Reactive Oxygen Species Burst Research Articles

Anti-diabetic effects of marine natural products through redox modulation via Nrf2/HO-1 cytoprotective pathways

Diabetes mellitus (DM), a major global health concern, is a chronic metabolic disorder. Bioactive compounds sourced from numerous marine natural products recently have drawn attention as novel therapeutic approaches. Considering these chemicals and their role in cellular redox modulation by involving the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, the current study attempts to highlight their anti-diabetic effects and the molecular mechanisms involved. Reactive oxygen species (ROS)-mediated oxidative stress, inflammation, and cellular damage are linked to most human pathologies specifically DM. The Nrf2/HO-1 pathway is a key defense mechanism developed by the cells to combat ROS burst. Marine natural compounds have strong pharmacological potential in triggering cellular antioxidant defense mechanisms by declining oxidative damage and inflammation linked to DM. How marine natural products potentially alleviate DM specifically type 2 diabetes (T2D) and its related issues is especially focused on. The literature was thoroughly analyzed to open a discussion about specific marine compounds and their well-established anti-diabetic effects to elucidate possible therapeutic applications. Furthermore, opportunities and the pros and cons of using these marine bioactive compounds as complementary treatment for DM are also discussed. The diverse characteristics of marine natural products, specifically with regard to redox control, offer promising opportunities for drug discovery and therapeutic interventions in clinical trials.

Vali@mPEG‐TK‐COS: A Dual‐Function Nano‐Pesticide for Fungicidal Action and Plant Immune Modulation

ABSTRACTPesticides play a crucial role in safeguarding crops against pathogens and pests, yet the limited bioavailability of conventional formulations leads to excessive usage, causing environmental and health concerns. In this study, we developed a novel intelligent response‐controlled release nano‐pesticide, Vali@mPEG‐TK‐COS, by coupling chitosan oligosaccharide (COS), a plant immunity regulator, and methoxy polyethylene glycols (mPEG) at either end of thioketal (TK), a material responsive to reactive oxygen species (ROS), and incorporating validamycin (Vali) for controlled release. Vali@mPEG‐TK‐COS exhibits ROS‐responsive behaviour, releasing Vali and COS in response to plant ROS bursts, exhibiting dual capabilities in pathogen control and plant immunity induction during pathogenic attacks. Plant disease experiments confirmed the superior efficacy of Vali@mPEG‐TK‐COS against Rhizoctonia solani, surpassing the control effects of Vali or COS alone. This study presents a sophisticated ROS‐responsive controlled‐release nano‐pesticide with dual fungicidal and plant immunomodulatory properties, offering an advanced strategy to enhance the efficiency of existing pesticides and promote sustainable crop production by reducing overall pesticide usage.

A novel protein elicitor (Cs08297) from Ciboria shiraiana enhances plant disease resistance.

Ciboria shiraiana is a necrotrophic fungus that causes mulberry sclerotinia disease resulting in huge economic losses in agriculture. During infection, the fungus uses immunity elicitors to induce plant tissue necrosis that could facilitate its colonization on plants. However, the key elicitors and immune mechanisms remain unclear in C. shiraiana. Herein, a novel elicitor Cs08297 secreted by C. shiraiana was identified, and it was found to target the apoplast in plants to induce cell death. Cs08297 is a cysteine-rich protein unique to C. shiraiana, and cysteine residues in Cs08297 were crucial for its ability to induce cell death. Cs08297 induced a series of defence responses in Nicotiana benthamiana, including the burst of reactive oxygen species (ROS), callose deposition, and activation of defence-related genes. Cs08297 induced-cell death was mediated by leucine-rich repeat (LRR) receptor-like kinases BAK1 and SOBIR1. Purified His-tagged Cs08297-thioredoxin fusion protein triggered cell death in different plants and enhanced plant resistance to diseases. Cs08297 was necessary for sclerotial development, oxidative-stress adaptation, and cell wall integrity but negatively regulated virulence of C. shiraiana. In conclusion, our results revealed that Cs08297 is a novel fungal elicitor in fungi inducing plant immunity. Furthermore, its potential to enhance plant resistance provides a new target to control agricultural diseases biologically.

