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Cyclobutanes are popular structural units in bioactive compounds and versatile intermediates in synthetic chemistry, but their synthesis is challenging owing to high ring strain. In this study, a novel method for highly regio‐ and diastereoselective synthesis of fluoroalkylcyclobutanes bearing vicinal quaternary and tertiary stereocenters is realized by a photocatalytic 4‐exo‐trig cyclization cascade of thioalkynes or trifluoromethylalkenes. Density functional theory calculations reveal that a unique fluorine effect, arising from hyperconjugative π→σ*C‐F interactions, accounts for the regio‐reversed radical addition at the sterically hindered alkene carbon, which facilitates an unprecedented 4‐exo‐trig ring closure. This chemistry enables the direct and controllable construction of medicinally valuable quaternary‐carbon‐containing cyclobutanes from readily available raw materials, nicely complementing the existing methods. [ABSTRACT FROM AUTHOR]

Energy management strategy (EMS) is a key technology for plug‐in hybrid electric vehicles (PHEVs). The energy management of certain series–parallel PHEVs involves the control of continuous variables, such as engine torque, and discrete variables, such as clutch engagement/disengagement. Herein, a control‐oriented model is established for a series–parallel plug‐in hybrid system with clutch engagement control from the perspective of mixed‐integer programming. Subsequently, an EMS based on continuous‐discrete reinforcement learning (CDRL), which enables simultaneous output of continuous and discrete variables, is designed. During training, state‐of‐charge (SOC) randomization is introduced to ensure that the hybrid system exhibits optimal energy‐saving performance in both high and low SOC. Finally, the effectiveness of the proposed CDRL strategy is verified by comparing EMS based on charge‐depleting charge‐sustaining (CD‐CS) with rule‐based clutch engagement control and dynamic programming (DP). In the simulation results, it is shown that, under a high SOC, the CDRL strategy proposed in this article can improve energy efficiency by 8.3% compared to CD‐CS, and the energy consumption is just 6.6% higher than the global optimum based on DP, while under a low SOC, the numbers are 4.1% and 3.9%, respectively. [ABSTRACT FROM AUTHOR]

Background The association between vitamin D/calcium and risk of ovarian cancer is still a debatable point. The aim of our study was to systematically investigate the association between vitamin D/calcium, and the risk of ovarian cancer and estimate their dose-response association quantitatively. Methods PubMed, EMBASE, and Web of Science databases were searched to identify relevant observational studies. Two investigators screened citations and extracted data independently. Data were extracted and the association between vitamin D/calcium and ovarian cancer risk was estimated by calculating pooled relative risks (RRs). Subgroup analyses, publication bias estimation, and dose-response analyses were carried out as well. Results In total, 21 articles involving 980,008 participants were included in our present study. No significant association was observed between total vitamin D intake and ovarian cancer risk (RR: 1.02; 95% CI, 0.89-1.16, p = 0.81). Further subgroup analysis suggested that neither dietary vitamin D intake (RR: 0.80; 95% CI, 0.62-1.03, p = 0.09) nor supplementary vitamin D intake (RR: 0.98; 95% CI, 0.85-1.13, p = 0.80) was associated with the risk of ovarian cancer. As for calcium, total calcium intake was found to be statistically inversely associated with ovarian cancer risk in case-control studies (RR: 0.73; 95% CI, 0.63-0.86, p < 0.001) but not in cohort studies (RR: 1.05; 95% CI, 0.90-1.24, p = 0.52). Besides, supplementation with calcium plus vitamin D was not effective for the prevention of ovarian cancer (p = 0.98). Of note, dose-response analysis based on cohort studies suggested a potential inverse U-shape relationship between calcium intake (including total calcium and dietary calcium) and ovarian cancer risk, which indicated that low dose of calcium intake might reduce ovarian cancer risk while high dose of calcium intake might not. Conclusions Taken together, vitamin D could not decrease the risk of ovarian cancer. The role of calcium intake was not proven for reducing ovarian cancer risk. Besides, no evidence showed combinative use of calcium and vitamin D have additional benefits for ovarian cancer prevention., Author(s): Jiawei Xu [sup.1] , Kelie Chen [sup.1] , Fan Zhao [sup.2] , Dongdong Huang [sup.3] , Honghe Zhang [sup.3] , Zhiqin Fu [sup.4] , Jinming Xu [sup.5] , Yongfeng [...]

