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Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid–liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 ( SNHG9 ) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9 ) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013 ), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM -NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM- NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development. Iron metabolism dysregulation is associated with various diseases including cancer. Here, the authors show that one iron-triggered lncRNA LncRIM regulates cellular iron metabolism effectively by wiring up the Hippo-YAP  signaling pathway and promotes breast cancer development.

Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In this study, we successfully expressed and purified a stable and highly pure form of seven times transmembrane protein Chlamydomonas reinhardtii HST ( Cr HST). The final yield of Cr HST protein obtained was 12.2 mg per liter of M9 medium. We evaluated the inhibitory effect on Cr HST using Des-Morpholinocarbony Cyclopyrimorate (DMC) and found its IC 50 value to be 3.63 ± 0.53 μM, indicating significant inhibitory potential. Additionally, we investigated the substrate affinity of Cr HST with two substrates, determining the K m values as 22.76 ± 1.70 μM for FPP and 48.54 ± 3.89 μM for HGA. Through sequence alignment analyses and three-dimensional structure predictions, we identified conserved amino acid residues forming the active cavity in the enzyme. The results from molecular docking and binding energy calculations indicate that DMC has a greater binding affinity with HST compared to HGA. These findings represent substantial progress in understanding Cr HST’s properties and potential for herbicide development. Key points •  First high-yield transmembrane CrHST protein via E. coli system •  Preliminarily identified active cavity composition via activity testing •  Determined substrate and inhibitor modes via molecular docking

The development of precision agriculture demands high accuracy and efficiency of cultivated land information extraction. As a new means of monitoring the ground in recent years, unmanned aerial vehicle （UAV） low-height remote sensing technique, which is flexible, efficient with low cost and with high resolution, is widely applied to investing various resources. Based on this, a novel extraction method for cultivated land information based on Deep Convolutional Neural Network and Transfer Learning （DTCLE） was proposed. First, linear features （roads and ridges etc.） were excluded based on Deep Convolutional Neural Network （DCNN）. Next, feature extraction method learned from DCNN was used to cultivated land information extraction by introducing transfer learning mechanism. Last, cultivated land information extraction results were completed by the DTCLE and eCognifion for cultivated land information extraction （ECLE）. The location of the Pengzhou County and Guanghan County, Sichuan Province were selected for the experimental purpose. The experimental results showed that the overall precision for the experimental image 1, 2 and 3 （of extracting cultivated land） with the DTCLE method was 91.7%, 88.1% and 88.2% respectively, and the overall precision of ECLE is 9o.7%, 90.5% and 87.0%, respectively. Accuracy of DTCLE was equivalent to that of ECLE, and also outperformed ECLE in terms of integrity and continuity.

Succinate dehydrogenase (SDH) is a key fungicidal target, but rational inhibitors design has been impeded by the lack of fungal SDH structure. Here, we show the cryo-EM structure of SDH from Saccharomyces cerevisiae ( Sc SDH) in apo (3.36 Å) and ubiquinone-1-bound (3.25 Å) states, revealing subunits architecture and quinone-binding sites (Q p ). Sc SDH is classified as a heme-deficient type-D SDH, utilizing conserved redox centers (FAD, [2Fe-2S], [4Fe-4S] and [3Fe-4S] clusters) for electron transfer. A 3.23 Å structure with pydiflumetofen (PYD) identified critical interactions, including hydrogen bonds with Trp_SDHB194 and Tyr_SDHD120, and a cation-π interaction with Arg_SDHC97. Leveraging this, we designed a SDH inhibitor E8 (enprocymid), exhibiting significant fungicidal activity ( K i  = 0.019 μM) and reduced zebrafish toxicity (LC 50 (96 h) = 1.01 mg a.i./L). This study elucidates the structure of fungal SDH and demonstrates the potential of Sc SDH for rational design of next-generation fungicides, addressing fungal resistance and environmental toxicity in agriculture. Fungal diseases threaten crops worldwide. By resolving the cryo-EM structure of fungal succinate dehydrogenase, researchers designed an inhibitor with broad antifungal activity, strong field performance, and reduced environmental toxicity.

