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Integrative pooled transcriptomic analysis reveals shared and distinct molecular signatures in adult T-cell leukemia/lymphoma and peripheral T-cell lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphomas (PTCLs) are aggressive neoplasms of mature T cells with poor prognosis and limited therapies. ATLL originates from HTLV-1 infection, while PTCL comprises heterogeneous subtypes without a defined etiologic factor. Comparative molecular profiling of these malignancies remains limited. We conducted an integrative pooled transcriptomic analysis of publicly available Gene Expression Omnibus (GEO) microarray datasets to compare ATLL, PTCL, and normal T-cell samples. Differential expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed using STRING, Cytoscape, and Gephi. Key hub genes and functional modules were further analyzed through KEGG and Enrichr databases. Comparative analyses revealed upregulation of extracellular matrix (ECM) components (COL1A1, COL3A1, FN1, SPARC, THBS1) and immune-regulatory molecules (CD163, CXCL12-CXCR4, complement subunits). Shared pathways included ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling. PTCL showed enrichment in coagulation and angiogenesis, while ATLL displayed distinct enrichment of cytoskeletal, chemokine, immune-regulatory, and signaling-associated pathways. PPI networks identified ECM and chemokine signaling as key hubs, with subtype-specific modules related to immune regulation, proliferation, and metabolism. This integrative approach uncovers common and distinct oncogenic programs in ATLL and PTCL, emphasizing ECM remodeling and immune modulation as shared hallmarks. Hub genes such as COL1A1, FN1, and CXCL12-CXCR4 may represent candidate molecular signatures that warrant validation in independent patient cohorts and functional studies before their clinical utility can be established.

Humans↗

Efficacy and safety of Vertebral Body Sliding Osteotomy (VBSO) versus Anterior Cervical Corpectomy and Fusion (ACCF): A systematic review and meta-analysis.

Anterior cervical corpectomy and fusion (ACCF) is an established treatment for complex cervical myelopathy and ossification of the posterior longitudinal ligament (OPLL), yet it carries risks of dural injury and graft-related failure. Vertebral body sliding osteotomy (VBSO) is a novel technique that avoids direct OPLL manipulation by translating the vertebral body anteriorly to enlarge the spinal canal. Although early studies suggest VBSO may reduce complications, evidence remains limited to retrospective cohorts from the technique's developers, with no high-level synthesis directly comparing it to ACCF. We therefore conducted this meta-analysis to compare clinical outcomes, complications, and radiographic parameters between VBSO and ACCF, while critically evaluating the certainty of the evidence and its generalizability. A systematic search of PubMed, Embase, Scopus, the Cochrane Library, and Web of Science (through June 2025) identified four retrospective cohort studies (449 patients; VBSO n&#x2009;=&#x2009;209, ACCF n&#x2009;=&#x2009;240). A critical limitation of the included evidence is that all studies originated from a single institution (Asan Medical Center, Seoul, Korea) with overlapping enrollment periods (2006-2020), increasing the risk of duplicate patient cohorts. Furthermore, the first author (D.-H. Lee) is the same across all included studies, introducing substantial surgeon-expertise bias. Outcomes included neurological recovery, functional outcomes, complications, and radiographic parameters. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Neurological recovery and functional outcomes were comparable between groups. ACCF showed slightly higher postoperative JOA scores (MD -0.59, 95% CI -0.96 to -0.22; p&#x2009;<&#x2009;0.01), though the clinical relevance is uncertain. VBSO was associated with reduced risks of graft subsidence (RR 0.23; p&#x2009;<&#x2009;0.01), pseudarthrosis (RR 0.25; p&#x2009;<&#x2009;0.01), revision surgery (RR 0.17; p&#x2009;<&#x2009;0.01), and neurological deterioration (RR 0.17; p&#x2009;=&#x2009;0.02). CSF leakage appeared to be less frequent with VBSO, but the difference was not statistically significant. VBSO was also associated with greater postoperative cervical lordosis and shorter hospital stays. However, these findings must be interpreted with extreme caution: leave-one-out sensitivity analyses revealed that the results for postoperative JOA score, neurological deterioration, and pseudarthrosis were fragile and driven by a single large study, meaning these apparent advantages may not be robust. In addition, GRADE assessment revealed very low certainty across all assessed outcomes. Given the very low certainty of evidence, the preliminary nature of the available data, the fragility of several key findings, and the critical limitations of the underlying studies (single institution, overlapping patient cohorts, developer bias, and systematic imbalance in follow-up duration), the observed differences should be considered hypothesis-generating rather than definitive. VBSO should not be considered a proven superior alternative to ACCF based on the current evidence. Prospective, multicenter, international studies with balanced follow-up durations conducted by independent surgical teams are required before broader adoption can be recommended.

