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Although reactive nitrogen (Nr) emissions from food and energy production contribute to multi-dimensional environmental damages, integrated management of Nr is still lacking owing to unclear future mitigation potentials and benefits. Here, we find that by 2050, high-ambition compared to low-ambition N interventions reduce global ammonia and nitrogen oxide emissions by 21 and 22 TgN/a, respectively, equivalent to 40 and 52% of their 2015 levels. This would mitigate population-weighted PM2.5 by 6 g/m3 and avoid premature deaths by 817 k (16%), mitigate ozone by 4 ppbv, avoid premature deaths by 252k (34%) and crop yield losses by 122 million tons (4.3%), and decrease terrestrial ecosystem areas exceeding critical load by 420 Mha (69%). Without nitrogen interventions, most environmental damages examined will deteriorate between 2015 and 2050; Africa and Asia are the most vulnerable but also benefit the most from interventions. Nitrogen interventions support sustainable development goals related to air, health, and ecosystems.
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Poluição do Ar , Ecossistema , Nitrogênio , Poluição do Ar/prevenção & controle , Poluentes Atmosféricos/análise , Amônia , OzônioRESUMO
A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.
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Developing a hemostatic material suitable for rapid hemostasis remains a challenge. This study presents a novel aminated gelatin sponge cross-linked with dialdehyde starch, exhibiting excellent biocompatibility and hemostatic ability. This aminated gelatin sponge features hydrophilic surface and rich porous structure with a porosity of up to 80 %. The results show that the aminated gelatin sponges exhibit superior liquid absorption capacity and can absorb up to 30-50 times their own mass of simulated body fluid within 5 min. Compared with the commercial gelatin hemostatic sponge and non-aminated gelatin hemostatic sponge, the aminated gelatin hemostatic sponge can accelerate the hemostatic process through electrostatic interactions, demonstrating superior hemostatic performance in both in vitro and in vivo hemostasis tests. The aminated gelatin sponge can effectively control the hemostatic time within 80 s in the in vivo rat femoral artery injury model, significantly outperforming both commercial and non-aminated gelatin sponges. In addition, the aminated gelatin sponge also exhibits good biocompatibility and certain antibacterial properties. The proposed aminated gelatin sponge has very good application prospects for the management of massive hemorrhage.
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Materiais Biocompatíveis , Gelatina , Hemostáticos , Amido , Animais , Amido/química , Amido/farmacologia , Amido/análogos & derivados , Ratos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Gelatina/química , Gelatina/farmacologia , Masculino , Porosidade , Ratos Sprague-Dawley , Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Esponja de Gelatina Absorvível/química , Esponja de Gelatina Absorvível/farmacologia , Reagentes de Ligações Cruzadas/química , Artéria Femoral/efeitos dos fármacos , HumanosRESUMO
BACKGROUND: Breast cancer patients exhibit various response patterns to neoadjuvant chemotherapy (NAC). However, it is uncertain whether diverse tumor response patterns to NAC in breast cancer patients can predict survival outcomes. We aimed to develop and validate radiomic signatures indicative of tumor shrinkage and therapeutic response for improved survival analysis. METHODS: This retrospective, multicohort study included three datasets. The development dataset, consisting of preoperative and early NAC DCE-MRI data from 255 patients, was used to create an imaging signature-based multitask model for predicting tumor shrinkage patterns and pathological complete response (pCR). Patients were categorized as pCR, nonpCR with concentric shrinkage (CS), or nonpCR with non-CS, with prediction performance measured by the area under the curve (AUC). The prognostic validation dataset (n = 174) was used to assess the prognostic value of the imaging signatures for overall survival (OS) and recurrence-free survival (RFS) using a multivariate Cox model. The gene expression data (genomic validation dataset, n = 112) were analyzed to determine the biological basis of the response patterns. RESULTS: The multitask learning model, utilizing 17 radiomic signatures, achieved AUCs of 0.886 for predicting tumor shrinkage and 0.760 for predicting pCR. Patients who achieved pCR had the best survival outcomes, while nonpCR patients with a CS pattern had better survival than non-CS patients did, with significant differences in OS and RFS (p = 0.00012 and p = 0.00063, respectively). Gene expression analysis highlighted the involvement of the IL-17 and estrogen signaling pathways in response variability. CONCLUSIONS: Radiomic signatures effectively predict NAC response patterns in breast cancer patients and are associated with specific survival outcomes. The CS pattern in nonpCR patients indicates better survival.
