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PURPOSE: Tacrolimus is the cornerstone of current immunosuppressive strategies after lung transplantation. However, its narrow therapeutic range and considerable pharmacokinetic variability pose challenges for individualized treatment. Several tacrolimus population pharmacokinetic (popPK) models have been developed for precision dosing in adult lung transplant patients. However, their applicability across different clinical settings remains uncertain. The aim of this study was to evaluate the external predictability of these models and identify influential factors. METHODS: Published models were systematically retrieved and assessed based on an external dataset of 39 patients (1240 tacrolimus trough concentrations) using three approaches: (1) prediction-based diagnosis using dosing records and patient characteristics; (2) simulation-based diagnosis, with prediction- and variability-corrected visual predictive checks (pvcVPC) and normalized prediction distribution error tests (NPDE); and (3) Bayesian forecasting using one to four observations for posterior predictions. We also investigated the impact of model structure and covariates on predictability. RESULTS: The predictive performance of six published models was externally evaluated, but none demonstrated satisfactory accuracy in prediction- and simulation-based diagnosis. Bayesian forecasting yielded satisfactory results with only one prior observation and optimal predictive performance with 2-3 priors for all included models. The structural model parameterized on plasma tacrolimus concentration outperformed others. Significant correlations were observed between prediction-error and daily tacrolimus dose, postoperative day, and voriconazole co-administration. CONCLUSIONS: The overall predictive performance of all published models was unsatisfactory, making direct extrapolation inappropriate. However, Bayesian forecasting significantly improves predictive performance. Utilizing plasma tacrolimus concentration for parameter estimation can improve the predictive ability of tacrolimus popPK models.
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Two-dimensional (2D) materials show promising applications in nanoelectronic devices due to their excellent physical and chemical properties, large specific surface area, and good flexibility. 2D AlSb, a representative of a new class of two-dimensional materials with a double-layer honeycomb (DLHC) structure was recently obtained in experiments and was reported to be a direct band gap semiconductor. Strain engineering is an effective way of tuning the properties of 2D materials. Here, by first-principles calculations, the strain effects on the electronic structure of AlSb were investigated. An interesting inversion of band order near the bottom of the conduction band can be induced by applying uniaxial strain, which will introduce a large electronic anisotropy. In addition, under tensile strain along the armchair direction larger than 5%, band inversion occurs, indicating possible topological insulator properties of AlSb. Small carrier effective mass and strain tunable electronic anisotropy pave the way for the application of AlSb in future nanoelectronic devices.
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BACKGROUND: Little empirical evidences were provided on the disparity in the level of loneliness between the migrant older with children (MOC) and their local counterpart in China. This study aimed to explore the association between social participation and loneliness and verify whether there was a local-migrant difference in this association. METHODS: A total of 1332 older people (60 +) were included in this study with 656 MOC and 676 natives. Loneliness was assessed by the University of California Los Angeles Loneliness Scale with eight items (ULS-8). Social participation was evaluated by three kinds of social activities concerning sports activities, hobby activities and community resident interaction. Univariate analysis was conducted to compare the local-migrant disparity as well as the level of loneliness between different subgroups. Hierarchical multiple linear regression analysis was used to examine the proposed relationship and the moderating influence of migration status. RESULTS: The average ULS-8 scores were 11.73 ± 4.02 for local subjects and 12.82 ± 4.05 for MOC respectively, indicating a lower level of loneliness among local older people. Participating in hobby activities (ß = -0.092, P = 0.003) and interacting with residents (ß = -0.216, P = 0.001) more frequently were related to lower level of loneliness while participating in square dancing was related to higher level of loneliness (ß = 0.087, P = 0.001). The negative relationships between hobby activities as well as resident interaction and loneliness were more profound in migrants than natives. CONCLUSIONS: Only two types of social participation could help alleviate loneliness. More attention to older migrants' loneliness and extending the scale and types of social activities were recommended for policymakers.
