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Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.
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Canales Iónicos Sensibles al Ácido , Isquemia Encefálica , Ácido Glutámico , Animales , Femenino , Humanos , Masculino , Ratones , 2-Amino-5-fosfonovalerato/efectos adversos , 2-Amino-5-fosfonovalerato/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , Canales Iónicos Sensibles al Ácido/química , Canales Iónicos Sensibles al Ácido/deficiencia , Canales Iónicos Sensibles al Ácido/efectos de los fármacos , Canales Iónicos Sensibles al Ácido/genética , Canales Iónicos Sensibles al Ácido/metabolismo , Regulación Alostérica/efectos de los fármacos , Sitios de Unión/genética , Isquemia Encefálica/inducido químicamente , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ácido Glutámico/análogos & derivados , Ácido Glutámico/metabolismo , Ácido Glutámico/farmacología , Ácido Glutámico/toxicidad , Ratones Noqueados , Mutagénesis Sitio-Dirigida , Protones , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
The endothelial glycocalyx, located at the luminal surface of the endothelium, plays an important role in the regulation of leukocyte adhesion, vascular permeability, and vascular homeostasis. Endomucin (EMCN), a component of the endothelial glycocalyx, is a mucin-like transmembrane glycoprotein selectively expressed by venous and capillary endothelium. We have previously shown that knockdown of EMCN impairs retinal vascular development in vivo and vascular endothelial growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, and tube formation by human retinal endothelial cells in vitro and that EMCN is essential for VEGF165-stimulated clathrin-mediated endocytosis and signaling of VEGF receptor 2 (VEGFR2). Clathrin-mediated endocytosis is an essential step in receptor signaling and is of paramount importance for a number of receptors for growth factors involved in angiogenesis. In this study, we further investigated the molecular mechanism underlying EMCN's involvement in the regulation of VEGF-induced endocytosis. In addition, we examined the specificity of EMCN's role in angiogenesis-related cell surface receptor tyrosine kinase endocytosis and signaling. We identified that EMCN interacts with AP2 complex, which is essential for clathrin-mediated endocytosis. Lack of EMCN did not affect clathrin recruitment to the AP2 complex following VEGF stimulation, but it is necessary for the interaction between VEGFR2 and the AP2 complex during endocytosis. EMCN does not inhibit VEGFR1 and FGFR1 internalization or their downstream activities since EMCN interacts with VEGFR2 but not VEGFR1 or FGFR1. Additionally, EMCN also regulates VEGF121-induced VEGFR2 phosphorylation and internalization.
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Células Endoteliales , Factor A de Crecimiento Endotelial Vascular , Humanos , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Sialomucinas/metabolismo , Endocitosis , Clatrina/metabolismoRESUMEN
BACKGROUND: Erectile dysfunction (ED) is closely associated with dyslipidemia; however, it is yet unknown how ED and remnant cholesterol (RC) are related. As such, this research sought to explore the correlation between RC and ED among individuals with diagnosed with diabetes. METHODS: This cross-sectional study used information from 215 males from National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. RC was calculated as follows: the values of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were subtracted from the total cholesterol (TC) value, while ED diagnoses were based on self-reports. Weighted logistic regression analyses using both univariate and multivariate approaches were conducted to assess the correlation between RC and ED. RESULTS: After comprehensive adjustment, multivariable logistic regression models revealed a strong correlation between RC and ED in subjects with diabetes (with an odds ratio (OR) of 7.49 and a 95% confidence interval (CI) of 1.98-28.37; P = 0.004). On categorizing RC into 3 grades (T1-T3), the OR corresponding to higher RC grade increased. Despite the results not reaching statistical significance upon categorization, a consistent and statistically significant trend (P for trend < 0.05) was observed. CONCLUSION: This study indicated a correlation between increased RC levels and a higher prevalence of ED in diabetic males. RC may serve as a promising predictor of ED in individuals with diabetes. However, additional studies are required to confirm these findings.
