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We investigated, both analytically and numerically, the dynamics of a noiseless overdamped active particle in a square lattice of planar counter-rotating convection rolls. Below a first threshold of the self-propulsion speed, a fraction of the simulated particle's trajectories spatially diffuse around the convection rolls, whereas the remaining trajectories remain trapped inside the injection roll. We detected two chaotic diffusion regimes: (i) below a second, higher threshold of the self-propulsion speed, the particle performs a random motion characterized by asymptotic normal diffusion. Long superdiffusive transients were observed for vanishing small self-propulsion speeds. (ii) above that threshold, the particle follows chaotic running trajectories with speed and orientation close to those of the self-propulsion vector at injection and its dynamics is superdiffusive. Chaotic diffusion disappears in the ballistic limit of extremely large self-propulsion speeds.
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BACKGROUND: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. METHODS: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. RESULTS: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. CONCLUSIONS: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide.
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Virus del Dengue , Dengue , Genotipo , Filogenia , Serogrupo , Virus del Dengue/genética , Virus del Dengue/clasificación , Virus del Dengue/fisiología , China/epidemiología , Dengue/epidemiología , Dengue/virología , Dengue/transmisión , Humanos , Brotes de Enfermedades , Filogeografía , Genoma ViralRESUMEN
Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.
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Membrana Eritrocítica , Nanopartículas , Animales , Ratones , Membrana Eritrocítica/inmunología , Transfusión Sanguínea/métodos , Modelos Animales de Enfermedad , Humanos , Eritrocitos/inmunología , Incompatibilidad de Grupos Sanguíneos/inmunologíaRESUMEN
BACKGROUND: More than half of the global population lives in areas at risk of dengue (DENV) transmission. Developing an efficient risk prediction system can help curb dengue outbreaks, but multiple variables, including mosquito-based surveillance indicators, still constrain our understanding. Mosquito or oviposition positive index (MOI) has been utilized in field surveillance to monitor the wild population density of Aedes albopictus in Guangzhou since 2005. METHODS: Based on the mosquito surveillance data using Mosq-ovitrap collection and human landing collection (HLC) launched at 12 sites in Guangzhou from 2015 to 2017, we established a MOI-based model of the basic dengue reproduction number (R0) using the classical Ross-Macdonald framework combined with a linear mixed-effects model. RESULTS: During the survey period, the mean MOI and adult mosquito density index (ADI) using HLC for Ae. albopictus were 12.96 ± 17.78 and 16.79 ± 55.92, respectively. The R0 estimated from the daily ADI (ADID) showed a significant seasonal variation. A 10-unit increase in MOI was associated with 1.08-fold (95% CI 1.05, 1.11) ADID and an increase of 0.14 (95% CI 0.05, 0.23) in the logarithmic transformation of R0. MOI-based R0 of dengue varied by month and average monthly temperature. During the active period of Ae. albopictus from April to November in Guangzhou region, a high risk of dengue outbreak was predicted by the MOI-based R0 model, especially from August to October, with the predicted R0 > 1. Meanwhile, from December to March, the estimates of MOI-based R0 were < 1. CONCLUSIONS: The present study enriched our knowledge about mosquito-based surveillance indicators and indicated that the MOI of Ae. albopictus could be valuable for application in estimating the R0 of dengue using a statistical model. The MOI-based R0 model prediction of the risk of dengue transmission varied by month and temperature in Guangzhou. Our findings lay a foundation for further development of a complex efficient dengue risk prediction system.
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Aedes , Dengue , Adulto , Animales , Femenino , Humanos , Dengue/epidemiología , Número Básico de Reproducción , Oviposición , Mosquitos VectoresRESUMEN
Glandular cancers are amongst the most prevalent types of cancer, which can develop in many different organs, presenting challenges in their detection as well as high treatment variability and failure rates. For that purpose, anticancer drugs are commonly tested in cancer cell lines grown in 2D tissue culture on plastic dishesin vitro, or in animal modelsin vivo. However, 2D culture models diverge significantly from the 3D characteristics of living tissues and animal models require extensive animal use and time. Glandular cancers, such as prostate cancer-the second leading cause of male cancer death-typically exist in co-centrical architectures where a cell layer surrounds an acellular lumen. Herein, this spatial cellular position and 3D architecture, containing dual compartments with different hydrogel materials, is engineered using a simple co-axial nozzle setup, in a single step utilizing prostate as a model of glandular cancer. The resulting hydrogel soft structures support viable prostate cancer cells of different cell lines and enable over-time maturation into cancer-mimicking aggregates surrounding the acellular core. The biofabricated cancer mimicking structures are then used as a model to predict the inhibitory efficacy of the poly ADP ribose polymerase inhibitor, Talazoparib, and the antiandrogen drug, Enzalutamide, in the growth of the cancer cell layer. Our results show that the obtained hydrogel constructs can be adapted to quickly obtain 3D cancer models which combine 3D physiological architectures with high-throughput screening to detect and optimize anti-cancer drugs in prostate and potentially other glandular cancer types.
