Methysticin Acts as a Mechanism-Based Inactivator of Cytochrome P450 2C9.

Methysticin is one of the naturally occurring bioactive constituents extracted from Piper methysticum Forst. In the present study, we intended to investigate the inhibitory effect of methysticin on cytochrome P450 (P450) enzymes. Methysticin exhibited time-, concentration-, and NADPH-dependent inhibition on CYP2C9 using diclofenac as a probe substrate. Approximately 85% of CYP2C9 activity was inhibited by methysticin at 50 µM after a 30 min preincubation with human liver microsomes in the presence of NADPH. The kinetic parameters KI, kinact, and t1/2,inact were 13.32 ± 1.35 µM, 0.054 ± 0.005 min-1, and 12.83 ± 3.23 min, respectively. Sulfaphenazole (competitive inhibitor of CYP2C9) displayed a significant protective effect on methysticin-induced CYP2C9 inactivation. However, the inclusion of catalase/superoxide dismutase or glutathione (GSH) showed no such protection. A carbene intermediate was postulated to be involved in methysticin-induced CYP2C9 inactivation as K3Fe(CN)6 recovered 14.96% of CYP2C9 activity. A methysticin-derived ortho-quinone intermediate dependent on NADPH was trapped by GSH, and this intermediate was believed to be involved in CYP2C9 inactivation. CYP1A2, 2C9, and 3A4 were the major enzymes responsible for methysticin bioactivation. Taken together, the present work demonstrated that methysticin was a mechanism-based inactivator of CYP2C9. Both ortho-quinone and carbene intermediates appeared to be involved in the inactivation of CYP2C9 induced by methysticin.

Comparing VA and Community-Based Care: Trends in Sleep Studies Following the Veterans Choice Act.

BACKGROUND: To address concerns about access to care, the Veterans Access, Choice, and Accountability Act of 2014 was enacted to make care available in the community when Veterans Health Administration (VA) care was unavailable or not timely. This paper examined VA referrals for diagnostic sleep studies from federal fiscal year (FY) 2015-2018. DESIGN: Sleep studies completed between FY2015 and 2018 for Veterans tested within VA facilities (VAF) or referred to VA community care (VACC) providers were identified using VA administrative data files. Sleep studies were divided into laboratory and home studies. KEY RESULTS: The number of sleep studies conducted increased over time; the proportion of home studies increased in VAF (32 to 47%). Veterans were more likely to be referred for a sleep study to VACC if they lived in a rural or highly rural area (ORs = 1.47 and 1.55, respectively), and had public or public and private insurance (ORs = 2.01 and 1.35), and were less likely to be referred to VACC if they were age 65+ (OR = 0.72) and were in the highest utilization risk based on Nosos score (OR = 0.78). Regression analysis of sleep study type revealed that lab studies were much more likely for VACC referrals (OR = 3.16), for persons living in rural areas (OR = 1.21), with higher comorbidity scores (OR = 1.28) and for ages 44-54, 55 to 64, and 65+ (ORs = 1.12, 1.28, 1.45, respectively) compared to younger Veterans. Veterans with some or full VA copayments (ORs = 0.91 and 0.86, respectively), and overweight Veterans (OR = 0.94) were less likely to have lab studies. CONCLUSIONS: The number of sleep studies performed on Veterans increased from 2015 to 2018. Access to sleep studies improved through a combination of providing care through the Veteran Choice Program, predominantly used by rural Veterans, and increased use of home sleep studies by VA.

Projected Future Changes in Tropical Cyclones Using the CMIP6 HighResMIP Multimodel Ensemble.

Future changes in tropical cyclone properties are an important component of climate change impacts and risk for many tropical and midlatitude countries. In this study we assess the performance of a multimodel ensemble of climate models, at resolutions ranging from 250 to 25 km. We use a common experimental design including both atmosphere-only and coupled simulations run over the period 1950-2050, with two tracking algorithms applied uniformly across the models. There are overall improvements in tropical cyclone frequency, spatial distribution, and intensity in models at 25 km resolution, with several of them able to represent very intense storms. Projected tropical cyclone activity by 2050 generally declines in the South Indian Ocean, while changes in other ocean basins are more uncertain and sensitive to both tracking algorithm and imposed forcings. Coupled models with smaller biases suggest a slight increase in average TC 10 m wind speeds by 2050.

