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Hypoxia featured in malignant tumors and the short lifespan of photo-induced reactive oxygen species (ROS) are two major issues that limit the efficiency of photodynamic therapy (PDT) in oncotherapy. Developing efficient type-I photosensitizers with long-term ËOH generation ability provides a possible solution. Herein, a semiconducting polymer-based photosensitizer PCPDTBT was found to generate 1O2, ËOH, and H2O2 through type-I/II PDT paths. After encapsulation within a mesoporous silica matrix, the NIR-II fluorescence and ROS generation are enhanced by 3-4 times compared with the traditional phase transfer method, which can be attributed to the excited-state lifetime being prolonged by one order of magnitude, resulting from restricted nonradiative decay channels, as confirmed by femtosecond spectroscopy. Notably, H2O2 production reaches 15.8 µM min-1 under a 730 nm laser (80 mW cm-2). Further adsorption of Fe2+ ions on mesoporous silica not only improves the loading capacity of the chemotherapy drug doxorubicin but also triggers a Fenton reaction with photo-generated H2O2 in situ to produce ËOH continuously after the termination of laser irradiation. Thus, semiconducting polymer-based nanocomposites enables NIR-II fluorescence imaging guided persistent PDT under hypoxic conditions. This work provides a promising paradigm to fabricate persistent photodynamic therapy platforms for hypoxia-tolerant phototheranostics.
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BACKGROUND: The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. METHODS: This study included 226 migraineurs and 452 age- and sex-matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP-SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. RESULTS: The RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [ORadj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068-2.281)]. One significant two-way SNP-SNP interaction was found (PRKCA rs2228945-BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. CONCLUSIONS: This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk.
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Trastornos Migrañosos , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-akt , Humanos , Trastornos Migrañosos/genética , Femenino , Masculino , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adulto , Transducción de Señal/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Persona de Mediana EdadRESUMEN
Plants primarily incorporate nitrate (NO3 -) and ammonium (NH4 +) as the primary source of inorganic nitrogen (N); the physiological mechanisms of photosynthesis (A) dropdown under NH4 + nutrition has been investigated in many studies. Leaf anatomy is a major determinant to mesophyll conductance (g m) and photosynthesis; however, it remains unclear whether the photosynthesis variations of plants exposed to different N forms is related to leaf anatomical variation. In this work, a common shrub, Lonicera japonica was hydroponically grown under NH4 +, NO3 - and 50% NH4 +/NO3 -. We found that leaf N significantly accumulated under NH4 +, whereas the photosynthesis was significantly decreased, which was mainly caused by a reduced g m. The reduced g m under NH4 + was related to the decreased intercellular air space, the reduced chloroplast number and especially the thicker cell walls. Among the cell wall components, lignin and hemicellulose contents under NH4 + nutrition were significantly higher than those in the other two N forms and were scaled negatively correlated with g m; while pectin content was independent from N forms. Pathway analysis further revealed that the cell wall components might indirectly regulate g m by influencing the thickness of the cell wall. These results highlight the importance of leaf anatomical variation characterized by modifications of chloroplasts number and cell wall thickness and compositions, in the regulation of photosynthesis in response to varied N sources.
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Despite various efforts to optimize the near-infrared (NIR) performance of perylene diimide (PDI) derivatives for bio-imaging, convenient and efficient strategies to amplify the fluorescence of PDI derivatives in biological environment and the intrinsic mechanism studies are still lacking. Herein, we propose an alkyl-doping strategy to amplify the fluorescence of PDI derivative-based nanoparticles for improved NIR fluorescence imaging. The developed PDI derivative, OPE-PDI, shows much brighter in n-Hexane (HE) compared with that in other organic media, and the excited state dynamics investigation experimentally elucidates the solvent effect-induced suppression of intermolecular energy transfer and intramolecular nonradiative decay as the underlying mechanism for the fluorescence improvement. Theoretical calculations reveal the lowest reorganization energies of OPE-PDI in HE among various solvents, indicating the effectively suppressed conformational relaxation to support the strongest radiative decay. Inspired by this, an alkyl atmosphere mimicking HE is constructed by incorporating the octadecane into OPE-PDI-based nanoparticles, permitting up to 3-fold fluorescence improvement compared with the counterpart nanoparticles. Owing to the merits of high brightness, anti-photobleaching, and low biotoxicity for the optimal nanoparticles, they have been employed for probing and long-term monitoring of tumor. This work highlights a facile strategy for the fluorescence enhancement of PDI derivative-based nanoparticles.
