RESUMO
BACKGROUND: While many populations struggle with health literacy, those who speak Spanish preferentially or exclusively, including Hispanic, immigrant, or migrant populations, may face particular barriers, as they navigate a predominantly English-language healthcare system. This population also faces greater morbidity and mortality from treatable chronic diseases, such as hypertension and diabetes. The aim of this systematic review was to describe existing health literacy interventions for patients with a Spanish-language preference and present their effectiveness. METHODS: We carried out a systematic review where Web of Science, EMBASE, and PubMed were queried using MeSH terms to identify relevant literature. Included articles described patients with a Spanish-language preference participating in interventions to improve health literacy levels in the United States. Screening and data abstraction were conducted independently and in pairs. Risk of bias assessments were conducted using validated appraisal tools. RESULTS: A total of 2823 studies were identified, of which 62 met our eligibility criteria. The studies took place in a variety of community and clinical settings and used varied tools for measuring health literacy. Of the interventions, 28 consisted of in-person education and 27 implemented multimedia education, with 89% of studies in each category finding significant results. The remaining seven studies featured multimodal interventions, all of which achieved significant results. CONCLUSION: Successful strategies included the addition of liaison roles, such as promotores (Hispanic community health workers), and the use of multimedia fotonovelas (photo comics) with linguistic and cultural adaptations. In some cases, the external validity of the results was limited. Improving low health literacy in patients with a Spanish-language preference, a population with existing barriers to high quality of care, may help them better navigate health infrastructure and make informed decisions regarding their health. REGISTRATION: PROSPERO (available at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257655.t ).
Assuntos
Letramento em Saúde , Hispânico ou Latino , Humanos , Estados Unidos , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , IdiomaRESUMO
In this study, the family GH10 xylanase AnXylA10 derived from Aspergillus niger JL15 strain was expressed in Pichia pastoris X33. The recombinant xylanase, reAnXylA10 exhibited optimal activity at 40 â and pH 5.0. The hydrolysates generated from beechwood xylan using reAnXylA10 primarily consisted of xylobiose (X2) to xylohexaose (X6) and demonstrated remarkable antioxidant capacity. Furthermore, the rice xylanase inhibitory protein (riceXIP) was observed to competitively inhibit reAnXylA10, exhibiting an inhibition constant (Ki) of 140.6â¯nM. Molecular dynamics (MD) simulations of AnXylA10-riceXIP complex revealed that the α-7 helix (Q225-S238) of riceXIP intruded into the catalytic pocket of AnXylA10, thereby obstructing substrate access to the active site. Specifically, residue K226 of riceXIP formed robust interactions with E136 and E242, the two catalytic sites of AnXylA10, predominantly through high-occupied hydrogen bonds. Based on QTAIM, electron densities for the atom pairs K226riceXIP@HZ1-E136AnXylA10@OE2 and K226riceXIP@HZ3-E242AnXylA10@OE1 were determined to be 0.04628 and 0.02914â¯a.u., respectively. Binding free energy of AnXylA10-riceXIP complex was -59.0±7.6â¯kcal/mol, significantly driven by electrostatic and van der Waals forces. Gaining insights into the interaction between xylanase and its inhibitors, and mining the inhibition mechanism in depth, will facilitate the design of innovative GH10 family xylanases that are both highly efficient and resistant to inhibitors.
