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The widespread clinical use of statins has contributed to significant reductions of cardiovascular morbidity and mortality. Increasing preclinical and epidemiological evidences have revealed that dyslipidemia is an important risk factor for carcinogenesis, invasion and metastasis, and that statins as powerful inhibitor of HMG-CoA reductase can exert prevention and intervention effects on cancers, and promote sensitivity to anti-cancer drugs. The anti-cancer mechanisms of statins include not only inhibition of cholesterol biosynthesis, but also their pleiotropic effects in modulating angiogenesis, apoptosis, autophagy, tumor metastasis, and tumor microenvironment. Moreover, recent clinical studies have provided growing insights into the therapeutic potentials of statins and the feasibility of combining statins with other anti-cancer agents. Here, we provide an updated review on the application potential of statins in cancer prevention and treatment and summarize the underneath mechanisms, with focuses on data from clinical studies.

To identify the root cause of the abnormal 186Hz vibration amplitude in Stand S4 of a cold rolling mill, this study analyzes the statistical characteristics of two distinct transverse hardness profiles across the strip width. The influence of both individual hardness distributions and their interaction with strip surface morphology on the amplitude frequency response of the Stand S4 is systematically investigated. A novel finite element simulation model is proposed to represent the spatially varying hardness distribution across the strip width, overcoming the limitations of conventional models that assume uniform or single-value hardness. The results demonstrate that the transverse hardness profile is a primary contributor to the excessive vibration at 186Hz. While surface morphology can amplify the vibration amplitude, the degree of amplification is modulated by the underlying hardness statistics. Specifically, the vibration amplitude exhibits a negative correlation with the mean hardness and a positive correlation with the standard deviation of hardness, highlighting the critical role of both average material properties and local non-uniformity in dynamic excitation.

In conventional ancient Chinese poetry learning, students tend to be under-motivated and fail to understand many aspects of poetry. As generative artificial intelligence (GAI) has been applied to education, image-GAI (iGAI) provides great opportunities for students to generate visualized images based on their descriptions of poems, and to situate students in a context similar to what a poem describes. In addition, the progressive prompt is a strategy that can progressively provide students with clues and guidance in technology-enhanced learning environments. Hence, this study proposed a progressive prompts-based image-GAI (PP-iGAI) approach to support students' ancient Chinese poetry learning. To evaluate its effectiveness, the present study employed a quasi-experiment design and recruited 80 fifth-grade elementary school students to engage in one of two conditions: one class was assigned as the experimental group and adopted the PP-iGAI approach, while the other class was assigned as the control group and used the conventional prompt-based iGAI (C-iGAI) approach. The results revealed that the PP-iGAI approach could better promote students' learning achievement, extrinsic motivation, problem-solving awareness, critical thinking, and learning performance. In addition, no significant differences were found in the two groups' cognitive load. Moreover, the results of the interview disclosed the learning perceptions and experiences of both groups. Accordingly, the present study can provide a reference not only for ancient Chinese poetry learning but also for the application of GAI in educational fields for future research.

Olivine lithium iron phosphate is a technologically important electrode material for lithium-ion batteries and a model system for studying electrochemically driven phase transformations. Despite extensive studies, many aspects of the phase transformation and lithium transport in this material are still not well understood. Here we combine operando hard X-ray spectroscopic imaging and phase-field modeling to elucidate the delithiation dynamics of single-crystal lithium iron phosphate microrods with long-axis along the [010] direction. Lithium diffusivity is found to be two-dimensional in microsized particles containing ~3% lithium-iron anti-site defects. Our study provides direct evidence for the previously predicted surface reaction-limited phase-boundary migration mechanism and the potential operation of a hybrid mode of phase growth, in which phase-boundary movement is controlled by surface reaction or lithium diffusion in different crystallographic directions. These findings uncover the rich phase-transformation behaviors in lithium iron phosphate and intercalation compounds in general and can help guide the design of better electrodes. Lithium transport and phase transformation kinetics in olivine LiFePO 4 electrode remain not fully understood. Here the authors show that microsized olivine particles possess 2D lithium diffusivity and exhibit a possible hybrid mode of phase boundary migration upon cycling.

Previous research provided a lot of discussion on the selection of regularization parameters when it comes to the application of regularization methods for high-dimensional regression. The popular “One Standard Error Rule” (1se rule) used with cross validation (CV) is to select the most parsimonious model whose prediction error is not much worse than the minimum CV error. This paper examines the validity of the 1se rule from a theoretical angle and also studies its estimation accuracy and performances in applications of regression estimation and variable selection, particularly for Lasso in a regression framework. Our theoretical result shows that when a regression procedure produces the regression estimator converging relatively fast to the true regression function, the standard error estimation formula in the 1se rule is justified asymptotically. The numerical results show the following: 1. the 1se rule in general does not necessarily provide a good estimation for the intended standard deviation of the cross validation error. The estimation bias can be 50–100% upwards or downwards in various situations; 2. the results tend to support that 1se rule usually outperforms the regular CV in sparse variable selection and alleviates the over-selection tendency of Lasso; 3. in regression estimation or prediction, the 1se rule often performs worse. In addition, comparisons are made over two real data sets: Boston Housing Prices (large sample size n, small/moderate number of variables p) and Bardet–Biedl data (large p, small n). Data guided simulations are done to provide insight on the relative performances of the 1se rule and the regular CV.