Reinforcement learning has shown success in solving complex control problems, yet safety remains paramount in engineering applications like energy management systems (EMS), particularly in hybrid electric vehicles (HEVs). An effective EMS is crucial for coordinating power flow while ensuring safety, such as maintaining the battery state of charge within safe limits, which presents a challenging task. Traditional reinforcement learning struggles with safety constraints, and the penalty method often leads to suboptimal performance. This study introduces Lagrangian-based parameterized soft actor–critic (PASACLag), a novel safe hybrid-action reinforcement learning algorithm for HEV energy management. PASACLag utilizes a unique composite action representation to handle continuous actions (e.g., engine torque) and discrete actions (e.g., gear shift and clutch engagement) concurrently. It integrates a Lagrangian method to separately address control objectives and constraints, simplifying the reward function and enhancing safety. We evaluate PASACLag's performance using the World Harmonized Vehicle Cycle (901 s), with a generalization analysis of four different cycles. The results indicate that PASACLag achieves a less than 10% increase in fuel consumption compared to dynamic programming. Moreover, PASACLag surpasses PASAC, an unsafe counterpart using penalty methods, in fuel economy and constraint satisfaction metrics during generalization. These findings highlight PASACLag's effectiveness in acquiring complex EMS for control within a hybrid action space while prioritizing safety. [ABSTRACT FROM AUTHOR]

The macroscopic engineering properties of sandstone are dominated primarily by mineral features in a microscopic scale. This study will investigate the microscopic physical and mechanical properties of the main minerals (quartz, K-feldspar, Na-feldspar and kaolinite) in Yungang Grottoes sandstone, using the molecular mechanics and the molecular dynamics simulations. The microscopic physical properties were represented by density and volume. The microscopic mechanical properties were represented by Young’s modulus and Poisson’s ratio. The microscopic mechanical properties of the minerals in various directions were then explored. The influences of water molecules and the surrounding temperature on the microscopic physical and mechanical properties of the minerals were furthermore investigated. It is found that the differences in the microscopic densities between the simulated results and those from the open data set are, respectively, 0.37%, 1.15% and 9.16%, for the quartz, Na-feldspar and kaolinite cells; the microscopic mechanical properties of various minerals have a significant anisotropy; the Young’s modulus of halloysite decreases by 75.86% compared with that of kaolinite; as the water molecule number increased from 0 to 5, the Young’s moduli of K-feldspar, Na-feldspar and kaolinite cells decreases by 31.31%, 55.05% and 42.60%, respectively; for each mineral, as the temperature increases from 243.15 to 303.15 K under one atmospheric pressure, the volume increases and the density decreases. Those results may have a theoretical significance for the analysis of microscopic mechanism of hydration in the Yungang Grottoes sandstone.

Brunner’s gland adenoma is a rare benign tumor arising from Brunner’s glands. It is mostly small in size, and patients with this tumor are asymptomatic.

In vitro and in vivo models play integral roles in preclinical drug research, evaluation, and precision medicine. In vitro models primarily involve research platforms based on cultured cells, typically in the form of two‐dimensional (2D) cell models. However, notable disparities exist between 2D cultured cells and in vivo cells across various aspects, rendering the former inadequate for replicating the physiologically relevant functions of human or animal organs and tissues. Consequently, these models failed to accurately reflect real‐life scenarios post‐drug administration. Complex in vitro models (CIVMs) refer to in vitro models that integrate a multicellular environment and a three‐dimensional structure using bio‐polymer or tissue‐derived matrices. These models seek to reconstruct the organ‐ or tissue‐specific characteristics of the extracellular microenvironment. The utilization of CIVMs allows for enhanced physiological correlation of cultured cells, thereby better mimicking in vivo conditions without ethical concerns associated with animal experimentation. Consequently, CIVMs have gained prominence in disease research and drug development. This review aimed to comprehensively examine and analyze the various types, manufacturing techniques, and applications of CIVM in the domains of drug discovery, drug development, and precision medicine. The objective of this study was to provide a comprehensive understanding of the progress made in CIVMs and their potential future use in these fields. [ABSTRACT FROM AUTHOR]

Although some simple and rapid colorimetric methods have been developed to detect organophosphorus pesticides (OPs), the difficult extraction and easy denaturation of acetylcholinesterase (AChE) are still drawbacks needing to be overcome. Here, we propose a MOF nanozyme-mediated AChE-free colorimetric strategy for the direct detection of OPs. In the presence of OPs (pirimiphos-methyl as a model), the intense blue of oxidized 3,3′,5,5′-tetramethylbenzidine (TMB) becomes light due to the quenching effect of OPs towards hydroxyl radicals (˙OH) that are generated by the decomposition of H2O2 catalyzed by the Cu4Co6 ZIF nanozyme with excellent peroxidase (POD)-like activity. The developed colorimetric sensor exhibits assay performance and offers a universal and promising analysis strategy for detecting OPs in practical samples. [ABSTRACT FROM AUTHOR]