Regulation of Energy and Glucose Homeostasis by the Nucleus of the Solitary Tract and the Area Postrema.

The central nervous system regulates feeding, weight and glucose homeostasis in rodents and humans, but the site-specific mechanisms remain unclear. The dorsal vagal complex in the brainstem that contains the nucleus of the solitary tract (NTS) and area postrema (AP) emerges as a regulatory center that impacts energy and glucose balance by monitoring hormonal and nutrient changes. However, the specific mechanistic metabolic roles of the NTS and AP remain elusive. This mini-review highlights methods to study their distinct roles and recent findings on their metabolic differences and similarities of growth differentiation factor 15 (GDF15) action and glucose sensing in the NTS and AP. In summary, future research aims to characterize hormonal and glucose sensing mechanisms in the AP and/or NTS carries potential to unveil novel targets that lower weight and glucose levels in obesity and diabetes.

Maxillary impacted canine replacing a central incisor with root resorption: Multidisciplinary treatment in a preadolescent patient.

Maxillary canines are often impacted, which can result in tooth disorders and adversely affect occlusal and facial development. The case report describes complete bilateral impaction of maxillary canines and significant root resorption of a central incisor. The multidisciplinary approach is the optimal strategy for addressing impacted maxillary canines.

The Effects of Different Developmental Stages on Bone Regeneration of Periodontal Ligament Stem Cells and Periodontal Ligament Cell Sheets In Vitro and Vivo.

Periodontal ligament stem cells (PDLSCs) have broad applications in tissue engineering and regeneration. However, the function of PDLSCs changes in different microenvironments. This study aimed to explore the effects of different developmental stages on the biological characteristics of PDLSCs. Here, PDLSCs were successfully cultured from the periodontal tissues of various groups, including a group with immature roots, a young group with mature roots, and an aging group with mature roots. By comparing the results of the three experimental groups, we found that the donors with immature roots exhibited the best proliferative ability and osteogenic differentiation, while the aging group demonstrated the worst proliferation. The trend for adipogenic differentiation was the opposite to that for osteogenic differentiation. The cell sheet and in vivo experiments revealed that in the immature root group, the cells produced more extracellular matrix (ECM) and new bone and better absorbed the implant materials. These results indicate that PDLSCs perform various functions at different stages of development. In clinical applications of PDLSCs for periodontal regeneration, donors with incompletely developed roots have stronger biological characteristics.

Repurposing Anidulafungin for Alzheimer's Disease via Fragment-Based Drug Discovery.

The misfolding and aggregation of beta-amyloid (Aß) peptides have been implicated as key pathogenic events in the early stages of Alzheimer's disease (AD). Inhibiting Aß aggregation represents a potential disease-modifying therapeutic approach to AD treatment. Previous studies have identified various molecules that inhibit Aß aggregation, some of which share common chemical substructures (fragments) that may be key to their inhibitory activity. Employing fragment-based drug discovery (FBDD) methods may facilitate the identification of these fragments, which can subsequently be used to screen new inhibitors and provide leads for further drug development. In this study, we used an in silico FBDD approach to identify 17 fragment clusters that are significantly enriched among Aß aggregation inhibitors. These fragments were then used to screen anti-infective agents, a promising drug class for repurposing against amyloid aggregation. This screening process identified 16 anti-infective drugs, 5 of which were chosen for further investigation. Among the 5 candidates, anidulafungin, an antifungal compound, showed high efficacy in inhibiting Aß aggregation in vitro. Kinetic analysis revealed that anidulafungin selectively blocks the primary nucleation step of Aß aggregation, substantially delaying Aß fibril formation. Cell viability assays demonstrated that anidulafungin can reduce the toxicity of oligomeric Aß on BV2 microglia cells. Molecular docking simulations predicted that anidulafungin interacted with various Aß species, including monomers, oligomers, and fibrils, potentially explaining its activity against Aß aggregation and toxicity. This study suggests that anidulafungin is a potential drug to be repurposed for AD, and FBDD is a promising approach for discovering drugs to combat Aß aggregation.

The policies on the use of large language models in radiological journals are lacking: a meta-research study.

