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Voltage-dependent anion channel 1 (VDAC1) is a pore protein located in the outer mitochondrial membrane. Its channel gating mediates mitochondrial respiration and cell metabolism, and it has been identified as a critical modulator of mitochondria-mediated apoptosis. In many diseases characterized by mitochondrial dysfunction, such as cancer and neurodegenerative diseases, VDAC1 is considered a promising potential therapeutic target. However, there is limited research on the regulatory factors involved in VDAC1 protein expression in both normal and pathological states. In this study, we find that VDAC1 protein expression is up-regulated in various neuronal cell lines in response to intracellular metabolic and oxidative stress. We further demonstrate that VDAC1 expression is modulated by intracellular ATP level. Through the use of pharmacological agonists and inhibitors and small interfering RNA (siRNA), we reveal that the AMPK/PGC-1α signaling pathway is involved in regulating VDAC1 expression. Additionally, based on bioinformatics predictions and biochemical verification, we identify p53 as a potential transcription factor that regulates VDAC1 promoter activity during metabolic oxidative stress. Our findings suggest that VDAC1 expression is regulated by the AMPK/PGC-1α and p53 pathways, which contributes to the maintenance of stress adaptation and apoptotic homeostasis in neuronal cells.

Background: Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited. Objective: We aimed to provide a comprehensive understanding of TDM guidelines for antineoplastic drugs and to promote the development of individualized drug therapy in oncology. Design: This study type is a systematic review. Data sources and methods: This study was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Databases including PubMed, Embase, the official websites of TDM-related associations and Chinese databases were comprehensively searched up to March 2023. Two investigators independently screened the literature and extracted data. The methodological and reporting quality was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT), respectively. Recommendations and quality evaluation results were presented by visual plots. This study was registered in PROSPERO (No. CRD42022325661). Results: A total of eight studies were included, with publication years ranging from 2014 to 2022. From the perspective of guideline development, two guidelines were developed using evidence-based methods. Among the included guidelines, four guidelines were for cytotoxic antineoplastic drugs, three for small molecule kinase inhibitors, and one for antineoplastic biosimilars. Currently available guidelines and clinical practice provided recommendations of individualized medication in oncology based on TDM, as well as influencing factors. With regard to methodological quality based on AGREE II, the average overall quality score was 55.21%. As for the reporting quality by RIGHT evaluation, the average reporting rate was 53.57%. Conclusion: From the perspective of current guidelines, TDM in oncology is now being expanded from cytotoxic antineoplastic drugs to newer targeted treatments. Whereas, the types of antineoplastic drugs involved are still small, and there is still room for quality improvement. Furthermore, the reflected gaps warrant future studies into the exposure–response relationships and population pharmacokinetics models. [ABSTRACT FROM AUTHOR]

Coprophagy prevention (CP) affects the growth performance, hepatic lipid synthesis, and gut microbiota in rabbits. Supplementation with Clostridium butyricum (C. butyricum, Strain number: CCTCC M 2019962) has been found to improve growth performance in rabbits. However, it remains unknown whether C. butyricum can ameliorate the effects of CP on hepatic lipid synthesis and the underlying mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the impact of CP on hepatic lipid synthesis and the underlying mechanism based on the gut–liver axis. The findings revealed that supplementation with C. butyricum could reverse CP-related growth performance, lipid accumulation, bile acid synthesis, and inflammation. Furthermore, C. butyricum exerted protective effects on the gut by preserving intestinal barrier integrity and modulating gut microbiota composition; these factors may represent potential mechanisms through which C. butyricum improves CP-related outcomes. Specifically, C. butyricum reshaped the microbiota by increasing butyric acid levels, thereby maintaining secondary bile acid (deoxycholic acid, chenodeoxycholic acid) balance and attenuating the inhibitory effects of the FXR/SHP pathway on lipid synthesis (SREBP1c/ApoA1). Moreover, the activation of butyrate/GPR43pathway by C. butyricum reduced damage to the intestinal barrier (ZO-1/Occludin/Claudin1) and restored the gut immune microenvironment in CP rabbits. In summary, supplementation with C. butyricum can alleviate the adverse effects of CP on growth performance and hepatic lipid synthesis by modulating the gut–liver axis. [ABSTRACT FROM AUTHOR]

In order to solve problem of limited working travel of coal mine detection robot, a coal mine detection robot was designed, which can independently increase its communication distance and automatically return. When wireless control signal is weakened, the robot will use repeater catapulting system to increase wireless communication distance. When wireless signal is suddenly interrupted, the robot will initiate automatic returning function, and return to a safe place automatically according to sensor data memorized in the scouting process. Automatic returning function of robot adopts integration data method between encoders and laser sensor, uses ICP algorithm to do double data matching and adjust position and orientation gradually of the robot, so as to realize high accuracy in the process of automatic returning. Testing results show that the robot has a long working travel distance and automatic returning function, can work stably and safely at the scene of unknown coal mine disaster, and can replace rescue workers to complete early dangerous detection work in coal mine, provide a significant on-site data information for coal mine rescue.

