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Apportioning pollution sources under compound pollution conditions is challenging in river pollution source analysis. The positive matrix factorization (PMF) model is widely used to analyze river pollution sources. However, the identification of pollutants in this model relies primarily on the subjective experience of the researchers, leading to ineffective identification of different contaminants from similar sources. In this study, we propose a comprehensive deviation index (CDI) to quantitatively identify pollution source types based on the PMF and observed source profiles. Taking the subtropical Xizhijiang River Basin as a case study, we quantitatively identified the pollution sources and their contributions to dissolved organic carbon (DOC), total nitrogen (TN), and total phosphorus (TP) using observed water quality and pollution sources data. The results showed that the eight major pollutants in the study region exhibited significant positive correlations, indicating the similarity of pollutant sources in the watershed. The PMF model identified three primary pollution sources with coefficients of determination for observed versus predicted concentrations ranging from 0.60 to 0.98. The CDI unveiled that the watershed's three pollution sources were farmland, rural, and wastewater treatment plants (WTPs). Farmland emerges as the predominant contributor to DOC (68.04 %), TC (63.29 %), and TDP (44.51 %). Rural notably contributes to NH3-N, PO4 3-, TDP, and TN, with percentages of 86.37 %, 57.65 %, 41.40 %, and 30.45 %, respectively. WTPs significantly contribute to NO2 -, NO3 -, and TN, accounting for 71.81 %, 57.39 %, and 37.26 %, respectively. Incorporating source fingerprints into the PMF model, the CDI can accurately identify pollution sources, improve the interpretability of source identification, and mitigate uncertainty in the multiple-source unknown receptor model. These findings have immediate and practical implications for river ecosystem management and pollution control, providing a more effective method for identifying and addressing pollution sources.
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Purpose: The objective of this study was to assess the accuracy of FreeStyle Libre Pro (FSL-Pro) flash continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods: A single-arm, single-center prospective study was conducted in the cardiac care unit from January 2021 to September 2023. Patients underwent finger-prick blood glucose (FPBG) testing before breakfast (6:00 am) and after meals (at 9:00, 13:00, 19:00 pm), along with CGM during their hospitalization. Statistical analyses included mean differences (MDs), mean absolute relative difference (MARDs) of blood glucose levels, and hypoglycemia occurrences. A Bland-Altman plot analysis and Pearson correlation were performed. Results: Ninety-seven T2DM and AMI patients underwent CGM for up to 72 h (1142 monitoring point). Mean daily BG, Fasting plasma glucose (FPG) and mean postprandial plasma glucose (PPG) were significantly lower by CGM than by FPBG with an estimated MD of -0.89 mmol/L in BG, -0.88 mmol/L in FPG, and -0.90 mmol/L in PPG, respectively. The maximum effect was mainly in the first day and then the difference was gradually declined (falling range, Day1, -1.24; Day 2, -0.70; Day 3, -0.68, mmol/L, respectively). The incidence rates of hypoglycemia and potential hypoglycemia was 1.57% and 8.5% higher, respectively, in CGM than in FBPG. A Bland-Altman Plot revealed some variability and bias between the two methods of measurement of glucose monitoring (p < .001). Pearson's correlation coefficient demonstrated a significant correlation between the mean BG, FPG, and PPG of CGM and FBPG (Pearson's coefficient: 0.92, 0.87, 0.92, respectively, p < .001). Conclusion: Compared with FPBG, FSL Pro-CGM showed lower mean glucose and higher hypoglycemia detection in T2DM and AMI patients, especially in the first 24â h.
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Hickory (Carya cathayensis) nuts are rich in epigallocatechin-3-gallate (EGCG) with multiple health functions. EGCG also regulates plant growth, development and stress responses. However, research on the synthesis mechanism of EGCG and its function in hickory is currently limited. Herein, 44 serine carboxypeptidase-like (SCPL) members were identified from the hickory genome and classified into three major categories: SCPL-I, SCPL-II, and SCPL-III. In the CcSCPLs-IA branch, CcSCPL3/4/5/8/9/11/13 showed differential expression patterns in various tissues, especially with relatively high expression levels in plant roots, female flowers and seed coat. These proteins have a catalytic triad composed of serine (Ser), aspartic acid (Asp) and histidine (His). Ser-His in the triad and arginine (Arg) mediated the docking of CcSCPL3/4/5/11 with 1-O-galloyl-ß-d-glucose (ßG) and epigallocatechin (EGC), whereas the Asp of the triad did not. CcSCPL4 was further confirmed to promote the synthesis of EGCG in tobacco leaves. CcSCPL4 may function as monomer and be mainly localized within cellular structures outside the nucleus. Notably, the expression level of CcSCPL4 significantly changed after drought, cold, and salt stress, with the highest expression level under drought stress. Meanwhile CcSCPL4 over-expression could enhance the drought resistance of Saccharomyces cerevisiae and Arabidopsis. This study elucidates key enzymes for EGCG synthesis and their role in drought resistance, providing insights into the EGCG synthesis pathway and molecular breeding of hickory in future.