In Situ Blood Vessel Regeneration Using SP (Substance P) and SDF (Stromal Cell-Derived Factor)-1α Peptide Eluting Vascular Grafts.

OBJECTIVE: The objective of this study was to develop small-diameter vascular grafts capable of eluting SDF (stromal cell-derived factor)-1α-derived peptide and SP (substance P) for in situ vascular regeneration. APPROACH AND RESULTS: Polycaprolactone (PCL)/collagen grafts containing SP or SDF-1α-derived peptide were fabricated by electrospinning. SP and SDF-1α peptide-loaded grafts recruited significantly higher numbers of mesenchymal stem cells than that of the control group. The in vivo potential of PCL/collagen, SDF-1, and SP grafts was assessed by implanting them in a rat abdominal aorta for up to 4 weeks. All grafts remained patent as observed using color Doppler and stereomicroscope. Host cells infiltrated into the graft wall and the neointima was formed in peptides-eluting grafts. The lumen of the SP grafts was covered by the endothelial cells with cobblestone-like morphology, which were elongated in the direction of the blood flow, as discerned using scanning electron microscopy. Moreover, SDF-1α and SP grafts led to the formation of a confluent endothelium as evaluated using immunofluorescence staining with von Willebrand factor antibody. SP and SDF-1α grafts also promoted smooth muscle cell regeneration, endogenous stem cell recruitment, and blood vessel formation, which was the most prominent in the SP grafts. Evaluation of inflammatory response showed that 3 groups did not significantly differ in terms of the numbers of proinflammatory macrophages, whereas SP grafts showed significantly higher numbers of proremodeling macrophages than that of the control and SDF-1α grafts. CONCLUSIONS: SDF-1α and SP grafts can be potential candidates for in situ vascular regeneration and are worthy for future investigations.

Reduced abscisic acid content is responsible for enhanced sucrose accumulation by potassium nutrition in vegetable soybean seeds.

In order to understand the physiological mechanism of potassium (K) application in enhancing sugar content of vegetable soybean seeds, pot experiments were conducted in 2014 and 2015 with two vegetable soybean (Glycine max L. Merr.) cultivars (c.v. Zhongkemaodou 1 and c.v. 121) under normal rate of nitrogen and phosphorus application. Three potassium (K) fertilization treatments were imposed: No K application (K0), 120 kg K2SO4 ha-1 at seeding (K1), and 120 kg K2SO4 ha-1 at seedling + 1% K2SO4 foliar application at flowering (K2). Contents of indole-3-acetic acid (IAA), gibberellins (GA), cytokinins (ZR) and abscisic acid (ABA) in seeds were determined from 4 to 8 weeks after flowering. K fertilization increased the contents of IAA, GA, ZR, soluble sugar, sucrose and fresh pod yield, but reduced ABA content consistently. When the contents of soluble sugar and sucrose reached the highest level at 7 weeks after flowering for the 2 cultivars, the contents of IAA、GA、ZR all reached the lowest level in general. The content of ABA in seed was negatively correlated with the sucrose content (P < 0.01, r = -0.749**, -0.768** in 2014 and -0.535**, -0.791** in 2015 for c.v.121 and c.v. Zhongkemaodou 1 respectively). The changes in ratio of the ABA to (IAA + GA + ZR) from 4 to 8 weeks after flowering affected by K application were coincident to the changes of sucrose accumulation. The reduced ratio of ABA/(IAA + GA + ZR) affected by K nutrition particularly reduced abscisic acid content plays a critical role in enhancing sucrose content, which might be a partial mechanism involved in K nutrition to improve the quality of vegetable soybean.

Effect of Intravenous Iron Supplementation on Acute Mountain Sickness: A Preliminary Randomized Controlled Study.