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Stable oxygen isotope ratio of tree-ring α-cellulose (δ18Ocel) yields valuable information on many aspects of tree-climate interactions. However, our current understanding of the mechanistic controls on δ18Ocel is incomplete, with a knowledge gap existent regarding the fractionation effect characterizing carbonyl-water oxygen exchange during sucrose translocation from leaf to phloem. To address this insufficiency, we set up an experimental system integrating a vapor 18O-labeling feature to manipulate leaf-level isotopic signatures in tree saplings enclosed within whole-canopy gas-exchange cuvettes. We applied this experimental system to three different tree species to determine their respective relationships between 18O enrichment of sucrose in leaf lamina (Δ18Ol_suc) and petiole phloem (Δ18Ophl_suc) under environmentally/physiologically stable conditions. Based on the determined Δ18Ophl_suc-Δ18Ol_suc relationships, we estimated that on average, at least 25% of the oxygen atoms in sucrose undergo isotopic exchange with water along the leaf-to-phloem translocation path and that the biochemical fractionation factor accounting for such exchange is c. 34, markedly higher than the conventionally assumed value of 27. Our study represents a significant step toward quantitative elucidation of the oxygen isotope dynamics during sucrose translocation in trees. This has important implications with respect to improving the δ18Ocel model and its related applications in paleoclimatic and ecophysiological contexts.
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Oxígeno , Árboles , Oxígeno/análisis , Sacarosa , Agua/análisis , Floema , Isótopos de Oxígeno/análisis , Hojas de la Planta/química , Isótopos de Carbono/análisisRESUMEN
BACKGROUND: Lodging is a major factor contributing to yield loss and constraining the mechanical harvesting of wheat crops. Genetic improvement through breeding effectively reduced the lodging and improved the grain yield, however, the physiological mechanisms involved in providing resistance to lodging are different in the breeding stage and are not clearly understood. The purpose of this study was to compare the differences in the lodging resistance (LR) of the wheat varieties released during the different decades and to explore the effect of the application of nitrogen (N) fertilizer on the plasticity of LR. RESULTS: A field study was conducted during the cultivation seasons of 2019-2020 and 2020-2021, in soil supplemented with three N levels: N0 (0 kg ha-1), N180 (200 kg ha-1), and N360 (360 kg ha-1) using eight varieties of wheat released for commercial cultivation from 1950 to date. The results obtained showed that genetic improvement had significantly enhanced the LR and grain yield in wheat. In the first breeding stage (from 1950 to 1980s) the lodging resistant index increased by 15.0%, which was primarily attributed to a reduced plant height and increased contents of cellulose, Si, and Zn. In the second breeding stage (the 1990s-2020s) it increased by 172.8%, which was mainly attributed to an increase in the stem diameter, wall thickness, and the contents of K, Ca, Fe, Mn, and Cu. The application of N fertilizer improved the grain yield but reduced the LR in wheat. This was mainly due to an increase in plant height resulting in an elevation of the plant center of gravity, a decrease in the contents of cellulose, and a reduction in the area of large-sized vascular bundles in the stems, even if N supplementation increased the concentrations of K, Ca, and Si. CONCLUSION: Although breeding strategies improved the stem strength, the trade-off between the grain yield and LR was more significantly influenced by the addition of N. Overcoming this peculiar situation will serve as a breakthrough in improving the seed yield in wheat crops in the future.