Assuntos
Antioxidantes , Aspergillus niger , Endo-1,4-beta-Xilanases , Proteínas Fúngicas , Glucuronatos , Oligossacarídeos , Proteínas Recombinantes , Xilanos , Glucuronatos/metabolismo , Glucuronatos/química , Xilanos/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Endo-1,4-beta-Xilanases/genética , Endo-1,4-beta-Xilanases/química , Aspergillus niger/enzimologia , Aspergillus niger/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Oligossacarídeos/metabolismo , Antioxidantes/metabolismo , Antioxidantes/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Simulação de Dinâmica Molecular , Oryza , Fagus , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Madeira , Pichia/genética , Pichia/metabolismo , Hidrólise , Domínio CatalíticoRESUMO
Cities are generally warmer than their adjacent rural land, a phenomenon known as the urban heat island (UHI). Often accompanying the UHI effect is another phenomenon called the urban dry island (UDI), whereby the humidity of urban land is lower than that of the surrounding rural land1-3. The UHI exacerbates heat stress on urban residents4,5, whereas the UDI may instead provide relief because the human body can cope with hot conditions better at lower humidity through perspiration6,7. The relative balance between the UHI and the UDI-as measured by changes in the wet-bulb temperature (Tw)-is a key yet largely unknown determinant of human heat stress in urban climates. Here we show that Tw is reduced in cities in dry and moderately wet climates, where the UDI more than offsets the UHI, but increased in wet climates (summer precipitation of more than 570 millimetres). Our results arise from analysis of urban and rural weather station data across the world and calculations with an urban climate model. In wet climates, the urban daytime Tw is 0.17 ± 0.14 degrees Celsius (mean ± 1 standard deviation) higher than rural Tw in the summer, primarily because of a weaker dynamic mixing in urban air. This Tw increment is small, but because of the high background Tw in wet climates, it is enough to cause two to six extra dangerous heat-stress days per summer for urban residents under current climate conditions. The risk of extreme humid heat is projected to increase in the future, and these urban effects may further amplify the risk.
Assuntos
Cidades , Clima , Transtornos de Estresse por Calor , Temperatura Alta , Umidade , Chuva , Humanos , Cidades/epidemiologia , Temperatura Alta/efeitos adversos , Tempo (Meteorologia) , Umidade/efeitos adversos , Fatores de Risco , Transtornos de Estresse por Calor/epidemiologia , Transtornos de Estresse por Calor/etiologia , Transtornos de Estresse por Calor/prevenção & controle , População Rural , Modelos Climáticos , População Urbana , Estações do AnoRESUMO
The family GH11 Aspergillus niger JL15 xylanase B (AnXylB11) was heterologously expressed in Pichia pastoris X33. The recombinant AnXylB11 (reAnXylB11) was secreted into the culture medium with a molecular weight of approximately 33.0 kDa. The optimal temperature and pH of reAnXylB11 were 40 â and 5.0, respectively. reAnXylB11 released xylobiose (X2)-xylohexaose (X6) from beechwood xylan, with xylotriose (X3) as the primary product. The hydrolysates showed significant antioxidant activity. reAnXylB11 was also competitively inhibited by recombinant rice xylanase inhibitory protein (rePriceXIP), with an inhibition constant (Ki) of 106.9 nM. Molecular dynamics (MD) simulations, non-covalent interactions (NCI), and binding free energy calculation and decomposition were conducted to decipher the interactional features between riceXIP and AnXyB11. Representative conformation of riceXIP-AnXylB11 complex showed that a U-shaped long loop between α4 and ß5 (K143-L152) of riceXIP was protruded into the catalytic groove and formed tight interaction with many key residues of AnXylB11. The binding free energy of riceXIP-AnXylB11 was calculated to be - 46.1 ± 10.5 kcal/mol, with Coulomb and van der Waals forces contributing the most. NCI analysis showed that the hydrogen bonding networks such as R148riceXIP-E98AnXyl11B, K143riceXIP-D138AnXyl11B and R148riceXIP-E189AnXyl11B provided terrific contributions to the interface interaction. The Laplacian of electron density values of atom pairs R148riceXIP@ 2HH1-E89AnXylB11@OE2 and N142riceXIP@ 1HD2-D138AnXylB11@OD1 were 0.12190 and 0.16009 a.u., respectively. Exploring the interactional features between xylanase and inhibitor protein may aid in constructing mutant xylanase that is insensitive to xylanase inhibitory proteins (XIs).