BACKGROUND: The aim of this study was to assess the role of intravenous iron supplementation in the prevention of AMS. MATERIAL AND METHODS: This was a randomized, double-blinded, placebo-controlled study. Forty-one (n=41) healthy Chinese low-altitude inhabitants living in Beijing, China (altitude of about 50 meters) were randomly assigned into intravenous iron supplementation (ISS group; n=21) and placebo (CON group; n=20) groups. Participants in the ISS group received iron sucrose supplement (200 mg) before flying to Lhasa, China (altitude of 4300 meters). Acute mountain sickness (AMS) severity was assessed with the Lake Louise scoring (LLS) system within 5 days after landing on the plateau (at high altitude). Routine check-ups, clinical biochemistry, and blood tests were performed before departure and 24 h after arrival. RESULTS: A total of 38 participants completed the study (ISS group: n=19; CON group: n=19). The rate of subjects with AMS (LLS>3) was lower in the ISS group compared with the CON group, but no significant differences were obtained (P>0.05). There were no differences in patients' baseline characteristics. The physiological indices were similar in both groups except for serum iron concentrations (19.44±10.02 vs. 85.10±26.78 µmol/L) and transferrin saturation rates (28.20±12.14 vs. 68.34±33.12%), which were significantly higher in the ISS group (P<0.05). Finally, heart rate was identified as a contributing factor of LLS. CONCLUSIONS: These preliminary findings suggest that intravenous iron supplementation has no significant protective effect on AMS in healthy Chinese low-altitude inhabitants.

Costs of care for lung and colon cancer patients receiving chemotherapy following FDA policy changes.

PURPOSE: Use of erythropoiesis-stimulating agents (ESAs) in US cancer care declined amidst post-marketing evidence of adverse effects and the Food and Drug Administration's (FDA) addition of a "black-box" warning to product labeling in March 2007. Because reduced ESA use may have led to more transfusions or increased anemia-related health care needs, we measured the policy's impact on health care costs of lung and colon cancer patients receiving chemotherapy. METHODS: In a retrospective cohort study of 13,630 lung and 3,198 colon cancer patients in the Department of Veterans Affairs (VA) between 2002 and 2008, we calculated anemia treatment (ESA and transfusion), cancer- and non-cancer-related, and total health care costs for the chemotherapy episode of care. We used multivariable regression to examine health care costs and utilization between patients whose chemotherapy was administered before (PRE) or after (POST) March 1, 2007. RESULTS: ESA costs declined and transfusion costs were similar, resulting in lower overall POST-period anemia treatment costs (lung, $526 lower, P < 0.01; colon, $504 lower, P < 0.01). Other cancer-related health care costs increased, resulting in markedly higher POST-period total health care costs (lung, $4,706 higher, P < 0.01; colon, $11,414 higher, P < 0.01). CONCLUSIONS: Although chemotherapy episode anemia treatment costs declined after the black-box warning, the savings were offset by increases in other cancer-related costs. Those increases were mainly in outpatient services and pharmacy, suggesting that likely drivers include adoption of new high-cost diagnostic approaches and therapeutic modalities. Additional research is needed to determine the effects of anemia management changes on patient outcomes and to more fully understand cost-benefit relationships in cancer treatment.

Contralateral C7 nerve transfer in the treatment of central hemiplegia after stroke under general anesthesia: A case report.

Similar reports in the past pay less attention to the anesthetic management of these patients. We reported a 46-year-old man who suffered from hypertensive cerebral apoplexy 5 months ago and accepted C7 nerve transfer to improve the central spastic paralysis in the right upper limb. After careful evaluation and anesthesia management before anesthesia, the operation was successfully completed under general anesthesia. The patient was cured and discharged without complications. The anesthesia management of C7 nerve transfer should choose appropriate operation opportunities for patients according to the type of stroke, improve the preoperative preparation, and form a multidisciplinary diagnosis and treatment.

Enhanced Atlantic Meridional Mode predictability in a high-resolution prediction system.

Accurate prediction of sea surface temperatures (SSTs) in the tropical North Atlantic on multiyear timescales is of paramount importance due to its notable impact on tropical cyclone activity. Recent advances in high-resolution climate predictions have demonstrated substantial improvements in the skill of multiyear SST prediction. This study reveals a notable enhancement in high-resolution tropical North Atlantic SST prediction that stems from a more realistic representation of the Atlantic Meridional Mode and the associated wind-evaporation-SST feedback. The key to this improvement lies in the enhanced surface wind response to changes in cross-equatorial SST gradients, resulting from Intertropical Convergence Zone bias reduction when atmospheric model resolution is increased, which, in turn, amplifies the positive feedback between latent and sensible surface heat fluxes and SST anomalies. These advances in high-resolution climate prediction hold promise for extending tropical cyclone forecasts at multiyear timescales.