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Leaching of dissolved organic nitrogen (DON) is a significant pathway for nitrogen (N) loss in agricultural ecosystems. The excessive application of N for enhanceing agricultural productivity often results in the leaching of N into groundwater. Yet not well understood, the extent of retention in the vadose zone has critical implications for risk management and remediation strategies. This study aims to advance simulation techniques for modelling the transport process of reactive DON within a heterogeneous vadose zone. Through a combination of laboratory experiments and numerical simulations, the study firstly examines the extent of DON retention in the vadose zone and quantitatively analyse groundwater contamination risk from this kind of accumulation. Our findings indicate that heavy N fertilizer application and high-intensity rainfall events led to elevated contents of DON in the vadose zone and increased DON leaching fluxes into groundwater. Besides, intensifier rainfall reduced the N storage more quickly in scenarios devoid of DON application with higher mineralization rate, while DON slowly mineralized to other forms, largely accumulated in the top layer and migrated deeper with intensifier rainfall after input of urea. In our scenarios, DON accounted for a substantial portion (33-68%) of the total dissolved nitrogen (TDN) leaching fluxes, with exogenous DON content contributing significantly (25-85%) to the overall DON leaching into the aquifer. These results underscore the need for effective strategies to mitigate groundwater contamination risks associated with agricultural N use.
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Background: Primary health-care (PHC) resource plays a critical role in addressing challenges related to healthcare accessibility and costs, as well as implementing a graded diagnosis and treatment system. This study aims to analyze the extent and components of inequality in PHC resource allocation in Guangzhou. Methods: By utilizing data from the Annual Report on Healthcare Institutions for community and township health centers in Guangzhou from 2012 to 2020, this paper analyses the distribution of human, material and financial resources. It examines inequities in health resource allocation using the Gini coefficient. Additionally, it investigates the internal structure of overall inequality through the two-stage nested Theil decomposition method and explores the influencing mechanisms of inequality using the concentration index decomposition method. Results: The findings indicate that between 2012 and 2020, except for beds in 2018 and 2019, the Gini coefficients for resource allocation relative to population size remained below 0.3. Moreover, the Gini coefficient for geographical area ranged from 0.1228 to 0.3481. The two-stage nested Theil decomposition results reveal that within-district disparity contributes the most to the overall inequality, exceeding 46 %. The Concentration indexes show negative values, and the decomposition analysis highlights the significant contribution of the number of individuals served (over 72 %) to the inequality in health resource allocation. Conclusion: At the administrative district level, the allocation of PHC resources in Guangzhou demonstrates overall equity, with within-district inequality identified as the primary contributor to the overall inequality. The distribution of PHC resources in Guangzhou follows a pro-poor pattern. The key factors influencing equity enhancement in PHC resource allocation in Guangzhou include the number of individuals served, the presence of township health centers among institution types, the number of hospital admissions per capita, and the proportion of children aged 0-3.
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Matrix metalloproteinases (MMPs) play critical roles in the degradation of collagens, while their mechanism remains unclear. In the present study, the involvement of matrix metalloproteinases (MMPs) in collagen degradation of sea bass muscle during cold storage was explored. Immunohistochemical staining results showed significant degradation of type I collagen in the connective tissue of muscle endomysium during cold storage, thus affecting the muscle structural integrity and quality. Western blot analysis revealed an increment in the α1 chain and a decrease in the ß and γ chains of type I collagen. Immunofluorescence staining showed that MMP-2, MMP-9, and MMP-13 were distributed in the endomysium surrounding the muscle fibers. Additionally, the catalytic domains of MMP-2, MMP-9, and MMP-13 with biological activities were successfully expressed. The degradation trend of type I collagen by MMPs under 4 °C was similar to that of muscle collagen during cold storage, suggesting that the degradation of type I collagen was attributed to the cooperative action of the MMPs. In conclusion, our study elucidated that the MMPs-engaged degradation of type I collagen is quite possibly the leading cause of sea bass muscle softening during cold storage.