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Diabetes Mellitus , Disfunción Eréctil , Hiperlipidemias , Masculino , Humanos , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Disfunción Eréctil/diagnóstico , Encuestas Nutricionales , Factores de Riesgo , Estudios Transversales , ColesterolRESUMEN
OBJECTIVE: To explore the association between cardiovascular health (CVH) measured by Life's Essential 8 (LE8) and the prevalence of urinary incontinence (UI). METHOD: A cross-section study was conducted using data from the National Health and Nutrition Examination Survey 2007-2012. 22,609 people aged ≥ 20 years with complete information on LE8 metrics and UI questionnaires were enrolled. Participants were divided into three groups (low: < 50, moderate: ≥ 50 and < 80, high: ≥ 80) based on the cut-off of LE8. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were performed to examine the association between LE8 and the prevalence of three types of UI separately (stress UI (SUI), urge UI (UUI), mixed UI (MUI)) by confounding factors adjusted. Spline smooth was conducted to find whether a linear relationship existed. In addition, sensitive analyses were also conducted to observe the stability. RESULT: A total of 22,609 adults were involved in the study, and participants were divided into three groups (low 42.2 ± 6.3, moderate 66.1 ± 8.1, high 86.8 ± 5.1) according to the cut-off points of LE8. The multivariable logistic regression suggested that LE8 is inversely associated with the prevalence of SUI (OR = 0.98, 95%CI 0.98 to 0.99), UUI (OR = 0.98, 95%CI 0.98 to 0.99), and MUI (OR = 0.98, 95%CI 0.97 to 0.98) in the fully-adjusted model. Compared with the low group, people with high scores of LE8 had a lower prevalence of SUI (OR = 0.45, 95%CI 0.37 to 0.55), UUI (OR = 0.49, 95%CI 0.40 to 0.60), and MUI (OR = 0.41, 95%CI 0.30 to 0.55). The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of UI (SUI, UUI, or MUI) is inversely associated with the LE8 score, which suggests that maintaining a good CVH with a higher LE8 score is accompanied by lower prevalence rates of UUI, SUI, and MUI.
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Enfermedades Cardiovasculares , Encuestas Nutricionales , Incontinencia Urinaria , Humanos , Femenino , Masculino , Prevalencia , Persona de Mediana Edad , Adulto , Estudios Transversales , Incontinencia Urinaria/epidemiología , Enfermedades Cardiovasculares/epidemiología , Anciano , Adulto Joven , Encuestas y CuestionariosRESUMEN
This paper studies a computational approach aimed at establishing equivalent dynamical responses within oscillatory impacting systems subject to soft and rigid constraints. The proposed method incorporates an adaptive differential evolution algorithm with the Metropolis criterion to determine the stiffness and damping parameters of the soft constraint for a prescribed coefficient of restitution governing the rigid constraint. The proposed algorithm aims to establish an equivalent dynamical response of the two models based on constraints regarding energy dissipation and contact time duration. Upon examining the dynamical responses of the two impact cases, they exhibit nearly identical outcomes in the two-parameter bifurcation diagrams when subjected to a large restitution coefficient. However, discrepancies arise between the results of the two models when the restitution coefficient is low. Detailed numerical tests, conducted using the proposed method, demonstrate enhanced effectiveness compared to previous techniques, such as the prediction formulas for the different related soft impact model outlined by Okolewski and Blazejczyk-Okolewska [Chaos 31(8), 083110 (2021)]. This method not only finds application in experimentally identifying the physical properties of an impact surface but also provides convenience in employing soft models within impacting systems, which could then avoid potential inaccuracies in handling discontinuities by some integrator during velocity jumps before and after impacts.
