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Targeted protein degradation (TPD) has risen as a promising therapeutic modality. Leveraging the catalytic nature of the ubiquitin-proteasome enzymatic machinery, TPD exhibits higher potency to eliminate disease-causing target proteins such as oncogenic transcription factors that may otherwise be difficult to abrogate by conventional inhibitors. However, there are challenges that remain. Currently, nearly all degraders engage CUL4CRBN or CUL2VHL as the E3 ligase for target ubiquitination. While their immediate efficacies are evident, the narrowed E3 ligase options make TPD vulnerable to potential drug resistance. In addition, E3 ligases show differential tissue expression and have intrinsic limitations in accessing varying types of disease-relevant targets. As the success of TPD is closely associated with the ability of E3 ligases to efficiently polyubiquitinate the target of interest, the long-term outlook of TPD drug development will depend on whether E3 ligases such as CUL4CRBN and CUL2VHL are accessible to the targets of interest. To overcome these potential caveats, a broad collection of actionable E3 ligases is required. Here, we designed a macrocyclic degrader engaging CUL3KLHL20 for targeting BET proteins and validated CUL3KLHL20 as an E3 ligase system suitable for TPD. This work thus contributes to the expansion of usable E3 ligases for potential drug development.
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Proteínas Adaptadoras Transductoras de Señales , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/metabolismo , Proteolisis , Ligandos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , UbiquitinaciónRESUMEN
BACKGROUND: Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time. AIMS: To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10-24 years. METHOD: Our research focused on young people (aged 10-24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019. RESULTS: The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20-24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males. CONCLUSIONS: Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.
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Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50-80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = - 0.002, t = - 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = - 0.001, t = - 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.
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Disfunción Cognitiva , Enfermedad de Parkinson , Humanos , Depresión/etiología , Proteína Sequestosoma-1 , Disfunción Cognitiva/complicaciones , Cognición , AutofagiaRESUMEN
BACKGROUND The correlation between serum creatinine levels and the long-term prognosis of patients undergoing percutaneous coronary intervention (PCI) has not yet been systematically investigated. This study aimed to evaluate the association between long-term prognosis and serum creatinine levels in patients after PCI. MATERIAL AND METHODS This was an observational cohort study of 2533 patients who received PCI and completed serum creatinine and other tests in China. The study's primary prognostic indicators were the frequency of clinical adverse events, all-cause death, cardiac death, acute myocardial infarction, and stroke. All-cause death referred to death from all causes during the follow-up period, whereas cardiac death was death due to cardiac injury resulting in severe cardiac dysfunction or failure. Clinical events included death, ischemia, and stroke. Yao et al completed the entire study and uploaded the data to the DATADRYAD website. We used only this data for secondary analysis. RESULTS The study involved 2533 participants, with a mean age of 59.9±11.1 years and a median follow-up of 29.8 months. The analysis, controlling for confounding factors, revealed a positive correlation between serum creatinine and all-cause death (OR: 2.178, 95% CI: 1.317-3.603, P<0.05), which was confirmed by the results of sensitivity analysis (P for trend <0.05). However, no direct linear correlation was found between serum creatinine and acute myocardial infarction, cardiac death, or stroke. CONCLUSIONS There was a linear correlation between serum creatinine and all-cause death in the long-term prognosis of patients after PCI, independent of acute myocardial infarction, cardiac death, and stroke.
