Reactive Oxygen Species Burst Research Articles

A Vacancy-Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co-Activated Immunotherapy.

Low efficacy of immunotherapy due to the poor immunogenicity of most tumors and their insufficient infiltration by immune cells highlights the importance of inducing immunogenic cell death and activating immune system for achieving better treatment outcomes. Herein, ferroelectric Bi2CuO4 nanoparticles (NPs) with rich copper vacancies (named BCO-VCu) were rationally designed and engineered for ferroelectricity enhanced apoptosis, cuproptosis, and the subsequently evoked immunotherapy. In this structure, the suppressed recombination of the electron-hole pairs by the vacancies and the band bending by the ferroelectric polarization lead to high catalytic activiy, triggering reactive oxygen species bursts and inducing apoptosis. The cell fragments produced by apoptosis serve as antigens to activate T cells. Moreover, due to the generated charge by the ferroelectric catalysis, this nanomedicine can act as "a smart switch" to open the cell membrane, promote nanomaterial endocytosis, and shut down the Cu+ outflow pathway to evoke cuproptosis, and thus a strong immune response is triggered by the reduced content of adenosine triphosphate. Ribonucleic acid transcription tests reveal the pathways related to immune response activation. Thus, our study firstly demonstrates a feasible strategy for enhancing the efficacy of immunotherapy using single ferroelectric semiconductor-induced apoptosis and cuproptosis. This article is protected by copyright. All rights reserved.

Redox signaling and oxidative stress in systemic acquired resistance.

Plants fully depend on their immune systems to defend against pathogens. Upon pathogen attack, plants not only activate immune responses at the infection site but also trigger a defense mechanism known as systemic acquired resistance (SAR) in distal systemic tissues to prevent subsequent infections by a broad-spectrum of pathogens. SAR is induced by mobile signals produced at the infection site. Accumulating evidence suggests that reactive oxygen species (ROS) play a central role in SAR signaling. ROS burst at the infection site is one of the earliest cellular responses following pathogen infection and can spread to systemic tissues through membrane-associated NADPH oxidase-dependent relay-production of ROS. It is well known that ROS ignite redox signaling and when in excess, cause oxidative stress damaging cellular components. In this review, we summarize current knowledge on redox regulation of several SAR signaling components. We discuss the ROS amplification loop in systemic tissues involving multiple SAR mobile signals. Moreover, we highlight the essential role of oxidative stress in generating SAR signals including azelaic acid and extracellular NAD(P) [eNAD(P)]. Finally, we propose that eNAD(P) is a damage-associated molecular pattern serving as a converging point of SAR mobile signals in systemic tissues.

The Truncated Peptide AtPEP1(9–23) Has the Same Function as AtPEP1(1–23) in Inhibiting Primary Root Growth and Triggering of ROS Burst

Currently, the widely used active form of plant elicitor peptide 1 (PEP1) from Arabidopsis thaliana is composed of 23 amino acids, hereafter AtPEP1(1–23), serving as an immune elicitor. The relatively less conserved N-terminal region in AtPEP family indicates that the amino acids in this region may be unrelated to the function and activity of AtPEP peptides. Consequently, we conducted an investigation to determine the necessity of the nonconserved amino acids in AtPEP1(1–23) peptide for its functional properties. By assessing the primary root growth and the burst of reactive oxygen species (ROS), we discovered that the first eight N-terminal amino acids of AtPEP1(1–23) are not crucial for its functionality, whereas the conserved C-terminal aspartic acid plays a significant role in its functionality. In this study, we identified a truncated peptide, AtPEP1(9–23), which exhibits comparable activity to AtPEP1(1–23) in inhibiting primary root growth and inducing ROS burst. Additionally, the truncated peptide AtPEP1(13–23) shows similar ability to induce ROS burst as AtPEP1(1–23), but its inhibitory effect on primary roots is significantly reduced. These findings are significant as they provide a novel approach to explore and understand the functionality of the AtPEP1(1–23) peptide. Moreover, exogenous application of AtPEP1(13–23) may enhance plant resistance to pathogens without affecting their growth and development. Therefore, AtPEP1(13–23) holds promise for development as a potentially applicable biopesticides.

Photosensitive AIEgens sensitize bacteria to oxidative damage and modulate the inflammatory responses of macrophages to salvage the photodynamic therapy against MRSA

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents.

