Khalishah Yusri, Sandra Jose, Karen S. Vermeulen
et al.
Abstract Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in a plethora of physiological reactions, with a key relevance in supporting mitochondrial function. Due to its critical role in these cellular processes, declining levels of NAD+ are associated with general aging and chronic disorders, including cognitive decline, sarcopenia, and metabolic diseases. These conditions are also typified by loss of mitochondrial health through dysfunction of homeostatic components such as mitophagy, unfolded protein response, and the antioxidant system. Therefore, raising cellular NAD+ through vitamin B3 family precursors or via drug-based interventions has become a broadly used strategy to restore mitochondrial and organismal homeostasis, with NAD+ precursors becoming a popular supplementation approach. As increasing components of the NAD+ biology are unraveled, this comprehensive review summarizes the advances in mechanisms of NAD+ metabolism and its modulation via compound-based strategies. Furthermore, it highlights the role of NAD+ in mitochondrial homeostasis in aging and disease conditions, the latest results of NAD+-boosting therapeutics in clinical trials, and areas of further translational development.
Tayomara Ferreira Nascimento, Silvia Cristina Mangini Bocchi, João Cesar Lyra
et al.
<b>Background/Objective</b>: The effectiveness of blue-light phototherapy (PT) is mainly dependent on the total dose of light (time under PT and amount of skin exposed) received by infants. The primary aim of this study was the development of a novel, flexible, and stretchable device to provide continuous PT treatment, avoiding temporary interruptions that are often observed in practice, such as during breastfeeding, for example. This study evaluated the biocompatibility of a novel, low-cost blanket equipped with light-emitting diode (LED) lamps designed to maintain therapeutic efficacy while facilitating uninterrupted skin-to-skin contact. <b>Methods</b>: Fourteen New Zealand White rabbits, weighing approximately 2.9 kg and aged 4 months, were randomly assigned to an experimental group (TG, n = 7) or a control group (CG, n = 7). The TG received phototherapy directly on the skin (irradiance: 19.3 [13.0–22.0] µW/cm<sup>−2</sup>/nm<sup>−1</sup>) during two 12 h sessions over consecutive days, while the CG remained under identical conditions with the device turned off. Biochemical, hematological, dermatological, and histological parameters, as well as rectal and skin temperatures, were assessed. <b>Results</b>: The results showed no differences in clinical appearance or histological analysis of skin tissue between the groups. Blood analysis indicated a reduction in absolute monocyte counts in the TG compared to the CG (<i>p =</i> 0.049), though levels remained within normal ranges. Skin temperature was consistently higher in the TG, except during the initial measurement. Rectal temperatures were similar on the first day but lower in the TG on the second day (mean 40.3 ± 0.21 °C vs. 40.7 ± 0.32 °C; <i>p =</i> 0.039). <b>Conclusions</b>: Temperature levels remained within physiological limits for both groups throughout the study. The device demonstrated biocompatibility and caused no adverse dermatological, hematological, or biochemical effects.
Abasalt Bahrami, Leonardo Y. Tanaka, Ricardo C. Massucatto
et al.
For more than fifty years, scientists have been gathering evidence of the biological impacts of weak magnetic fields. However, the lack of systematics in experimental studies has hampered research progress on this subject. To systematically quantify magnetic field effects in cell biology, it is crucial to produce fields that can be automatically adjusted and that are stable throughout an experiment's duration, usually operating inside an incubator. Here, we report on the design of a fully automated 1D Helmholtz coil setup that is internally water cooled, thus eliminating any confounding effects caused by temperature fluctuations. The coils also allow cells to be exposed to magnetic fields from multiple directions through automated controlled rotation. Preliminary data, acquired with the coils placed inside an incubator and on a rat vascular smooth muscle cell line, confirm previous reports that both microtubule and actin polymerization and dynamics are altered by weak magnetic fields.
Maria Paola Belfiore, Valerio Nardone, Ida D’Onofrio
et al.
Squamous cell carcinoma of the head and neck (SCCHN) is among the ten most common cancers worldwide, with advanced SCCHN presenting with a 5-year survival of 34% in the case of nodal involvement and 8% in the case of metastatic disease. Disease-free survival at 2 years is 67% for stage II and 33% for stage III tumors, whereas 12–30% of patients undergo distant failures after curative treatment. Previous treatments often hinder the success of salvage surgery and/or reirradiation, while the standard of care for the majority of metastatic SCCHN remains palliative chemo- and immuno-therapy, with few patients eligible for locoregional treatments. The aim of this paper is to review the characteristics of recurrent SCCHN, based on different recurrence sites, and metastatic disease; we will also explore the possibilities not only of salvage surgery and reirradiation but also systemic therapy choices and locoregional treatment for metastatic SCCHN.