Humans↗

Unlocking the molecular engineering of Geobacillus glycoside hydrolases as a source of industrial biocatalysts.

This review examines Geobacillus sensu stricto as a source of thermostable glycoside hydrolases (GH) for biomass conversion, food processing, and enzyme engineering. Recent peer-reviewed literature was assessed with emphasis on taxonomy, genome-based Carbohydrate-Active Enzymes (CAZyme) prediction, biochemical validation, structural data, and engineering case studies. Taxonomic boundaries were interpreted using current Anoxybacillaceae frameworks, with Parageobacillus treated as a related comparator rather than as Geobacillus. The strongest evidence supports GH13 alpha-amylases, xylan-active systems, beta-xylosidases, and selected accessory enzymes. Recent studies also show that genome mining must be coupled with enzymatic assays and product profiling because CAZyme annotation alone does not prove industrial function. Molecular engineering has improved relevant traits, including the longer thermal half-life of engineered G. stearothermophilus alpha-amylase variants, the increased catalytic efficiency of oligo-alpha-1,6-glucosidase variants, and improved AmyS expression in Bacillus subtilis. Geobacillus glycoside hydrolases are best interpreted as process-specific, engineerable biocatalytic templates. Their translation requires reliable taxonomy, functional validation, structural interpretation, scalable expression and testing on realistic substrates. This synthesis also recognises current limitations: many predicted CAZymes still lack biochemical validation, complete cellulolytic systems remain less mature than xylan- and starch-active systems, and scale-up data remain scarce.

Geobacillus↗

Real-world estrogen receptor alpha 1 (ESR1) testing patterns and results for ER+/HER2- metastatic breast cancer in the United States, 2018-2024.

PURPOSE: To understand historical and recent ESR1 testing rates, and when ESR1 mutations emerge during first-line (1&#xa0;L) treatment. METHODS: This retrospective, observational cohort study used the Flatiron Health Research Database (FHRD) and the Flatiron Health-Foundation Medicine metastatic breast cancer (mBC) Clinico-Genomic Database (CGDB). Adult patients with a confirmed diagnosis of hormone receptor-positive/human epidermal growth factor receptor 2-negative mBC from 1/1/2018 to 6/30/2024 were included. ESR1 testing patterns and test results were descriptively analyzed. RESULTS: Among 7772 patients with mBC in the FHRD who initiated 1&#xa0;L therapy, tumor ESR1 mutation status was evaluated for 222 (3%) patients at baseline (&#x2264;&#x2009;90 days before 1&#xa0;L) and 1355 (17%) during 1&#xa0;L. The percentage of patients who had an ESR1 test result reported during 1&#xa0;L increased over time (11% in 2018-19, 19% in 2020-21, 22% in 2022-24). Median time from 1&#xa0;L start to first ESR1 test was 7.4 months (mos) among tested patients. A positive test result was reported for 29/222 (13%) patients tested at baseline and 240/1355 (18%) tested during 1&#xa0;L. Most (60%) tests during 1&#xa0;L used tissue specimens, while the remaining 40% were liquid biopsies, and the median time from specimen collection to result reporting in 1&#xa0;L was 28 (IQR:10-84) days. Focusing on time periods wherein specimens were provided, ESR1 test positivity was 6.7% (76/1,127) for specimens provided at baseline, 23% (15/65) for specimens provided 9 to 12 months into 1L therapy, 38% (26/69) for those provided 15 to 18 months into 1L, and 40% (38/94) for those provided from 18 to 24 months into 1L. CONCLUSIONS: ESR1 mutations can be detected at any time interval during 1L. CLINICAL TRIAL NUMBER: Not applicable.

