ABSTRACT
Phytoplankton blooms in coastal oceans can be beneficial to coastal fisheries production and ecosystem function, but can also cause major environmental problems1,2-yet detailed characterizations of bloom incidence and distribution are not available worldwide. Here we map daily marine coastal algal blooms between 2003 and 2020 using global satellite observations at 1-km spatial resolution. We found that algal blooms occurred in 126 out of the 153 coastal countries examined. Globally, the spatial extent (+13.2%) and frequency (+59.2%) of blooms increased significantly (P < 0.05) over the study period, whereas blooms weakened in tropical and subtropical areas of the Northern Hemisphere. We documented the relationship between the bloom trends and ocean circulation, and identified the stimulatory effects of recent increases in sea surface temperature. Our compilation of daily mapped coastal phytoplankton blooms provides the basis for global assessments of bloom risks and benefits, and for the formulation or evaluation of management or policy actions.
Subject(s)
Ecosystem , Eutrophication , Oceans and Seas , Phytoplankton , Phytoplankton/growth & development , Temperature , Water Movements , Risk Assessment , Environmental Policy , Ecology , Harmful Algal Bloom , Tropical Climate , History, 21st Century , Geographic MappingABSTRACT
Aberrant cell proliferation is a hallmark of cancer, including glioblastoma (GBM). Here we report that protein arginine methyltransferase (PRMT) 6 activity is required for the proliferation, stem-like properties, and tumorigenicity of glioblastoma stem cells (GSCs), a subpopulation in GBM critical for malignancy. We identified a casein kinase 2 (CK2)-PRMT6-regulator of chromatin condensation 1 (RCC1) signaling axis whose activity is an important contributor to the stem-like properties and tumor biology of GSCs. CK2 phosphorylates and stabilizes PRMT6 through deubiquitylation, which promotes PRMT6 methylation of RCC1, which in turn is required for RCC1 association with chromatin and activation of RAN. Disruption of this pathway results in defects in mitosis. EPZ020411, a specific small-molecule inhibitor for PRMT6, suppresses RCC1 arginine methylation and improves the cytotoxic activity of radiotherapy against GSC brain tumor xenografts. This study identifies a CK2α-PRMT6-RCC1 signaling axis that can be therapeutically targeted in the treatment of GBM.
Subject(s)
Brain Neoplasms , Carcinogenesis , Cell Cycle Proteins , Glioblastoma , Guanine Nucleotide Exchange Factors , Mitosis/radiation effects , Neoplasm Proteins , Nuclear Proteins , Protein-Arginine N-Methyltransferases , Animals , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/radiotherapy , Carcinogenesis/genetics , Carcinogenesis/metabolism , Carcinogenesis/radiation effects , Casein Kinase II/genetics , Casein Kinase II/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Female , Glioblastoma/genetics , Glioblastoma/metabolism , Glioblastoma/radiotherapy , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , HEK293 Cells , Humans , Male , Mice , Mitosis/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Signal Transduction/genetics , Signal Transduction/radiation effects , Xenograft Model Antitumor AssaysABSTRACT
The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.
Subject(s)
Ataxia Telangiectasia Mutated Proteins/metabolism , Beclin-1/metabolism , Checkpoint Kinase 2/metabolism , Ischemic Stroke/metabolism , Reactive Oxygen Species/metabolism , Animals , Autophagy , Cell Line , Disease Models, Animal , HCT116 Cells , HEK293 Cells , HeLa Cells , Humans , Mice , Oxidative Stress , PhosphorylationABSTRACT
Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.