An effector essential for virulence of necrotrophic fungi targets plant HIRs to inhibit host immunity

Phytopathogens often secrete effectors to enhance their infection of plants. In the case of Sclerotinia sclerotiorum, a necrotrophic phytopathogen, a secreted protein named SsPEIE1 (Sclerotinia sclerotiorum Plant Early Immunosuppressive Effector 1) plays a crucial role in its virulence. During the early stages of infection, SsPEIE1 is significantly up-regulated. Additionally, transgenic plants expressing SsPEIE1 exhibit increased susceptibility to different phytopathogens. Further investigations revealed that SsPEIE1 interacts with a plasma membrane protein known as hypersensitive induced reaction (HIR) that dampens immune responses. SsPEIE1 is required for S. sclerotiorum virulence on wild-type Arabidopsis but not on Arabidopsis hir4 mutants. Moreover, Arabidopsis hir2 and hir4 mutants exhibit suppressed pathogen-associated molecular pattern-triggered reactive oxygen species (ROS) bursts and salicylic acid (SA)-associated immune gene induction, all of which are phenocopied by the SsPEIE1 transgenic plants. We find that the oligomerization of AtHIR4 is essential for its role in mediating immunity, and that SsPEIE1 inhibits its oligomerization through competitively binding to AtHIR4. Remarkably, both Arabidopsis and rapeseed plants overexpress AtHIR4 display significantly increased resistance to S. sclerotiorum. In summary, these results demonstrate that SsPEIE1 inhibits AtHIR4 oligomerization-mediated immune responses by interacting with the key immune factor AtHIR4, thereby promoting S. sclerotiorum infection.

The ability in managing reactive oxygen species affects Escherichia coli persistence to ampicillin after nutrient shifts.

This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on Escherichia coli and how the switch from different carbon sources to fatty acids influences the formation of persister-resilient bacterial cells resistant to antibiotics. The findings reveal a striking variation in survival rates, with a significant number of cells surviving ampicillin treatment after transitioning from glucose to oleic acid. The key revelation is the role of reactive oxygen species (ROS) in cell killing, particularly after switching from gluconeogenic carbons. The timing of ROS bursts aligns with the rapid killing phase, highlighting the critical impact of oxidative stress regulation on persistence frequency. This research provides valuable insights into bacterial persistence mechanisms, offering potential avenues for targeted therapeutic interventions to combat bacterial resistance effectively.

Post-Flowering Photoperiod Sensitivity of Soybean in Pod-Setting Responses

The development of soybean (Glycine max) is regulated by the photoperiod, with genes related to photoperiod sensitivity primarily focused on the flowering time. However, their roles in post-flowering reproductive development and the mechanisms by which the photoperiod affects them are not yet determined. In this study, we found that pod formation is sensitive to the photoperiod. Long-day conditions tended to extend the time from flowering to pod formation, and the first wave of flowers tended to fall off. Additionally, the photoperiod affected the pistil morphology; under short-day conditions, the stigma had a curved hook-like structure that facilitated better interaction with the filaments when pollen was released, ultimately influencing the timing of pod formation. Photoperiod-insensitive mutants, lacking E1 family and Evening Complex (EC) genes, showed no difference in the pod formation time under long-day or short-day conditions. Hormone content analysis and transcriptome data analysis indicated that various hormones, reactive oxygen species (ROS) burst pathway signals, and the application of sucrose solution in vitro might influence floral organ abscission.

The key pathogenic factor GcSP2 of Geotrichum citri-aurantii plays an important role in disrupting citrus metabolism and immunity

The pathogen Geotrichum citri-aurantii (G. citri-aurantii) causes postharvest sour rot disease in citrus fruits worldwide, severely impacting citrus economic value. However, the pathogenic mechanisms of this fungus remain inadequately understood. Here, we identified 15 candidate effector proteins from G. citri-aurantii genome, of which five were highly expressed during infection and were capable of suppressing BAX-induced cell death, indicating their role in inhibiting plant immunity. Gene expression analysis showed that these five effector proteins primarily induced the upregulation of pattern-triggered immunity (PTI)-related gene expression. Diaminobenzidine (DAB) staining results indicated that only GcSP2 triggered reactive oxygen species (ROS) burst. Notably, GcSP2 contains a known carbohydrate-binding module 1 (CBM1) domain and exhibits low overall conservation. Gene knockout experiments revealed that the absence of GcSP2 delayed disease onset by 1–2 days and significantly reduced lesion size, establishing it as a key pathogenic factor. Assessments of total phenols, flavonoids, and pathogenesis-related protein expression indicated that GcSP2 significantly affects citrus metabolism at 72 hours post-infection.