Adult↗

Exploring trop-2-directed ADCs monotherapy and combination therapy in pretreated mTNBC: a real-world study.

PURPOSE: Although Trop-2 antibody-drug conjugates (ADCs) have improved outcomes in pretreated metastatic triple-negative breast cancer (mTNBC), resistance remains common and the optimal combination strategy in routine practice is unclear. METHODS: In this retrospective real-world study, we identified patients with mTNBC from a health record-derived database who received sacituzumab govitecan or sacituzumab tirumotecan in the later-line setting between April 2020 and December 2025. Patients received at least two cycles of Trop-2 ADC therapy as monotherapy, plus a PD-1 inhibitor (dual-agent combination), or plus a PD-1 inhibitor and an antiangiogenic agent (triple-agent combination). RESULTS: Descriptively, the ORR was 57.1% in the triple-agent combination group, 38.5% in the dual-agent combination group, and 31.7% in the monotherapy group. Median follow-up was 15.2 months (95% CI, 8.7-20.6). Median progression-free survival (mPFS) was 15.4 months (95% CI, 5.3-NA) in the triple-agent combination group, 10.0 months (95% CI, 4.2-NA) in the dual-agent combination group, and 3.8 months (95% CI, 3.2-5.2) in the monotherapy group. Severe treatment-related toxicity was not increased in the combination groups. Exploratory analyses identified a genomic scoring system that may enable stratification of patients with a higher likelihood of benefiting from the triple-agent combination. CONCLUSION: To our knowledge, this study represents one of the earliest real-world evaluations of this triple-agent strategy in previously treated mTNBC, providing a basis for further prospective validation and biomarker-guided application.

Humans↗

The effect of compression dressing on postoperative outcomes after upper eyelid blepharoplasty: a randomized, controlled, observer-blinded evaluation study.

PURPOSE: This study aimed to evaluate the impact of a compression dressing on postoperative pain, ocular surface changes, edema, ecchymosis, and aesthetic outcomes following upper eyelid blepharoplasty. METHODS: This observer-blinded, randomized, controlled trial included 112 eyelids from 56 patients who underwent bilateral upper eyelid blepharoplasty between June and August 2025. After surgery, one eyelid received a compression dressing (CD), while the other eyelid received no dressing (ND). Edema and ecchymosis were graded by masked observers on postoperative days 1, 7, 30, and 90. Aesthetic outcomes were evaluated using the Global Aesthetic Improvement Score. Pain was evaluated using a visual analog scale, and patient comfort was assessed by side preference. RESULTS: On postoperative day 1, ecchymosis scores were significantly lower in the CD group than in the ND group (unadjusted p = 0.002; Holm-adjusted p = 0.012). Edema scores were also lower on the CD side (unadjusted p = 0.012) and aesthetic scores were higher (unadjusted p = 0.046); however, neither difference remained statistically significant after Holm-Bonferroni correction for multiple comparisons (adjusted p = 0.060 and p = 0.138, respectively). No significant differences were observed in any parameter on postoperative days 7, 30, or 90 (all adjusted p > 0.05). Corneal staining scores were comparable between groups at all follow-ups, and no corneal erosions were observed. Pain scores on day 1 were similar (p = 0.977). CONCLUSIONS: Compression dressing after upper eyelid blepharoplasty was associated with a significant reduction in early postoperative ecchymosis, an effect that persisted after correction for multiple comparisons. Reductions in edema and improvements in aesthetic scores were observed on postoperative day 1 but did not remain statistically significant after adjustment. Overall, the benefits of compression dressing were limited in magnitude and transient, and routine use may not be necessary; its application should be individualized according to patient needs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT07701265 (retrospectively registered on July 8, 2026).

