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Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

BackgroundThe incidence of cancer pain increases in discharged patients because of discontinued standard treatments and reductions in medication adherence. Motivated by the need for better pain management in discharged patients, we developed a mobile phone app (Pain Guard) to provide continuous treatment information and feedback to discharged cancer patients suffering from pain. ObjectiveThe aim was to design, construct, and test the Pain Guard app in patients managing cancer pain, evaluate the total remission rate of pain and the improvement in quality of life (QoL) to improve pain management for cancer pain patients, and assess patient acceptance of the app. MethodsThis randomized controlled double-arm study involved 58 patients with cancer pain symptoms. Participants were randomly assigned to a group receiving care through the Pain Guard app (n=31) or to a control group (n=27) who received only traditional pharmaceutical care. In a pretest, participants were rated using a baseline cancer pain assessment and QoL evaluation. During treatment, the consumption levels of analgesic drugs were recorded every week. After a 4-week study period, another round of cancer pain assessment and QoL evaluation was conducted. The system’s usability, feasibility, app compliance, and satisfaction were also assessed. Our primary outcome was remission rate of pain, and secondary outcomes were medication adherence, improvements in QoL, frequency of breakthrough cancer pain (BTcP), incidence of adverse reactions, and satisfaction of patients. ResultsAll participants (N=58) successfully completed the study. There were no significant differences in baseline pain scores or baseline QoL scores between groups. At the end of the study, the rate of pain remission in the trial group was significantly higher than that in the control group (P

In this article, we consider the existence of solutions for nonlinear elliptic equations of the form −Δu+V(∣x∣)u=Q(∣x∣)f(u),x∈R2,-\Delta u+V\left(| x| )u=Q\left(| x| )f\left(u),\hspace{1em}x\in {{\mathbb{R}}}^{2}, where the nonlinear term f(s)f\left(s) has critical exponential growth which behaves like eαs2{e}^{\alpha {s}^{2}}, the radial potentials V,Q:R+→RV,Q:{{\mathbb{R}}}^{+}\to {\mathbb{R}} are unbounded, singular at the origin or decaying to zero at infinity. By combining the variational methods, Trudinger-Moser inequality, and some new approaches to estimate precisely the minimax level of the energy functional, we prove the existence of a Mountain-pass-type solution for the above problem under some weak assumptions.

In this paper, we consider the existence of solutions for nonlinear elliptic equations of the form (0.1)−Δu+V(x)u=f(x,u)+λa(x)∣u∣q−2u,x∈R2,-\Delta u+V\left(x)u=f\left(x,u)+\lambda a\left(x)| u{| }^{q-2}u,\hspace{1em}x\in {{\mathbb{R}}}^{2}, where λ>0\lambda \gt 0, q∈(1,2)q\in \left(1,2), a∈L2/(2−q)(R2)a\in {L}^{2\text{/}\left(2-q)}\left({{\mathbb{R}}}^{2}), V(x)V\left(x), and f(x,t)f\left(x,t) are 1-periodic with respect to xx, and f(x,t)f\left(x,t) has critical exponential growth at t=∞t=\infty . By combining the variational methods, Trudinger-Moser inequality, and some new techniques with detailed estimates for the minimax level of the energy functional, we prove the existence of a nontrivial solution for the aforementioned equation under some weak assumptions. Our results show that the presence of the concave term (i.e. λ>0\lambda \gt 0) is very helpful to the existence of nontrivial solutions for equation (0.1) in one sense.

Background: Medication safety issues occur frequently among older-adult patients with chronic diseases during the transition from the hospital to their homes. Patient participation in medication safety has been found to be an effective measure for improving patient safety. However, few studies have been conducted on the safety of older-adult patients with chronic disease during the hospital to family transition period. This study aimed to understand the experiences and perceptions of such patients regarding participation in medication safety during the hospital to family transition period and to explore the actual situation and obstacles during this period in the Chinese context. Methods: A descriptive, qualitative research approach was adopted using purposive sampling. Eighteen patients with chronic disease (aged 61–84 years) participated, all of whom were in the period of transition from hospital to home. Data were collected through semi-structured face-to-face interviews and analysed using directed qualitative content analysis. Results: Four themes and 12 sub-themes were identified in this study. The four themes were participation in medication decision-making, participation in medication self-management, participation support, and barriers to patient participation. Conclusions: Patient participation is important in ensuring medication safety during the hospital to family transition period. This study highlights that older-adult patients' participation in medication safety includes three aspects: participation in medication decision-making, participation in medication self-management, and participation support. Health literacy, medical communication, and family care support are the key factors affecting patient participation in medication safety. Effective intervention strategies for this patient group during the transition period would target improving patients' cognition, health literacy, doctor-prescription communication, and family care support to encourage patients to be more actively involved in the process of drug treatment. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms. Plain language summary: Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better. [ABSTRACT FROM AUTHOR]

Fungal contamination in rice and mycotoxins present significant challenges to both rice quality and food safety. However, there is a dearth of comprehensive research on the compositional and structural changes within fungal colonies in rice, particularly in typical rice-producing regions, as well as their underlying influencing factors. In this study, a comprehensive analysis of fungal taxa in rice grains was conducted using amplicon sequencing and bioinformatics methods on 99 rice samples collected in three major rice-producing regions in China: Northeast Plain (NP), Yangtze River Basin (YR), and Southeast Coastal Area (SC). A total of 6,019,722 fungal ITS sequences were obtained with an average sequence length of 235 base pairs, and effective ASVs (2014) accounted for approximately 97.58% of the total ASVs (2064). The fungal community diversity in rice grains exhibited significant variations across the three regions, with deterministic processes playing a predominant role in shaping the ecological dynamics of fungal taxa. Among the core microbiota (92 shared ASVs), the first five species (Alternaria, Fusarium, Curvularia, Epicoccum, and Ustilaginoidea) accounting for a proportion greater than 5% had been reported as potential pathogens for plants. Geographical variations in fungal community composition were evident, with a significantly higher number of shared populations observed between YR and CS regions compared to those in the NP region. Nutrient elements and climatic conditions were the internal and external driving factors of rice fungal community composition. Additionally, notable regional variations in fungal functionality were observed. The findings have significant implications for gaining a comprehensive understanding of the distribution patterns of fungal communities in the major rice-producing regions in China. Additionally, it provides valuable insights into controlling key influencing factors to effectively reduce the occurrence of toxin-producing fungi and mitigate the associated risks related to mycotoxin contamination, thereby contributing to improved risk management and assessment. [ABSTRACT FROM AUTHOR]