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Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Prognóstico , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética , Resultado do Tratamento , Estudos de Coortes , Idoso , Estudos Retrospectivos , Reprodutibilidade dos Testes , RadiômicaRESUMO
Secondary inorganic aerosols play an important role in air pollution and climate change, and their formation modulates the atmospheric deposition of reactive nitrogen (including oxidized and reduced nitrogen), thus impacting the nitrogen cycle. Large-scale and long-term analyses of secondary inorganic aerosol formation based on model simulations have substantial uncertainties. Here we improve constraints on secondary inorganic aerosol formation using decade-long in situ observations of aerosol composition and gaseous precursors from multiple monitoring networks across the United States. We reveal a shift in the secondary inorganic aerosol formation regime in the rural United States between 2011 and 2020, making rural areas less sensitive to changes in ammonia concentrations and shortening the effective atmospheric lifetime of reduced forms of reactive nitrogen. This leads to potential increases in reactive nitrogen deposition near ammonia emission hotspots, with ecosystem impacts warranting further investigation. Ammonia (NH3), a critical but not directly regulated precursor of fine particulate matter in the United States, has been increasingly scrutinized to improve air quality. Our findings, however, show that controlling NH3 became significantly less effective for mitigating fine particulate matter in the rural United States. We highlight the need for more collocated aerosol and precursor observations for better characterization of secondary inorganic aerosols formation in urban areas.
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Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.
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Nanopartículas , Polissacarídeos , Polissacarídeos/química , Nanopartículas/química , Animais , Humanos , Camundongos , Técnicas de Transferência de Genes , Terapêutica com RNAi/métodos , Interferência de RNA , Masculino , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/terapiaRESUMO
Previous meta-analyses of multiple studies have suggested that dietary intake and blood concentrations of carotenoids, as well as dietary supplement of certain carotenoids, play a role in reducing the risk of cancer. However, the conclusions of these studies have been subject to controversy. We conducted an umbrella review of meta-analyses to comprehensively analyze and evaluate the evidence pertaining the association between carotenoids and cancer outcomes. We searched PubMed, Web of Science, Embase, and Cochrane Library databases of meta-analyses and systematic reviews up to June 2023. Our selection criteria encompassed meta-analyses of cohort and case-control studies, as well as randomized controlled clinical trials, which investigated the associations between carotenoids and cancer risk. We also determined the levels of evidence for these associations with AMSTAR 2 criteria. We included 51 eligible articles, including 198 meta-analyses for qualitative synthesis in the umbrella review. Despite the presence of moderate to high heterogeneity among the studies, dietary intake, supplementation, and blood concentrations of carotenoids were inversely associated with the risk of total cancer, and certain specific cancers of lung, digestive system, prostate, breast, head and neck, and others. Subgroup analysis also showed that individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, and lycopene) offer certain protection against specific types of cancers. However, high doses of carotenoid supplements, especially ß-carotene, significantly increased the risk of total cancer, lung cancer, and bladder cancer. Our umbrella meta-analysis supported that high intake of dietary carotenoids as a whole food approach could be more beneficial in reducing cancer risk. Concurrently, the findings suggest that the efficacy of single-carotenoid supplementation in cancer prevention remains a subject of controversy.
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The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.
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Biologia Computacional , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas de Ligação a Ácido Graxo , Glutationa Peroxidase , Selênio , Humanos , Selênio/sangue , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/sangue , Estudos de Casos e Controles , Neoplasias Esofágicas/prevenção & controle , Neoplasias Esofágicas/genética , Biologia Computacional/métodos , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Carcinoma de Células Escamosas do Esôfago/prevenção & controle , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Masculino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , IdosoRESUMO
OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research. METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search. RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation. CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.
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Carnitina , Transtornos Mentais , Doenças do Sistema Nervoso , Humanos , Carnitina/uso terapêutico , Suplementos Nutricionais , Transtornos Mentais/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológicoRESUMO
BACKGROUND: Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients. METHODS: The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS: A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74). CONCLUSION: This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies.