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Creatinina , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Masculino , Persona de Mediana Edad , Femenino , Creatinina/sangre , Pronóstico , Anciano , China/epidemiología , Infarto del Miocardio/sangre , Infarto del Miocardio/mortalidad , Causas de Muerte , Factores de Riesgo , Estudios de Cohortes , Accidente Cerebrovascular/sangreRESUMEN
BACKGROUND: The growing prevalence of non-alcoholic fatty liver disease (NAFLD) in younger populations, particularly those of working age (15-64 years), has become a public health concern. Being diagnosed at a younger age implies a greater likelihood of accruing disability-adjusted life years (DALYs) later in life due to potential progression to conditions such as cirrhosis or hepatocellular carcinoma. This study aims to analyze NAFLD prevalence trends over three decades globally, regionally, and nationally, with a focus on age, period, and birth cohort associations. METHODS: Global, regional, and country time trends in the prevalence of NAFLD among working-age people from 1990 to 2019: Age-period-cohort analysis based on Global Burden of Disease Study 2019 estimates and 95% uncertainty interval (UI) of NAFLD prevalence in the working age population was extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. Age-period-cohort models were used to estimate the prevalence within each age group from 1990 to 2019 (local drift, % per year), fitted longitudinal age-specific rates adjusted for period bias (age effect), and period/cohort relative risk (period/cohort effect). RESULTS: The global age-standardized prevalence (ASPR) of NAFLD increased significantly from 1990 (14,477.6 per 100 000) to 2019 (19,837.6 per 100 000). In the Western Pacific, there were 42,903.8 NAFLD cases in 2019, 54.15% higher than in 1990. The ASPR also increased significantly in the region over the past three decades. At the national level, Palau had the highest ASPR while Brunei Darussalam had the lowest. Age-period-cohort analysis showed that in the Western Pacific, unlike globally, the risk of NAFLD declined after age 60-64 years. Relative to 1980-1989, incidence and DALY risks decreased but prevalence increased in subsequent birth cohorts. Future predictions indicate an upward trend in NAFLD burden, especially among women and medium (SDI) regions like China. CONCLUSION: Non-alcoholic fatty liver disease imparts an immense health burden that continues to grow globally and in the Asia Pacific region. Our work highlights working age adults as an at-risk group and calls attention to socioeconomic gradients within Western Pacific countries. Upward future projections demonstrate that NAFLD prevention is an urgent priority.
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Carga Global de Enfermedades , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Persona de Mediana Edad , Adulto , Carga Global de Enfermedades/tendencias , Femenino , Masculino , Adulto Joven , Adolescente , Prevalencia , Estudios de Cohortes , Factores de Riesgo , Años de Vida Ajustados por DiscapacidadRESUMEN
BACKGROUND: In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040. METHODS: Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends. RESULTS: In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI. CONCLUSION: NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019-exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options.
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Años de Vida Ajustados por Discapacidad , Carga Global de Enfermedades , Salud Global , Enfermedades Desatendidas , Humanos , Adolescente , Adulto Joven , Carga Global de Enfermedades/tendencias , Masculino , Femenino , Adulto , Salud Global/estadística & datos numéricos , Enfermedades Desatendidas/epidemiología , Años de Vida Ajustados por Discapacidad/tendencias , Medicina Tropical , Prevalencia , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.
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Encuestas Nutricionales , Antígeno Prostático Específico , Neoplasias de la Próstata , Riboflavina , Humanos , Masculino , Antígeno Prostático Específico/sangre , Persona de Mediana Edad , Estados Unidos/epidemiología , Anciano , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Riboflavina/administración & dosificación , AdultoRESUMEN
BACKGROUND: Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15-39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. METHODS: Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. RESULTS: Between 1990 and 2021, the worldwide prevalence of migraine among 15-39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35-39 age group. Notably, female rates consistently exceeded male rates across all age categories. CONCLUSION: The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.