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Solidão , Participação Social , Humanos , Solidão/psicologia , Masculino , Feminino , Idoso , China/epidemiologia , Participação Social/psicologia , Pessoa de Meia-Idade , Migrantes/psicologia , Idoso de 80 Anos ou mais , População do Leste AsiáticoRESUMO
Background: The preoperative predictors of residual or recurrent tricuspid regurgitation (TR) after cone reconstruction (CR) remains unclear in patients with Ebstein anomaly (EA). We aimed to determine the predictive value of right ventricular longitudinal strain, assessed using cardiac magnetic resonance (CMR) imaging, for residual or recurrent TR after CR in patients with EA. Methods: This single-centre, retrospective study analysed data from 48 patients with EA [mean ± standard deviation (SD), age, 35.0±13.6 years; 13 males] who underwent CMR before CR between January 2017 and February 2023. Two-dimensional colour Doppler echocardiography was performed before CR and mid-term (>6 months) after CR to evaluate the degree of TR in patients with EA. Thirty healthy volunteers served as controls. Univariate and multivariate logistic regression analyses were performed to identify CMR predictors of moderate or severe TR >6 months after CR. Results: Mid-term postoperative results revealed severe, moderate, and mild TR in 8 (17%), 7 (15%), and 33 (69%) patients, respectively. For patients with EA and moderate or severe TR after CR, left ventricular global longitudinal strain (GLS), left ventricular ejection fraction, right ventricular global longitudinal strain (RVGLS), and right ventricular ejection fraction (RVEF) were significantly worse compared to patients with mild TR (all P<0.05). Multivariate logistic regression analyses revealed that RVGLS was independently associated with moderate or severe TR >6 months after CR [odds ratio (OR) 1.193, 95% confidence interval (CI): 1.025-1.388; P=0.02]. Conclusions: RVGLS was a significant predictor of moderate or severe TR >6 months after CR. This finding emphasizes that early and accurate measurement of RV function may help to identify patients at high risk for severe residual or recurrent TR.
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BACKGROUND: Middle cerebral artery (MCA) plaques are a leading cause of ischemic stroke (IS). Plaque inflammation is crucial for plaque stability and urgently needs quantitative detection. PURPOSE: To explore the utility of Controlled Aliasing in Parallel Imaging Results in Higher Acceleration (CAIPIRINHA)-Dixon-Time-resolved angiography With Interleaved Stochastic Trajectories (TWIST) (CDT) dynamic contrast-enhanced MRI (DCE-MRI) for evaluating MCA culprit plaque inflammation changes over stroke time and with diabetes mellitus (DM). STUDY TYPE: Prospective. POPULATION: Ninety-four patients (51.6 ± 12.23 years, 32 females, 23 DM) with acute IS (AIS; N = 43) and non-acute IS (non-AIS; 14 days < stroke time ≤ 3 months; N = 51). FIELD STRENGTH/SEQUENCE: 3-T, CDT DCE-MRI and three-dimensional (3D) Sampling Perfection with Application optimized Contrast using different flip angle Evolution (3D-SPACE) T1-weighted imaging (T1WI). ASSESSMENT: Stroke time (from initial IS symptoms to MRI) and DM were registered. For 94 MCA culprit plaques, Ktrans from CDT DCE-MRI and enhancement ratio (ER) from 3D-SPACE T1WI were compared between groups with and without AIS and DM. STATISTICAL TESTS: Shapiro-Wilk test, Bland-Altman analysis, Passing and Bablok test, independent t-test, Mann-Whitney U test, Chi-squared test, Fisher's exact test, receiver operating characteristics (ROC) with the area under the curve (AUC), DeLong's test, and Spearman rank correlation test with the P-value significance level of 0.05. RESULTS: Ktrans and ER of MCA culprit plaques were significantly higher in AIS than non-AIS patients (Ktrans = 0.098 s-1 vs. 0.037 s-1; ER = 0.86 vs. 0.55). Ktrans showed better AUC for distinguishing AIS from non-AIS patients (0.87 vs. 0.75) and stronger negative correlation with stroke time than ER (r = -0.60 vs. -0.34). DM patients had significantly higher Ktrans and ER than non-DM patients in IS and AIS groups. DATA CONCLUSION: Imaging by CDT DCE-MRI may allow to quantitatively evaluate MCA culprit plaques over stroke time and DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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KEY MESSAGE: Rice OsSPL11 activates the expression of GW5L through binding to its promoter and positively regulates grain size. Grain size (GS) is an important determinant of grain weight and yield potential in cereal. Here, we report the functional analysis of OsSPL11 in grain length (GL), grain width (GW), and 1000-grain weight (TGW). OsSPL11 mutant plants, osspl11 lines, exhibited a decrease in GL, GW, and TGW, and OsSPL11-OE lines showed an increase in GL and TGW. Expression analysis revealed that OsSPL11 was located in the nucleus and highly expressed in spikelet hull and young development grains, consistent with its function in determining GS. Further analysis confirmed that OsSPL11 directly activates the expression of GW5L to regulate GS, meanwhile OsSPL11 expression is negatively regulated by OsGBP3. Taken together, our findings demonstrate that OsSPL11 could be a key regulator of affecting GS during the spikelet hull development and facilitate the process of improving grain yield by GS modification in rice.