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Fertilizantes , Triticum , Triticum/genética , Estaciones del Año , Fitomejoramiento , China , Celulosa , Productos Agrícolas , Grano ComestibleRESUMEN
Background: Perampanel, a highly selective glutamate AMPA receptor antagonist, is widely used to treat epilepsy. Since the existence of common pathophysiological features between epilepsy and migraine, the aim of this study was to investigate whether perampanel could exert an antimigraine effect. Methods: Nitroglycerin (NTG) was used to induce a migraine model in rats, and the model animals were pretreatment with 50 µg/kg and 100 µg/kg perampanel. The expression of pituitary adenylate-cyclase-activating polypeptide (PACAP) was quantified by western blot and quantitative real-time PCR in the trigeminal ganglion, and rat-specific enzyme-linked immunosorbent assay in serum. Western blot was also conducted to explore the effects of perampanel treatment on the phospholipase C (PLC)/protein kinase C (PKC) and protein kinase A (PKA)/cAMP-responsive-element-binding protein (CREB) signaling pathways. Moreover, the cAMP/PKA/CREB-dependent mechanism was evaluated via in vitro stimulation of hippocampal neurons. The cells were treated with perampanel, antagonists and agonists for 24 hours and cell lysates were prepared for western blot analysis. Results: Perampanel treatment notably increased the mechanical withdrawal threshold and decreased head grooming and light-aversive behaviors in NTG-treated rats. It also decreased PACAP expression and affected cAMP/PKA/CREB signaling pathway. However, PLC/PKC signaling pathway may not be involved in this treatment. In in vitro studies, perampanel notably decreased PACAP expression by inhibiting cAMP/PKA/CREB signaling pathway. Conclusions: This study shows that perampanel inhibits the migraine-like pain response and that this beneficial effect might be attributable to regulation of the cAMP/PKA/CREB signaling pathway.
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Background: Genetic and environmental factors contribute to migraine and the comorbidities of anxiety and depression. However, the association between genetic polymorphisms in the transient receptor potential (TRP) channels and glutamatergic synapse genes with the risk of migraine and the comorbidities of anxiety and depression remain unclear. Methods: 251 migraine patients containing 49 comorbidities with anxiety and 112 with depression and 600 controls were recruited. A customized 48-plex SNPscan kit was used for genotyping 13 SNPs of nine target genes. Logistic regression was conducted to analyze these SNPs' association with the susceptibility of migraine and comorbidities. The generalized multifactor dimension reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interactions. The GTEx database was used to examine the effects of the significant SNPs on gene expressions. Results: The TRPV1 rs8065080 and TRPV3 rs7217270 were associated with an increased risk of migraine in the dominant model [ORadj (95% CI): 1.75 (1.09-2.90), p = 0.025; 1.63 (1.02-2.58), p = 0.039, respectively]. GRIK2 rs2227283 was associated with migraine in the edge of significance [ORadj (95% CI) = 1.36 (0.99-1.89), p = 0.062]. In migraine patients, TRPV1 rs222741 was associated with both anxiety risk and depression risk in the recessive model [ORadj (95% CI): 2.64 (1.24-5.73), p = 0.012; 1.97 (1.02-3.85), p = 0.046, respectively]. TRPM8 rs7577262 was associated with anxiety (ORadj = 0.27, 95% CI = 0.10-0.76, p = 0.011). TRPV4 rs3742037, TRPM8 rs17862920 and SLC17A8 rs11110359 were associated with depression in dominant model [ORadj (95% CI): 2.03 (1.06-3.96), p = 0.035; 0.48 (0.23-0.96), p = 0.042; 0.42 (0.20-0.84), p = 0.016, respectively]. Significant eQTL and sQTL signals were observed for SNP rs8065080. Individuals with GRS (Genetic risk scores) of Q4 (14-17) had a higher risk of migraine and a lower risk of comorbidity anxiety than those with Genetic risk scores scores of Q1 (0-9) groups [ORadj (95% CI): 2.31 (1.39-3.86), p = 0.001; 0.28 (0.08-0.88), p = 0.034, respectively]. Conclusion: This study suggests that TRPV1 rs8065080, TRPV3 rs7217270, and GRIK2 rs2227283 polymorphism may associate with migraine risk. TRPV1 rs222741 and TRPM8 rs7577262 may associate with migraine comorbidity anxiety risk. rs222741, rs3742037, rs17862920, and rs11110359 may associate with migraine comorbidity depression risk. Higher GRS scores may increase migraine risk and decrease comorbidity anxiety risk.