Humans↗

Molecular-networking-based characterization of cytotoxic metabolites produced by the cyanobacterium Nostoc edaphicum CCNP1411.

Cyanobacteria of the genus Nostoc, known for their large genomes and rich repertoire of biosynthetic gene clusters, represent a prolific source of structurally diverse secondary metabolites with diverse biological activities, including cytotoxic effects. However, the identification of bioactive compounds is often hindered by low metabolite abundance and difficulties in isolating sufficient quantities for individual testing. In this study, we investigated the cytotoxic potential of chromatographic fractions obtained from&#xa0;Nostoc edaphicum CCNP1411 using a combination of bioassay-guided fractionation and LC-MS/MS-based feature-based molecular networking (FBMN). Cytotoxic activity was evaluated using the MTT assay across a panel of epithelial and neuronal cancer cell lines, as well as normal human dermal fibroblasts. The most active fractions, eluted with 80-90% MeOH, exhibited broad cytotoxic effects across all tested cancer cell lines. Molecular networking analysis revealed that these fractions were dominated by lipid derivatives, including lysophospholipids, monoacylglycerols, and free fatty acids, whereas previously described peptide metabolites were distributed across all fractions and were unlikely to be the main agents responsible for the observed activity. Targeted testing of selected commercially available lipid compounds confirmed their cytotoxic effects, with lysophospholipids showing the highest potency in selected cell lines. However, dose-response analysis indicated that most compounds exhibited limited potency at lower concentrations, as reflected by relatively high IC&#x2085;&#x2080; values. Overall, our results demonstrate that lipid constituents, previously overlooked as bioactive metabolites produced by N. edaphicum CCNP1411, contribute significantly to the cytotoxic activity of the tested fractions. The application of molecular networking enabled the prioritization of bioactive metabolites and highlights its utility in linking chemical composition with biological effects in complex cyanobacterial extracts.

Bioactivity-guided fractionation↗

Pinpointing genomic regions conferring herbicide tolerance in cassava via genome-wide association mapping.

Cassava (Manihot esculenta Crantz) is a tropical crop of major socioeconomic importance, whose productivity can be limited by sensitivity to herbicides used for weed management. This study aimed to perform a genome-wide association study (GWAS) in 194 cassava genotypes to identify genomic regions associated with tolerance to the herbicides mesotrione, S-metolachlor, and chloransulam-methyl. The evaluations performed at 3, 6, 9, 15, and 30 days after application (DAA) were used to characterize the temporal progression of phytotoxicity. Based on this analysis, the phenotype obtained at 9 days after application (PhytoX9DAA) was selected for genome-wide association analyses because it represented the period of greatest symptom expression and the highest discrimination among genotypes. GWAS analyses were performed using de-regressed BLUPs and the MLM, MLMM, and BLINK models, incorporating kinship (K) and population structure (Q) matrices. Significant markers were detected across multiple chromosomes, and the corresponding genomic windows contained candidate genes with functional annotations related to herbicide response. The predominant functional categories included membrane transport, channel activity, signal peptide processing, protein phosphorylation, cellular signaling, and metabolic regulation. Key candidate genes included Manes.02G151900 and Manes.02G152700 (chromosome 2), associated with transmembrane transport and signal peptide processing; Manes.09G060900 (chromosome 9), associated with protein kinase activity, ATP binding, and protein phosphorylation; and Manes.15G083800 and Manes.15G084000 (chromosome 15), associated with S-adenosylmethionine-dependent methyltransferase activity, membrane-related functions, and protein phosphorylation. These genes participate in biochemical pathways involved in cellular signaling, membrane transport, and metabolic regulation that may contribute to herbicide tolerance. Overall, the results demonstrate that herbicide tolerance in cassava is a quantitative and polygenic trait governed by numerous small-effect loci. The integration of cellular signaling, metabolic regulation, and membrane transport supports the physiological resilience of the species under chemical exposure, providing valuable insights for breeding strategies and marker-assisted selection.