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Carga Global de Enfermedades , Salud Global , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/epidemiología , Adolescente , Adulto Joven , Adulto , Masculino , Femenino , Carga Global de Enfermedades/tendencias , Prevalencia , Salud Global/estadística & datos numéricos , Incidencia , Años de Vida Ajustados por Calidad de Vida , Años de Vida Ajustados por Discapacidad/tendenciasRESUMEN
High-capacity Ni-rich layered oxides are promising cathode materials for fabrication of lithium-ion batteries (LIBs) with high energy density. However, thermal runaway of LIBs with these cathodes leads to great safety concerns. In this study, single crystalline LiNi0.9Co0.05Mn0.05O2 (NCM-SC) has been prepared and a flexible optical fiber was buried inside the pouch-type LIBs with NCM-SC cathode to in situ study its real-time temperature evolution during charge/discharge process. NCM-SC exhibits an enhanced Li+ ions transportation efficiency and electrode reaction kinetics, which can effectively reduce the generation of polarization heat and mitigate the internal temperature rise of the pouch-type battery. Meanwhile, solid-electrolyte interface (SEI) film decomposition and gas accumulation are effectively alleviated, due to the enhanced thermal stability of SEI film formed on NCM-SC. Moreover, the single crystal architecture can effectively retard layered to spinal and rock-salt phase transition, mitigate the crack formation and structural collapse. Consequently, NCM-SC exhibits an excellent electrochemical performance and enhanced thermal stability.
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Ni-rich layered oxides are promising lithium-ion batteries (LIBs) cathode materials for their high reversible capacity, but they suffer from fast structural degradation during cycling. Here, we report the Ce/Gd incorporated single-crystalline LiNi0.83 Co0.07 Mn0.10 O2 (SC-NCM) cathode materials with significantly enhanced cycling stability. The Gd ions are adequately incorporated in SC-NCM while Ce ions are prone to aggregate in the outer surface, resulting in the formation of a high-entropy zone in the near-surface of SC-NCM, including a Gd doped LiCeO2 (LCGO) shell and Ce/Gd dopant-concentrated layer. The high-entropy zone can effectively inhibit the oxygen evolution and prevent the formation of oxygen vacancies. Meanwhile, it leads to a greatly improved H2-H3 phase transformation reversibility and mitigated stress/strain caused by Li-ion extraction/insertion during (de)lithiation process. The synergetic effects of reduced oxygen vacancies concentration and mitigated stress/strain can effectively prevent the in-plane migration of TM ions, lattice planar gliding as well as the formation of intragranular nanocracks. Consequently, Ce/Gd incorporated SC-NCM (SC-NCM@CG2) delivers a high initial discharge specific capacity of 219.7â mAh g-1 at 0.1â C and an excellent cycling stability with a capacity retention of 90.2 % after 100â cycles at 1.0â C.
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Large Eddy Simulation (LES) and Ffowcs Williams-Hawkings acoustic analogy are performed to study the effect of trailing-edge blowing on airfoil self-noise. Simulations were conducted using a National Advisory Committee for Aeronautics 0012 airfoil at zero angle of attack and a chord-based Reynolds number of 4 × 10 5. The aerodynamic and aeroacoustic characteristics of the baseline airfoil were thoroughly verified by comparison with previous numerical and experimental data. The noise reduction effects of continuous and local blowing with different blowing ratios and blowing momentum coefficients were compared. A maximum noise reduction of 20 dB was achieved via trailing-edge blowing and the noise reduction mechanisms of the two blowing methods were discussed. The LES results show a pair of recirculation bubbles in the airfoil wake which are suppressed by trailing-edge blowing. As the blowing vortices convect into the wake, they stretch and stabilize the shear flows from airfoil surfaces. Instantaneous vorticity and root mean square velocity fluctuations are also weakened. There is a decrease in the spanwise coherence and an increase in the phase difference, which contribute to noise reduction. It is concluded that the suppression of turbulence fluctuations in the near wake is the main mechanism of noise reduction for airfoil trailing-edge blowing.