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Magnesium is an essential macronutrient for plant photosynthesis, and in response to Mg deficiency, dicots appear more sensitive than monocots. Under Mg deficiency, we investigated the causes of differing photosynthetic sensitivities in a dicot and a monocot species. Rice (Oryza sativa L.) and cucumber (Cucumis sativus L.) were grown in hydroponic culture to explore their physiological responses to Mg deficiency stress. Both Mg-deficient rice and cucumber plants exhibited lower biomass, leaf area, Mg concentration, and chlorophyll content (Chl) compared with Mg-sufficient plants. However, a more marked decline in Chl and carotenoid content (Car) occurred in cucumber. A lower CO2 concentration in chloroplasts (C c) was accompanied by a decrease in the maximum rate of electron transport (J max) and the maximum rate of ribulose 1,5-bisphosphate carboxylation (V cmax), restricting CO2 utilization in Mg-deficient plants. Rice and cucumber photorespiration rate (P r) increased under Mg deficiency. Additionally, for cucumber, Car and non-photochemical quenching (NPQ) were reduced under lower Mg supply. Meanwhile, cucumber Mg deficiency significantly increased the fraction of absorbed light energy dissipated by an additional quenching mechanism (Φf,D). Under Mg deficiency, suppressed photosynthesis was attributed to comprehensive restrictions of mesophyll conductance (g m), J max, and V cmax. Cucumber was more sensitive to Mg deficiency than rice due to lower NPQ, higher rates of electron transport to alternative pathways, and subsequently, photooxidation damage.
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Developing photostable two-photon dyes with high brightness and negligible photocytotoxicity is of key importance in fluorescence imaging but remains a huge challenge. Here, a two-photon dye with ultrahigh brightness and photostability is demonstrated for high-performance long-term two-photon fluorescence imaging. By terminated donor engineering, the designed DBD shows a higher two-photon absorption cross-section (δ, 418â GM vs 329â GM) and photoluminescence quantum yield (ΦPL , 62.74% vs 54.63%) than its counterpart DBA. As a consequence, two-photon fluorescence brightness (δ×ΦPL ) of DBD exhibits a 10-folded enhancement (262â GM vs 19â GM) in comparison with typical Coumarin 307 dye. More importantly, DBD displays ultrahigh photostability and negligible photobleaching under 10â min femtosecond laser irradiation, which stands in marked contrast to Coumarin 307. Furthermore, femtosecond transient absorption spectroscopy ascribes this ultrahigh photostability and negligible photobleaching to the inefficient intersystem crossing. With these merits, DBD can be used long-term two-photon fluorescence imaging inâ vitro.
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Colorantes Fluorescentes , Fotones , Colorantes Fluorescentes/química , Imagen ÓpticaRESUMEN
Migraine is a common disease of the nervous system that seriously affects the quality of life of patients and constitutes a growing global health crisis. However, many limitations and challenges exist in migraine research, including the unclear etiology and the lack of specific biomarkers for diagnosis and treatment. Electroencephalography (EEG) is a neurophysiological technique for measuring brain activity. With the updating of data processing and analysis methods in recent years, EEG offers the possibility to explore altered brain functional patterns and brain network characteristics of migraines in depth. In this paper, we provide an overview of the methodology that can be applied to EEG data processing and analysis and a narrative review of EEG-based migraine-related research. To better understand the neural changes of migraine or to provide a new idea for the clinical diagnosis and treatment of migraine in the future, we discussed the study of EEG and evoked potential in migraine, compared the relevant research methods, and put forwards suggestions for future migraine EEG studies.