Influences of shallow groundwater depth on N2O diffusion along the soil profile of summer maize fields in North China Plain.

The emissions of nitrous oxide (N2O) from agricultural fields are a significant contribution to global warming. Understanding the mechanisms of N2O emissions from agricultural fields is essential for the development of N2O emission mitigation strategies. Currently, there are extensive studies on N2O emissions on the surface of agricultural soils, while studies on N2O fluxes at the interface between the saturated and unsaturated zones (ISU) are limited. Uncertainties exist regarding N2O emissions from the soil-shallow groundwater systems in agricultural fields. In this study, a three-year lysimeter experiment (2019-2020, 2022) was conducted to simulate the soil-shallow groundwater systems under four controlled shallow groundwater depth (SGD) (i.e., SGD = 40, 70, 110, and 150 cm) conditions in North China Plain (NCP). Weekly continuous monitoring of N2O emissions from soil surface, N2O concentration in the shallow groundwater and the upper 10 cm of pores at the ISU, and nitrogen cycling-related parameters in the soil and groundwater was conducted. The results showed that soil surface N2O emissions increased with decreased shallow groundwater depth, and the highest emissions of 96.44 kg ha-1 and 104.32 kg ha-1 were observed at G2 (SGD = 40 cm) in 2020 and 2022. During the observation period of one maize growing season, shallow groundwater acted as a sink for the unsaturated zone when the groundwater depth was 40 cm, 70 cm, and 110 cm. However, when SGD was 150 cm, shallow groundwater became a source for the unsaturated zone. After fertilization, the groundwater in all treatment plots behaved as a sink for the unsaturated zone, and the diffusion intensity decreased with increasing SGD. The results would provide a theoretical basis for cropland water management to reduce N2O emissions.

COVID-19 antibody responses in individuals with natural immunity and with vaccination-induced immunity: a systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has caused a large mortality and morbidity burden globally. For individuals, a strong immune response is the most effective means to block SARS-CoV-2 infection. To inform clinical case management of COVID-19, development of improved vaccines, and public health policy, a better understanding of antibody response dynamics and duration following SARS-CoV-2 infection and after vaccination is imperatively needed. METHODS: We systematically analyzed antibody response rates in naturally infected COVID-19 patients and vaccinated individuals. Specifically, we searched all published and pre-published literature between 1 December 2019 and 31 July 2023 using MeSH terms and "all field" terms comprising "COVID-19" or "SARS-CoV-2," and "antibody response" or "immunity response" or "humoral immune." We included experimental and observational studies that provided antibody positivity rates following natural COVID-19 infection or vaccination. A total of 44 studies reporting antibody positivity rate changes over time were included. RESULTS: The meta-analysis showed that within the first week after COVID-19 symptom onset/diagnosis or vaccination, antibody response rates in vaccinated individuals were lower than those in infected patients (p < 0.01), but no significant difference was observed from the second week to the sixth month. IgG, IgA, and IgM positivity rates increased during the first 3 weeks; thereafter, IgG positivity rates were maintained at a relatively high level, while the IgM seroconversion rate dropped. CONCLUSIONS: Antibody production following vaccination might not occur as quickly or strongly as after natural infection, and the IgM antibody response was less persistent than the IgG response.

Non-negligible N2O emission hotspots: Rivers impacted by ion-adsorption rare earth mining.

Rare earth mining causes severe riverine nitrogen pollution, but its effect on nitrous oxide (N2O) emissions and the associated nitrogen transformation processes remain unclear. Here, we characterized N2O fluxes from China's largest ion-adsorption rare earth mining watershed and elucidated the mechanisms that drove N2O production and consumption using advanced isotope mapping and molecular biology techniques. Compared to the undisturbed river, the mining-affected river exhibited higher N2O fluxes (7.96 ± 10.18 mmol m-2d-1 vs. 2.88 ± 8.27 mmol m-2d-1, P = 0.002), confirming that mining-affected rivers are N2O emission hotspots. Flux variations scaled with high nitrogen supply (resulting from mining activities), and were mainly attributed to changes in water chemistry (i.e., pH, and metal concentrations), sediment property (i.e., particle size), and hydrogeomorphic factors (e.g., river order and slope). Coupled nitrification-denitrification and N2O reduction were the dominant processes controlling the N2O dynamics. Of these, the contribution of incomplete denitrification to N2O production was greater than that of nitrification, especially in the heavily mining-affected reaches. Co-occurrence network analysis identified Thiomonas and Rhodanobacter as the key genus closely associated with N2O production, suggesting their potential roles for denitrification. This is the first study to elucidate N2O emission and influential mechanisms in mining-affected rivers using combined isotopic and molecular techniques. The discovery of this study enhances our understanding of the distinctive processes driving N2O production and consumption in highly anthropogenically disturbed aquatic systems, and also provides the foundation for accurate assessment of N2O emissions from mining-affected rivers on regional and global scales.

