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1.
Circ Res ; 135(3): 434-449, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38864216

RESUMEN

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.


Asunto(s)
Cardiomegalia , Ratones Noqueados , ARN Largo no Codificante , Animales , Humanos , Masculino , Ratones , Cardiomegalia/metabolismo , Cardiomegalia/genética , Cardiomegalia/prevención & control , Cardiomegalia/patología , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/prevención & control , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Remodelación Ventricular
2.
J Virol ; 98(4): e0013924, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38501663

RESUMEN

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus, and the broad interspecies infection of SADS-CoV poses a potential threat to human health. This study provides experimental evidence to dissect the roles of distinct domains within the SADS-CoV spike S1 subunit in cellular entry. Specifically, we expressed the S1 and its subdomains, S1A and S1B. Cell binding and invasion inhibition assays revealed a preference for the S1B subdomain in binding to the receptors on the cell surface, and this unknown receptor is not utilized by the porcine epidemic diarrhea virus. Nanoparticle display demonstrated hemagglutination of erythrocytes from pigs, humans, and mice, linking the S1A subdomain to the binding of sialic acid (Sia) involved in virus attachment. We successfully rescued GFP-labeled SADS-CoV (rSADS-GFP) from a recombinant cDNA clone to track viral infection. Antisera raised against S1, S1A, or S1B contained highly potent neutralizing antibodies, with anti-S1B showing better efficiency in neutralizing rSADS-GFP infection compared to anti-S1A. Furthermore, depletion of heparan sulfate (HS) by heparinase treatment or pre-incubation of rSADS-GFP with HS or constituent monosaccharides could inhibit SADS-CoV entry. Finally, we demonstrated that active furin cleavage of S glycoprotein and the presence of type II transmembrane serine protease (TMPRSS2) are essential for SADS-CoV infection. These combined observations suggest that the wide cell tropism of SADS-CoV may be related to the distribution of Sia or HS on the cell surface, whereas the S1B contains the main protein receptor binding site. Specific host proteases also play important roles in facilitating SADS-CoV entry.IMPORTANCESwine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel pathogen infecting piglet, and its unique genetic evolution characteristics and broad species tropism suggest the potential for cross-species transmission. The virus enters cells through its spike (S) glycoprotein. In this study, we identify the receptor binding domain on the C-terminal part of the S1 subunit (S1B) of SADS-CoV, whereas the sugar-binding domain located at the S1 N-terminal part of S1 (S1A). Sialic acid, heparan sulfate, and specific host proteases play essential roles in viral attachment and entry. The dissection of SADS-CoV S1 subunit's functional domains and identification of cellular entry cofactors will help to explore the receptors used by SADS-CoV, which may contribute to exploring the mechanisms behind cross-species transmission and host tropism.


Asunto(s)
Alphacoronavirus , Infecciones por Coronavirus , Glicoproteína de la Espiga del Coronavirus , Animales , Humanos , Ratones , Alphacoronavirus/química , Alphacoronavirus/fisiología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Heparitina Sulfato , Ácido N-Acetilneuramínico/metabolismo , Péptido Hidrolasas , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Porcinos
3.
Nano Lett ; 24(5): 1808-1815, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38198566

RESUMEN

The novel depth-sensing system presented here revolutionizes structured light (SL) technology by employing metasurfaces and photonic crystal surface-emitting lasers (PCSELs) for efficient facial recognition in monocular depth-sensing. Unlike conventional dot projectors relying on diffractive optical elements (DOEs) and collimators, our system projects approximately 45,700 infrared dots from a compact 297-µm-dimention metasurface, drastically more spots (1.43 times) and smaller (233 times) than the DOE-based dot projector in an iPhone. With a measured field-of-view (FOV) of 158° and a 0.611° dot sampling angle, the system is lens-free and lightweight and boasts lower power consumption than vertical-cavity surface-emitting laser (VCSEL) arrays, resulting in a 5-10 times reduction in power. Utilizing a GaAs-based metasurface and a simplified optical architecture, this innovation not only addresses the drawbacks of traditional SL depth-sensing but also opens avenues for compact integration into wearable devices, offering remarkable advantages in size, power efficiency, and potential for widespread adoption.

