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Sanghwa Lee,1,* Jung-Man Namgoong,2,* Miyeon Jue,1 Yujin Joung,1 Chae-Min Ryu,3,4 Dong-Myung Shin,4 Myung-Soo Choo,3 Jun Ki Kim1,5 1Biomedical Engineering Research Center, Asan Medical Center, Seoul 05505, Republic of Korea; 2Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; 3Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; 4Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; 5Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea*These authors contributed equally to this workCorrespondence: Jun Ki Kim Email kim@amc.seoul.krBackground: This study investigated the diagnosis of renal diseases using a biochip capable of detecting nano-sized biomarkers. Raman measurements from a kidney injury model were taken, and the feasibility of early diagnosis was assessed.Materials and Methods: Rat models with mild and severe unilateral ureteral obstructions were created, with the injury to the kidney varying according to the tightness of the stricture. After generating the animal ureteral obstruction models, urine was collected from the kidney and bladder.Results and Discussion: After confirming the presence of renal injury, urine drops were placed onto a Raman chip whose surface had been enhanced with Au-ZnO nanorods, allowing nano-sized biomarkers that diffused into the nanogaps to be selectively amplified. The Raman signals varied according to the severity of the renal damage, and these differences were statistically confirmed.Conclusion: These results confirm that ureteral stricture causes kidney injury and that signals in the urine from the release of nano-biomarkers can be monitored using surface-enhanced Raman spectroscopy.Keywords: ureteral obstruction, renal injury, nano-sized biomarker, ZnO nanorods, surface-enhanced Raman spectroscopy, principal component analysis

Lipid nanoparticles (LNPs) can assist in the delivery of nucleic acid inside animal cells, as demonstrated by their use in COVID-19 vaccine development. However, LNPs applicable to bacteria have not been reported. Here, the screening of 511 LNPs containing random combinations of different lipid components identified two LNPs, LNP 496 and LNP 470, that efficiently delivered plasmids into Escherichia coli BW25113. Since Gram-negative bacteria have lipid bilayers, the bacteria are pretreated with LNP-helper that weakens the bacterial membrane. The cationic lipid DOTAP improved delivery of LNP-encapsulated plasmid DNA when present at a molar ratio of 10-25 mol% in the LNP. LNP encapsulation of the Cas13a/gRNA expression vector controlled infection by a clinical Escherichia strain in Galleria mellonela larvae and mouse infection models when used in combination with non-cytotoxic concentrations of polymyxin B, a bacterial membrane disruptor. Together, the results show that LNPs can be useful as a delivery platform for agents that counteract pathogenic bacterial infections., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Polyethylene is widely used but highly resistant to biodegradation, owing to its composition of only a hydrocarbon backbone. For biodegradation to occur, oxidation within the polymer needs to be initiated. Galleria mellonella was the first insect discovered to autonomously oxidize polyethylene without the aid of gut microbes. However, the specific enzyme remains unidentified. Here, we identified for the first time two polyethylene oxidation enzyme candidates of cytochrome P450 (CYP) 6B2-GP04 and CYP6B2-13G08 from the G. mellonella midgut. Both candidate clones oxidized polyethylene efficiently, generating short-chain aliphatic compounds, with CYP6B2-GP04 exhibiting higher activity than CYP6B2-13G08 in yeast and insect cells. In silico structural modeling approaches revealed that the CYP6B2-GP04 Phe118 was essential for interacting with hydrocarbons, which was further validated by mutating phenylalanine to glycine. Furthermore, directed enzyme evolution led to the identification of an enzyme variant with significantly increased oxidation efficiency. Our findings offer promising enzyme-based solutions for polyethylene biodegradation, potentially mitigating polyethylene-driven plastic pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ralstonia solanacearum and R. pseudosolanacearum , the causative agents of bacterial wilt, ranks as the second most devastating phytopathogens, affecting over 310 plant species and causing substantial economic losses worldwide. R. solanacearum and R. pseudosolanacearum infect plants through the underground root system, where it interacts with both the host and the surrounding microbiota and multiply in the xylem where bacteria cell and its polysaccharide product block the water transportation from root to aboveground. Currently, effective control methods are limited, as resistance genes are unavailable and antibiotics prove ineffective. In current Commentary, we review recent advancements in combating bacterial wilt, categorizing the approaches (weapons) into three distinct strategies. The physical and chemical weapons focus on leveraging sound waves to trigger crop immunity and reducing bacterial virulence signaling, respectively. The biological weapon employs predatory protists to directly consume Ralstonia cells in the root zone, while also reshaping the protective rhizosphere microbiome to fortify the plant. We believe that these novel methods hold the potential to revolutionize crop protection from bacterial wilt and inspire new era in sustainable agriculture.

Ralstonia pseudosolanacearum , a notorious phytopathogen, is responsible for causing bacterial wilt, leading to significant economic losses globally in many crops within the Solanaceae family. Despite various cultural and chemical control strategies, managing bacterial wilt remains a substantial challenge. This study demonstrates, for the first time, the effective use of plant-induced bacterial gene silencing against R. pseudosolanacearum , facilitated by Tobacco rattle virus -mediated gene silencing, to control bacterial wilt symptoms in Nicotiana benthamiana . The methodology described in this study could be utilized to identify novel phytobacterial virulence factors through both forward and reverse genetic approaches. To validate plant-induced gene silencing, small RNA fractions extracted from plant exudates were employed to silence bacterial gene expression, as indicated by the reduction in the expression of GFP and virulence genes in R. pseudosolanacearum . Furthermore, treatment of human and plant pathogenic Gram-negative and Gram-positive bacteria with plant-generated small RNAs resulted in the silencing of target genes within 48 hours. Taken together, the results suggest that this technology could be applied under field conditions, offering precise, gene-based control of target bacterial pathogens while preserving the indigenous microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jang, Kim, Lee and Ryu.)

