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Protein S-acylation catalyzed by protein S-acyl transferases (PATs) is a reversible lipid modification regulating protein targeting, stability, and interaction profiles. PATs are encoded by large gene families in plants, and many proteins including receptor-like cytoplasmic kinases (RLCKs) and receptor-like kinases (RLKs) are subject to S-acylation. However, few PATs have been assigned substrates, and few S-acylated proteins have known upstream enzymes. We report that Arabidopsis (Arabidopsis thaliana) class A PATs redundantly mediate pollen tube guidance and participate in the S-acylation of POLLEN RECEPTOR KINASE1 (PRK1) and LOST IN POLLEN TUBE GUIDANCE1 (LIP1), a critical RLK or RLCK for pollen tube guidance, respectively. PAT1, PAT2, PAT3, PAT4, and PAT8, collectively named PENTAPAT for simplicity, are enriched in pollen and show similar subcellular distribution. Functional loss of PENTAPAT reduces seed set due to male gametophytic defects. Specifically, pentapat pollen tubes are compromised in directional growth. We determine that PRK1 and LIP1 interact with PENTAPAT, and their S-acylation is reduced in pentapat pollen. The plasma membrane (PM) association of LIP1 is reduced in pentapat pollen, whereas point mutations reducing PRK1 S-acylation affect its affinity with its interacting proteins. Our results suggest a key role of S-acylation in pollen tube guidance through modulating PM receptor complexes.
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Root growth is sustained by cell division and differentiation of the root apical meristem (RAM), in which brassinosteroid (BR) signaling mediated via the dynamic targeting of BRASSINOSTEROID-INSENSITIVE1 (BRI1) plays complex roles. BRI1 is constitutively secreted to the plasma membrane (PM), internalized, and recycled or delivered into vacuoles, whose PM abundance is critical for BR signaling. Vesicle-target membrane fusion is regulated by heterotetrameric SNARE complexes. SNARE proteins have been implicated in BRI1 targeting, but how SNAREs affect RAM development is unclear. We report that Arabidopsis (Arabidopsis thaliana) YKT61, an atypical R-SNARE protein, is critical for BR-controlled RAM development through the dynamic targeting of BRI1. Functional loss of YKT61 is lethal for both male and female gametophytes. By using weak mutant alleles of YKT61, ykt61-partially complemented (ykt61-pc), we show that YKT61 knockdown results in a reduction of RAM length due to reduced cell division, similar to that in bri1-116. YKT61 physically interacts with BRI1 and is critical for the dynamic recycling of BRI1 to the PM. We further determine that YKT61 is critical for the dynamic biogenesis of vacuoles, for the maintenance of Golgi morphology, and for endocytosis, which may have a broad effect on development. Endomembrane compartments connected via vesicular machinery, such as SNAREs, influence nuclear-controlled cellular activities such as division and differentiation by affecting the dynamic targeting of membrane proteins, supporting a retro-signaling pathway from the endomembrane system to the nucleus.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Brassinosteroides , Divisão Celular , Meristema/genética , Proteínas R-SNARE/genética , Proteínas SNARERESUMO
The prompt species identification from biological samples at a crime scene can rapidly filter out truly valuable biometric information for subsequent personal identification. Meanwhile, early sex determination can assist in narrowing the pool of suspects. However, the current methods for forensic DNA analysis, particularly in point-of-care scenarios, are often limited by the intricate equipment for signal generation and the laborious procedure for DNA purification. The present study introduces a novel portable lateral flow biosensor that possesses extraction-free and anti-aerosol characteristics for on-site determination of species and sex. The bloodstain can be directly submitted to loop-mediated isothermal amplification (LAMP) for the analysis of both mitochondrial and nuclear DNA. The incorporation of a lateral flow device with gold magnetic nanoparticle probes allows for visual interpretation of results through colorimetric signals while also preventing interference on result judgment from pigments such as hemoglobin. Carryover contamination, which is a disharmonious factor in LAMP, especially as the inherent contradiction derived from uncapping in the lateral flow strategy, has been effectively addressed through the integration of uracil DNA glycosylase without compromising the isothermy throughout the process. As a proof-of-concept experiment, species and sex can be accurately identified within 40 min from trace bloodstains amidst significant background interference by targeting cytochrome b and Y-chromosomal amelogenin. Furthermore, the single-blind study revealed a concordance rate of up to 100% in both simulative degraded and true dated bloodstains. This suggests that this biosensor has the potential to be utilized in forensic DNA analysis at crime scenes.
