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Increasing global food demand will require more food production1 without further exceeding the planetary boundaries2 while simultaneously adapting to climate change3. We used an ensemble of wheat simulation models with improved sink and source traits from the highest-yielding wheat genotypes4 to quantify potential yield gains and associated nitrogen requirements. This was explored for current and climate change scenarios across representative sites of major world wheat producing regions. The improved sink and source traits increased yield by 16% with current nitrogen fertilizer applications under both current climate and mid-century climate change scenarios. To achieve the full yield potential-a 52% increase in global average yield under a mid-century high warming climate scenario (RCP8.5), fertilizer use would need to increase fourfold over current use, which would unavoidably lead to higher environmental impacts from wheat production. Our results show the need to improve soil nitrogen availability and nitrogen use efficiency, along with yield potential.
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Mudança Climática , Fertilizantes , Nitrogênio , Triticum , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Fertilizantes/análise , Nitrogênio/metabolismo , Solo/químicaRESUMO
This study aims to elucidate the therapeutic effect and mechanism of Jingfang Granules on acute lung injury, and to investigate the regulatory effect of Jingfang Granules on the metabolic disorders of endogenous metabolites in feces and the homeostasis of intestinal microbiota in acute lung injury, mice were randomly divided into a sham group, a model group, and a Jingfang Granules group. After modeling, the mice were continuously administered for 6 days. Using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry(UHPLC-HESI-QE-Orbitrap-MS/MS) metabolomics technology and 16S rRNA high-throughput sequencing technology, changes in endogenous small molecule substances and gut microbiota in mouse intestines were determined, and potential biomarkers were identified. The results showed that Jingfang Granules can regulate 11 biomarkers, including L-glutamic acid, succinic acid, arachidonic acid, linoleic acid, linolenic acid, phenylalanine, sphingosine, 2-hydroxy-2-methyl butyric acid, pyruvate, tryptophan, and palmitic acid. Metabolic pathway analysis was conducted on these 11 biomarkers using the online software MetaboAnalyst, identifying potential major metabolic pathways. Among them, a total of 10 metabolic pathways are closely related to the treatment of acute lung injury with Jingfang Granules, including alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate cycle(TCA cycle), alyoxylate and dicarboxylate metabolism, arginine and proline metabolism, linoleic acid metabolism and linolenic acid metabolism, nitrogen metabolism, D-glutamine and D-gluta-matemetabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism. The results of gut microbiota showed significant differences in bacteria, mainly including Bacteroides, Akkermansia, Lachnospiraceae_NK4A136_group, Lachnochlostridium, and Klebsiella. Spearman analysis confirms that Akkermansia and Lachnospiraceae_NK4A136_group is a significant positive correlation between the abundance of succinic acid, arachidonic acid, linolenic acid, linoleic acid, butyric acid, and pyruvate in the group; Bacteroides, Klebsiella, Lachnochlostrium are significantly positively correlated with the abundance of L-glutamic acid, phenylalanine, and sphingosine. The above results indicate that the therapeutic effect of Jingfang Granules on acute lung injury is achieved by improving the imbalance of gut microbiota in mice with acute lung injury, balancing the metabolism of alanine, biosynthesis of aminoacyl tRNA, aspartic acid, glutamate, tricarboxylic acid cycle, biosynthesis of phenylalanine, tyrosine, tryptophan, and metabolism of linoleic acid.
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Lesão Pulmonar Aguda , Medicamentos de Ervas Chinesas , Fezes , Microbioma Gastrointestinal , Metabolômica , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/microbiologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Fezes/microbiologia , Fezes/química , Humanos , Cromatografia Líquida de Alta PressãoRESUMO
Co-optimization of multiple management practices may facilitate climate-smart agriculture, but is challenged by complex climate-crop-soil management interconnections across space and over time. Here we develop a hybrid approach combining agricultural system modelling, machine learning and life cycle assessment to spatiotemporally co-optimize fertilizer application, irrigation and residue management to achieve yield potential of wheat and maize and minimize greenhouse gas emissions in the North China Plain. We found that the optimal fertilizer application rate and irrigation for the historical period (1995-2014) are lower than local farmers' practices as well as trial-derived recommendations. With the optimized practices, the projected annual requirement of fertilizer, irrigation water and residue inputs across the North China Plain in the period 2051-2070 is reduced by 16% (14-21%) (mean with 95% confidence interval), 19% (7-32%) and 20% (16-26%), respectively, compared with the current supposed optimal management in the historical reference period, with substantial greenhouse gas emission reductions. We demonstrate the potential of spatiotemporal co-optimization of multiple management practices and present digital mapping of management practices as a benchmark for site-specific management across the region.