Plant immunity suppression by an β-1,3-glucanase of the maize anthracnose pathogen Colletotrichum graminicola

BackgroundMany phytopathogens secrete a large number of cell wall degrading enzymes (CWDEs) to decompose host cell walls in order to penetrate the host, obtain nutrients and accelerate colonization. There is a wide variety of CWDEs produced by plant pathogens, including glycoside hydrolases (GHs), which determine the virulence, pathogenicity, and host specificity of phytopathogens. The specific molecular mechanisms by which pathogens suppress host immunity remain obscure.ResultIn this study, we found that CgEC124 encodes a glycosyl hydrolase with a signal peptide and a conserved Glyco_hydro_cc domain which belongs to glycoside hydrolase 128 family. The expression of CgEC124 was significantly induced in the early stage of Colletotrichum graminicola infection, especially at 12 hpi. Furthermore, CgEC124 positively regulated the pathogenicity, but it did not impact the vegetative growth of mycelia. Ecotopic transient expression of CgEC124 decreased the disease resistance and callose deposition in maize. Moreover, CgEC124 exhibited the β-1,3-glucanase activity and suppresses glucan-induced ROS burst in maize leaves.ConclusionsOur results indicate that CgEC124 is required for full virulence of C. graminicola but not for vegetative growth. CgEC124 increases maize susceptibility by inhibiting host reactive oxygen species burst as well as callose deposition. Meanwhile, our data suggests that CgEC124 explores its β-1,3-glucanase activity to prevent induction of host defenses.

Three new discovery effector proteins from Candidatus Liberibacter asiaticus psy62 inhibit plant defense through interaction with AtCAT3 and AtGAPA.

We identify three SDEs that inhibiting host defence from Candidatus Liberibacter asiaticus psy62, which is an important supplement to the pathogenesis of HLB. Candidatus Liberibacter asiaticus (CLas) is the main pathogen of citrus Huanglongbing (HLB). 38 new possible sec-dependent effectors (SDEs) of CLas psy62 were predicted by updated predictor SignalP 5.0, which 12 new SDEs were found using alkaline phosphate assay. Among them, SDE4310, SDE4435 and SDE4955 inhibited hypersensitivity reactions (HR) in Arabidopsis thaliana (Arabidopsis, At) and Nicotiana benthamiana leaves induced by pathogens, which lead to a decrease in cell death and reactive oxygen species (ROS) accumulation. And the expression levels of SDE4310, SDE4435, and SDE4955 genes elevated significantly in mild symptom citrus leaves. When SDE4310, SDE4435 and SDE4955 were overexpressed in Arabidopsis, HR pathway key genes pathogenesis-related 2 (PR2), PR5, nonexpressor of pathogenesis-related 1 (NPR1) and isochorismate synthase 1 (ICS1) expression significantly decreased and the growth of pathogen was greatly increased relative to control with Pst DC3000/AvrRps4 treatment. Our findings also indicated that SDE4310, SDE4435 and SDE4955 interacted with AtCAT3 (catalase 3) and AtGAPA (glyceraldehyde-3-phosphate dehydrogenase A). In conclusion, our results suggest that SDE4310, SDE4435 and SDE4955 are CLas psy62 effector proteins that may have redundant functions. They inhibit ROS burst and cell death by interacting with AtCAT3 and AtGAPA to negatively regulate host defense.

Diallyl Trisulfide Acts as a Soil Disinfestation Against the Ilyonectria destructans through Inducing the Burst of Reactive Oxygen Species.

Soil-borne diseases represent an impediment to the sustainable development of agriculture. A soil-borne disease caused by Ilyonectria destructans severely impacts Panax species, and soil disinfestation has proven to be an effective management approach. Here, diallyl trisulfide (DATS), derived from garlic, exhibited pronounced inhibitory effects on the growth of I. destructans in vitro tests and contributed to the alleviation of soil-borne diseases in the field. A comprehensive analysis demonstrated that DATS inhibits the growth of I. destructans by activating detoxifying enzymes, such as GSTs, disrupting the equilibrium of redox reactions. A series of antioxidant amino acids were suppressed by DATS. Particularly noteworthy is the substantial depletion of glutathione by DATS, resulting in the accumulation of ROS, ultimately culminating in the inhibition of I. destructans growth. Briefly, DATS could effectively suppress soil-borne diseases by inhibiting pathogen growth through the activation of ROS, and it holds promise as a potential environmentally friendly soil disinfestation.

MnO2-based capacitive system enhances ozone inactivation of bacteria by disrupting cell membrane

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.

Ferrous gluconate triggers ferroptosis in Escherichia coli: Implications of lipid peroxidation and DNA damage

Microbial ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular reactive oxygen species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.