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Amorphophallus muelleri is an Araceae plant with perennial tuber, widely used in food, pharmaceutical and chemical industry due to its richness in glucomannan. In April 2022, an outbreak of a target spot on A. muelleri plantlets was observed in a nursery in Ruili, Yunnan, China. The leafstalks of the diseased plantlets in the nursery turned brown and decayed (Fig.1 A-B), then gradually some water-soaked spots on the true leaves developed along the veins (Fig.1 A). Subquencely, the spots on the true leaves turned dark green to white-grayish in the center, which formed light to dark brown concentric rings with a target-like appearance surrounded by a yellow halo (Fig.1 C). When the temperature was 20-34â and the relatively humidity was 25-80%, dark-green to black sporodochia with white hypha appeared on the lower and upper leaf surfaces. Finally, 5-8% of the plants surveyed on 800 m2 of one-year-old plantlets in the nursery showed the symptoms and some plants with infected leafstalks would be death. Similar symptoms were also observed on about 10% of the transplanted plants surveyed on 12000 m2 (1.2 ha) of two-year-old plantlets in the field. Five diseased leaves from five distinct plantlets in the nursery were collected for pathogen isolation. Leaf pieces(5 x 5 mm) were cut from the edge of necrotic lesions, and surface-sterilized with 2.5% sodium hypochlorite for 1 min, 75% ethanol for 30 s, then rinsed 5 times by sterilized distilled water, finally put the leaf pieces on sterilized filter paper for 3-5 minutes to dry them and transferred onto potato dextrose agar (PDA) in petri dishes at 25â for three days. Five pure cultures identical to colony and conidial characteristics were isolated from five individual plants. The representative pure culture (M1) was grayish-white and circular colonies were 7.50 cm in diamter after 15 days at 25â, with dark green concentric rings of sporodochia, the dorsal view of the colonies were yellowish. Conidia were aseptate, smooth, cylindrical, 5.00-6.25 (5.71) x 1.25-1.67 (1.63) µm (n = 20) rounded at both ends. A spore suspension (1 x 106 spores/ml) was prepared by harvesting spores from 15-day-old cultures grown in the dark at 25â, then a thirty-ml of spore suspension was sprayed on the healthy leaves of 10 two-year-old plantlets. Thirty-ml of sterile water was sprayed on the healthy leaves of another 10 seedlings and used as the control. All seedlings were placed in a nursery at 20 to 34â and a relative humidity of 25 to 80%. Similar symptoms (Fig.1 D-F) to those observed in the nursery and field developed on all the 10 seedlings inoculated with M1 after two days, but not on the control leaves. The pathogenicity tests were repeated for three times. Fungal cultures reisolated from the infected leaves were identical to the original colonies and conidia, completing Koch's postulates. The internal transcribed spacer (ITS, primers ITS1 and ITS4) region of ribosomal DNA (OQ553785), calmodulin (cmdA, primers CAL-228F and CAL2Rd)(OQ559103), RNA polymerase II second largest subunit (rpb2, primers RPB2-5F2 and RPB2-7cR) (OQ559104) and ß-tubulin (tub2, primers Bt2a and Bt2b) (OQ559105) of M1 had 100%, 98.52%, 98.98% and 98.98% identity with the sequences of Paramyrothecium breviseta CBS544.75 (KU846289 for ITS, KU846262 for cmdA, KU846351 for rpb2, and KU846406 for tub2), respectively. In the phylogenic tree based on ITS, cmdA, rpb2 and tub2 gene sequences, the pure culture M1 clustered with P. breviseta CBS544.75, SDBR-CMU387, DRL4 and DRL3, which has been reported as the pathogen of leaf spot of Coffea arabica in China, C. canephora in China and Thailand (Wu et al. 2021; Withee et al. 2022). Molecular and morphological observations showed the pure culture M1 were P. breviseta (Withee et al. 2022), in addition the disease was named as target spot dueing to the typical target symptom on the leaves. To our knowledge, this is the first report of P. breviseta on A. muelleri from Yunnan, China, as well as worldwide. This disease can caused serious economic losses of A. muelleri dueing to that it can result 5-8% death of the plants in the nursery.
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Self-assembly formation is a key research topic for realizing practical applications in swarm robotics. Due to its inherent complexity, designing high-performance self-assembly formation strategies and proposing corresponding macroscopic models remain formidable challenges and present an open research frontier. Taking inspiration from crystallization, this paper introduces a distributed self-assembly formation strategy by defining free, moving, growing, and solid states for robots. Robots in these states can spontaneously organize into user-specified two-dimensional shape formations with lattice structures through local interactions and communications. To address the challenges posed by complex spatial structures in modeling a macroscopic model, this work introduces the structural features estimation method. Subsequently, a corresponding non-spatial macroscopic model is developed to predict and analyze the self-assembly behavior, employing the proposed estimation method and a stock and flow diagram. Real-robot experiments and simulations validate the flexibility, scalability, and high efficiency of the proposed self-assembly formation strategy. Moreover, extensive experimental and simulation results demonstrate the model's accuracy in predicting the self-assembly process under different conditions. Model-based analysis indicates that the proposed self-assembly formation strategy can fully utilize the performance of individual robots and exhibits strong self-stability.