4.
Nano Lett ; 24(33): 10055-10061, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39047260

RESUMEN

Nonlocal metasurfaces, exemplified by resonant waveguide gratings (RWGs), spatially and angularly configure optical wavefronts through narrow-band resonant modes, unlike the broad-band and broad-angle responses of local metasurfaces. However, forward design techniques for RWGs remain constrained at lower efficiency. Here, we present a topology-optimized metasurface resonant waveguide grating (MRWG) composed of titanium dioxide on a glass substrate capable of operating simultaneously at red, yellow, green, and blue wavelengths. Through adjoint-based topology optimization, while considering nonlocal effects, we significantly enhance its diffraction efficiency, achieving numerical efficiencies up to 78% and Q-factors as high as 1362. Experimentally, we demonstrated efficiencies of up to 59% with a Q-factor of 93. Additionally, we applied our topology-optimized metasurface to color selectivity, producing vivid colors at 4 narrow-band wavelengths. Our investigation represents a significant advancement in metasurface technology, with potential applications in see-through optical combiners and augmented reality platforms.

5.
Mol Plant Microbe Interact ; 37(7): 583-593, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38598845

RESUMEN

MicroRNAs (miRNAs) play an essential regulatory role in plant-virus interaction. However, few studies have focused on the roles of miRNAs and their targets after sugarcane mosaic virus (SCMV) infection in sugarcane. To address this issue, we conducted small RNA (sRNA) and degradome sequencing on two contrasting sugarcanes (SCMV-resistant 'Fuoguo1' [FG1] and susceptible 'Badila') infected by SCMV at five time points. A total of 1,578 miRNAs were profiled from 30 sRNA libraries, comprising 660 known miRNAs and 380 novel miRNAs. Differential expression analysis of miRNAs revealed that most were highly expressed during the SCMV exponential phase in Badila at 18 h postinfection, with expression profiles positively correlated with virus replication dynamics as observed through clustering. Analysis of degradome data indicated a higher number of differential miRNA targets in Badila compared to FG1 at 18 h postinfection. Gene ontology (GO) enrichment analysis significantly enriched the stimulus-response pathway, suggesting negative regulatory roles to SCMV resistance. Specifically, miR160 upregulated expression patterns and validated in Badila through quantitative real-time PCR (qRT-PCR) in the early stages of SCMV multiplication. Our research provides new insights into the dynamic response of plant miRNA and virus replication and contributes valuable information on the intricate interplay between miRNAs and SCMV infection dynamics. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , MicroARNs , Enfermedades de las Plantas , Potyvirus , ARN de Planta , Saccharum , MicroARNs/genética , MicroARNs/metabolismo , Potyvirus/fisiología , Potyvirus/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Saccharum/virología , Saccharum/genética , ARN de Planta/genética , ARN de Planta/metabolismo , Estabilidad del ARN , Resistencia a la Enfermedad/genética
6.
J Cell Physiol ; 239(2): e31129, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38192063

RESUMEN

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age-paired patients with lower-risk MDS (N = 15), higher-risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro-inflammatory monocyte subsets and a decreased classically activated (M1) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher-risk MDS compared to lower-risk MDS. BM MФs from patients with higher-risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower-risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower-risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher-risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower-risk MDS. Gene Ontology enrichment comparing BM MΦs from lower-risk MDS and higher-risk MDS for genes was involved in hematopoiesis- and immunity-related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS.


Asunto(s)
Infecciones , Macrófagos , Síndromes Mielodisplásicos , Humanos , Médula Ósea/patología , Hematopoyesis , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Macrófagos/patología , Síndromes Mielodisplásicos/genética , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Infecciones/patología
7.
Int J Cancer ; 154(3): 530-537, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37815300

RESUMEN

Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures.