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BACKGROUND: In recent years, headache disorders have garnered significant attention as a pressing global health issue. This concern is especially pronounced in low- to middle-income countries and exhibits a notable increase in prevalence among adolescents and young adults. Such a surge in these disorders has invariably diminished the quality of life for affected individuals. Despite its global impact, comprehensive studies exploring the ramifications of headache disorders in the younger population remain scant. Our study endeavored to quantify the global prevalence of headache disorders in individuals between the ages of 15 and 39, over a three-decade span from 1990 to 2019. METHODS: Our study, conducted from 1990 to 2019, evaluated the impact of headache disorders, specifically migraines and tension-type headaches (TTH), in 204 different countries and territories. This comprehensive assessment included a detailed analysis of incidence rates, prevalence, and disability-adjusted life-years (DALYs) across various demographics such as age, gender, year, geographical location, and Socio-demographic Index (SDI). RESULTS: In 2019, there were an estimated 581,761,847.2 migraine cases globally (95% UI: 488,309,998.1 to 696,291,713.7), marking a 16% increase from 1990. Concurrently, TTH cases numbered at 964,808,567.1 (95% UI: 809,582,531.8 to 1,155,235,337.2), reflecting a 37% rise since 1990. South Asia reported the highest migraine prevalence with 154,490,169.8 cases (95% UI: 130,296,054.6 to 182,464,065.6). High SDI regions exhibited the most substantial migraine prevalence rates both in 1990 (22,429 per 100,000 population) and 2019 (22,606 per 100,000 population). Among the five SDI classifications, the middle SDI region recorded the highest tally of TTH cases in both 1990 (210,136,691.6 cases) and 2019 (287,577,250 cases). Over the past 30 years, East Asia experienced the most pronounced surge in the number of migraine cases. On the whole, there was a discernible positive correlation between the disease burden of migraine and TTH and the SDI. CONCLUSION: Migraine and TTH represent formidable challenges in global health. The intensity of their impact exhibits marked disparities across nations and is distinctly elevated among women, individuals within the 30-39 age bracket, and populations characterized by a high SDI. The results of our research emphasize the imperative of assimilating migraine and TTH management into contemporary healthcare paradigms. Such strategic integration holds the potential to amplify public cognizance regarding pertinent risk factors and the spectrum of therapeutic interventions at hand.
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Trastornos de Cefalalgia , Trastornos Migrañosos , Cefalea de Tipo Tensional , Adolescente , Femenino , Humanos , Adulto Joven , Adulto , Cefalea de Tipo Tensional/epidemiología , Carga Global de Enfermedades , Calidad de Vida , Trastornos Migrañosos/epidemiologíaRESUMEN
Venous calcification has been observed in post-thrombotic syndrome (PTS) patients; yet, the cell types and possible mechanisms regulating this process are still unclear. We evaluated the calcium deposition within the venous wall, the cell type involved in the calcified remodelling of the venous wall after thrombosis and explored possible mechanisms in vitro. Calcium deposition was found in human specimens of superficial thrombotic veins and was co-localized with VSMCs markers αSMA and TAGLN (also known as SM22α). Besides, the expression of osteogenesis-related genes was dramatically changed in superficial thrombotic veins. Moreover, the inhibition of the TGFß signalling pathway after TNFα treatment effectively induced the expression of osteogenic phenotype markers, the calcium salt deposits and the obvious phosphorylation of ERK1/2 and JNK2 in the VSMCs calcification model. Supplementing TGFß2 or blocking the activation of the ERK/MAPK signalling pathway prevented the transformation of VSMCs into osteoblast-like cells in vitro. Taken together, VSMCs have an important role in venous calcification after thrombosis. Supplementing TGFß2 or inhibiting the ERK/MAPK signalling pathway can reduce the appearance of VSMCs osteogenic phenotype. Our findings may present a novel therapeutic approach to prevent of vascular calcification after venous thrombosis.
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Calcificación Vascular , Trombosis de la Vena , Calcio/metabolismo , Células Cultivadas , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Osteogénesis/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Calcificación Vascular/metabolismo , Trombosis de la Vena/genética , Trombosis de la Vena/metabolismoRESUMEN
Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from ß-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.
