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Microglial phagoptosis in development, health, and disease
No full textMicroglial phagoptosis, defined as the phagocytosis of a viable cell by microglia that ultimately causes the death of the engulfed cell, has emerged as a pivotal process in sculpting neural circuits within the central nervous system (CNS). Essential for neurodevelopmental circuit refinement and ongoing tissue homeostasis, this process relies on dynamic molecular cues that direct microglia to specific cellular substrates. Physiologically, phagoptosis contributes to neural circuit refinement and cell number regulation during development; however, its dysregulation can drive neurodevelopmental and neurodegenerative disorders via aberrant cell removal. Recent advances have elucidated the distinct signaling pathways involved in target recognition and engulfment, revealing the dual roles of microglial phagoptosis in both CNS health and disease. Deeper mechanistic insight into this process offers new therapeutic opportunities for conditions characterized by defective or excessive cell clearance. This review summarizes current progress, highlights unresolved challenges, and discusses future perspectives on targeting microglial phagoptosis for intervention in CNS disorders
The skeletal muscle function deficit: From an operational definition to clinic results from the InCHIANTI longitudinal study
No full textAge-related muscle dysfunction is a major contributor to disability, frailty, and poor clinical outcomes in older adults. Skeletal Muscle Function Deficit (SMFD) framework integrates multiple domains as: muscle mass, muscle density, strength, and power to capture a broader spectrum of age-related muscle dysfunction. The primary aims of these analyses are to develop and validate a composite SMFD score and evaluate its association with key geriatric outcome.This study used data from the InCHIANTI follow-up study, involving an initial cohort of 1035 older participants, with a total of 3196 assessments. The SMFD score was computed by assigning quintile-based values of muscle area, density, strength, and lower limb power. Associations with adverse health outcomes, and major chronic diseases were analyzed using mixed-effects models.The SMFD score declined over time from baseline to the third follow-up was: β ± SE:-0.64 ± 0.12 (p-value < 0.001), β ± SE:-1.94 ± 0.13 (p-value < 0.001), and β ± SE:-4.43 ± 0.14 (p-value < 0.001), respectively, and was associated with: BADL (OR = 0.57; 95 %CI: 0.46–0.69), IADL (OR = 0.70; 95 %CI: 0.66–0.75), poor physical performance (SPPB < 7) (OR = 0.68; 95 %CI: 0.64–0.73), Fried's frailty phenotype (OR = 0.72; 95 % CI: 0.68–0.76), hospitalization (OR = 0.96; 95 %CI: 0.93–0.99), and falls' number (OR = 0.96; 95 %CI: 0.92–0.99). Whereas higher SMFD scores were negatively associated with Parkinson's disease, stroke, and hip osteoarthritis.The SMFD score is a valid, multidimensional measure that predicts adverse outcomes in older adults. It holds promise for use in clinical assessment, risk stratification, and targeted interventions
Thermodynamic invariance of the energy-momentum tensor under matter-Lagrangian choices and its astrophysical implications in f(R, T) gravity
No full textThe correct choice for the matter Lagrangian (LM) in the framework of f(R, T) theory of gravity, has been a fundamental yet often overlooked ambiguity. It has been a long-standing issue, whether to choose LM=p or −ρ as the proper definition of matter sector. In this work, we show that both choices lead to the same energy-momentum tensor, from thermodynamic point of view. However, for these two choices, the structure of the TOV equations are different. We construct and solve TOV equations using MIT bag model equation of state for LM=p and −ρ, and study the impact of the choices for matter Lagrangian on the maximum mass limit as well as M-R plot of compact stars. It is interesting to note that allowed range of gravity-matter coupling constant (αc) is also different for LM=p and LM=−ρ, i.e., αc can not be taken arbitrarily. Notably, through LM=p, we achieve a maximum mass of 2.78 M⊙, whereas for LM=−ρ, we obtain a maximum mass of 2.41 M⊙. So, despite the same energy-momentum tensor for different choices of LM, the upper limit of maximum mass is significantly modified
Metabolomics analysis uncovered the dynamic changes and aroma characteristics of volatile metabolites in Dendrobium thyrsiflorum at different flowering stages