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Gases de Efeito Estufa , Fertilizantes/análise , Produtos Agrícolas , Agricultura , Produção AgrícolaRESUMO
The organ-specific critical nitrogen (Nc) dilution curves are widely thought to represent a new approach for crop nitrogen (N) nutrition diagnosis, N management, and crop modeling. The Nc dilution curve can be described by a power function (Nc = A1·W-A2), while parameters A1 and A2 control the starting point and slope. This study aimed to investigate the uncertainty and drivers of organ-specific curves under different conditions. By using hierarchical Bayesian theory, parameters A1 and A2 of the organ-specific Nc dilution curves for wheat were derived and evaluated under 14 different genotype × environment × management (G × E × M) N fertilizer experiments. Our results show that parameters A1 and A2 are highly correlated. Although the variation of parameter A1 was less than that of A2, the values of both parameters can change significantly in response to G × E × M. Nitrogen nutrition index (NNI) calculated using organ-specific Nc is in general consistent with NNI estimated with overall shoot Nc, indicating that a simple organ-specific Nc dilution curve may be used for wheat N diagnosis to assist N management. However, the significant differences in organ-specific Nc dilution curves across G × E × M conditions imply potential errors in Nc and crop N demand estimated using a general Nc dilution curve in crop models, highlighting a clear need for improvement in Nc calculations in such models. Our results provide new insights into how to improve modeling of crop nitrogen-biomass relations and N management practices under G × E × M.
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Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine and metabolic disease. Orlistat as a lipase inhibitor may improve the pathological characteristics of PCOS and is the sole antiobesity agent available in various countries. In this study, the PCOS rat models were established using letrozole and high-fat diet. Tandem Mass Tag labeling peptide coupled with liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach was employed to investigate the differentially expressed ovarian proteins (DEPs) in the PCOS and control rats for the effect of PCOS, and in the PCOS and orlistat-treated PCOS rats for the effect of orlistat in PCOS. The orlistat attenuated the body weight gain; decreased the levels of testosterone, luteinizing hormone, a ratio of luteinizing/follicle-stimulating hormones; increased the level of estradiol; and recovered the estrous cycle in PCOS rats. In addition, 795 and 119 DEPs were found in PCOS and orlistat-treated PCOS groups, respectively. Based on the Gene Ontology and Kyoto Encyclopedia of Gene and Genomes pathway analysis of DEPs, orlistat restored the disturbed metabolism of linoleic acid, arachidonic acid, galactose, and glycerolipids, and then improved the chronic inflammation in PCOS rats. This study analyzed the ovarian proteome of orlistat-treated PCOS rats and identified targeted proteins, which explored the pathogenesis of PCOS and the potential effects of orlistat in PCOS rats.
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BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats.
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Microbiota , Síndrome do Ovário Policístico , Humanos , Feminino , Ratos , Animais , Síndrome do Ovário Policístico/metabolismo , Orlistate/uso terapêutico , Letrozol/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , RNA Ribossômico 16S/genética , Hormônios Esteroides Gonadais , Metabolômica , Esteroides/uso terapêuticoRESUMO
Extreme weather events threaten food security, yet global assessments of impacts caused by crop waterlogging are rare. Here we first develop a paradigm that distils common stress patterns across environments, genotypes and climate horizons. Second, we embed improved process-based understanding into a farming systems model to discern changes in global crop waterlogging under future climates. Third, we develop avenues for adapting cropping systems to waterlogging contextualised by environment. We find that yield penalties caused by waterlogging increase from 3-11% historically to 10-20% by 2080, with penalties reflecting a trade-off between the duration of waterlogging and the timing of waterlogging relative to crop stage. We document greater potential for waterlogging-tolerant genotypes in environments with longer temperate growing seasons (e.g., UK, France, Russia, China), compared with environments with higher annualised ratios of evapotranspiration to precipitation (e.g., Australia). Under future climates, altering sowing time and adoption of waterlogging-tolerant genotypes reduces yield penalties by 18%, while earlier sowing of winter genotypes alleviates waterlogging by 8%. We highlight the serendipitous outcome wherein waterlogging stress patterns under present conditions are likely to be similar to those in the future, suggesting that adaptations for future climates could be designed using stress patterns realised today.
