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Ubiquitination, a multifaceted post-translational modification, regulates protein function, degradation, and gene expression. The pivotal role of ubiquitination in the pathogenesis and progression of cancer, including colorectal, breast, and liver cancer, is well-established. Osteosarcoma, an aggressive bone tumor predominantly affecting adolescents, also exhibits dysregulation of the ubiquitination system, encompassing both ubiquitination and deubiquitination processes. This dysregulation is now recognized as a key driver of osteosarcoma development, progression, and chemoresistance. This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways. We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function. Finally, we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy. By unraveling the impact of ubiquitination on osteosarcoma cell physiology, we aim to facilitate the development of novel strategies for prognosis, staging, treatment, and overcoming chemoresistance.

Abstract The prevalence of age-related degenerative joint diseases, particularly intervertebral disc degeneration and osteoarthritis, is increasing, thereby posing significant challenges for the elderly population. Mitochondrial dysfunction is a critical factor in the etiology and progression of these disorders. Therapeutic interventions that incorporate mitochondrial transplantation exhibit considerable promise by increasing mitochondrial numbers and improving their functionality. Existing evidence suggests that exogenous mitochondrial therapy improves clinical outcomes for patients with degenerative joint diseases. This review elucidates the mitochondrial abnormalities associated with degenerative joint diseases and examines the mechanisms of mitochondrial intercellular transfer and artificial mitochondrial transplantation. Furthermore, therapeutic strategies for mitochondrial transplantation in degenerative joint diseases are synthesized, and the concept of engineered mitochondrial transplantation is proposed.

Abstract Background Pain from osteoarthritis (OA) is one of the top causes of disability worldwide, but effective treatment is lacking. Nociceptive factors are released by activated synovial macrophages in OA, but depletion of synovial macrophages paradoxically worsens inflammation and tissue damage in previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing tissue damage. We aimed to identify key mechanisms mediating synovial macrophage activation and test the role of STAT signaling in macrophages on pain outcomes in experimental knee OA. Methods We induced experimental knee OA in rats via knee destabilization surgery, and performed RNA sequencing analysis on sorted synovial tissue macrophages to identify macrophage activation mechanisms. Liposomes laden with STAT1 or STAT6 inhibitors, vehicle (control), or clodronate (depletion control) were delivered selectively to synovial macrophages via serial intra-articular injections up to 12 weeks after OA induction. Treatment effects on knee and hindpaw mechanical pain sensitivity were measured during OA development, along with synovitis, cartilage damage, and synovial macrophage infiltration using histopathology and immunofluorescence. Lastly, crosstalk between drug-treated synovial tissue and articular chondrocytes was assessed in co-culture. Results The majority of pathways identified by transcriptomic analyses in OA synovial macrophages involve STAT signaling. As expected, macrophage depletion reduced pain, but increased synovial tissue fibrosis and vascularization. In contrast, STAT6 inhibition in macrophages led to marked, sustained improvements in mechanical pain sensitivity and synovial inflammation without worsening synovial or cartilage pathology. During co-culture, STAT6 inhibitor-treated synovial tissue had minimal effects on healthy chondrocyte gene expression, whereas STAT1 inhibitor-treated synovium induced changes in numerous cartilage turnover-related genes. Conclusion These results suggest that STAT signaling is a major mediator of synovial macrophage activation in experimental knee OA. STAT6 may be a key mechanism mediating the release of nociceptive factors from macrophages and the development of mechanical pain sensitivity. Whereas therapeutic depletion of macrophages paradoxically increases inflammation and fibrosis, blocking STAT6-mediated synovial macrophage activation may be a novel strategy for OA-pain management without accelerating tissue damage.

Low back pain (LBP) is a major public health problem worldwide and a significant health and economic burden. Intervertebral disc degeneration (IDD) is the reason for LBP. However, we have not identified effective therapeutic strategies to address this challenge. With accumulating knowledge on the role of circular RNAs in the pathogenesis of IDD, we realised that circular RNAs (circRNAs) may have tremendous therapeutic potential and clinical application prospects in this field. This review presents an overview of the current understanding of characteristics, classification, biogenesis, and function of circRNAs and summarises the protective and detrimental circRNAs involved in the intervertebral disc that have been studied thus far. This review is aimed to help researchers better understand the regulatory role of circRNAs in the progression of IDD, reveal their clinical therapeutic potential, and provide a theoretical basis for the prevention and targeted treatment of IDD.

