Inhibition of mitochondrial function by approved drugs overcomes nasopharyngeal carcinoma chemoresistance.

The development of chemo-resistance in nasopharyngeal carcinoma (NPC) presents a significant therapeutic challenge, and its underlying mechanisms remain poorly understood. In our previous studies, we highlighted the association between isoprenylcysteine carboxylmethyltransferase (ICMT) and chemoresistance in NPC. In this current research, we revealed that both 5-FU and cisplatin-resistant NPC cells exhibited elevated mitochondrial function and increased expression of mitochondrial genes, independent of ICMT. Our investigations further showed that classic mitochondrial inhibitors, such as oligomycin, antimycin, and rotenone, were notably more effective in reducing viability in chemo-resistant NPC cells compared to parental cells. Moreover, we identified two antimicrobial drugs, tigecycline and atovaquone, recognized as mitochondrial inhibitors, as potent agents for decreasing chemo-resistant NPC cells by targeting mitochondrial respiration. Remarkably, tigecycline and atovaquone, administered at tolerable doses, inhibited chemo-resistant NPC growth in mouse models and extended overall survival rates. This work unveils the efficacy of mitochondrial inhibition as a promising strategy to overcome chemo-resistance in NPC. Additionally, our findings highlight the potential repurposing of clinically available drugs like tigecycline and atovaquone for treating NPC patients who develop chemoresistance.

Isoprenylcysteine carboxylmethyltransferase is associated with nasopharyngeal carcinoma chemoresistance and Ras activation.

Development of chemo-resistance in nasopharyngeal carcinoma (NPC) poses the therapeutic challenge and its mechanisms are still poorly understood. In this work, we demonstrate that targeting isoprenylcysteine carboxylmethyltransferase (Icmt) is a therapeutic strategy to overcome NPC chemo-resistance. We found that Icmt mRNA and protein levels were increased in NPC cells after prolonged exposure to chemotherapy. Using pharmacological inhibitor cysmethynil or genetic siRNA approaches, we showed that Icmt inhibition was more effective against chemoresistant compared to chemosensitive NPC cells, suggesting that chemoresistant NPC cells is more dependent on Icmt function. The combination of Icmt inhibition with 5-FU or cisplatin resulted in greater efficacy than single chemotherapeutic agent alone in NPC. Notably, we demonstrated that the in vitro observations were translatable to in vivo NPC cancer xenograft mouse model. Mechanism analysis indicated that Icmt inhibition decreased Ras and RhoA activities, leading to the suppression of Ras and RhoA-mediated downstream signaling in NPC cells. The reverse of the inhibitory effects of cysmethynil by constitutively active Ras suggests that Ras is the critical effector of Icmt in NPC cells. Our work is the first to show that Icmt plays an important role in the development of NPC chemoresistance. Our findings also suggest that targeting Icmt represents a promising strategy to inhibit Ras function.

A brief review of monoclonal antibody technology and its representative applications in immunoassays.

Modern immunoassay methods and techniques are important tools in labs of basic biology, biomedicine, clinical medicine, and even in home tests, such as pregnant test, many of which utilize antibody-antigen binding mechanism as their foundational principle in common. Meanwhile, compared with polyclonal anitbody, monoclonal antibody shows obvious advantages in their application of modern immunoassays. Furthermore, the progress of other technologies have also promoted the development of modern immunoassays robustly, and widely made it extend into more research and industry fields. In this review, we will first look back to the discovery of antibody-antigen binding mechanism, antibody structure, and the development of monoclonal antibody technology. Then, a brief description of different classical immunoassays will be introduced, such as enzyme-linked immunosorbent assay, flow cytometry, Immunoprecipitation, and lateral flow immunoassays, through of which, we hope a brief and clear picture can be displayed in front of readers. ABBREVIATIONS: ELISA: Enzyme-Linked Immunosorbent Assay; WB: western blot; Mab: monoclonal antibody; IP: immunoprecipitation; LFIAs: lateral flow immunoassays.

Fast Batch Production of High-Quality Graphene Films in a Sealed Thermal Molecular Movement System.

Chemical vapor deposition (CVD) growth of high-quality graphene has emerged as the most promising technique in terms of its integrated manufacturing. However, there lacks a controllable growth method for producing high-quality and a large-quantity graphene films, simultaneously, at a fast growth rate, regardless of roll-to-roll (R2R) or batch-to-batch (B2B) methods. Here, a stationary-atmospheric-pressure CVD (SAPCVD) system based on thermal molecular movement, which enables fast B2B growth of continuous and uniform graphene films on tens of stacked Cu(111) foils, with a growth rate of 1.5 µm s-1 , is demonstrated. The monolayer graphene of batch production is found to nucleate from arrays of well-aligned domains, and the films possess few defects and exhibit high carrier mobility up to 6944 cm2 V-1 s-1 at room temperature. The results indicate that the SAPCVD system combined with single-domain Cu(111) substrates makes it possible to realize fast batch-growth of high-quality graphene films, which opens up enormous opportunities to use this unique 2D material for industrial device applications.

Construction of a self-reporting molecularly-imprinted electrochemical sensor based on CuHCF modified by rGNR-rGO for the detection of zearalenone.

A self-reporting molecularly-imprinted electrochemical sensor is prepared for the detection of Zearalenone (ZEA). Firstly, the reduced graphene nanoribbons and reduced graphene oxide (rGNR-rGO) were simultaneously modified onto a glassy carbon electrode (GCE) to improve the sensor's sensitivity. After electrodepositing copper nanoparticles onto the rGNR-rGO/GCE, cyclic voltammetry scanning was performed in potassium ferrocyanide solution, and copper hexacyanoferrate (CuHCF) was deposited onto rGNR-rGO/GCE to further improve the sensor's sensitivity while giving it self-reporting capability. Then, molecularly-imprinted polymer films were prepared on the CuHCF/rGNR-rGO/GCE to ensure the selectivity of the sensor. It is found that the linear range of ZEA detection by the constructed sensor is 0.25-500 ng·mL -1, with a detection limit of 0.09 ng·mL -1. This sensor shows the merits of good selectivity, high sensitivity and accurate detection, providing a great possibility for the precise detection of low concentration ZEA in food.

Identification and quality control strategy of impurities in Zhengqing Fengtongning injection.

Zhengqing Fengtongning injection is the sterile aqueous solution of Sinomenine Hydrochloride extracted from the root and stem of Sinomenium acutum, and is widely used to treat rheumatoid arthritis. Due to the processes of extraction, separation, purification, preparation and storage, some related impurities might be formed, which may cause side effects on patients. It is important to rapidly separate and identify the related impurities to ensure the safe use of Zhengqing Fengtongning injection. However, there are few literatures about the impurity in Zhengqing Fengtongning injection. In this work, ultra-high performance liquid chromatography- quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was developed to analyze impurities in both Zhengqing Fengtongning injection and its drug substance, with Sinomenine Hydrochloride as its active pharmaceutical ingredient (API). Six impurities of the Zhengqing Fengtongning injection were found. Structures of impurities 1 and 6 were confirmed by NMR and other impurities were identified from the fragmentation pattern of Sinomenine, the similarity of molecular weight and fragment ions in references. Finally, the HPLC analytical technique was developed to achieve the quantification of impurities 1 and 6. In addition, some reasonable suggestions are put forward on the quality control of Zhengqing Fengtongning injection and its drug substance based on the processes and structural characteristics of the related substances. The technical system established in this paper is helpful to strengthen the quality control of Zhengqing Fengtongning injection and improve production, and can also provide references for the production and quality control of similar drugs.