The emergence of waterlogged Oryza species ∼15Mya (million years ago) supplied an anoxic warm bed for methane-producing microorganisms, and methane emissions have hence accompanied the entire evolutionary history of the genus Oryza. However, to date no study has addressed how methane emission has been altered during Oryza evolution. In this paper we used a diverse collection of wild and cultivated Oryza species to study the relation between Oryza evolution and methane emissions. Phylogenetic analyses and methane detection identified a co-evolutionary pattern between Oryza and methane emissions, mediated by the diversity of the rhizospheric ecosystems arising from different oxygen levels. Fumarate was identified as an oxygen substitute used to retain the electron transport/energy production in the anoxic rice root, and the contribution of fumarate reductase to Oryza evolution and methane emissions has also been assessed. We confirmed the between-species patterns using genetic dissection of the traits in a cross between a low and high methane-emitting species. Our findings provide novel insights on the evolutionary processes of rice paddy methane emissions: the evolution of wild rice produces different Oryza species with divergent rhizospheric ecosystem attributing to the different oxygen levels and fumarate reductase activities, methane emissions are comprehensively assessed by the rhizospheric environment of diversity Oryza species and result in a co-evolution pattern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The year 2023 was the warmest year since 1850. Greenhouse gases, including CO 2 and methane, played a significant role in increasing global warming. Among these gases, methane has a 25-fold greater impact on global warming than CO 2 . Methane is emitted during rice cultivation by a group of rice rhizosphere microbes, termed methanogens, in low oxygen (hypoxic) conditions. To reduce methane emissions, it is crucial to decrease the methane production capacity of methanogens through water and fertilizer management, breeding of new rice cultivars, regulating root exudation, and manipulating rhizosphere microbiota. In this opinion article we review the recent developments in hypoxia ecology and methane emission mitigation and propose potential solutions based on the manipulation of microbiota and methanogens for the mitigation of methane emissions., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease with limited treatment options. Current multidisciplinary approach targeting bladder inflammation and urothelial dysfunction has limited durable effect that major surgery is ultimately required for both Hunner and non-Hunner type IC. Various investigational attempts are underway to avoid such operations and preserve the urinary bladder. Stem cell therapy is a fascinating option for treating chronic illnesses. Stem cells can self-renew, restore damaged tissue, and have paracrine effects. The therapeutic efficacy and safety of stem cell therapy have been demonstrated in numerous preclinical models, primarily chemically induced cystitis rat models. Only one clinical trial (phase 1 study) has investigated the safety of human embryonic stem cell-derived mesenchymal stem cells in three Hunner-type IC patients. Under general anesthesia, participants underwent cystoscopic submucosal stem cell injection (2.0 × 10 7 stem cells/5 mL). No safety issues were reported up to 12 months of follow-up and long-term follow-up (up to 3 years). Although there were variations in therapeutic response, all patients reported significant improvement in pain at 1 month postoperatively. One patient underwent fulguration of the Hunner lesion after the trial, but others reported an overall improvement in pain. The analysis on phase 1/2a trial which had several modifications in protocol is currently ongoing. Despite several limitations that need to be overcome, stem cell therapy could be a potential therapeutic option for treating IC/BPS. Clinical outcome on phase 1/2a trial is important and might provide more insight into the clinical application of stem cell therapy for IC/BPS., (© 2024 John Wiley & Sons Australia, Ltd.)

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia., (© 2024. The Author(s).)

During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as 'maskne' (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either 'pathogen helper (PH)' or 'pathogen inhibitor (PIn)' strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen., (© 2024. The Author(s).)

In recent years, the idea has flourished that plants emit and perceive sound and could even be capable of exchanging information through the acoustic channel. While research into plant bioacoustics is still in its infancy, with potentially fascinating discoveries awaiting ahead, here we show that the current knowledge is not conclusive. While plants do emit sounds under biotic and abiotic stresses such as drought, these sounds are high-pitched, of low intensity, and propagate only to a short distance. Most studies suggesting plant sensitivity to airborne sound actually concern the perception of substrate vibrations from the soil or plant part. In short, while low-frequency, high-intensity sounds emitted by a loudspeaker close to the plant seem to have tangible effects on various plant processes such as growth - a finding with possible applications in agriculture - it is unlikely that plants can perceive the sounds they produce, at least over long distances. So far, there is no evidence of plants communicating with each other via the acoustic channel., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively). CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.

Bemisia tabaci (whitefly) is a polyphagous agroeconomic pest species complex. Two members of this species complex, Mediterranean (MED) and Middle-East-Asia Minor 1 (MEAM1), have a worldwide distribution and have been shown to manipulate plant defenses through effectors. In this study, we used three different strategies to identify three MEAM1 proteins that can act as effectors. Effector B1 was identified using a bioinformatics-driven effector-mining strategy, whereas effectors S1 and P1 were identified in the saliva of whiteflies collected from artificial diet and in phloem exudate of tomato on which nymphs were feeding, respectively. These three effectors were B. tabaci specific and able to increase whitefly fecundity when transiently expressed in tobacco plants ( Nicotiana tabacum ). Moreover, they reduced growth of Pseudomonas syringae pv. tabaci in Nicotiana benthamiana . All three effectors changed gene expression in planta, and B1 and S1 also changed phytohormone levels. Gene ontology and KEGG pathway enrichment analysis pinpointed plant-pathogen interaction and photosynthesis as the main enriched pathways for all three effectors. Our data thus show the discovery and validation of three new B. tabaci MEAM1 effectors that increase whitefly fecundity and modulate plant immunity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license., Competing Interests: The author(s) declare no conflict of interest.

Despite extensive knowledge of antibiotic-targeted bacterial cell death, deeper understanding of antibiotic tolerance mechanisms is necessary to combat multi-drug resistance in the global healthcare settings. Regulatory RNAs in bacteria control important cellular processes such as cell division, cellular respiration, metabolism, and virulence. Here, we investigated how exposing Escherichia coli to the moderately effective first-generation antibiotic cephalothin alters transcriptional and post-transcriptional dynamics. Bacteria switched from active aerobic respiration to anaerobic adaptation via an FnrS and Tp2 small RNA-mediated post-transcriptional regulatory circuit. From the early hours of antibiotic exposure, FnrS was involved in regulating reactive oxygen species levels, and delayed oxygen consumption in bacteria. We demonstrated that bacteria strive to maintain cellular homeostasis via sRNA-mediated sudden respiratory changes upon sublethal antibiotic exposure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Bhat, Kim, Lee and Ryu.)