Subject(s)
Calcium , Heart Failure , Humans , Heart Failure/metabolism , Heart Failure/physiopathology , Phosphorylation , Calcium/metabolism , Calcium Channels, L-Type/metabolism , Endoplasmic Reticulum/metabolism , Myocardium/metabolism , Myofibrils/metabolismABSTRACT
High-concentrate diet induce subacute ruminal acidosis (SARA) and cause liver damage in ruminants. It has been reported that forkhead box protein A2 (FOXA2) can enhance mitochondrial membrane potential but its function in mitochondrial dysfunction induced by high concentrate diets is still unknown. Therefore, the aim of this study was to elucidate the effect of high-concentrate (HC) diet on hepatic FOXA2 expression, mitochondrial unfolded protein response (UPRmt), mitochondrial dysfunction and oxidative stress. A total of 12 healthy mid-lactation Holstein cows were selected and randomized into 2 groups: the low concentrate (LC) diet group (concentrate:forage = 4:6) and HC diet group (concentrate:forage = 6:4). The trial lasted 21 d. The rumen fluid, blood and liver tissue were collected at the end of the experiment. The results showed that the rumen fluid pH level was reduced in the HC group and the pH was lower than 5.6 for more than 4 h/d, indicating that feeding HC diets successfully induced SARA in dairy cows. Both FOXA2 mRNA and protein abundance were significantly reduced in the liver of the HC group compared with the LC group. The activity of antioxidant enzymes (CAT, G6PDH, T-SOD, Cu/Zn SOD, Mn SOD) and mtDNA copy number in the liver tissue of the HC group decreased, while the level of H2O2 significantly increased, this increase was accompanied by a decrease in oxidative phosphorylation (OXPHOS). The balance of mitochondrial division and fusion was disrupted in the HC group, as evidenced by the decreased mRNA level of OPA1, MFN1, and MFN2 and increased mRNA level of Drp1, Fis1, and MFF. At the same time, HC diet downregulated the expression level of SIRT1, SIRT3, PGC-1α, TFAM, and Nrf 1 to inhibit mitochondrial biogenesis. The HC group induced UPRmt in liver tissue by upregulating the mRNA and protein levels of CLPP, LONP1, CHOP, Hsp10, and Hsp60. In addition, HC diet could increase the protein abundance of Bax, CytoC, Caspase 3 and Cleaved-Caspase 3, while decrease the protein abundance of Bcl-2 and the Bcl-2/Bax ratio. Overall, our study suggests that the decreased expression of FOXA2 may be related to UPRmt, mitochondrial dysfunction, oxidative stress, and apoptosis in the liver of dairy cows fed a high concentrate diet.
Subject(s)
Hydrogen Peroxide , Mitochondrial Diseases , Animals , Female , Cattle , Caspase 3/metabolism , Hydrogen Peroxide/metabolism , bcl-2-Associated X Protein/metabolism , Diet/veterinary , Liver/metabolism , Lactation , Oxidative Stress , Superoxide Dismutase/metabolism , RNA, Messenger/metabolism , Unfolded Protein Response , Mitochondrial Diseases/metabolism , Forkhead Transcription Factors/metabolism , Milk/metabolism , Hydrogen-Ion Concentration , Animal FeedABSTRACT
Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.
Subject(s)
Drugs, Chinese Herbal , Liver Diseases, Alcoholic , Molecular Docking Simulation , Network Pharmacology , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/drug therapy , Animals , Mice , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Male , Tablets , Cyclooxygenase 2/metabolism , Mice, Inbred C57BL , Chromatography, High Pressure Liquid , Liver/metabolism , Liver/drug effectsABSTRACT
The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1ß, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1ß and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1ß and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.
Subject(s)
Olfaction Disorders , Receptors, Purinergic P2X7 , Rhinitis, Allergic , Animals , Mice , Adenosine Triphosphate , Caspase 1 , Culture Media, Conditioned , Disease Models, Animal , Interleukin 1 Receptor Antagonist Protein , Microglia , Olfactory Bulb , Ovalbumin , Receptors, Purinergic P2X7/genetics , Rhinitis, Allergic/complicationsABSTRACT
BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.
Subject(s)
Gallbladder Neoplasms , Neoadjuvant Therapy , Propensity Score , SEER Program , Humans , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/therapy , Female , Male , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/statistics & numerical data , Middle Aged , Prognosis , Aged , Chemotherapy, Adjuvant/statistics & numerical data , Chemotherapy, Adjuvant/methods , Neoplasm Staging , Kaplan-Meier EstimateABSTRACT
A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.