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Lactobacillus , Metanálise em Rede , Hepatopatia Gordurosa não Alcoólica , Probióticos , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Bifidobacterium , Streptococcus , Resultado do TratamentoRESUMO
A new species of pomatiopsid freshwater snail, Fenouiliaundata Chen & He, sp. nov., is described from Guangxi, China, based on morphological and molecular evidence. The new species can be distinguished from its congeners by the following combination of characters: shell with low, prosocline, rounded axial ribs and fine spiral striae, broader than high; aperture broader than shell height; radula with lateral teeth have only two or three faint, wavy ridges on inner side. A molecular analysis of partial mitochondrial COI and 16S DNA sequences supports the systematic position of the new taxon.
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BACKGROUND: Hypertension is one of the major public health problems in China. Limited evidence exists regarding sex differences in the association between hypertension and air pollutants, as well as the impact of dietary factors on the relationship between air pollutants and hypertension. The aim of this study was to investigate the sex-specific effects of dietary patterns on the association between fine particulate matter (PM2.5), ozone(O3) and hypertension in adults residing in Jiangsu Province of China. METHODS: A total of 3189 adults from the 2015 China Adult Chronic Disease and Nutrition Surveillance in Jiangsu Province were included in this study. PM2.5 and O3 concentrations were estimated using satellite space-time models and assigned to each participant. Dietary patterns were determined by reduced rank regression (RRR), and multivariate logistic regression was used to assess the associations of the obtained dietary patterns with air pollutants and hypertension risk. RESULTS: After adjusting for confounding variables, we found that males were more sensitive to long-term exposure to PM2.5 (Odds ratio (OR) = 1.42 95%CI:1.08,1.87), and females were more sensitive to long-term exposure to O3 (OR = 1.61 95%CI:1.15,2.23). Traditional southern pattern identified through RRR exhibited a protective effect against hypertension in males (OR = 0.73 95%CI: 0.56,1.00). The results of the interaction between dietary pattern score and PM2.5 revealed that adherence to traditional southern pattern was significantly associated with a decreased risk of hypertension in males (P < 0.05), while no significant association was observed among females. CONCLUSIONS: Our findings suggested that sex differences existed in the association between dietary patterns, air pollutants and hypertension. Furthermore, we found that adherence to traditional southern pattern may mitigate the risk of long-term PM2.5 exposure-induced hypertension in males.
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Poluentes Atmosféricos , Hipertensão , Ozônio , Material Particulado , Humanos , Masculino , Feminino , Hipertensão/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Material Particulado/análise , Material Particulado/efeitos adversos , Adulto , Ozônio/análise , Ozônio/efeitos adversos , Fatores Sexuais , Dieta/estatística & dados numéricos , Idoso , Exposição Ambiental/efeitos adversos , Padrões DietéticosRESUMO
This study aims to update the evidence and clarify whether cranberry possesses lipid-lowering and hypoglycemic properties in humans. PubMed, Web of Science, and Scopus were searched to identify relevant articles published up to December 2023. In total, 3145 publications were reviewed and 16 of them were included for qualitative synthesis and meta-analysis. Stata 15.0 and Review Manager 5.4 were applied for statistical analyses. The results revealed a significant decrease in the total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) (MD = -0.24; 95% CI: -0.45, -0.04; peffect = 0.02) and homeostasis model assessment of insulin resistance (HOMA-IR) (MD = -0.59; 95% CI: -1.05, -0.14; peffect = 0.01) with cranberry consumption. However, it did not influence total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and fasting insulin. In subgroup analysis, cranberry consumption in dried form (capsules, powder, and tablets) was found to significantly decrease the fasting insulin level (three studies, one hundred sixty-five participants, MD = -2.16; 95% CI: -4.24, -0.07; peffect = 0.04), while intervention duration, health conditions, and dosage of polyphenols and anthocyanins had no impact on blood lipid and glycemic parameters. In summary, cranberry might have potential benefits in regulating lipid and glucose profiles.