Pollution caused by mining reshaped the structure and function of bacterial communities in China's largest ion-adsorption rare earth mine watershed.

Ion-adsorption rare earth mining results in the production of high levels of nitrogen, multiple metals, and strong acidic mine drainage (AMD), the impacts of which on microbial assembly and ecological functions remain unclear. To address this knowledge gap, we collected river sediments from the watershed of China's largest ion-adsorption rare earth mine and analyzed the bacterial community's structure, function, and assembly mechanisms. Results showed that bacterial community assembly was weakly affected by spatial dispersion, and dispersal limitation and homogeneous selection were the dominant ecological processes, with the latter increasing with pollution gradients. Bacterial alpha diversity decreased with pollution, which was mainly influenced by lead (Pb), pH, rare earth elements (REEs), and electrical conductivity (EC). However, bacteria developed survival strategies (i.e., enhanced acid tolerance and interspecific competition) to adapt to extreme environments, sustaining species diversity and community stability. Community structure and function showed a consistent response to the polluted environment (r = 0.662, P = 0.001). Enhanced environmental selection reshaped key microbial-mediated biogeochemical processes in the mining area, in particular weakening the potential for microbial denitrification. These findings provide new insights into the ecological response of microbes to compound pollution and offer theoretical support for proposing effective remediation and management strategies for polluted areas.

Developmental dynamic transcriptome and systematic analysis reveal the major genes underlying isoflavone accumulation in soybean.

Introduction: Soy isoflavone, a class of polyphenolic compounds exclusively occurred in legumes, is an important bioactive compound for both plants and human beings. The outline of isoflavones biosynthesis pathway has been drawn up basically in the previous research. However, research on the subject has been mostly restricted to investigate the static regulation of isoflavone content in soybean, rather than characterize its dynamic variation and modulation network in developing seeds. Methods: In this study, by using eight recombinant inbred lines (RIL), the contents of six isoflavone components in the different stages of developing soybean seeds were determined to characterize the dynamic variation of isoflavones, and the isoflavones accumulation pattern at physiological level was investigated. Meanwhile, we integrated and analyzed the whole genome expression profile of four lines and 42 meta-transcriptome data, based on the multiple algorithms. Results: This study: 1) obtained 4 molecular modules strongly correlated with isoflavone accumulation; 2) identified 28 novel major genes that could affect the accumulation of isoflavones in developing seeds free from the limitation of environments; 3) discussed the dynamic molecular patterns regulating isoflavones accumulation in developing seed; 4) expanded the isoflavone biosynthesis pathway. Discussion: The results not only promote the understandings on the biosynthesis and regulation of isoflavones at physiological and molecular level, but also facilitate to breed elite soybean cultivars with high isoflavone contents.

Association of volatile anesthesia exposure and depth with emergence agitation and delirium in children: Prospective observational cohort study.