No full textThe flowers of Dendrobium thyrsiflorum possess a distinctive aroma and serve as an important member of horticultural plants. Their components vary significantly at different flowering stages, thereby influencing the sensory characteristics perceived by consumers. However, systematic research on the aroma characteristics and component profiles of D. thyrsiflorum at different flowering stages has not been fully elucidated. We speculate that there is a unique spectrum of volatile metabolites in the full bloom period, which is the basis for the formation of its unique aroma. This study aims to test this hypothesis by analyzing the dynamic changes of volatile compounds. In this study, gas chromatography-mass spectrometry (GC–MS) combined with multivariate statistical analysis methods were used to systematically analyze the dynamic changes of volatile metabolites in D. thyrsiflorum during different flowering stages. There are 22 volatile metabolites can serve as aroma components to distinguish the full bloom stage from other stages, and five key volatile metabolites were further screened out, which jointly contributed to the unique sweet, minty, fresh, and floral aroma during this stage. KEGG enrichment analysis revealed that these aromas were mainly regulated by three major synthetic pathways. Flavor metabolomics results demonstrated that compared to other developmental stages, the full bloom stage exhibits significantly more distinct and pleasant flavor characteristics. This study establishes a theoretical foundation for optimizing the flower harvesting period of D. thyrsiflorum and provides a scientific basis for its comprehensive utilization
Microstructure and compression behavior of powder-metallurgy processed fine-grained TWIP steel
No full textTo enhance the strength of twinning-induced plasticity (TWIP) steels and promote their engineering application, powder metallurgy (PM) was employed in this study to directly produce fine-grained TWIP steels with average grain sizes of 2.93–11.93 μm, bypassing complex conventional processes involving induction melting, plastic deformation, and heat treatment. The quasi-static and dynamic compression properties of these samples exhibited a typical grain size dependence. Compared to the quasi-statically compressed samples, the dynamically compressed samples demonstrated enhanced work hardening, characterized by a higher flow stress and an increased work-hardening rate, along with a notable positive strain rate sensitivity. High-speed impact activated significant dislocation glide, leading to rapid dislocation multiplication, extensive twin nucleation, and particle deformation that generated high-energy distortion zones. This process also produced a high density of low-angle boundaries (LABs). Grain boundaries (GBs) and precipitation strengthening were the main drivers of work hardening. These mechanisms involved dislocation interactions with single Mn-rich particles, GB-associated particles, and those linked to twins. In contrast, twinning strengthening played a minor role due to the poor twin structure resulting from the suppressed twinning
Synergistic optimization of strength and ductility in layered ferrite-martensite dual-phase steel
No full textThe development of ultrafine-grained (UFG) structural materials with high yield strength and superior ductility is crucial for the exploitation of marine energy.This study employed a synergistic regulation strategy involving intercritical quenching and large-strain warm rolling (WR) to prepare a UFG layered ferrite-martensite (F-M) structure steel. The test steel exhibited a high yield strength of 830 ± 10 MPa, while maintaining an elongation of 23.7 %. The excellent performance is attributed to the significant dislocation strengthening effect induced by WR. This effect effectively reduces the hardness difference between microstructures (ΔHV 500 MPa). The superior strength-ductility balance achieved in F-M steel, attained through the optimization of grain size and microstructural distribution, offers a novel strategy for developing high-performance marine steels
Efecto de una intervención grupal interdisciplinar en pacientes frágiles: un estudio cuasiexperimental pre-post