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Grão Comestível , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Mutação/genéticaRESUMO
Down syndrome (DS), caused by an additional chromosome 21, has a high risk of congenital heart defects (CHD), one of the primary causes of mortality in DS newborns. To elucidate the pathogenetic mechanisms underlying this condition, we explored the role of RNA m6A methylation, regulated by METTL3, in DS cardiac development and its impact on the expression of SH3BGR, a gene located at Down syndrome congenital heart disease (DS-CHD) minimal region. We analyzed DS fetal cardiac tissues to assess RNA m6A methylation levels and identify potential contributors. RNA sequencing was performed to detect differentially expressed genes in the same tissues. To further understand METTL3's function in heart development, we inactivated Mettl3 in the developing mouse heart to mimic the significantly reduced METTL3 observed in DS cardiac development. Additionally, human cardiomyocyte AC16 cells were used to investigate the molecular mechanism by which METTL3 regulates SH3BGR expression. Apoptosis was analyzed to evaluate METTL3's effect on heart development through SH3BGR regulation. Reduced m6A modification and decreased METTL3 expression were observed in human DS fetal hearts, along with a significant increase of SH3BGR expression. METTL3, through m6A modification, was found to regulate SH3BGR expression, by influencing mRNA stability. METTL3-deficient mouse embryos exhibited heart malformation with increased apoptosis, emphasizing its role in heart development. In DS hearts, METTL3 downregulation and SH3BGR upregulation, potentially orchestrated by abnormal m6A modification, contribute to gene dysregulation and apoptosis. This study reveals novel insights into DS cardiac pathology, highlighting the intricate role of METTL3 in DS congenital heart defects and presenting the m6A modification of SH3BGR as a potential therapeutic target.
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Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC(0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC(0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.
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Converting CO2 into high-value chemical fuels through green photoelectrocatalytic reaction path is considered as a potential strategy to solve energy and environmental problems. In this work, BiVO4/ZIF-8 heterojunctions are prepared by in-situ synthesis of ZIF-8 nanocrystals with unique pore structure on the surface of BiVO4. The experimental results show that the silkworm pupa-like BiVO4 is successfully combined with porous ZIF-8, and the introduction of ZIF-8 can provide more sites for CO2 capture. The optimal composite ratio of 4:1-BiVO4/ZIF-8 showed excellent CO2 reduction activity and the lowest electrochemical transport resistance. In the electrocatalytic system, 4:1-BiVO4/ZIF-8 exhibits formate Faraday efficiency of 82.60% at -1.0 V vs. RHE. Furthermore, the Faraday efficiency increases to 91.24% at - 0.9 V vs. RHE in the photoelectrocatalytic system, which is 10.8 times that of pristine BiVO4. The results show that photoelectric synergism can not only reduce energy consumption, but also improve the Faraday efficiency of formate. In addition, the current density did not decrease during 34 h electrolysis, showing long-term stability. This work highlights the importance of the construction of heterojunction to improve the performance of photoelectrocatalytic CO2 reduction.