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Aclimatação , Água , Estações do Ano , Adaptação Fisiológica , AgriculturaRESUMO
BACKGROUND: Axillary lymph node metastasis (ALNM) is one of the most important prognostic factors for breast cancer patients, and DNA methylation is involved in ALNM of breast cancer. However, the methylation profile of breast cancer ALNM remains unknown. METHODS: Breast cancer tissues were collected from patients with and without ALNM. We investigated the genome-wide DNA methylation profile in breast cancer with and without ALNM using reduced representation bisulfite sequencing (RRBS). Then, differentially methylated regions (DMRs) were verified by targeted bisulfite sequencing. RESULTS: A total of 21491 DMRs were identified between the lymph node positive group and negative group. Compared to the LN-negative breast cancer, LN-positive breast cancer had 10,920 hypermethylated DMRs and 10,571 hypomethylated DMRs. Then, 10 DMRs in the gene promoter region were detected by targeted bisulfite sequencing, these gene included HOXA5, PTOV1-AS1, RHOF, PAX6, GSTP1, RASGRF2, AKR1B1, BNIP3, CRMP1, ING5. Compared with negative lymph node, the promoter methylation levels of RASGRF2, AKR1B1 and CRMP1 increased in positive lymph node, while the promoter methylation level of RHOF decreased in positive lymph node. In addition, Cancer Genome Atlas (TCGA) data showed that RASGRF2, AKR1B1 and CRMP1 were low expressed in breast Cancer tissues, while RHOF was high expressed in breast Cancer tissues. Furthermore, in addition to highly methylated AKR1B1, RASGRF2 and CRMP1 gene promoters, BNIP3, GSTP1, HOXA5 and PAX6 gene promoters were also methylated in ER-positive and HER2-negative breast cancer with ALNM. CONCLUSIONS: When compared to negative lymph node breast cancer, the positive lymph node breast cancer has a differential methylation status. Promoter methylation of RASGRF2, AKR1B1, CRMP1 and RHOF in lymph node positive breast cancer tissues was significantly different from that in lymph node negative breast cancer tissues. AKR1B1, RASGRF2, CRMP1, BNIP3, GSTP1, HOXA5 and PAX6 genes were methylated in ER-positive and HER2-negative breast cancer with ALNM. The study provides an important biological base for understanding breast cancer with ALNM and developing therapeutic targets for breast cancer with ALNM.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/genética , Metilação de DNA/genética , Linfonodos , Metástase Linfática/genéticaRESUMO
To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1ß(IL-1ß) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-ß(TGF-ß), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1ß in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-ß, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-ß/Smad4 signaling pathway.
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Interleucina-6 , Fator de Necrose Tumoral alfa , Camundongos , Masculino , Animais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Azeite de Oliva/metabolismo , Azeite de Oliva/farmacologia , Azeite de Oliva/uso terapêutico , Tetracloreto de Carbono/efeitos adversos , Tetracloreto de Carbono/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fígado , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Although oral probiotics can improve breast microecology and alleviate the inflammatory response, there are no data regarding cases with existing abscesses. We aimed to investigate the effect of Lactobacillus fermentum CECT5716 during needle aspiration in patients with lactational breast abscesses. Patients (aged 20-41 years) with lactational single-cavity breast abscesses (diameter 3-6 cm) from 12 hospitals were randomly assigned to the experimental (n = 51) and control groups (n = 50). Outcome measures included the abscess cure rate on treatment day-5, delactation rate, relieving pain rate, and number of needle aspirations until day-28. The experimental group's 5-day cure rate (43.1%) was significantly higher (p < 0.05). Breastfeeding continuation on day-5 did not differ significantly (experimental group: 88.2%, control group: 96.0%, p = 0.269). In the experimental and control groups, 19.6% and 14.0% of patients experienced moderate to severe pain on day-5, respectively, with no statistically significant differences (p = 0.451). Four patients in each group developed diarrhea, with adverse reaction rates of 7.84% and 8.0%, respectively. No adverse reactions were reported in the infants. L. fermentum can shorten the healing time in patients with lactational breast abscesses.Trial registration This study was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), registration number: ChiCTR2000032682, registration date: 6/May/ 2020; first entry date: 11/May/2020.
