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1.
Int J Biol Macromol ; 281(Pt 1): 136282, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39368581

RESUMEN

The glomerular basement membrane (GBM) is a critical component of the glomerular filtration barrier (GFB), with its thickness directly influencing renal function. While a uniformly thinned GBM can cause hematuria while preserving normal renal function, this condition is typically diagnosed as thin basement membrane nephropathy (TBMN). However, the pathogenesis and potential progression to renal insufficiency of TBMN are not fully understood. In this study, we analyzed clinical cohorts presenting with microscopic hematuria who underwent genetic testing and identified five novel pathogenic FN1 mutations. Through bioinformatics analysis of these variants, expression localization analysis of GBM-related molecules in renal biopsies, and functional studies of the mutants, we found that these variants exhibited gain-of-function characteristics. This led to the excessive deposition of aberrant serum-derived FN1 variants on glomerular endothelial cells rather than cell-type-specific variants. The deposition competitively binds FN1 variants to Integrin ß1, disrupting the interaction with Laminin α5ß2γ1 and subsequently reducing the expression of key GBM components, resulting in TBMN. This study elucidated, for the first time, the genetic pathogenesis of TBMN caused by FN1 variants. It provides a crucial foundation for understanding the progression of renal dysfunction associated with simple hematuria, highlights the potential for targeted therapeutic strategies, and differentiates TBMN from early-stage Alport syndrome.

3.
J Clin Invest ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316444

RESUMEN

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging due to the fragile nature of fear extinction, for which ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed fear extinction. Gamma entrainment of vCA1 by deep brain stimulation (DBS) or noninvasive transcranial alternating current stimulation (tACS) of LEC persistently enhanced the PV-IN activity in vCA1, thereby promoting fear extinction. These results demonstrate that the LEC-vCA1 pathway forms a top-down motif to empower low gamma-band oscillations that facilitate fear extinction. Finally, application of low gamma DBS and tACS to a mouse model with persistent PTSD showed potent efficacy, suggesting that the dedicated LEC-vCA1 pathway can be stimulated for therapy to remove traumatic memory trace.

4.
PeerJ ; 12: e17972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39285919

RESUMEN

The Xiao Jiang River, as a crucial element of ecological restoration in the upper reaches of the Yangtze River, plays an indispensable role in agricultural water utilization and water ecology within its watersheds. The water quality status of the Xiao Jiang River not only impacts local water-ecological equilibrium and economic benefits but also holds paramount importance for sustaining ecosystem health in the Yangtze River basin. Plankton surveys and environmental physicochemical detection were conducted in the major channel region of the Xiao Jiang River in dry and wet periods in 2022 to better understand the diversity of eukaryotic plankton and its community structure characteristics. Environmental DNA is an emerging method that combines traditional ecology with second-generation sequencing technology. It can detect species from a single sample that are difficult to find by traditional microscopy, making the results of plankton diversity studies more comprehensive. For the first time, environmental DNA was used to investigate eukaryotic plankton in the Xiao Jiang River . The results showed that a total of 881 species of plankton from 592 genera in 17 phyla were observed. During the dry period, 480 species belonging to 384 genera within17 phyla were detected, while, during the wet period, a total of 805 species belonging to 463 genera within 17 phyla were recorded. The phylum Ciliophora dominated the zooplankton, while the phylum Chlorophyta and Bacillariophyta dominated the phytoplankton. The presence of these dominant species indicate that the water quality conditions in the study area are oligotrophic and mesotrophic. Principal coordinate analysis and difference test showed that the number of plankton ASVs, abundance, species richness, dominating species, and diversity indices differed between the dry and wet periods. Spearman correlation analysis and redundancy analysis (RDA) of relative abundance data with environmental physicochemical factors revealed that water temperature (WT), dissolved oxygen (DO), potential of hydrogenacidity (pH), ammonia nitrogen (NH3-N), total nitrogen (TN), electrical conductivity (EC) and the determination of redox potential (ORP) were the main environmental physicochemical factors impacting the plankton community structure. The results of this study can serve as a provide data reference at the plankton level for water pollution management in the Xiao Jiang River, and they are extremely important for river ecological restoration and biodiversity recovery in the Yangtze River basin.


