The Important Role Played by Occupational Therapy in the Process of China's Community-Based Rehabilitation System

Community-Based Rehabilitation started in China in the 1990s, which is the inevitable result of the rapid development of social scienceã€technology, and the continuous improvement of economic level and the gradual improvement of people's quality of life.Community-Based Rehabilitation (CBR) is an emerging social medical model that is people-oriented, community-linked, led by rehabilitation therapists and supported by various social forces.Different from the traditional biomedical model, the treatment scope of this model is not limited to individuals, but often extends to groups with common living habits. And this model is not disease-oriented, but with "Do Something" as the core of value

The Synthesizability of Molecules Proposed by Generative Models

The discovery of functional molecules is an expensive and time-consuming process, exemplified by the rising costs of small molecule therapeutic discovery. One class of techniques of growing interest for early-stage drug discovery is de novo molecular generation and optimization, catalyzed by the development of new deep learning approaches. These techniques can suggest novel molecular structures intended to maximize a multi-objective function, e.g., suitability as a therapeutic against a particular target, without relying on brute-force exploration of a chemical space. However, the utility of these approaches is stymied by ignorance of synthesizability. To highlight the severity of this issue, we use a data-driven computer-aided synthesis planning program to quantify how often molecules proposed by state-of-the-art generative models cannot be readily synthesized. Our analysis demonstrates that there are several tasks for which these models generate unrealistic molecular structures despite performing well on popular quantitative benchmarks. Synthetic complexity heuristics can successfully bias generation toward synthetically-tractable chemical space, although doing so necessarily detracts from the primary objective. This analysis suggests that to improve the utility of these models in real discovery workflows, new algorithm development is warranted

Sample Efficiency Matters: A Benchmark for Practical Molecular Optimization

Molecular optimization is a fundamental goal in the chemical sciences and is of central interest to drug and material design. In recent years, significant progress has been made in solving challenging problems across various aspects of computational molecular optimizations, emphasizing high validity, diversity, and, most recently, synthesizability. Despite this progress, many papers report results on trivial or self-designed tasks, bringing additional challenges to directly assessing the performance of new methods. Moreover, the sample efficiency of the optimization--the number of molecules evaluated by the oracle--is rarely discussed, despite being an essential consideration for realistic discovery applications. To fill this gap, we have created an open-source benchmark for practical molecular optimization, PMO, to facilitate the transparent and reproducible evaluation of algorithmic advances in molecular optimization. This paper thoroughly investigates the performance of 25 molecular design algorithms on 23 tasks with a particular focus on sample efficiency. Our results show that most "state-of-the-art" methods fail to outperform their predecessors under a limited oracle budget allowing 10K queries and that no existing algorithm can efficiently solve certain molecular optimization problems in this setting. We analyze the influence of the optimization algorithm choices, molecular assembly strategies, and oracle landscapes on the optimization performance to inform future algorithm development and benchmarking. PMO provides a standardized experimental setup to comprehensively evaluate and compare new molecule optimization methods with existing ones. All code can be found at https://github.com/wenhao-gao/mol_opt

Technical Difficulties and Countermeasures of Drilling of Φ118mm Sidetracking Horizontal Well in Changqing Oilfield

The boreholes of the horizontal side-drilled wells with casing windows in Changqing Oilfield are all Φ118mm. Difficulties in the construction of small-hole drilling include high landing risk in the horizontal section, difficulty in slope prediction and trajectory control, and limited extension capacity of small wellbore. By optimizing the trajectory of the borehole, designing the trajectory adjustment section before the horizontal landing well, and introducing the equilibrium trend angle method to predict the slope of the directional tool, we improved the trajectory control ability; by calculating the stability of the drill string and the loss of cyclic pressure and analyzing the displacement extension ability, we optimized drill string selection and formed a precise trajectory control method based on sidetrack horizontal well trajectory optimization. Based on the analysis of displacement and extension ability, a non-standard drill pipe with a large diameter of 88.9mm and a small hydrophthalmia was selected. It is considered that the technical countermeasures and suggestions in this paper are of good reference and guiding significance for the development of sidetracked horizontal wells drilling in Changqing Oilfield

Seasonal variability does not impact in vitro fertilization success

Peer reviewedPublisher PD

Xe Affinities of Water-Soluble Cryptophanes and the Role of Confined Water

Given their relevance to drug design and chemical sensing, host–guest interactions are of broad interest in molecular science. Natural and synthetic host molecules provide vehicles for understanding selective molecular recognition in aqueous solution. Here, cryptophane–Xe host–guest systems are considered in aqueous media as a model molecular system that also has important applications. 129Xe–cryptophane systems can be used in the creation of biosensors and powerful contrast agents for magnetic resonance imaging applications. Detailed molecular information on the determinants of Xe affinity is difficult to obtain experimentally. Thus, molecular simulation and free energy perturbation methods were applied to estimate the affinities of Xe for six water-soluble cryptophanes. The calculated affinities correlated well with the previously measured experimental values. The simulations provided molecular insight on the differences in affinities and the roles of conformational fluctuations, solvent, and counter ions on Xe binding to these host molecules. Displacement of confined water from the host interior cavity is a key component of the binding equilibrium, and the average number of water molecules within the host cavity is correlated with the free energy of Xe binding to the different cryptophanes. The findings highlight roles for molecular simulation and design in modulating the relative strengths of host–guest and host–solvent interactions

Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

Ferroptosis is a newly identified form of regulated cell death that is associated with iron metabolism and oxidative stress. As a physiological mechanism, ferroptosis selectively removes cancer cells by regulating the expression of vital chemical molecules. Current findings on regulation of ferroptosis have largely focused on the function of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), in mediating ferroptotic cell death, while the sponging effect of circular RNAs (circRNAs) has not been widely studied. In this review, we discuss the molecular regulation of ferroptosis and highlight the value of circRNAs in controlling ferroptosis and carcinogenesis. Herein, we deliberate future role of this emerging form of regulated cell death in cancer therapeutics and predict the progression and prognosis of oncogenesis in future clinical therapy.publishedVersio