Strategies for enhancing non-small cell lung cancer treatment: Integrating Chinese herbal medicines with epidermal growth factor receptor-tyrosine kinase inhibitors therapy.

Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.

Chemical control of CRISPR/Cpf1 editing via orthogonal activation and deactivation of crosslinked crRNA.

Through the integration of CRISPR/Cpf1 with optogenetics and a reduction-responsive motif, we have developed a photoactivatable cross-linked crRNA that enables precise genome editing upon light exposure. This system also allows for termination of editing activity through external application of reducing agent. The dual-stimuli-responsive CRISPR/Cpf1 editing process operates in a unique OFF → ON → OFF sequence, making it a valuable tool for investigating time-sensitive biological events.

A Conformational Restriction Strategy for the Control of CRISPR/Cas Gene Editing with Photoactivatable Guide RNAs.

The CRISPR/Cas system is one of the most powerful tools for gene editing. However, approaches for precise control of genome editing and regulatory events are still desirable. Here, we report the spatiotemporal and efficient control of CRISPR/Cas9- and Cas12a-mediated editing with conformationally restricted guide RNAs (gRNAs). This approach relied on only two or three pre-installed photo-labile substituents followed by an intramolecular cyclization, representing a robust synthetic method in comparison to the heavily modified linear gRNAs that often require extensive screening and time-consuming optimization. This tactic could direct the precise cleavage of the genes encoding green fluorescent protein (GFP) and the vascular endothelial growth factor A (VEGFA) protein within a predefined cutting region without notable editing leakage in live cells. We also achieved light-mediated myostatin (MSTN) gene editing in embryos, wherein a new bow-knot-type gRNA was constructed with excellent OFF/ON switch efficiency. Overall, our work provides a significant new strategy in CRISPR/Cas editing with modified circular gRNAs to precisely manipulate where and when genes are edited.

[Intercellular electron transfer and its eco-physiological significance: A review]. / ç»†èŒèƒžé™ ç”µå­è½¬ç§»åŠå ¶ç”Ÿæ€ç”Ÿç†å­¦æ„ä¹‰ç ”ç©¶è¿›å±•.

Intercellular electron transfer (IET) refers to the process within which electrons being indirectly or directly transferred to the exterior of cells and eventually delivered to the electron acceptors around cells. IET widely exists in nature, especially when electron acceptor are deficient. IET can be divided into two categories: indirect IET and direct IET. Indirect IET (intercellular substrate transfer) always occurs with electron transfer of hydrogen, formate, and other metabolites. Direct intracellular electron transfer is achieved by the coupling of intracellular and extracellular electron transfer. IET boosts the activity of cellular substrate metabolism and expands the acting space of cells. Moreover, IET generates electric current which provides driving-power for energy sharing between bacteria and transformation of extracellular material (such as heavy metals and humus). There is no doubt that IET has physiological and ecological significance. This review summarized recent advances, making a systematic analysis of the process, characteristics, mechanism and eco-physiological significance of IET.

Role of Extracellular Polymeric Substances in a Methane Based Membrane Biofilm Reactor Reducing Vanadate.

For the first time, we demonstrated vanadate (V(V)) reduction in a membrane biofilm reactor (MBfR) using CH4 as the sole electron donor. The V(V)-reducing capability of the biofilm kept increasing, with complete removal of V(V) achieved when the influent surface loading of V(V) was 363 mg m-2 day-1. Almost all V(V) was reduced to V(IV) precipitates, which is confirmed by a scanning electron microscope coupled to energy dispersive X-ray spectroscopy (SEM-EDS) and X-ray photoelectron spectroscopy (XPS). Microbial community analysis revealed that denitrifiers Methylomonas and Denitratisoma might be the main genera responsible for V(V) reduction. The constant enrichment of Methylophilus suggests that the intermediate (i.e., methanol) from CH4 metabolism might be used as the electron carriers for V(V) bioreduction. Intrusion of V(V) (2-5 mg/L, at the surface loading of 150-378 mg m-2 day-1) into the biofilm stimulated the secretion of extracellular polymeric substances (EPS), but high loading of V(V) (10 mg/L, at the surface loading of 668 mg m-2 day-1) decreased the amount of EPS. Metagenomic prediction analysis established the strong correlation between the secretion of EPS and the microbial metabolism associated with V(V) reduction, tricarboxylic acid cycle (TCA) cycle, methane oxidation, and ATP production, and EPS might relieve the oxidative stress induced by high loading of V(V). Colorimetric determination and a three-dimensional excitation-emission matrix (3D-EEM) showed that tryptophan and humic acid-like substances might play important roles in microbial cell protection and V(V) binding. Fourier transform infrared (FTIR) spectroscopy identified hydroxyl (-OH) and carboxyl (COO-) groups in EPS as the candidate functional groups for binding V(V).