Asunto(s)
Biodiversidad , Plancton , Ríos , China , Ríos/química , Plancton/genética , Plancton/clasificación , Monitoreo del Ambiente/métodos , Ecosistema , Eucariontes/genética , Eucariontes/clasificación , Eucariontes/aislamiento & purificación , ADN Ambiental/genética , ADN Ambiental/análisis , Calidad del Agua
5.
J Health Popul Nutr ; 43(1): 137, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223682

RESUMEN

BACKGROUND: Previous studies have established a correlation between the pathogenesis of oxidative stress and sarcopenia. The Oxidative Balance Score (OBS) is an integrated measure that reflects the overall balance of antioxidants and pro-oxidants in dietary components and lifestyle. However, there are limited reports on the association between OBS and lean mass and the impact of protein intake on the association between OBS and lean mass. METHODS: Using data from the National Health and Nutrition Examination Survey from 2011 to 2018, multivariate linear and logistic regression analyses were conducted to explore the associations between OBS and outcomes. The findings were then illustrated through fitted smoothing curves and threshold effect analyses. RESULTS: This study included 2,441 participants, demonstrating that higher OBS is significantly associated with an increased ratio of appendicular lean mass to body mass index. Key inflection points at OBS 31 mark pronounced changes in these associations, with age and protein intake notably affecting the association. The effect of OBS on lean mass varies among populations with high and low protein intake. CONCLUSIONS: Our findings suggest that OBS is significantly and positively associated with lean mass. A high protein intake of more than 84.5 g/day may enhance the role of OBS in influencing muscle health to improve muscle outcomes.


Asunto(s)
Composición Corporal , Índice de Masa Corporal , Proteínas en la Dieta , Encuestas Nutricionales , Estrés Oxidativo , Humanos , Masculino , Femenino , Adulto , Proteínas en la Dieta/administración & dosificación , Persona de Mediana Edad , Adulto Joven , Sarcopenia/metabolismo , Estudios Transversales , Estados Unidos
6.
J Environ Manage ; 369: 122330, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39226808

RESUMEN

Extreme meteorological events and rapid urbanization have led to serious urban flooding problems. Characterizing spatial variations in flooding susceptibility and elucidating its driving factors are essential for preventing damages from urban pluvial flooding. However, conventional methods, limited by spatial heterogeneity and the intricate mechanisms of urban flooding, frequently demonstrated a deficiency in precision when assessing flooding susceptibility in dense urban areas. Therefore, this study proposed a novel framework for an integrated assessment of urban flood susceptibility, based on a comprehensive cascade modeling chain consisting of XGBoost, SHapley Additive exPlanations (SHAP), and Partial Dependence Plots (PDP) in combination with K-means. It aimed to recognize the specific influence of urban morphology and the spatial patterns of flooding risk agglomeration under different rainfall scenarios in high-density urban areas. The XGBoost model demonstrated enhanced accuracy and robustness relative to other three benchmark models: RF, SVR, and BPDNN. This superiority was effectively validated during both training and independent testing in Shenzhen. The results indicated that urban 3D morphology characteristics were the dominant factors for waterlogging magnitude, which occupied 46.02 % of relative contribution. Through PDP analysis, multi-staged trends highlighted critical thresholds and interactions between significant indicators like building congestion degree (BCD) and floor area ratio (FAR). Specifically, optimal intervals like BCD between 0 and 0.075 coupled with FAR values between 0.5 and 1 have the potential to substantially mitigate flooding risks. These findings emphasize the need for strategic building configuration within urban planning frameworks. In terms of the spatial-temporal assessment, a significant aggregation effect of high-risk areas that prone to prolonged duration or high-intensity rainfall scenarios emerged in the old urban districts. The approach in the present study provides quantitative insights into waterlogging adaptation strategies for sustainable urban planning and design.


Asunto(s)
Planificación de Ciudades , Modelos Teóricos , Urbanización , Cambio Climático
7.
Plant J ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189381

RESUMEN

The casein kinase II (CK2) complex consists of catalytic (α) and regulatory (ß) subunits and is highly conserved throughout eukaryotes. Plant CK2 plays critical roles in multiple physiological processes; however, its function in plant immunity remains obscure. In this study, we demonstrated that the unique chloroplast-localized CK2 α subunit (CPCK2) is a negative regulator of Arabidopsis thaliana innate immunity. cpck2 mutants displayed enhanced resistance against the fungal pathogen powdery mildew, Golovinomyces cichoracearum and the virulent bacterial pathogen, Pseudomonas syringae pv. tomato (Pto) DC3000. Moreover, the cpck2-1 mutant accumulated higher salicylic acid (SA) levels and mutations that disabled SA biosynthesis or signaling inhibited cpck2-1-mediated disease resistance. CPCK2 interacted with the chloroplast-localized carbonic anhydrase (CA), SA-binding protein 3 (SABP3), which was required for cpck2-mediated immunity. Significantly, CPCK2 phosphorylated SABP3, which promoted S-nitrosylation of this enzyme. It has previously been established that S-nitrosylation of SABP3 reduces both its SA binding function and its CA activity, which compromises the immune-related function of SABP3. Taken together, our results establish CPCK2 as a negative regulator of SA accumulation and associated immunity. Importantly, our findings unveil a mechanism by which CPCK2 negatively regulates plant immunity by promoting S-nitrosylation of SABP3 through phosphorylation, which provides the first example in plants of S-nitrosylation being promoted by cognate phosphorylation.