ABSTRACT
L-type lectins (LTLs) contain a carbohydrate recognition domain homologous to leguminous lectins, and have functions in selective protein traï¬cking, sorting and targeting in the secretory pathway of animals. In this study, a novel LTL, designated as ToERGIC-53, was cloned and identified from obscure puffer Takifugu obscurus. The open reading frame of ToERGIC-53 contained 1554 nucleotides encoding 517 amino acid residues. The deduced ToERGIC-53 protein consisted of a signal peptide, a leguminous lectin domain (LTLD), a coiled-coil region, and a transmembrane region. Quantitative real-time PCR showed that ToERGIC-53 was expressed in all examined tissues, with the highest expression level in the liver. The expression of ToERGIC-53 was significantly upregulated after infection with Vibrio harveyi and Staphylococcus aureus. Recombinant ToERGIC-53-LTLD (rToERGIC-53-LTLD) protein could not only agglutinate and bind to one Gram-positive bacterium (S. aureus) and three Gram-negative bacteria (V. harveyi, V. parahaemolyticus and Aeromonas hydrophila), but also bind to glycoconjugates on the surface of bacteria such as lipopolysaccharide, peptidoglycan, mannose and galactose. In addition, rToERGIC-53-LTLD inhibited the growth of bacteria in vitro. All these results suggested that ToERGIC-53 might be a pattern recognition receptor involved in antibacterial immune response of T. obscurus.
Subject(s)
Bacterial Infections , Lectins , Animals , Lectins/genetics , Takifugu/genetics , Takifugu/metabolism , Staphylococcus aureus/metabolism , Receptors, Pattern Recognition/genetics , Phylogeny , Immunity, Innate/genetics , Lectins, C-Type/geneticsABSTRACT
Alginate is a commercially important polysaccharide composed of mannuronic acid and its C5 differential isomer guluronic acid. Comprehensive research on alginate and alginate lyases requires efficient and precise analytical methods for alginate oligosaccharides. In this research, high-performance anion exchange chromatography (HPAEC) in parallel with pulsed amperometric detection (PAD) and mass spectrometry (MS) was applied to the analysis of oligosaccharides obtained by alginate lyase. By optimizing the chromatographic conditions including mobile phase concentration, flow rate, and elution gradient, the analysis of a single sample could be completed in 30 min. Seven unsaturated alginate oligosaccharides were separated and identified through their analysis time observed with PAD, including all structurally different unsaturated disaccharides and trisaccharides. The quantitative analysis of seven oligosaccharides was performed based on the quantitative capability of PAD. The method exhibited adequate linearity and precision parameters. All the calibration curves showed good linearity at least in the concentration range of 0.002 to 0.1 mg/mL. The HPAEC-PAD/MS method provides a general and efficient online method to analyze alginate oligosaccharides.
Subject(s)
Alginates , Mass Spectrometry , Oligosaccharides , Alginates/chemistry , Oligosaccharides/analysis , Oligosaccharides/chemistry , Chromatography, Ion Exchange/methods , Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Polysaccharide-Lyases/chemistry , Polysaccharide-Lyases/metabolism , Hexuronic Acids/chemistry , Hexuronic Acids/analysis , Limit of DetectionABSTRACT
In this Letter, errors in Supplementary Table 1 have been corrected.
ABSTRACT
Land change is a cause and consequence of global environmental change1,2. Changes in land use and land cover considerably alter the Earth's energy balance and biogeochemical cycles, which contributes to climate change and-in turn-affects land surface properties and the provision of ecosystem services1-4. However, quantification of global land change is lacking. Here we analyse 35 years' worth of satellite data and provide a comprehensive record of global land-change dynamics during the period 1982-2016. We show that-contrary to the prevailing view that forest area has declined globally5-tree cover has increased by 2.24 million km2 (+7.1% relative to the 1982 level). This overall net gain is the result of a net loss in the tropics being outweighed by a net gain in the extratropics. Global bare ground cover has decreased by 1.16 million km2 (-3.1%), most notably in agricultural regions in Asia. Of all land changes, 60% are associated with direct human activities and 40% with indirect drivers such as climate change. Land-use change exhibits regional dominance, including tropical deforestation and agricultural expansion, temperate reforestation or afforestation, cropland intensification and urbanization. Consistently across all climate domains, montane systems have gained tree cover and many arid and semi-arid ecosystems have lost vegetation cover. The mapped land changes and the driver attributions reflect a human-dominated Earth system. The dataset we developed may be used to improve the modelling of land-use changes, biogeochemical cycles and vegetation-climate interactions to advance our understanding of global environmental change1-4,6.
Subject(s)
Earth, Planet , Ecosystem , Environmental Monitoring , Human Activities/statistics & numerical data , Agriculture/statistics & numerical data , Agriculture/trends , Climate Change/statistics & numerical data , Forestry/statistics & numerical data , Forestry/trends , Human Activities/trends , Satellite Imagery , Trees/growth & developmentABSTRACT
BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).