Asunto(s)
Estudio de Asociación del Genoma Completo , Neoplasias Hepáticas , Adulto , Humanos , Análisis de la Aleatorización Mendeliana , Obesidad/complicaciones , Obesidad/genética , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple
8.
Small ; 20(24): e2309559, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38243884

RESUMEN

Hopper-shaped microcrystals, an unusual type of crystal with a large specific surface area, are promising for use in catalysis, drug delivery, and gas sensors. In contrast to well-studied inorganic hopper-shaped crystals, organic phosphorescent concave hopper-shaped microstructures are rarely reported. This study reports the synthesis of two types of organic stepped indented hopper-shaped microstructures with efficient room temperature phosphorescence (RTP) using a liquid phase self-assembly strategy. The formation mechanism is attributed to the interfacial instability induced by the concentration gradient and selective etching. Compared with flat microstructures, the stepped indented hopper-like RTP microstructures exhibit high sensitivity to oxygen. This work also demonstrates that packing the photochromic material into the concave hopper "vessel" effectively controls the switch of phosphorescence from energy transfer, expanding the potential applications of phosphorescent materials.

9.
Planta ; 259(5): 120, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607398

RESUMEN

MAIN CONCLUSION: This study reveals miRNA indirect regulation of C4 genes in sugarcane through transcription factors, highlighting potential key regulators like SsHAM3a. C4 photosynthesis is crucial for the high productivity and biomass of sugarcane, however, the miRNA regulation of C4 genes in sugarcane remains elusive. We have identified 384 miRNAs along the leaf gradients, including 293 known miRNAs and 91 novel miRNAs. Among these, 86 unique miRNAs exhibited differential expression patterns, and we identified 3511 potential expressed targets of these differentially expressed miRNAs (DEmiRNAs). Analyses using Pearson correlation coefficient (PCC) and Gene Ontology (GO) enrichment revealed that targets of miRNAs with positive correlations are integral to chlorophyll-related photosynthetic processes. In contrast, negatively correlated pairs are primarily associated with metabolic functions. It is worth noting that no C4 genes were predicted as targets of DEmiRNAs. Our application of weighted gene co-expression network analysis (WGCNA) led to a gene regulatory network (GRN) suggesting miRNAs might indirectly regulate C4 genes via transcription factors (TFs). The GRAS TF SsHAM3a emerged as a potential regulator of C4 genes, targeted by miR171y and miR171am, and exhibiting a negative correlation with miRNA expression along the leaf gradient. This study sheds light on the complex involvement of miRNAs in regulating C4 genes, offering a foundation for future research into enhancing sugarcane's photosynthetic efficiency.


Asunto(s)
MicroARNs , Saccharum , Transcriptoma/genética , Saccharum/genética , Factores de Transcripción/genética , Redes Reguladoras de Genes , MicroARNs/genética
10.
J Med Virol ; 96(2): e29472, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38373201

RESUMEN

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNß treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Replicación Viral , Pulmón , Interferones , Células Epiteliales , Antivirales/farmacología
11.
Osteoporos Int ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844560

RESUMEN

We conducted a retrospective cohort analysis to examine the association between hemoglobin (Hb) levels and refracture risk in elderly patients with osteoporotic fractures (OPFs). Our findings suggest a nonlinear relationship exists in females, and females with Hb levels below 10.7 g/dL may be at a higher risk of refracture. INTRODUCTION: Hematopoiesis and bone health have a reciprocal influence on each other. Nevertheless, there is a scarcity of in-depth research on the association between Hb levels and the occurrence of fractures. The present research aimed to investigate the correlation between Hb levels and the rate of refracture within 5 years among individuals with OPFs. METHODS: A retrospective cohort analysis was undertaken between 2017 and 2022. The study included 1906 individuals who were inhabitants of Kunshan and were over 60 years old. These individuals had experienced an OPF between January 1, 2017, and July 27, 2022, resulting in their hospitalization. Cox proportional hazard regression models were used to evaluate the risk of refracture within 5 years based on the Hb levels acquired during the admission examination, with consideration for sex differences. A nonlinear relationship was identified using smoothed curve fitting and threshold analysis. Kaplan-Meier curves were used to compare refracture rates between patients with low and high Hb levels. RESULTS: Elderly female patients with OPFs and lower Hb levels exhibited a significantly higher risk of a 5-year refracture. Conversely, no significant associations were observed between the two variables in male patients. A nonlinear correlation was found between Hb levels and the probability of refracture in females, with a turning point identified at 10.7 g/dL of Hb levels. A strong negative association was observed with the five-year refracture rate when Hb levels fell below 10.7 g/dL (hazard ratio (HR) = 0.63; 95% confidence interval (CI) 0.48 to 0.83; P-value = 0.0008). This finding suggests that for every 1 g/dL increase in Hb below 10.7 g/dL, the risk of refracture reduced by 37%. However, no statistically significant association was observed when Hb levels were above 10.7 g/dL. CONCLUSIONS: The findings demonstrated a significant negative correlation between Hb levels and the likelihood of refracture in elderly female patients with OPFs and suggested that elderly females with recent OPFs and Hb levels below 10.7 g/dL may be at a higher risk of refracture. Additionally, the Hb levels can serve as an indicator of bone fragility in elderly female patients with OPFs. These findings highlight the importance of monitoring Hb levels as a part of comprehensive management strategies to both assess skeletal health and prevent refractures in this population.