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Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an "axis-referenced coordinate system" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer's disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.
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Atrofia , Demência , Hipocampo , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Atrofia/patologia , Demência/diagnóstico por imagem , Demência/patologia , Masculino , Idoso , Feminino , Processamento de Imagem Assistida por Computador/métodos , Idoso de 80 Anos ou mais , Pessoa de Meia-IdadeRESUMO
Metal-free aqueous batteries can potentially address the projected shortages of strategic metals and safety issues found in lithium-ion batteries. More specifically, redox-active non-conjugated radical polymers are promising candidates for metal-free aqueous batteries because of the polymers' high discharge voltage and fast redox kinetics. However, little is known regarding the energy storage mechanism of these polymers in an aqueous environment. The reaction itself is complex and difficult to resolve because of the simultaneous transfer of electrons, ions and water molecules. Here we demonstrate the nature of the redox reaction for poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl acrylamide) by examining aqueous electrolytes of varying chao-/kosmotropic character using electrochemical quartz crystal microbalance with dissipation monitoring at a range of timescales. Surprisingly, the capacity can vary by as much as 1,000% depending on the electrolyte, in which certain ions enable better kinetics, higher capacity and higher cycling stability.
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Ultrasound coupling is one of the critical challenges for traditional photoacoustic (or optoacoustic) microscopy (PAM) techniques transferred to the clinical examination of chronic wounds and open tissues. A promising alternative potential solution for breaking the limitation of ultrasound coupling in PAM is photoacoustic remote sensing (PARS), which implements all-optical non-interferometric photoacoustic measurements. Functional imaging of PARS microscopy was demonstrated from the aspects of histopathology and oxygen metabolism, while its performance in hemodynamic quantification remains unexplored. In this Letter, we present an all-optical thermal-tagging flowmetry approach for PARS microscopy and demonstrate it with comprehensive mathematical modeling and ex vivo and in vivo experimental validations. Experimental results demonstrated that the detectable range of the blood flow rate was from 0 to 12â mm/s with a high accuracy (measurement error:±1.2%) at 10-kHz laser pulse repetition rate. The proposed all-optical thermal-tagging flowmetry offers an effective alternative approach for PARS microscopy realizing non-contact dye-free hemodynamic imaging.
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Técnicas Fotoacústicas , Tecnologia de Sensoriamento Remoto , Técnicas Fotoacústicas/métodos , Reologia/métodos , Ultrassonografia/métodos , Microscopia/métodosRESUMO
BACKGROUND AND OBJECTIVES: Diagnostic blood loss is a significant factor in the development of anaemia in neonates with very low birth weight. This study aimed to assess the clinical efficacy of intervention approaches involving varying diagnostic blood loss and red blood cell transfusion volumes in neonates with very low birth weights experiencing anaemia during hospitalization. MATERIALS AND METHODS: A total of 785 newborns with anaemia weighing less than 1500 g were enrolled from 32 hospitals in China. The study involved monitoring diagnostic blood loss and red blood cell transfusion and evaluating relevant interventions such as red blood cell transfusion and clinical outcomes. Three intervention approaches were established based on the difference between blood loss and transfusion (Intervention Approaches 0, 1 and 2). The primary outcomes measured were unsatisfactory weight gain during hospitalization and neonatal mortality. The secondary outcomes included related complications. RESULTS: In the non-hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.081-8.431, p = 0.035). Multivariate analysis revealed that Intervention Approach 1 had a protective effect on weight gain. In the hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (OR: 3.335, 95% CI: 1.785-6.234, p = 0.000) and mortality (OR: 5.341, 95% CI: 2.449-11.645, p = 0.000), while Intervention Approach 1 had the lowest incidence of intraventricular haemorrhage. Intervention Approach 1 demonstrated favourable outcomes in both anaemia groups. CONCLUSION: Intervention Approach 1 improved weight gain and reduced mortality and complications in both the non-hospital-acquired and hospital-acquired anaemia groups.