No full textResumen: Objetivo: Evaluar el efecto de una intervención grupal interdisciplinar en pacientes frágiles en relación con su índice de fragilidad, sus hábitos alimentarios, su calidad de vida y su pauta farmacológica prescrita. Diseño: Estudio cuasi-experimental longitudinal no controlado. Intervención pre-post. Emplazamiento: Centro de Atención Primaria Sant Hipòlit de Voltregà, Barcelona. Participantes: Se reclutaron 61 participantes que cumplían con el diagnóstico de fragilidad inicial (0,20-0,35 índice frágil-VIG). Finalmente 6 participantes abandonaron la intervención y 55 participantes completaron el estudio. Intervenciones: Intervención individualizada con valoración psicosocial y de adecuación del plan terapéutico e intervención grupal interdisciplinar de 12 sesiones para informar sobre el manejo de la fragilidad. Mediciones principales: Se recogió la información sociodemográfica/psicosocial de la historia clínica, se valoró el nivel de fragilidad del paciente mediante el test frágil-VIG, la calidad de vida con el cuestionario EuroQol (EQ-5D), la adherencia a la dieta mediterránea con el cuestionario PREDIMED y la adecuación del plan terapéutico midiendo la disminución de incidencias relacionadas con la medicación. Resultados: Se observaron mejoras estadísticamente significativas en el test de adherencia a la dieta mediterránea PREDIMED (p-valor = 0,001) y en los aspectos del test EuroQol relacionados con el nivel de ansiedad/depresión (p-valor = 0,037). Se redujeron las incidencias farmacológicas un 45,28%. Conclusiones: La presente intervención interdisciplinar con finalidad preventiva ayuda a las personas con fragilidad inicial a construir hábitos de alimentación saludables, promueve el bienestar emocional y reduce las incidencias relacionadas con la medicación. Abstract: Objective: To evaluate the effect of an interdisciplinary group intervention in frail patients in relation to their frailty index, eating habits, quality of life and prescribed pharmacological regimen. Design: Non-controlled, quasi-experimental longitudinal study. A pre-post intervention. Location: Sant Hipòlit de Voltregà Primary Health Care Center, Barcelona. Participants: Sixty-one participants were recruited who met the initial frailty diagnosis (0.20-0.35 VIG frailty index). Finally 6 participants dropped out of the intervention and 55 participants completed the study. Intervention: Individualized intervention with psychosocial assessment, adequacy of the therapeutic plan assessment and interdisciplinary group intervention of 12 sessions to inform on the management of frailty. Main measurements: Sociodemographic/psychosocial information was collected from the clinical history, the participant's level of frailty was assessed using the VIG-frail test, quality of life was assessed using the EuroQol questionnaire, adherence to the Mediterranean diet using the PREDIMED questionnaire and the adequacy of the therapeutic plan by measuring the decrease in medication-related incidents. Results: Statistically significant improvements were observed in the PREDIMED Mediterranean diet adherence test (p-valor=001) and in the aspects of the EuroQol test related to the level of anxiety/depression (p-valor=037). Pharmacological incidences were reduced by 45.28%. Conclusions: This interdisciplinary preventive intervention helps people with initial frailty to build healthy eating habits, promotes emotional well-being and reduces medication-related incidences
Sulfur mediates cadmium accumulation and detoxification through distinct pathways in two Nicotiana species
No full textCadmium (Cd) is a heavy metal pollutant that impedes plant growth. Sulfur (S), a nutrient, possesses the ability to detoxify Cd. Nevertheless, the dose effect of S on Cd detoxification and the mechanism by which S modulates Cd accumulation and detoxification, remain insufficiently understood. Here, two Nicotiana species with distinct Cd accumulation strategies were hydroponically cultivated under varying S:Cd molar ratios (250:1, 500:1, 750:1, 1000:1). This study aimed to assess the effects of different S doses on Cd accumulation and detoxification and to clarify the underlying mechanisms from multiple perspectives. Results identified 500:1 as the optimal S:Cd ratio, beyond which detoxification diminished, reflecting a hormetic response. Integrated physiological, biochemical, transcriptomic, and metabolomic analyses revealed species-specific pathways of S-mediated detoxification between two Nicotiana species. Specifically, the S-mediated Cd translocation factor from roots to leaves in N. tabacum increased from 1.22 to 2.70, whereas it decreased from 0.25 to 0.20 in N. rustica. N. tabacum prioritizes shoot-based Cd detoxification via glutathione mobilization (62.96 % increase), transporter activation (NRAMP/HMA/ZIP), and enhanced trichome secretion (1.12-fold glandular trichome density). Conversely, in N. rustica, S redirected metabolism towards phytochelatins-dominated thiols (1.22-fold), enhancing Cd chelation detoxification, along with lignin fortification (3 % increase in cell wall Cd) and vacuolar sequestration (ABC/CAX) in roots. These findings demonstrate that S mediates divergent detoxification strategies across species, offering potentially valuable information for developing targeted strategies to enhance crop Cd remediation, either via shoot-driven phytoextraction or root-based immobilization for food safety