Skin microbiota, such as acne-related Cutibacterium acnes , Staphylococcus aureus , and fungal Candida albicans , can form polymicrobial biofilms with greater antimicrobial tolerance to traditional antimicrobial agents and host immune systems. In this study, the phytopigment shikonin was investigated against single-species and multispecies biofilms under aerobic and anaerobic conditions. Minimum inhibitory concentrations of shikonin were 10 µg/mL against C. acnes , S. aureus , and C. albicans , and at 1-5 µg/mL, shikonin efficiently inhibited single biofilm formation and multispecies biofilm development by these three microbes. Shikonin increased porphyrin production in C. acnes , inhibited cell aggregation and hyphal formation by C. albicans , decreased lipase production, and increased hydrophilicity in S. aureus . In addition, shikonin at 5 or 10 µg/mL repressed the transcription of various biofilm-related genes and virulence-related genes in C. acnes and downregulated the gene expression levels of the quorum-sensing agrA and RNAIII , α-hemolysin hla , and nuclease nuc1 in S. aureus , supporting biofilm inhibition. In addition, shikonin prevented multispecies biofilm development on porcine skin, and the antimicrobial efficacy of shikonin was recapitulated in a mouse infection model, in which it promoted skin regeneration. The study shows that shikonin inhibits multispecies biofilm development by acne-related skin microbes and might be useful for controlling bacterial infections.

The holobiont Holobiont theory is more than 80 years old, while the importance of microbial communities for plant holobionts was already identified by Lorenz Hiltner more than a century ago. Both concepts are strongly supported by results from the new field of microbiome research. Here, we present ecological and genetic features of the plant holobiont that underpin principles of a shared governance between hosts and microbes and summarize the relevance of plant holobionts in the context of global change. Moreover, we uncover knowledge gaps that arise when integrating plant holobionts in the broader perspective of the holobiome as well as one and planetary health concepts. Action is needed to consider interacting holobionts at the holobiome scale, for prediction and control of microbiome function to improve human and environmental health outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Abstract: Introduction: Gut microbiota dysbiosis is associated with susceptibility to sepsis and poor outcomes. However, changes to the intestinal microbiota during sepsis and their value as biomarkers are unclear. In this study, we compared the intestinal microbiota of patients with sepsis and healthy controls. Methods: Stool was collected from patients with sepsis (subdivided according to mortality) and controls. Microbiome diversity and composition were analyzed by 16S rRNA gene pyrosequencing. The α-diversity of the intestinal microbiome was determined using operational taxonomic unit counts and the Chao1, Shannon, and ACE indices. Adjusted Cox regression analyses assessed 6-month mortality risk factors. Results: Fifty-nine patients (14 in-hospital deaths) and 29 healthy controls were enrolled. Operational taxonomic unit counts and Chao1 and ACE indices were lower in the nonsurvivor than in the other groups. The controls showed a higher Shannon and lower Simpson index than did the sepsis group. The genus Blautia was more abundant in controls than in the sepsis group, and Faecalibacterium less abundant in the nonsurvivor than in the other groups. Regression analysis associated low Shannon index with 6-month mortality. Conclusions: Survivors of sepsis, nonsurvivors, and healthy controls have different gut microbiomes, and a low Shannon index is a risk factor for 6-month mortality., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Active plant immune response involving programmed cell death called the hypersensitive response (HR) is elicited by microbial effectors delivered through the type III secretion system (T3SS). The marine bacterium Hahella chejuensis contains two T3SSs that are similar to those of animal pathogens, but it was able to elicit HR-like cell death in the land plant Nicotiana benthamiana. The cell death was comparable with the transcriptional patterns of H. chejuensis T3SS-1 genes, was mediated by SGT1, a general regulator of plant resistance, and was suppressed by AvrPto1, a type III-secreted effector of a plant pathogen that inhibits HR. Thus, type III-secreted effectors of a marine bacterium are capable of inducing the nonhost HR in a land plant it has never encountered before. This suggests that plants may have evolved to cope with a potential threat posed by alien pathogen effectors. Our work documents an exceptional case of nonhost HR and provides an expanded perspective for studying plant nonhost resistance.