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Empiema Pleural , Mastite , Probióticos , Abscesso/terapia , Aleitamento Materno/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mastite/terapia , Dor , Probióticos/uso terapêuticoRESUMO
Potato production plays an important role in safeguarding food security in China since the central government implemented the 'Potato-as-Staple-Food' policy in 2015. However, a key challenge facing China's potato production is to realize a tradeoff between economic return and environmental impact. Effective strategies for reducing carbon emission without compromising potato yield remain to be developed. This study conducted a comprehensive assessment by integrating climate, soil, crop, and agricultural input data, crop model and life cycle impact assessment model to quantify potato yields, GHG emission amounts and intensities (GHGI), and economic benefits under the conventional planting pattern (CPP), the lowest GHG emission pattern (LEP), and the highest yield pattern (HYP) across China's potato planting regions including four sub-regions, i.e., North Single planting region (NS), Central Double planting region (CD), South Winter planting region (SW), and Southwest Mixed planting region (SWM). Averaged fresh potato yield, GHG emission amount, and GHGI under the CPP were 21.7 t ha-1, 2815.1 kg CO2eq ha-1, and 137.3 kg CO2eq t-1, respectively, in China's potato planting region. Compared with the CPP, averaged GHG emission amount and GHGI under the LEP could be decreased by 48.2 % and 51.5 % respectively while the fresh potato yield and economic benefit could be enhanced by 8.1 % and 18.5 %, respectively. For the HYP, averaged GHG emission amount and GHGI could be decreased by 24.2 % and 39.8 % respectively while the fresh potato yield and economic benefit could be enhanced by 18.7 % and 39.6 %, respectively, compared with the CPP. Across the four potato planting regions, SW had the largest potential in reducing GHG emissions owing to a high reduction amount of nitrogen application rate. Our study demonstrates that optimizing agronomic management could reduce environmental impact without compromising economic benefit and provides a scientific method for assessing crop potential to realize the climate-smart planting.
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Solanum tuberosum , Agricultura/métodos , Carbono , China , Fertilizantes , Nitrogênio , SoloRESUMO
Crop multi-model ensembles (MME) have proven to be effective in increasing the accuracy of simulations in modelling experiments. However, the ability of MME to capture crop responses to changes in sowing dates and densities has not yet been investigated. These management interventions are some of the main levers for adapting cropping systems to climate change. Here, we explore the performance of a MME of 29 wheat crop models to predict the effect of changing sowing dates and rates on yield and yield components, on two sites located in a high-yielding environment in New Zealand. The experiment was conducted for 6 years and provided 50 combinations of sowing date, sowing density and growing season. We show that the MME simulates seasonal growth of wheat well under standard sowing conditions, but fails under early sowing and high sowing rates. The comparison between observed and simulated in-season fraction of intercepted photosynthetically active radiation (FIPAR) for early sown wheat shows that the MME does not capture the decrease of crop above ground biomass during winter months due to senescence. Models need to better account for tiller competition for light, nutrients, and water during vegetative growth, and early tiller senescence and tiller mortality, which are exacerbated by early sowing, high sowing densities, and warmer winter temperatures.
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Mudança Climática , Triticum , Biomassa , Estações do Ano , TemperaturaRESUMO
Importance: Acupoint hot compress during the early postpartum period may benefit patients after a vaginal delivery, but the evidence of this effect is limited. Objective: To assess whether acupoint hot compress involving the abdominal, lumbosacral, and plantar regions could reduce the incidence of postpartum urinary retention, relieve postpartum uterine contraction pain, prevent emotional disorders, and promote lactation. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted at 12 hospitals in China. Pregnant patients were screened for eligibility (n = 13â¯949) and enrolled after vaginal delivery (n = 1200) between January 17 and August 15, 2021; data collection was completed on August 18, 2021. After vaginal delivery, these participants were randomized 1:1 to either the intervention group or control group. Statistical analysis was based on per-protocol population. Interventions: Participants in the control group received routine postpartum care. Participants in the intervention group received routine postpartum care plus 3 sessions of a 4-hour acupoint hot compress involving the abdominal, lumbosacral, and plantar regions within 30 minutes, 24 hours, and 48 hours after delivery. Main Outcomes and Measures: The primary outcome was the incidence of postpartum urinary retention, defined as the first urination occurring more than 6.5 hours after delivery and/or use of an indwelling catheter within 72 hours after delivery. The secondary outcomes were postpartum uterine contraction pain intensity (assessed with the visual analog scale [VAS]), depressive symptoms (assessed with the Edinburgh Postnatal Depression Scale), and lactation conditions (including lactation initiation time, breastfeeding milk volume, feeding mood and times, and newborn weight). Results: Of the 1200 participants randomized, 1085 completed the study (537 in the intervention group and 548 in the control group, with a median [IQR] age of 26.0 [24.0-29.0] years). Participants in the intervention group compared with the control group had significantly decreased incidence of postpartum urinary retention (relative risk [RR], 0.58; 95% CI, 0.35-0.98; P = .03); improved postpartum uterine contraction pain when measured at 6.5 hours (median [IQR] VAS score, 1 [1-2] vs 2 [1-2]; P < .001), 28.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [1-2]; P < .001), 52.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [0-1]; P < .001), and 76.5 hours (median [IQR] VAS score, 0 [0-1] vs 0 [0-1]; P = .01) after delivery; reduced depressive symptoms (RR, 0.73; 95% CI, 0.54-0.98; P = .01); and increased breastfeeding milk volume measured at 28.5, 52.5, and 76.5 hours after delivery. No adverse events occurred in either of the 2 groups. Conclusions and Relevance: Results of this trial showed that acupoint hot compress after vaginal delivery decreased postpartum urinary retention, uterine contraction pain, and depressive symptoms and increased breastfeeding milk volume. Acupoint hot compress may be considered as an adjunctive intervention in postnatal care that meets patient self-care needs. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038417.