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Células Endoteliales , Hidrogeles , Animales , Becaplermina , Colágeno/metabolismo , Células Endoteliales/metabolismo , Epítopos , Ratones , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Cicatrización de HeridasRESUMEN
Long-term exposure to ultraviolet-B (UVB) can cause photoaging. Peptides from Pinctada martensii meat have been shown to have anti-photoaging activities, but their mechanism of action is rarely studied. In this study, Pinctada martensii meat hydrolysates (PME) were prepared by digestive enzymes and then separated by ultrafiltration and Sephadex G-25 gel filtration chromatography to obtain a purified fraction (G2). The fraction G2 was identified by ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), and peptide sequences were synthesized by solid-phase synthesis. The mechanism of anti-photoaging activities was investigated using a human immortalised epidermal (HaCaT) cell model. Results showed that peptides from Pinctada martensii meat increased UVB-induced cell viability and reduced the contents of interstitial collagenase (MMP-1) and matrix lysing enzyme (MMP-3) in HaCaT cells. Furthermore, the fraction of G2 significantly downregulated the expression of p38, EKR, JNK, MMP-1, and MMP-3 in HaCaT cells. The peptide sequences Phe-His (FH), Ala-Leu (AL), Met-Tyr (MY), Ala-Gly-Phe (AGF), and Ile-Tyr-Pro (IYP) were identified and synthesized. Besides, FH reduced the contents of MMP-1 and MMP-3 in HaCaT cells, combining them effectively in molecular docking analysis. Thus, peptides from Pinctada martensii meat showed anti-photoaging activities and might have the potential to be used as an anti-photoaging agent in functional foods.
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Metaloproteinasa 1 de la Matriz , Péptidos , Pinctada , Envejecimiento de la Piel , Animales , Humanos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Carne , Simulación del Acoplamiento Molecular , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Pinctada/química , Espectrometría de Masas en Tándem , Rayos Ultravioleta , Envejecimiento de la Piel/efectos de los fármacosRESUMEN
Noise reduction by collars applied to rod-airfoil was studied numerically. The flow field and acoustic far-field are predicted using a large eddy simulation and the Ffowcs Williams and Hawking acoustic analogy. The present numerical method is first validated by existing experimental and numerical results for the baseline case. Then, to reduce interaction noise, a rod with collars is designed (denoted as the Col case). The main noise reduction mechanisms of the collars are investigated in detail. The numerical results show that the collars reduce the noise in the low- and medium-frequency bands of the rod, for which the tonal noise is reduced by 24.83 dB. The airfoil noise throughout the frequency band is thereby reduced as the main sound source. The upstream wake is regularized, and vortex shedding is suppressed. The surface pressure fluctuations along the rod, leading edge, and trailing edge of airfoil exhibit an obvious attenuation in the Col case compared with the baseline, which leads to a decrease in the sound source strength. It is also found that there exist spanwise decorrelation and decoherence effects along the rod with collars, which means the evolution of the turbulent vortices is regularized and the physical size of eddies is minified.
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The multiscale structural and rheological features of a series of dilute and semidilute low-methoxyl (LM) pectin solutions and a representative pectin/calcium sol-gel sample were systematically explored using a comprehensive combination of dynamic (DLS) and static light/X-ray scattering (SALS/SLS/SAXS), rheology, and microscopy (OM/SEM) characterizations. The study focused on the rarely explored colloidal aspect of LM pectin solutions and sol-gel transition, in contrast to the polymeric features extensively explored in previous studies. A highly uniform colloid-like, micron-sized agglomerate species was revealed in dilute solutions, with a progressively increased degree of flocculation in the semidilute regime (≥1.5 wt%). The agglomerate species in these solutions was resolved to be formed by random associations of individual pectin chains (L = 30 nm, r = 0.4 nm). Adding a critical amount of Ca2+ (10 wt%) to a semidilute solution (2 wt%) has an instant and pronounced effect of enhancing the agglomerate flocculation and resulting in a locally jammed state. Meanwhile, the agglomerate interior underwent microstructural transformation, leading to hierarchical structures defined by intermediate (spherical) aggregate species (Rg,aggregate ≈ 150 nm) and its packing cylindrical bundle (d ≈ 4 nm) composed of five pectin chains. Novel rheological features observed during the LM pectin/Ca2+ sol-gel transition include the following: the dynamic modulus data exhibited excellent TTS (gelling time/relaxation time superposition) as previously observed for weakly attractive colloidal gels. Three yield points were noticed for the final gel sample, suggested to mark the bond breaking of the cluster network, cage breaking of the resulting jammed flocculates, and, eventually, breakup of a flocculate into smaller agglomerates with increasing stress amplitude.