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Vaccinium macrocarpon , Humanos , Antocianinas , Glicemia , HDL-Colesterol , Insulina , Lipídeos , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , TriglicerídeosRESUMO
Objectives: This study aimed to explore the relationship between red blood cell distribution width (RDW) and all-cause mortality in critically ill patients undergoing intra-aortic balloon pumping (IABP) in the intensive care unit (ICU). Methods: This study retrospectively analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was the 30-day mortality rate, while the secondary endpoint was the in-hospital mortality rate. Restricted cubic splines were used to assess the dose-response relationship. The receiver operating characteristic (ROC) curve and Kaplan-Meier curve analysis were carried out to evaluate the predictive performance of RDW. Moreover, multiple logistic regression analyses and subgroup analyses were conducted to investigate the relationship between RDW and 30-day mortality. Finally, propensity score matching (PSM) was performed to adjust for the imbalance of covariates. Results: In total, 732 patients were finally identified from the MIMIC-IV database in this study. The RDW of patients in the non-survivor group was significantly higher compared with those in the survivor group (P < 0.01). Multiple logistic regression analyses corroborated RDW was an independent predictor of all-cause 30-day mortality in critically ill patients post-IABP. Meanwhile, ROC analysis identified an RDW cutoff of 14.2%. High RDW patients exhibited a 131% (OR = 2.31, 95% CI: 1.49-3.61) elevated risk of 30-day mortality after adjusting for confounders in multivariable logistic regression. After PSM, 412 patients were included in the matched cohort. In the original and matched cohorts, the high RDW group had higher 30-day and in-hospital mortality rates, as well as longer ICU stays. Lastly, the area under the ROC curve for 30-day mortality was 0.686, with an optimal cutoff point of 14.2 for RDW (sensitivity: 69.09 % and specificity: 63.32%). Conclusion: RDW could be a simple and valuable prognostic tool to predict mortality in critically ill patients after IABP.
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BACKGROUND: Accumulating data show that probiotics may be beneficial for reducing depressive, anxiety, and stress symptoms. However, the best combinations and species of probiotics have not been identified. The objective of our study was to assess the most effective combinations and components of different probiotics through network meta-analysis. METHOD: A systematic search of four databases, PubMed, Web of Science, Cochrane, and Embase, was conducted from inception to 11 January 2024. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS: We deemed 45 trials eligible, these included 4053 participants and 10 types of interventions. The quality of evidence was rated as high or moderate. The NMA revealed that Bifidobacterium exhibited a greater probability of being the optimal probiotic species for improving anxiety symptoms (SMD = -0.80; 95% CI -1.49 to -0.11), followed by Lactobacillus (SMD = -0.49; 95% CI -0.85 to -0.12). In addition, for multiple strains, compared with the other interventions, Lactobacillus + Bifidobacterium (SMD = -0.41; 95% CI -0.73 to -0.10) had a positive effect on depression. CONCLUSION: The NMA revealed that Lactobacillus and Bifidobacterium had prominent efficacy in the treatment of individuals with anxiety, depression, and combination of Lactobacillus + Bifidobacterium had a similar effect. With few direct comparisons available between probiotic species, this NMA may be instrumental in shaping the guidelines for probiotic treatment of psychological disorders.
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Peptide stapling is recognized as an effective strategy for improving the proteolytic stability and cell permeability of peptides. In this study, we present a novel approach for the site-selective unsymmetric perfluoroaryl stapling of Ser and Cys residues in unprotected peptides. The stapling reaction proceeds smoothly under very mild conditions, exhibiting a remarkably rapid reaction rate. It can furnish stapled products in both liquid and solid phases, and the presence of nucleophilic groups other than Cys thiol within the peptide does not impede the reaction, resulting in uniformly high yields. Importantly, the chemoselective activation of Ser ß-C(sp3)-H enables the unreacted -OH to serve as a reactive handle for subsequent divergent modification of the staple moiety with various therapeutic functionalities, including a clickable azido group, a polar moiety, a lipid tag, and a fluorescent dye. In our study, we have also developed a visible-light-induced chemoselective C(sp3)-H polyfluoroarylation of the Ser ß-position. This reaction avoids interference with the competitive reaction of Ser -OH, enabling the precise late-stage polyfluoroarylative modification of Ser residues in various unprotected peptides containing other highly reactive amino acid residues. The biological assay suggested that our peptide stapling strategy would potentially enhance the proteolytic stability and cellular permeability of peptides.
