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Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion: These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

Abstract S-palmitoylation is a reversible and widespread post-translational modification, but its role in the regulation of ferroptosis has been poorly understood. Here, we elucidate that GPX4, an essential regulator of ferroptosis, is reversibly palmitoylated on cysteine 66. The acyltransferase ZDHHC20 palmitoylates GPX4 and increases its protein stability. ZDHHC20 depletion or inhibition of protein palmitoylation by 2-BP sensitizes cancer cells to ferroptosis. Moreover, we identify APT2 as the depalmitoylase of GPX4. Genetic silencing or pharmacological inhibition of APT2 with ML349 increases GPX4 palmitoylation, thereby stabilizing the protein and conferring resistance to ferroptosis. Notably, disrupting GPX4 palmitoylation markedly potentiates ferroptosis in xenografted and orthotopically implanted tumor models, and inhibits tumor metastasis through blood vessels. In the chemically induced colorectal cancer model, knockout of APT2 significantly aggravates cancer progression. Furthermore, pharmacologically modulating GPX4 palmitoylation impacts liver ischemia–reperfusion injury. Overall, our findings uncover the intricate network regulating GPX4 palmitoylation, highlighting its pivotal role in modulating ferroptosis sensitivity.

Abstract Triple-negative breast cancer (TNBC) is a diverse category with a subset that displays particularly aggressive characteristics, referred to in this study as “rapid relapse” TNBC (rrTNBC). This term is defined as the occurrence of distant metastasis or death within 24 months post-diagnosis. The paper mainly studies the clinicopathologic traits of TNBC patients experiencing rapid disease progression and chemotherapy resistance and identify predictive markers for this outcome. A retrospective evaluation was conducted on 2294 TNBC patients who underwent surgery at Tianjin Medical University Cancer Hospital. Of these, 369 were categorized as experiencing rapid relapse, while 1925 did not relapse rapidly. Logistic regression analysis was applied to determine potential markers predictive of rapid relapse post-chemotherapy. Both univariate and multivariate logistic regression analyses pinpointed several predictors of rapid relapse in TNBC patients post-chemotherapy. These include age at diagnosis (≥ 50 years, OR = 0.413, 95% CI: 0.289–0.590), postoperative pathological T staging (T2, OR = 2.557, 95% CI: 1.766–3.703; T3 + T4, OR = 3.725, 95% CI: 1.355–10.454), and N staging (N1, OR = 3.056, 95% CI: 2.021–4.619; N2, OR = 6.917, 95% CI: 3.920–12.206; N3, OR = 24.597, 95% CI: 11.875–50.948). Additionally, sTIL expression (intermediate, OR = 0.204, 95% CI: 0.139–0.300; high, OR = 0.020, 95% CI: 0.011–0.035) and Her2 expression (Her2 1+, OR = 0.470, 95% CI: 0.321–0.688) were identified as protective indicators against rapid relapse. A predictive model incorporating these predictors yielded a C-index of 0.898 in the training set and 0.938 in the validation set, with respective Brier scores of 0.079 and 0.073. The study successfully established and validated a predictive model for rapid disease progression and chemotherapy resistance in TNBC patients post-chemotherapy, demonstrating robust discrimination and accuracy.

[Objective] Marketization of collective commercial construction land is a strategic initiative to prioritize agricultural and rural development. After carrying out the “three land” reform pilot in 2015, China launched the second round of pilot work again in 2023 and put forward new requirements, and the associated practices urgently need the support of relevant theoretical research. The willingness of farmers plays an important role in the implementation of land policies, but there had been relatively few studies on farmers’ awareness and willingness to enter the market, for collectively commercial construction land. Therefore, the research conduct a comparative study of farmers’ willingness to enter the market in pilot and non-pilot areas. [Methods] The research group constructed a Theory of Planned Behavior (TPB) model of farmers’ willingness to enter the market from the three dimensions of behavioral attitudes, subjective norms, and perceptions of behavioral control, and conducted research in 13 prefectural-level cities in Jiangsu Province, which is at the forefront of the marketization of collective commercial construction land in the country, to obtain 1029 valid questionnaires from farmers in pilot and non-pilot areas, and analyzed their willingness to enter the market in both pilot and non-pilot areas using the ordered Probit model. The model compared and analyzed the willingness of farmers to enter the market and its influencing factors in pilot and non-pilot areas. [Results] (1) The proportion of farmers willing to enter the market in pilot areas is 95.2%, while the proportion of farmers willing to enter the market in non-pilot areas is 90.5%. (2) Behavioral attitudes had a significant influence on farmers’ willingness to enter the market. Among them, the level of policy comprehension had a positive and significant effect on the willingness to enter the market, while the attachment to land had a significant negative impact in pilot and non-pilot areas and a negative impact (not significant) in pilot areas. Farmers’market entry mode preference had a significant negative impact in pilot areas, while the transaction method had a significant negative effect on their willingness to enter the market in non-pilot areas. (3) The subjective norms had a significant effect on the farmers’willingness to enter the market. The policy promotion had a positive and significant impact in pilot areas, and the village positions had a positive and significant impact in non-pilot areas. (4) The perception of behavioral control had a significant impact on farmers’ willingness to enter the market, with the impact of agricultural land area on farmers’ willingness to enter the market being opposite in pilot and non-pilot areas. [Conclusion] The overall willingness of farmers in Jiangsu Province to enter the market is relatively high. Policy advocacy contributed significantly to farmers’ willingness to enter the market, and farmers’ recognition of the benefits of entering the market would improve their attitudes and behavioral willingness to enter the market. Therefore, this article put forward corresponding policy recommendations from three aspects, including intensifying policy publicity, standardizing the proportion of government benefit allocation, and developing diversified income payment methods.