Background: Sevoflurane anesthesia is widely used in pediatric ambulatory surgery. However, emergency agitation (EA) and emergency delirium (ED), as major complications following sevoflurane anesthesia in children, pose risks to surgery and prognosis. Identifying the high risk of EA/ED, especially anesthesia exposure and the depth of anesthesia, may allow preemptive treatment. Methods: A total of 137 patients were prospectively enrolled in this single-center observational cohort study to assess the incidence of EA or ED. Multivariable logistic regression analyses were used to test the association between volatile anesthesia exposure and depth with EA or ED. The Richmond Agitation and Sedation Scale (RASS), Pediatric Anesthesia Emergence Delirium Scale (PAED) and Face, Legs, Activity, Cry, and Consolability (FLACC) behavioural pain scale was used to assess the severity of EA or ED severity and pain. Bispectral index (BIS) to monitor the depth of anesthesia, as well as TimeLOW-BIS/TimeANES %, EtSevo (%) and EtSevo-time AUC were included in the multivariate logistic regression model as independent variables to analyze their association with EA or ED. Results: The overall prevalence of EA and ED was 73/137 (53.3%) and 75/137 (54.7%) respectively, where 48/137 (35.0%), 19/137 (13.9%), and 6/137 (4.4%) had mild, moderate, and severe EA. When the recovery period was lengthened, the prevalence of ED and extent of FLACC decreased and finally normalized within 30 min in recovered period. Multivariable logistic regression demonstrated that intraoperative agitation [2.84 (1.08, 7.47) p = 0.034], peak FLACC [2.56 (1.70, 3.85) p < 0.001] and adverse event (respiratory complications) [0.03 (0.00, 0.29) p = 0.003] were independently associated with higher odds of EA. Taking EtSevo-time AUC ≤ 2,000 as a reference, the incidence of EA were [15.84 (2.15, 116.98) p = 0.002] times and 16.59 (2.42, 113.83) p = 0.009] times for EtSevo-time AUC 2,500-3,000 and EtSevo-time AUC > 3,000, respectively. Peak FLACC [3.46 (2.13, 5.62) p < 0.001] and intraoperative agitation [5.61 (1.99, 15.86) p = 0.001] were independently associated with higher odds of developing ED. EtSevo (%), intraoperative BIS value and the percentage of the duration of anesthesia at different depths of anesthesia (BIS ≤ 40, BIS ≤ 30, BIS ≤ 20) were not associated with EA and ED. Conclusions: For pediatrics undergoing ambulatory surgery where sevoflurane anesthesia was administered, EA was associated with surgical time, peak FLACC, respiratory complications, and "EtSevo-time AUC" with a dose-response relationship; ED was associated with peak FLACC and intraoperative agitation.

m6A Methyltransferase, WTAP, Promotes Cancer Progression in Laryngeal Squamous Cell Carcinoma by Regulating PLAU Stability.

OBJECTIVE: Laryngeal squamous cell carcinoma (LSCC) is a malignancy originating from laryngeal squamous cell lesions. Wilm's tumor 1-associated protein (WTAP)-mediated N6-methyladenosine (m6A) modification has been verified to stimulate the progression of numerous cancers, except for LSCC. This study was aimed at exploring the role of WTAP and its mechanism of action in LSCC. METHODS: The expression of WTAP and plasminogen activator urokinase (PLAU) mRNAs in LSCC tissues and cells was quantified using qRT-PCR. Western blotting was performed to estimate PLAU levels in LSCC cells. The relationship between WTAP and PLAU was ascertained using luciferase reporter and methylated-RNA immunoprecipitation (Me-RIP) assays. Functionally, the interaction of WTAP with PLAU in LSCC cells was investigated using CCK-8, EdU, and Transwell assays. RESULTS: The expression of WTAP and PLAU was increased in LSCC, and was positively correlated. WTAP regulated PLAU stability in an m6A-dependent manner. WTAP deficiency suppressed the migration, invasion, and proliferation of LSCC cells. Overexpression of PLAU rescued the phenotype induced by WTAP knockdown in vitro. CONCLUSIONS: These results indicate that WTAP mediates the m6A modification of PLAU to accelerate the growth, migration, and invasion of cells in LSCC. To our knowledge, this is the first report to clarify the functions of WTAP in LSCC and the underlying mechanisms in detail. Based on these findings, we suggest that WTAP may serve as a therapeutic target for LSCC.

Performance of anammox enchanced by pulsed electric fields under added organic carbon sources using integrated network and metagenomics analyses.

This paper aims to investigate the function of a pulsed electric field (PEF) in the anaerobic ammonia oxidation (anammox) process after adding certain chemical oxygen demand (COD) through integrated network and metagenomics analyses. The findings showed that the presence of COD was detrimental to anammox, but PEF could significantly reduce the adverse effect. The total nitrogen removal in the reactor for applying PEF was 16.99% higher on average than the reactor for only dosing COD. Additionally, PEF upgraded the abundance of anammox bacteria subordinate to the phylum Planctomycetes by 9.64%. The analysis of molecular ecological networks promulgated that PEF resulted in an increase in network scale and topology complexity, thereby boosting the potential collaboration of the communities. Metagenomics analyses demonstrated that PEF dramatically promoted anammox central metabolism in the presence of COD, specifically enhancing pivotal N functional genes (hzs, hdh, amo, hao, nas, nor and nos).