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Antineoplásicos , Neoplasias de la Próstata , Humanos , Animales , Masculino , Hidrogeles/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Línea CelularRESUMEN
INTRODUCTION: Borderline personality disorder (BPD) is a disorder of pervasive emotion dysregulation associated with high rates of self-injurious thoughts and behaviors (SITB). Understanding specific emotion states in relation to SITB is important for effective intervention. METHODS: The current study examined whether, and how, the specific emotion of shame contributes to suicide ideation and urges to engage in non-suicidal self-injury (NSSI) both directly, and indirectly via anger, among individuals with BPD. Participants (N = 100) were enrolled in a 6-month comprehensive dialectical behavior therapy (DBT) program and provided daily ratings of shame, anger, suicide ideation, and urges for NSSI. RESULTS: We found that higher daily ratings of shame and anger were directly associated with higher same-day ratings of both suicidal ideation and urges for NSSI. Furthermore, anger partially mediated the relationships between shame and both suicidal ideation and urges for NSSI. CONCLUSION: These findings highlight shame and anger as potential antecedents of SITB among individuals with BPD. Clinical approaches, such as DBT, that include personalized, ongoing, clinical assessment of these specific affective states may be particularly important for treatment of SITB.
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Trastorno de Personalidad Limítrofe , Terapia Conductual Dialéctica , Conducta Autodestructiva , Humanos , Ideación Suicida , Trastorno de Personalidad Limítrofe/terapia , Trastorno de Personalidad Limítrofe/psicología , Resultado del Tratamiento , Conducta Autodestructiva/terapia , Conducta Autodestructiva/psicología , Ira , Vergüenza , Terapia ConductistaRESUMEN
Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of UCHL1 inhibitors with cisplatin, the standard of care used for neuroendocrine carcinomas, significantly delays tumor growth in pre-clinical settings. Our study reveals mechanisms of UCHL1 function in regulating the progression of neuroendocrine carcinomas and identifies UCHL1 as a therapeutic target and potential molecular indicator for diagnosing and monitoring treatment responses in these malignancies.
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Carcinoma Neuroendocrino , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Masculino , Humanos , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Glicoproteínas de MembranaRESUMEN
CAR (chimeric antigen receptor) T cell therapy has shown clinical success in treating hematological malignancies, but its treatment of solid tumors has been limited. One major challenge is on-target, off-tumor toxicity, where CAR T cells also damage normal tissues that express the targeted antigen. To reduce this detrimental side-effect, Boolean-logic gates like AND-NOT gates have utilized an inhibitory CAR (iCAR) to specifically curb CAR T cell activity at selected nonmalignant tissue sites. However, the strategy seems inefficient, requiring high levels of iCAR and its target antigen for inhibition. Using a TROP2-targeting iCAR with a single PD1 inhibitory domain to inhibit a CEACAM5-targeting CAR (CEACAR), we observed that the inefficiency was due to a kinetic delay in iCAR inhibition of cytotoxicity. To improve iCAR efficiency, we modified three features of the iCAR-the avidity, the affinity, and the intracellular signaling domains. Increasing the avidity but not the affinity of the iCAR led to significant reductions in the delay. iCARs containing twelve different inhibitory signaling domains were screened for improved inhibition, and three domains (BTLA, LAIR-1, and SIGLEC-9) each suppressed CAR T function but did not enhance inhibitory kinetics. When inhibitory domains of LAIR-1 or SIGLEC-9 were combined with PD-1 into a single dual-inhibitory domain iCAR (DiCARs) and tested with the CEACAR, inhibition efficiency improved as evidenced by a significant reduction in the inhibitory delay. These data indicate that a delicate balance between CAR and iCAR signaling strength and kinetics must be achieved to regulate AND-NOT gate CAR T cell selectivity.