Due to the pet and goods trade, several animals are now present in regions outside of their traditional native ranges. A peculiar situation has arisen in mantises, insects that are becoming more popular as pets: two genera (Hierodula and Tenodera) have begun to spread around the world, with two Hierodula species overlapping in Europe and two Tenodera species doing the same in North America. Such an event can lead to possible competition with both local taxa and alien congeneric sister species; the latter may reduce the impact of one of the invaders. Additionally, the situation allows the comparisons of niche shifts in displaced mantises, allowing us to understand whether such animals respect general patterns shown in terrestrial ectothermic invasive species. To do this, I adapted scripts from previous publications for analyzing niche overlap (Schoener’s D), niche expansion (E), and unfilling (U) through the centroid shift, overlap, unfilling, and expansion (COUE) scheme using presence records from GBIF and iNaturalist Research-Grade observations and bioclimatic variables available in BIOCLIM, selected according to variance inflation factor (VIF) values. I also evaluated the overlap between the sister species in the non-native range with D. Overall, there was relatively high niche expansion and unfilling patterns shared among the taxa, although species tended to have low abiotic overlap between native and alien ranges, and a relatively high niche overlap was present among congeneric species in the shared non-native area. However, such analyses may be biased due to chosen variables, taxonomic uncertainty, and lack of information on mantises’ ecology; particularly, the situation regarding H. tenuidentata/transcaucasica should be monitored and clarified, given the higher potential invasion risk of these species compared to other mantises and the uncertainties regarding which populations have reached Europe. Additionally, the biology of alien mantises should be studied in more detail in both native and non-native environments given the current critical lack of information.
La crisis ambiental por el cambio climático ha obligado a muchos Estados a dirigir esfuerzos hacia la transición medioambiental para reducir la probabilidad de ocurrencia de una situación con un impacto negativo sobre su población o medioambiente. El Perú no es la excepción. En tal sentido, surge la necesidad de identificar y categorizar sus distritos según un determinado riesgo socioambiental. Ante tal reto, se construyó e implementó una metodología cuantitativa multietápica, la cual hizo uso tanto del aprendizaje automatizado (supervisado y no supervisado) como de la econometría espacial. Los resultados de la metodología, visualizados a través de índices de riesgo emergentes, evidenciaron la existencia de 165 distritos considerados zonas con riesgo socioambiental (ZRS), ubicados en su mayoría en la franja costera. Finalmente, se concluye que el patrón y replicabilidad del modelo de desarrollo urbanístico en el Perú actualmente no es coherente con los esfuerzos de conservación y preservación del medioambiente.
We integrate foundational theories of meaning with a mathematical formalism of artificial general intelligence (AGI) to offer a comprehensive mechanistic explanation of meaning, communication, and symbol emergence. This synthesis holds significance for both AGI and broader debates concerning the nature of language, as it unifies pragmatics, logical truth conditional semantics, Peircean semiotics, and a computable model of enactive cognition, addressing phenomena that have traditionally evaded mechanistic explanation. By examining the conditions under which a machine can generate meaningful utterances or comprehend human meaning, we establish that the current generation of language models do not possess the same understanding of meaning as humans nor intend any meaning that we might attribute to their responses. To address this, we propose simulating human feelings and optimising models to construct weak representations. Our findings shed light on the relationship between meaning and intelligence, and how we can build machines that comprehend and intend meaning.
Autoimmune encephalitis (AE) is a neurological emergency. We aimed to analyze the application and effectiveness of the currently available prediction tools for AE patients in Taiwan. We retrospectively collected 27 AE patients between January 2008 and December 2019. Antibody Prevalence in Epilepsy (APE) score, Response to Immunotherapy in Epilepsy (RITE) score, and anti-NMDAR Encephalitis One Year Functional Status (NEOS) score were applied to validate their usability. Based on the defined cutoff values, the sensitivity and specificity of each score were calculated. A receiver operating characteristic (ROC) curve and the area under the curve (AUC) were generated for each scoring system. The AUC value of APE was 0.571. The AUC value of RITE was 0.550. The AUC values for the NEOS score at discharge and long-term follow-up were 0.645 and 0.796, respectively. The performance of APE and RITE scores was suboptimal in the Taiwanese cohort, probably due to the limitations of the small sample size and single ethnicity. On the other hand, the NEOS score performed better on long-term follow-up than at discharge.
Seyeon Oh, Do-Young Rhee, Sosorburam Batsukh
et al.