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Enhancing photosynthetic capacity is widely accepted as critical to advancing crop yield. Therefore, identifying photosynthetic parameters positively related to biomass accumulation in elite cultivars is the major focus of current rice research. In this work, we assessed leaf photosynthetic performance, canopy photosynthesis, and yield attributes of super hybrid rice cultivars Y-liangyou 3218 (YLY3218) and Y-liangyou 5867 (YLY5867) at tillering stage and flowering stage, using inbred super rice cultivars Zhendao11(ZD11) and Nanjing 9108 (NJ9108) as control. A diurnal canopy photosynthesis model was applied to estimate the influence of key environmental factors, canopy attributes, and canopy nitrogen status on daily aboveground biomass increment (AMDAY). Results showed that primarily the light-saturated photosynthetic rate at tillering stage contributed to the advancing yield and biomass of super hybrid rice in comparison to inbred super rice, and the light-saturated photosynthetic rate between them was similar at flowering stage. At tillering stage, the higher CO2 diffusion capacity, together with higher biochemical capacity (i.e., maximum carboxylation rate of Rubisco, maximum electron transport rate (J max), and triose phosphate utilization rate) favored leaf photosynthesis of super hybrid rice. Similarly, AMDAY in super hybrid rice was higher than inbred super rice at tillering stage, and comparable at flowering stage partially due to increased canopy nitrogen concentration (SLNave) of inbred super rice. At tillering stage, model simulation revealed that replacement of J max and g m in inbred super rice by super hybrid rice always had a positive effect on AMDAY, and the averaged AMDAY increment was 5.7% and 3.4%, respectively. Simultaneously, the 20% enhancement of total canopy nitrogen concentration through the improvement of SLNave (TNC-SLNave) resulted in the highest AMDAY across cultivars, with an average increase of 11.2%. In conclusion, the advancing yield performance of YLY3218 and YLY5867 was due to the higher J max and g m at tillering stage, and TCN-SLNave is a promising target for future super rice breeding programs.
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Developing conjugated small molecules (CSM) with intense NIR-II (1000-1700â nm) absorption for phototheranostic is highly desirable but remains a tremendous challenge due to a lack of reliable design guidelines. This study reports a high-performance NIR-II CSM for phototheranostic by tailoring molecular planarity. A series of CSM show bathochromic absorption extended to the NIR-II region upon the increasing thiophene number, but an excessive number of thiophene results in decreased NIR-IIa (1300-1400â nm) brightness and photothermal effects. Further introduction of terminal nonconjugated alkyl chain can enhance NIR-II absorption coefficient, NIR-IIa brightness, and photothermal effects. Mechanism studies ascribe this overall enhancement to molecular planarity stemming from the collective contribution of donor/side-chain engineering. This finding directs the design of NIR-II CSM by rational manipulating molecular planarity to perform 1064â nm mediated phototheranostic at high efficiency.
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BACKGROUND: Adherence to evidence-based hospital stroke care is variable and may change over time. It is important to determine which process measures are associated with variation in outcome. In a large dataset, we analyzed the association between process and outcome and the fluctuations of indicators over time, and identified quality indicators (QIs) that should be prioritized for improving the quality of stroke care. METHODS: We analyzed data from 123,259 patients diagnosed with acute ischemic stroke (AIS) who were treated at 109 large tertiary hospitals in China between January 2011 and May 2017. In total, 12 stroke treatment indicators were selected to calculate the hospital process composite performance (HPCP). Hospitals were divided into subgroups according to the time trend of HPCP estimated by the Group-Based Model. We analyzed the influence of hospital subgroups on the patient outcomes using a multi-level model and explored the QIs that led to variation. RESULTS: The HPCP trends for stroke indicators of 109 hospitals over 7 years were divided into two groups (Group 1, low-HPCP; Group 2, high-HPCP). After adjusting for patient age, medical insurance, comorbidities, patterns of admission, and NIHSS-scores, patients in the high-HPCP group presented higher rate of independence and longer length of stay compared to the low-HPCP group. The multi-level model showed that there was a statistically significant difference in the utilization rate between the two groups, with most marked differences seen in emergency assessment and function evaluation indicators. CONCLUSION: Variation in the quality of stroke care exists across hospitals, and better adherence to guideline-based care is associated with improved outcomes. We found that QIs related to emergency examination and functional assessment were the main factors differing between good and poor adherers to stroke indicators, suggesting that quality improvement in stroke care could prioritize these QIs.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/diagnóstico , Indicadores de Calidad de la Atención de Salud , Comorbilidad , Centros de Atención TerciariaRESUMEN
The excited-state dynamics of indocyanine green (ICG) fundamentally determine its photophysical properties for phototheranostic. However, its dynamics are predictable to be susceptible toward intracellular viscosity due to its almost freely rotating structure, making the precise phototheranostic very challenging. Therefore, correlating the viscosity with the dynamics of ICG is of great importance and urgency for precise phototheranostic prospects. This study presents systemic investigations on the viscosity-dependent dynamics of ICG for phototheranostic. Femtosecond transient absorption (fs-TA) experiments elucidate a prolonged radiative transition (225â ps vs 152â ps) for ICG in a viscous environment, which benefits fluorescence. High viscosity remarkably extends the triplet excited-state lifetime of ICG but reduces its internal conversion (6.2â ps vs 2.2â ps). The extended triplet lifetime affords sufficient photosensitization time to enhance photodynamic therapy. A moderative internal conversion is unfavorable for heat production, resulting in inferior photothermal therapy. With this clear picture of excitation energy state dissipation in mind, we readily identified the safety laser power density for precise phototheranostic. This work provides an insightful understanding of viscosity-relevant excited-state dynamics toward phototheranostic, which is also beneficial for designing novel ICG derivatives with improved phototheranostic performance.