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PURPOSE: We explored the dosimetric efficacy of the abdominal deep inspiration breath hold (aDIBH) technique using an audio-guided device in patients with left breast cancer undergoing postoperative adjuvant radiotherapy compared to free breathing (FB). METHODS: A total of 35 patients with early stage left breast cancer underwent two computed tomography simulation scans each with aDIBH and FB after breast-conserving surgery. Treatment planning was optimized using the Pinnacle3 9.10 planning system. The heart, left anterior descending coronary artery (LADCA), and left lung was defined as organs at risk (OARs). The dosimetric differences in the planning target volume (PTV) and OARs were compared between aDIBH and FB. RESULTS: Compared with FB, the heart moved farther caudally and away from the chest wall, and the volume of heart became smaller under aDIBH due to expansion of the lungs. The D mean of the heart, LADCA and left lung of aDIBH were respectively reduced by 332.79 ± 264.61 cGy (P < 0.001), 1290.37 ± 612.09 cGy (P < 0.047) and 69.94 ± 117.73 cGy (P < 0.001). The V20 and V30 of the OARs were also significantly reduced with statistical differences (P < 0.05). In addition, there was no significant difference in the dosimetric parameters of the PTV between the two groups (P > 0.05). CONCLUSIONS: Implementation of the aDIBH technique for postoperative radiotherapy after breast-conserving surgery of the left breast cancer could reduce irradiation of the heart dose, LADCA dose and left lung dose, without compromising target coverage.
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Suspensão da Respiração , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias Unilaterais da Mama , Humanos , Feminino , Radioterapia Adjuvante/métodos , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias Unilaterais da Mama/cirurgia , Órgãos em Risco/efeitos da radiação , Adulto , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Idoso , Coração/efeitos da radiação , Tomografia Computadorizada por Raios X , Pulmão/efeitos da radiação , Pulmão/cirurgia , InalaçãoRESUMO
Objective: Dual use of combustible cigarettes and e-cigarettes is common among U.S. tobacco users, yet mis-perceptions about the harm of dual use persist, often oversimplifying its multifaceted exposure and health impacts. To address this gap, we evaluated the association of prolonged dual use (consecutive use for more than 1 year) with psychosocial factors, including perceptions of absolute and relative harm of e-cigarettes, social norms, and intentions to quit smoking, among U.S. adult smokers over time. Methods: Using the data from Waves 1 to 5 (2013-2019) from the Population Assessment of Tobacco and Health (PATH) Study, we characterized dual use and prolonged dual use by sociodemographics and psychosocial factors among U.S. adult smokers. We examined the association between dual use, including prolonged dual use, and psychosocial factors over time using logistic regression. Results: Dual use of smokers decreased from 19.8 % in 2013 to 16.4 % in 2019, and prolonged dual use among dual users decreased from 40.0 % in 2013 to 27.4 % in 2019. Prolonged dual users, independent of frequency of use, presented significantly higher cigarette dependence than temporary dual users. The perception of absolute e-cigarette harm (perceiving e-cigarettes as very or extremely harmful) was negatively associated with prolonged dual use. No significant association was found between prolonged dual use and perception of relative e-cigarette harm (perceiving e-cigarettes are less harmful than cigarettes) as well as with intentions to quit smoking and beliefs that most people disapprove of e-cigarette use. Conclusion: Increased perceptions of absolute harm of e-cigarettes, rather than relative harm, appear to decrease prolonged dual use. Public health strategies should consider further emphasis in educating users of the absolute harm, as opposed to endorsing e-cigarette use as a harm reduction alternative, in their tobacco cessation efforts to further discourage dual use.