Adaptation and psychometric evaluation of the Indonesian Maladaptive Daydreaming Scale-16 (MDS-16-Ina)
No full textMaladaptive Daydreaming (MD) is characterized by excessive immersion in internal fantasies, resulting in significant distress and clinical impairment. Despite indications of high MD prevalence in Indonesia, the condition has not been deeply examined, and existing publications rely on unstandardized measurements. This study focuses on adapting the Maladaptive Daydreaming Scale-16 (MDS-16) for use in the Indonesian population. The adaptation followed the International Test Commission (ITC) guidelines. The translation process involved 5 forward translators, 1 reconciler, and 1 back-translator with the final version reviewed by three experts. Two rounds of cognitive interviews were conducted with 15 participants each to assess item clarity. Psychometric properties—including internal structure, reliability, convergent validity, and cut-off score—were evaluated in a sample of 253 Indonesian students in Jatinangor (Mage = 19.30, SDage = 1.02). Participants completed several instruments, and a subset of 28 participants retook some of these instruments after 2–3 weeks to assess test–retest reliability. The Indonesian version of the MDS-16 demonstrated good internal consistency and ambiguous test–retest reliability. Experts' judgment and cognitive interview suggested the clarity and comprehensiveness of the measurement. Confirmatory factor analysis indicated a 4-factor structure with a correlated error. Maladaptive daydreaming is moderately correlated with anxiety and depression, providing evidence of its convergent validity. Its relationship with CEQ is explored. Receiver Operating Characteristic curve analysis found a preliminary cut-off score of 49 %. Overall, MDS-16-Ina has sound psychometric properties and is suitable for research purposes in the Indonesian population. Future research with larger and more diverse participants is needed
Intratumoral dendritic cell immunotherapy controls dissemination of metastasis-initiating cancer cells, even in patients with metastatic breast cancer
No full textPatients with metastatic breast cancer (MBC) have limited opportunities for a cure, as they develop resistance to therapies and continually form new metastases. Clinical overt metastases emerge from metastasis-initiating cancer cells (MICs) that disseminate during breast cancer (BC) progression. Currently, there are no available therapies that inhibit MIC dissemination to prevent overt metastasis. We provide preclinical evidence that intratumoral (IT) delivery of type I polarized dendritic cells (DC1) limited the MIC dissemination mechanisms in tumor lesions of human epidermal growth factor receptor 2 (HER2)+ mammary carcinoma. Interferon gamma, a prominent cytokine secreted by T helper 1 and innate-like immune effector cells, inhibited dissemination of MICs from the tumor lesions via the modulation of HER2/progesterone receptor/Wnt family member 4/receptor activator of nuclear factor kappa beta ligand signaling. Importantly, we provide clinical evidence that in patients with stage I–III HER2+ BC, there was significant regression of the primary tumor treated with IT DC1, as well as inhibition of disseminating MIC phenotypes. We observed a reduced burden of MICs in the bone marrow (BM) of patients with stage I–III HER2+BC treated with IT DC1, compared with untreated patients and those treated with standard neoadjuvant HER2 therapies paclitaxel, with or without carboplatin, trastuzumab and pertuzumab (Taxol, Carboplatin, Herceptin and Perjeta or THP). We also treated a single patient with de novo stage IV HER2+ MBC with trastuzumab, pertuzumab and tamoxifen in combination with IT DC1. Remarkably, this treatment resulted in near-complete regression of primary tumor and metastatic disease, along with inhibition of MIC seeding in the BM. These findings suggest an intriguing strategy to inhibit the dissemination of MICs and prevent further overt metastasis in all patients with BC
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