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The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.

The FIC domain-containing protein Sofic has recently been shown to provide robust protection to bacteria against phage infection. Sofic acts as a toxic protein, inducing abortive infection through the AMPylation of target proteins during phage invasion. However, the molecular mechanisms regulating Sofic’s toxic activity remain elusive. In this study, we identified a small gene encoding a short protein located downstream of Sofic in the genome, named AS1 (anti-Sofic1), which functions as an antitoxic protein to counteract Sofic’s toxicity. The crystal structure of Sofic revealed that the protein functions as a dimer in solution, with dimerization being indispensable for its toxic activity. Importantly, structural analysis indicated that ATP binding induces a conformational change in the C-terminal domain (CTD) of Sofic, underscoring the critical role of the CTD in mediating its toxic effects. In vitro colony-forming assays confirmed that the interaction between the CTD and the Amylase domain is crucial for Sofic’s toxic activity. Overall, our results provide molecular insights into the regulatory mechanisms of Sofic in antiviral immunity.

How to perform accurate calculation of heat balance and quantitative analysis of energy efficiency for building clusters is an urgent problem to be solved to reduce building energy consumption and improve energy utilization efficiency. This article proposes a method for the heat balance calculation and energy efficiency analysis of building clusters based on enthalpy and humidity diagrams and applies it to the energy management of building clusters containing primary return air systems and heating pipe networks. Firstly, the basic structure and energy management principle of building clusters with a primary return air system and a heating pipe network were given, and the heat balance calculation and energy efficiency analysis method based on i-d diagram was proposed to realize the accurate calculation of heat load and the quantification of energy utilization. Secondly, the energy management model of the building cluster with a primary return air system and a heating pipe network was established to efficiently manage the indoor temperature and the heating schedule of ASHP, HN and HI. Finally, the proposed method was validated by calculation examples, and the results showed that the proposed method is beneficial for improving the energy economy and energy efficiency of building clusters.

Polydopamine (PDA) as a melanin-like biomimetic material with excellent biocompatibility, full spectrum light absorption capacity and antioxidation property has been extensively applied in the biomedical field. Based on the high reactivity of dopamine (DA), exploiting new strategies to fabricate novel PDA-based nano-biomaterials with controllable size and improved performance is valuable and desirable. Herein, we reported a facile way to synthesize pyrrole-doped polydopamine-pyrrole nanoparticles (PDA-nPY NPs) with tunable size and enhanced near-infrared (NIR) absorption capacity through self-oxidative polymerization of DA with PY in an alkaline ethanol/H2O/NH4OH solution. The PDA-nPY NPs maintain excellent biocompatibility and surface reactivity as PDA. By regulating the volume of added PY, PDA-150PY NPs with a smaller size (<100 nm) and four-fold higher absorption intensity at 808 nm than that of PDA can be successfully fabricated. In vitro and in vivo experiments effectively further demonstrate that PDA-150PY NPs can effectively inhibit tumor growth and completely thermally ablate a tumor. It is believed that these PY doped PDA-nPY NPs can be a potential photothermal (PT) agent in biomedical application.

Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo . The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.

In order to realize the financial quality management of listed energy companies and realize the economical development of enterprises, the author proposes a refined evaluation method for the financial management quality of listed energy companies based on the Internet of Things and the ERP model. By introducing the concept of IoT, ERP and the financial characteristics of listed energy companies select an energy power supply enterprise as a pilot unit, combine the development strategy and the current challenges, and conducting a comprehensive analysis of the process and effect of its implementation of the financial management system, this reflects the superiority of the refined evaluation method of financial management quality of listed energy companies based on the Internet of Things and the ERP model. Pilot experiments show that, comparing before the pilot program, the financial operation status of listed companies has increased by 13.59% in total assets, positive growth achieved. The refined evaluation method of the financial management quality of listed energy companies based on the Internet of Things and the ERP model can realize the economic development of enterprises.

Aim. In order to effectively integrate and rationally allocate the complex information flow of people, finance, and materials in the daily operation of the enterprise and improve the daily operation efficiency and management effect of the enterprise, the author proposes a method for the application of big data and Internet of Things technology in the management of financial operating income of electric power enterprises. The method specifically includes an overview of the relevant theories of financial management based on ERP and an analysis of the needs of a power company’s financial management system based on ERP so as to construct an evaluation index system for the financial management system. The experimental results show that the return on assets of the experimental enterprises has increased from 27.48% in 2015 to 55.18% in 2019, an increase of 27.7%, and the profitability has been continuously enhanced. In 2019, the company achieved a net profit of 392 million yuan, an increase of about 4 times compared with the previous 77 million yuan in 2015. Conclusion. The application can further optimize the allocation of various resources of the enterprise and ensure the effective implementation of the long-term strategy and management goals of the enterprise on the basis of realizing the management needs of the enterprise.

Background The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment. Results Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3. Conclusions EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC.

The emergence and spread of metallo-β-lactamase (MBL)-mediated resistance to β-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse β-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 μM. Investigations of 5l against other B1 MBLs and the serine β-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.

The efficiency of mechanical crushing is a key metric for evaluating machinery performance. However, traditional contact-based methods for measuring this efficiency are unable to provide real-time data monitoring and can potentially disrupt the production process. In this paper, we introduce a non-contact measurement technique for mechanical crushing efficiency based on deep learning algorithms. This technique utilizes close-range imaging equipment to capture images of crushed particles and employs deeply trained algorithmic programs rooted in symmetrical logical structures to extract statistical data on particle size. Additionally, we establish a relationship between particle size and crushing energy through experimental analysis, enabling the calculation of crushing efficiency data. Taking cement crushing equipment as an example, we apply this non-contact measurement technique to inspect cement particles of different sizes. Using deep learning algorithms, we automatically categorize and summarize the particle size ranges of cement particles. The results demonstrate that the crushing efficiencies of ore crushing particles, raw material crushing particles, and cement crushing particles can respectively reach 80.7%, 70.15%, and 80.27%, which exhibit a high degree of consistency with the rated value of the samples. The method proposed in this paper holds significant importance for energy efficiency monitoring in industries that require mechanical crushing.