Assuntos
Endo-1,4-beta-Xilanases , Pichia , Endo-1,4-beta-Xilanases/genética , Endo-1,4-beta-Xilanases/química , Endo-1,4-beta-Xilanases/metabolismo , Pichia/genética , Pichia/metabolismo , Aspergillus niger/genética , Concentração de Íons de Hidrogênio , Proteínas Recombinantes/química , Temperatura , Estabilidade EnzimáticaRESUMO
BACKGROUND: Ulcerative colitis (UC) is pathologically characterized by an inappropriate immune response to the gut commensal microbes accompanied by persistent epithelial barrier dysfunction, and its progression increases the susceptibility to colitis-associated cancer (CAC), as well as other complications. Fructus ligustri lucidi (FLL) has a long historical application in traditional Chinese medicine due to its various pharmacological effects, including antioxidation and anti-inflammation. The present study aimed to explore the molecular and cellular mechanisms of FLL in treating colitis. METHODS: A high-performance liquid chromatography (HPLC) combined with ultraviolet (UV) was performed to validate the quality of FLL; Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) based on The Cancer Genome Atlas (TCGA) database predicted the therapeutic value of FLL against UC and CAC; 2% dextran sodium sulfate (DSS) was administered to mice to establish murine models of experimental colitis, and FLL was given for the next 14 days at different concentrations; 16S rRNA sequencing and untargeted metabolomics were performed on fecal samples to delineate the alteration in microbiome profile; Western blotting, flow cytometry, and immunocytochemistry experiments were conducted to confirm the predicted cellular mechanisms. RESULTS: Network pharmacology analysis and WGCNA predicted that the targets of the FLL were associated with the progression of UC and the survival of patients with colorectal cancer by regulating tumor necrosis factor (TNF) and IL-17 signaling pathways, immune cell functions, responses to bacterial and reactive oxygen species (ROS), and cell proliferation. In vivo experiments corroborated that the high dose of FLL significantly attenuated the progression of experimental colitis by reversing the weight loss and bloody stool, reconstructing the integrity of colorectal epithelium, and suppressing the concentration of pro-inflammatory cytokines. Moreover, FLL treatment reduced the transition of macrophages (Mφs) to the proinflammatory phenotype and promoted Mφs-regulated wound healing, and suppressed the production of ROS in intestinal organoids (IOs) and crypts. 16S rRNA and untargeted metabolomics showed that the administration of FLL inhibited DSS-caused colonization of the potentially pathogenic gut microorganisms and reversed DSS-influenced metabolic profile. CONCLUSION: FLL is a potent anti-colitis drug by suppressing inflammation and rescuing dysbiosis.
Assuntos
Colite Ulcerativa , Colite , Ligustrum , Microbiota , Animais , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/patologia , Interleucina-17 , Ligustrum/química , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S , Espécies Reativas de Oxigênio/metabolismo , Fatores de Necrose Tumoral/uso terapêuticoRESUMO
The catalytic domain of family GH10 xylanase, XYN-LXY_CD derived from Hu sheep rumen microbiota was expressed in Pichia pastoris X33. The special activity of reXYN-LXY_CD in the culture supernatant was 232.56 U/mg. The optima of reXYN-LXY_CD were 53 °C and pH 7.0. Recombinant Oryza sativa xylanase inhibitor protein (rePOsXIP) competitively inhibited reXYN-LXY_CD with an inhibition constant (Ki) value of 237.37 nM. The concentration of hydrolysates released from beechwood xylan by reXYN-LXY_CD reduced when rePOsXIP was added into the hydrolytic system. Fluorescence of reXYN-LXY_CD was statically quenched by rePOsXIP in a dose-dependent manner. The details in intermolecular interaction between XYN-LXY_CD and OsXIP were investigated by using molecular dynamics (MD) simulations, binding free energy computation and non-covalent interactions (NCI) analysis. Hydrogen bonding and van der Waals played indispensable roles in the XYN-LXY_CD/OsXIP interaction. The α-7 helix of OsXIP tightly occupied the catalytic pocket of XYN-LXY_CD with hydrogen bonding such as K239OsXIP-N261/Q292/E197XYN-LXY_CD (E197, the acid-base catalytic residue), D236OsXIP-K327XYN-LXY_CD and Q242OsXIP-E211/Q212XYN-LXY_CD. Based on the quantum theory of atoms in molecules (QTAIM), the Laplacian of electron density and core-valence bifurcation index of HZ3K239-OE2E197 were 0.1025 a.u. and 0.002218, respectively. Elucidating the mechanism underlying xylanase-inhibitor interactions might help construct XYN-LXY_CD mutants that gain resistance to XIPs and high catalytic activity, which would be more efficient in feed additives in livestock.