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Transfusão de Eritrócitos , Recém-Nascido de muito Baixo Peso , Humanos , Recém-Nascido , Feminino , Masculino , Estudos Retrospectivos , Hospitalização , Anemia/terapia , Anemia Neonatal/terapia , Anemia Neonatal/sangue , China/epidemiologiaRESUMO
The abnormal activation of Cullin RING E3 Ligases (CRLs) is closely associated with the occurrence and development of various cancers. Targeting the neddylation pathway represents an effective approach for cancer treatment. In this work, we reported that WS-299, structurally featuring a coumarin moiety attached to the triazolopyrimidine, exhibited excellent anti-proliferative activity in MGC-803 and HGC-27 cells. WS-299 exerted potent anticancer effects by inhibiting clone formation, EdU incorporation and inducing cell cycle arrest. WS-299 inhibited CUL3/5 neddylation and caused an obvious accumulation of Nrf2 and NOXA, substrates of CRL3 and CRL5, respectively. Biochemical studies showed that WS-299 inhibited CUL3 neddylation by inhibiting RBX1-UBE2M interaction. The anti-proliferative effect of WS-299 was mainly induced by NOXA-mediated apoptosis. Of note, Nrf2 attenuated WS-299-induced reactive oxygen species (ROS) levels. Furthermore, Nrf2 accumulation also had an antagonistic effect on NOXA-induced apoptosis. Therefore, WS-299 and siNrf2 synergistically increased ROS levels, apoptotic cells and suppressed tumor growth in vivo. Taken together, our research clarified the anti-cancer mechanisms of WS-299 through targeting the RBX1-UBE2M protein-protein interaction and inhibiting the neddylation modification of CUL3 and CUL5. More importantly, our studies also demonstrated that combination of WS-299 with shNrf2 could be an effective strategy for treating gastric cancers.
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Fator 2 Relacionado a NF-E2 , Neoplasias Gástricas , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Pontos de Checagem do Ciclo Celular , Estresse Oxidativo , Proteínas de Transporte/metabolismo , Proteínas Culina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
Developing efficient catalytic systems for water contamination removal is a topic of great interest. However, the use of heterogeneous catalysts faces challenges due to insufficient active sites and electron cycling. In this study, results from first-principles calculations demonstrate that dual reaction centers (DRCs) are produced around the Cu and Mn sites in Cu1.0/Mn1.0-ZnO due to the electronegativity difference. Experimental results reveal the material with DRCs greatly enhances electron transfer efficiency and significantly impacts the oxidation and reduction of peroxymonosulfate (PMS). In addition, the self-consistent potential correction (SCPC) method was introduced to correct the energy and charge of charged periodic systems simulating a catalytic process, resulting in more precise catalytic results. Specifically, the material exhibits a preference for adsorbing negatively charged PMS anions at electron-deficient Mn sites, facilitating PMS oxidation for the generation of 1O2, and PMS reduction around the electron-rich Cu for the formation of â¢OH and SO4â¢-. The major reactive oxygen species is 1O2, showcasing effective performance in various degradation systems. Overall, our work provides novel insights into the persulfate-based heterogeneous catalytic oxidation process, paving the way for the development of high-performance catalytic systems for water purification.
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Óxido de Zinco , Peróxidos , Espécies Reativas de Oxigênio , CatáliseRESUMO
BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.
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INTRODUCTION: As medical students around the world enter their chosen profession, they inherit a system that they did not design nor create, yet are still responsible for it. This system is rooted in centuries of social harm and inequity. This study examines trainees' professional acts of resistance to understand what trainees hope to accomplish in their resistance efforts, why they are resisting, and the tactics they use. METHODS: Drawing on counter-storytelling and critical theory, we collected in-depth qualitative interviews from nine medical students and nine residents/fellows across North America. Using theoretical guidance on how to study acts of resistance, data were analysed using a combination of coding techniques to understand resistors' intentions in resisting and the tactics they used to understand what, why, and how trainees were resisting. The analysis was returned to participants for member checking. RESULTS: Trainees described resisting systems of harm and injustice bequeathed to them by an older generation whose values and practices were reflective of a different time. Their motivations stemmed from deep-seated moral distress from the mistreatment of patients and learners. They hoped to re-envision medical education to be patient- and learner-centred. The tactics they chose depended on the level of power they had in the system and the extent to which they wished to have their efforts known. DISCUSSION: Trainees described intentional and deliberate acts of resistance to the social harm and injustice embedded in the broader profession to re-create the profession. Given that these acts spanned a large geographical area, this study suggests that trainees may be part of a larger social movement aimed at creating widespread change within the profession.