Exploring host cell specificity, pathogenicity, and molecular mechanisms of the vacuolating cytotoxin A (VacA), secreted by Helicobacter pylori (Hp) is crucial for developing novel treatment strategies. VacA affects subcellular events, particularly mitochondria, at a cell-type-specific level. However, the lack of reliable models that mimic VacA-induced subcellular damages and enable novel drug screening linked to the human stomach clinically limits our understanding of the mitochondrial networks in vivo. Here, human antrum gastric organoids (hAGOs) and tissue samples from Hp-infected patients were used to show the toxic effects of VacA-induced mitochondrial damage mainly in mucus-producing gastric pit cells by employing transcriptional, translational, and functional analyses. In VacA-intoxicated or Hp-infected hAGOs, robust mitochondrial fragmentation in gastric pit cells reduced ATP production during respiration, and loss of mucosal barrier integrity was first demonstrated experimentally. Using hAGOs, clinically relevant small molecules were screened for efficacy, and MLN8054, an Aurora kinase A inhibitor, reversed VacA-induced mitochondrial damage and loss of gastric epithelium integrity. MLN8054 was effective in VacA-treated and Hp-infected hAGOs and mice, highlighting hAGOs as a promising drug-screening model. These findings suggest that mitochondrial quality control may serve as a promising therapeutic target for Hp VacA-mediated toxicity and disease progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) is a network of funders supporting research on infectious diseases of epidemic/pandemic potential. GloPID-R is establishing regional hubs to strengthen stakeholder engagement particularly among low-income and middle-income countries. The first pilot hub, led from Republic of Korea (South Korea), has been launched in the Asia-Pacific region, a region highly prone to outbreaks of emerging infectious diseases. We present findings of mapping research undertaken in support of the hub's development., Methods: We analysed five COVID-19 research databases in September 2022 to identify research funders and intermediary funding sources supporting research in infectious diseases in the Asia-Pacific region. This was complemented with an in-depth analysis of the UK Collaborative on Development Research (UKCDR) and GloPID-R COVID-19 Research Project Tracker to assess the alignment of funded projects in the region to the WHO COVID-19 research priorities., Results: We identified 453 funders and funding sources supporting COVID-19 research in the Asia-Pacific Region including public, private and philanthropic organisations and universities. However, these organisations were clustered in few countries in the region. The in-depth analysis of the UKCDR and GloPID-R COVID-19 Research project Tracker found limited research involving Asia-Pacific countries with the 117 funders supporting these projects investing at least US$604m in COVID-19 research in the region. Social Sciences was the dominant theme on which funded projects focused whereas the priority areas with the least number of projects were research on 'animal and environmental health' and 'ethics considerations for research'., Conclusion: Our analyses show the diversity of funding sources for research on infectious diseases in the Asia-Pacific region. Engagement between multiple actors in the health research system is likely to promote enhanced coordination for greater research impact. GloPID-R's Asia-Pacific regional hub aims to support activities for the enhancement of preparedness for outbreaks of emerging infectious diseases in the region., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs., Competing Interests: Declaration of interests D.-M.S. cofounded Cell2in, a company focused on developing FreSHtracer-based GRC assays., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bacillus velezensis strain GB03 is a Gram-positive rhizosphere bacterium known for its ability to promote plant growth and immunity. This review provides a comprehensive overview of the research on GB03 from its initial discovery in Australian wheat fields in 1971 to its current applications. Recognized as a model plant growth-promoting rhizobacterium (PGPR), GB03 has exhibited outstanding performance in enhancing the growth and protection of many crop plants including cucumber, pepper, wheat, barley, soybean, and cotton. Notably, GB03 has been reported to elicit plant immune response, referred to as induced systemic resistance (ISR), against above-ground pathogens and insect pests. Moreover, a pivotal finding in GB03 was the first-ever identification of its bacterial volatile compounds, which are known to boost plant growth and activate ISR. Research conducted over the past five decades has clearly demonstrated the potential of GB03 as an eco-friendly substitute for conventional pesticides and fertilizers. Validating its safety, the U.S. Environmental Protection Agency endorsed GB03 for commercial use as Kodiak ® in 1998. Subsequently, other compounds, such as BioYield™, were released as a biological control agent against soil-borne pathogens and as a biofertilizer, utilizing a durable spore formulation. More recently, GB03 has been utilized as a keystone modulator for engineering the rhizosphere microbiome and for eliciting microbe-induced plant volatiles. These extensive studies on GB03 underscore its significant role in sustainable agriculture, positioning it as a safe and environmentally-friendly solution for crop protection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Jang, Choi, Zhang, Zhang, Ryu and Kloepper.)

Microbes found in the digestive tracts of insects are known to play an important role in their host's behavior. Although Lepidoptera is one of the most varied insect orders, the link between microbial symbiosis and host development is still poorly understood. In particular, little is known about the role of gut bacteria in metamorphosis. Here, we explored gut microbial biodiversity throughout the life cycle of Galleria mellonella, using amplicon pyrosequencing with the V1 to V3 regions, and found that Enterococcus spp. were abundant in larvae, while Enterobacter spp. were predominant in pupae. Interestingly, eradication of Enterococcus spp. from the digestive system accelerated the larval-to-pupal transition. Furthermore, host transcriptome analysis demonstrated that immune response genes were upregulated in pupae, whereas hormone genes were upregulated in larvae. In particular, regulation of antimicrobial peptide production in the host gut correlated with developmental stage. Certain antimicrobial peptides inhibited the growth of Enterococcus innesii, a dominant bacterial species in the gut of G. mellonella larvae. Our study highlights the importance of gut microbiota dynamics on metamorphosis as a consequence of the active secretion of antimicrobial peptides in the G. mellonella gut. IMPORTANCE First, we demonstrated that the presence of Enterococcus spp. is a driving force for insect metamorphosis. RNA sequencing and peptide production subsequently revealed that antimicrobial peptides targeted against microorganisms in the gut of Galleria mellonella (wax moth) did not kill Enterobacteria species, but did kill Enterococcus species, when the moth was at a certain stage of growth, and this promoted moth pupation., Competing Interests: The authors declare no conflict of interest.

To investigate the therapeutic effects of axitinib, a tyrosine kinase inhibitor, in an interstitial cystitis (IC) rat model. IC patients with or without Hunner lesion and non-IC controls were enrolled (n = 5/group). Bladder tissues were stained with vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), platelet-derived growth factor (PDGF), and PDGF receptor B (PDGFR-B). The IC group showed extensive VEGFR-2 and PDGFR-B staining compared with controls. Next, ten-week-old female Sprague Dawley rats were divided into three groups (n = 10/group): sham, hydrochloride (HCl), and axitinib groups. One week after HCl instillation (day 0), the axitinib group received oral axitinib (1 mg/kg) for five consecutive days and pain was evaluated daily. Bladder function, histology and genetics were evaluated on day 7. The pain threshold significantly improved 3 days after axitinib administration. Axitinib decreased non-voiding contraction and increased the micturition interval and micturition volume and alleviated urothelial denudation, angiogenesis, mast cell infiltration, and fibrosis. HCl instillation increased the expression of tyrosine kinase receptors, including VEGFR-2 and PDGFR-B; axitinib administration inhibited their expression. Oral administration of axitinib improved pain, voiding profiles, and urothelial integrity by inhibiting angiogenesis in IC rat model. Axitinib may have potential therapeutic efficacy in IC patients., (© 2023. The Author(s).)