Subject(s)
Amoxicillin , Anti-Bacterial Agents , Bismuth , Clarithromycin , Drug Administration Schedule , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Sulfonamides , Tetracycline , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/diagnosis , Helicobacter pylori/drug effects , Middle Aged , Male , Female , Tetracycline/administration & dosage , Tetracycline/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Bismuth/administration & dosage , Bismuth/therapeutic use , Bismuth/adverse effects , Adult , Clarithromycin/administration & dosage , Amoxicillin/administration & dosage , Sulfonamides/administration & dosage , Pyrroles/administration & dosage , Pyrroles/adverse effects , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Breath Tests , Treatment Outcome , Aged , ChinaABSTRACT
Alginate oligosaccharides (AOS), products of alginate degradation by endotype alginate lyases, possess favorable biological activities and have broad applications. Although many have been reported, alginate lyases with homogeneous AOS products and secretory production by an engineered host are scarce. Herein, the alginate lyase AlyC7 from Vibrio sp. C42 was characterized as a trisaccharide-producing lyase exhibiting high activity and broad substrate specificity. With PelB as the signal peptide and 500 mM glycine as the additive, the extracellular production of AlyC7 in Escherichia coli reached 1122.8 U/mL after 27 h cultivation in Luria-Bertani medium. The yield of trisaccharides from sodium alginate degradation by the produced AlyC7 reached 758.6 mg/g, with a purity of 85.1%. The prepared AOS at 20 µg/mL increased the root length of lettuce, tomato, wheat, and maize by 27.5%, 25.7%, 9.7%, and 11.1%, respectively. This study establishes a robust foundation for the industrial and agricultural applications of AlyC7.
Subject(s)
Escherichia coli , Polysaccharide-Lyases , Trisaccharides , Vibrio , Polysaccharide-Lyases/metabolism , Trisaccharides/biosynthesis , Vibrio/enzymology , Substrate Specificity , Alginates , Zea mays , OligosaccharidesABSTRACT
We examine the health implications of electricity generation from the 2018 stock of coal-fired power plants in India, as well as the health impacts of the expansion in coal-fired generation capacity expected to occur by 2030. We estimate emissions of SO2, NOX, and particulate matter 2.5 µm (PM2.5) for each plant and use a chemical transport model to estimate the impact of power plant emissions on ambient PM2.5 Concentration-response functions from the 2019 Global Burden of Disease (GBD) are used to project the impacts of changes in PM2.5 on mortality. Current plus planned plants will contribute, on average, 13% of ambient PM2.5 in India. This reflects large absolute contributions to PM2.5 in central India and parts of the Indo-Gangetic plain (up to 20 µg/m3). In the south of India, coal-fired power plants account for 20-25% of ambient PM2.5 We estimate 112,000 deaths are attributable annually to current plus planned coal-fired power plants. Not building planned plants would avoid at least 844,000 premature deaths over the life of these plants. Imposing a tax on electricity that reflects these local health benefits would incentivize the adoption of renewable energy.
Subject(s)
Coal , Power Plants , Geography , India/epidemiology , Mortality , Particulate Matter/analysisABSTRACT
Epimedium genus is a traditional Chinese medicine, which has functions of tonifying kidney and yang, strengthening tendons and bones, dispelling wind and emoving dampness. It is mainly used for the treatment of impotence and spermatorrhea, osteoporosis, Parkinson's, Alzheimer's, and cardiovascular diseases. The aim of this review is to provide a systematic summary of the phytochemistry, pharmacology, and clinical applications of the Epimedium Linn. In this paper, the relevant literature on Epimedium Linn. was collected from 1987 to the present day, and more than 274 chemical constituents, including flavonoids, phenylpropanoids, lignans, phenanthrenes, and others, were isolated from this genus. Modern pharmacological studies have shown that Epimedium Linn. has osteoprotective, neuroprotective, cardiovascular protective, and immune enhancing pharmacological effects. In addition, Epimedium Linn. has been commonly used to treat osteoporosis, erectile dysfunction, hypertension and cardiovascular disease. In this paper, the distribution of resources, chemical compositions, pharmacological effects, clinical applications and quality control of Epimedium Linn. are progressed to provide a reference for further research and development of the resources of this genus.