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Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Linfocitos T , Complejo Hierro-Dextran , Inmunoterapia Adoptiva , Lectinas Similares a la Inmunoglobulina de Unión a Ácido SiálicoRESUMEN
Research and clinical experience highlight the variability of suicidal ideation (SI) within and between individuals. Although the idiographic emotional contexts in which SI occurs may offer explanations for its dynamic nature, most statistical methods focus on nomothetic patterns, making it difficult to advance our understanding of SI. Furthermore, the gap between nomothetic methods and a need for idiographic understanding of SI poses challenges to translating empirical knowledge into individualized clinical treatment. Group iterative multiple model estimation (GIMME) is a method that may bridge the idiographic-nomothetic divide by analyzing temporal relationships among a network of variables at both group- and individual-levels. This study explored the feasibility and clinical utility of GIMME applied to examine the relationships between various emotions and SI among individuals with borderline personality disorder who underwent Dialectical Behavior Therapy. We present graphic outputs that emerged throughout treatment and discuss how they could aid clinical assessment and case formulation (ClinicalTrials.gov Identifier: NCT03123198.).
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Trastorno de Personalidad Limítrofe , Terapia Conductual Dialéctica , Humanos , Ideación Suicida , Trastorno de Personalidad Limítrofe/psicología , EmocionesRESUMEN
BACKGROUND AND AIMS: It remains unknown about the relationship between vertebrobasilar artery (VBA) calcification and plaque instability. We aimed to investigate the characteristics of VBA calcification using vessel wall magnetic resonance imaging (MRI) and computed tomography (CT) and its association with acute cerebral infarction (ACI). METHODS: Nine hundred and thirty patients with VBA stenosis who underwent vessel wall MRI and CT examinations were evaluated retrospectively. Calcification morphology was classified as either intimal or non-intimal predominant using a CT-pathology-validated grading method. Qualitative and quantitative plaque MRI variables and calcification characteristics were compared between culprit and non-culprit lesions. The association between VBA calcification and the occurrence of culprit lesions was investigated using multivariate logistic regression. RESULTS: A total of 150 patients with ACI and 142 patients without ACI were eligible for subsequent analyses, respectively. In the qualitative analysis, T1 hyperintensity (p < 0.001) and intimal predominant calcification (p = 0.021) were more frequently observed in the culprit than non-culprit lesions. In the quantitative analyses, culprit lesions had a larger stenosis degree, plaque length, normal wall index, contrast enhancement ratio, lower calcification density and smaller calcification volume than non-culprit lesions (p all < 0.05). Intimal predominant calcification (odds ratio [OR], 2.51; 95 % confident interval [CI], 1.31-4.82, p = 0.006) and calcification density (OR, 0.53; 95 % CI, 0.35-0.78, p = 0.001) were independently associated with the presence of ACI after adjusting for clinical risk factors and plaque variables. CONCLUSIONS: Intimal predominant calcification in vertebrobasilar atherosclerosis is associated with the likelihood of having caused acute cerebral infarction. The morphology and density of VBA calcification may provide insight into stroke risk stratification in the posterior circulation.
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Isquemia Encefálica , Placa Aterosclerótica , Accidente Cerebrovascular , Humanos , Constricción Patológica , Estudios Retrospectivos , Imagen por Resonancia Magnética/efectos adversos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Isquemia Encefálica/etiología , Tomografía Computarizada por Rayos X/efectos adversos , Infarto Cerebral , ArteriasRESUMEN
BACKGROUND: Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. METHODS: A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015-2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. RESULTS: A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. CONCLUSIONS: Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management.
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Aedes , Ecosistema , Animales , Urbanización , Mosquitos Vectores , Óvulo , LarvaRESUMEN
BACKGROUND: Increasing evidence has linked the thyroid dysfunction to the pathogenesis of dementia. Evidence from clinical studies has demonstrated that hypothyroidism is related to an increased risk of dementia. But the association of hyperthyroidism with dementia is largely unknown. METHODS: We used the adenovirus containing thyrotropin receptor (TSHR) amino acid residues 1-289 (Ad-TSHR289)-induced Graves' disease (GD) phenotype in Alzheimer's disease (AD) model mice (APP/PS1 mice) to evaluate the effect of hyperthyroidism on the cognitive function and ß-amyloid (Aß) accumulation. RESULTS: GD mice exhibited a stable long-term hyperthyroidism and cognitive deficits. Single Cell RNA-sequencing analysis indicated that microglia function played a critical role in the pathophysiological processes in GD mice. Neuroinflammation and polarization of microglia (M1/M2 phenotype) and activated receptor-interacting serine/threonine protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudo-kinase (MLKL)-mediated necroptosis contributed to the pathological process, including Aß deposition and neuronal loss. RIPK3 inhibitor could inhibit GD-mediated Aß accumulation and neuronal loss. CONCLUSIONS: Our findings reveal that GD hyperthyroidism aggravates cognitive deficits in AD mice and induces Aß deposition and neuronal loss by inducing neuroinflammation and RIPK3/MLKL-mediated necroptosis.
