Search Results (1,572)

The present review offers a comprehensive synthesis of the structural diversity, natural occurrence, and therapeutic promise of key ellagitannins (punicalagin, sanguiin H-6, corilagin, geraniin, oenothein B, chebulagic, and chebulinic acids) within the hydrolyzable ellagitannin pool. Distributed in medicinal and dietary plants long used in traditional medicine, ellagitannin-rich species serve as sources of both complex polyphenolic scaffolds and their bioactive metabolites, urolithins, which mediate many of their health-promoting effects. Special emphasis is placed on the multifaceted mechanisms that contribute to their potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects, extending to both non-communicable and communicable diseases. Despite their broad therapeutic spectrum, clinical translation is limited by challenges such as poor bioavailability, host-gut microbiota variability, and a lack of robust in vivo evidence. The review highlights future directions aimed at unlocking ellagitannins’ potential, including microbiota-targeted strategies for urolithin production, the design of stable prodrugs and analogs, and innovative delivery platforms. By integrating phytochemical, mechanistic and translational insights, this article positions ellagitannins as promising candidates for the development of novel polyphenol-based interventions. Full article

The human endometrium, previously considered a sterile environment, is now recognized as a low-biomass but biologically active microbial niche critical to reproductive health. Advances in sequencing technologies, particularly shotgun metagenomics, have provided unprecedented insights into the taxonomic and functional complexity of the endometrial microbiome. While 16S rRNA sequencing has delineated the distinction between Lactobacillus-dominant and non-dominant microbial communities, shotgun metagenomics has revealed additional diversity at the species and strain level, uncovering microbial signatures that remain undetected by amplicon-based approaches. Current evidence supports the association of Lactobacillus dominance with endometrial homeostasis and favorable reproductive outcomes. Dysbiosis, characterized by increased microbial diversity and enrichment of anaerobic taxa such as Gardnerella, Atopobium, Prevotella, and Streptococcus, is linked to chronic endometritis, implantation failure, and adverse IVF results. Beyond compositional differences, the endometrial microbiome interacts with the host through immunological, metabolic, and epigenetic mechanisms. These interactions modulate cytokine signaling, epithelial barrier integrity, and receptivity-associated gene expression, ultimately influencing embryo implantation. However, discrepancies between published studies reflect the lack of standardized protocols for sampling, DNA extraction, and bioinformatic analysis, as well as the inherent challenges of studying low-biomass environments. Factors such as geography, ethnicity, hormonal status, and antibiotic exposure further contribute to interindividual variability. Culturomics approaches complement sequencing by enabling the isolation of viable bacterial strains, offering perspectives for microbiome-based biotherapeutics. Emerging 3D endometrial models provide additional tools to dissect microbiome–host interactions under controlled conditions. Taken together, the growing body of data highlights the potential of endometrial microbiome profiling as a biomarker for reproductive success and as a target for personalized interventions. Future research should focus on integrating multi-omics approaches and functional analyses to establish causal relationships and translate findings into clinical practice. This review gives a new insight into current knowledge on the uterine microbiome and its impact on implantation success, analyzed through the lenses of microbiology, immunology, and oxidative stress. Full article

The cotton aphid Aphis gossypii is a globally significant agricultural pest that threatens crop production through its prolific reproduction. While the parasitoid wasp Binodoxys communis offers promising potential for biological control, the molecular mechanisms underlying its reproductive manipulation of aphid hosts remain poorly understood. Here, we investigated the stage-specific parasitism strategies of B. communis on A. gossypii using integrated biological observations and transcriptomic analysis. Parasitism significantly prolonged aphid development and suppressed reproduction across all host stages, with severity inversely correlated with host age at parasitism. Transcriptomic analysis of ovaries of parasitized aphids revealed 1168 differentially expressed genes, with temporal progression from minimal changes in nymphs (7 DEGs at day 1) to extensive disruption in adults (549 DEGs at day 3). Notably, juvenile hormone acid methyltransferase (JHAMT), the rate-limiting enzyme in juvenile hormone biosynthesis, emerged as a master regulator that is differentially targeted across host stages. In 3rd instar nymphs, single-gene suppression of JHAMT (−3.23-fold change) achieved effective reproductive control, whereas adult parasitism required progressive manipulation of multiple genes including JHAMT, FOHSDR, ALDH, and JHEH. The vitellogenin-vitellogenin receptor system only showed coordinated downregulation in adults, whereas nymphs exhibited preemptive receptor suppression before vitellogenesis onset. These findings demonstrate that B. communis has evolved to exploit a developmental window where host manipulation is most efficient—3rd instar nymphs, which possess sufficient resources for parasitoid development and lack the complex compensatory mechanisms found in adults. This “low-cost, high-reward” strategy based on precision targeting of master regulators in nymphs compared to multi-gene assault in adults, revealing the evolutionary optimization of parasitoid manipulation strategies. Our results provide molecular insights into parasitoid-host coevolution and identified key regulatory targets for developing innovative biological control strategies against this important agricultural pest. Full article