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In this paper, we propose what we believe to be a novel coupling mechanism for generating quasi-bound states in the continuum (quasi-BIC) in symmetrical metasurface structures. We demonstrate for the first time in theoretical predictions that supercell coupling can induce quasi-BIC(s). We utilize the coupled mode theory (CMT) to analyze the physical mechanism for the generation of quasi-bound states in such symmetrical structures, which result from our investigation of the coupling between sub-cells that are separated from supercells. We verify our theory by using both full-wave simulations and experiments.
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Cyano-bridged 4d-4f molecular nanomagnets have re-called increasing research interests in molecular magnetism since they offer more possibilities in achieving novel nanomagnets with versatile structures and magnetic interactions. In this work, four ß-diketone ligands bearing different substitution N-sites were designed and synthesized, namely 1-(2-pyridyl)-3-(3-pyridyl)-1,3-propanedione (HL1 ), 1,3-Bis (3-pyridyl)-1,3-propanedione (HL2 ), 1-(4-pyridyl)-3-(3-pyridyl)-1,3-propanedione (HL3 ), and 1,3-Bis (4-pyridyl)-1,3-propanedione (HL4 ), to tune the magnetic relaxation behaviors of cyano-bridged {DyIII MoV } systems. By reacting with DyCl3 â 6H2 O and K4 Mo(CN)8 â 2H2 O, four cyano-bridged complexes, namely {[Dy[MoV (CN)8 ](HL1 )2 (H2 O)3 ]} â 6H2 O (1), {[Dy[MoV (CN)8 ](HL2 )(H2 O)3 (CH3 OH)]}2 â 2CH3 OH â 3H2 O (2), {[Dy[MoV (CN)8 ](HL3 )(H2 O)2 (CH3 OH)] â H2 O}n (3), and {[Dy[MoV (CN)8 ](HL4 )2 (H2 O)3 ]} â 2H2 Oâ CH3 OH (4) were obtained. Structural analyses revealed that 1 and 4 are binuclear complexes, 2 has a tetragonal structure, and 3 exhibits a stair-like polymer chain structure. The DyIII ions in all complexes have eight-coordinated configurations with the coordination spheres DyO7 N1 for 1 and 4, DyO6 N2 for 2, and DyO5 N3 for 3. Magnetic measurements indicate that 1 is a zero-field single-molecule magnet (SMM) and complexes 2-4 are field-induced SMMs, with complex 4 featuring a two-step relaxation process. The magnetic characterizations and ab initio calculations revealed that changing the N-sites in the ß-diketone ligands can effectively alter the structures and magnetic properties of cyano-bridged 4d-4f nanomagnets by adjusting the coordination environments of the DyIII centers.
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Bistable materials with multiphysical channels, such as optical, electrical, and magnetic properties, have been paid dramatic attention due to their alternativity of the signal status in electronic devices. Herein, three stable supramolecular radicals ([(NH3-TEMPO)(18-crown-6)][XF6] (1, X = P; 2, X = As; 3, X = Sb)) were synthesized and characterized. The former two molecules present ferroelectric phase transitions around 381.7 and 382.7 K, respectively, with bistability in dielectric property and second-harmonic generation (SHG) effect, which are first found in supramolecular radicals. Their ferroelectric transition and bistable properties are generated from a net polar crystal structure owing to the static ordered packing of NH3-TEMPO radical cations in the low-temperature phase (LTP) to a nonpolar structure owing to a distinctive symmetric scissoring motion of NH3-TEMPO radical cations between two 18-crown-6 molecules in the high-temperature phase (HTP). Both of them exhibit paramagnetic properties in HTP and LTP states since no intermolecular spin-spin interaction occurs due to the long distances among the radicals in their crystals. These results make us possible to design bistable optoelectronic radical materials with bistability in magnetic property in the future.