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Verde de Indocianina , Fotoquimioterapia , Fluorescencia , Verde de Indocianina/química , Rayos Láser , ViscosidadRESUMEN
It is well documented that yield superiority of super hybrid rice is linked with its improved photosynthetic capacity and/or efficiency. In natural environments, the amounts of CO2 assimilated by plants was also impacted by the rapidity of leaf photosynthesis response to fluctuations of light. However, it remains unknow whether the high yield of super hybrid rice was associated with photosynthetic traits under dynamic state. Here, photosynthetic traits under steady-and dynamic state in two super hybrid rice varieties (Ylinagyou 3218 and Yliangyou 5867) with high yield and two inbred super rice varieties (Zhendao 11 and Nanjing 9108) with lower yield. Under steady state, the net photosynthetic rate (A*) in super hybrid rice was 25.3% larger compared with inbred super rice. During photosynthetic induction, there was no obvious association of the rapidity of net photosynthesis rate (A) to sunflecks with rice subpopulations. Stomatal conductance (gs) of super hybrid rice increased slower than that of inbred super rice. The cumulative CO2 fixation (CCF) during photosynthetic induction was 25.2% larger in super hybrid rice than that in inbred super rice. The primary limitation during induction was biochemical limitation rather than stomatal limitation. There was a significantly positive relationship between A* and CCF, while A* was not related with the induction response rate of A. Overall, A* and CCF in super hybrid rice have been improved together, which contributed to its yield superiority, whereas its yield potential still can be improved by increasing induction rate of A under fluctuations of irradiance.
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Oryza , Ambiente , Oryza/genética , Fotosíntesis/fisiología , Hojas de la Planta/fisiologíaRESUMEN
Objective: To analyze the differences in efficacy and safety of different types of novel coronavirus pneumonia (COVID-19) vaccines in different age groups (young adults and elderly). Methods: Randomized controlled trials (RCTs) on COVID-19 vaccine in PubMed, Embase, Web of Science, and Cochrane library were searched by computer, and eight eligible studies were analyzed. Meta-analysis was performed using Stata 16.0 and RevMan5.4 software. Results: The mean geometric titer (GMT) of the virus in the elderly was significantly higher than that in the placebo group (SMD = 0.91, 95% CI (0.68, 1.15), p < 0.01), presenting no obvious difference compared with the young adults (SMD = 0.19, 95% CI (0.38, 0.01), p = 0.06). Meanwhile, the effect of multiple vaccinations was better than that of single vaccination (SMD = 0.83, 95% CI (0.33, 1.34), p < 0.01). However, the number of adverse events (AEs) in the elderly was lower than that in the young adults (OR = 0.35, 95% CI (0.29, 0.42), p < 0.01). Conclusions: The immunization effect of COVID-19 vaccine in the elderly is obvious, especially after multiple vaccinations, and the incidence of AEs in the elderly is low, which proves that the vaccination of the elderly is safe and effective.