Genome-Wide Association Study↗

Generation of germline-transmitting transgenic sheep by piggyBac-mediated transgenesis using pronuclear and cytoplasmic gene injection approaches.

Sheep represent an important large-animal model for biomedical research and biopharmaceutical production. Although the piggyBac transposon system offers efficient and stable genomic integration, the optimal gene delivery strategy for ovine embryos remains unclear. This study evaluated piggyBac-mediated transgenesis using pronuclear injection (PNI) in both in vivo- and in vitro-derived embryos and assessed cytoplasmic injection (CTI) as an alternative approach. In vivo-derived embryos were obtained from superovulated K&#x131;v&#x131;rc&#x131;k ewes approximately 40&#x2009;h after gonadotropin-releasing hormone administration, whereas in vitro-derived embryos were produced from slaughterhouse-derived oocytes. All embryos were injected with the hyperactive piggyBac transposase-based pmhyGENIE-3 construct (10&#x2009;ng/&#xb5;L). In vivo-derived embryos were transferred immediately after injection, whereas in vitro-derived embryos were cultured for 3&#x2009;days and screened for EGFP expression prior to transfer. Among 65 in vitro-derived embryos injected by PNI, no transgenic offspring was obtained. In contrast, PNI of 19 in vivo-derived embryos resulted in one transgenic lamb (5.3%). CTI of 12 in vivo-derived embryos similarly produced one transgenic lamb (8.3%). Whole-genome sequencing of the healthy founder male produced by CTI identified a single detectable genomic integration locus on chromosome 10 within a non-coding RNA locus (LOC121820439). Germline transmission was confirmed by in vitro fertilization using sperm from the founder male, with EGFP expression detected in 10.1% (10/99) resulting embryos. These findings provide proof-of-concept evidence for piggyBac-mediated transgenesis in sheep and support the feasibility of cytoplasmic injection as an alternative gene-delivery approach under the conditions tested.

Animals↗

Advancing genetic evaluation of milk yield and composition using a genomic-polygenic model in smallholder dairy cattle farms in Thailand.

Improving the accuracy of genetic evaluation in smallholder dairy systems is essential for sustainable productivity. However, traditional polygenic models (PM) are often constrained by incomplete pedigree, heterogeneous management, and limited genotyping resources. This study evaluated a genomic-polygenic model (GPM) relative to a PM using data from a multibreed dairy population raised under Thai tropical smallholder conditions. Phenotypic records for 305-day milk yield (MY), fat percentage (FP), protein percentage (PP), and somatic cell count (SCC) from 14,417 first-lactation cows across 1,321 farms were analyzed together with genotypes from 5,479 animals generated using GeneSeek Genomic Profiler (GGP) arrays ranging from 9&#xa0;K to 150&#xa0;K SNPs. Both models included herd-year-season of calving, age at first calving, and heterosis as fixed effects, and additive genetic and residual components treated as random. The GPM yielded higher additive genetic variances and heritability estimates and produced more biologically consistent antagonistic correlations among traits than the PM. Prediction accuracy was improved for all animal groups under the GPM, with the largest gain observed in genotyped young sires (18.36%). Pedigree connectedness analysis indicated that genotyping animals with low to moderate relationships enhances accuracy cost-effectively. Despite persistent challenges associated with heterogeneous management and limited pedigree depth, the results demonstrate the practical value of genomic-polygenic evaluation for smallholder multibreed dairy populations in tropical environments.

Animals↗

Integration of domestic wastewater and native Tetradesmus obliquus for bioremediation and production of biomass rich in protein and polyunsaturated fatty acids.