Background: Hyperuricemia (HUA), a metabolic disorder characterized by high serum uric acid (UA) level, presents a growing global health challenge. Method: In this study, a stable murine model of HUA was established by orally administering adenine (100 mg/kg) and potassium oxonate (600 mg/kg) in C57BL/6J mice, resulting in significant elevation of serum UA and xanthine oxidase (XOD) activity, as well as renal pathological alterations. Given the anti-hyperuricemia potential of Lactiplantibacillus plantarum WLPL04, a strain from a human breast milk was evaluated. Conclusions: Oral administration of L. plantarum WLPL04 significantly reduced serum UA level and XOD activity in a dose-dependent manner. Moreover, L. plantarum WLPL04 treatment enhanced UA excretion by upregulating ABCG2 and downregulating URAT1 and GLUT9 expression. It ameliorated renal injury and suppressed inflammation via downregulation of the NLRP3 inflammasome pathway. 16S rRNA gene sequencing revealed that L. plantarum WLPL04 restored gut microbial diversity and promoted the enrichment of beneficial genera such as Bacteroides, which was negatively correlated with UA in serum, creatinine, and inflammatory cytokines. Moreover, transcript analysis revealed upregulation of purine salvage genes (hpt and xpt), suggesting enhanced salvage pathway recycling of purine bases and reduced urate production. Those findings suggest that L. plantarum WLPL04 exerted multi-targeted anti-hyperuricemia effects through coordinated regulation of host purine metabolism, urate transport, inflammation, and gut microbiota composition, providing a promising probiotic candidate for HUA management. Full article

Background/Objectives: Bacteriophages are considered promising alternatives for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. Methods: Five bacteriophages with lytic activity against MDR P. aeruginosa were isolated from lake and sewage samples and characterized for their biological properties, host range, and efficacy in biofilm and in vitro infection models. Results: The phages displayed broad host ranges, producing zones of lysis in 40–53% of MDR isolates. The average burst size was 112 ± 70 PFU per cell. All phages, either individually or in combination, inhibited biofilm formation and were capable of disrupting preformed biofilms. While treatment with single phages led to bacterial regrowth, the cocktail of all five phages achieved complete bacterial lysis with no regrowth observed. In an in vitro wound and burn infection model, the phage cocktail significantly enhanced cell proliferation and promoted healing. Transmission electron microscopy (TEM) analysis identified phage PA2 as a Myovirus based on its morphology. Conclusions: The phage isolates demonstrated strong activity in multiple in vitro models, effectively targeting both planktonic and biofilm-associated P. aeruginosa. Notably, the five-phage combination prevented the emergence of bacterial resistance, supporting its potential as a biocontrol strategy against MDR P. aeruginosa. Full article

Insect establishment and dispersal are often influenced by temperature, with gut microbiota playing a critical role in host adaptation to environmental stress. This study investigated how gut bacterial structure and function in the invasive red-haired bark beetle (RHB), Hylurgus ligniperda (Fabricius) respond to temperature fluctuations, focusing on three core culturable bacteria: Rahnella perminowiae, Serratia marcescens, and Hafnia psychrotolerans. We found that temperature variations induced specific structural changes in the gut bacterial community, which in turn affected key functional processes such as carbohydrate metabolism. Notably, the relative abundance of Rahnella increased by more than 10% during the cold period (CP), and it maintained stable production of proteases and lipases under low temperatures—a trait that may be crucial for supporting host development in cold environments. Feeding on the diet converted by R. perminowiae at 5 °C resulted in a 20.9-day reduction in pupation time and a 1.8-fold increase in adult body mass compared to the blank control group, respectively. We propose that temperature remodels the gut microbiota by modulating competitive relationships among functional bacteria. This regulatory mechanism, based on functional redundancy and dynamic balance, serves as a buffer strategy that aids insect adaptation to temperature changes. Our findings provide new insights and a theoretical foundation for understanding pest outbreak patterns under climate warming and developing microbe-targeted control strategies. Full article