Biochemical Defence of Plants against Parasitic Nematodes.

Plant parasitic nematodes (PPNs), such as Meloidogyne spp., Heterodera spp. and Pratylenchus spp., are obligate parasites on a wide range of crops, causing significant agricultural production losses worldwide. These PPNs mainly feed on and within roots, impairing both the below-ground and the above-ground parts, resulting in reduced plant performance. Plants have developed a multi-component defence mechanism against diverse pathogens, including PPNs. Several natural molecules, ranging from cell wall components to secondary metabolites, have been found to protect plants from PPN attack by conferring nematode-specific resistance. Recent advances in omics analytical tools have encouraged researchers to shed light on nematode detection and the biochemical defence mechanisms of plants during nematode infection. Here, we discuss the recent progress on revealing the nematode-associated molecular patterns (NAMPs) and their receptors in plants. The biochemical defence responses of plants, comprising cell wall reinforcement; reactive oxygen species burst; receptor-like cytoplasmic kinases; mitogen-activated protein kinases; antioxidant activities; phytohormone biosynthesis and signalling; transcription factor activation; and the production of anti-PPN phytochemicals are also described. Finally, we also examine the role of epigenetics in regulating the transcriptional response to nematode attack. Understanding the plant defence mechanism against PPN attack is of paramount importance in developing new, effective and sustainable control strategies.

Shortening the early diagnostic window of Hg2+-induced liver injury with a H2O2-activated fluorescence/afterglow imaging assay

Mercury ions (Hg2+) and mercury derivatives are a serious threat to ecosystems and human health due to their toxicity, and their toxicological effects are associated with a burst of reactive oxygen species (ROS) due to the oxidative stress. Endogenous hydrogen peroxide (H2O2), a featured ROS in vivo, plays an irreplaceable role in a significant number of pathological processes. However, the exact bioeffect role that H2O2 plays in Hg2+-induced oxidative stress in a specific disease has not been well answered. In particular, optical imaging probes for H2O2 endowed with afterglow emission properties are very rare. Here, the first fluorescence/afterglow probe (FA-H2O2) for accurate and specific detection of H2O2 in cells, zebrafish, and mice under Hg2+-induced oxidative stress is reported. Moreover, FA-H2O2 in its afterglow emission enables efficient monitoring of endogenous H2O2 with a higher signal-to-noise ratio (SNR) in comparison to its fluorescence signals. More importantly, by virtue of the merits of afterglow emission that can eliminate autofluorescence, thus for the first time, shortening the diagnostic window of Hg2+-induced liver injury with FA-H2O2 via noninvasive afterglow emission tracking of H2O2 is achieved, which definitely provides a new opportunity and promising tool for early diagnosis of Hg2+-induced liver injury.

Bio-heterointerface charging through ultrasound-boosted extracellular and intracellular electron transfer for rapid bacterial killing

The deep-seated drug-resistant bacterial infection is one of the most noticeable public-health threat owing to poor drug therapeutic effect, high recurrence, and devastating complication. Herein, we propose a bactericidal strategy of bio-heterointerface charging through ultrasound-boosted bacterial extracellular and intracellular electron transfer for eradicating implant-related drug-resistant bacterial infection, where a TiO2-modified porphyrin-based two-dimensional metal-organic framework (2DMOF-TiO2) is selected as a sonosensitizer. The ultrasound-boosted extracellular and intracellular electron transfer between methicillin-resistant Staphylococcus aureus and 2DMOF-TiO2 induces rapid reactive oxygen species (ROS) burst surrounding bacterial outer and inner, contributing to intracellular oxidation, membrane potential decrease (∼5 mV), membrane disruption, and pyrimidine metabolism disorder, thus causing bacterial death. The in vivo results of 2DMOF-TiO2 implant exhibit rapid sonocatalytic anti-infection and enhanced osseointegration at bone-implant interface. This platform may inspire the universal thinking about ultrasound-boosted extracellular and intracellular electron-transfer-induced ROS and provide a superior therapeutic candidate for various deep-seated infectious diseases.