Assuntos
Microbiota , Oryza , Animais , Endo-1,4-beta-Xilanases/química , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Oryza/metabolismo , Proteínas Recombinantes/genética , Rúmen/metabolismo , Ovinos , Xilanos/metabolismoRESUMO
Glycoside hydrolase (GH) family 10 and 11 xylanases are inhibited by many xylanase inhibitor proteins (XIPs). We recombinantly expressed the Oryza sativa xylanase inhibitor protein (OsXIP) in Pichia pastoris GS115, with a molecular mass of 47.0 kDa. Family GH11 Bacillus amyloliquefaciens xylanase A (BaxA) and the mutant T33I (DS199) were inhibited by the recombinant OsXIP (rePOsXIP) through competive inhibition, with corresponding inhibition constants (Ki) of 54.09 and 12.16 nM. After incubation with rePOsXIP (70 nM) at 40 °C for 40 min, inhibitory rates of reBaxA and DS199 (0.2 U) were 23.7% and 76.7%, respectively. Xylooligosaccharides with low concentration were released from beechwood xylan by reBaxA and DS199 in the presence of reOsXIP. Intrinsic fluorescences of reBaxA and DS199 were statically quenched by rePOsXIP in a concentration-dependent manner. Molecular dynamics (MD) simulations and conformational analysis of OsXIP-BaxA and OsXIP-DS199 revealed that the long loop (Lα4ß5) of OsXIP inserted into the catalytic grooves of BaxA and DS199. The DS199 enhanced the binding affinity to OsXIP, causing conformational alterations on protein-protein interface residues, thereby forming more hydrogen bonds and van der Waals forces. MM/GBSA analysis revealed that the binding free energy (∆Gbind) of OsXIP-DS199 was enhanced by 2.08 kcal/mol compared to that of OsXIP-BaxA. The OsXIP binding induced a conformational changes among residues in the cord and thumb regions of BaxA and DS199. In particular, the T111RYNAP116 residues in the thumb region of DS199 was maintained close to OsXIP by specific bonds. Additional MD simulations revealed that Y113A or T93A mutation of BaxA suppressed the binding affinity by diminishing interface associations of OsXIP-BaxA. This study partially elucidats the molecular basis of inhibitory mechanism and structure-function relationships of GH11 xylanases. Our findings inform rational designs of mutant xylanases with higher resistance to inhibitor proteins.