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Educação Médica , Humanos , Comunicação , Princípios Morais , América do NorteRESUMO
BACKGROUND: Much of the literature on harm and injustice in medical education focuses on the impact of oppression rather than trainees' efforts to create change. To acknowledge and make visible these efforts, medical education professionals must grasp how trainees perceive resistance and their role in effecting change. Employing functional linguistic and 'everyday' resistance theories, this critical qualitative study aims to understand trainees' conceptions of resistance practices and their representational choices in moments when they talked about and conceptualised resistance. METHODS: Gathering participants through professional networks and snowball sampling, this study employed in-depth interviews to explore the conceptualisations of resistance among North American medical trainees (9 medical students, 9 residents and fellows). With the use of an applied functional linguistic analysis framework, we analysed the representational metafunction in trainees' conceptualisation of their resistance efforts against social injustice. We began with open coding for 'everyday' acts of resistance and then shifted to focused coding on verbal process types in participants' language to characterise their conceptualisations of resistance. FINDINGS: Participants conceptualised their resistance practices in three distinct ways: first, an almost physical pushing back, drawing largely on material process types (doing); second, an embodied standing up and being present, based predominantly on material and relational process types (being); and third, an epistemic bringing to light, grounded mostly in mental and verbal process types (thinking). These processes of resistance reflect participants' conceptualisations of their efforts to challenge the status quo around inequity, harm and injustice in medical education. CONCLUSION: This study builds on resistance literature, offering a potential typology of resistance practices as pushing back, being and bringing to light. Because these are 'everyday' acts of resistance, these are tactics available to everyone, including faculty; we all have the power to resist, whether it is in teaching and learning or interacting with larger structures in medicine.
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INTRODUCTION: Researchers who study acts of resistance largely focus on efforts when they are at their peak, giving the impression that those who resist are in a constant state of arousal. What is missing in such studies is the variable of time, which is theorised to be intimately connected to power and resistance. To explore this aspect, we followed a group of trainees engaged in professional resistance against social injustice over the period of 1 year to understand how their efforts shifted across time. This longitudinal approach was meant to capture the temporality of resistance, specifically how time affects resistance efforts. METHODS: Using a constructivist grounded theory approach for data collection and analysis, we conducted follow-up interviews with 13 trainees approximately 10 months apart. Interviews were analysed using holistic narrative analysis, in which we analysed contexts, subjectivities and interactions across the two time points. We then conducted a cross-case analysis and restoried the data to develop an understanding of how resistance shifts across time. Finally, we contextualised the data using the metaphor of open and zombie wildfires. RESULTS: The findings demonstrate that when trainees transition to new institutions or professional positions, their access to power and interactions with colleagues shift, thus making it challenging for them to resist in ways they had done so earlier. In transitions where trainees were given power, the flames of resistance continued to blaze visibly. In other cases, without an appreciable change in power, resistance resembled more of a 'zombie fire', smouldering quietly underfoot. DISCUSSION: Examining trainees' acts of resistance across time demonstrates that the work of advocacy and resistance is extremely taxing for trainees. Therefore, when they experience shifts in their context or subjectivity, they conserve energy and strategise their next move. This study provides new insight on the relationship between time and resistance.
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OBJECTIVE: To explore the effect of repetitive transcranial magnetic stimulation (rTMS)-assisted training on lower limb motor function in children with hemiplegic cerebral palsy (HCP). METHOD: Thirty-one children with HCP who met the inclusion criteria were selected and randomly divided into a control group (n = 16) and an experimental group (n = 15). The control group received routine rehabilitation treatment for 30 min each time, twice a day, 5 days a week for 4 weeks. Based on the control group, the experimental group received rTMS for 20 min each time, once a day, 5 days a week for 4 weeks. The outcome measures included a 10-metre walk test (10MWT), a 6-minute walk distance (6MWD) test, D- and E-zone gross motor function measurements (GMFM), the symmetry ratio of the step length and stance time and the muscle tone of the triceps surae and the hamstrings (evaluated according to the modified Ashworth scale), which were obtained in both groups of children before and after treatment. RESULTS: After training, the 10MWT (P < 0.05), 6MWD (P < 0.01), GMFM (P < 0.001) and the symmetry ratio of the step length and stance time of the two groups were significantly improved (P < 0.05), there was more of an improvement in the experimental group compared with the control group. There was no significant change in the muscle tone of the hamstrings between the two groups before and after treatment (P > 0.05). After treatment, the muscle tone of the triceps surae in the experimental group was significantly reduced (P < 0.05), but there was no significant change in the control group (P > 0.05). CONCLUSION: Repetitive TMS-assisted training can improve lower limb motor function in children with HCP.