12.
Ann Bot ; 134(1): 71-84, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38470192

RESUMEN

BACKGROUND AND AIMS: Niche differentiation is a crucial issue in speciation. Although it has a well-known role in adaptive processes of hybrid angiosperms, it is less understood in hybrid ferns. Here, we investigate whether an intermediate ecological niche of a fern hybrid is a novel adaptation that provides insights into fern hybrid speciation. METHODS: Pteris fauriei (Pteridaceae) is a natural hybrid fern, occurring in environments between its parent species. The maternal Pteris minor is found in sunny areas, but the habitat of the paternal Pteris latipinna is shady. We combined data from morphology, leaf anatomy and photosynthetic traits to explore adaptation and differentiation, along with measuring the environmental features of their niches. We also performed experiments in a common garden to understand ecological plasticity. KEY RESULTS: The hybrid P. fauriei was intermediate between the parent species in stomatal density, leaf anatomical features and photosynthetic characteristics in both natural habitats and a common garden. Interestingly, the maternal P. minor showed significant environmental plasticity and was more similar to the hybrid P. fauriei in the common garden, suggesting that the maternal species experiences stress in its natural habitats but thrives in environments similar to those of the hybrid. CONCLUSIONS: Based on the similar niche preferences of the hybrid and parents, we propose hybrid superiority. Our results indicate that the hybrid P. fauriei exhibits greater fitness and can compete with and occupy the initial niches of the maternal P. minor. Consequently, we suggest that the maternal P. minor has experienced a niche shift, elucidating the pattern of niche differentiation in this hybrid group. These findings offer a potential explanation for the frequent occurrence of hybridization in ferns and provide new insights into fern hybrid speciation, enhancing our understanding of fern diversity.


Asunto(s)
Ecosistema , Hibridación Genética , Fenotipo , Pteris , Pteris/fisiología , Pteris/anatomía & histología , Pteris/genética , Hojas de la Planta/anatomía & histología , Hojas de la Planta/fisiología , Hojas de la Planta/crecimiento & desarrollo , Especiación Genética , Fotosíntesis/fisiología , Helechos/fisiología , Helechos/anatomía & histología , Adaptación Fisiológica
13.
J Org Chem ; 89(3): 1748-1752, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38262733

RESUMEN

A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.

14.
J Org Chem ; 89(10): 6877-6891, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38662908

RESUMEN

Anions have a profound effect on the properties of soluble proteins. Such Hofmeister effects have implications in biologics stability, protein aggregation, amyloidogenesis, and crystallization. However, the interplay between the important noncovalent interactions (NCIs) responsible for Hofmeister effects is poorly understood. To contribute to improving this state of affairs, we report on the NCIs between anions and ammonium and guanidinium hosts 1 and 2, and the consequences of these. Specifically, we investigate the properties of cavitands designed to mimic two prime residues for anion-protein NCIs─lysines and arginines─and the solubility consequences of complex formation. Thus, we report NMR and ITC affinity studies, X-ray analysis, MD simulations, and anion-induced critical precipitation concentrations. Our findings emphasize the multitude of NCIs that guanidiniums can form and how this repertoire qualitatively surpasses that of ammoniums. Additionally, our studies demonstrate the ease by which anions can dispense with a fraction of their hydration-shell waters, rearrange those that remain, and form direct NCIs with the hosts. This raises many questions concerning how solvent shell plasticity varies as a function of anion, how the energetics of this impact the different NCIs between anions and ammoniums/guanidiniums, and how this affects the aggregation of solutes at high anion concentrations.