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Increased vegetation peak growth and phenological shifts toward spring have been observed in response to climate warming in the temperate regions. Such changes have the potential to modify warming by perturbing landâatmosphere energy exchanges; however, the signs and magnitudes of biophysical feedback on surface temperature in different biomes are largely unknown. Here, we synthesized information from vegetation growth proxies, land surface temperature (LST), and surface energy balance factors (surface evapotranspiration (ET), albedo, and broadband emissivity (BBE)) to investigate the variations in timing (PPT) and productivity (PPmax) of seasonal peak photosynthesis and their time-lagged biophysical feedbacks to the post-season LST in Inner Mongolia (IM) during 2001-2020. We found that increased PPmax, rather than advanced PPT, exhibited a significant impact on LST, with divergent signs and magnitudes across diurnal periods and among different biomes. In the grassland biome, increased PPmax cooled both LST during daytime (LSTday) and nighttime (LSTnight) throughout the post-season period, with a more pronounced response during daytime and diminishing gradually from July to September. This cooling effect on LST was primarily attributed to enhanced ET, as evidenced by the greater effect of ET cooling than that of albedo warming and BBE cooling based on a structural equation model (SEM). In the forest biome, increased PPmax led to a symmetrical warming effect on LSTday and LSTnight, and none of the surface energy balance factors were identified as significant intermediate explanatory factors for the observed warming effect. Moreover, the responses of average LST (LSTmean) and diurnal temperature range of LST (LSTDTR) to variations in PPmax were consistent with those of LSTday at two biomes. The observations above elucidate the divergent feedback mechanisms of vegetation peak growth on LST among different biomes and diurnal cycles, which could facilitate the improvement of the realistic parameterization of surface processes in global climate models.
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BACKGROUND: Contrast-enhanced ultrasound in percutaneous nephrolithotomy (CEUS-PCNL) is an economical and practical technique for the treatment of patients with renal stones without significant collecting system dilatation. The aim of this systematic review is to compare the safety and efficacy of CEUS-PCNL and conventional ultrasound (US)-guided (US-PCNL) treatment of patients with renal calculi without significant hydronephrosis. METHODS: This review was conducted with strict adherence to the PRISMA guidelines. Comparative studies on CEUS-PCNL and US-PCNL published in PubMed, SinoMed, Google Scholar, Embase, and Web of science until March 1, 2023, were systematically searched. RevMan 5.1 software was used for meta-analysis. Pooled odds ratios (ORs), weight mean differences (WMDs) and standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using the fixed-effects or random-effects model. Publication bias was evaluated using funnel plots. RESULTS: Four randomized controlled trials involving 334 patients (168 with CEUS-guided PCNL and 166 with US-guided PCNL) were identified. There was no statistically significant difference between CEUS-guided PCNL and US-guided PCNL in terms of the operation time (SMD: - 0.14; 95% CI - 0.35 to 0.08; p = 0.21), minor complications (p = 0.48), major complications (p = 0.28) and overall complications (p = 0.25). However, CEUS-guided PCNL had a higher stone-free rate (OR: 2.22; 95% CI 1.2 to 4.12; p = 0.01), higher success rate of single-needle punctures (OR:3.29; 95% CI 1.82 to 5.95; p < 0.0001), shorter puncture time (SMD: - 1.35; 95% CI - 1.9 to - 0.79; p < 0.00001), shorter hospital stay (SMD: - 0.34; 95% CI - 0.55 to - 0.12; p = 0.002) and lesser hemoglobin loss (SMD: - 0.83; 95% CI - 1.06 to - 0.61; p < 0.00001) as compared with conventional US-guided PCNL. CONCLUSIONS: According to almost all pooled data, CEUS-guided PCNL is superior to US-guided PCNL in terms of the perioperative outcomes. However, many rigorous clinical randomized controlled studies are required to obtain more accurate results. Registration The study protocol was registered with PROSPERO (CRD42022367060).