NADPH oxidase-mediated sulfenylation of cysteine derivatives is key regulatory events for plant immune responses.

Reactive oxygen species (ROS) are rapidly generated during plant immune responses by RBOH, which is a plasma membrane-localizing NADPH oxidase. Although regulatory mechanisms of RBOH activity have been well documented, the ROS-mediated downstream signaling is unclear. We here demonstrated that ROS sensor proteins play a central role in the ROS signaling via oxidative post-translational modification of cysteine residues, sulfenylation. To detect protein sulfenylation, we used dimedone, which specifically and irreversibly binds to sulfenylated proteins. The sulfenylated proteins were labeled by dimedone in Nicotiana benthamiana leaves, and the conjugates were detected by immunoblot analyses. In addition, a reductant dissociated H2O2-induced conjugates, suggesting that cysteine persulfide and/or polysulfides are involved in sulfenylation. These sulfenylated proteins were continuously increased during both PTI and ETI in a RBOH-dependent manner. Pharmacological inhibition of ROS sensor proteins by dimedone perturbated cell death, ROS accumulation induced by INF1 and MEK2DD, and defense against fungal pathogens. On the other hand, Rpi-blb2-mediated ETI responses were rather enhanced by dimedone. These results suggest that the sulfenylation of cysteine and its derivatives in various ROS sensor proteins are important events in downstream of RBOH-dependent ROS burst to regulate plant immune responses.

Naringenin restricts the colonization and growth of Ralstonia solanacearum in tobacco mutant KCB-1.

Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first demonstrated that the roots of bacterial wilt-resistant tobacco mutant KCB-1 can limit the growth and reproduction of Ralstonia solanacearum. Secondly, we demonstrated that KCB-1 specifically induced an upregulation of naringenin content in root metabolites and root secretions. Further experiments showed that naringenin can disrupt the structure of R. solanacearum, inhibit the growth and reproduction of R. solanacearum, and exert a controlling effect on bacterial wilt. Exogenous naringenin application activated the resistance response in tobacco by inducing the burst of reactive oxygen species and salicylic acid deposition, leading to transcriptional reprogramming in tobacco roots. Additionally, both external application of naringenin in CB-1 and overexpression of the Nicotiana tabacum chalcone isomerase (NtCHI) gene, which regulates naringenin biosynthesis, in CB-1 resulted in a higher complexity of their inter-root bacterial communities than in untreated CB-1. Further analysis showed that naringenin could be used as a marker for resistant tobacco. The present study provides a reference for analyzing the resistance mechanism of bacterial wilt-resistant tobacco and controlling tobacco bacterial wilt.

The critical role of CmCIPK1-CmRbohD1/D2 complexes in generating H2O2 signals for enhancing salt tolerance in pumpkins

Pumpkin is of great economic importance not only as food resources but also as the most widely used rootstock to graft cucurbit crops. Pumpkin rootstock improves salt tolerance of cucumber scion through respiratory burst oxidase homolog protein D (CmRbohD)-mediated reactive oxygen species (ROS) burst, which further enhances Na+ export and K+ uptake. RbohD activation requires calcium signaling. However, the underlying mechanism remains largely unknown. In this study, we discovered two RbohD members from pumpkin involved in the ROS burst at the early stage of salt stress. CmRbohD1 and CmRbohD2 were functionally redundant and double mutation significantly impaired salt tolerance in pumpkin. Overexpression of CmRbohD1 and CmRbohD2 mitigated salinity-induced damage and maintained a relatively low Na+ content and high K+ content. We screened the potential calcineurin B-like interacting protein kinases (CmCIPKs) which could bind with CmRbohD1 and CmRbohD2. Our results revealed that two RbohDs formed complexes specifically with CmCIPK1, thereby bursting ROS production. Overexpression of CmCIPK1 promoted the early ROS burst under salt stress condition and maintained a relatively balanced Na+/K+ homeostasis. Altogether, we proposed a CmCIPK1-CmRbohD1/D2 complex for pumpkin salt stress signaling transduction, which regulates the ROS burst and Na+/K+ homeostasis. Our findings offer unprecedented insights into the general mechanism of pumpkin salt tolerance.