Nonylphenol displays immunotoxicity by triggering hemocyte extracellular traps in Manila clam via ROS burst, ERK pathway and glycolysis

Nonylphenol (NP), an endocrine disruptor, has been demonstrated to be a harmful environmental contaminant and toxic to organisms. In this study, to address concerns regarding the immunotoxicity of NP, we treated clam Ruditapes philippinarum hemocytes with NP in vitro and explored the underlying mechanisms of NP-induced extracellular traps (ETs). NP could induce the formation of hemocytes ETs in a dose-dependent manner. Transcriptomics analysis revealed changes of signaling pathway involved in immunity and energy metabolism in hemocytes after NP stimulation. In this process, both reactive oxygen species (ROS) and myeloperoxidase (MPO) were up-regulated. Moreover, mitogen-activated protein kinase (MAPK) signaling pathway was proved to be activated in the formation of NP-induced ETs, manifested as enhanced phosphorylation of extracellular signal-regulated kinase (ERK) but not p38 or c-Jun N-terminal kinase (JNK). In the presence of U0126, an ERK phosphorylation inhibitor, the NP-induced expression of NADPH oxidase enzyme (NOX) was significantly decreased, which further alleviated the ROS production and ultimately limited the release of ETs. NP exposure increased glucose uptake, along with enhanced activities of glycolysis-related enzymes such as hexokinase (HK) and pyruvate kinase (PK). After inhibiting glycolysis by the inhibitor 2-DG, the formation of NP-induced ETs was significantly suppressed. ERK could regulate mTOR signaling and the PI3K/AKT pathway, potentially directing ETs formation by orchestrating the glycolysis through the activation of key transcription factors c-Myc and HIF-1α. Collectively, the results preliminary confirm that the ERK-NOX-ROS axis and glycolysis are involved in NP-induced ETs formation, contributing to the cellular immunotoxicity in clam.

Bufotalin Induces Oxidative Stress-Mediated Apoptosis by Blocking the ITGB4/FAK/ERK Pathway in Glioblastoma.

Bufotalin (BT), a major active constituent of Chansu, has been found to possess multiple pharmacological activities. Although previous studies have shown that BT could inhibit the growth of glioblastoma (GBM), the safety of BT in vivo and the potential mechanism are still unclear. We conducted a systematic assessment to investigate the impact of BT on GBM cell viability, migration, invasion, and colony formation. Furthermore, in vivo results were obtained to evaluate the effect of BT on tumor growth. The preliminary findings of our study demonstrate the effective inhibition of GBM cell growth and subcutaneous tumor development in mice by BT, with tolerable levels of tolerance observed. Mechanistically, BT treatment induced mitochondrial dysfunction, bursts of reactive oxygen species (ROS), and subsequent cell apoptosis. More importantly, proteomic-based differentially expressed proteins analysis revealed a significant downregulation of integrin β4 (ITGB4) following BT treatment. Furthermore, our evidence suggested that the ITGB4/focal adhesion kinase (FAK)/extracellular signal-related kinase (ERK) pathway involved BT-induced apoptosis. Overall, our study demonstrates the anti-GBM effects of BT and elucidates the underlying mechanism, highlighting BT as a potential therapeutic option for GBM.

An Overview of the Mechanisms through Which Plants Regulate ROS Homeostasis under Cadmium Stress.

Cadmium (Cd2+) is a non-essential and highly toxic element to all organic life forms, including plants and humans. In response to Cd stress, plants have evolved multiple protective mechanisms, such as Cd2+ chelation, vesicle sequestration, the regulation of Cd2+ uptake, and enhanced antioxidant defenses. When Cd2+ accumulates in plants to a certain level, it triggers a burst of reactive oxygen species (ROS), leading to chlorosis, growth retardation, and potentially death. To counteract this, plants utilize a complex network of enzymatic and non-enzymatic antioxidant systems to manage ROS and protect cells from oxidative damage. This review systematically summarizes how various elements, including nitrogen, phosphorus, calcium, iron, and zinc, as well as phytohormones such as abscisic acid, auxin, brassinosteroids, and ethylene, and signaling molecules like nitric oxide, hydrogen peroxide, and hydrogen sulfide, regulate the antioxidant system under Cd stress. Furthermore, it explores the mechanisms by which exogenous regulators can enhance the antioxidant capacity and mitigate Cd toxicity.