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Enfermedad de Alzheimer , Enfermedad de Graves , Hipertiroidismo , Animales , Ratones , Necroptosis , Enfermedades Neuroinflamatorias , Hipertiroidismo/complicaciones , Cognición , Enfermedad de Alzheimer/complicacionesRESUMEN
Tumour-associated macrophages (TAMs), as one of the most abundant tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, limiting an effective antigen cross-presentation. How to selectively reprogram M2-like TAMs to reinvigorate anti-tumour immune responses is challenging. Here, we report a pH-gated nanoadjuvant (PGN) that selectively targets the lysosomes of M2-like TAMs in tumours rather than the corresponding organelles from macrophages in healthy tissues. Enabled by the PGN nanotechnology, M2-like TAMs are specifically switched to a M1-like phenotype with attenuated lysosomal acidity and cathepsin activity for improved antigen cross-presentation, thus eliciting adaptive immune response and sustained tumour regression in tumour-bearing female mice. Our findings provide insights into how to specifically regulate lysosomal function of TAMs for efficient cancer immunotherapy.
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Nanopartículas , Neoplasias , Femenino , Animales , Ratones , Macrófagos Asociados a Tumores , Lisosomas , Inmunoterapia , Concentración de Iones de Hidrógeno , Neoplasias/terapiaRESUMEN
The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.
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Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.
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Candida albicans , Candidiasis Vulvovaginal , Células Epiteliales , Humanos , Animales , Ratones , Células Cultivadas , Candidiasis Vulvovaginal/terapia , Fototerapia , Fármacos Fotosensibilizantes/farmacologíaRESUMEN
Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.
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COVID-19 , Apnea Obstructiva del Sueño , Anciano , Persona de Mediana Edad , Humanos , COVID-19/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/terapia , Hipoxia , Obesidad , FaringeRESUMEN
The current study examined the potential bi-directional associations between urges to die by suicide and to use alcohol or drugs as well as sadness and anger in relation to these urges. Forty individuals with suicidal thoughts, binge drinking behaviors, and emotion regulation difficulties, who were recruited for a clinical trial of internet-delivered Dialectical Behavior Therapy skills training, completed daily diaries on suicide and substance use urges and emotions over twenty-one days. Results indicated that higher daily peak substance use urges were associated with a greater likelihood of reporting suicide urges on the next day. Participants with higher and an increase in peak substance use urges (relative to their daily average) were both more likely to report suicide urges on the same day. Furthermore, both daily peak sadness and anger ratings predicted next-day suicide urges while accounting for substance use urges, though sadness may be a stronger predictor. These findings suggested a possible unidirectional pathway from urges to use substances to subsequent urges to die by suicide and a unique role of sadness.
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Trastornos Relacionados con Sustancias , Suicidio , Humanos , Suicidio/psicología , Emociones , Ideación Suicida , Ira , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
Taurine upregulated gene 1 (TUG1) has been implicated in the onset and progression of various malignancies. The current study aimed to evaluate the biological function and potential mechanisms of TUG1 in multiple myeloma (MM) progression. TUG1 knockdown in MM cells was investigated in vitro and in vivo to evaluate the role of TUG1. We also predicted the transcription factor (TF) that bound to TUG1 together with the downstream target genes of the TUG1-TF interaction, and evaluated the regulatory mechanism of TUG1 in cell assays. TUG1 knockdown reduced the cell's proliferative and migratory capabilities while increasing apoptosis and bortezomib sensitivity in vitro and inhibiting tumorigenesis in vivo. TUG1 was found in the nucleus of MM cells and was found to be positively regulated by the TF-YY1. Further in vitro mechanistic investigations indicated that the YY1-TUG1 complex targeted YOD1 to regulate MM progression.