8.
BMC Psychol ; 12(1): 457, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198911

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is the third most common cause of death after cancer and heart disease. The continuous treatment of children with CKD was greatly challenged during the COVID-19 pandemic, which significantly impacted the CKD children's prognosis and the caregivers' psychological status. However, the influence mechanism of socioeconomic status, medical delay duration, traffic pressure, and online consultation duration on caregivers' hope and psychological resilience still lacks relevant evidence. METHODS: This study investigated the general social information, hope, and psychological resilience of 247 caregivers with CKD in 13 provinces of China in March 2020. Factor analysis and an exploratory Structural Equation Model ( SEM ) were used to find the best-fit model, and Bootstrapping was used to calculate the 95% CI of indirect effects. RESULTS: The factor analysis obtained four common factors, namely, socioeconomic status (annual family income, education, and career stability), medical accessibility (online consultation duration, medical delay duration, and traffic pressure), hope (positive attitude, positive action, and intimate relationship) and psychological resilience (optimism, tenacity, and strength), with the cumulative contribution rate of 65.34%. Bootstrapping obtains the socioeconomic status ß = 0.30 (95% CI [0.14, 0.47], P = 0.002), medical accessibility ß = 0.31 (95% CI [0.12, 0.47], P = 0.002), and hope ß = 0.40 (95% CI [0.27, 0.52], P = 0.002) has a direct impact on psychological resilience of CKD children caregivers, followed by medical accessibility ß = 0.20 (95% CI [0.10, 0.38], P = 0.001) and hope ß = 0.23 (95% CI [0.16, 0.32], P = 0.001) plays a mediating role between socioeconomic status and psychological resilience. The indirect impact effect ß = 0.35 (95% CI [0.25, 0.50], P = 0.001) is greater than the direct impact effect ß = 0.30 (95% CI [0.14, 0.47], P = 0.002). CONCLUSIONS: Sufficient attention should still be given to children with immunodeficiency after the COVID-19 pandemic, such as CKD, to avoid infection of deadly. Secondly, the government should vigorously develop Primary medical institutions to ensure efficient treatment of severe patients in tertiary hospitals; Finally, the professional literacy of medical workers in remote diagnosis and treatment should be improved to enhance the country's emergency response capacity for similar major public events and the requirements for normalised epidemic prevention and control.


Asunto(s)
COVID-19 , Cuidadores , Accesibilidad a los Servicios de Salud , Esperanza , Insuficiencia Renal Crónica , Resiliencia Psicológica , Clase Social , Humanos , Insuficiencia Renal Crónica/psicología , China , Masculino , Femenino , Cuidadores/psicología , Adulto , Niño , COVID-19/psicología , COVID-19/epidemiología , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Análisis de Clases Latentes , Persona de Mediana Edad , Adolescente , SARS-CoV-2
9.
Lipids Health Dis ; 23(1): 274, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198823

RESUMEN

BACKGROUND: The ratio between non-high-density lipoprotein cholesterol and high-density lipoprotein cholesterol (NHHR) is a reliable marker for assessing the risk linked to lipid metabolism disorders. Sarcopenia, characterized by age-related loss of muscle mass and strength/function, includes the assessment of muscle mass, muscle strength, and muscle-specific strength. However, research into NHHR's relationship with low muscle mass risk remains unexplored. METHODS: Our study utilized a cross-sectional approach, examining data derived from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Through multivariable linear and logistic regression, we investigated the relationships of the NHHR with muscle mass and low muscle mass. We visualized the results using smoothing curves and assessed threshold effects. We also performed various subgroup and sensitivity analyses. RESULTS: This research encompassed 9,012 participants and demonstrated significant nonlinear associations between NHHR and ALMBMI or low muscle mass risk in a generalized additive model (GAM), pinpointing critical NHHR values (3.328 and 3.367) where changes in NHHR significantly impacted ALMBMI and low muscle mass risk. CONCLUSIONS: The NHHR demonstrates a significant association with an increased risk of low muscle mass among middle-aged Americans. This ratio has potential as a predictive marker for low muscle mass. Further exploration of NHHR is expected to aid in advancing preventive and therapeutic measures for this condition.