Low-dose of oligosaccharins boosts antiviral immunity through induction of multiple defense pathways in rice

Oligosaccharins, widely recognized as plant immunity inducers, have been applied and studied for enhancing antiviral defenses in rice over the years. However, due to the complex induction mechanism in rice, further studies are needed. In this study, we demonstrated that oligosaccharins enhanced rice resistance to southern rice black-streaked dwarf virus (SRBSDV) at both the symptomatic and molecular levels. RNA-seq analysis revealed that oligosaccharins enhanced rice antiviral defense by activating multiple defense pathways. Among them, the jasmonic acid (JA) signaling pathway, a crucial antiviral pathway in rice, was investigated in detail. Interestingly, RNA-seq data showed that genes related to JA signaling pathway were significantly induced after 1 h but not after 24 h of oligosaccharins treatment, suggesting that JA induction by oligosaccharins was rapid and sensitive. Furthermore, JA levels and sensitivity analysis showed that oligosaccharins induced JA accumulation, making treated rice plants more sensitive to methyl jasmonate (MeJA). Additionally, oligosaccharins treatment also induced a burst of reactive oxygen species (ROS) in rice. Notably, oligosaccharins demonstrated a low-dose effect, within a certain dilution range from 6000-fold to 1000-fold diluted solution of 5% oligosaccharins, with the 4000-fold diluted solution exhibiting a stronger ability to induce elevated production of JA and ROS. Moreover, the application of low-dose oligosaccharins also enhanced rice resistance to SRBSDV. These data suggest that low-dose of oligosaccharins can enhance rice antiviral defense by inducing multiple defense pathways, including the JA signaling pathway and ROS production.

Exogenous nicotinamide accelerates pyridine nucleotides metabolism and redox homeostasis: A novel strategy for extension of potato dormancy

The sprout of potatoes during storage threatens the post-harvest potato market supply chain. To reduce the massive economic losses in potato production industry, herein, the exogenous nicotinamide (NAM) was taken into consideration to maintain the potato quality. This study focused on the role of NAM on potato sprout development and revealed the possible mechanisms from the perspectives of energy and pyridine nucleotides metabolism. It was found that NAM delayed the sprouting and quality deterioration by down-regulating respiration rate and energy charge. Additionally, NAM stimulated the synthesis of nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADPH) in pyridine nucleotides cycle, which maintained redox balance and reduced the burst of reactive oxygen species (ROS) at the sprouting site. Our findings provide a novel perspective on the possible strategies of NAM for improving the quality of fresh produce.

OsWRKY70 Plays Opposite Roles in Blast Resistance and Cold Stress Tolerance in Rice

The transcription factor WRKYs play pivotal roles in the adapting to adverse environments in plants. Prior research has demonstrated the involvement of OsWRKY70 in resistance against herbivores and its response to abiotic stress. Here, we reported the functional analysis of OsWRKY70 in immunity against fungal diseases and cold tolerance. The results revealed that OsWRKY70 was induced by various Magnaporthe oryzae strains. Knock out mutants of OsWRKY70, which were generated by the CRISPR/Cas9 system, exhibited enhanced resistance to M. oryzae. This was consistent with fortifying the reactive oxygen species (ROS) burst after inoculation in the mutants, elevated transcript levels of defense-responsive genes (OsPR1b, OsPBZ1, OsPOX8.1 and OsPOX22.3) and the observation of the sluggish growth of invasive hyphae under fluorescence microscope. RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) validations demonstrated that differentially expressed genes were related to plant-pathogen interactions, hormone transduction and MAPK cascades. Notably, OsbHLH6, a key component of the JA signaling pathway, was down-regulated in the mutants compared to wild type plants. Further investigation confirmed that OsWRKY70 bound to the promoter of OsbHLH6 by semi-in vivo chromatin immunoprecipitation (ChIP). Additionally, the loss-function of OsWRKY70 impaired cold tolerance in rice. The enhanced susceptibility in the mutants characterized by excessive ROS production, elevated ion leakage rate and increased malondialdehyde content, as well as decreased activity of catalase (CAT) and peroxidase (POD) under low temperature stress was, which might be attributed to down-regulation of cold-responsive genes (OsLti6b and OsICE1). In conclusion, our findings indicate that OsWRKY70 negatively contributes to blast resistance but positively regulates cold tolerance in rice, providing a strategy for crop breeding with tolerance to stress.

Adaptative responses of Neurospora crassa by histidine kinases upon the attack of the arthropod Sinella curviseta.

Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of β-glucan, ergothioneine, ergosterol, and carotenoids. β-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli.