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Pontos de Acupuntura , Retenção Urinária , Adulto , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Dor , Período Pós-Parto , Gravidez , Retenção Urinária/etiologia , Retenção Urinária/terapia , Adulto JovemRESUMO
Small cell lung cancer (SCLC) is a type of neuroendocrine tumor with high malignancy and poor prognosis. Besides the de novo SCLC, there is transformed SCLC, which has similar characteristics of pathological morphology, molecular characteristics, clinical manifestations and drug sensitivity. However, de novo SCLC and transformed SCLC have different pathogenesis and tumor microenvironment. SCLC transformation is one of the mechanisms of resistance to chemotherapy, immunotherapy, and targeted therapy in NSCLC. Two hypotheses have been used to explain the pathogenesis of SCLC transformation. Although SCLC transformation is not common in clinical practice, it has been repeatedly identified in many small patient series and case reports. It usually occurs in epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma after treatment with tyrosine kinase inhibitors (TKIs). SCLC transformation can also occur in anaplastic lymphoma kinase (ALK)-positive lung cancer after treatment with ALK inhibitors and in wild-type EGFR or ALK NSCLC treated with immunotherapy. Chemotherapy was previously used to treat transformed SCLC, yet it is associated with an unsatisfactory prognosis. We comprehensively review the advancements in transformed SCLC, including clinical and pathological characteristics, and the potential effective treatment after SCLC transformation, aiming to give a better understanding of transformed SCLC and provide support for clinical uses.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia , Mutação , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Transformação Celular Neoplásica/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND AND AIMS: Functional-structural plant (FSP) models provide insights into the complex interactions between plant architecture and underlying developmental mechanisms. However, parameter estimation of FSP models remains challenging. We therefore used pattern-oriented modelling (POM) to test whether parameterization of FSP models can be made more efficient, systematic and powerful. With POM, a set of weak patterns is used to determine uncertain parameter values, instead of measuring them in experiments or observations, which often is infeasible. METHODS: We used an existing FSP model of avocado (Persea americana 'Hass') and tested whether POM parameterization would converge to an existing manual parameterization. The model was run for 10 000 parameter sets and model outputs were compared with verification patterns. Each verification pattern served as a filter for rejecting unrealistic parameter sets. The model was then validated by running it with the surviving parameter sets that passed all filters and then comparing their pooled model outputs with additional validation patterns that were not used for parameterization. KEY RESULTS: POM calibration led to 22 surviving parameter sets. Within these sets, most individual parameters varied over a large range. One of the resulting sets was similar to the manually parameterized set. Using the entire suite of surviving parameter sets, the model successfully predicted all validation patterns. However, two of the surviving parameter sets could not make the model predict all validation patterns. CONCLUSIONS: Our findings suggest strong interactions among model parameters and their corresponding processes, respectively. Using all surviving parameter sets takes these interactions into account fully, thereby improving model performance regarding validation and model output uncertainty. We conclude that POM calibration allows FSP models to be developed in a timely manner without having to rely on field or laboratory experiments, or on cumbersome manual parameterization. POM also increases the predictive power of FSP models.