Besides genomic and proteomic analyses of bulk and individual cancer cells, cancer research focuses on the mechanical analysis of cancers, such as cancer cells. Throughout the oncogenic evolution of cancer, mechanical inputs are stored as epigenetic memory, which ensures versatile coding of malignant characteristics and a quicker response to external environmental influences in comparison to solely mutation-based clonal evolutionary mechanisms. Cancer’s mechanical memory is a proposed mechanism for how complex details such as metastatic phenotypes, treatment resistance, and the interaction of cancers with their environment could be stored at multiple levels. The mechanism appears to be similar to the formation of memories in the brain and immune system like epigenetic alterations in individual cells and scattered state changes in groups of cells. Carcinogenesis could therefore be the outcome of physiological multistage feedback mechanisms triggered by specific heritable oncogenic alterations, resulting in a tumor-specific disruption of the integration of the target site/tissue into the overall organism. This review highlights and discusses the impact of the ECM on cancer cells’ mechanical memory during their metastatic spread. Additionally, it demonstrates how the emergence of a mechanical memory of cancer can give rise to new degrees of individuality within the host organism, and a connection to the cancer entity is established by discussing a connection to the metastasis cascade. The aim is to identify common mechanical memory mechanisms of different types of cancer. Finally, it is emphasized that efforts to identify the malignant potency of tumors should go way beyond sequencing approaches and include a functional diagnosis of cancer physiology and a dynamic mechanical assessment of cancer cells. Full article

Background/Objectives: Lipid nanoparticles (LNPs) have demonstrated notable clinical success as advanced drug delivery systems. However, the development of novel covalently bonded ionizable lipids faces substantial technical challenges, as their modification is difficult and they have a high molecular weight. To address this issue, we report the use of host–guest complexes in supramolecular chemistry as functional lipid motifs for constructing LNPs. Methods: Ionizable amine β-cyclodextrin (amine β-CD)-derived host–guest amphiphilic lipid molecules (HGLs) were designed for the construction of multi-stage assembly supramolecular LNPs (MSLNPs). The structure–function relationships and stability of MSLNPs were explored by screening eight types of amine β-CDs and varying the ratio of HGL to yolk phosphatidylcholine. Stability screening and molecular dynamics simulations were performed to clarify the self-assembly mechanisms and optimal formulations, followed by a systematic evaluation of delivery performance. Results: MSLNPs showed a high drug-loading efficiency (> 30%), a rapid-response release in acidic environments, and multi-pathway cellular uptake. In vivo delivery experiments using ethylenediamine β-CD-based MSLNPs in mice revealed no significant immunogenicity, no significant abnormalities in organs/tissues or their functions, a unique biodistribution pattern, and pronounced renal targeting. The successful development of MSLNPs with acidic pH-responsive control, a high delivery efficiency, and renal-targeting properties simplifies LNP preparation. Conclusions: This study offers novel insights into the design of simplified LNPs and the optimization of targeted delivery, with potential applications in renal disease therapy. Full article

The use of fungal entomopathogens, such as Metarhizium anisopliae, is a promising alternative for pest biocontrol but suffers the disadvantage of a relatively slower killing speed when compared with chemical pesticides. Nilaparvata lugens (brown planthopper, BPH) is a destructive sap-sucking pest that seriously threatens rice production worldwide. In the present study, we characterized a key immune-regulating protein, Spätzle (SPZ), encoding gene NlSPZ5 in BPH, and constructed a transgenic strain of M. anisopliae that expressed a specific dsRNA targeting the NlSPZ5 gene for enhancing the fungal virulence. Expression pattern analysis revealed that NlSPZ5 was expressed with the highest levels in the second-instar nymphs and hemolymph and could be largely activated by M. anisopliae infection. Microinjection of dsNlSPZ5 resulted in a markedly decreased survival rate and increased susceptibility to fungal infection in BPH. Notably, a transgenic strain of M. anisopliae expressing dsNlSPZ5 could effectively suppress the target gene expression and promote fungal proliferation in BPH upon fungal challenge. Compared to the wild-type strain, the transgenic fungal strain exhibited significantly enhanced insecticidal efficacy against BPH without compromising mycelial growth and sporulation. Our results demonstrate that fungal entomopathogens used as a delivery vector to express dsRNAs targeting insect immune defense-associated genes can effectively augment their virulence to the host insect, providing clues to develop novel pest management strategies through the combination of RNAi-based biotechnology and entomopathogen-based biocontrol. Full article

