PPtase-activated production of borrelidin from extremophilic actinobacteria against multidrug-resistant cotton pathogen Verticillium dahliae
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Prevalence and transmission risk of colistin and multidrug resistance in long-distance coastal aquaculture
Due to the wide use of antibiotics, intensive aquaculture farms have been recognized as a significant reservoir of antibiotic resistomes. Although the prevalence of colistin resistance genes and multidrug-resistant bacteria (MDRB) has been documented, empirical evidence for the transmission of colistin and multidrug resistance between bacterial communities in aquaculture farms through horizontal gene transfer (HGT) is lacking. Here, we report the prevalence and transmission risk of colistin and multidrug resistance in 27 aquaculture water samples from 9 aquaculture zones from over 5000 km of subtropical coastlines in southern China. The colistin resistance gene mcr−1, mobile genetic element (MGE) intl1 and 13 typical antibiotic resistance genes (ARGs) were prevalent in all the aquaculture water samples. Most types of antibiotic (especially colistin) resistance are transmissible in bacterial communities based on evidence from laboratory conjugation and transformation experiments. Diverse MDRB were detected in most of the aquaculture water samples, and a strain with high-level colistin resistance, named Ralstonia pickettii MCR, was isolated. The risk of horizontal transfer of the colistin resistance of R. pickettii MCR through conjugation and transformation was low, but the colistin resistance could be steadily transmitted to offspring through vertical transfer. The findings have important implications for the future regulation of antibiotic use in aquaculture farms globally to address the growing threat posed by antibiotic resistance to human health.
Microbiota transplantation for cotton leaf curl disease suppression—core microbiome and transcriptome dynamics
Microbiota transplantation is a strong tool for managing plant disease. This study investigates the effects of microbiota transplantation on Cotton Leaf Curl Disease (CLCuD) resistance in Gossypium hirsutum, a species with good fiber length but high susceptibility to biotic stresses. Using metabarcoding for V3-V4 16S rRNA gene amplicon, microbial fractions from both rhizosphere and phyllosphere of CLCuD-resistant species Gossypium arboreum, and susceptible cotton varieties are analyzed. Unique bacterial taxa have been identified associated with disease resistance. Interspecies and intraspecies microbiota transplantation is conducted, followed by CLCuD incidence assays. It is seen that rhizospheric microbiota transplantation from G. arboreum FDH228 significantly suppresses CLCuD in G. hirsutum varieties, outperforming exogenous salicylic acid application. While phyllospheric transplants also reduce disease incidence, they are less effective than rhizospheric transplants. Differential expression analysis DESeq2 is utilized to identify key bacterial genera correlated with CLCuD suppression, including Pseudoxanthomonas and Stenotrophomonas in the rhizosphere of G. arboreum FDH228. Functional pathway analysis reveals upregulation of stress response and metabolism in tolerant species. Transcriptomics reveals upregulation of genes involved in protein phosphorylation and stress response in interspecies rhizospheric microbiota transplants. This study highlights microbiota transplantation as a sustainable method for controlling CLCuD along with specific microbial and genetic mechanisms contributing to CLCuD resistance.
Pathogen stress heightens sensorimotor dimensions in the human collective semantic space
Infectious diseases have been major causes of death throughout human history and are assumed to broadly affect human psychology. However, whether and how conceptual processing, an internal world model central to various cognitive processes, adapts to such salient stress variables remains largely unknown. To address this, we conducted three studies examining the relationship between pathogen severity and semantic space, probed through the main neurocognitive semantic dimensions revealed by large-scale text analyses: one cross-cultural study (across 43 countries) and two historical studies (over the past 100 years). Across all three studies, we observed that increasing pathogen severity was associated with an enhancement of the sensory-motor dimension in the collective semantic space. These patterns remained robust after controlling for the effects of sociocultural variables, including economic wealth and societal norms of tightness. These results highlight the universal dynamic mechanisms of collective semantics, such that pathogen stress potentially drives sensorially oriented semantic processing.
Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention
Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members. Notably, the re-introduction of BIM into resistant cells restored VTX sensitivity and synergized with MCL-1 inhibitors. Upstream signaling pathways, including growth factor receptor tyrosine kinase (RTK) and phosphoinositide-3-kinase (PI3K) were implicated in this dysregulation. Simultaneous inhibition of MCL-1, BCL-XL, and upstream PI3K, RTK (FGF, EGF, and IGF1) mediated signaling enhanced VTX sensitivity. Post-translational modifications of MCL-1, particularly its stabilization via acetylation and phosphorylation, were investigated, although their inhibition only marginally increased VTX sensitivity. Lastly, the inhibition of AURKA and mitochondrial respiration also improved VTX sensitivity in some resistant HMCLs. Our findings suggest that combining VTX with MCL-1 and BCL-XL inhibitors or PIK3/RTK inhibitors holds potential for overcoming resistance. The study illustrates the importance of understanding molecular determinants of resistance to develop tailored therapeutic strategies.
Low-carbon ammonia production is essential for resilient and sustainable agriculture
Ammonia-based synthetic nitrogen fertilizers (N fertilizers) are critical for global food security. However, their production, primarily dependent on fossil fuels, is energy- and carbon-intensive and vulnerable to supply chain disruptions, affecting 1.8 billion people reliant on either imported fertilizers or natural gas. Here we examine the global N-fertilizer supply chain and analyse context-specific trade-offs of low-carbon ammonia production pathways. Carbon capture and storage can reduce overall emissions by up to 70%, but still relies on natural gas. Electrolytic and biochemical processes minimize emissions but are 2–3 times more expensive and require 100–300 times more land and water than the business-as-usual production. Decentralized production has the potential to reduce transportation costs, emissions, reliance on imports and price volatility, increasing agricultural productivity in the global south, but requires policy support. Interdisciplinary approaches are essential to understand these trade-offs and find resilient ways to feed a growing population while minimizing climate impacts.
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