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This experiment was aimed to investigate the effects of Phytosterol Ester (PSE) supplementation on egg weight, biochemical indices, liver immunity and gut microbiota of Hy-Line Brown laying hens during peak laying period. A total of 256 healthy Hy-Line Brown laying hens were randomly allocated into 4 groups. Laying hens in the control group were fed a basal diet (CON), while those in the experimental groups received a basal diet containing 10 mg/kg (PSE10), 20 mg/kg (PSE20), or 40 mg/kg (PSE40) mg/kg PSE, respectively. We found that PSE supplementation significantly increased the egg weight in PSE20 and PSE40 groups (P < 0.05) and the serum magnesium (Mg) content in PSE10 and PSE20 groups (P < 0.05), but significantly decreased the serum calcium (Ca) content in PSE40 group (P < 0.05). Moreover, PSE supplementation significantly increased the total protein (TP) content of ovary in all experimental groups (P < 0.01) and decreased the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) contents of the ovary in PSE20 and PSE40 groups (P < 0.001). In serum, PSE supplementation significantly increased TP content in all experimental groups (P < 0.01) and albumin (ALB) content in PSE20 group (P < 0.05). Alkaline phosphatase (AKP) in PSE20 group, TC content in all experimental groups and LDL-C content in PSE20 and PSE40 groups were significantly decreased (P < 0.05). In egg yolk, PSE supplementation significantly increased TP content in PSE20 and PSE40 groups (P < 0.01) and decreased TC content in PSE20 group (P < 0.01). In liver immunofluorescence, PSE supplementation altered the content of CD163, especially in PSE20 group. Dietary PSE significantly decreased the relative abundance of Bacteroides and Desulfovibrio, while increased the relative abundance of Faecalibacterium, g_unclassified_f_Lachnospiraceae, g_norank_f_Ruminococcaceae, g__unclassified_f__Oscillospiraceae and other bacteria. In conclusion, PSE supplementation increased the average egg weight and total protein, lowered egg yolk, serum and ovary cholesterol of Hy-Line Brown laying hens. At the same time, it can also promote serum magnesium levels, enhanced liver immunity, and improved gut microflora.
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In the field of soil remediation, the importance of bioavailability of pollutants has not received adequate attention, leading to the excessive application of remediation measures. Therefore, to ensure the safe use of farmland soil, a scientific method is needed to assess labile contaminants and their translocation in plants. To evaluate soil remediation effect based on bioavailability, the concentrations of these heavy metals in soil were analyzed using by the method for total metal content, the Community Bureau of Reference (BCR) extraction, and the diffusive gradients in thin films (DGT) technique. The results reveal that the correlation coefficients between metal concentrations measured by DGT and those accumulated in rice grains are the highest (Cr-R2 = 0.8966, Pb-R2 = 0.9045). However, the capability of method for total metal content to evaluate the remediation effect of heavy metals is very limited. In contrast, although Cr and Pb measured by BCR show a high correlation with HMs in rice plants, the method still falls short in precisely assessing bioavailability. Significantly, DGT proves to be more effective, successfully distinguishing the remediation effects of different treatments. Generally, DGT offers a more accurate and simpler assessment method, underscoring its practical significance for monitoring soil remediation and environmental management.
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Cromo , Recuperação e Remediação Ambiental , Chumbo , Poluentes do Solo , Solo , Poluentes do Solo/análise , Recuperação e Remediação Ambiental/métodos , Chumbo/análise , Solo/química , Cromo/análise , Disponibilidade Biológica , Monitoramento Ambiental/métodos , OryzaRESUMO
Light-emitting electrochemical cells (LECs) are appealing for cost-effective, large-area emission applications; however, their luminescence efficiency is significantly limited by exciton annihilation caused by high concentration polarons. Here, we present thermally activated delayed fluorescence (TADF) sensitized fluorescence LECs (TSF-LECs) that achieve a record 9% EQE. The TADF sensitizers with rapid reverse intersystem crossing (RISC) rates can effectively convert triplet excitons to singlet excitons in LECs, thereby establishing a more efficient overall energy transfer pathway. Importantly, magneto-electroluminescence measurements indicate that the additional RISC route in TSF-LECs significantly suppresses the annihilation of triplet excitons and thus reduces exciton loss under high concentration polaron conditions. Compared to LECs without a sensitizer, TSF-LECs exhibit improved EQE and luminance, extended operational lifetimes, and suppressed efficiency roll-off. A flexible display prototype based on TSF-LECs was further fabricated, capable of stably displaying high-brightness preset patterns for extended periods. The exploration of the exciton dynamics in high concentration polaron environments offers valuable insights for future developments in high-efficiency LEC technology.