Childhood obesity is a newly emerging public health and an emerging concern in environmental health in rapidly urbanized areas of China. This preliminary study investigated the gut microbiome composition and toxic metabolite pathways of school-aged children in Nanjing. Using 16S rRNA sequencing and PICRUSt2-based functional predictions, we observed significant microbial structural changes between the normal weight group and the overweight/obese group, although α diversity was similar. Overweight and obese children exhibited a markedly higher Firmicutes/Bacteroidetes ratio as well as an enrichment of genera such as Subdoligranulum, Ruminococcus, and Lachnospira, indicating increased energy harvesting and inflammation. Functionally, the downregulation of tryptophan metabolism in obese children suggests a reduction in anti-inflammatory indole and an increase in the production of pro-inflammatory kynurenine. In contrast, the upregulation of thiamine metabolism may be linked to enhanced carbohydrate utilization and lipid biosynthetic activity. Our toxicology network analysis and molecular docking experiments suggest that AhR and thiamine-related metabolic enzymes are targets of tryptophan and thiamine metabolism, respectively, and that PPARG is also a potential molecular target mediating thiamine metabolism in childhood obesity. These findings highlight the environment–microbiome–host axis as a potential pathway for metabolic toxicity in childhood obesity. Further studies are needed to validate these toxicological mechanisms and identify microbial biomarkers for early intervention. Full article

Oropouche virus (OROV), an emerging orthobunyavirus of increasing public health concern in the Americas, currently lacks approved antiviral therapies. In this study, we employed a structure-based in silico approach to identify natural antiviral scaffolds capable of targeting the Gc glycoprotein, a class II fusion protein essential for host membrane fusion and viral entry. A library of 537 plant-derived compounds was screened against the Gc head domain (PDB ID: 6H3X) through molecular docking and redocking, followed by 100-nanosecond molecular dynamics simulations, MM-PBSA free energy calculations, and ADMET profiling. Curcumin and Berberine emerged as standout candidates. Curcumin demonstrated a balanced profile, with stable binding (−38.14 kcal/mol), low backbone RMSD (1.82 Å), and consistent radius of gyration (Rg ~ 18.8 Å), suggesting strong conformational stability and compactness of the protein–ligand complex. Berberine exhibited the most favorable binding energy (−13.10 kcal/mol) and retained dynamic stability (RMSD 1.86 Å; Rg ~ 19.0 Å), though accompanied by predicted cytotoxicity that may require structural refinement. Both compounds induced reduced residue-level fluctuations (RMSF < 2.5 Å) in functionally critical regions of the Gc protein, consistent with a mechanism of action that involves stabilization of the prefusion conformation and interference with the structural transitions required for viral entry. These findings identify curcumin and berberine as promising scaffolds for anti-OROV drug development and offer a rational foundation for future experimental validation targeting viral fusion mechanisms. Full article

Periodontitis (PD) is a multifactorial, progressive inflammatory disease affecting the teeth-supporting tissues, characterized by an imbalance of the oral microbiota and the presence of bacterial biofilms leading to host response. Nowadays, reliable biochemical markers for early and objective diagnosis, and for predicting disease progression, are still lacking. Our previous proteomic investigations revealed the significant overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in periodontal pocket tissue, gingival crevicular fluid (GCF), and tooth-surface-collected material (TSCM) from PD patients in comparison to periodontally healthy controls, proposing it as a possible biomarker of PD. This study aimed to evaluate the expression of GAPDH in saliva, a more accessible, non-invasive, and clinically relevant oral sample. The whole saliva was analyzed by a preliminary mass spectrometry-based proteomic approach, identifying significantly increased levels of GAPDH also in salivary samples from periodontal-affected subjects. These data were further validated by enzyme-linked-immunosorbent assay (ELISA). Additionally, protein–protein interaction networks were generated through the Human Protein Atlas database, using different datasets (OpenCell, IntAct, and BioGRID). Bioinformatic analysis provided noteworthy GAPDH-associated networks potentially relevant to periodontal pathology. The scientific significance of this study lies in the detection of salivary GAPDH as a novel strategy to advance periodontal clinical diagnostics from the perspective of a non-invasive screening test. In correlation with other protein markers, salivary GAPDH could constitute a promising set of distinctive and predictive targets to enhance early diagnosis of PD, disease monitoring, and treatment planning in periodontology. Full article