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Designing and synthesizing highly stable anode materials with high capacity is critical for the practical application of sodium ion batteries (SIBs), however, to date, this remains an insurmountable barrier. The introduction of hierarchical architectures and carbon supports is proving an effective strategy for addressing these challenges. Thus, we have fabricated a hierarchical CoSe2 @nitrogen-doped carbon (CoSe2 @NC) microcube composite using the Prussian blue analogue Co3 [Co(CN)6 ]2 as template. The rational combination of the unique hierarchical construction from one to three dimensions and a nitrogen-doped carbon skeleton facilitates sodium ion and electron transport as well as stabilizing the host structure during repeated discharge/charge processes, which contributes to its excellent sodium storage capability. As expected, the as-prepared CoSe2 @NC composite delivered remarkable reversible capacity and ultralong cycling lifespan even at a high rate of 2.0â A g-1 (384.3â mA h g-1 after1800 loops) when serving as the anode material for SIBs. This work shows the great potential of the CoSe2 -based anode for practical application in SIBs, and the original strategy may be extended to other anode materials.
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Constructing a solid electrolyte interface (SEI) is a highly effective approach to overcome the poor reversibility of lithium (Li) metal anodes. Herein, an adhesive and self-healable supramolecular copolymer, comprising of pendant poly(ethylene oxide) (PEO) segments and ureido-pyrimidinone (UPy) quadruple-hydrogen-bonding moieties, is developed as a protection layer of Li anode by a simple drop-coating. The protection performance of in-situ-formed LiPEO-UPy SEI layer is significantly enhanced owing to the strong binding and improved stability arising from a spontaneous reaction between UPy groups and Li metal. An ultrathin (approximately 70â nm) LiPEO-UPy layer can contribute to stable and dendrite-free cycling at a high areal capacity of 10â mAh cm-2 at 5â mA cm-2 for 1000â h. This coating together with the promising electrochemical performance offers a new strategy for the development of dendrite-free metal anodes.
RESUMEN
Antidepressant agents have been proven their utilities in treating depression, but they also could serve as candidate drugs for misuse or abuse due to diverse pharmacologic properties. Potential detriments had also been multidimensionally investigated. However, there had been no study exploring whether treatment with antidepressants causes psychological and/or behavioral alterations in offspring. In this regard, we chronically treated normal female mice with different dosages (0, 10, and 20 mg/kg) of fluoxetine (FLU) for 2 weeks before mating them with drug-free male mice and then tested the offspring for anxiety/depression-like behaviors with the elevated plus maze and the tail-suspension test after exposing to acute or chronic stress in adult period. We found that there were significant increases for immobility time in the tail-suspension test as well as percentage of open arm entries and percentage of open arm time in the elevated plus maze test detected in the female offspring of the 20 mg group compared to both baseline and all other groups, with the exception that the female offspring of the 10 mg group showed an increased percentage of open arm entries after chronic stress exposure. Locomotor activity assessments showed that neither acute nor chronic stress protocol could significantly affect locomotor activities of mice. Conclusionally, we found that high-dosage FLU increased the risk of the female offspring developing into depression/anxiety-like behaviors after stress exposure, with chronic stress as the environmental-risk factor. Our study has important implications for the safe use of antidepressant agents and raises more concerns regarding long-term use of even second-generation antidepressants in clinical practice.