MdWRKY45 contributes to resistance against Botryosphaeria dothidea in apple

Malus domestica “Fuji” is the predominant apple cultivar grown around the world, but it is highly susceptible to apple ring rot caused by Botryosphaeria dothidea. WRKY transcription factors (TFs) play key roles in multiple physiological responses to plant defense. We have previously reported the involvement of several MdWRKY TFs in plant defense against. In this study, we identified a new MdWRKY TF, MdWRKY45, which is induced by B. dothidea infection. MdWRKY45 was localized in the nucleus and exhibited transcriptional activity. Over-expression of MdWRKY45 enhanced the resistance of transgenic apple calli and fruits to B. dothidea infection. Conversely, suppression of MdWRKY45 decreased the disease resistance of apple calli and fruits. Further transcriptome profiling and expression analysis showed that various genes regulating the release of salicylic acid (SA), jasmonic acid (JA), and reactive oxygen species (ROS) were either up-regulated or down-regulated in MdWRKY45-RNAi transgenic apple calli compared with wild-type (WT). During B. dothidea infection, MdWRKY45 modulated the levels of SA and JA, as well as ROS burst. Moreover, MdWRKY45 could bind to the W-box cis-element in the promoters of MdPR1, MdJAZ1, and MdRbohF genes, thereby regulating their expression. In conclusion, MdWRKY45 primarily confers resistance to B. dothidea infection through pathways involving SA, JA, and ROS burst defense.

Functional screening of the Arabidopsis 2C protein phosphatases family identifies PP2C15 as a negative regulator of plant immunity by targeting BRI1-associated receptor kinase 1.

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.

Unveiling the structural properties and induced resistance activity in rice of Chitin/Chitosan-Glucan Complex of Rhizoctonia solani AG1 IA inner cell wall

Phytopathogen cell wall polysaccharides have important physiological functions. In this study, we isolated and characterized the alkali-insoluble residue on the inner layers of the Rhizoctonia solani AG1 IA cell wall (RsCW-AIR). Through chemical composition and structural analysis, RsCW-AIR was mainly identified as a complex of chitin/chitosan and glucan (ChCsGC), with glucose and glucosamine were present in a molar ratio of 2.7:1.0. The predominant glycosidic bond linkage of glucan in ChCsGC was β-1,3-linked Glcp, both the α and β-polymorphic forms of chitin were presented in it by IR, XRD, and solid-state NMR, and the ChCsGC exhibited a degree of deacetylation measuring 67.08 %. RsCW-AIR pretreatment effectively reduced the incidence of rice sheath blight, and its induced resistance activity in rice was evaluated, such as inducing a reactive oxygen species (ROS) burst, leading to the accumulation of salicylic acid (SA) and the up-regulation of SA-related gene expression. The recognition of RsCW-AIR in rice is partially dependent on CERK1.

Trichoderma-secreted anthranilic acid promotes lateral root development via auxin signaling and RBOHF-induced endodermal cell wall remodeling

Trichoderma spp. have evolved the capacity to communicate with plants by producing various secondary metabolites (SMs). Nonhormonal SMs play important roles in plant root development, while specific SMs from rhizosphere microbes and their underlying mechanisms to control plant root branching are still largely unknown. In this study, a compound, anthranilic acid (2-AA), is identified from T.guizhouense NJAU4742 to promote lateral root development. Further studies demonstrate that 2-AA positively regulates auxin signaling and transport in the canonical auxin pathway. 2-AA also partly rescues the lateral root numbers of CASP1pro:shy2-2, which regulates endodermal cell wall remodeling via an RBOHF-induced reactive oxygen species burst. In addition, our work reports another role for microbial 2-AA in the regulation of lateral root development, which is different from its better-known role in plant indole-3-acetic acid biosynthesis. In summary, this study identifies 2-AA from T.guizhouense NJAU4742, which plays versatile roles in regulating plant root development.

Abstract 6861: PIK3CA activating mutation promotes an immune suppressive microenvironment in squamous cell carcinoma

