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The quality of pharmaceuticals has always been a hot issue in the world, and it involves public health, economic development of countries, social stability, and national security. Cleaner production is a prerequisite for ensuring the quality of medicines. However, the various types of counterfeit pharmaceuticals and fake vaccines exposed in the recent years have revealed many problems, such as lacking government regulation, loose quality management of companies, illegal profit of medical service agencies, and failure of patient complaints. This paper’s two innovations are as follows: first, it not only considers the collusion between pharmaceutical companies and medical service agencies, but also introduces patient feedback to study drug quality regulation strategies from a microperspective; second, this paper constructs a tripartite evolutionary game model involving cleaner production pharmaceutical companies, medical service agencies, and the governments to analyze the evolutionary stability using the Lyapunov first rule. The results of the research show that, first, improvement of patient complaint rates can effectively curb collusive behavior and promote the stable improvement of cleaner production drug quality; second, the governments must impose sufficient fines on pharmaceutical companies to avoid a stable strategic combination of collusion; third, enhancing patient feedback can speed up the evolution of the stable choice of legitimate strategies by pharmaceutical companies and the medical service agencies; finally, the government reducing the strict regulation costs can increase the strict regulation rate employed in the evolution process and slow down the pace of evolution to loose regulation. In addition, the simulation analysis was carried out using Matlab 2017b, which verified the validity of the model and proved the practical meaning of countermeasures and suggestions for improving government quality regulation.

Deep brain stimulation (DBS) is widely used to treat Parkinson’s disease (PD), but its efficacy varies. This study aimed to investigate how preoperative structural network influences subthalamic nucleus deep brain stimulation (STN-DBS) outcome in Parkinson’s disease (PD). This study retrospectively collected 93 patients, and divided them into a low improvement group (LIG) and a high improvement group (HIG). Preoperative structural networks were constructed from diffusion tensor images using probability constrained spherical deconvolution algorithm. This study compared topological characteristics between groups and explored the prognostic value of structural networks. Compared to HIG, LIG has a longer normalized characteristic path length and diminished inter-regional connections within left frontal lobe. Normalized characteristic path length is negatively correlated with DBS outcome, while connection strength is positively correlated with DBS outcome. Notably, the fusion method of clinical phenotype and network characteristics has better predictive power for postoperative DBS outcome than either the clinical method or the network method. This study reveals that both normalized characteristic path length and connectivity between the left superior frontal gyrus (central region) and the left medial frontal gyrus (ventral lateral region) are associated with initial DBS efficacy, which could be preoperative biomarkers of DBS outcome.

Manganese-rich NASICON-type materials have triggered widespread attention for developing advanced polyanionic cathodes, primarily driven by their abundant reserves and promising cycling performance with high operating voltages (~3.8 V for Mn 2+/3+/4+ , versus Na + /Na). However, the charge/discharge profiles exhibit significant voltage hysteresis, which leads to a limited reversible capacity, thereby preventing their application. Here, we demonstrate that the voltage hysteresis in manganese-rich NASICON-type cathodes (Na 3 MnTi(PO 4 ) 3 ) is closely related to the intrinsic anti-site defect (IASD), which forms during synthesis and is captured in our characterizations. Combining electrochemical analysis and spectroscopic techniques, we draw a comprehensive picture of sluggish Na + diffusion behaviours in the IASD-affected structure during cycling, and rationalize the relationship of voltage hysteresis, phase separation and delayed charge compensation. Furthermore, a Mo-doping strategy is developed to decrease the defect concentration, which enhances the initial Coulombic efficiency from 76.2% to 85.9%. Overall, this work sheds light on the voltage hysteresis in NASICON-type cathodes and provides guidelines for designing high-performance polyanionic electrodes. Manganese-rich NASICON-type compounds are promising cathode materials for sodium-ion batteries, but they suffer from severe voltage hysteresis. Here the authors uncover the root cause of voltage hysteresis in Na 3 MnTi(PO 4 ) 3 and demonstrate a doping strategy to mitigate the issue.

Solid-state batteries offer an alternative promising power source for electric vehicles. However, the interfacial mechanical stability of inorganic electrolytes is inferior to that of organic electrolytes. A high stack pressure (several to hundreds of megapascals) is often required to maintain intimate contact with electrodes. Here we report a class of viscoelastic inorganic glass (VIGLAS) to serve as solid electrolytes by simply replacing chlorine of tetrachloroaluminates with oxygen. The VIGLAS possesses high ionic conductivity (~1 mS cm − 1 at 30 °C) for both Li + and Na + , superior chemo-mechanical compatibility with 4.3 V cathodes and the ability to enable pressure-less Li- and Na-based solid-state batteries (<0.1 MPa). The low melting temperature (<160 °C) allows the electrolytes to efficiently infiltrate electrode materials, akin to a liquid battery. Additionally, the deformability of the electrolytes facilitates the feasibility of scale-up through the production of thin films via a rolling process. Solid-state electrolytes lie at the heart of the development of solid-state batteries that offer a promising storage technology. Yong-Sheng Hu and colleagues report a class of viscoelastic inorganic glass featuring merits of both inorganic crystalline electrolytes and organic polymer electrolytes and demonstrate pressure-less Li- and Na-based solid-state batteries.