Asunto(s)
Compuestos de Amonio , Aniones , Arginina , Guanidina , Lisina , Guanidina/química , Aniones/química , Arginina/química , Compuestos de Amonio/química , Lisina/química , Simulación de Dinámica Molecular
15.
Prev Med ; 185: 108055, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38925512

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) stands as a persistent systemic inflammatory autoimmune condition. Despite this understanding, the precise impact of the systemic inflammation response index (SIRI) on the prognosis of RA patients remains elusive. This study aims to elucidate the correlation between the inflammatory biomarker SIRI and both all-cause mortality and cardiovascular mortality among RA patients. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020, a retrospective analysis was conducted. Survival data were depicted through Kaplan-Meier survival curves, while the relationship between SIRI and all-cause or cardiovascular mortality in RA patients was scrutinized via multivariable Cox proportional hazards regression analysis and restricted cubic spline plots. Furthermore, subgroup analysis and mediation analysis were also performed. RESULTS: This study encompassed 2656 RA patients with a comprehensive 20-year follow-up, during which 935 all-cause deaths and 273 deaths attributed to cardiovascular disease were recorded. We observed a nonlinear positive correlation between SIRI with both all-cause and cardiovascular mortality in RA patients. Notably, at a SIRI level of 1.12, the hazard ratio reached 1, indicating a shift from low to high mortality risk. Furthermore, mediation analysis revealed that 12.6% of the association between RA and mortality risk was mediated through SIRI. Subgroup analysis indicated a more pronounced association between SIRI and mortality in female patients or those with a high BMI. CONCLUSION: This study underscores a non-linear positive correlation between the biomarker SIRI and both all-cause mortality and cardiovascular mortality in RA patients.


Asunto(s)
Artritis Reumatoide , Enfermedades Cardiovasculares , Inflamación , Encuestas Nutricionales , Humanos , Artritis Reumatoide/mortalidad , Femenino , Masculino , Enfermedades Cardiovasculares/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiología , Causas de Muerte , Biomarcadores/sangre , Adulto , Modelos de Riesgos Proporcionales , Anciano , Factores de Riesgo
16.
Dig Dis Sci ; 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38949750

RESUMEN

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

17.
BMC Geriatr ; 24(1): 585, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977983

RESUMEN

BACKGROUND: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. METHODS: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. RESULTS: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. CONCLUSIONS: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. CLINICAL TRIAL NUMBER: NCT06473324.


Asunto(s)
Delirio , Fracturas de Cadera , Hiperglucemia , Complicaciones Posoperatorias , Humanos , Fracturas de Cadera/cirugía , Fracturas de Cadera/sangre , Hiperglucemia/epidemiología , Hiperglucemia/sangre , Femenino , Masculino , Estudios Retrospectivos , Anciano , Anciano de 80 o más Años , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/sangre , Delirio/sangre , Delirio/epidemiología , Delirio/diagnóstico , Delirio/etiología , Glucemia/metabolismo , Glucemia/análisis , Periodo Preoperatorio , Incidencia , Factores de Riesgo , Puntaje de Propensión
18.
BMC Musculoskelet Disord ; 25(1): 234, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528491

RESUMEN

PURPOSE: This study aimed to evaluate the correlation admission albumin levels and 30-day readmission after hip fracture surgery in geriatric patients. METHODS: In this retrospective cohort study, 1270 geriatric patients admitted for hip fractures to a level I trauma center were included. Patients were stratified by clinical thresholds and albumin level quartiles. The association between admission albumin levels and 30-day readmission risk was assessed using multivariate logistic regression and propensity score-matched analyses. The predictive accuracy of albumin levels for readmission was evaluated by ROC curves. The dose-response relationship between albumin levels and readmission risk was examined. RESULTS: The incidence of 30-day readmission was significantly higher among hypoalbuminemia patients than those with normal albumin levels (OR = 2.090, 95%CI:1.296-3.370, p = 0.003). Furthermore, propensity score-matched analyses demonstrated that patients in the Q2(35.0-37.9 g/L) (OR 0.621, 95%CI 0.370-1.041, p = 0.070), Q3(38.0-40.9 g/L) (OR 0.378, 95%CI 0.199-0.717, p < 0.001) and Q4 (≥ 41 g/L) (OR 0.465, 95%CI 0.211-0.859, p = 0.047) quartiles had a significantly lower risk of 30-day readmission compared to those in the Q1(< 35 g/L) quartile. These associations remained significant after propensity score matching (PSM) and subgroup analyses. Dose-response relationships between albumin levels and 30-day readmission were observed. CONCLUSIONS: Lower admission albumin levels were independently associated with higher 30-day readmission rates in elderly hip fracture patients. Our findings indicate that serum albumin may assist perioperative risk assessment, and prompt correction of hypoalbuminemia and malnutrition could reduce short-term readmissions after hip fracture surgery in this high-risk population.


