In this Part 2 of a three-part review of advances in cobalt corrinoid research published between 2020 and 2025, we examine the biochemistry and microbiology of the cobalt corrinoids. Central to this literature is the chemical complementarity between cobalt and the corrin macrocycle, which enables distinct catalytic strategies including methyl transfer, radical rearrangement, reductive dehalogenation, and hybrid radical-SAM transformations. Recent work shows that corrinoid-dependent enzymes do not merely exploit intrinsic cobalt reactivity, but actively shape it through structural, electronic, and kinetic control over Co-C bond activation, intermediate stabilisation, and reaction selectivity. Equally prominent is the requirement for rigorous cofactor management, as corrinoid chemistry remains vulnerable to oxidative damage, misligation, and incomplete cofactor maturation, necessitating specialised systems for trafficking, remodelling, repair, and selective deployment. Genomic, evolutionary, and ecological studies further reveal that corrinoid metabolism is unevenly distributed, with widespread auxotrophy, selective transport, and cobamide exchange creating extensive metabolic interdependence within microbial communities. These patterns reflect evolutionary partitioning of biosynthetic capacity while emphasising the importance of environmental constraints, particularly cobalt availability and horizontal gene transfer, in shaping corrinoid cycling. In host-associated systems, corrinoid availability influences metabolic flux, microbial community structure, and functional outputs with implications for host physiology. Corrinoid metabolism emerges from this literature as a multiscale biological system in which inorganic chemistry, enzyme architecture, genomic organisation, and ecological context are functionally intertwined.
Banana production has suffered from Potyvirus musae (banana bract mosaic virus, BBrMV) in the Philippines and India; however, its occurrence and biological characteristics in Taiwan remain poorly understood. In this study, field surveys conducted between 2017 and 2018 identified 13 BBrMV-infected samples from commercial banana production areas in Taiwan. Among these, isolate F92 was successfully preserved by aphid transmission and used for further characterization. An infectious clone of BBrMV isolate F92 was constructed to establish a reliable inoculation system. In addition, poly(A) tail length was found to affect viral infectivity, and a longer poly(A) tail produced more consistent systemic infection. Using this system, the susceptibility of five banana cultivars commonly grown in Taiwan was evaluated. Most cultivars showed relatively mild symptoms and stable or declining viral accumulation, whereas the cultivar 'Rose' was more susceptible. This study reports the first infectious clone of BBrMV and provides a useful tool for evaluating cultivar susceptibility. Because BBrMV has not yet become widely established in Taiwan, these results may provide useful information for future disease management if the virus spreads in Taiwan.
The emergence of β-lactamase-producing bacteria is a critical global public health threat that undermines the efficacy of last-resort antibiotics. In Ethiopia, studies exploring resistance genes in drinking water systems are scarce. This study investigated bacterial profiles, antimicrobial susceptibility, and associated Extended-Spectrum β-Lactamase (ESBL) genes, including blaTEM, blaCTXM and blaSHV. A cross-sectional study was conducted between March 2023 and April 2024 by sampling raw, finished, reservoir, tap, and storage tank water in Addis Ababa. The samples were processed aseptically with routine microbiological culture and characterization methods. Antibiotic susceptibility testing was conducted using standardized Kirby-Bauer disc diffusion method as described by Clinical Laboratory Standards Institute (CLSI) version 33 guidelines. All data recorded were validated and then analyzed by Statistical Package for the Social Sciences version 25.0 Armonk. The associated parameters were compared using Fishers' exact test to determine their correlation. In all cases, a p-value less than or equal to 0.05 was considered statistically significant. From 45 samples, 94 bacterial species were characterized. Dominant isolates included E. coli (23.4%), Enterobacter spp. (16%), Citrobacter spp. (10.6%), K. pneumoniae (10.6%), Proteus spp. (8.5%), and Coagulase negative Staphylococcus species. Multi-drug resistant (MDR) is a non-susceptibility of an isolate to at least one antibiotic agent in three or more antimicrobial classes. Disc diffusion tests revealed that 63.8% (60/94) of isolates were MDR. The highest resistance levels were observed for ampicillin (86%), tetracycline (72.7%), cefuroxime (66.2%), and cefoxitin (53.5%). The principal MDR isolates were E. coli, Enterobacter, and Klebsiella species. Multiplex PCR on genomic DNA of MDR isolates showed a 26.6% (16/60) occurrence of ESBL genes; the combination of blaCTXM + blaTEM 11.7% (7/60) being the most frequent, followed by blaTEM (10%), blaCTXM (3.3%), and blaSHV (1.7%). In plasmid DNA of Gram-negative MDR isolates, ESBL genes occurred in 10.9% (6/54), with blaTEM (7.3%) being dominant, followed by blaCTXM (0.18%) and co-occurring blaSHV + blaTEM (0.18%). This study confirms the presence of ESBL genes in both the genomic and plasmid DNA of MDR bacteria in the water supply, particularly in storage tanks, tap and raw water. These findings indicate the transmission of β-lactamase-producing bacteria into drinking water supply systems. Regular monitoring, surveillance, and rigorous studies to identify contamination sources and mitigation strategies are urgently recommended.