Accurate phase identification is essential for characterising complex mineral systems but remains a challenge in SEM-based automated mineralogy (AM) for compositionally variable rock-forming or accessory minerals. While platforms such as the Tescan Integrated Mineral Analyzer (TIMA) offer high-resolution phase mapping through BSE-EDS data, classification accuracy depends on the quality of the user-defined phase library. Generic libraries often fail to capture site-specific mineral compositions, resulting in misclassification and unclassified pixels, particularly in systems with solid solution behaviour, compositional zoning, and textural complexity. We present a refined approach to developing and validating custom TIMA phase libraries. We outline strategies for iterative rule refinement using mineral chemistry, textures, and BSE-EDS responses. Phase assignments were validated using complementary microanalytical techniques, primarily electron probe microanalysis (EPMA) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Three Queensland case studies demonstrate this approach: amphiboles in an IOCG deposit; cobalt-bearing phases in a sediment-hosted Cu-Au-Co deposit; and Li-micas in an LCT pegmatite system. Targeted refinement of phases improves identification, reduces unclassified phases, and enables rare phase recognition. Expert-guided phase library development strengthens mineral systems research and downstream applications in geoscience, ore deposits, and critical minerals while integrating datasets across scales from cores to mineral mapping. Full article

Toxoplasma gondii, the causative agent of toxoplasmosis widespread in animals and humans, is an intracellular apicomplexan protozoan parasite infecting a variety of host cells. Gene editing using CRISPR-Cas9 has become a standard tool to investigate the molecular genetics of this interaction. With respect to gene knock-out (KO) studies, the general paradigm implies that the gene of interest is expressed in the wildtype and that only the gene of interest is affected by the knock-out. Consequently, the observed phenotype depends on the presence or absence of genes of interest. To challenge this paradigm, we knocked out two open reading frames (ORFs) constitutively expressed in T. gondii ShSp1 tachyzoites, but not essential, namely ORF 297720 encoding a trehalose-6-phosphatase homolog and ORF 319730 encoding a You2 C2C2 zinc finger homolog. We analyzed the proteomes of tachyzoites isolated at a late stage of infection, as well as intracellular tachyzoites and host cells at an early stage of infection. The intended KO proteins were present in the T. gondii Sp1 wildtype but absent in the KO clones. Moreover, besides differentially expressed (DE) proteins specific to each KO, 17 DE proteins common to both KOs were identified in isolated tachyzoites and 39 in intracellular tachyzoites. Moreover, 76 common DE proteins were identified in host cells. Network and enrichment analyses showed that these proteins were functionally related to antiviral defense mechanisms. These results indicate that the KO of a gene of interest may not only affect the expression of other genes of the target organism, which in our case is T. gondii, but also the gene expression of its host cells. Therefore, phenotypes of KO strains may not be causally related to the KO of a given gene. Overall, this study highlights that genetic manipulation in T. gondii can lead to system-wide proteomic shifts in both parasite and host, emphasizing the need for cautious interpretation of knock-out-based functional analyses. Full article

Against the backdrop of safety becoming a key objective in the restructuring of industrial chains, the impact of China’s outbound foreign direct investment (OFDI) on industrial chain risks warrants further exploration. Based on the Asian Development Bank’s Multi-Regional Input-Output Data (ADB-MRIOD) from 2007 to 2023, this study measures the external risk exposure of industrial chains from both supply-side and demand-side perspectives across 41 Belt and Road Initiative (BRI) economies. Utilizing a two-way fixed effects panel model with lagged variables and instrumental techniques to mitigate endogeneity, we empirically investigate the mechanisms through which China’s OFDI influences the external risk exposure of industrial chains. The findings reveal that (1) China’s OFDI significantly reduces such risk exposure, and (2) effect heterogeneity observed across country groups and sectors—showing stronger mitigation in high-innovation and developing countries, as well as in capital-intensive industries. (3) Mechanism analysis identifies three transmission channels: enhancing the host country’s trade network status, rationalizing its industrial structure, and strengthening Sino-host country industrial linkages. The study provides empirical support for formulating targeted investment policies to enhance supply chain resilience under the BRI framework. Full article