Background Plant fungal diseases present a major challenge to global agricultural production. Despite extensive efforts to develop fungicides, particularly succinate dehydrogenase inhibitors (SDHIs), their effectiveness is often limited by poor retention of fungicide droplets on hydrophobic leaves. The off-target losses and unintended release cause fungal resistance and severe environmental pollution. Results To update the structure of existing SDHIs and synchronously realize the efficient utilization, we have employed a sophisticated supramolecular strategy to optimize a structurally novel SDH inhibitor (AoH25), creating an innovative supramolecular SDH fungicide (AoH25@ β -CD), driven by the host-guest recognition principle between AoH25 and β -cyclodextrin ( β -CD). Intriguingly, AoH25@ β -CD self-assembles into biocompatible supramolecular nanovesicles, which reinforce the droplet/foliage (liquid-solid) interface interaction and the effective wetting and retention on leaf surfaces, setting the foundation for enhancing fungicide utilization. Mechanistic studies revealed that AoH25@ β -CD exhibited significantly higher inhibition of SDH (IC 50  = 1.56 µ M) compared to fluopyram (IC 50  = 244.41 µ M) and AoH25 alone (IC 50  = 2.29 µ M). Additionally, AoH25@ β -CD increased the permeability of cell membranes in Botryosphaeria dothidea , facilitating better penetration of active ingredients into pathogenic cells. Further experimental outcomes confirmed that AoH25@ β -CD was 88.5% effective against kiwifruit soft rot at a low-dose of 100 µ g mL -1 , outperforming commercial fungicides such as fluopyram (52.4%) and azoxystrobin (65.4%). Moreover, AoH25@ β -CD showed broad-spectrum bioactivity against oilseed rape sclerotinia, achieving an efficacy of 87.2%, outstripping those of fluopyram (48.7%) and azoxystrobin (76.7%). Conclusion This innovative approach addresses key challenges related to fungicide deposition and resistance, improving the bioavailability of agricultural chemicals. The findings highlight AoH25@ β -CD as a novel supramolecular SDH inhibitor, demonstrating its potential as an efficient and sustainable solution for plant disease management. Graphical Abstract

Background New therapeutic strategies are needed to treat tuberculosis (TB). The antimicrobial peptide PK34 has a good ability to clear Mycobacterium tuberculosis ( Mtb ) and is not prone to drug resistance and adverse reactions. Mesenchymal stem cells (MSCs) can also be used as an adjunctive therapy for the treatment of TB. However, there have been no studies combining the two for the treatment of Mtb infection. Methods We aimed to construct bone-derived mesenchymal stem cells secreting the antimicrobial peptide PK34 (named Plent-PK34-BMSCs) and to investigate their roles in both in vitro and in vivo Mtb H37Rv infection models. Results We successfully constructed Plent-PK34-BMSCs that secrete and express the antimicrobial peptide PK34, and demonstrated that PK34 modified MSCs significantly enhanced their in vitro and in vivo antibacterial ability and cytoprotective effects. The cytokine results showed that Plent-PK34-BMSCs increased the levels of anti-inflammatory factors IL-4 and IL-10 in the cell supernatant, decreased the levels of pro-inflammatory factors IL-6 in the serum of the mice. In addition, lung tissue analysis results showed that mice treated with Plent-PK34-BMSCs had reduced infiltration and congestion of inflammatory cells in lung tissue, significantly reduced lung injury, and exhibited better preservation of lung structure. Conclusions PK34 modification enhanced the therapeutic efficacy of MSCs in Mtb infection models, and Plent-PK34-BMSCs transplantation has the potential to treat TB.