To systematically analyze the global research landscape, collaboration patterns, knowledge flow pathways, and frontier trends in the synergistic effects between the microbiome and cancer immunotherapy. A systematic bibliometric analysis of publications on the synergistic effects between the microbiome and cancer immunotherapy (2010-2026) was performed using the Web of Science Core Collection. After deduplication, 3,058 publications were analyzed with CiteSpace 6.3.1 (co-citation, keyword burst, timeline), VOSviewer 1.6.19 (co-authorship, co-occurrence networks), and bibliometrix R package 4.4.1 (dual-map overlay, knowledge flow). Annual publications grew at an average rate of 23.0%, reaching 715 in 2025. China and the United States contributed 60.1% of global output, with MD Anderson Cancer Center, Shanghai Jiao Tong University, and Paris-Saclay University serving as core collaboration hubs. Three major academic lineages (fundamental mechanisms, clinical translation, tumor-specific research) and three knowledge flow pathways (mathematical modeling → molecular genetics; clinical medicine → molecular biology; ecology → molecular biology) were identified, shaping distinct research paradigms. Hotspots evolved from "gut microbiota-ICIs" toward "oral microbiota," "engineered bacteria," and "precision prediction." The field has transitioned from mechanistic exploration to precision intervention, with multidisciplinary integration and clinical translation as future priorities. The identified knowledge flow pathways and academic lineages provide a framework for understanding the intellectual structure of this rapidly evolving domain.
Polyethylene glycol (PEG) is widely used to improve the stability, solubility, and circulation half-life of nanoparticles, proteins, and small-molecule drugs. However, anti-PEG antibodies are increasingly recognized as a clinically relevant variable that can reshape the in vivo fate of PEGylated therapeutics, contributing to accelerated blood clearance, altered biodistribution, loss of efficacy, and, in a subset of individuals, hypersensitivity. This review integrates molecular, formulation, and host determinants of PEG immunogenicity using evidence from preclinical models and human studies. We summarize the prevalence and sources of pre-existing anti-PEG antibodies, including environmental exposure and host genetic associations, and discuss how antibody binding remodels the biomolecular corona, engages Fc- and complement-mediated pathways, and promotes phagocytic uptake that undermines PEG-mediated "stealth". We then evaluate mitigation strategies spanning polymer and lipid design, emerging PEG alternatives, and patient-centered approaches such as baseline antibody profiling and pre-treatment with free PEG in animal models. Finally, we highlight an emerging paradigm that exploits anti-PEG binding for benefit: bispecific anti-PEG antibodies and sequential pre-targeting strategies that convert PEG into a modular handle for active targeting across polymer nanoparticles, liposomes, and mRNA-lipid nanoparticles. Together, this review frames anti-PEG immunity as a central design variable in nanomedicine, linking PEG-mediated stealth, circulation time, targeting efficiency, biomolecular corona formation, and immune recognition. We propose guiding principles for deciding when PEG should be retained and optimized, replaced with alternative stealth materials, managed through patient-level screening or pre-treatment, or deliberately exploited as a modular handle for targeted delivery.