The large-scale deployment of microalgae-based bioprocesses is often limited by high freshwater and nutrient demands. Domestic wastewater represents a sustainable alternative, enabling simultaneous pollutant removal and biomass production. In this study, a native strain of Tetradesmus obliquus, isolated in southern Brazil, was cultivated in raw domestic wastewater (RDW) and primary-treated domestic wastewater (TDW) at three initial inoculum densities (10%, 20%, and 30% v/v) for 14&#xa0;days. Tetradesmus obliquus in TDW inoculated at 10% (v/v) removed 62.46% of ammonium and 98.56% of phosphate, simultaneously exhibiting the highest specific growth rate (0.16 d&#x207b;1) and the highest biomass productivity (42.54&#xa0;mg L&#x207b;1 d&#x207b;1). Iron and manganese concentrations decreased significantly with a native strain in TDW, indicating effective removal of them under the evaluated conditions. RDW was associated with higher carbohydrate accumulation (32.68%) and pigment production, whereas TDW was associated with higher protein content (45.83%) and a lipid fraction with a high relative proportion of polyunsaturated fatty acids (72.70-78.90%), primarily represented by &#x3b1;-linolenic and linoleic acids. The combined assessment of wastewater condition and initial inoculum density revealed distinct effects on the cultivation system. These aspects influence the biochemical composition of biomass, initial inoculum density, nutrient removal, specific growth rate, and biomass productivity. Thus, the present study supports the potential to integrate domestic wastewater treatment with the cultivation of a native Tetradesmus obliquus strain and indicates that, under the evaluated conditions, both the wastewater treatment conditions and the initial inoculum density influenced bioremediation performance and the biochemical composition of biomass.

Biochemical composition↗

Copper and iron engage distinct metabolic programs for cellular survival.

Copper and iron are redox-active micronutrients with tightly coupled homeostasis, yet how copper modulates iron-dependent stress responses remains unclear. Using&#xa0;Saccharomyces cerevisiae under nutrient-limited conditions, we uncoupled proliferative growth from long-term survival to dissect metal-dependent adaptation. Copper selectively preserved survival without affecting growth, whereas iron showed similar effects. Iron chelation impaired growth and suppressed electron transport chain gene expression; copper partially rescued these defects but required iron availability for its pro-survival activity. Despite this interdependence, copper and iron engaged distinct signaling programs. Iron-dependent survival required a Target of Rapamycin complex 1 (TORC1)-permissive state and was attenuated by rapamycin, whereas copper remained active under TORC1 inhibition. In contrast, copper promoted survival through AMP-activated protein kinase (AMPK) and antioxidant pathways, while iron exhibited context-dependent AMPK reliance. Together, these findings reveal that copper and iron support cellular survival through distinct metabolic programs and suggest that the consequences of micronutrient availability are shaped by the underlying nutrient-sensing and metabolic state of the cell. This framework provides insight into how alterations in micronutrient homeostasis and metabolic signaling may influence cellular resilience during aging.

AMPK↗

Protein arginine methyltransferases as metabolic regulators: many roles beyond cancer.

Metabolic syndrome (MetS) comprises a cluster of interconnected metabolic abnormalities that collectively elevate the risk of cardiovascular disease and mortality. With its global prevalence escalating, understanding the molecular underpinnings of MetS has become increasingly imperative. Protein arginine methyltransferases (PRMTs), classically studied for their epigenetic functions and oncogenic properties, are now recognized as pivotal regulators of metabolic homeostasis. Emerging research reveals that these enzymes coordinate crucial aspects of cellular metabolism through multiple mechanisms, including methylation of metabolic transcription factors, modulation of nutrient-sensing pathways, and direct regulation of enzymatic activities in glucose and lipid metabolism. This review summarizes current knowledge on the metabolic roles of PRMTs, specifying their roles in the development and function of major metabolic tissues and their associations with various metabolic disorders. We further review how PRMTs influence metabolic processes by modifying key transcriptional networks and signaling cascades through methylation of different substrates. By integrating these insights, we establish PRMTs as central players in metabolic regulation and assess their potential as therapeutic targets for metabolic diseases beyond their established roles in cancer biology, thereby providing a framework for future research and clinical development.

glucose metabolism↗

The removal of iron and phosphate from culture medium by Rhodococcus ruber SiAl.