Background: Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect., Objectives: To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued. Here we tried to develop novel therapies that do not rely on direct antimicrobial activity and thus do not promote antibiotic resistance., Methods: By a high-throughout screening system based on bacterial respiration, chemical compounds accelerating the antimicrobial effects of polymyxin B were screened. In vitro and in vivo tests were performed to validate adjuvanticity. In addition, membrane depolarization and total transcriptome analysis were used to determine molecular mechanisms., Results: PA108, a newly discovered chemical compound, was used to eradicate polymyxin-resistant A. baumannii and three other species in the presence of polymyxin B at concentrations less than the MIC. Since this molecule lacks self-bactericidal action, we hypothesized that PA108 acts as an antibiotic adjuvant, enhancing the antimicrobial activity of polymyxin B against resistant bacteria. At working concentrations, no toxicity was observed in cell lines or mice, although co-treatment with PA108 and polymyxin B increased survival of infected mouse and decreased bacterial loads in organs., Conclusions: Boosting antibiotic efficiency through the use of antibiotic adjuvants holds significant promise for tackling the rise in bacterial antibiotic resistance., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Glutathione (GSH), an abundant nonprotein thiol antioxidant, participates in several biological processes and determines the functionality of stem cells. A detailed understanding of the molecular network mediating GSH dynamics is still lacking. Here, we show that activating transcription factor-2 (ATF2), a cAMP-response element binding protein (CREB), plays a crucial role in maintaining the level and activity of GSH in human mesenchymal stem cells (MSCs) by crosstalking with nuclear factor erythroid-2 like-2 (NRF2), a well-known master regulator of cellular redox homeostasis. Priming with ascorbic acid 2-glucoside (AA2G), a stable vitamin C derivative, increased the expression and activity of ATF2 in MSCs derived from human embryonic stem cells and umbilical cord. Subsequently, activated ATF2 crosstalked with the CREB1-NRF2 pathway to preserve the GSH dynamics of MSCs through the induction of genes involved in GSH synthesis (GCLC and GCLM) and redox cycling (GSR and PRDX1). Accordingly, shRNA-mediated silencing of ATF2 significantly impaired the self-renewal, migratory, proangiogenic, and anti-inflammatory capacities of MSCs, and these defects were rescued by supplementation of the cells with GSH. In addition, silencing ATF2 attenuated the ability of MSCs to alleviate airway inflammatory responses in an ovalbumin-induced mouse model of allergic asthma. Consistently, activation of ATF2 by overexpression or the AA2G-based priming procedure enhanced the core functions of MSCs, improving the in vivo therapeutic efficacy of MSCs for treating asthma. Collectively, our findings suggest that ATF2 is a novel modulator of GSH dynamics that determines the core functionality and therapeutic potency of MSCs used to treat allergic asthma., (© 2023. The Author(s).)

The characterization of an electron-positron beam generated from the interaction of a multi-GeV electron beam with a lead plate is performed using GEANT4 simulations. The dependence of the positron beam size on driver electron beam energy and lead converter thickness is investigated in detail. A pancake-like positron beam structure is generated with a monoenergetic multi-GeV driver electron beam, with the results indicating that a 5 GeV driver electron beam with 1 nC charge can generate a positron beam with a density of 10 15 -10 16  cm -3 at one radiation length of lead. In addition, we find that electron-positron beams generated using above-GeV electron beams have neutralities greater than 0.3 at one radiation length of lead, whereas neutralities of 0.2 are observed when using a 200 MeV electron beam. The possibility of observing plasma instabilities in experiments is also examined by comparing the plasma skin depth with the electron-positron beam size. A quasi-neutral electron-positron plasma can be produced in the interaction between a 1 nC, 5 GeV electron beam and lead with a thickness of five radiation lengths. Our findings will aid in analyzing and interpreting laser-produced electron-positron plasma for laboratory astrophysics research., (© 2023. The Author(s).)

Plant diseases caused by phytopathogens result in huge economic losses in agriculture. In addition, the use of chemical products to control such diseases causes many problems to the environment and to human health. However, some bacteria and fungi have a mutualistic relationship with plants in nature, mainly exchanging nutrients and protection. Thus, exploring those beneficial microorganisms has been an interesting and promising alternative for mitigating the use of agrochemicals and, consequently, achieving a more sustainable agriculture. Microorganisms are able to produce and excrete several metabolites, but volatile organic compounds (VOCs) have huge biotechnology potential. Microbial VOCs are small molecules from different chemical classes, such as alkenes, alcohols, ketones, organic acids, terpenes, benzenoids and pyrazines. Interestingly, volatilomes are species-specific and also change according to microbial growth conditions. The interaction of VOCs with other organisms, such as plants, insects, and other bacteria and fungi, can cause a wide range of effects. In this review, we show that a large variety of plant pathogens are inhibited by microbial VOCs with a focus on the in vitro and in vivo inhibition of phytopathogens of greater scientific and economic importance in agriculture, such as Ralstonia solanacearum , Botrytis cinerea , Xanthomonas and Fusarium species. In this scenario, some genera of VOC-producing microorganisms stand out as antagonists, including Bacillus , Pseudomonas , Serratia and Streptomyces . We also highlight the known molecular and physiological mechanisms by which VOCs inhibit the growth of phytopathogens. Microbial VOCs can provoke many changes in these microorganisms, such as vacuolization, fungal hyphal rupture, loss of intracellular components, regulation of metabolism and pathogenicity genes, plus the expression of proteins important in the host response. Furthermore, we demonstrate that there are aspects to investigate by discussing questions that are still not very clear in this research area, especially those that are essential for the future use of such beneficial microorganisms as biocontrol products in field crops. Therefore, we bring to light the great biotechnological potential of VOCs to help make agriculture more sustainable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Almeida, de Araujo, Dias, de Sant’Anna Freitas, Coerini, Ryu and de Castro Oliveira.)

