAdV-3, HAdV-2, and HAdV-1 based on the hexon and fiber genotype. Among H2F2 isolates, P1H2F2 was most common, followed by P2H2F2 and HAdV-89. The clinical symptoms of HAdV-1 or HAdV-2 infected patients were more severe than HAdV-3 infected patients, the prognosis of HAdV-1, HAdV-2, and HAdV-3 infected patients was indifference. Genomic and proteotyping analysis demonstrated that DT15 was different from HAdV-6 prototype, with high-discrepant sequences localized in the E3 region. In conclusion, HAdV-1 and HAdV-2 have a high affinity to infect younger children and cause more severe symptoms than HAdV-3. The E3 gene of HAdV-C species was considered as highly recombination and mutation region.

Importance of lipid ratios for predicting intracranial atherosclerotic stenosis.

BACKGROUND: This study aims to investigate the association of lipid ratios with intracranial atherosclerotic stenosis (ICAS) in a Chinese population. METHODS: This cross-sectional study included 658 consecutive patients with ischemic stroke. Intracranial and extracranial arteries were evaluated for atherosclerotic stenosis using digital subtraction angiography or computed tomography angiography. Lipid ratios [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG)/HDL-C, low-density lipoprotein-cholesterol (LDL-C)/HDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C)/HDL-C, remnant cholesterol (RC)/HDL-C, apolipoprotein B (apo B)/apolipoprotein A-I (apo A-I), and apo B/HDL-C] were calculated. RESULTS: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C, apo B/HDL-C and apo B/apo A-I ratios (all P < 0.05) were significantly associated with ICAS but not with extracranial atherosclerotic stenosis after adjustment for confounding factors. Receiver operating characteristic (ROC) curves analysis revealed that the apo B/apo A-I ratio had the largest area under the ROC curve (AUC) among lipid levels alone and for lipid ratios (AUC = 0.588). Lipid ratios had higher AUC values than those for lipid levels alone for the identification of ICAS. CONCLUSION: The TC/HDL-C, LDL-C/HDL-C, RC/HDL-C, non-HDL-C/HDL-C apo B/HDL-C, and apo B/apo A-I ratios were significantly related to ICAS risk. Compared with the other variables tested, the apo B/apo A-I ratio appeared to be a better discriminator for identifying ICAS risk in stroke patients.

Deep-sea coral evidence for lower Southern Ocean surface nitrate concentrations during the last ice age.

The Southern Ocean regulates the ocean's biological sequestration of CO2 and is widely suspected to underpin much of the ice age decline in atmospheric CO2 concentration, but the specific changes in the region are debated. Although more complete drawdown of surface nutrients by phytoplankton during the ice ages is supported by some sediment core-based measurements, the use of different proxies in different regions has precluded a unified view of Southern Ocean biogeochemical change. Here, we report measurements of the 15N/14N of fossil-bound organic matter in the stony deep-sea coral Desmophyllum dianthus, a tool for reconstructing surface ocean nutrient conditions. The central robust observation is of higher 15N/14N across the Southern Ocean during the Last Glacial Maximum (LGM), 18-25 thousand years ago. These data suggest a reduced summer surface nitrate concentration in both the Antarctic and Subantarctic Zones during the LGM, with little surface nitrate transport between them. After the ice age, the increase in Antarctic surface nitrate occurred through the deglaciation and continued in the Holocene. The rise in Subantarctic surface nitrate appears to have had both early deglacial and late deglacial/Holocene components, preliminarily attributed to the end of Subantarctic iron fertilization and increasing nitrate input from the surface Antarctic Zone, respectively.

Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts suppress LPS-induced pro-inflammatory responses through NF-кB, MAPK, and PI3K-Akt signaling pathways in alveolar epithelial type II cells.

Acacia catechu (L.f.) Willd (ACW) and Scutellaria baicalensis Georgi (SBG) are one of the most famous couplet Chinese medicines, widely used for treating infantile cough, phlegm, and fever caused by pulmonary infection. However, the underlying molecular mechanism of their anti-inflammatory activity has not been determined. The aim of this study was to evaluate the protective effect of this couplet Chinese medicines (ACW-SBG) on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI) model of rats and the potential molecular mechanisms responsible for anti-inflammatory activities in alveolar epithelial type II cells (AEC-II). Standardization of the 70% ethanol extract of ACW and SBG was performed by using a validated reversed-phase high-pressure liquid chromatography method. Rats were pretreated with ACW-SBG for 7 days prior to LPS challenge. We assessed the effects of ACW-SBG on the LPS-induced production of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) in the bronchoalveolar lavage fluid (BALF). The wet-to-dry weight ratio was calculated, and hematoxylin and eosin staining of lung tissue was performed. Cell viability of AEC-II was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time quantitative reverse transcription polymerase chain reaction assay was carried out to quantify the relative gene expression of TNF-α and IL-1ß in AEC-II. The western blotting analysis was executed to elucidate the expression of mediators linked to nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol-3 kinase-protein kinase B (PI3K-Akt) signaling pathways. ACW-SBG significantly decreased lung wet-to-dry weight ratio, ameliorated LPS-induced lung histopathological changes, and reduced the release of inflammatory mediators such as TNF-α and IL-1ß in BALF. In AEC-II, we found that the expression of TNF-α mRNA was also inhibited by ACW-SBG. ACW-SBG blocked NF-κB activation by preventing the phosphorylation of NF-κB (p65) as well as the phosphorylation and degradation of the inhibitor of kappa B kinase. ACW-SBG extracts also inhibited the phosphorylation of respective MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38) as well as Akt. The present study demonstrated that ACW-SBG played a potent anti-inflammatory role in LPS-induced ALI in rats. The potential molecular mechanism was involved in attenuating the NF-κB, MAPKs, and PI3K-Akt signaling pathways in LPS-induced AEC-II.