Background Sleep variability and social jetlag are associated with adverse cardiometabolic outcomes via circadian disruption. Variable eating patterns also lead to circadian disruption, but associations with cardiometabolic health are unknown. Methods and Results Women (n=115, mean age: 33±12 years) completed a 1‐week food record using the Automated Self‐Administered 24‐Hour Dietary Assessment Tool at baseline and 1 year. Timing of first and last eating occasions, nightly fasting duration, and %kcal consumed after 5 pm (%kcal 5 pm) and 8 pm (%kcal 8 pm) were estimated. Day‐to‐day eating variability was assessed from the SD of these variables. Eating jetlag was defined as weekday‐weekend differences in these metrics. Multivariable‐adjusted linear models examined cross‐sectional and longitudinal associations of day‐to‐day variability and eating jetlag metrics with cardiometabolic risk. Greater jetlag in eating start time, nightly fasting duration, and %kcal 8 pm related to higher body mass index and waist circumference at baseline (P

From the perspective of whole-area sponge city construction, it is important to scientifically determine the layout plan of LID facilities for controlling urban rainfall and flooding problems, given the topographical features and rainfall runoff characteristics of shallow urban mountainous areas. Current research on the optimization of low-impact development facilities is limited to the central urban area level, with insufficient research on shallow urban mountainous areas, and there is great uncertainty in the layout of LID facilities when multiple objectives are considered. Therefore, this paper applied a genetic algorithm (NSGA-II) to optimize the layout scheme of LID facilities. Multiple objectives of the peak runoff abatement rate, cost, and land area were selected as the optimization objectives, and the optimized results were ranked using the EWM-TOPSIS and VCWM-TOPSIS methods. The 2nd Hebei Provincial Garden Flower Expo (Qinhuangdao) Park was used as the research object for the optimization design. The results showed that, under the premise of water safety, the lowest cost priority was given to the LID facility with a 15.49% share, 99.43% peak runoff reduction rate, and a cost of CNY 1.215 × 107; the lowest area priority was given to the LID facility with a 15.25% share, 99.42% peak runoff reduction rate, and a cost of CNY 1.267 × 107. The EWM-TOPSIS method was also used to obtain the best optimized solution with 16.18% LID facilities, 99.64% peak runoff abatement rate, and a cost of CNY 1.26 × 107, and the worst optimized solution with 12.55% LID facilities, 97.91% peak runoff abatement rate, and a cost of CNY 1.061 × 107. The decision results under different decision-maker preferences were obtained by the VCWM-TOPSIS method. This study showed that the combination of a genetic algorithm and TOPSIS can optimize the layout of LID facilities in shallow mountainous areas more scientifically and efficiently compared to the actual construction plan for building a sponge city.

Fusobacterium nucleatum (F. nucleatum) is an oral anaerobe that plays a role in several oral diseases. However, F. nucleatum is also found in other tissues of the digestive tract, and several studies have recently reported that the level of F. nucleatum is significantly elevated in malignant tumors of the digestive tract. F. nucleatum is proposed as one of the risk factors in the initiation and progression of digestive tract malignant tumors. In this review, we summarize recent reports on F. nucleatum and its role in digestive tract cancers and evaluate the mechanisms underlying the action of F. nucleatum in digestive tract cancers.

Nightly fasting duration (NFD) and eating timing and frequency may influence cardiometabolic health via their impact on circadian rhythms, which are entrained by food intake, but observational studies are limited. This 1-year prospective study of 116 US women (33 ± 12y, 45% Hispanic) investigated associations of habitual NFD and eating timing and frequency with cardiovascular health (CVH; American Heart Association Life’s Simple 7 score) and cardiometabolic risk factors. NFD, eating timing and frequency, and nighttime eating levels were evaluated from 1-week electronic food records completed at baseline and 1 y. In multivariable-adjusted linear regression models, longer NFD was associated with poorer CVH (β = −0.22, p = 0.016 and β = −0.22, p = 0.050) and higher diastolic blood pressure (DBP) (β = 1.08, p < 0.01 and β = 1.74, p < 0.01) in cross-sectional and prospective analyses, respectively. Later timing of the first eating occasion at baseline was associated with poorer CVH (β = −0.20, p = 0.013) and higher DBP (β = 1.18, p < 0.01) and fasting glucose (β = 1.43, p = 0.045) at 1 y. After adjustment for baseline outcomes, longer NFD and later eating times were also associated with higher waist circumference (β = 0.35, p = 0.021 and β = 0.27, p < 0.01, respectively). Eating frequency was inversely related to DBP in cross-sectional (β = −1.94, p = 0.033) and prospective analyses (β = −3.37, p < 0.01). In cross-sectional analyses of baseline data and prospective analyses, a higher percentage of daily calories consumed at the largest evening meal was associated with higher DBP (β = 1.69, p = 0.046 and β = 2.32, p = 0.029, respectively). Findings suggest that frequent and earlier eating may lower cardiometabolic risk, while longer NFD may have adverse effects. Results warrant confirmation in larger multi-ethnic cohort studies with longer follow-up periods.