Hollow mesoporous Prussian blue nanoenzymes as Rapamycin carrier for targeted treatment of ischemia/reperfusion-induced acute kidney injury through pro-mitophagy and oxidative stress alleviation

The kidney’s abundant mitochondrial content and substantial oxygen requirements make it particularly vulnerable to a series of detrimental events following ischemia/reperfusion (I/R). These events encompass oxidative stress, mitochondrial impairment, depletion of adenosine triphosphate (ATP), and inflammation, cumulatively leading to acute kidney injury (AKI). Currently, no approved therapy beyond supportive care is available for AKI. While numerous studies have focused on neutralizing pre-existing reactive oxygen species (ROS) to mitigate AKI, insufficient attention has been paid to addressing the root causes of ROS. Here, we prepared Rapamycin (Rapa)-loaded hollow mesoporous Prussian blue nanoparticles (HMPB-Rapa) and grafted injured renal-targeted hyaluronic acid (HA) onto HMPB-Rapa (HA-HMPB-Rapa), which effectively scavenge pre-existing ROS and the source (massive damaged mitochondria) through the dual function of HMPB carrier and Rapa, thus preventing the further burst of ROS. In the I/R-induced AKI rat model, a single-dose of HA-HMPB-Rapa 6 h after I/R injury effectively inhibited oxidative stress and inflammation, protected renal cells from apoptotic damage, as well as ultimately restored renal function, and attenuated pathological changes. Mechanistically, HA-HMPB-Rapa cleared damaged mitochondria by activating the pro-mitophagy signaling pathway (PINK-1/Parkin-P62-LC3), cutting off the conduction in the intrinsic apoptotic pathway mediated by the Bax-Cyt-c-Cleaved Casp-3 signaling axis, and reduced the expression of renal tubular marker kidney injury molecule-1. HA-HMPB-Rapa represents an exciting new avenue for the treatment of diseases related to I/R-induced injury.

Novel platinum therapeutics induce rapid cancer cell death through triggering intracellular ROS storm

Induction of reactive oxygen species (ROS) production in cancer cells plays a critical role for cancer treatment. However, therapeutic efficiency remains challenging due to insufficient ROS production of current ROS inducers. We designed a novel platinum (Pt)-based drug named “carrier-platin” that integrates ultrasmall Pt-based nanoparticles uniformly confined within a poly(amino acids) carrier. Carrier-platin dramatically triggered a burst of ROS in cancer cells, leading to cancer cell death as quick as 30 min. Unlike traditional Pt-based drugs which induce cell apoptosis through DNA intercalation, carrier-platin with superior ROS catalytic activities induces a unique pattern of cancer cell death that is neither apoptosis nor ferroptosis and operates independently of DNA damage. Importantly, carrier-platin demonstrates superior anti-tumor efficacy against a broad spectrum of cancers, particularly those with multidrug resistance, while maintaining minimal systemic toxicity. Our findings reveal a distinct mechanism of action of Pt in cancer cell eradication, positioning carrier-platin as a novel category of anti-cancer chemotherapeutics.

A secreted fungal laccase targets the receptor kinase OsSRF3 to inhibit OsBAK1–OsSRF3-mediated immunity in rice

The identification effector targets and characterization of their functions are crucial for understanding pathogen infection mechanisms and components of plant immunity. Here, we identify the effector UgsL, a ustilaginoidin synthetase with a key role in regulating virulence of the rice false smut fungus Ustilaginoidea virens. Heterologous expression of UgsL in rice (Oryza sativa) enhances plant susceptibility to multiple pathogens, and host-induced gene silencing of UgsL enhances plant resistance to U. virens, indicating that UgsL inhibits rice immunity. UgsL interacts with STRUBBELIG RECEPTOR KINASE 3 (OsSRF3). Genome editing and overexpression of OsSRF3 demonstrate that OsSRF3 plays a pivotal role in the resistance of rice to multiple pathogens. Remarkably, overexpressing OsSRF3 enhances resistance without adversely affecting plant growth or yield. We show that BRASSINOSTEROID RECEPTOR-ASSOCIATED KINASE 1 (OsBAK1) interacts with and phosphorylates OsSRF3 to activate pathogen-triggered immunity, inducing the mitogen-activated protein kinase cascade, a reactive oxygen species burst, callose deposition, and expression of defense-related genes. UgsL interferes with the phosphorylation of OsSRF3 by OsBAK1. Furthermore, UgsL mediates OsSRF3 degradation by facilitating its association with the ubiquitin-26S proteasome. Our results reveal that OsSRF3 positively regulates immunity in rice and that UgsL mediates its degradation, thereby inhibiting the activation of OsBAK1–OsSRF3-mediated immune pathways.