Asunto(s)
Fracturas de Cadera , Hipoalbuminemia , Albúmina Sérica Humana , Anciano , Humanos , Fracturas de Cadera/cirugía , Fracturas de Cadera/complicaciones , Hipoalbuminemia/epidemiología , Hipoalbuminemia/complicaciones , Readmisión del Paciente , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica Humana/análisis , Albúmina Sérica Humana/química
19.
BMC Musculoskelet Disord ; 25(1): 6, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166762

RESUMEN

OBJECTIVE: This study aimed to systematically assess the incidence and risk factors for hospital-acquired pneumonia (HAP) in hip fracture patients by meta-analysis. METHODS: Systematically searched four English databases (PubMed, EMBASE, The Cochrane Library, and Web Of Science) and four Chinese databases (CNKI, CQVIP, Sinomed, and WAN FANG) from inception until 20 November 2023. All studies involving risk factors of HAP in patients with hip fractures were considered. Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. The results were presented with the pooled odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Of 35 articles (337,818 patients) included in this study, the incidence of HAP was 89 per 1000 cases. Twenty-three risk factors were eventually involved in the meta-analysis, and 21 risk factors were significant. Our study has identified four significant risk factors (advanced age, preoperative time, COPD, and hypoalbuminemia) associated with HAP, as follows: Advanced age as a continuous variable (OR 1.07, 95% CI 1.05-1.10), Advanced age > 70 years (OR 2.34, 95% CI 1.77-3.09), Advanced age > 80 years (OR 2.98, 95% CI 2.06-4.31), Chronic obstructive pulmonary disease (COPD) (OR 3.44, 95% CI 2.83-4.19), Time from injury to operation as a continuous variable (OR 1.09, 95% CI 1.07-1.12), Time from injury to operation ≥48 h (OR 3.59, 95% CI 2.88-4.48), Hypoalbuminemia < 3.0 g/dL (OR 3.03, 95% CI 1.93-4.73), and Hypoalbuminemia < 3.5 g/dL (OR 2.68, 95% CI 2.15-3.36). However, it is important to note that all the studies included in our research were retrospective in nature, which introduces certain limitations to the level of evidence and the ability to establish causal inferences. DISCUSSION: Patients who have suffered hip fractures are at an increased risk of developing postoperative hospital-acquired pneumonia, which can lead to prolonged hospital stays and adverse clinical outcomes. Consequently, the identification of these risk factors offers novel insights and methodologies for healthcare professionals in terms of both prevention and treatment. TRIAL REGISTRATION: Registration number: INPLASY2022100091.


Asunto(s)
Fracturas de Cadera , Hipoalbuminemia , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Fracturas de Cadera/epidemiología , Fracturas de Cadera/cirugía , Neumonía/epidemiología , Factores de Riesgo , Hospitales
20.
Chaos ; 34(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39042505

RESUMEN

Electromagnetic radiation (EMR) affects the dynamical behavior of the nervous system, and appropriate EMR helps to study the dynamic mechanism of the nervous system. This paper uses a sophisticated four-dimensional Hopfield neural network (HNN) model augmented with one or more memristors to simulate the effects of EMR. We focus on the chaotic dynamics of HNN under the influence of EMR. Complex dynamical behaviors are found and transient chaotic phenomena have the same initial value sensitivity, showing how transient chaos is affected by EMR. Multiperiodic phenomena induced by quasi-periodic alternations are found in the dual EMR, as well as the suppression properties of the dual EMR for system chaos. This implies that the dynamical behavior of the HNN system can be controlled by varying the amount of EMR or the number of affected neurons in the HNN. Finally, a strong validation of our proposed model is provided by Multisim and Field Programmable Gate Array(FPGA) hardware.

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