Gastrointestinal disorders are a common complication following solid organ transplantation, but they also pose a real diagnostic challenge. There are many possible causes, ranging from immunosuppressive treatment toxicity to bacterial, parasitic, and viral infections. The use of syndromic molecular tests in microbiology has highlighted the important role played by enteric viruses, particularly norovirus, in the onset of diarrhea in transplant patients. These viruses, which are mostly benign in immunocompetent individuals, can cause severe and, above all, chronic infections responsible for significant morbidity and mortality and graft dysfunction. This review describes the characteristics of viral gastroenteritis in solid organ transplant patients, its epidemiology, pathophysiology, and clinical presentation. Finally, while the treatment of viral diarrhea is still based on symptomatic measures and the reduction of immunosuppression, it reviews the new specific antiviral therapies currently being evaluated. Overall, a better understanding of viral gastroenteritis in solid organ transplant patients is essential, as it is a major issue and diagnosis is crucial for appropriate management, at a time when the number of individuals with a functional transplant is increasing every year in France and worldwide.
The Adverse Outcome Pathway (AOP) framework has become a powerful tool in mechanistic toxicology, linking molecular initiating events through key biological changes to adverse health outcomes. In food safety, where chronic exposure to diverse contaminants is common, AOPs offer a promising alternative to traditional animal testing by supporting in vitro and in silico approaches. This review evaluates current AOPs developed for major dietary contaminants such as mycotoxins, heavy metals, acrylamide, dioxins, and packaging-related chemicals. It critically assesses the quality of AOPs in the AOP-Wiki, focusing on the strength and biological relevance of key event relationships. The study also examines how regulatory agencies incorporate AOPs into risk assessment, revealing limited formal adoption despite their potential. Key gaps are identified, including insufficient quantitative data, challenges in addressing mixture toxicity, and limited cross-species applicability. Additionally, the role of computational tools in AOP development and validation is analyzed. Overall, the review highlights a disconnect between AOP research and regulatory implementation and provides recommendations to enhance their integration into food safety assessment frameworks, ultimately supporting more efficient, ethical, and mechanism-based risk evaluation.
Brucellosis is a globally important disease but its prevalence, distribution, and impacts remain poorly known in many countries. With the world's largest livestock population, and the second largest human population, the scale of brucellosis in China dwarfs that of the disease in other countries and is a preeminent One Health challenge. As a result, an overall understanding of the extent and burden of this disease and its impacts have been elusive and concerted efforts to reduce disease burden have been sporadic. Brucellosis is relatively common in many regions of China and infects humans and a range of livestock and wildlife. Reported human brucellosis cases increased from 45,046 in 2019 to 70,439 in 2023, reflecting the growing national burden. We reviewed the status of brucellosis in China from 1950 to 2025, with a particular focus on its distribution and molecular epidemiology of human and animal infections in the past decade. Human brucellosis cases have substantially and progressively increased since 1950, reflecting the growing national burden but also showing short periods of decline and then resurgence. For example, genetic analyses using MLVA and whole‑genome sequencing of Brucella isolates have identified Brucella melitensis (specifically the Eastern Mediterranean lineage and biovar 3) as the predominant genotype circulating in country, placing these samples into a global context. Moreover, some regions appear to be hotspots of disease, such as high disease incidence in animals in Inner Mongolia that corresponds with high infection rates in humans. Brucellosis also appears to be changing its distribution, expanding from northern pastoral and agricultural areas such as Inner Mongolia, Shanxi, Heilongjiang, Hebei, Jilin, and Shaanxi to more industrial provinces such as Henan, Guangdong, and Fujian, driven by livestock trade, transboundary spread, and north‑to‑south expansion. Notably, novel transmission routes have become evident that are not associated with occupational exposure. Furthermore, brucellosis is increasingly being found in wildlife, with the potential for cross-species transmission, unique strains, and additional host species that may remain to be discovered. Finally, we discuss vaccination, disease control strategies, and the comprehensive animal and public health measures that are needed to reduce brucellosis prevalence in China. Vaccination faces particular challenges due to a scarcity of efficacy studies. These findings directly impact control strategies by highlighting the need for region‑specific vaccination policies, enhanced surveillance in non‑traditional southern provinces, and targeted interventions along livestock trade routes to counter the clonal expansion of the dominant GT42 genotype.