Trends in anemia management in lung and colon cancer patients in the US Department of Veterans Affairs, 2002-2008.

PURPOSE: In 2007, growing concerns about adverse impacts of erythropoiesis-stimulating agents (ESAs) in cancer patients led to an FDA-mandated black box warning on product labeling, publication of revised clinical guidelines, and a Medicare coverage decision limiting ESA coverage. We examined ESA therapy in lung and colon cancer patients receiving chemotherapy in the VA from 2002 to 2008 to ascertain trends in and predictors of ESA use. METHODS: A retrospective study employed national VA databases to "observe" treatment for a 12-month period following diagnosis. Multivariable logistic regression analyses evaluated changes in ESA use following the FDA-mandated black box warning in March 2007 and examined trends in ESA administration between 2002 and 2008. RESULTS: Among 17,014 lung and 4,225 colon cancer patients, those treated after the March 2007 FDA decision had 65% (lung OR 0.35, CI(95%) 0.30-0.42) and 53% (colon OR 0.47, CI(95%) 0.36-0.63) reduced odds of ESA treatment compared to those treated before. Declines in predicted probabilities of ESA use began in 2006. The magnitude of the declines differed across age groups among colon patients (p = 0.01) and levels of hemoglobin among lung cancer patients (p = 0.04). CONCLUSIONS: Use of ESA treatment for anemia in VA cancer care declined markedly after 2005, well before the 2007 changes in product labeling and clinical guidelines. This suggests that earlier dissemination of research results had marked impacts on practice patterns with these agents.

The Use of Deep Learning-Based Intelligent Music Signal Identification and Generation Technology in National Music Teaching.

The research expects to explore the application of intelligent music recognition technology in music teaching. Based on the Long Short-Term Memory network knowledge, an algorithm model which can distinguish various music signals and generate various genres of music is designed and implemented. First, by analyzing the application of machine learning and deep learning in the field of music, the algorithm model is designed to realize the function of intelligent music generation, which provides a theoretical basis for relevant research. Then, by selecting massive music data, the music style discrimination and generation model is tested. The experimental results show that when the number of hidden layers of the designed model is 4 and the number of neurons in each layer is 1,024, 512, 256, and 128, the training result difference of the model is the smallest. The classification accuracy of jazz, classical, rock, country, and disco music types can be more than 60% using the designed algorithm model. Among them, the classification effect of jazz schools is the best, which is 77.5%. Moreover, compared with the traditional algorithm, the frequency distribution of the music score generated by the designed algorithm is almost consistent with the spectrum of the original music. Therefore, the methods and models proposed can distinguish music signals and generate different music, and the discrimination accuracy of different music signals is higher, which is superior to the traditional restricted Boltzmann machine method.

Fluvial CO2 and CH4 in a lowland agriculturally impacted river network: Importance of local and longitudinal controls.

Despite streams and rivers play a critical role as conduits of terrestrially produced organic carbon to the atmosphere, fluvial CO2 and CH4 are seldom integrated into regional carbon budgets. High spatial variability hinders our ability to understand how local and longitudinal controls affect underlying processes of riverine CO2 and CH4 and challenge the prediction and upscaling across large areas. Here, we conducted a survey of fluvial CO2 and CH4 concentrations spanning multiple stream orders within an agriculturally impacted region, the North China Plain. We explored the spatial patterns of fluvial CO2 and CH4 concentrations, and then examined whether catchment and network properties and water chemical parameters can explain the variations in both carbon gases. Streams and rivers were systematically supersaturated with CO2 and CH4 with the mean concentrations being 111 and 0.63 µmol L-1, respectively. Spatial variability of both gases was regulated by network properties and catchment features. Fluvial CO2 and CH4 declined longitudinally and could be modeled as functions of stream order, dissolved oxygen, and water temperature. Both models explained about half of the variability and reflected longitudinal and local drivers simultaneously, albeit CO2 was more local-influenced and CH4 more longitudinal-influenced. Our empirical models in this work contribute to the upscaling and prediction of CO2 and CH4 emissions from streams and rivers and the understanding of proximal and remote controls on spatial patterns of both gases in agriculturally impacted regions.