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Desarrollo Sostenible , Humanos , Objetivos , Conservación de los Recursos Naturales , CienciaRESUMEN
Background: CDK4/6 inhibitors (CDK4/6i) have shown promising results in the treatment of hormone receptor-positive (HR+) metastatic breast cancer (MBC) when combined with endocrine therapy (ET). It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice, as well as to analyze the factors that can predict their outcomes. Methods: Patients with HR+ MBC who received CDK4/6i-based therapy between May 2016 and May 2023 at Hunan Cancer Hospital were evaluated for progression-free survival (PFS). Adverse reactions were assessed based on the National Cancer Institute Common Toxicity Criteria (version 5.0). Results: This study included 344 patients, with a median PFS (mPFS) of 12.8 months (range: 10.4-15.2 months). After adjustment, Cox multivariate regression analysis revealed that visceral metastasis (specifically liver and brain metastases), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 1, estrogen receptor ≤ 80%, progesterone receptor ≤ 10%, Ki-67 > 30%, and treatment in later stages were significant factors associated with reduced PFS. Based on this, we created a prognostic nomogram and validated its performance, obtaining a C-index of 0.714 (95% confidence interval: 0.640-0.787) as well as reliable calibration and clinical impact. The mPFS of CDK4/6i rechallenge was 7.7 months; for patients who initially discontinued CDK4/6i for reasons other than disease progression, CDK4/6i rechallenge still provided a mPFS of 11.4 months. The tolerability and safety of combining CDK4/6is with ET were manageable. Adverse events led to treatment discontinuation in 3.8% of patients. Neutropenia (29.1%), leukopenia (13.7%), and anemia (4.1%) were the primary grade 3/4 adverse reactions. Conclusions: This real-world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+ MBC. Individualized treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.
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BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a prevalent complication during pregnancy with significant implications for maternal and perinatal health globally. Maternal obesity is a known risk factor for HDP. This review sought to identify adiposity indicators in early pregnancy that are linked to the development of HDP. METHODS: We conducted a systematic search of the PubMed, Science Citation Index (Web of Science), and Embase databases. Screening and quality evaluation of studies was conducted independently by two reviewers. Both random effects meta-analysis and narrative synthesis were performed. RESULTS: Thirty-one studies were included with a pooled sample of 81,311 women. The meta-analysis showed that the odds of HDP were significantly increased by higher pregnancy measures of adiposity (pre-pregnancy body mass index (OR = 2.14, 95%CI: 1.67-2.75), visceral adipose tissue (OR = 1.79, 95%CI: 1.01-3.16), subcutaneous adiposity thickness (OR = 1.67, 95%CI: 1.36-2.05), waist circumference (OR = 2.20, 95%CI: 1.37-3.54), waist to-hip ratio (OR = 3.08, 95% CI: 1.38-6.87), weight gain (OR = 1.69, 95%CI: 1.42-2.02) and percentage body fat (OR = 1.71, 95%CI: 1.16-2.53)). Epicardial fat thickness was significantly associated with HDP, although limited data were available. CONCLUSIONS: The results of our study highlight the importance of investigating the predictive value of adiposity measures in identifying the risk of HDP to tailor care towards women at the highest risk.