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Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Humanos , Nefrolitotomía Percutánea/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Cálculos Renales/diagnóstico por imagen , Cálculos Renales/cirugía , Ultrasonografía Intervencional , Nefrostomía Percutánea/métodosRESUMEN
INTRODUCTION AND OBJECTIVES: The relationship between anemia and the outcome of patients with cirrhosis is not completely clear. Therefore, we performed this large-scale epidemiological study to investigate the prevalence and severity of anemia in patients with cirrhosis and acute decompensation or liver injury and how anemia impacts short-term and long-term outcomes. PATIENTS AND METHODS: Patients with cirrhosis and acute decompensation (AD) or acute liver injury (ALI) were enrolled in the Chinese AcuTe on CHronic LIver FailurE (CATCH-LIFE) studies, which consisted of two large, multicenter, prospective, observational cohorts between January 2015 and December 2016 and July 2018 and January 2019. We conducted data analysis on the prevalence of anemia and determined the relationship between anemia and prognosis. RESULTS: Among 1979 patients, 1389 (70.2%) had anemia, among whom 599 (41.3%) had mild anemia, 595 (15.8%) had moderate anemia and 195 (2.4%) had severe anemia. A linear association between hemoglobin level and 90-day or 1-year LT-free mortality was shown, and a 10 g/L decrease in hemoglobin level was associated with a 6.8% extra risk of 90-day death and a 5.7% extra risk of 1-year death. Severe anemia was an independent risk factor for 90-day [HR=1.649 (1.100, 2.473), p=0.016] and 1-year LT-free mortality [HR=1.610 (1.159, 2.238), p=0.005]. Multinomial logistic regression analysis further identified that severe anemia was significantly associated with post-28-day mortality but not within-28-day mortality. CONCLUSIONS: Anemia is common in patients with cirrhosis admitted for acute events. Severe anemia was associated with poor 90-day and 1-year prognoses in these patients.
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OBJECTIVE: To explore the association between circadian syndrome (CircS) and the prevalence of kidney stones in overweight people. MATERIALS AND METHODS: A cross-sectional analysis was conducted based on the NHANES 2007-2018. Overweight people aged ≥ 20 years were the target population. Three multivariable logistic regression models were built to examine the association between CircS and kidney stones. Subgroup analysis based on age, gender, and race were also employed. Interaction and stratification analysis was also conducted to identify whether some factors modify the association. RESULT: A total of 4,603 overweight participants were included in the study. The multivariable logistic regression suggested that CircS was positively associated with the prevalence of kidney stones (OR = 1.422, 95% CI 1.057 to 1.912). The subgroup analysis showed that the association was more obvious in females (OR = 1.604, 95% CI 1.023 to 2.516) or in the population aged 35 to 49 years old (OR = 2.739, 95% CI 1.428 to 5.254). Additionally, the same trend was present when people were Mexican American (OR = 3.834, 95% CI 1.790 to 8.215) or other races (OR = 4.925, 95% CI 1.776 to 13.656). The interaction and stratification analysis showed that the results above were robust. CONCLUSION: CircS was positively associated with the prevalence of kidney stones in overweight people, especially people as females, aged 35 to 49, and Mexican Americans.
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Cálculos Renales , Sobrepeso , Femenino , Adulto , Humanos , Persona de Mediana Edad , Sobrepeso/epidemiología , Encuestas Nutricionales , Estudios Transversales , Prevalencia , Cálculos Renales/epidemiología , SíndromeRESUMEN
OBJECTIVE: Systematic evaluation of the effectiveness and safety of laparoscopic radical nephrectomy (LRN) for renal tumor (>7 cm). METHODS: The databases PubMed, Scopus, SinoMed, ScienceDirect, and Google Scholar were systematically searched for trials up to November 2022. The pooled results were evaluated by weighted mean difference (WMD), odds ratio (OR), and hazard ratio (HR). RESULTS: This meta-analysis (18 trials) demonstrated that compared to open radical nephrectomy (ORN), LRN had a longer operative time (OT) (WMD=15.99, 95% CI: 6.74 to 25.24, p = 0.0007), lower estimated blood loss (EBL) (WMD = -237.07, 95% CI: -300.02 to -174.12, p < 0.00001), lower transfusion rates (OR = 0.37, 95% CI: 0.24 to 0.55, p < 0.00001), and shorter length of stay (LOS) (WMD = -2.95, 95% CI: -3.86 to -2.03, p < 0.00001). No statistically relevant differences were found in overall survival (OS) (HR = 1.04, 95% CI: 0.81 to 1.35, p = 0.76), cancer-specific survival (CSS) (HR = 1.28, 95% CI: 0.97 to 1.68, p = 0.08), progression-free survival (PFS) (HR = 1.20, 95% CI 0.97 to 1.48, p = 0.1), recurrence-free survival (RFS) (OR = 1.27, 95% CI: 0.89 to 1.81, p = 0.56), local recurrence rate (OR = 0.85, 95% CI: 0.42 to 1.71, p = 0.65), and intraoperative and postoperative complications. CONCLUSION: For patients with renal tumors (> 7 cm), LRN has specific perioperative advantages over ORN (LOS, EBL, and transfusion rates). However, the OT was prolonged in the LRN group. In addition, no differences in complication or oncological outcomes (OS, CSS, PFS, RFS, and local recurrence rate) were reported. TRIAL REGISTRATION: PROSPERO CRD42022367114.