OBJECTIVE: To evaluate whether and how the radiological journals present their policies on the use of large language models (LLMs), and identify the journal characteristic variables that are associated with the presence. METHODS: In this meta-research study, we screened Journals from the Radiology, Nuclear Medicine and Medical Imaging Category, 2022 Journal Citation Reports, excluding journals in non-English languages and relevant documents unavailable. We assessed their LLM use policies: (1) whether the policy is present; (2) whether the policy for the authors, the reviewers, and the editors is present; and (3) whether the policy asks the author to report the usage of LLMs, the name of LLMs, the section that used LLMs, the role of LLMs, the verification of LLMs, and the potential influence of LLMs. The association between the presence of policies and journal characteristic variables was evaluated. RESULTS: The LLM use policies were presented in 43.9% (83/189) of journals, and those for the authors, the reviewers, and the editor were presented in 43.4% (82/189), 29.6% (56/189) and 25.9% (49/189) of journals, respectively. Many journals mentioned the aspects of the usage (43.4%, 82/189), the name (34.9%, 66/189), the verification (33.3%, 63/189), and the role (31.7%, 60/189) of LLMs, while the potential influence of LLMs (4.2%, 8/189), and the section that used LLMs (1.6%, 3/189) were seldomly touched. The publisher is related to the presence of LLM use policies (p < 0.001). CONCLUSION: The presence of LLM use policies is suboptimal in radiological journals. A reporting guideline is encouraged to facilitate reporting quality and transparency. CRITICAL RELEVANCE STATEMENT: It may facilitate the quality and transparency of the use of LLMs in scientific writing if a shared complete reporting guideline is developed by stakeholders and then endorsed by journals. KEY POINTS: The policies on LLM use in radiological journals are unexplored. Some of the radiological journals presented policies on LLM use. A shared complete reporting guideline for LLM use is desired.

Exploring the reticulo-ruminal motility pattern in goats through medical barium meal imaging technology.

The motility pattern of the reticulo-rumen is a key factor affecting feed intake, rumen digesta residence time, and rumen fermentation. However, it is difficult to study reticulo-ruminal motility using general methods owing to the complexity of the reticulo-ruminal structure. Thus, we aimed to develop a technique to demonstrate the reticulo-ruminal motility pattern in static goats. Six Xiangdong black goats (half bucks and half does, body weight 29.5 ± 1.0 kg) were used as model specimens. Reticulo-ruminal motility videos were obtained using medical barium meal imaging technology. Videos were then analyzed using image annotation and the centroid method. The results showed that reticulo-ruminal motility was divided into primary (stages I, II, III, and IV) and secondary contraction, and the movements of ruminal digesta depended on reticulo-ruminal motility. Our results indicated common motility between the ruminal dorsal sac and ruminal dorsal blind sac. We observed that stages I (3.92 vs. 3.21 s) (P < 0.01), II (4.81 vs. 4.23 s) (P < 0.01), and III (5.65 vs. 5.15 s) (P < 0.05); interval (53.79 vs. 50.95 s); secondary contraction time (10.5 vs. 10 s); and were longer, whereas stage IV appeared to be shorter in the bucks than in the does (7.83 vs. 14.67 s) (P < 0.01). The feasibility of using barium meal imaging technology for assessing reticulo-ruminal and digesta motility was verified in our study. We determined the duration of each stage of reticulo-ruminal motility and collected data on the duration and interval of each stage of ruminal motility in goats. This research provides new insights for the study of gastrointestinal motility and lays a solid foundation for the study of artificial rumen.

GRADE Guidance 39: Using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

INTRODUCTION: The GRADE-ADOLOPMENT methodology has been widely used to adopt, adapt or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. This guidance refines the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings and email communications, the GRADE-ADOLOPMENT Project Group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned Adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE Working Group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people) and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing EtDs when available or developing new EtDs if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over six years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.

Association of Life's Essential 8 cardiovascular health with breast cancer incidence and mortality according to genetic susceptibility of breast cancer: a prospective cohort study.

BACKGROUND: Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life's Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women. METHODS: We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage. RESULTS: A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70-0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36-0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60-0.87) and mortality (HR: 0.29, 95% CI: 0.10-0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43-8.84). CONCLUSIONS: The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.

Association between heavy metals exposure and persistent infections: the mediating role of immune function.