Assuntos
Bacillus amyloliquefaciens , Oryza , Bacillus amyloliquefaciens/genética , Bacillus amyloliquefaciens/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Oryza/metabolismo , Proteínas Recombinantes/genética , Xilanos/metabolismoRESUMO
The family GH10 Aspergillus fumigatus xylanase A (AfXylA10) gene, afxyla10 was cloned and recombinantly expressed in Pichia pastoris X33. The optimum temperature and pH of reAfXylA10 was 53 °C and 7.0, and Mn2+ remarkably activated the catalytic activity. The recombinant Oryza sativa xylanase inhibitor protein, rePOsXIP significantly inhibited reAfXylA10 with inhibition constant (Ki) of 177.94 nM via competitive inhibition and decreased the concentration of hydrolysate from beechwood xylan. Optimal inhibition of rePOsXIP on reAfXylA10 occurred at 45 °C for 40 min. The fluorescence of reAfXylA10 was statically quenched by rePOsXIP, indicating the formation of reAfXylA10-rePOsXIP complex during their interaction. Furthermore, molecular dynamics (MD) simulations were performed to obtain the detailed information on enzyme-inhibitor interaction. The binding free energy (ΔG) of AfXylA10-OsXIP complex was -30 ± 9 kcal/mol by MM-PBSA calculation, and the α-7 helix of OsXIP anchored in the catalytic cleft of AfXylA10 by competition with the xylan substrate. K239OsXIP stably interacted with the catalytic site E140AfXylA10 through hydrogen bond and vdW interaction. Intermolecular hydrogen bonds T104AfXylA10/V99AfXylA10-Q5OsXIP, R256AfXylA10-E235OsXIP, D155AfXylA10-Y243OsXIP and D145AfXylA10-R194OsXIP on the upper of the TIM barrel were essential for strengthening the stability of complex. Therefore, these non-covalent interactions (NCI) played key role in the interaction between AfXylA10 and OsXIP.
Assuntos
Aspergillus fumigatus/metabolismo , Oryza/metabolismo , Xilanos/metabolismo , Domínio Catalítico/fisiologia , Estabilidade Enzimática/fisiologia , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Simulação de Dinâmica Molecular , Pichia/metabolismo , Proteínas Recombinantes/metabolismo , TemperaturaRESUMO
Restless legs syndrome is a sleep-related sensorimotor neurological disease affecting up to 10% of the population. Genetic analyses have identified Myeloid Ecotropic viral Integration Site 1 (MEIS1), a transcriptional regulator, to be associated with not only the restless legs syndrome but also self-reported symptoms of insomnia and sleep. This study is to determine if Meis1 deficiency in mice can lead to restless legs syndrome-like phenotypes, and if it is the case, what the underlying mechanisms are. We used two genetic model systems, Caenorhabditis elegans and mice. Egg retention assay and fluorescent reporters were used with C. elegans. For mice, we performed behavioral tests, serum and brain iron detection, qRT-PCR, western blot, immunohistochemistry, and in vitro brain-slice recording. Our results showed that with C. elegans, the function of dop-3, an orthologue of DRD2, was diminished after the knockdown of unc-62, an ortholog of MEIS1. Additionally, unc-62 knockdown led to enhanced transcription of the orthologue of tyrosine hydroxylase, cat-2. Meis1 knockout mice were hyperactive and had a rest-phase-specific increased probability of waking. Moreover, Meis1 knockout mice had increased serum ferritin and altered striatal dopaminergic and cholinergic systems. Specifically, Meis1 knockout mice showed an increased mRNA level but decreased protein level of tyrosine hydroxylase in the striatum. Furthermore, Meis1 knockout mice had increased striatal dopamine turnover and decreased spontaneous firing regularity of striatal cholinergic interneurons. Our data suggest that Meis1 knockout mice have restless legs syndrome-like motor restlessness and changes in serum ferritin levels. The symptoms may be related to dysfunctional dopaminergic and cholinergic systems.