Human papillomavirus (HPV) 18 E6 oncoprotein drives cervical carcinogenesis by degrading p53, enabling uncontrolled cell proliferation. In this study, we developed novel trans-activator of transcription (TAT)-conjugated Affibody molecules (TAT-ZHPV18E6) targeting HPV18 E6 for therapeutic applications. High-affinity Affibody variants were screened by phage display using recombinant HPV18 E6 expressed in Escherichia coli. Three candidates (TAT-ZHPV18E6: 4, 59, 352) exhibited high binding affinity, with equilibrium dissociation constant (KD) ranging from 10-6 to 10-4 M, with TAT-ZHPV18E6: 59 showing superior specificity for native HPV18 E6 in HeLa229 cells, as validated by surface plasmon resonance (SPR), enzyme-linked immunosorbent assay (ELISA), and immuno-fluorescence. In vivo near-infrared fluorescence imaging of DyLight 755-labeled TAT-ZHPV18E6: 59 in tumor-bearing mice demonstrated rapid tumor accumulation (peak at 2 h) and prolonged retention (> 12 h). Mechanistically, TAT-ZHPV18E6: 59 restored p53 stability and upregulated pro-apoptotic factors (Bax, PUMA) and cell cycle regulator p21. Notably, combined treatment with TAT-ZHPV18E6: 59 and E7-targeting TAT-ZHPV18E7: 228 combinatorial enhanced apoptosis and suppressed HeLa229 proliferation, as confirmed by CCK-8 and clonogenic assays. These results demonstrate the utility of TAT-ZHPV18E6 Affibody molecules as targeted agents, highlighting combinatorial E6/E7 targeting as a potent strategy for HPV18-driven cervical cancer therapy. KEY POINTS: • TAT-ZHPV18E6: 59 achieved high affinity for HPV18 E6, enabling precise molecular targeting. • Demonstrates dual utility for in vivo imaging and p53-dependent tumor suppression. • Dual targeting of E6/E7 yields synergistic therapeutic efficacy in cervical cancer models.
Kiwifruit is favored by consumers for its exceptional nutrients and appealing flavor, which lures its steady increase in global cultivation areas and yields. Kiwifruit, however, encounters numerous postharvest preservation challenges, resulting in economic losses. Resistance induction strategies are emerging as a promising means for sustaining postharvest quality of kiwifruit. This review summarizes various factors affecting postharvest kiwifruit quality, such as mechanical damage, intrinsic senescence, chilling injury, and pathogen infection. A comprehensive overview of recent studies on resistance induction strategies for maintaining postharvest kiwifruit quality is presented, including physical, chemical, microbial, and integrated treatments. It is discussed that the application of exogenous inducers can enhance kiwifruit resistance, thereby alleviating mechanical damage, delaying intrinsic senescence, mitigating chilling injury, and defending against pathogen infection. The molecular mechanisms underlying resistance induction are also elaborated. Specifically, induced-resistance mechanisms primarily involved the regulation of antioxidant system, reactive oxygen species homeostasis, phenylpropanoid biosynthesis, plant hormone signaling pathways, and jasmonic acid pathway. This review also highlights the developmental potential of preharvest applications of resistance inducers in kiwifruit. Shifting the application of resistance inducers to preharvest stage may provide greater potential for effectively mitigating postharvest spoilage of kiwifruit. In conclusion, resistance inducers have become a promising preservation strategy for kiwifruit but still face challenges regarding sustained efficacy, safety regulations, and large-scale commercial implementation.