Abstract In order to address the problem of data heterogeneity, in recent years, personalized federated learning has tailored models to individual user data to enhance model performance on clients with diverse data distributions. However, the existing personalized federated learning methods do not adequately address the problem of data heterogeneity, and lack the processing of system heterogeneity. Consequently, these issues lead to diminished training efficiency and suboptimal model performance of personalized federated learning in heterogeneous environments. In response to these challenges, we propose FedPRL, a novel approach to personalized federated learning designed specifically for heterogeneous environments. Our method tackles data heterogeneity by implementing a personalized strategy centered on local data storage, enabling the accurate extraction of features tailored to the data distribution of individual clients. This personalized approach enhances the performance of federated learning models when dealing with non-IID data. To overcome system heterogeneity, we design a client selection mechanism grounded in reinforcement learning and user quality evaluation. This mechanism optimizes the selection of clients based on data quality and training time, thereby boosting the efficiency of the training process and elevating the overall performance of personalized models. Moreover, we devise a local training method that utilizes global knowledge distillation of non-target classes, which combined with traditional federated learning can effectively address the issue of catastrophic forgetting during global model updates. This approach enhances the generalization capability of the global model and further improves the performance of personalized models. Extensive experiments on both standard and real-world datasets demonstrate that FedPRL effectively resolves the challenges of data and system heterogeneity, enhancing the efficiency and model performance of personalized federated learning methods in heterogeneous environments, and outperforming state-of-the-art methods in terms of model accuracy and training efficiency.

Abstract This study employed energy-dispersive X-ray fluorescence spectrometry, Raman spectroscopy, X-ray photoelectron spectroscopy, and ultraviolet–visible-near infrared spectrophotometry to analyse eleven overglaze pigment porcelain specimens. The results show that the colouring element of the overglaze yellow pigment of Jingdezhen imperial kilns in the Ming dynasty is Fe2O3, and most of Fe2O3 can be dissolved in the lead glaze in an ionic state to make the lead glaze yellow. The chromogenic of the overglazed yellow pigment primarily depends on the concentration and coordination field of the colouring ions. The connection between the internal structure and the appearance of the overglaze yellow pigment is discussed.

Abstract Background Early-life exposure to famine may influence the occurrence of chronic diseases and aging in midlife among those exposed. This study aims to explore the relationship between exposure to the Chinese Great Famine and aging in middle-aged individuals. Methods Participants born in 1963–1965 (unexposed), 1959–1961 (in utero exposure), and 1955–1957 (childhood exposure) from the Kailuan Study were included. Their biological age at 2010, 2014, and 2018 was investigated, and age acceleration (biological age minus actual age) was calculated to assess aging. Logistic regression analysis was employed to describe the relationship between famine exposure and the aging risk. Subgroup and sensitivity analysis were conducted to explore differences and stability in this relationship among different groups. Results A total of 17,543 participants were included in this study. Among them, 12,762 (72.7%) were male, and 4,781 (27.3%) were female, with 2,543 participants experiencing aging events. Compared to unexposed participants, those exposed during childhood and in utero exhibited a 1.69-fold (OR = 1.69, 95%CI: 1.53–1.87) and 1.22-fold (OR = 1.22, 95%CI: 1.08–1.37) increased risk of aging. Subgroup analysis revealed an interaction with income (P for interaction = 0.008), and additional interaction analysis suggested that increasing income could partially mitigate the detrimental effects of early-life famine exposure. Furthermore, experiencing famine in severely affected regions exacerbated the risk of aging (OR = 1.41, 95%CI: 1.21–1.63). Conclusion Exposure to famine in utero or during childhood may elevate the risk of midlife aging among exposed individuals, and these relationships are influenced by the severity of famine exposure. Increasing income may also help mitigate these effects. Trial registration: Kailuan study, ChiCTRTNRC11001489. Registered July 19, 2015 Retrospectively registered, https//www.chictr.org.cn/showprojEN.html?proj=8050&u_atoken=af46a0dee8d73f320bb5459ab7bbcfa9&u_asig=1a0c381017255295896468605e00cf .

Abstract Membranes with switchable wettability, solvent resistance, and toughness have emerged as promising materials for separation applications. However, challenges like limited mechanical strength, poor chemical stability, and structural defects during membrane fabrication hinder their widespread adoption. Covalent organic frameworks (COFs), crystalline materials constructed from organic molecules connected by covalent bonds, offer a promising solution due to their high porosity, stability, and customizable properties. The ordered structures and customizable functionality provide COFs with a lightweight framework, large surface area, and tunable pore sizes, which have attracted increasing attention for their applications in membrane separations. Recent research has extensively explored the preparation strategies of COF membranes and their applications in various separation processes. This review uniquely delves into the influence of various COF membrane fabrication techniques, including interfacial polymerization, layer‐by‐layer assembly, and in situ growth, on membrane thickness and performance. It comprehensively explores the design strategies and potential applications of these methods, with a particular focus on gas separation, oil/water separation, and organic solvent nanofiltration. Furthermore, future opportunities, challenges within this field, and potential directions for future development are proposed.

Abstract Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.