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets. KIM1 is dramatically upregulated in acute kidney injury (AKI) and but how KIM1 affects AKI remains unknown. Here, the authors report that renal specific Kim1 knockout relieves AKI, unveil a YY1-KIM1-DR5 axis in the progression of AKI, and suggest potential therapeutic strategies against AKI.

Global obesity epidemics impacts human health and causes obesity-related illnesses, including the obesity-related kidney and liver diseases. UTX, a histone H3K27 demethylase, plays important roles in development and differentiation. Here we show that kidney-specific knockout Utx inhibits high-fat diet induced lipid accumulation in the kidney and liver via upregulating circulating serine levels. Mechanistically, UTX recruits E3 ligase RNF114 to ubiquitinate phosphoglycerate dehydrogenase, the rate limiting enzyme for de novo serine synthesis, at Lys 310 and Lys 330 , which leads to its degradation, and thus suppresses renal and circulating serine levels. Consistently, phosphoglycerate dehydrogenase and serine levels are markedly downregulated in human subjects with diabetic kidney disease or obesity-related renal dysfunction. Notably, oral administration of serine ameliorates high-fat diet induced fatty liver and renal dysfunction, suggesting a potential approach against obesity related metabolic disorders. Together, our results reveal a metabolic homeostasis regulation mediated by a renal UTX-PHGDH-serine axis. Chen et al. report on a renal UTX-phosphoglycerate dehydrogenase axis that regulates serine secretion to affect lipid metabolism in the kidney and liver upon over-nutrition, suggesting potential treatment targets for obesity-related diseases.

Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials. The authors report a Yin-Yang balance between α-Synuclein and β-Synuclein via regulating phase separation in physiological states and Parkinson’s disease. AI-designed peptides mitigate the symptoms and prolong the lifespan of C. elegans PD models.

Metformin is a first-line drug for the clinical treatment of type 2 diabetes; however, it always leads to gastrointestinal tolerance, low bioavailability, short half-life, etc. Liposome acts as an excellent delivery system that could reduce drug side effects and promote bioavailability. Hyodeoxycholic acid, a cholesterol-like structure, can regulate glucose homeostasis and reduce the blood glucose levels. As an anti-diabetic active ingredient, hyodeoxycholic acid modifies liposomes to make it overcome the disadvantages of metformin as well as enhance the hypoglycemic effect. By adapting the thin-film dispersion method, three types of liposomes with different proportions of hyodeoxycholic acid and metformin were prepared (HDCA:ME-(0.5:1)-Lips, HDCA:ME-(1:1)-Lips, and HDCA:ME-(2:1)-Lips). Further, the liposomes were characterized, and the anti-type 2 diabetes activity of liposomes was evaluated. The results from this study indicated that three types of liposomes exhibited different characteristics—Excessive hyodeoxycholic acid decreased encapsulation efficiency and drug loading. In the in vivo experiments, liposomes could reduce the fasting blood glucose levels, improve glucose tolerance, regulate oxidative stress markers and protect liver tissue in type 2 diabetic mice. These results indicated that HDCA:ME-(1:1)-Lips was the most effective among the three types of liposomes prepared and showed better effects than metformin. Hyodeoxycholic acid can enhance the hypoglycemic effect of metformin and play a suitable role as an excipient in the liposome.

Collaborative argumentation allows groups to express, criticize, and integrate arguments to achieve the co-construction of collective knowledge. However, students often face challenges when proposing diversified arguments, gathering evidence, and rebutting others reasonably. Incorporating generative conversational agents (GCAs) into collaborative argumentation has been demonstrated to effectively broaden the perspective of the argument and to stimulate the generation of new ideas. For this study, we designed rhetorical argumentation customized strategies (RACS), dialectical argumentation customized strategies (DACS) for collaborative argumentation, and a mixed-strategy (RACS+DACS), and compared their effects on the quality of argumentation mappings and argumentation discourse patterns. A total of 121 first-year postgraduate students were enrolled: 33 for the control group, 33 for the RACS group, 27 for the DACS group, and 28 for the mixed-strategy group. Results found that: (1) Regarding the quality of argumentation mappings, DACS could help students select high-quality evidence and learn the logical skills from evidence reasoning to claims. In addition, the mixed-strategy could help students search for multiple types of evidence to support their position; (2) Regarding argumentation discourse patterns, in the characteristics of the structural dimension, DACS could help students use evidence to support higher-order claims during argumentation. The mixed-strategy could help students use evidence to rebut others' arguments in group discourses. However, no significant differences were detected among the four groups in the characteristics of the social dimension.