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Persea , Calibragem , Modelos Estruturais , IncertezaRESUMO
In the last decade, crop production in China has dramatically improved due to greater phosphorus (P) input. As P fertilizer application rates increased from 88 to 123 kg PO ha yr during 2004 to 2014, total P use efficiency (total P output in crops as a percentage of total P input) dropped from 68 to 20%, leading to an accumulation of >90 kg PO ha in the soil each year. Phosphorus lost from agriculture is the second greatest contributor to waterbody eutrophication in China, accounting for 25% of total P losses in 2010; the main contributor is livestock husbandry. Given these problems, as well as the finite nature of P reserves, three strategies are proposed here to reduce P fertilizer application rates, improve P use efficiency, and minimize the environmental risk caused by P loss in China: (i) improving soil legacy P utilization by modifying cropping systems, rhizosphere management, or microbial engineering, (ii) increasing P use efficiency by reducing P fertilizer applications and minimizing P fertilizer fixation, and (iii) promoting the extension of soil P management strategies. For these management strategies to succeed in China, close cooperation should be established among farmers, scientists, and governments in the future.
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Fertilizantes , Solo , Agricultura , Animais , China , FósforoRESUMO
Soil organic carbon (SOC) in the subsoil below 0.3 m accounts for the majority of total SOC and may be as sensitive to climate change as topsoil SOC. Here we map global SOC turnover times (τ) in the subsoil layer at 1 km resolution using observational databases. Global mean τ is estimated to be [Formula: see text] yr (mean with 95% confidence interval), and deserts and tundra show the shortest ([Formula: see text] yr) and longest ([Formula: see text] yr) τ respectively. Across the globe, mean τ ranges from 9 (the 5% quantile) to 6332 years (the 95% quantile). Temperature is the most important factor negatively affecting τ, but the overall effect of climate (including temperature and precipitation) is secondary compared with the overall effect of assessed soil properties (e.g., soil texture and pH). The high-resolution mapping of τ and the quantification of its controls provide a benchmark for diagnosing subsoil SOC dynamics under climate change.
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Early vigour, or faster early leaf area development, has been considered an important trait for rainfed wheat in dryland regions such as Australia. However, early vigour is a genetically complex trait, and results from field experiments have been highly variable. Whether early vigour can lead to improved water use efficiency and crop yields is strongly dependent on climate and management conditions across the entire growing season. Here, we present a modelling framework for simulating the impact of early vigour on wheat growth and yield at eight sites representing the major climate types in Australia. On a typical soil with plant available water capacity (PAWC) of 147 mm, simulated yield increase with early vigour associated with larger seed size was on average 4% higher compared with normal vigour wheat. Early vigour through selection of doubled early leaf sizes could increase yield by 16%. Increase in yield was mainly from increase in biomass and grain number, and was reduced at sites with seasonal rainfall plus initial soil water <300 mm. Opportunities exists for development of early vigour wheat varieties for wetter sites. Soil PAWC could play a significant role in delivering the benefit of early vigour and would require particular attention.
Assuntos
Folhas de Planta/fisiologia , Triticum/fisiologia , Austrália , Genótipo , Folhas de Planta/genética , Triticum/genéticaRESUMO
In spite of the increasing expectation for process-based crop modelling to capture genotype (G) by environment (E) by management (M) interactions to support breeding selections, it remains a challenge to use current crop models to accurately predict phenotypes from genotypes or from candidate genes. We use wheat as a target crop and the APSIM farming systems model (Holzworth et al., 2014) as an example to analyse the current status of process-based crop models with a major focus on need to improve simulation of specific eco-physiological processes and their linkage to underlying genetic controls. For challenging production environments in Australia, we examine the potential opportunities to capture physiological traits, and to integrate genetic and molecular approaches for future model development and applications. Model improvement will require both reducing the uncertainty in simulating key physiological processes and enhancing the capture of key observable traits and underlying genetic control of key physiological responses to environment. An approach consisting of three interactive stages is outlined to (i) improve modelling of crop physiology, (ii) develop linkage from model parameter to genotypes and further to loci or alleles, and (iii) further link to gene expression pathways. This helps to facilitate the integration of modelling, phenotyping, and functional gene detection and to effectively advance modelling of G×E×M interactions. While gene-based modelling is not always needed to simulate G×E×M, including well-understood gene effects can improve the estimation of genotype effects and prediction of phenotypes. Specific examples are given for enhanced modelling of wheat in the APSIM framework.