Mismatch repair deficiency (dMMR) and microsatellite instability (MSI-H) are rare in prostate cancer, occurring in 2%-4% of cases. These defects result in increased genomic instability and elevated tumor mutational burden (TMB), which can support responses to immune checkpoint inhibitors (ICIs). Here, we report a patient with locally advanced Gleason 5 + 5 = 10 prostatic adenocarcinoma harboring MSH2 and MSH6 genomic deletions with ultrahigh TMB (>250 mutations/megabase) in whom pembrolizumab resulted in a striking complete radiographic, pathologic, and molecular response. Using digital-spatial microscopy, single-cell RNA/T cell receptor (TCR) sequencing, and multiplex cytometry, we identify atypical tumor-infiltrating T cells with natural killer-like phenotypes and CD4+CD8+ (double-positive) lymphocytes. These clonal T cell populations expand preferentially following ICI and adopt terminally differentiated and cytotoxic profiles that may drive clinical response. Similar T cells are also present in diverse cancers and expand exclusively in ICI-responsive patients. These findings inform on the cellular mechanisms by which immunotherapies may mediate profound responses in patients with dMMR solid tumors.
Enteropathogenic Escherichia coli (EPEC) is a major etiological agent of persistent diarrhea in pediatric and adult population globally and it is a leading cause of infant mortality in developing countries. Bacterial culture and biochemical assays are insufficient for accurately identifying EPEC strains. In contrast, PCR serves as a major molecular diagnostic method for EPEC. However, the application of PCR is limited due to high cost, time taking and technical requirements. In this study loop mediated isothermal amplification LAMP) was developed for rapid, specific, easy and resource-friendly detection of EPEC. The LAMP assay was developed by designing specific lamp primers targeting eae genes, in combination with stx1 and stx2 lamp primers to enable EPEC detection. The reaction mixture, which contained 2.5 µL of isothermal amplification buffer, 10 mM of MgSO4 solution, 1.4 mM of dNTPs, 1.8 mM of FIP and BIP, 0.4 mM of F3 and B3, 0.2 mM of LB, 8U of Bst polymerase, and 2.0 µL of the target DNA template, was incubated at 62 C0 for 60 minutes. The designed lamp assay's performance was assessed utilizing 60 bacterial trains that were isolated locally. The assay attained 100% efficiency (60/60), 100% sensitivity (10/10), and 100% specificity (50/50). Furthermore, both the positive and negative predictive scores were 100%. Up to 0.05 pg of DNA could be detected in each reaction using the developed LAMP test. The traditional PCR, on the other hand, showed a detection limit of 5 pg/reaction. Additionally, the developed LAMP assay was able to detect up to 7 x 102 cfu/g stool in a spiked stool sample. PCR, however, can identify up to 7 x 104 cfu/g of stool. Notably, compared to conventional PCR, the LAMP assay has a 100-fold greater sensitivity. The result obtained from LAMP and PCR tests showed a perfect agreement with a kappa value of 1 (k = 1). The developed LAMP assay demonstrated promising performance for the detection of EPEC under controlled laboratory conditions, offering a rapid and straightforward alternative to conventional diagnostic methods. Clinical validation using patient stool sample and further studies with larger sample sets are needed to fully establish the assay's performance and support its broader clinical application.
Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and remains a leading cause of global morbidity and mortality. Despite decades of research, most biologically targeted therapies have failed to improve survival, highlighting the need for new treatment strategies that address the complex pathophysiology of sepsis. A defining feature of sepsis is immunothrombosis, characterized by widespread activation of inflammation and coagulation, endothelial injury, platelet activation, and neutrophil extracellular trap (NET) formation, resulting in both macrovascular thrombosis and microvascular occlusion. Heparin is commonly used as an anticoagulant and has re-emerged as a potential therapeutic agent for sepsis due to its pleiotropic properties that extend beyond anticoagulant effects. Heparin exhibits anti-inflammatory and antimicrobial activities, inhibits immune activation, neutralizes damage-associated molecular patterns (DAMPs), and modulates NET-mediated pathology. Clinical evidence for efficacy in sepsis remains limited, and no adequately powered randomized trials have confirmed a net survival benefit of therapeutic-dose heparin. This may reflect historical challenges with trial methodology and the heterogeneous nature of human sepsis. Data from COVID-19-associated sepsis suggest that severity may influence outcomes, with potential benefits in earlier disease stages and possible harm in advanced stages. Emerging interest in non-anticoagulant heparin derivatives and biomarker-guided patient selection may offer scientific opportunities to optimize therapeutic benefit while minimizing bleeding, but these approaches remain investigational. This review synthesizes current mechanistic, preclinical, and clinical evidence supporting heparin-based strategies in sepsis and emphasizes that therapeutic use beyond standard thromboprophylaxis should be evaluated in clinical trials before being applied in practice.
This study aimed to develop and evaluate a dual-drug-loaded PLGA nanoparticle system incorporating quercetin (QUE) and chlorhexidine (CHX) for localized, sustained delivery, with potential application in biofilm-associated pathologies. Single- and dual-drug systems containing CHX and QUE at different concentrations (1.5%, 5%, and 15%) were successfully loaded into poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) with high encapsulation efficiency. Physicochemical characterization was performed using dynamic light scattering (DLS), zeta potential analysis, SEM-EDX, FTIR, and thermal analysis (DSC and TGA). Release kinetics of QUE- and CHX-loaded nanoparticles were evaluated in an artificial saliva environment, and the amounts of CHX and QUE released were quantified by high-performance liquid chromatography (HPLC). Antimicrobial activity was assessed against Staphylococcus aureus and Escherichia coli using the disc diffusion method. The prepared nanoparticles displayed spherical morphology with sizes ranging from 54.08 to 356.1 nm and zeta potentials from - 2.11 to -12.46 mV, indicating colloidal stability. FTIR and thermal analysis confirmed molecular dispersion of drugs and polymer-drug interactions. QUE showed complete release within 168 h in the single-drug system, whereas co-loading with CHX extended QUE retention, with 20% remaining after 240 h. CHX release reached ∼80% in both formulations. CHX/QUE nanoparticles demonstrated superior antibacterial activity compared to QUE-only systems, effectively inhibiting both Gram-positive and Gram-negative bacteria. These compounds and formulations are designed for clinical applications due to their slow, controlled release of the dual-active PLGA NP system.
Carbapenem-resistant Acinetobacter baumannii (CRAb) causes hard-to-control healthcare outbreaks, but the mobile resistance determinants that sustain regional spread are often underrecognized. We characterized 70 CRAb isolates from 11 hospitals in southern Poland (2019-2022) using whole-genome sequencing and core genome multilocus sequence typing (cgMLST), with reconstruction of carbapenemase context and plasmid structure. All isolates belonged to international clone 2 (IC2; ST2, Pasteur scheme) or to ST425 (n = 47), ST195 (n = 19), ST208 (n = 2), and ST348 (n = 1) according to the Oxford scheme. In silico KL/OCL typing further differentiated the collection. All isolates were OCL18, whereas the K-locus distribution was dominated by KL125 (n = 48) and KL3 (n = 19), with two KL2 isolates and one KL9 isolate. blaOXA-72 was detected in 50/70 isolates (71.4%), indicating an atypically high regional dominance. The OXA-72-encoding gene was carried on the same ~10.9 kb GR2/repAci1 plasmid (p398AB) in all isolates, which was sequence-identical across centers and contained two oppositely oriented copies of blaOXA-72. Transformation of p398AB into susceptible A. baumannii ATCC17978 conferred a carbapenem-resistant phenotype. cgMLST identified a large multicenter cluster of blaOXA-72-positive isolates spanning multiple cities and hospitals, supporting inter-facility dissemination of a successful IC2 lineage, together with a conserved resistance plasmid. The strict conservation of p398AB during regional spread provides a practical target for rapid molecular screening in outbreak investigations. In contrast, blaOXA-23 and a novel blaOXA-23-like variant (blaOXA-1223) were confined to a minority of isolates. Overall, these data highlight an unusual dominance of plasmid-encoded blaOXA-72 in a multicenter IC2 outbreak and underscore the need for surveillance integrating clonal relatedness with tracking of transferable resistance plasmids.