Salinity is among the most significant abiotic stresses that negatively affects plant growth and agricultural productivity worldwide. One ecofriendly tool for broadly improving plant tolerance to salt stress is the use of bio-inoculum with plant growth-promoting rhizobacteria (PGPR). In this study, a bacterium strain CNUC9, which was isolated from maize rhizosphere, showed several plant growth-promoting characteristics including the production of 1-aminocyclopropane-1-carboxylate deaminase, indole acetic acid, siderophore, and phosphate solubilization. Based on 16S rRNA and recA gene sequence analysis, we identified strain CNUC9 as Burkholderia pyrrocinia . Out of bacterial determinants to elicit plant physiological changes, we investigated the effects of volatile organic compounds (VOCs) produced by B . pyrrocinia CNUC9 on growth promotion and salinity tolerance in Arabidopsis thaliana . Higher germination and survival rates were observed after CNUC9 VOCs exposure under 100 mM NaCl stress. CNUC9 VOCs altered the root system architecture and total leaf area of A . thaliana compared to the control. A. thaliana exposed to VOCs induced salt tolerance by increasing its total soluble sugar and chlorophyll content. In addition, lower levels of reactive oxygen species, proline, and malondialdehyde were detected in CNUC9 VOCs-treated A . thaliana seedlings under stress conditions, indicating that VOCs emitted by CNUC9 protected the plant from oxidative damage induced by salt stress. VOC profiles were obtained through solid-phase microextraction and analyzed by gas chromatography coupled with mass spectrometry. Dimethyl disulfide (DMDS), methyl thioacetate, and 2-undecanone were identified as products of CNUC9. Our results indicate that optimal concentrations of DMDS and 2-undecanone promoted growth in A . thaliana seedlings. Our findings provide greater insight into the salt stress alleviation of VOCs produced by B . pyrrocinia CNUC9, as well as potential sustainable agriculture applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Riu, Ryu and Yu.)

There are still no definite treatment modalities for interstitial cystitis (IC). Meanwhile, stem cell therapy is rising as potential alternative for various chronic diseases. This study aimed to investigate the safety of the clinical-grade mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs), code name MR-MC-01 (SNU42-MMSCs), in IC patients. Three female IC patients with (1) symptom duration >6 months, (2) visual pain analog scale (VAS) ≥4, and (3) one or two Hunner lesions <2 cm in-office cystoscopy within 1 month were included. Under general anesthesia, participants received cystoscopic submucosal injection of SNU42-MMSCs (2.0 × 107/5 mL) at the center or margin of Hunner lesions and other parts of the bladder wall except trigone with each injection volume of 1 mL. Follow-up was 1, 3, 6, 9, and 12 months postoperatively. Patients underwent scheduled follow-ups, and symptoms were evaluated with validated questionnaires at each visit. No SNU42-MMSCs-related adverse events including immune reaction and abnormalities on laboratory tests and image examinations were reported up to 12-month follow-up. VAS pain was temporarily improved in all subjects. No de novo Hunner lesions were observed and one lesion of the first subject was not identifiable on 12-month cystoscopy. This study reports the first clinical application of transurethral hESC-derived MSC injection in three patients with IC. hESC-based therapeutics was safe and proved to have potential therapeutic efficacy in IC patients. Stem cell therapy could be a potential therapeutic option for treating IC., (© The Author(s) 2022. Published by Oxford University Press.)

Organic interfacial compounds (OICs) are required as linkers for the highly stable and efficient immobilization of bioprobes in nanobiosensors using 2D nanomaterials such as graphene. Herein, we first demonstrated the fabrication of a field-effect transistor (FET) via a microelectromechanical system process after covalent functionalization on large-scale graphene by introducing oligo(phenylene-ethynylene)amine (OPE). OPE was compared to various OICs by density functional theory simulations and was confirmed to have a higher binding energy with graphene and a lower band gap than other OICs. OPE can improve the immobilization efficiency of a bioprobe by forming a self-assembly monolayer via anion-based reaction. Using this technology, Magainin I-conjugated OGMFET (MOGMFET) showed a high sensitivity, high selectivity, with a limit of detection of 10 0  cfu mL -1 . These results indicate that the OPE OIC can be applied for stable and comfortable interfacing technology for biosensor fabrication., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Plants and animals serve as hosts for microbes. To protect themselves from microbe-induced damage, plants and animals need to differentiate self-molecules/signals from non-self, microbe-derived molecules. Damage-associated molecular patterns (DAMPs) are danger signals released from the damaged host tissue or present on the surface of stressed cells. Although a self-extracellular DNA has previously been shown to act as a DAMP in different plant species, the existence of a self-extracellular RNA (eRNA) as a danger signal in plants remains unknown. Here, we firstly evaluated the ability of a pepper self-eRNA to activate immunity against viral and bacterial pathogens under field conditions. Pepper leaves pre-infiltrated with self-eRNA exhibited reduced titer of the naturally occurring Tomato spotted wilt virus and diminished symptoms of Xanthomonas axonopodis pv. vesicatoria infection through eliciting defense priming of abscisic acid signaling. At the end of the growing season at 90 days after transplanting, pepper plants treated with self- and non-self-eRNAs showed no difference in fruit yield. Taken together, our discovery demonstrated that self-eRNA can successfully activate plant systemic immunity without any growth penalty, indicating its potential as a novel disease management agent against a broad range of pathogenic microbes., Competing Interests: DK, MR, and CM-R were employed by the company KRIBB. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Riu, Oh and Ryu.)

Bacterial volatile compounds (BVCs) exert beneficial effects on plant protection both directly and indirectly. Although BVCs have been detected in vitro, their detection in situ remains challenging. The purpose of this study was to investigate the possibility of BVCs detection under in situ condition and estimate the potentials of in situ BVC to plants at below detection limit. We developed a method for detecting BVCs released by the soil bacteria Bacillus velezensis strain GB03 and Streptomyces griseus strain S4-7 in situ using solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). Additionally, we evaluated the BVC detection limit in the rhizosphere and induction of systemic immune response in tomato plants grown in the greenhouse. Two signature BVCs, 2-nonanone and caryolan-1-ol, of GB03 and S4-7 respectively were successfully detected using the soil-vial system. However, these BVCs could not be detected in the rhizosphere pretreated with strains GB03 and S4-7. The detection limit of 2-nonanone in the tomato rhizosphere was 1 µM. Unexpectedly, drench application of 2-nonanone at 10 nM concentration, which is below its detection limit, protected tomato seedlings against Pseudomonas syringae pv. tomato. Our finding highlights that BVCs, including 2-nonanone, released by a soil bacterium are functional even when present at a concentration below the detection limit of SPME-GC-MS.