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Paralisia Cerebral , Estimulação Magnética Transcraniana , Criança , Humanos , Hemiplegia/etiologia , Extremidade Inferior , CaminhadaRESUMO
Southern China and Southeast Asia witnessed some of their most significant economic and social changes relevant to human land use during the Late Holocene, including the intensification and spread of rice agriculture. Despite rice growth being associated with a number of earth systems impacts, how these changes transformed tropical vegetation in this region of immense endemic biodiversity remains poorly understood. Here, we compile a pollen dataset incorporating â¼150,000 identifications and 233 pollen taxa to examine past changes in floral biodiversity, together with a compilation of records of forest decline across the region using 14 pollen records spanning lowland to mountain sites. Our results demonstrate that the rise of intensive rice agriculture from approximately 2,000 y ago led not only to extensive deforestation but also to remarkable changes of vegetation composition and a reduction in arboreal diversity. Focusing specifically on the Tertiary relic tree species, the freshwater wetland conifer Glyptostrobus (Glyptostrobus pensilis), we demonstrate how key species that had survived changing environmental conditions across millions of years shrank in the face of paddy rice farming and human disturbance.
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Efeitos Antropogênicos , Biodiversidade , Ecologia , Plantas/classificação , Sudeste Asiático , Fósseis , PaleontologiaRESUMO
INTRODUCTION: The spatial and temporal patterns of cortical mean diffusivity (cMD), as well as its association with Alzheimer's disease (AD) and suspected non-Alzheimer's pathophysiology (SNAP), are not yet fully understood. METHODS: We compared baseline (n = 617) and longitudinal changes (n = 421) of cMD, cortical thickness, and gray matter volume and their relations to vascular risk factors, amyloid beta (Aß), and tau positron emission tomography (PET), and longitudinal cognitive decline in Aß PET negative and positive older adults. RESULTS: cMD increases were more sensitive to detecting brain structural alterations than cortical thinning and gray matter atrophy. Tau-related cMD increases partially mediated Aß-related cognitive decline in AD, whereas vascular disease-related increased cMD levels substantially mediated age-related cognitive decline in SNAP. DISCUSSION: These findings revealed the dynamic changes of microstructural and macrostructural indicators and their associations with AD and SNAP, providing novel insights into understanding upstream and downstream events of cMD in neurodegenerative disease. HIGHLIGHTS: Cortical mean diffusivity (cMD) was more sensitive to detecting structural changes than macrostructural factors. Tau-related cMD increases partially mediated amyloid beta-related cognitive decline in Alzheimer's disease (AD). White matter hyperintensity-related higher cMD mainly explained the age-related cognitive decline in suspected non-Alzheimer's pathophysiology (SNAP). cMD may assist in tracking earlier neurodegenerative signs in AD and SNAP.
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Wildland fire incident commanders make wildfire response decisions within an increasingly complex socio-environmental context. Threats to human safety and property, along with public pressures and agency cultures, often lead commanders to emphasize full suppression. However, commanders may use less-than-full suppression to enhance responder safety, reduce firefighting costs, and encourage beneficial effects of fire. This study asks: what management, socioeconomic, environmental, and fire behavior characteristics are associated with full suppression and the less-than-full suppression methods of point-zone protection, confinement/containment, and maintain/monitor? We analyzed incident report data from 374 wildfires in the United States northern Rocky Mountains between 2008 and 2013. Regression models showed that full suppression was most strongly associated with higher housing density and earlier dates in the calendar year, along with non-federal land jurisdiction, regional and national incident management teams, human-caused ignitions, low fire-growth potential, and greater fire size. Interviews with commanders provided decision-making context for these regression results. Future efforts to encourage less-than-full suppression should address the complex management context, in addition to the biophysical context, of fire response.