Assuntos
Atividade Motora/fisiologia , Proteína Meis1/deficiência , Proteína Meis1/genética , Síndrome das Pernas Inquietas/genética , Síndrome das Pernas Inquietas/metabolismo , Animais , Caenorhabditis elegans , Hipercinese/genética , Hipercinese/metabolismo , Masculino , Camundongos , Camundongos Knockout , Fatores de Transcrição/deficiência , Fatores de Transcrição/genéticaRESUMO
We employ computational fluid dynamics (CFD) simulations with NO-NO2-O3 chemistry to investigate the impacts of aspect ratios (H/W = 1,3,5), elevated-building design, wind catchers and two background ozone concentrations ([O3]b = 100/20 ppb) on reactive pollutant dispersion in two-dimensional (2D) street canyons. Personal intake fraction of NO2 (P_IFNO2) and its spatial mean value in entire street (i.e. street intake fraction
RESUMO
Restless legs syndrome (RLS) is a nocturnal neurological disorder affecting up to 10% of the population. It is characterized by an urge to move and uncomfortable sensations in the legs which can be relieved by movements. Mutations in BTBD9 may confer a higher risk of RLS. We developed Btbd9 knockout mice as an animal model. Functional alterations in the cerebral cortex, especially the sensorimotor cortex, have been found in RLS patients in several imaging studies. However, the role of cerebral cortex in the pathogenesis of RLS remains unclear. To explore this, we used in vivo manganese-enhanced MRI and found that the Btbd9 knockout mice had significantly increased neural activities in the primary somatosensory cortex (S1) and the rostral piriform cortex. Morphometry study revealed a decreased thickness in a part of S1 representing the hindlimb (S1HL) and M1. The electrophysiological recording showed Btbd9 knockout mice had enhanced short-term plasticity at the corticostriatal terminals to D1 medium spiny neurons (MSNs). Furthermore, we specifically knocked out Btbd9 in the cerebral cortex of mice (Btbd9 cKO). The Btbd9 cKO mice showed a rest-phase specific motor restlessness, decreased thermal sensation, and a thinner S1HL and M1. Both Btbd9 knockout and Btbd9 cKO exhibited motor deficits. Our results indicate that systematic BTBD9 deficiency leads to both functional and morphometrical changes of the cerebral cortex, and an alteration in the corticostriatal pathway to D1 MSNs. Loss of BTBD9 only in the cerebral cortex is sufficient to cause similar phenotypes as observed in the Btbd9 complete knockout mice.
Assuntos
Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Proteínas do Tecido Nervoso/deficiência , Síndrome das Pernas Inquietas/fisiopatologia , Animais , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Vias Neurais/metabolismo , Vias Neurais/patologia , Neurônios/metabolismo , Neurônios/patologia , Síndrome das Pernas Inquietas/genéticaRESUMO
High-rise deep street canyons usually experience poor ventilation and large vehicular pollutant exposure to residents in near-road buildings. Investigations are still required to clarify the flow and dispersion mechanisms in deep street canyons and explore techniques to reduce such large pollutant exposure. By conducting computational fluid dynamics (CFD) simulations validated by wind tunnel data and scale-model outdoor field measurements, we investigate the integrated impacts of aspect ratios, first-floor and second-floor elevated building designs, viaduct settings, height variations and wind catchers on the flow, personal intake fraction (P_IF) of CO (carbon dioxide) and its spatial mean value ãP_IFã in two-dimensional (2D) street canyons. Results show that cases with H/Wâ¯=â¯5 experience two counter-rotating vortices, much poorer ventilation and 1-2 orders larger ãP_IFã (43.6-120.8â¯ppm) than H/Wâ¯=â¯1 and 3 (3.8-4.3 and 5.6-5.8â¯ppm). Moreover, in cases with H/Wâ¯=â¯5 the height variation results in three vertically-aligned vortices and much weaker wind, subsequently produces greater ãP_IFã (1402-2047â¯ppm). To reduce ãP_IFã with H/Wâ¯=â¯5, various urban designs are evaluated. The first-floor elevated building design creates more effective ventilation pathways than the second-floor elevated type does and reduces ãP_IFã at H/Wâ¯=â¯5 by five orders (1402 to ~0.01â¯ppm) or two orders (43.6 to ~0.1â¯ppm) in cases with or without the height variation. However, such reductions at H/Wâ¯=â¯1 and 3 are only 76.8%-81.4% and 22.4%-36.2% respectively. Wind catchers destroy the multi-vortex flow pattern as H/Wâ¯=â¯5, produce a contra-clockwise main vortex and reduce ãP_IFã by 1-2 orders for cases with or without the height variation.