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Adiposidad , Índice de Masa Corporal , Hipertensión Inducida en el Embarazo , Humanos , Femenino , Embarazo , Factores de Riesgo , Circunferencia de la Cintura , Relación Cintura-Cadera , Grasa Intraabdominal , Obesidad Materna/complicacionesRESUMEN
Forest structural complexity can mediate the light and water distribution within forest canopies, and has a direct impact on forest biodiversity and carbon storage capability. It is believed that increases in forest structural complexity can enhance tree species diversity and forest productivity, but inconsistent relationships among them have been reported. Here, we quantified forest structural complexity in three aspects (i.e., horizontal, vertical, and internal structural complexity) from unmanned aerial vehicle light detection and ranging data, and investigated their correlations with tree species diversity and forest productivity by incorporating field measurements in three forest biomes with large latitude gradients in China. Our results show that internal structural complexity had a stronger correlation (correlation coefficient = 0.85) with tree species richness than horizontal structural complexity (correlation coefficient = -0.16) and vertical structural complexity (correlation coefficient = 0.61), and it was the only forest structural complexity attribute having significant correlations with both tree species richness and tree species evenness. A strong scale effect was observed in the correlations among forest structural complexity, tree species diversity, and forest productivity. Moreover, forest internal structural complexity had a tight positive coordinated contribution with tree species diversity to forest productivity through structure equation model analysis, while horizontal and vertical structural complexity attributes have insignificant or weaker coordinated effects than internal structural complexity, which indicated that the neglect of forest internal structural complexity might partially lead to the current inconsistent observations among forest structural complexity, tree species diversity, and forest productivity. The results of this study can provide a new angle to understand the observed inconsistent correlations among forest structural complexity, tree species diversity, and forest productivity.
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Lymphopenia is a unique manifestation of anti-MDA5 positive dermatomyositis with interstitial lung disease (MDA5 + DM-ILD). This study aimed to investigate the relationship between dynamic changes in peripheral lymphocytes and short-term prognosis in patients of MDA5 + DM-ILD. Two hundred sixty-three MDA5 + DM-ILD patients were divided into different groups according to lymphocyte count and death or survival within 1 month, then the differences in clinical features and outcomes were compared. Associations between lymphocytes and risk of death within 1 month were also investigated in different lymphocyte groups using Cox proportional hazard models. A generalized additive mixed model (GAMM) was established to analyze the dynamic changes of lymphocytes in the death 1-month group. Lymphocytes of the patients who died within 1 month were significantly lower than survivors by different lymphocyte grouping methods, and the total lymphocytes showed a gradually decreasing trend in non-survivors. And the difference between survivors and non-survivors was more obvious over time. The lowest tertile of baseline lymphocytes as a reference, the hazard ratios for death within 1 month in the highest tertile were 0.497 (95% CI 0.26-0.949, P for trend = 0.033) after adjustment for potential confounders. GAMM analysis found a mean daily decrease of lymphocytes (0.034 × 10^9/L) after admission in death 1-month patients. Low baseline lymphocytes and gradually declined lymphocytes are both associated with a high risk of death within 1 month. However dynamic changes in lymphocytes can better reflect the disease status and better predict the short-term prognosis than baseline lymphocytes in MDA5 + DM-ILD patients. Key points â¢Low baseline lymphocytes and gradually decreased trend along time correlated with poor short-term prognosis in MDA5 + DM-ILD patients. â¢Dynamic changes of lymphocytes can better reflect the disease status and better predict the 1-month prognosis than baseline lymphocytes in MDA5 + DM-ILD patients. â¢Generalized additive mixed model (GAMM) analysis found that in 1-month non-survivors, peripheral blood lymphocytes decreased by 0.034 × 10^9/L per day, while the lymphocytes in survivors gradually increased.
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Dermatomiositis , Helicasa Inducida por Interferón IFIH1 , Enfermedades Pulmonares Intersticiales , Linfocitos , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/complicaciones , Dermatomiositis/complicaciones , Dermatomiositis/sangre , Dermatomiositis/inmunología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Helicasa Inducida por Interferón IFIH1/inmunología , Pronóstico , Adulto , Recuento de Linfocitos , Anciano , Linfopenia/sangre , Linfopenia/complicaciones , Linfopenia/inmunología , Modelos de Riesgos Proporcionales , Autoanticuerpos/sangreRESUMEN
We used 11 years of census data from 450 seedling quadrats established in a 20-ha forest dynamics plot to study seedling dynamics in tree species of a tropical seasonal rainforest in Xishuangbanna, southwestern China. We found that overall seedling recruitment rate and relative growth rate were higher in the rainy season than in the dry season. Both the recruitment rate of seedlings from canopy tree species (two species) and the relative growth rate of seedlings from understory species (nine species) were higher in the rainy season than in the dry season. However, in the rainy season, the recruitment rate of seedlings was higher for canopy tree species than for understory tree species. In addition, relative growth rate of seedlings was higher in the canopy species than in understory seedlings in the dry season. We also observed that, in both rainy and dry seasons, mortality rate of seedlings was higher for canopy species than for understory species. Overall, canopy tree species appear to have evolved a flexible strategy to adapt to the seasonal changes of a monsoon climate. In contrast, understory tree species seem to have adopted a conservative strategy. Specifically, these species mainly release seedlings in the rainy season and maintain relatively stable populations with a lower mortality rate and recruitment rate in both dry and rainy seasons. Our study suggests that canopy and understory seedling populations growing in forest understory may respond to future climate change scenarios with distinct regeneration strategies.