The regulatory mechanism that governs pH-regulated filamentation is not clear in dimorphic fungi except in Candida albicans . Here, we investigated the regulation of alkaline pH-induced filamentation in Yarrowia lipolytica , a dimorphic yeast distantly related to C. albicans . Environmental pH influences cell growth and differentiation. In the dimorphic yeast Yarrowia lipolytica , neutral-alkaline pH strongly induces the yeast-to-filament transition. However, the regulatory mechanism that governs alkaline pH-induced filamentation has been unclear. Here, we show that the pH-responsive transcription factor Y. lipolytica Rim101 (YlRim101) is a major regulator of alkaline-induced filamentation, since the deletion of Yl RIM101 severely impaired filamentation at alkaline pH, whereas the constitutively active Yl RIM101 1-330 mutant mildly induced filamentation at acidic pH. YlRim101 controls the expression of the majority of alkaline-regulated cell wall protein genes. One of these, the cell surface glycosidase gene Yl PHR1 , plays a critical role in growth, cell wall function, and filamentation at alkaline pH. This finding suggests that YlRim101 promotes filamentation at alkaline pH via controlling the expression of these genes. We also show that, in addition to YlRim101, the Msn2/Msn4-like transcription factor Mhy1 is highly upregulated at alkaline pH and is essential for filamentation. However, unlike YlRim101, which specifically regulates alkaline-induced filamentation, Mhy1 regulates both alkaline- and glucose-induced filamentation, since the deletion of MHY1 abolished them both, whereas the overexpression of MHY1 induced strong filamentation irrespective of the pH or the presence of glucose. Finally, we show that YlRim101 and Mhy1 positively coregulate seven cell wall protein genes at alkaline pH, including Yl PHR1 and five cell surface adhesin-like genes, three of which appear to promote filamentation. Together, these results reveal a conserved role of YlRim101 and a novel role of Mhy1 in the regulation of alkaline-induced filamentation in Y. lipolytica . IMPORTANCE The regulatory mechanism that governs pH-regulated filamentation is not clear in dimorphic fungi except in Candida albicans . Here, we investigated the regulation of alkaline pH-induced filamentation in Yarrowia lipolytica , a dimorphic yeast distantly related to C. albicans . Our results show that the transcription factor YlRim101 and the Msn2/Msn4-like transcription factor Mhy1 are the major regulators that promote filamentation at alkaline pH. They control the expression of a number of cell wall protein genes important for cell wall organization and filamentation. Our results suggest that the Rim101/PacC homologs play a conserved role in pH-regulated filamentation in dimorphic fungi.

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD‐induced PND include uncontrolled central nervous inflammation, blood–brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep‐improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive‐behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first‐generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD. This review examines sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly, focusing on their prevalence and interrelation. It highlights SD's role in increasing postoperative delirium, although more evidence is needed regarding its effect on postoperative cognitive dysfunction. Possible mechanisms linking SD to PND include central nervous inflammation, blood–brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic anomalies, impaired clearance of central metabolic waste, gut microbiome dysbiosis, and oxidative stress. The review also evaluates sleep interventions' impact on PND, including earplugs, eye masks, circadian rhythm restoration, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists, which reduce PND incidence. The influence of other sleep‐improving drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive behavioral therapy for insomnia) on PND remains uncertain, whereas some SD treatments (e.g., antidepressants and antihistamines) might increase PND risk.

Rainstorm disasters cause serious threats to people’s lives and property. Enhancing emergency response and decision-making capabilities for rainstorm disasters is necessary. In this paper, 87 rainstorm disasters worldwide were first analysed, and secondary events across 15 urban lifeline systems were summarized. Based on the obtained findings and the characteristics of rainstorm disaster evolution and complex network theory, a model of rainstorm disaster chains in urban lifeline systems was constructed, and both partial and overall analyses of this model were performed. With the use of the PageRank risk matrix method, quantitative node risk levels were calculated for different parts of the model, and complex network theory was applied to assess the overall chain risk. The results showed that the highest risk disaster chain was flood → houses submerged or collapsed → road damaged → traffic congestion or paralysis. The most important node was traffic congestion or paralysis, underlining the acute need for emergency response measures in urban traffic systems during rainstorm disasters. Overall, this research provides a crucial direction for preventing rainstorm disasters in urban lifeline systems.