Here, we report the genome sequence of Ralstonia pseudosolanacearum (R. solanacearum phylotype I) strain SL1931 (KACC10711), isolated from pepper (Capsicum annuum L.) stems; R. solanacearum is the causal pathogen of bacterial wilt. Strain SL1931 had a different type III effector profile than that of the reference genome strain GMI1000.

Aberrant activation of embryogenesis-related molecular programs in urothelial bladder cancer (BC) is associated with stemness features related to oncogenic dedifferentiation and tumor metastasis. Recently, we reported that overexpression of transcription factor CP2-like protein-1 (TFCP2L1) and its phosphorylation at Thr177 by cyclin-dependent kinase-1 (CDK1) play key roles in regulating bladder carcinogenesis. However, the clinical relevance and therapeutic potential of this novel CDK1-TFCP2L1 molecular network remain elusive. Here, we demonstrated that inhibitor of DNA binding-2 (ID2) functions as a crucial mediator by acting as a direct repressive target of TFCP2L1 to modulate the stemness features and survival of BC cells. Low ID2 and high CDK1 expression were significantly associated with unfavorable clinical characteristics. TFCP2L1 downregulated ID2 by directly binding to its promoter region. Consistent with these findings, ectopic expression of ID2 or treatment with apigenin, a chemical activator of ID2, triggered apoptosis and impaired the proliferation, suppressed the stemness features, and reduced the invasive capacity of BC cells. Combination treatment with the specific CDK1 inhibitor RO-3306 and apigenin significantly suppressed tumor growth in an orthotopic BC xenograft animal model. This study demonstrates the biological role and clinical utility of ID2 as a direct target of the CDK1-TFCP2L1 pathway for modulating the stemness features of BC cells., (© 2022. The Author(s).)

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with a single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced T h 1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with a single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.

Bacteria emit volatile compounds that modulate plant growth. Previous studies reported the impacts of bacterial volatile compounds on plant growth; however, the results varied depending on bacterial nutrient availability. We investigated whether the effects of plant growth-inhibiting volatiles (PGIVs) and plant growth-promoting volatiles (PGPVs) depended on the perceived dose by evaluating the growth of Arabidopsis thaliana seedlings placed at 7, 14, and 21 cm away from Bacillus amyloliquefaciens GB03 colonies growing in rich medium. A large bacterial colony (500 μl inoculum) inhibited plant growth at 7 cm and promoted growth at 21 cm, whereas a small bacterial colony (100 μl inoculum) induced the opposite pattern of response. We identified pyrazine and 2,5-dimethylpyrazine as candidate PGIVs that significantly reduced plant growth at a distance of 7 cm. PGIV effects were validated by exposing plants to synthetic 2,5-dimethylpyrazine and bacteria emitting PGPVs, which showed that PGIVs overwhelm PGPVs to rapidly increase salicylic acid content and related gene expression. This is referred to as the defence-growth trade-off. Our results indicate that high PGIV concentrations suppress plant growth and promote immunity, whereas low PGPV concentrations promote growth. This study provides novel insights into the complex effects of bacterial volatile mixtures and fine-tuning of bacteria-plant interactions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Volatile compounds play important roles in rhizosphere biological communications and interactions. The emission of plant and microbial volatiles is a dynamic phenomenon that is affected by several endogenous and exogenous signals. Diffusion of volatiles can be limited by their adsorption, degradation, and dissolution under specific environmental conditions. Therefore, rhizosphere volatiles need to be investigated on a micro and spatiotemporal scale. Plant and microbial volatiles can expand and specialize the rhizobacterial niche not only by improving the root system architecture such that it serves as a nutrient-rich shelter, but also by inhibiting or promoting the growth, chemotaxis, survival, and robustness of neighboring organisms. Root volatiles play an important role in engineering the belowground microbiome by shaping the microbial community structure and recruiting beneficial microbes. Microbial volatiles are appropriate candidates for improving plant growth and health during environmental challenges and climate change. However, some technical and experimental challenges limit the non-destructive monitoring of volatile emissions in the rhizosphere in real-time. In this review, we attempt to clarify the volatile-mediated intra- and inter-kingdom communications in the rhizosphere, and propose improvements in experimental design for future research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Host tp53 mutations are frequently found during the early stages of colitis-associated colorectal cancer (CAC), but whether such mutations induce gut microbiota dysbiosis and chronic intestinal inflammation that contributes to the development of CAC, remains unknown., Results: We found that zebrafish tp53 mutant larvae exhibited elevated intestinal inflammation, by monitoring the NFκB activity in the mid-distal intestines of zebrafish larvae using an NFκB:EGFP transgenic reporter line in vivo as well as neutrophil infiltration into the intestine. This inflammation was due to dysbiotic gut microbiota with reduced diversity, revealed using both 16S rRNA amplicon sequencing and a germfree larva model. In this dysbiosis, Aeromonas spp. were aberrantly enriched as major pathobionts and exhibited the capacity for aggressive colonization in tp53 mutants. Importantly, the ex-germfree experiments supported the causality of the host tp53 mutation for inducing the inflammation. Transcriptome and high-performance liquid chromatography analyses of the host gastrointestinal tracts identified dysregulated sialic acid (SA) metabolism concomitant with increased host Neu5Gc levels as the key determinant of aberrant inflammation, which was reversed by the sialidase inhibitors oseltamivir and Philippin A., Conclusions: These results demonstrate a crucial role for host tp53 in maintaining symbiosis and immune homeostasis via SA metabolism. Disturbed SA metabolism via a tp53 mutation may be exploited by specific elements of the gut microbiome, eliciting both dysbiosis and inflammation. Manipulating sialometabolism may therefore provide an efficacious therapeutic strategy for tp53 mutation-induced dysbiosis, inflammation, and ultimately, related cancers. Video Abstract., (© 2022. The Author(s).)