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Carcinoma de Células Renales , Neoplasias Renales , Laparoscopía , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Nefrectomía/efectos adversos , Nefrectomía/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Recently, there has been a significant amount of debate concerning the question of whether laparoscopic surgery should be performed transperitoneally or retroperitoneally for treating large renal tumors. AIM: The purpose of this research is to conduct a comprehensive review and meta-analysis of the previous research on the safety and efficacy of transperitoneal laparoscopic radical nephrectomy (TLRN) and retroperitoneal laparoscopic radical nephrectomy (RLRN) in the treatment of large-volume renal malignancies. METHODS: An extensive search of the scientific literature was carried out utilizing PubMed, Scopus, Embase, SinoMed, and Google Scholar in order to locate randomized controlled trials (RCTs) and prospective and retrospective studies that compared the effectiveness of RLRN versus TLRN in the treatment of for large renal malignancies. For the purpose of comparing the oncologic and perioperative outcomes of the two techniques, data were taken from the research studies that were included and pooled together. RESULTS: A total of 14 studies (five RCTs and nine retrospective studies) were incorporated into this meta-analysis. The overall RLRN had an association with significantly shorter operating time (OT) (MD [mean difference]: - 26.57; 95% CI [confidence interval]: - 33.39 to - 19.75; p < 0.00001); less estimated blood loss (EBL) (MD: - 20.55; CI: - 32.86 to - 8.23; p = 0.001); faster postoperative intestinal exhaust (MD: - 0.65; CI: - 0.95 to - 0.36; p < 0.00001). The terms of length of stay (LOS) (p = 0.26), blood transfusion (p = 0.26), conversion rate (p = 0.26), intraoperative complications (p = 0.5), postoperative complications (p = 0.18), local recurrence rate (p = 0.56), positive surgical margin (PSM) (p = 0.45), and distant recurrence rate (p = 0.7) did not show any differences. CONCLUSIONS: RLRN provides surgical and oncologic results similar to TLRN, with potential advantages regarding shorter OT, EBL, and postoperative intestinal exhaust. Due to the high heterogeneity among the studies, long-term randomized clinical trials are required to obtain more definitive results.
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Carcinoma de Células Renales , Neoplasias Renales , Laparoscopía , Humanos , Carcinoma de Células Renales/patología , Resultado del Tratamiento , Neoplasias Renales/patología , Laparoscopía/efectos adversos , Laparoscopía/métodos , Nefrectomía/efectos adversos , Nefrectomía/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugíaRESUMEN
BACKGROUND: The debate on whether to choose a transperitoneal (TP) or retroperitoneal (RP) approach for treating upper urinary tract urothelial carcinoma (UTUC) with laparoscopic surgery has been drawing attention. This study aimed to systematically review and meta-analyze the existing evidence regarding oncologic and perioperative outcomes of transperitoneal laparoscopic radical nephroureterectomy (TLNU) and retroperitoneal laparoscopic radical nephroureterectomy (RLNU) in managing UTUC. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Embase, and Google Scholar for identifying randomized controlled trials (RCTs) and observational studies that evaluated the outcomes of TLNU and RLNU for UTUC. Continuous variables were represented by weighted mean difference (WMD) and standard mean difference (SMD), while binary variables were represented by odds ratio (OR), with 95% confidence intervals (CIs). The quality was assessed using the Newcastle-Ottawa scale. A sensitivity analysis was performed to evaluate the robustness of the estimates. RESULT: Six observational studies were incorporated into this meta-analysis. The overall TLNU was associated with significantly shorter operating time (WMD - 19.85; 95% CI - 38.03 to - 1.68; P = 0.03); longer recovery time of intestinal function (SMD 0.46; 95% CI 0.08 to 0.84; P = 0.02). However, the terms of estimated blood loss (WMD - 5.72; 95% CI - 19.6 to - 8.15; P = 0.42); length of stay (WMD - 0.35; 95% CI - 1.61 to 0.91; P = 0.59), visual analog pain scale (WMD - 0.38; 