Abstract Head and neck squamous cell carcinoma (HNSCC) is a leader in cancer incidence worldwide. Recently, immunotherapies such as immune checkpoint blockade (ICB) have offered great promise in treating many solid tumors, including HNSCCs, that are refractory to chemotherapy and radiation. Challengingly, HNSCC patients often relapse following ICB treatment due to the lack of a thorough understanding of the mechanisms underlying cancer immune evasion. These disparities in patient outcomes strongly suggest the existence of genetic variations that underlie their distinct responses to ICB. Although the specific oncogenic mutations responsible for driving relapse in SCC patients remain unclear, it is imperative to grasp the mechanisms of cancer immune evasion in individuals with specific genetic profiles to enhance the precision of immunotherapy. Cancer immune evasion has emerged as a hallmark of cancer and is facilitated by a highly complex tumor microenvironment (TME). We aim to understand the genetic basis shaping the immune suppressive TME and hypothesize that oncogenic driver mutations play a dominant role in preventing the immune clearance of transformed cells by reprogramming the immune landscape in the tumors. To determine the critical genetic signatures enriched in SCC patients that can impact anti-tumor immunity, we analyzed TCGA data which revealed a strong negative correlation between PIK3CA level and CD8 T cell signatures. We have identified that activating mutations in the PIK3CA gene, found in 20% of HNSCCs, promote rapid tumor relapse after initial response to anti-PD-L1 and anti-CTLA-4 ICB treatments. Utilizing single-cell analysis, quantitative immune profiling, and multiplexed imaging, our lab showed that tumor-initiating cells (TICs) in SCCs can have an intricate dialogue with myeloid-derived suppressor cells (MDSCs) where TICs secrete factors to enhance MDSC recruitment and suppressive function on cytotoxic T cells. Additionally, our data supports that the tumor interstitial fluid (TIF) of PIK3CA mutant SCC tumors can enhance the suppressive activity of MDSCs on cytotoxic T cells. These results suggest that the acquisition of PIK3CA mutation may trigger TICs to release additional factors to further modify MDSC activities. A critical method by which MDSCs suppress T cells is through the production and respiratory burst of reactive oxygen species (ROS). RNA sequencing revealed that PIK3CA mutant SCCs have multiple mechanisms of increasing ROS in the TME and specifically in MDSCs, while simultaneously upregulating lipid metabolism genes, such as SCD1, to protect itself from MDSC-derived ROS. This study reveals a potential strategy for targeting PIK3CA mutant SCCs as a promising precision immunotherapy to enhance the efficacy of ICB treatments. Citation Format: Benjamin T. Nicholson, Weijie Guo, Yuxuan Miao. PIK3CA activating mutation promotes an immune suppressive microenvironment in squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6861.

Scalable and Versatile Metal Ion Solidificated Alginate Hydrogel for Skin Wound Infection Therapy.

Bacterial infections in wounds continue to be a major challenge in clinical settings worldwide and represent a significant threat to human health. This work proposes novel expandable and versatile methods for solidifying sodium alginate (SA) with metal ions (such as Fe3+ , Co2+ , Ni2+ , Cu2+ , and Zn2+ ) to create Metal-Alginate (M-Alg) hydrogel with adjustable morphology, composition, and microstructure. It conforms to the wound site, protects against second infection, reduces inflammation, and promotes the healing of infected wounds. Among these hydrogels, Cu-Alginate (Cu-Alg) shows excellent sterilization effect and good efficacy against both gram-positive and gram-negative bacteria, including multidrug-resistant (MDR) strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) due to its dual antibacterial mechanisms: contact-killing and reactive oxygen species (ROS) burst. Importantly, it exhibits low cytotoxicity and biodegradability. This simple and cost-effective gel-based system has the potential to introduce an innovative approach to the management of wound infection and offers promising new perspectives for the advancement of wound care practice.

Oxidation-reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium.

Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.

When the microbiome shapes the host: immune evolution implications for infectious disease.

The microbiome includes both 'mutualist' and 'pathogen' microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests hosts can selectively activate innate immunity upon pathogenic infection, but not mutualist colonization. Another idea posits that hosts can selectively attack pathogens, but not mutualists. Here I review evolutionary principles of microbe recognition and immune activation, and reflect on newly observed immune effector-microbe specificity perhaps supporting the latter idea. Recent work in Drosophila has found a surprising importance for single antimicrobial peptides in combatting specific ecologically relevant microbes. The developing picture suggests these effectors have evolved for this purpose. Other defence responses like reactive oxygen species bursts can also be uniquely effective against specific microbes. Signals in other model systems including nematodes, Hydra, oysters, and mammals, suggest that effector-microbe specificity may be a fundamental principle of host-pathogen interactions. I propose this effector-microbe specificity stems from weaknesses of the microbes themselves: if microbes have intrinsic weaknesses, hosts can evolve effectors that exploit those weaknesses. I define this host-microbe relationship as 'the Achilles principle of immune evolution'. Incorporating this view helps interpret why some host-microbe interactions develop in a coevolutionary framework (e.g. Red Queen dynamics), or as a one-sided evolutionary response. This clarification should be valuable to better understand the principles behind host susceptibilities to infectious diseases. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.