Addiction is a chronic and relapsing disorder that affects millions of people worldwide; nonetheless, currently available FDA-approved treatments are limited in number and effectiveness. In past years, the gut-brain axis has emerged as a key modulatory factor associated with different psychiatric disorders, including addiction. Working in mice, we have shown that cocaine exposure alters the composition of the gut microbiome, increasing the abundance of Proteobacteria. This microbial shift, in turn, leads to a depletion in host glycine levels, altering cocaine-induced transcriptional changes in the Nucleus Accumbens (NAc) and facilitating the development of behavioral sensitization and conditioned place preference. Among the behavioral models to study psychostimulant use disorders, cocaine self-administration (SA) remains the most translational. Therefore, here we investigated whether Proteobacteria-induced glycine depletion can affect cocaine SA in mice. Using the human Escherichia coli HS and the glycine-uptake-deficient mutant E. coli HS ΔCycA, we build upon our previous findings and demonstrate that the ability of gut Proteobacteria to use glycine during cocaine SA shapes the trajectory and long-term neurobehavioral plasticity induced by the drug. Furthermore, we show that this bacterial-induced glycine depletion impacts the NAc proteome, altering its vulnerability to undergo molecular adaptations across different stages of the SA paradigm. Altogether, our findings show that the gut microbiome, and particularly the Proteobacteria phylum, is a crucial factor influencing short and long-term adaptation underlying motivation and cocaine-seeking behaviors.
Oat anthracnose, primarily caused by Colletotrichum cereale, represents a significant threat to oat production, necessitating the development of sustainable biocontrol alternatives. In this study, we characterized an oat endophytic bacterium, Bacillus velezensis JN.Y2, isolated from healthy oat leaves in Inner Mongolia. In vitro assays demonstrated that B. velezensis JN.Y2 (designated as Bv. JN.Y2) possesses an inhibitory activity against C. cereale (74.49%) and exhibits a broad antifungal spectrum. Greenhouse and three-year multi-location field trials confirmed its beneficial biocontrol efficacy, which remained stable even under fluctuating climatic conditions and high disease pressure, consistently outperforming conventional chemical treatments. Beyond disease suppression, Bv. JN.Y2 significantly enhanced oat growth and grain yield, supported by its ability to produce IAA, solubilize nutrients, and secrete diverse hydrolytic enzymes. Complete genome sequencing revealed a 3.87 Mb circular chromosome containing 13 secondary metabolite BGCs and 4 AOIs for RiPPs, including Amylocyclicin and LCI. Comparative genomic analysis highlighted an "open" pangenome and identified 411 unique genes associated with specialized metabolism and environmental sensing. While Bv. JN.Y2 shares high sequence synteny with B. velezensis CBMB205, distinct variations in the sporulation kinase kinA and secondary metabolite pathways suggest a fine-tuned adaptation to the oat endosphere. Furthermore, biosafety evaluations confirmed a relatively high level of genetic stability and a lack of active antibiotic resistance. Collectively, these findings provide a beneficial molecular foundation for the application of Bv. JN.Y2 as a reliable and secure biocontrol agent in sustainable agriculture.