Introduction: Persistent infections caused by certain viruses and parasites have been associated with multiple diseases and substantial mortality. Heavy metals are ubiquitous environmental pollutants with immunosuppressive properties. This study aimed to determine whether heavy metals exposure suppress the immune system, thereby increasing the susceptibility to persistent infections. Methods: Using data from NHANES 1999-2016, we explored the associations between heavy metals exposure and persistent infections: Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Hepatitis C Virus (HCV), Herpes Simplex Virus Type-1 (HSV-1), Toxoplasma gondii (T. gondii), and Toxocara canis and Toxocara cati (Toxocara spp.) by performing logistic regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Mediation analysis was used to determine the mediating role of host immune function in these associations. Results: Logistic regression analysis revealed positive associations between multiple heavy metals and the increased risk of persistent infections. In WQS models, the heavy metals mixture was associated with increased risks of several persistent infections: CMV (OR: 1.58; 95% CI: 1.17, 2.14), HCV (OR: 2.94; 95% CI: 1.68, 5.16), HSV-1 (OR: 1.25; 95% CI: 1.11, 1.42), T. gondii (OR: 1.97; 95% CI: 1.41, 2.76), and Toxocara spp. (OR: 1.76; 95% CI: 1.16, 2.66). BKMR models further confirmed the combined effects of heavy metals mixture and also identified the individual effect of arsenic, cadmium, and lead. On mediation analysis, the systemic immune inflammation index, which reflects the host's immune status, mediated 12.14% of the association of mixed heavy metals exposure with HSV-1 infection. Discussion: The findings of this study revealed that heavy metals exposure may increase susceptibility to persistent infections, with the host's immune status potentially mediating this relationship. Reducing exposure to heavy metals may have preventive implications for persistent infections, and further prospective studies are needed to confirm these findings.

Negative Emotions Are Associated With Older Self-perceived Age: A Cross-section Study From the UK Biobank.

BACKGROUND: Prior research has indicated a potential connection between psychological stress and how individuals perceive their own age. Building on this foundation, the current study explores the relationship between negative emotions and self-perceived age. METHODS: We conducted a cross-sectional analysis using data from the UK Biobank, a comprehensive cohort study representing the UK population. The analysis included 347 892 participants, aged between 39 and 73 years, of which 184 765 were women, accounting for 53.1% of the sample. Participants were categorized into three groups based on their self-perceived age: feeling younger than their chronological age (group Younger), feeling older than their chronological age (group Older), and feeling as old as their actual age (group Same). To investigate the relationship between negative emotions and self-perceived age, we utilized a multinomial logistic regression model with the Younger group serving as the reference category. RESULTS: Of 347 892 participants, after adjusted for covariates, the results showed that participants with irritability, nervous feelings, worrier/anxious feelings or fed-up feelings, worry too long and loneliness/isolation are more likely to be rated as "about your age" or "older than you are," with "younger than you are" as the reference group, indicating that negative emotions may influence one's self-perceived age. Among those negative emotions, irritability has the most significant impact self-perceived age, with the odds ratios (ORs) being 1.44 (95% CI: 1.35-1.54) and 1.11 (95% CI: 1.09-1.14). CONCLUSION: Negative emotions are associated with older self-perceived age, and irritability has the greatest impact. Further studies analyzing self-perceived age are needed to take psychological factors into consideration.

Advances and clinical challenges of mesenchymal stem cell therapy.

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stem cells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and non-genetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions.

The efficacy and tendency of the gender digital divide and Smart Aging Policy in China.

China is one of the most rapidly aging countries in the world, challenging the sustainable aging. The booming of digital technology is a double-edged sword. According to the Smart Aging Policies (SAPs), digital technology is supposed to be an effective way to address the challenges of the elder care system. However, the digital divide is causing additional problems. In this study, researchers aim to investigate whether the digital divide among older people could lead to gender-based discrepancies in elder care utilization, using data from the "China Elder Care Satisfaction Survey (CECSS)." Through logit regression analysis, in this study, researchers assessed the relationship between gender and digital elder care utilization, indicating the presence of a gender digital divide among older people. Our findings have important implications for facilitating minority groups to benefit more from SAPs and for advancing research on the gender digital divide among elders to promote sustainable aging.

Progression of frailty and cardiovascular outcomes among Medicare beneficiaries.

BACKGROUND: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. METHODS: To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. RESULTS: There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). CONCLUSIONS: In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression.

Construction and Identification of Eukaryotic Expression Vector pEGFP-N1-MIC-1 for Mouse MIC-1 Gene and Its Effect on Gastric Cancer Cells.