The microbial accumulation of heavy metals and phosphate is of interest for the bioremediation of polluted waters. In this work, we showed that at cultivation of the bacterium Rhodococcus ruber SiAl in the medium with 2.0 mM Fe&#xb3;&#x207a; for stationary growth stage, up to 99% of the iron was associated with the biomass. Magnesium ion accumulation from the medium with 2 mM Mg&#xb2;&#x207a; did not exceed 5% of the initial content. The cells did not remove manganese ions from the medium; moreover, the presence of MnSO4 inhibited growth. The cells of Rhodococcus ruber SiAl removed phosphate from the medium: 75, 20, and 10% of the initial phosphate content was removed during cultivation in the presence of 6 mM phosphate and 2 mM Fe&#xb3;&#x207a;, 2 mM Mg&#xb2;&#x207a;, or 2 mM Mn&#xb2;&#x207a;, respectively. In the genome of R. ruber SiAl, genes encoding proteins of the siderophore synthesis systems and phosphate transport systems were identified. The strain was the most efficient for iron accumulation, which suggests a promising application for the removal of phosphate and iron from polluted waters.

Rhodococcus ruber↗

Harnessing Probiotic LAB and Bacteriocins for Clean-Label Food Processing and Biopreservation: Omics, Molecular Innovations and Industrial Applications.

The persistence of microbial agents in foods, especially spore forming bacteria is one of the most significant challenges to food preservation and safety, undermining product quality, shelf life, and consumer health. The use of traditional control methods, including thermal processing and chemical preservatives, are increasingly limited by consumer demands for minimally processed foods, and the emergence of resistant microbial strains. Advances have been made in the use of probiotics like lactic acid bacteria (LAB) and their biometabolites like bacteriocins in food processing and preservation, particularly to control biofilm and endospore forming pathogens including Bacillus sp., Listeria sp., Staphylococcus sp., Clostridium sp., E. coli etc. in foods and food processing plants/surfaces. Given the ability of these organisms to cause foodborne illness and form resilient biofilms in the food processing ecosystem and their resistance to the conventional method of their elimination, the antimicrobial peptides (bacteriocins) are gaining increasing prominence as useful alternatives to synthetic antimicrobials in enhancing food safety and combating the threats of these pathogens. This review addresses current information on the inhibition of persistent microbial spoilage contaminants, biofilm-forming pathogens, and spore formers of interest to the food industry using LAB and their bacteriocins. Current developments in isolation, characterization, and mode of action of bacteriocins are explored, including synergistic activity with other preservative hurdle techniques such as encapsulation, and nanobiotechnology. Importantly, there is a focus on the utilization of molecular and omics-based approaches to enable a better understanding of bacteriocin biosynthesis, gene regulation, host-microbe interactions and gut microbiome regulation potential of probiotic LABs, permitting the rational development of targeted and strain-specific interventions. Developments in the incorporation of bacteriocin-producing LAB into functional starter cultures and bio-protective products, and challenges in stability, regulatory approval, and scalability for industrial use, are also discussed in the paper. Despite their considerable potential, broader translation remains constrained by regulatory requirements, production and formulation costs, variable efficacy in complex food matrices, and the limited validation of many candidate bacteriocins beyond laboratory and model-food systems. Collectively, these advances position LAB and their bacteriocins at the leading edge of developing sustainable, clean-label, and efficacious functional foods and food preservation systems. Their functionality can be expanded by integrating genomics, synthetic biology, and predictive modeling for the maximization of their biopreservative potential in diverse food matrices and in gut microbiota modulation.

Bioactive Peptides↗

Hyperpolarized NMR study of the impact of alzheimer's disease on diabetes using a novel rat model.