Human bocavirus (HBoV) is a member of the genus Bocavirus, family Parvoviridae, and subfamily Parvovirus and was first identified in nasopharyngeal aspirates of Swedish children with acute respiratory tract infection (ARTI) in 2005. It is the causative agent of nasopharyngeal aspirate disease and death in children. The HboV genomic structure is a linear single-stranded DNA (ssDNA). Its clinical pathogenic characteristics have been extensively studied, however, at present the molecular mechanism underlying the pathogenesis of HBoV infection is not completely clear. In this study, a total of 293 differentially expressed proteins (DEPs) between ARTI cases and healthy plasma samples were characterized using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled bioinformatics analysis, among which 148 were up-regulated and 135 were down-regulated. Gene Ontology (GO) and Cluster of Orthologous Groups of proteins (COG) annotated an enrichment of DEPs in complement activation and biological processes like immunity, inflammation, signal transduction, substance synthesis, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enriched DEPs mainly in the Wnt signaling pathway (ko04310), PPAR signaling pathway (ko03320), intestinal immune network for IgA production (ko04672), complement and coagulation cascades (ko04610), Toll-like receptor signaling pathway (ko04620) and B cell receptor signaling pathway (ko04662). Further, expression levels of three candidate proteins (upregulated PPP2R1A and CUL1, and downregulated CETP) were validated using western blotting. Our investigation is the first analysis of the proteomic profile of HBoV-infected ARTI cases using the iTRAQ approach, providing a foundation for a better molecular understanding of the pathogenesis of ARTI in children.

Over the past approximately 40 years, Chinese drug regulations have undergone many major reforms to accelerate the approval of drugs and keep pace with the scientific innovation of drugs in the world, especially developed countries. In 2018 and 2023 China's National Health Commission in collaboration with other departments released China's \"First Batch of Rare Diseases Catalogue\" and \"Second Batch of Rare Disease Catalogue\". However, there is currently less relevant research on the overview and speed of the approval of rare disease drugs in China. This study used cross-sectional analysis of rare disease drugs approved in China and the USA from 1983 to 2022 through official drug search databases and systematically analyzed and compared rare disease drugs approved in the USA and China, including the number, approval time, related laws and regulations, and expedited programs. Between 1983 and 2022, the USA Food and Drug Administration (FDA) approved a total of 693 orphan drugs (covering 1228 formulations/specifications). Among these, 201 drugs (425 formulations/specifications) were approved by China's National Medical Products Administration (NMPA), accounting for 29.0% (201/693) of the approved drugs and 34.6%(425/1228) of the approved formulations/specifications. The number of China's rare diseases drugs is increasing year by year, and the approval speed has gradually accelerated. The median approval lag time was 32.3 years (IQR: 22.9-33.6) from 1983 to 1987. In contrast, the shortest median lag time occurred between 2018 and 2022, at approximately 1.4 years (IQR: 0.5-2.6)-a reduction of 94.2% that reflects the success of China's ongoing drug regulatory reforms. The special procedures for drug approval have a great promoting effect on rare diseases drugs' approval. This research provides evidence of breakthroughs in the review and approval of rare disease drugs in China and demonstrates the tremendous boost to rare disease drugs from China's ongoing restructuring and reform of the drug regulatory ecosystem, as well as a stimulus for future rare disease drugs development in China.

Abstract Objectives Tibetan pork inhabit plateau regions and engage in extensive exercise. Their meat is firm and less palatable, but appropriate cooking conditions can improve the flavor of the meat. This study aimed to explore the impact of cooking temperature and time on the cooking loss rate, moisture content, tenderness, and color of Tibetan pork to elucidate their effects on the eating quality of this meat. Materials and Methods Physicochemical properties such as cooking losses and tenderness were evaluated, and protein structure was analyzed using Fourier-transform infrared and fluorescence spectroscopy. Results The results indicated a negative correlation between temperature and moisture content, which decreased from 72% to 65% as the temperature increased. Meanwhile, the oxidation of myofibrillar proteins substantially increased with cooking temperature and time, resulting in a gradual augmentation of the cooking loss and shear force of the pork. The migration of bound water and the release of free water from the pork were faster after treatment at 80 °C compared with 50 °C. The results of infrared spectroscopy suggested that prolonged cooking led to the conversion of the α-helix into the β-sheet in the secondary structure of myofibrillar proteins. The microstructures observed through scanning electron microscopy exhibited a gradual degradation of connective tissues in the muscles at high temperatures, and the fiber structure of the muscles became more condensed and granular, blurring the textural appearance of the muscles. Conclusion These results indicated that prolonged cooking time at a low temperature (steaming for 6 h at 50 °C) was conducive to the optimal tenderness of Tibetan pork. This study provides a theoretical basis for improving the meat quality of Tibetan pork products and developing more rational processing methods. Graphical Abstract Graphical Abstract

Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-β1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1’s direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.