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Shrews (Soricidae) are common small wild mammals. Some species of shrews, such as Asian house shrews (Suncus murinus), have a significant overlap in their habitats with humans and domestic animals. Currently, over 190 species of viruses in 32 families, including Adenoviridae, Arenaviridae, Arteriviridae, Astroviridae, Anelloviridae, Bornaviridae, Caliciviridae, Chuviridae, Coronaviridae, Filoviridae, Flaviviridae, Hantaviridae, Hepadnaviridae, Hepeviridae, Nairoviridae, Nodaviridae, Orthoherpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Phenuiviridae, Picobirnaviridae, Picornaviridae, Polyomaviridae, Poxviridae, Rhabdoviridae, Sedoreoviridae, Spinareoviridae, and three unclassified families, have been identified in shrews. Diverse shrew viruses, such as Borna disease virus 1, Langya virus, and severe fever with thrombocytopenia syndrome virus, cause diseases in humans and/or domestic animals, posing significant threats to public health and animal health. This review compiled fundamental information about shrews and provided a comprehensive summary of the viruses that have been detected in shrews, with the aim of facilitating a deep understanding of shrews and the diversity, epidemiology, and risks of their viruses.
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Musaranhos , Viroses , Vírus , Animais , Musaranhos/virologia , Vírus/classificação , Vírus/isolamento & purificação , Vírus/genética , Viroses/veterinária , Viroses/virologia , Filogenia , HumanosRESUMO
Respiratory syncytial virus (RSV)-induced viral pneumonia in children is common worldwide. Its high occurrence and lack of an effective vaccine make it a leading cause of death in children. Severe RSV infection can trigger uncontrolled inflammatory responses in patients, so the development of small molecule drugs with the dual function of "direct antivirus" and "inflammatory response regulation" is welcome. Resveratrol (Res) has been reported to have antiviral and anti-inflammatory pharmacological effects, but its application is limited because of its poor water solubility and oral bioavailability. Based on small-molecule nanotechnology, we developed a sonication-assisted self-assembly method for preparing insoluble Res into highly soluble resveratrol nanoparticles (Res NPs). The obtained Res NPs exhibited a higher water solubility and a faster dissolution rate, which was more conducive to the effectiveness of Res in addressing RSV-induced viral pneumonia. In vitro studies had shown that Res NPs played an antiviral role by inhibiting RSV replication and reducing the production of pro-inflammatory cytokines. Nebulized inhalation administration of Res NPs prolonged the drug's residence time in the lungs, which appears to increase the accumulation and effectiveness of Res NPs. Additionally, in vivo studies had demonstrated significant benefits of Res NPs in inhibiting RSV viral load and improving the pulmonary microenvironment in RSV-infected mice. Both antiviral and anti-inflammatory experiments had confirmed that the pharmacological activity of Res NPs is superior to that of Res. This suggested that nanosizing Res was an effective way to enhance the original pharmacological activity of Res and also offered a new formulation strategy for treating viral pneumonia.
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Anti-Inflamatórios , Antivirais , Nanopartículas , Infecções por Vírus Respiratório Sincicial , Resveratrol , Sonicação , Resveratrol/farmacologia , Resveratrol/química , Resveratrol/administração & dosagem , Nanopartículas/química , Animais , Antivirais/química , Antivirais/farmacologia , Antivirais/administração & dosagem , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Camundongos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Humanos , Camundongos Endogâmicos BALB C , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Feminino , Replicação Viral/efeitos dos fármacos , Pulmão/virologia , Pulmão/efeitos dos fármacos , Pulmão/patologiaRESUMO
Background: The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). Methods: PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3-18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. Findings: The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51-0.74), with T1D at 0.44/1000 (95% CI: 0.35-0.54) and T2D at 0.18/1000 (95% CI: 0.13-0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. Interpretation: The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. Funding: The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.
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In this study, vortex-assisted liquid-liquid microextraction (VA-LLME) based on hydrophobic deep eutectic solvents (HDES) was used to efficiently and sustainably extract five phenolic acids and tetramethylpyrazine (TMP) from Shanxi aged vinegar (SAV). The VA-LLME technique was employed to investigate the extraction mechanism of HDES with the best extraction performance for the target compounds using a conductor-like screening model for real solvents (COSMO-RS). An artificial neural network combined with a genetic algorithm (ANN-GA) was developed to optimize the extraction conditions based on single-factor and response surface methodology, while also analyzing the interactive effects on the phenolic acids and TMP in the extracted solution during the extraction phase. The optimized conditions were determined, and the greenness of the procedure was evaluated using an analytical greenness metric, indicating that this technique can serve as a green alternative for the determination of phenolic acids and TMP in SAV.
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The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.