Drought is an increasingly important constraint on plant productivity, affecting agricultural yields, forest dynamics, and ecosystem functioning worldwide. Mycorrhizal symbioses formed by arbuscular (AM) and ectomycorrhizal (EcM) fungi are key regulators of plant responses to water limitation, influencing water acquisition, transport, and maintenance of plant water status at the soil-plant interface. This review synthesizes current knowledge of the mechanistic pathways through which mycorrhizal associations enhance plant drought tolerance. We distinguish between direct hydraulic contributions, including expanded soil exploration via extraradical hyphal networks, hyphal water uptake, redistribution, and modifications of rhizosphere hydraulic properties, and indirect physiological and biochemical effects, such as changes in root system architecture, regulation of aquaporins, osmotic adjustment, antioxidant capacity, and phytohormonal signaling. Particular emphasis is placed on structural and functional differences between AM and EcM symbioses. We examine how contrasting intraradical interfaces (i.e., arbuscules versus Hartig net) and extraradical networks influence water movement, plant hydraulic conductance, and whole-plant performance under drought. We assess the implications of these processes for agriculture and forestry, highlighting context-dependent fungal-plant compatibility, maintenance of diverse mycorrhizal communities, and management practices that preserve soil structure and mycorrhizal networks. Despite substantial evidence that mycorrhizal fungi improve plant performance under water deficit, their quantitative contributions to plant water transport and growth remain insufficiently resolved, particularly in EcM-dominated systems. Addressing these knowledge gaps will require integrative, multi-scale approaches linking molecular regulation, root and hyphal hydraulics, and ecosystem-level water fluxes. Such advances are critical for predicting vegetation responses to intensifying drought conditions under global change.
Colorectal cancer (CRC), which includes malignancies of the colon and rectum, constitutes a major global health challenge. Though there are several drugs that targets CRC-related genes/proteins, but their performance is not yet reach to the satisfactory level. Moreover, their effectiveness gradually decreases over time with long-term use, a phenomenon known as drug resistance. Therefore, it is required to explore new alternative candidate drugs against CRC. Several studies recommended CRC-related dysregulated host-genes guided candidate drugs. However, microbiome guided drug discovery particularly targeting bacterial key genes (bKGs) within CRC-associated gut microbiota remains very limited. This study aims to identify bKGs as antibacterial targets within CRC-associated bacterial taxa for exploring anti-bacterial agents. At first, we analysed a 16S rRNA-seq profile dataset that contained 24 CRC and 50 healthy samples, where beta diversity analysis results showed significant differences in bacterial compositions between CRC and HC groups. Differential abundance analysis with threshold values at |log2FC| > 1.0 and adjusted p-value < 0.05 identified 42 significantly altered bacterial taxa of which Bacteroides fragilis, Bacteroides ovatus, Bacteroides uniformis, and Flavonifractor plautii were prioritized based on effect size and published literature reporting their association with CRC. Further, an integrative subtractive genomics and protein-protein interaction (PPI) network analyses was used to identify top-ranked 10 essential bKGs (ribD, ribBA, murA, alr, hisI, hisE, hisD, hisG, hisH, and hisB) from these four CRC-associated bacterial taxa as putative antibacterial targets. Finally, three candidate drug molecules (Sulfasalazine, Aminoglutethimide, and Tipiracil) were recommended as the preliminary bKGs-guided candidate anti-bacterial agents for CRC through molecular docking and ADME/T analyses. Further experimental and clinical validation is required to establish these compounds as the effective drugs targeting the bKGs for CRC. Thus, these findings may provide insights for developing innovative anti-bacterial treatment approach relevant to CRC.
Staphylococcus condimenti is a coagulase-negative staphylococcus previously considered nonpathogenic. We report to our knowledge the first documented case of native-valve infective endocarditis caused by this pathogen. A 67-year-old man with rheumatic heart disease presented with fever and purpura. Initial IgA-dominant glomerulonephritis and leukocytoclastic vasculitis suggested systemic vasculitis. However, echocardiography revealed a large mitral vegetation. Scondimenti was identified by MALDI-TOF mass spectrometry and 16S rRNA sequencing from blood cultures and was subsequently confirmed by resected valve culture. After urgent mitral valve replacement and targeted cefazolin, the patient achieved full recovery and resolution of all immune-mediated complications. This report identifies Scondimenti as an emerging pathogen capable of significant valvular destruction and immune-mediated phenomena mimicking systemic vasculitis. Rare coagulase-negative staphylococci require integrating clinical context and species-level molecular identification to avoid dismissal as contaminants. Emerging pathogens can present with misleading systemic immunological manifestations, requiring high clinical suspicion for infective endocarditis.