Asunto(s)
HDL-Colesterol , Encuestas Nutricionales , Sarcopenia , Humanos , Adulto , Masculino , Persona de Mediana Edad , Femenino , HDL-Colesterol/sangre , Estados Unidos/epidemiología , Estudios Transversales , Sarcopenia/sangre , Sarcopenia/epidemiología , Adulto Joven , Músculo Esquelético/metabolismo , Biomarcadores/sangre , Fuerza Muscular , Factores de Riesgo
10.
Sci Total Environ ; 951: 175505, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147037

RESUMEN

Stormwater management problems have been deteriorated with the high frequency and intensity of precipitation owing to rapid urbanization and climate variability, especially in urban highly built-up area. Nature-based solutions (NBS) have emerged as a powerful measure for rising these challenges due to their ability to mitigate urban waterlogging and increase carbon sequestration. Identifying optimal locations for NBS implementation remains a critical research focus. This study integrates carbon and water footprint accounting into NBS-based planning for sustainable urban development in central Guangzhou, China, to enhance urban flooding mitigation and carbon sequestration. Through carbon-water footprint analysis and weighting, we prioritized NBS planning. To achieve the objectives of increasing sequestered carbon and reducing urban runoff, three types of NBS-green roofs, permeable pavements, and bioretention systems-were optimized for a high-priority town street. The results showed that the implementation of green roof and permeable pavement reduced the surface runoff by 3.58 %, while the biological retention system reduced the runoff gray water by 27 %. Moreover, the application of green roof and biological retention increased the carbon sequestration by 2.57 million kg CO2-eq (life cycle). The findings of this study provide comprehensive insights into optimization of NBS planning based on carbon-water footprint accounting, facilitating to enhance mitigation of urban flooding vulnerability and carbon sequestration.

11.
J Med Chem ; 67(14): 11469-11487, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38980167

RESUMEN

Antibody-drug conjugates (ADCs) comprise antibodies, cytotoxic payloads, and linkers, which can integrate the advantages of antibodies and small molecule drugs to achieve targeted cancer treatment. However, ADCs also have some shortcomings, such as non-negligible drug resistance, a low therapeutic index, and payload-related toxicity. Many studies have focused on changing the composition of ADCs, and some have even further extended the concept and types of targeted conjugated drugs by replacing the targeted antibodies in ADCs with peptides, revolutionarily introducing peptide-drug conjugates (PDCs). This Perspective summarizes the current research status of ADCs and PDCs and highlights the structural innovations of ADC components. In particular, PDCs are regarded as the next generation of potential targeted drugs after ADCs, and the current challenges of PDCs are analyzed. Our aim is to offer fresh insights for the efficient design and expedited development of innovative targeted conjugated drugs.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Neoplasias , Humanos , Inmunoconjugados/uso terapéutico , Inmunoconjugados/química , Inmunoconjugados/farmacología , Neoplasias/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Péptidos/química , Péptidos/uso terapéutico , Péptidos/farmacología , Animales , Terapia Molecular Dirigida/métodos
12.
Nat Commun ; 15(1): 6285, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060247

RESUMEN

Amid the escalating global climatic challenges, hydrological risks significantly influence human settlement patterns, underscoring the imperative for an in-depth comprehension of hydrological change's ramifications on human migration. However, predominant research has been circumscribed to the national level. The study delves into the nonlinear effects of hydrological risks on migration dynamics in 46,776 global subnational units. Meanwhile, leveraging remote sensing, we procured globally consistent metrics of hydrological intrusion exposure, offering a holistic risk assessment encompassing hazard, exposure, and vulnerability dimensions, thus complementing previous work. Here, we show that exposure is the primary migration driver, surpassing socioeconomic factors. Surrounding disparities further intensified exposure's impact. Vulnerable groups, especially the economically disadvantaged and elderly, tend to remain in high-risk areas, with the former predominantly migrating within proximate vicinities. The nonlinear analysis delineates an S-shaped trajectory for hydrological exposure, transitioning from resistance to migration and culminating in entrapment, revealing dependence on settlement resilience and adaptability.


Asunto(s)
Migración Humana , Hidrología , Humanos , Factores Socioeconómicos , Medición de Riesgo , Cambio Climático
13.
Front Immunol ; 15: 1369969, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915395

RESUMEN

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.