This study aimed to construct an eukaryotic expression vector, pEGFP-N1-MIC-1, for overexpressing the mouse macrophage inhibitory cytokine-1 (MIC-1) gene. Additionally, we transfected the MFC cell line to observe the upregulation of MIC-1 gene expression and assess its impact on macrophage phenotype conversion. Enzyme digestion and DNA sequencing confirmed the successful construction of the pEGFP-N1-MIC-1 vector. The transfected MFC cells exhibited a significant increase in MIC-1 protein expression levels. Furthermore, transfection with pEGFP-N1-MIC-1 increased the migration and colony formation capabilities of MFC cells. These results may contribute to future research and the development of therapeutic interventions targeting MIC-1 in macrophages, particularly in the context of gastric cancer.

The Role of Fluid Mechanics in Coronary Atherosclerotic Plaques: An Up-to-Date Review.

Most acute coronary syndromes are due to a sudden luminal embolism caused by the rupturing or erosion of atherosclerotic plaques. Prevention and treatment of plaque development have become an effective strategy to reduce mortality and morbidity from coronary heart disease. It is now generally accepted that plaques with thin-cap fibroatheroma (TCFA) are precursors to rupturing and that larger plaques and high-risk plaque features (including low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification) constitute unstable plaque morphologies. However, plaque vulnerability or rupturing is a complex evolutionary process caused by a combination of multiple factors. Using a combination of medicine, engineering mechanics, and computer software, researchers have turned their attention to computational fluid mechanics. The importance of fluid mechanics in pathological states for promoting plaque progression, inducing plaque tendency to vulnerability, or even rupture, as well as the high value of functional evaluation of myocardial ischemia has become a new area of research. This article reviews recent research advances in coronary plaque fluid mechanics, aiming to describe the concept, research implications, current status of clinical studies, and limitations of fluid mechanic's characteristic parameters: wall shear stress (WSS), axial plaque shear (APS), and fractional flow reserve (FFR). Previously, most computational fluid dynamics were obtained using invasive methods, such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). In recent years, the image quality and spatial resolution of coronary computed tomography angiography (CCTA) have greatly improved, making it possible to compute fluid dynamics by noninvasive methods. In the future, the combination of CCTA-based anatomical stenosis, plaque high-risk features, and fluid mechanics can further improve the prediction of plaque development, vulnerability, and risk of rupturing, as well as enabling noninvasive means to assess the degree of myocardial ischemia, thereby providing an important aid to guide clinical decision-making and optimize treatment.

Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0/G1 arrest and mitochondrial apoptosis.

Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ's effects on MM are unclear. We investigated CTZ's effect on MM cell proliferation and apoptosis induction mechanisms. CTZ's effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Screening of optimal cleaning methods to reduce microplastic residues on strawberry surfaces: Characterization of microplastics in strawberry wash water.

Microplastics are widespread in facility strawberry greenhouses and can be deposited on the surface of strawberries through air currents. Investigating effective cleaning methods represents a viable strategy to reduce human ingestion of MPs. Therefore, different cleaning methods were compared: ultrasonic cleaning for 30 min, deionized water rinsing once, deionized water immersion for 30 min, and fruit immersion in washing salt for 30 min. The MPs in strawberry washing water were analyzed and compared using laser direct infrared imaging to investigate their characteristics and the optimal reduction of MPs on the surface of strawberries. The quality of the cleaning results was in the following order: water immersion > washing salt immersion > water rinsing > ultrasound. Water immersion was 1.3-2 times more effective in removing microplastics than other treatments. Furthermore, 21 polymer types were detected in the samples. Most MPs were less than 50 µm in size. The main polymers in this size range were polyamide, chlorinated polyethylene, and polyethylene terephthalate, and they mainly existed as fragments, fibers, and beads. This study provides a valuable reference for reducing human intake of microplastics through fresh fruits and vegetables.

Multi-degradation-adaptation network for fundus image enhancement with degradation representation learning.

Fundus image quality serves a crucial asset for medical diagnosis and applications. However, such images often suffer degradation during image acquisition where multiple types of degradation can occur in each image. Although recent deep learning based methods have shown promising results in image enhancement, they tend to focus on restoring one aspect of degradation and lack generalisability to multiple modes of degradation. We propose an adaptive image enhancement network that can simultaneously handle a mixture of different degradations. The main contribution of this work is to introduce our Multi-Degradation-Adaptive module which dynamically generates filters for different types of degradation. Moreover, we explore degradation representation learning and propose the degradation representation network and Multi-Degradation-Adaptive discriminator for our accompanying image enhancement network. Experimental results demonstrate that our method outperforms several existing state-of-the-art methods in fundus image enhancement. Code will be available at https://github.com/RuoyuGuo/MDA-Net.