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS-FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recently, Sieber et al. discovered the new diazeniumdiolate volatile signaling molecule, leudiazen. They confirmed that inactivation of leudiazen by KMnO 4 can reduce the production of mangotoxin. This alleviates the pathogenicity of Pseudomonas syringae pv. syringae on mango trees, providing a new strategy for plant protection, compatible with organic farming., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Upon sensing attack by pathogens and insect herbivores, plants release complex mixtures of volatile compounds. Here, we show that the infection of lima bean (Phaseolus lunatus L.) plants with the non-host bacterial pathogen Pseudomonas syringae pv. tomato led to the production of microbe-induced plant volatiles (MIPVs). Surprisingly, the bacterial type III secretion system, which injects effector proteins directly into the plant cytosol to subvert host functions, was found to prime both intra- and inter-specific defense responses in neighbouring wild tobacco (Nicotiana benthamiana) plants. Screening of each of 16 effectors using the Pseudomonas fluorescens effector-to-host analyser revealed that an effector, HopP1, was responsible for immune activation in receiver tobacco plants. Further study demonstrated that 1-octen-3-ol, 3-octanone and 3-octanol are novel MIPVs emitted by the lima bean plant in a HopP1-dependent manner. Exposure to synthetic 1-octen-3-ol activated immunity in tobacco plants against a virulent pathogen Pseudomonas syringae pv. tabaci. Our results show for the first time that a bacterial type III effector can trigger the emission of C8 plant volatiles that mediate defense priming via plant-plant interactions. These results provide novel insights into the role of airborne chemicals in bacterial pathogen-induced inter-specific plant-plant interactions., (© 2021 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Background: The therapeutic effects of human embryonic stem cell-derived multipotent mesenchymal stem cells (M-MSCs) were evaluated for detrusor underactivity (DUA) in a rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and associated mechanisms., Methods: Sixteen-week-old male Sprague-Dawley rats were divided into five groups (n = 10). The DUA groups underwent 30 bilateral repetitions of endothelial injury to the iliac arteries to induce CBI, while the sham control group underwent a sham operation. All rats used in this study received a 1.25% cholesterol diet for 8 weeks. M-MSCs at a density of 2.5, 5.0, or 10.0 × 10 5 cells (250 K, 500 K, or 1000 K; K = a thousand) were injected directly into the bladder 7 weeks post-injury, while the sham and DUA group were treated only with vehicle (phosphate buffer solution). One week after M-MSC injection, awake cystometry was performed on the rats. Then, the bladders were harvested, studied in an organ bath, and prepared for histological and gene expression analyses., Results: CBI by iliac artery injury reproduced voiding defects characteristic of DUA with decreased micturition pressure, increased micturition interval, and a larger residual volume. The pathological DUA properties were improved by M-MSC treatment in a dose-dependent manner, with the 1000 K group producing the best efficacy. Histological analysis revealed that M-MSC therapy reduced CBI-induced injuries including bladder fibrosis, muscular loss, and apoptosis. Transplanted M-MSCs mainly engrafted as vimentin and NG2 positive pericytes rather than myocytes, leading to increased angiogenesis in the CBI bladder. Transcriptomes of the CBI-injured bladders were characterized by the complement system, inflammatory, and ion transport-related pathways, which were restored by M-MSC therapy., Conclusions: Single injection of M-MSCs directly into the bladder of a CBI-induced DUA rat model improved voiding profiles and repaired the bladder muscle atrophy in a dose-dependent manner., (© 2021. The Author(s).)

Germinal centers (GCs) elicit protective humoral immunity through a combination of antibody-secreting cells and memory B cells, following pathogen invasion or vaccination. However, the possibility of a GC response inducing protective immunity against reinfection following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. We found GC activity was consistent with seroconversion observed in recovered macaques and humans. Rechallenge with a different clade of virus resulted in significant reduction in replicating virus titers in respiratory tracts in macaques with high GC activity. However, diffuse alveolar damage and increased fibrotic tissue were observed in lungs of reinfected macaques. Our study highlights the importance of GCs developed during natural SARS-CoV-2 infection in managing viral loads in subsequent infections. However, their ability to alleviate lung damage remains to be determined. These results may improve understanding of SARS-CoV-2-induced immune responses, resulting in better coronavirus disease 2019 (COVID-19) diagnosis, treatment, and vaccine development., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Bacteria produce a huge diversity of metabolites, many of which mediate ecological relations. Among these, volatile compounds cause broad-range effects at low doses and, therefore, may be exploited for plant defence strategies and agricultural production, but such applications are still in their early development. Here, we review the latest technologies involving the use of bacterial volatile compounds for phytosanitary inspection, biological control, plant growth promotion, and crop quality. We highlight a variety of effects with a potential applicative interest, based on either live biocontrol and/or biostimulant agents, or the isolated metabolites responsible for the interaction with hosts or competitors. Future agricultural technologies may benefit from the development of new analytical tools to understand bacterial interactions with the environment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been continuously reported worldwide. However, the precise evaluation of SARS-CoV-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. In this report, we performed deep sequencing for seed virus and SARS-CoV-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucleotide polymorphisms (SNPs) in SARS-CoV-2 by variant analysis. A total of 69 single-nucleotide variants (SNVs) were present in the 5'-untranslated region (UTR), 3'-UTR, ORF1ab , S , ORF3a , ORF8 , and N genes of the seed virus passaged in VERO cells. Between those present on the seed virus and those on each SARS-CoV-2 isolated from the lungs of the macaques, a total of 29 variants was identified in 4 coding proteins (ORF1ab, S, ORF3a, and N) and non-coding regions (5'- and 3'-UTR). Variant number was significantly different according to individuals and ranged from 2 to 11. Moreover, the average major frequency variation was identified in six sites between the cynomolgus monkeys and rhesus macaques. As with diverse SNPs in SARS-CoV-2, the values of viral titers in lungs were significantly different according to individuals and species. Our study first revealed that the genomes of SARS-CoV-2 differ according to individuals and species despite infection of the identical virus in non-human primates (NHPs). These results are important for the interpretation of longitudinal studies evaluating the evolution of the SARS-CoV-2 in human beings and development of new diagnostics, vaccine, and therapeutics targeting SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hwang, Chung, Kim, Oh, An, Kang, Ryu, Park, Hong and Koo.)