Asunto(s)
Lupus Eritematoso Sistémico , Adolescente , Niño , Femenino , Humanos , Masculino , China/epidemiología , Pueblos del Este de Asia , Estudios de Seguimiento , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
14.
Cancer Lett ; 593: 216956, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38735381

RESUMEN

Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.


Asunto(s)
Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Neoplasias de Cabeza y Cuello , Inhibidores de Proteínas Quinasas , Factor de Transcripción STAT3 , Carcinoma de Células Escamosas de Cabeza y Cuello , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Animales , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Femenino , Masculino , Ratones Desnudos , Ratones , Proteína de Retinoblastoma/metabolismo , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Fosforilación
15.
Hortic Res ; 11(5): uhae077, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38779140

RESUMEN

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

16.
bioRxiv ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38712205

RESUMEN

Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGFß signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGFß-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.

17.
Clin Kidney J ; 17(5): sfae115, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38742208

RESUMEN

Background: This study aimed to observe the efficacy and safety of tacrolimus in the treatment of refractory immunoglobulin A vasculitis nephritis (IgAVN). Methods: Sixteen patients with IgAVN who had been previously treated with cyclophosphamide shock therapy at least five times, some of whom had also received mycophenolate but still had persistent proteinuria, were enrolled. The clinical and pathological data were collected and analysed. Results: The average (mean ± standard deviation) age at the initial assessment for the group of 16 patients was 10 ± 2.7 years. Finally, at the end of their respective follow-up time point, 6 of the 16 patients achieved complete remission (37.5%), 5 achieved partial remission (31.2%), and 5 had no remission (31.2%). A significant difference was found in the median proteinuria before and after a 6-month course of tacrolimus treatment [19.2 (11.2, 31.9) vs 7.8 (4.3, 13.9) mg/kg/day] (P < .05). During the first 6 months of tacrolimus treatment, all patients' estimated glomerular filtration rate levels remained normal. The mean tacrolimus blood concentration was 6.0 ± 2.6 ng/mL. The median prednisone dosage was decreased from 10 mg/day to 5 mg/day, and prednisone was eventually stopped in three individuals. No drug-related adverse effects were observed during treatment. Conclusions: Tacrolimus has demonstrated efficacy in increasing remission rates, significantly lowering urinary protein levels, and reducing steroid use in children with refractory IgAVN. Further research is required to investigate its optimal blood concentrations, long-term effects and renoprotective properties.

18.
Clin Chem Lab Med ; 62(10): 2082-2090, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-38563053

RESUMEN

OBJECTIVES: The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing with liquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. METHODS: Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. RESULTS: All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (-14.4 to -3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (-8.3 to -2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (-18.3 to -3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (-17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. CONCLUSIONS: The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants.


Asunto(s)
Hemoglobina Glucada , Espectrometría de Masas en Tándem , Humanos , Hemoglobina Glucada/análisis , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Hemoglobinas Anormales/análisis , Hemoglobinas Anormales/genética
19.
J Appl Psychol ; 109(9): 1408-1430, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38602796

RESUMEN

While the previous research has examined antecedents of supervisors' voice endorsement, it has generally overlooked its effects on voicers' affective and behavioral reactions, probably because of the underlying assumption that supervisors' voice endorsement is inherently beneficial and likely to encourage more proactive behaviors in the future. In this research, we offer a theoretical model of the double-edged effects of supervisors' voice endorsement on voicers' subsequent personal initiative. Drawing on cognitive appraisal theory and related research, we proposed that supervisors' voice endorsement prompts two different cognitive appraisal processes in voicers that evoke two distinct emotional experiences-feeling pride and feeling envied-with countervailing effects on voicers' subsequent personal initiative. Specifically, voice endorsement results in voicers not only feeling pride, which enhances their subsequent personal initiative, but also in their feeling envied, which reduces their later personal initiative. Moreover, we extend the cognitive appraisal theory of emotion from a social constructionist approach by incorporating coworker support-an important relational context-as a contingent factor shaping the effects of voice endorsement on feeling pride and feeling envied and on voicers' subsequent personal initiative. The results from two field studies-a weekly experience sampling study with 574 observations from 119 employees and an event-based daily experience sampling study with 787 observations from 180 employees-largely support our theoretical model. This research suggests the importance of considering the perspectives of all the stakeholders in the proactivity triad (i.e., the focal employee, the supervisor, and coworkers) in order to sustain employee proactivity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Emociones , Empleo , Humanos , Adulto , Masculino , Femenino , Empleo/psicología , Relaciones Interpersonales
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