ABSTRACT
Curcumae Radix (CuR) is a traditional Chinese medicine that has been used in China for more than 1,000â years. It has the traditional efficacy of activating blood and relieving pain, promoting qi and relieving depression, clearing heart and cooling blood, and promoting gallbladder and removing jaundice. Based on this, many domestic and foreign scholars have conducted systematic studies on its chemical composition, pharmacological effects, toxicity and quality control. Currently, 250 compounds, mainly including terpenoids and curcuminoids, have been isolated and identified from CuR, which has pharmacological activities, including antitumor, anti-inflammatory and analgesic, antidepressant, hepatoprotective, hemostatic, hematopoietic, and treatment of diabetes mellitus. In modern clinical practice, CuR is widely used in the treatment of tumors, breast hyperplasia, hepatitis, and stroke. However, the generation of toxicity and clinical application of CuR and Caryophylli Flos, the determination of the concoction process of artifacts, the determination of specific Quality Marker, and the establishment of the quality control system of CuR, are problems that need to be solved urgently at present.
Subject(s)
Curcuma , Quality Control , Humans , Curcuma/chemistry , Medicine, Chinese Traditional , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/isolation & purification , Animals , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purificationABSTRACT
Lacto-N-triose II (LNT II), an essential human milk oligosaccharide and precursor to lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), was evaluated for safety. Genotoxicity was assessed through in vitro tests including Bacterial Reverse Mutation Test and mammalian cell micronucleus test, and a subchronic oral gavage toxicity study was conducted on juvenile Sprague-Dawley rats. In this study, LNT II was administered at dose levels of 0, 1,500, 2,500, or 5,000 mg/kg body weight (bw)/day for 90 days, followed by a 4-week treatment-free recovery period. LNT II was non-genotoxic in the in vitro assays. No compound-related effects were observed across all dosage levels based on various measures, including clinical observations, body weight gain, feed consumption, clinical pathology, organ weights, and histopathology. Consequently, the highest dosage of 5,000 mg/kg bw/day was established as the no-observed-adverse-effect-level (NOAEL). These results suggest the safe use of LNT II in young children formula and as a food ingredient, within the limits found naturally in human breast milk.
Subject(s)
Milk, Human , Oligosaccharides , Trisaccharides , Humans , Rats , Animals , Female , Child , Child, Preschool , Rats, Sprague-Dawley , Body Weight , MammalsABSTRACT
Ammonia-oxidation process directly contribute to soil nitrous oxide (N2O) emissions in agricultural soils. However, taxonomy of the key nitrifiers (within ammonia oxidising bacteria (AOB), archaea (AOA) and complete ammonia oxidisers (comammox Nitrospira)) responsible for substantial N2O emissions in agricultural soils is unknown, as is their regulation by soil biotic and abiotic factors. In this study, cumulative N2O emissions, nitrification rates, abundance and community structure of nitrifiers were investigated in 16 agricultural soils from major crop production regions of China using microcosm experiments with amended nitrogen (N) supplemented or not with a nitrification inhibitor (nitrapyrin). Key nitrifier groups involved in N2O emissions were identified by comparative analyses of the different treatments, combining sequencing and random forest analyses. Soil cumulative N2O emissions significantly increased with soil pH in all agricultural soils. However, they decreased with soil organic carbon (SOC) in alkaline soils. Nitrapyrin significantly inhibited soil cumulative N2O emissions and AOB growth, with a significant inhibition of the AOB Nitrosospira cluster 3a.2 (D11) abundance. One Nitrosospira multiformis-like OTU phylotype (OTU34), which was classified within the AOB Nitrosospira cluster 3a.2 (D11), had the greatest importance on cumulative N2O emissions and its growth significantly depended on soil pH and SOC contents, with higher growth at high pH and low SOC conditions. Collectively, our results demonstrate that alkaline soils with low SOC contents have high N2O emissions, which were mainly driven by AOB Nitrosospira cluster 3a.2 (D11). Nitrapyrin can efficiently reduce nitrification-related N2O emissions by inhibiting the activity of AOB Nitrosospira cluster 3a.2 (D11). This study advances our understanding of key nitrifiers responsible for high N2O emissions in agricultural soils and their controlling factors, and provides vital knowledge for N2O emission mitigation in agricultural ecosystems.