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BACKGROUND: CircRNAs are noncoding RNA molecules that have recently been described and shown to regulate miRNA functionality. While recent studies have suggested such circRNAs to be associated with pain related diseases in humans, no comprehensive migraine-related circRNA profiles have been generated, and there is currently no clear understanding of whether they can serve as regulators of migraine pathology. METHODS: We initially conducted a circRNA microarray analysis of the plasma of migraine patients and healthy controls. Based upon these data, we then selected 8 differentially expressed circRNAs and confirmed their expression in more migraine patient plasma samples via real-time PCR. We then performed functional and pathway enrichment analyses. Lastly, using a robust rank aggregation approach, we constructed a ceRNA network according to predicted circRNA-miRNA and miRNA-mRNA pairs in these migraine patient samples. RESULTS: We were able to detect 2039 circRNAs in our patient samples, with 794 of 1245 these circRNAs being up- and downregulated in migraine patients relative to controls, respectively (fold change ≥ 1.5, p < 0.01). A qRT-PCR analysis confirmed that the expression of hsa_circRNA_100236, hsa_circRNA_102413, and hsa_circRNA_000367 was significantly enhanced in migraine patients, whereas the expression of hsa_circRNA_103809, hsa_circRNA_103670, and hsa_circRNA_101833 was significantly reduced in these individuals relative to healthy controls. We found these differentially regulated circRNAs to be associated with numerous predicted biological processes, with enrichment analyses suggesting that they may modulate the PI3K-Akt signaling so as to promote inflammation to drive migraine development. However, further research will be needed to formally test these mechanistic possibilities and to validate these circRNAs as potential biomarkers of migraine patients. CONCLUSIONS: Our results offer new potential insights into the mechanistic basis of this condition and suggest that hsa_circRNA_000367 and hsa_circRNA_102413 may offer value as regulators of migraine pathology.
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Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Trastornos Migrañosos/genética , ARN Circular/genética , Regulación hacia Abajo/genética , Ontología de Genes , Redes Reguladoras de Genes , Humanos , ARN Circular/metabolismo , Reproducibilidad de los Resultados , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: Increasing morbidity and misdiagnosis of vestibular migraine (VM) gravely affect the treatment of the disease as well as the patients' quality of life. A powerful diagnostic prediction model is of great importance for management of the disease in the clinical setting. MATERIALS AND METHODS: Patients with a main complaint of dizziness were invited to join this prospective study. The diagnosis of VM was made according to the International Classification of Headache Disorders. Study variables were collected from a rigorous questionnaire survey, clinical evaluation, and laboratory tests for the development of a novel predictive diagnosis model for VM. RESULTS: A total of 235 patients were included in this study: 73 were diagnosed with VM and 162 were diagnosed with non-VM vertigo. Compared with non-VM vertigo patients, serum magnesium levels in VM patients were lower. Following the logistic regression analysis of risk factors, a predictive model was developed based on 6 variables: age, sex, autonomic symptoms, hypertension, cognitive impairment, and serum Mg2+ concentration. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.856, which was better than some of the reported predictive models. CONCLUSION: With high sensitivity and specificity, the proposed logistic model has a very good predictive capability for the diagnosis of VM. It can be used as a screening tool as well as a complementary diagnostic tool for primary care providers and other clinicians who are non-experts of VM.
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Background: Vestibular migraine (VM) is the most common cause of spontaneous vertigo with no specific physical and laboratory examinations, and is an under-recognized entity with substantial burden for the individual and the society. In this study, by observing the brainstem auditory evoked potential (BAEP) and cognitive function of VM patients, the possible laboratory diagnostic indicators of VM and the influence of disease on cognitive function were discussed. Method: The study included 78 VM patients, 76 migraine patients, and 79 healthy individuals. The age, gender, and other clinical history of the three groups matched. All participants underwent BAEP examinations, in which patients in the migraine group and outpatients of the VM group were in the interictal period, and inpatients in the VM group were examined during episodes, while all patients tested for the Addenbrooke's cognitive examination-revised (ACE-R) scale were in the interictal period. The differences in BAEP and ACE-R scores between the three groups of members and their relationship with the clinical features of VM patients were analyzed. Result: The peak latency of I, III, and V wave in the BAEP of the VM group was longer than that of the migraine group and the control group (p < 0.05). The peak latency of V wave in the BAEP of the migraine group was longer than that of the control group (p < 0.05). The ACE-R of the VM group scored lower than the migraine group in terms of language fluency and language (p < 0.05), and lower than the control group in terms of total score, language fluency, language, and visuospatial (p < 0.05); and the ACE-R of the migraine group scored lower than the control group in the total score and visuospatial (p < 0.05). Conclusion: Migraine patients have brainstem dysfunction, and VM patients have more severe brainstem dysfunction than migraine patients, suggesting that VM patients have both central nervous system damage and peripheral nerve damage. Migraine patients have cognitive impairment, while cognitive impairment in VM patients is more severe than in migraine patients.