In order to maintain robotic manipulators at a high level of performance, their controllers should be able to address nonlinearities in the closed-loop system, such as input nonlinearities. Meanwhile, computational efficiency is also required for real-time implementation. In this paper, an unknown input Bouc−Wen hysteresis control problem is investigated for robotic manipulators using adaptive control and a dynamical gain-based approach. The dynamics of hysteresis are modeled as an additional control unit in the closed-loop system and are integrated with the robotic manipulators. Two adaptive parameters are developed for improving the computational efficiency of the proposed control scheme, based on which the outputs of robotic manipulators are driven to track desired trajectories. Lyapunov theory is adopted to prove the effectiveness of the proposed method. Moreover, the tracking error is improved from ultimately bounded to asymptotic tracking compared to most of the existing results. This is of important significance to improve the control quality of robotic manipulators with unknown input Bouc−Wen hysteresis. Numerical examples including fixed-point and trajectory controls are provided to show the validity of our method.

Background: Advanced practice nurses (APNs) have been responding to worldwide changing patient comorbidities, inequalities within access to care, and a shortage of primary care physicians. The scope of practice for these nurses has been expanding internationally but varies across different jurisdictions. For a period of time during the COVID-19 pandemic, APN trainees' opportunities to work with international mentors in-person were limited. Objective: This study aimed to evaluate the effectiveness of a virtual seminar series in supporting growth in clinical judgment, skills in nursing leadership, and advocacy to optimize APNs' scope of practice. Methods: A preexperimental study was conducted in one cohort of students in the Doctor of Nursing (DN) program at The Chinese University of Hong Kong. A total of 10 prerecorded seminars were presented by nurse practitioners (NPs) in Canada on various disease topics. The evaluation of these seminars focused on the effectiveness of teaching by each speaker and the perceived confidence of learners in carrying out each domain of the APN scope of practice. Results: The study found that the virtual seminar series was effective in improving learners' perceived confidence in carrying out each domain of the APN scope of practice. The perceived teaching effectiveness of each speaker was also evaluated and found to be positive. Conclusions: The virtual seminar series was an effective strategy in supporting newly graduated APNs' professional transitions, particularly when opportunities for collaboration and education were limited due to the COVID-19 pandemic. Implications for Nursing: Mentorship, experiential learning, interprofessional training, and professional socialization are vital strategies for supporting APNs' professional development. The virtual seminar series can be an effective strategy for supporting APNs' scope of practice growth, especially in the current global pandemic context. [ABSTRACT FROM AUTHOR]

Psychoeducation with an active participation component is effective in facilitating family caregivers of people living with dementia to learn about the disease and gain relevant caregiving skills. However, research into the best strategies to promote active participation has received little attention, and the factors hindering active participation are also unknown. Therefore, the nine-stage framework of the Joanna Briggs Institute methodology for scoping reviews was adopted to map and identify information about the active participation of family caregivers of people living with dementia in psychoeducation. The search criteria focused on identifying primary research studies and grey literature relevant to psychoeducation with active participation that had the family caregivers of community dwelling people living with dementia as the target population. Two reviewers independently screened and selected items from the literature. Content analysis was conducted to thematically synthesise strategies mentioned in 29 articles published from 2011 and 2021. Content analysis revealed six strategies that promoted active participation: (1) the involvement of interventionist and qualifications; (2) the teaching and learning methods used to conduct psychoeducation with active participation; (3) tailoring the contents and formats to the experiences, preferences, and resources of the caregivers; (4) collaborating with caregivers; (5) facilitating sharing and support between peers; and (6) providing experiential learning opportunities. Two factors hindering active caregiver participation were negative caregiver emotions and cultural taboos. This review offers ideas for evidence-based practices that can be used by health and social care providers when planning psychoeducation with active participation for the family caregivers of people living with dementia. [ABSTRACT FROM AUTHOR]

Objectives Using a dyadic approach, this study examined the mediating effect of depressive symptoms on the longitudinal relationships between husbands' and wives' memory trajectories and their prospective disability status. Methods Longitudinal data from the Health and Retirement Study 2004–2018 were used. Older (aged 50+) heterosexual couples who had no limitations in the activity of daily living at the baseline (2004) were included (N = 1,310). Latent class growth analysis grouped wives and husbands into distinct memory trajectories in 2004–2014. A structural equation model examined the actor and partner effects of memory trajectories on depressive symptoms in 2016 and disability status in 2018. The mediating effect of depressive symptoms was tested. Results A total of 4 distinct memory trajectories were found: persistently high, high and slow decline, moderate and slow decline, and low and rapid decline. Only the wife's low and rapid decline memory trajectory predicted her own more depressive symptoms (β = 0.588, 95% CI: 0.209, 0.967) and her husband's more depressive symptoms (β = 0.326, 95% CI: 0.004, 0.648). Meanwhile, depressive symptoms had strong and significant actor effects on disability (β = 0.046, 95% CI: = 0.036, 0.057 for wives; β = 0.060, 95% CI: = 0.046, 0.074 for husbands). Discussion The wife's low and rapid declin e trajectory was associated with her own and her husband's more depressive symptoms, which in turn increased the disability risk for both partners. Timely identification and treatment of memory decline among wives have the potential to mitigate couples' depressive symptoms and, ultimately, disability risks. [ABSTRACT FROM AUTHOR]