Zhenglin Zhu

Radiation enteritis, a complication following cancer radiotherapy, is caused by reactive oxygen species (ROS)-mediated oxidative damage, coupled with inflammatory dysregulation and disruption of the gut microbiota. Recent advancements in phytotherapy have highlighted the potential application of plant-derived bioactive compounds (e.g., curcumin from Curcuma longa, epigallocatechin gallate [EGCG], and resveratrol) as mitigators in treating radiation-induced intestinal injury. These compounds, characterized by potent ROS-scavenging activity, excellent biocompatibility, and minimal toxicity, exhibit promising attributes for therapeutic intervention. To better understand the botanical diversity and underlying mechanisms of radiation enteritis, this review systematically profiles the alkaloid-, flavonoid-, and polyphenol-rich medicinal plants, relevant bioactive constituents, and their associated therapeutic effects in synergistic modulation of oxidative, inflammatory, and apoptotic cascades. These natural compounds effectively leverage dual antioxidant mechanisms, including direct ROS scavenging via phenolic hydroxyl groups, indirect activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1), upregulation of endogenous antioxidants, suppression of pro-inflammatory cytokines, and enhancement of tight junction proteins for barrier repair. Despite their potential as adjuvant therapies, challenges remain in identifying exact antioxidant targets and translating these into clinical applications. To address this issue, we propose a framework that integrates phytochemistry, multi-omics profiling, and AI-enabled prediction of antioxidant targets. This review aims to facilitate the development of plant-based radioprotectants as next-generation adjuvant therapies.

How SARS-CoV-2 Omicron evolved remains obscure. T492I, an Omicron-specific mutation encountered in SARS-CoV-2 nonstructural protein 4 (NSP4), enhances viral replication and alters nonstructural protein cleavage, inferring potentials to drive evolution. Through evolve-and-resequence experiments of SARS-CoV-2 wild-type (hCoV-19/USA/WA-CDC-02982585-001/2020, A) and Delta strains (B.1.617) with or without T492I, this study demonstrates that the NSP4 mutation T492I confers accelerated phenotypic adaption and a predisposition to the emergence of SARS-CoV-2 Omicron-like variants. The T492I-driven evolution results in accelerated enhancement in viral replication, infectivity, immune evasion capacity, receptor-binding affinity and potential for cross-species transmission. Aside from elevated mutation rates and impact on deaminases, positive epistasis between T492I and adaptive mutations could potentially mechanistically facilitate the shifts in mutation spectra and indirectly determines the Omicron-predisposing evolution. These suggest a potentially important role of the driver mutation T492I in the evolution of SARS-CoV-2 Omicron variants. Our findings highlight the existence and importance of mutation-driven predisposition in viral evolution.

Late blight, caused by Phytophthora infestans, is a devastating disease of potato. Our previous work illustrated that scopolamine, the main bioactive substance of Datura extract, exerts direct inhibitory effects on P. infestans, but it is unclear whether scopolamine and Datura extract can boost resistance to late blight in potato. In this study, P. infestans is used to infect scopolamine-treated potato pieces and leaves, as well as whole potatoes. We found that scopolamine-treated potato is resistant to P. infestans both in vitro and in vivo. The treatment of 4.5 g/L scopolamine reduces the lesion size of whole potato to 54% compared with the control after 20 d of the infection of P. infestans. The disease-resistant substance detection based on the kit method shows that scopolamine triggers the upregulation of polyphenoloxidase, peroxidase, superoxide dismutase activities, and H₂O₂ contents in potato tubers, and the decline of phenylalanine ammonia lyase and catalase activity. A total of 1682 significantly differentially expressed genes were detected with or without scopolamine treatment through high-throughput transcriptome sequencing and the DESeq2 software (version 1.24.0), including 705 upregulated and 977 downregulated genes. Scopolamine may affect the genes functioning in the cell wall, membrane and the plant-pathogen interaction. The addition of Datura extract could directly inhibit the mycelial growth of P. infestans on rye plate medium. In addition, P. infestans was found to be resistant to late blight in potato pieces treated with Datura extract. Datura extract can also be utilized in combination with the chemical fungicide Infinito in field experiments to lessen late blight symptoms and enhance potato yield. To our knowledge, this is the first study to detect the induction of disease resistance by scopolamine, and it also explores the feasibility of Datura extract in potato disease resistance.

For research on HIV/AIDS, it is important to elucidate the complex viral–host interaction, host dependency factors (HDFs), and restriction factors. However, the regulatory network of HIV-resistance-related factors remains not well understood. Therefore, we integrated four publicly available HIV-related transcriptome datasets, along with three datasets on HIV-infection-related DNA methylation, miRNA, and ChIP-seq, to predict the factors influencing HIV resistance and infection. Our approach involved differential analysis, functional annotation, and protein–protein interaction network analysis. Through comprehensive analyses, we identified 25 potential HIV-resistance-related genes (including shared EGF) and 24 HIV-infection-related hub genes (including shared JUN). Additionally, we pinpointed five key differentially methylated genes, five crucial differentially expressed microRNAs, and five significant pathways associated with HIV resistance. We mapped the potential regulatory pathways involving these HIV-resistance-related factors. Among the predicted factors, RHOA, RAD51, GATA1, IRF4, and CXCL8 have been validated as HDFs or restriction factors. The identified factors, such as JUN, EGF, and PLEK, are potential HDFs or restriction factors. This study uncovers the gene signatures and regulatory networks associated with HIV-1 resistance, suggesting potential targets for the development of new therapies against HIV/AIDS.

The Ficus genus, having radiated from the tropics and subtropics to the temperate zone worldwide, is the largest genus among woody plants, comprising over 800 species. Evolution of the Ficus species results in genetic diversity, global radiation and geographical differentiations, suggesting adaption to diverse environments and coping with stresses. Apart from familiar physiological changes, such as stomatal closure and alteration in plant hormone levels, the Ficus species exhibit a unique mechanism in response to abiotic stress, such as regulation of leaf temperature and retention of drought memory. The stress-resistance genes harbored by Ficus result in effective responses to abiotic stress. Understanding the stress-resistance mechanisms in Ficus provides insights into the genetic breeding toward stress-tolerant crop cultivars. Following upon these issues, we comprehensively reviewed recent progress concerning the Ficus genes and relevant mechanisms that play important roles in the abiotic stress responses. These highlight prospectively important application potentials of the stress-resistance genes in Ficus.

T492I, a mutation encountered in SARS-CoV-2 nonstructural protein 4 (NSP4), enhances viral replication and alters nonstructural protein cleavage, causing potential evolutionary impacts. Through comprehensive comparative analyses based on evolve-and-resequence experiments of SARS-CoV-2 wild-type and Delta strains with or without T492I, we demonstrate that NSP4 T492I not only increases the mutation rate, but also accelerates the emergence of many mutations characteristic for Omicron variants. Accordingly, viral populations that evolved from ancestors with T492I, show Omicron-biased selective forces and increases in viral replication, infectivity, immune evasion capacity, potentials for cross-species transmission and receptor-binding affinity. Aside from enhanced replication, we observed stronger epistasis regarding viral replication and infectivity in T492I than in S N501Y and NSP6 ∆SGF; this facilitates the regulation of mutation types, which can drive fast evolution of Omicron specific mutations. Our results highlight the role of an important replication-enhancing mutation in regulating the evolutionary rates and mutational trends of SARS-CoV-2.