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Aminoácidos , Peptídeos , Peptídeos/química , Compostos de Sulfidrila/química , Corantes Fluorescentes , Peptídeo HidrolasesRESUMO
Most cases of delayed wound healing are associated with bacterial biofilm infections due to high antibiotic resistance. To improve patient compliance and recovery rates, it is critical to develop minimally invasive and efficient methods to eliminate bacterial biofilms as an alternative to clinical debridement techniques. Herein, we develop a dissolving microneedle system containing Ag nanoparticles (AgNPs)-decorated silk fibroin microspheres (SFM-AgNPs) and antibiotics for synergistic treatment of bacterial biofilm infection. Silk fibroin microspheres (SFM) are controllably prepared in an incompatible system formed by a mixture of protein and carbohydrate solutions by using a mild all-aqueous phase method and serve as biological templates for the synthesis of AgNPs. The SFM-AgNPs exert dose- and time-dependent broad-spectrum antibacterial effects by inducing bacterial adhesion. The combination of SFM-AgNPs with antibiotics breaks the limitation of the antibacterial spectrum and achieves better efficacy with reduced antibiotic dosage. Using hyaluronic acid (HA) as the soluble matrix, the microneedle system containing SFM-AgNPs and anti-Gram-positive coccus drug (Mupirocin) inserts into the bacterial biofilms with sufficient strength, thereby effectively delivering the antibacterial agents and realizing good antibiofilm effect on Staphylococcus aureus-infected wounds. This work demonstrates the great potential for the development of novel therapeutic systems for eradicating bacterial biofilm infections.
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Fibroínas , Nanopartículas Metálicas , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Fibroínas/farmacologia , Prata/farmacologia , Microesferas , Bactérias , Biofilmes , SedaRESUMO
This study was performed to explore the association between attention-deficit/hyperactivity disorder (ADHD) and the risk of overweight/obesity in both children and adolescents. The PubMed, Web of Science, and Cochrane Library databases were searched for relevant studies published before July 12, 2022. Studies with data for calculating the odds ratio (OR) of childhood overweight/obesity and ADHD were included. The literature value was assessed by the cross-sectional evaluation criteria proposed by the Agency for Healthcare Research and Quality (AHRQ). All analyses were conducted using StataSE 11 and RevMan 5.3 software with random-effects models. This review included a total of 16 studies covering 14,981 cases and 128,916 controls.According to the meta-analysis, children with ADHD had a significant risk for co-occurring overweight and obesity [OR 1.56; 95% confidence intervals (CI) 1.32-1.85], especially boys (OR 1.45; 95% CI 1.10-1.90), people in Asia (OR 3.25; 95% CI 1.70-6.21) and Europe (OR 1.85; 95% CI 1.61-2.12), and patients not using medication (OR 1.54; 95% CI 1.22-1.94).ADHD has a significant association with overweight and obesity in both children and adolescents, which may be altered by factors such as geography, gender, and medication use. Timely treatment should be provided to children and adolescents diagnosed with ADHD to inhibit the emergence of overweight and obesity.
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Transtorno do Deficit de Atenção com Hiperatividade , Sobrepeso , Obesidade Infantil , Adolescente , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos Transversais , Bases de Dados Factuais , Sobrepeso/complicações , Sobrepeso/epidemiologia , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Estados Unidos/epidemiologiaRESUMO
The numerous naturally-fragmented sky islands (SIs) in the Hengduan Mountains Region (HMR) of southwestern China constitute discontinuous landscapes where montane habitats are isolated by dry-hot valleys which have fostered exceptional species diversification and endemicity. However, studies documenting the crucial role of SI on the speciation dynamics of native freshwater organisms are scarce. Here we used a novel set of comprehensive genetic markers (24 nuclear DNA sequences and complete mitogenomes), morphological characters, and biogeographical information to reveal the evolutionary history and speciation mechanisms of a group of small-bodied montane potamids in the genus Tenuipotamon. Our results provide a robustly supported phylogeny, and suggest that the vicariance events of these montane crabs correlate well with the emergence of SIs due to the uplift of the HMR during the Late Oligocene. Furthermore, ancestrally, mountain ridges provided corridors for the dispersal of these montane crabs that led to the colonization of moist montane-specific habitats, aided by past climatic conditions that were the crucial determinants of their evolutionary history. The present results illustrated that the mechanisms isolating SIs are reinforced by the harsh-dry isolating climatic features of dry-hot valleys separating SIs and continue to affect local diversification. This offers insights into the causes of the high biodiversity and endemism shown by the freshwater crabs of the HMR-SIs in southwestern China.
Assuntos
Braquiúros , Animais , Filogenia , Braquiúros/genética , China , Biodiversidade , Água DoceRESUMO
INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.