95% CI - 0.99 to 0.84; P = 0.22); drainage duration (WMD - 0.22; 95% CI - 0.61 to 0.17; P = 0.26); overall complication rates (OR 1.24; 95% CI 0.58 to 2.63; P = 0.58); local recurrence rate (OR 0.6; 95% CI 0.3 to 1.21; P = 0.16); distant metastasis (OR 0.94; 95% CI 0.04 to 20.77; P = 0.97); 1-year overall survival (OS) (OR 0.45; 95% CI 0.1 to 2.01; P = 0.3) showed no difference between TLNU and RLUN. CONCLUSION: TLNU provides similar surgical outcomes and oncologic results compared to RLUN; however, TLNU has a shorter procedure time and prolonged intestinal function recovery time. Due to the heterogeneity among the studies, randomized clinical trials with follow-ups in the long term are required to obtain more definite results. TRIAL REGISTRATION: www.crd.york.ac.uk/prospero/ , identifier CRD42023388554.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Renales , Laparoscopía , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Sistema Urinario , Humanos , Nefroureterectomía/métodos , Neoplasias Renales/cirugía , Neoplasias Ureterales/cirugía , Laparoscopía/métodos , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/cirugía , Sistema Urinario/patología , Estudios Observacionales como AsuntoRESUMEN
Oocyte in vitro maturation is necessary for the study and application of animal-assisted reproduction technology in animal reproduction and breeding. The comprehensive transcriptional profile of equine oocyte maturated in vitro has not been fully mined yet, which makes many key transcriptional events still unidentified. Here, Smart-seq2 was performed to analyse the gene expression pattern and the underlying regulatory mechanism of horse germinal vesicle (GV) and in vitro metaphase II (MII) oocytes. The results showed that 6402 genes (2640 up-regulated and 3762 down-regulated in MII samples compared to GV) and 4021 lncRNA transcripts (1210 up-regulated and 2811 down-regulated in MII samples compared to GV) were differentially expressed in GV and MII oocytes. Further, GO and KEGG analysis found that differentially expressed mRNAs and lncRNAs were mainly enriched in the pathways related to energy and lipid metabolism. In addition, LGALS3 was found a key gene in mediating the regulation of oocyte meiosis recovery and fertilization ability. This study provides novel knowledge about gene expression and energy metabolism during equine oocyte maturation and a reference for the further study and application of assisted reproductive technology in horse reproduction and breeding.
Asunto(s)
Oocitos , Oogénesis , Caballos/genética , Animales , Oocitos/fisiología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , Meiosis , Perfilación de la Expresión Génica/veterinariaRESUMEN
Colossal and anisotropic thermal expansion is a key function for microscale or nanoscale actuators in material science. Herein, we present a hexanuclear compound of [(Tp*)FeIII (CN)3 ]4 [FeII (Ppmp)]2 â 2 CH3 OH (1, Tp*=hydrotris(3,5-dimethyl-pyrazol-1-yl)borate and Ppmp=2-[3-(2'-pyridyl)pyrazol-1-ylmethyl]pyridine), which has a rhombic core structure abbreviated as {FeIII 2 FeII 2 }. Magnetic susceptibility measurements and single-crystal X-ray diffraction analyses revealed that 1 underwent thermally-induced spin transition with the thermal hysteresis. The FeII site in 1 behaved as a spin crossover (SCO) unit, and significant deformation of its octahedron was observed during the spin transition process. Moreover, the distortion of the FeII centers actuated anisotropic deformation of the rhombic {FeIII 2 FeII 2 } core, which was spread over the whole crystal through the subsequent molecular rearrangements, leading to the colossal anisotropic thermal expansion. Our results provide a rational strategy for realizing the colossal anisotropic thermal expansion and shape memory effects by tuning the magnetic bistability.
RESUMEN
BACKGROUND: Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive. METHODS: Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE-/- mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [3H]-labeled cholesterol. RESULTS: Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE-/- mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas. CONCLUSION: Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE-/- mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.