Caveolin-1 (Cav-1) induces cellular senescence by reducing extracellular signal-regulated kinase (ERK)1/2 phosphorylation and activating p53 via inhibition of mouse double minute 2 homolog (MDM2) and sirtuin 1 (Sirt1), promoting cell cycle arrest and decreasing fibroblast proliferation and collagen synthesis. High-intensity focused ultrasound (HIFU) treatment increases collagen synthesis, rejuvenating skin. Using H<sub>2</sub>O<sub>2</sub>-induced senescent fibroblasts and the skin of 12-month-old mice, we tested the hypothesis that HIFU increases collagen production through Cav-1 modulation. HIFU was administered at 0.3, 0.5, or 0.7 J in the LINEAR and DOT modes. In both models, HIFU administration decreased Cav-1 levels, increased ERK1/2 phosphorylation, and decreased the binding of Cav-1 with both MDM2 and Sirt1. HIFU administration decreased p53 activation (acetylated p53) and p21 levels and increased cyclin D1, cyclin-dependent kinase 2, and proliferating cell nuclear antigen levels in both models. HIFU treatment increased collagen and elastin expression, collagen fiber accumulation, and elastin fiber density in aging skin, with 0.5 J in LINEAR mode resulting in the most prominent effects. HIFU treatment increased collagen synthesis to levels similar to those in Cav-1-silenced senescent fibroblasts. Our results suggest that HIFU administration increases dermal collagen and elastin fibers in aging skin via Cav-1 modulation and reduced p53 activity.
The rotary tillage knife roller, as one of the typical soil-touching parts of the tillage equipment cutting process, is in direct contact with the soil. During the cutting process, there are problems related to structural bending, deformation, and high power consumption, caused by impact and load, and it is difficult to observe the micro-change law of the rotary tillage tool and soil. In view of the above problems, we took the soil of the cotton experimental field in Shihezi, Xinjiang, and the soil-contacting parts of the rotary tillage equipment, specifically the rotary tiller roller, as the research subject. Using the finite-element method (FEM) to simulate the structure of the rotary tiller with different bending angle parameters, we obtained its average stress and deformation position information, and obtained a range linear relationship between the bending angle and the structural performance of the rotary tiller tool. Using discrete element method (DEM)-based simulation to build the corresponding contact model, soil particle model, and soil–rotary tillage knife roll interaction model to simulate the dynamic process of a rotary tillage knife roll cutting soil, we obtained the change rules of the soil deformation area, cutting process energy, cutting resistance, and soil particle movement. By using the orthogonal simulation test and the response surface method, we optimized the kinematic parameters of the rotary tiller roller and the key design parameters of a single rotary tiller. Taking the reduction of cutting power consumption as the optimization goal and considering the influence of the bending angle on its structural performance, the optimal parameter combination was obtained as follows: the forward speed was 900 m/h, the rotation speed was 100 rad/min, the bending angle was 115°, and the minimum power consumption of the cutter roller was 0.181 kW. The corresponding average stress and deformation were 0.983 mm and 41.826 MPa, which were 15.8%, 13%, and 7.9% lower than the simulation results of power consumption, stress, and deformation under the initial parameter setting, respectively. Finally, the effectiveness of the simulation optimization model in reducing power consumption and the accuracy of the soil-cutting simulation were verified by a rotary tilling inter-field test, which provided theoretical reference and technical support for the design and optimization of other typical soil-touching parts of tillage and related equipment, such as disc harrow, ploughshare, and sub-soiling shovel.
Let k be an algebraically closed field of characteristic p>0 and let G be a symplectic or general linear group over k. We consider induced modules for G under the assumption that p is bigger than the greatest hook length in the partitions involved. We give explicit constructions of left resolutions of induced modules by tilting modules. Furthermore, we give injective resolutions for induced modules in certain truncated categories. We show that the multiplicities of the indecomposable tilting and injective modules in these resolutions are the coefficients of certain Kazhdan-Lusztig polynomials. We also show that our truncated categories have a Kazhdan-Lusztig theory in the sense of Cline, Parshall and Scott. This builds further on work of Cox-De Visscher and Brundan-Stroppel.
Iason Batzianoulis, Fumiaki Iwane, Shupeng Wei
et al.
Teaching an assistive robotic manipulator to move objects in a cluttered table requires demonstrations from expert operators, but what if the experts are individuals with motor disabilities? Batzianoulis et al. propose a learning approach which combines robot autonomy and a brain-computer interfacing that decodes whether the generated trajectories meet the user’s criteria, and show how their system enables the robot to learn individual user’s preferred behaviors using less than five demonstrations that are not necessarily optimal.
Proposed mechanism. A Doxorubicin (DOX) targets the BCAA catabolic pathway in TNBCs, by downregulating BCKDK and augmenting clearance of intracellular BCKAs. B Genetic or pharmacological (high BT2 concentration) inhibition of BCKDK results in increased cell death, decreased intracellular BCKAs, dysregulated mitochondrial function, ATP insufficiency, SESN2 activation, and inhibition of mTORC1 signaling and protein synthesis. C BCKDK inhibition (siRNA mediated or low-BT2 concentration) exacerbates DOX-induced cytotoxicity and caspase activity.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cytology