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Early social isolation (SI) leads to various abnormalities in emotion and behavior during adulthood. However, the negative impact of SI on offspring remains unclear. This study has discovered that paternal early SI causes social memory deficits and anxiety-like behavior in F1 young adult mice, with alterations of myelin and synapses in the medial prefrontal cortex (mPFC). The 2-week SI in the F1 progeny exacerbates social memory impairment and hypomyelination in the mPFC. Furthermore, the down-regulation of miR-124, a key inhibitor of myelinogenesis, or over-expression of its target gene Nr4a1 in the mPFC of the F1 mice improves social interaction ability and enhances oligodendrocyte maturation and myelin formation. Mechanistically, elevated levels of miR-124 in the sperm of paternal SI mice are transmitted epigenetically to offspring, altering the expression levels of miR-124/Nr4a1/glucocorticoid receptors in mPFC oligodendrocytes. This, in turn, impedes the establishment of myelinogenesis-dependent social behavior. This study unveils a novel mechanism through which miR-124 mediates the intergenerational effects of early isolation stress, ultimately impairing the establishment of social behavior and neurodevelopment.
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MicroARNs , Corteza Prefrontal , Conducta Social , Aislamiento Social , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratones , Masculino , Corteza Prefrontal/metabolismo , Oligodendroglía/metabolismo , Ratones Endogámicos C57BL , Trastornos de la Memoria/genética , Trastornos de la Memoria/metabolismo , Conducta Animal/fisiología , Vaina de Mielina/metabolismo , Vaina de Mielina/genética , Ansiedad/genética , Ansiedad/metabolismo , FemeninoRESUMEN
Traditional Fenton principles for degrading polysaccharides, including chondroitin sulfate (CS), are fraught with limitations, such as strict pH-dependence, higher temperature requirements, desulfurization, and environmentally perilous. In this study, an effective Fenton-like system comprising trimetallic-doped carbon nitride material (tri-CN) with hydrogen-bonded melamine-cyanuric acid (MCA) supramolecular aggregates as its basic skeleton was engineered to overcome the challenges of traditional methods. Detailed material characterizations revealed that, compared to monometallic-doped or bimetallic-doped counterparts, tri-CN offered a larger surface area, higher porosity, and increased metal loading, thereby enhancing reactant accessibility and polysaccharide degradation efficiency. The characterization and activity assessment of the degraded polysaccharide revealed structurally intact products without significant desulfurization, indicating the effectiveness of the designed approach. Moreover, the degraded chondroitin sulfate CS3 catalyzed by tri-CN, exhibited promising antioxidant activity and anti-CRISPR potential. The results elucidated that the high-valent iron species in the material served as primary active sites, catalyzing the cleavage of hydrogen peroxide to generate hydroxyl radicals that subsequently attacked CS chains, leading to their fragmentation. Hence, the designed material can be efficiently applied to polysaccharide degradation, but not limited to photocatalysis, electrocatalysis, sensor, energy storage materials, and wastewater treatment.
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The healing of chronic diabetic wounds remains a formidable challenge in modern times. In this study, a novel traditional Chinese medicine microneedle patch was designed based on the physiological characteristics of wounds, with properties including hemostasis, anti-inflammatory, antioxidant, antimicrobial, and induction of angiogenesis. Initially, white peony polysaccharide (BSP) with hemostatic properties and carboxymethyl chitosan (CMCS) with antimicrobial capabilities were used as materials for microneedle fabrication. To endow it with antimicrobial, procoagulant, and adhesive properties. Among them, loaded with ROS-sensitive nanoparticles of Astragalus polysaccharides (APS) based on effective components baicalein (Bai) and berberine (Ber) from Scutellaria baicalensis (SB) and Coptis chinensis (CC) drugs (APB@Ber). Together, they are constructed into multifunctional traditional Chinese medicine composite microneedles (C/B@APB@Ber). Bai and Ber synergistically exert anti-inflammatory and antimicrobial effects. Microneedle patches loaded with BSP and APS exhibited significant effects on cell proliferation and angiogenesis induction. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. Therefore, traditional Chinese medicine multifunctional microneedle patches offer potential medical value in promoting the healing of diabetic wounds.