In the present work, a coupled three-dimensional numerical model of fluid flow, heat transfer, and inclusion motion during the solidification of molten steel in slab continuous casting mold has been developed. Based on the model, this paper has studied the inclusion capture during the process. The influence of the primary dendrite arm spacing on inclusion capture has been considered. The inclusion distributions, total masses, and average diameters at different depth from the slab surface have been given out in the present paper. The simulation results revealed the inclusion concentration existed in the solidification process, and the inclusion capturing area varies with the depth from the slab surface.

Nanosized spinel ferrites MFe2O4 (M = Mn, Co, Ni, Cu, Zn)-coated flaky FeSiAl alloy composites were synthesized successfully. Nano-ferrites preferentially grow into nanoplatelets due to induced or restricted growth on the flaky surface of FeSiAl. With annealing temperature increasing, the ferrites' nanosheets thicken gradually and then grow into irregular particles. The annealing temperature not only affects the nanosized morphology and coating but also the magnetic properties of flaky FeSiAl composites. The saturation magnetization of CuFe2O4- or NiFe2O4-coated FeSiAl is approximate 69 emu/g, where the value of MnFe2O4-, CoFe2O4- and ZnFe2O4-coated FeSiAl show a decreasing trend generally from 64 emu/g to 55.7 emu/g annealing at 800 °C, respectively. The saturation magnetization of flaky FeSiAl composites was improved with the increased annealing temperature, except for those coated with ZnFe2O4 and NiFe2O4. These results are useful for improving the comprehensive properties of ferrite-coated flaky FeSiAl alloy composites. [ABSTRACT FROM AUTHOR]

Laser direct writing of polyimide (PI) film to induce porous graphene as a flexible electrode facilitates the development of efficient, low-cost, and large-scale preparation of flexible planar micro-supercapacitors (MSCs). Nevertheless, current flexible MSCs based on laser-induced graphene (LIG) face bottlenecks such as poor LIG electrode wettability, inhomogeneous doping of heterogeneous components, and limited electrochemical performance. In view of this, a simple and effective process for in situ fabrication of flexible FeOx nanoparticles embedded N-doped LIG (FeOx@NLIG) electrode is developed by laser direct writing in this study. The as-assembled in-plane FeOx@NLIG MSCs exhibit an excellent areal specific capacitance of 13.82 mF cm−2, a remarkable energy density of 1.228 mW h cm−2 at a high power density of 0.024 mW cm−2, good flexibility, and conspicuous cycling stability. Besides, these high-performance in-plane FeOx@NLIG MSCs as a vital micro-energy storage component can be easily miniaturized, modularized, and integrated to suit customized needs of wearable electronics due to great advantages in terms of identicality and stability of the as-fabricated FeOx@NLIG. [ABSTRACT FROM AUTHOR]

Background: Classifying the progression pattern had been proved to be momentous for predicting efficacy and guiding treatment in the 1st/2nd generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), while lack evidence in the 3rd generation EGFR-TKIs. This study aimed to classify tumor progression of osimertinib in EGFR+ advanced non-small cell lung cancer (NSCLC), exploring the characteristics and the clinical significance of each progression pattern., Methods: After screening 1,125 lung cancer patients, 168 EGFR T790M+ advanced patients using osimertinib were enrolled and divided into two groups and five clinical progression models according to the time course of the tumor progression. The prognosis and characteristics, such as gender, age, metastases, of each model were analyzed and compared by Kaplan-Meier method, t- test, and linear regression., Results: Complete follow-up data were available for 117 of the 168 patients. Progressive disease (PD) occurred in 89 patients at an average onset of 6.59 months since using osimertinib, with 79.78% of patients experiencing enlargement of some preexisting lesions before PD. Among the five progression models, the 'Rapid Enlargement' (10.11%) model, the 'Rapid New Lesion' model (10.11%), the 'Delayed Enlargement' model (29.21%), the 'Delayed New Lesion' model (15.73%), and the 'Non-targeted Enlargement' model (34.83%), the 'Non-targeted Enlargement' model had the worst prognosis, with a median progression-free survival (mPFS) of 7.1 months (P=0.046). The mPFS of other models was similar, with the largest difference in the time interval between the beginning of osimertinib treatment to the first appearance of target lesion enlargement (T m-e ). Smoking history (P=0.046) and the location of the initial (P=0.048), enlarged (P=0.003), and progressive lesions (P=0.002) affected the progression models, while gender, age, and treatment lines had no effect. The T m-e was related to the overall disease control time with a correlation coefficient of 0.667 (P=0.000). The appearance of a malignant pleural effusion had an impact on progression., Conclusions: We tried to create a classification system for describing the failure of the third-generation EGFR-TKI osimertinib including two groups, subdivided into five progression models based on the time course of tumor lesion changes. The system might be conducive to predict the prognosis and be potential to assist in selecting subsequent treatment strategies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-315/coif). KI reports personal fees from Boehringer Ingelheim, AstraZeneca, Pfizer, Eli Lilly, Chugai Pharmaceutical, Merk Sharp & Dohme (MSD), Ono Pharmaceutical, Takeda Pharmaceutical and Taiho Pharmaceutical. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)