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Incêndios , Incêndios Florestais , Estados Unidos , Humanos , Previsões , Gestão de RiscosRESUMO
BACKGROUND: Artificial intelligence is a growing phenomenon that will soon facilitate wide-scale changes in many professions, and is expected to play an important role in the field of medical education. This study explored the realistic feelings and experiences of nursing undergraduates participating in different stages of artificial intelligence + project task driven learning, and provide a basis for artificial intelligence participation in nursing teaching. METHODS: We conducted face-to-face semi-structured interviews with nursing undergraduates participating in Nursing Research Course which adopts artificial intelligence + project task driven learning from a medical university in Ningxia from September to November 2023, to understand their experience of using artificial intelligence for learning and the emotional changes at different stages. The interview guide included items about their personal experience and feelings of completing project tasks through dialogue with artificial intelligence, and suggestions for course content. Thematic analysis was used to analyze interview data. This study followed the COREQ checklist. RESULTS: According to the interview data, three themes were summarized. Undergraduate nursing students have different experiences in participating in artificial intelligence + project task driven learning at different stages, mainly manifested as diverse emotional experiences under initial knowledge deficiency, the individual growth supported by external forces during the adaptation period, and the expectations and suggestions after the birth of the results in the end period. CONCLUSIONS: Nursing undergraduates can actively adapt to the integration of artificial intelligence into nursing teaching, dynamically observe students' learning experience, strengthen positive guidance, and provide support for personalized teaching models, better leveraging the advantages of artificial intelligence participation in teaching.
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INTRODUCTION: This study aimed to analyze the comprehensive maxillofacial features of patients with skeletal Class III malocclusion and facial asymmetry to develop a classification system for diagnosis and surgical planning. METHODS: A total of 161 adult patients were included, with 121 patients in the asymmetry group (menton deviation >2 mm) and 40 patients in the symmetry group (menton deviation ≤2 mm). Twenty-eight variables were determined, including transverse translation, roll and yaw of each facial unit, transverse width, mandibular morphology, and transverse dental compensation. Principal component (PC) analysis was conducted to extract PCs, and cluster analysis was performed using these components to classify the asymmetry group. A decision tree was constructed on the basis of the clustering results. RESULTS: Six PCs were extracted, explaining 80.622% of the data variability. The asymmetry group was classified into 4 subgroups: (1) atypical type (15.7%) showed an opposite roll direction of maxillary dentition than of menton deviation; (2) compound type (34.71%) demonstrated significant ramus height differences, maxillary roll, and mandibular roll and yaw; (3) mandibular yaw type (44.63%) showed slight mandibular yaw without mandibular morphology asymmetry; and (4) maxillary-shift type (4.96%) shared similarities with the compound type but showed significant maxillary translation. The classification and regression tree model achieved a prediction accuracy of up to 85.11%. CONCLUSIONS: This study identified 4 distinct phenotypes using cluster analysis and proposed tailored treatment recommendations on the basis of their specific characteristics. The classification results emphasized the importance of spatial displacement features, especially mandibular yaw, in diagnosing facial asymmetry. The established classification and regression tree model enables clinicians to identify patients conveniently.
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BACKGROUND: Cardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes (CMs). However, certain animals readily regenerate lost myocardium through a process involving dedifferentiation, which unlocks their proliferative capacities. METHODS: We bred mice with inducible, CM-specific expression of the Yamanaka factors, enabling adult CM reprogramming and dedifferentiation in vivo. RESULTS: Two days after induction, adult CMs presented a dedifferentiated phenotype and increased proliferation in vivo. Microarray analysis revealed that upregulation of ketogenesis was central to this process. Adeno-associated virus-driven HMGCS2 overexpression induced ketogenesis in adult CMs and recapitulated CM dedifferentiation and proliferation observed during partial reprogramming. This same phenomenon was found to occur after myocardial infarction, specifically in the border zone tissue, and HMGCS2 knockout mice showed impaired cardiac function and response to injury. Finally, we showed that exogenous HMGCS2 rescues cardiac function after ischemic injury. CONCLUSIONS: Our data demonstrate the importance of HMGCS2-induced ketogenesis as a means to regulate metabolic response to CM injury, thus allowing cell dedifferentiation and proliferation as a regenerative response.