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Astragalus propinquus , FN-kappa B , Nanopartículas , Polisacáridos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Astragalus propinquus/química , Ratones , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Células RAW 264.7 , Agujas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Quitosano/química , Quitosano/farmacología , Proliferación Celular/efectos de los fármacosRESUMEN
The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0-2 years (18.09%, 1054/5,828) and lowest among adults aged 45-64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time.
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Infecciones por Caliciviridae , Heces , Gastroenteritis , Variación Genética , Genotipo , Norovirus , Filogenia , Estaciones del Año , Humanos , China/epidemiología , Norovirus/genética , Norovirus/clasificación , Norovirus/aislamiento & purificación , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Preescolar , Lactante , Niño , Adulto , Persona de Mediana Edad , Prevalencia , Adulto Joven , Adolescente , Heces/virología , Masculino , Recién Nacido , Femenino , Gastroenteritis/virología , Gastroenteritis/epidemiología , Anciano , ARN Viral/genética , Anciano de 80 o más AñosRESUMEN
Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.
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Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Germinación , Semillas , Germinación/efectos de los fármacos , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Arabidopsis/genética , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Multimerización de Proteína/efectos de los fármacos , Cristalografía por Rayos X , Sulfonamidas/farmacología , Sulfonamidas/química , Proteínas de Transporte de MembranaRESUMEN
Pituitary neuroendocrine tumors (PitNETs) are a special class of tumors of the central nervous system that are closely related to metabolism, endocrine functions, and immunity. In this study, network pharmacology was used to explore the metabolites and pharmacological mechanisms of PitNET regulation by gut microbiota. The metabolites of the gut microbiota were obtained from the gutMGene database, and the targets related to the metabolites and PitNETs were determined using public databases. A total of 208 metabolites were mined from the gutMGene database; 1,192 metabolite targets were screened from the similarity ensemble approach database; and 2,303 PitNET-related targets were screened from the GeneCards database. From these, 392 overlapping targets were screened between the metabolite and PitNET-related targets, and the intersection between these overlapping and gutMGene database targets (223 targets) were obtained as the core targets (43 targets). Using the protein-protein interaction (PPI) network analysis, Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway and metabolic pathway analysis, CXCL8 was obtained as a hub target, tryptophan metabolism was found to be a key metabolic pathway, and IL-17 signaling was screened as the key KEGG signaling pathway. In addition, molecular docking analysis of the active metabolites and target were performed, and the results showed that baicalin, baicalein, and compound K had good binding activities with CXCL8. We also describe the potential mechanisms for treating PitNETs using the information on the microbiota (Bifidobacterium adolescentis), signaling pathway (IL-17), target (CXCL8), and metabolites (baicalin, baicalein, and compound K); we expect that these will provide a scientific basis for further study.
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Near-infrared phosphor-converted light emitting diodes (NIR pc-LEDs) are considered as desirable NIR light sources to satisfy current needs owing to their numerous remarkable features. Nevertheless, as an essential component, previously reported NIR phosphors with broadband emission often suffer from inferior efficiency or thermal stability, therefore restricting their use and promotion. Herein, a novel Cr3+-doped garnet phosphor Y2CaScAl3GeO12:Cr3+ (YCSAG:Cr3+) is developed via regulating the near-neighbor coordination polyhedron. Under the excitation of blue light, it exhibits a broadband NIR emission peaking near 800 nm with a full width at half-maximum (fwhm) exceeding 150 nm, owing to the increased structural distortion of the octahedron. Particularly, due to the enhanced local structural rigidity induced by lattice shrinkage, the optimal sample achieves a balance of high internal quantum efficiency (IQE) of approximately 83% and thermal stability of approximately 90% at 393 K, facilitating its practical application as an NIR light source. Eventually, using the typical YCSAG:0.04Cr3+ phosphor and 450 nm blue LED chip, a high-performance NIR pc-LED device has been manufactured, demonstrating potential applications in anticounterfeiting and night vision.