Most researchers have long focused on linkage between type 2 diabetes (T2D) and the increased risk of Alzheimer's disease (AD) but have often overlooked whether AD modulates T2D. Investigating the reciprocal interaction between two complex diseases provides perspectives on the mechanistic linkage. The endeavor, however, confronts challenges without a robust rodent model that develops T2D and AD as the animal ages. Cross breeding a T2D rat with a hemizygous TgF344AD +/- rat that contains the mutant human amyloid precursor protein (APPsw) and the presenilin 1 (PS1&#x394;E9) genes has produced a new T2D-AD +/- rat model. The T2D-AD +/- rat expresses both the T2D and AD phenotypes as the animal ages. As AD progresses, the time to T2D onset decreases, and the diabetes severity increases. Hyperpolarized NMR experiments using dynamic nuclear polarization (DNP) show that T2D and T2D-AD rats share a common metabolic impairment in the brain pyruvate dehydrogenase (PDH) activity as reflected in the NMR determined decline in the bicarbonate/lactate (bic/lac) ratio. The bic/lac ratio decreases in both T2D and T2D-AD brain. AD exacerbates the decline of the bic/lac ratio.

Animals↗

From bacterial to microbiome-derived vesicles: genome-informed identity, source qualification, and translational quality for skin-directed cosmetics.

Bacterial extracellular vesicles (BEVs) are increasingly proposed as materials for skin-directed cosmetics, yet rapid adoption of "exosome" terminology has outpaced clarity on their origin, composition, and manufacturing quality. This review argues that the value of BEVs depends on scientific discipline rather than marketing appeal, and that they are promising because they are biologically potent, not because they are intrinsically benign. We retain BEVs as the scientific umbrella term for vesicles released by bacteria and we propose the term microbiome-derived vesicles (MDVs) as the consumer-facing designation for qualified commensal BEVs - a surface term that avoids the difficulty of "bacterial" while its definition preserves bacterial provenance. We develop a three-axis framework for BEV identity that integrates compositional analysis, producer-strain genomics, and functional or safety profiling, and we position whole-genome sequencing (WGS) as decisive for source qualification and mechanistic interpretation but insufficient to prove the efficacy of a purified preparation. Building on this framework, we summarize isolation, purification, and analytical characterization requirements; interpret current skin-efficacy evidence in light of its methodological limits; and discuss formulation, cosmetic application, regulatory positioning, and manufacturable quality. We conclude that transparent bacterial provenance, reproducible preparation, and evidence proportionate to the claims made are prerequisites for evaluating commensal BEVs, described for skin applications as MDVs, as a scientifically defined cosmetic platform.

Bacterial extracellular vesicles↗

Unveiling novel transcriptomic prognostic biomarkers for specific breast cancer subtypes and treatment regimens.

BACKGROUND: Breast cancer (BRCA) is the most common cancer in women worldwide, yet current gene expression panels offer limited insight into treatment responses across different subtypes and therapies. This study aimed to identify reliable biomarkers for predicting treatment outcomes in specific BRCA subtypes and treatment regimens. METHODS: This study analyzed transcriptomic data from The Cancer Genome Atlas to identify differentially expressed genes (DEGs) in patient groups treated with different combinations of hormone therapy (H), chemotherapy (C), radiotherapy (R), and targeted therapy (T). Non-negative matrix factorization clustering was performed to stratify patients into clusters representing different BRCA subtypes. Functional enrichment analysis was performed, and survival assessments were conducted using the METABRIC dataset. RESULTS: A total of 1,148 DEGs were identified across treatment regimens, with 75 common DEGs shared across multiple regimens. Among these, 12 candidate biomarkers were associated with luminal subtypes treated with H, including LRP1B, of which high expression predicted cancer recurrence. In triple-negative breast cancer (TNBC) treated with C, 76 candidate biomarkers were identified, including TTYH1 for recurrence and ANXA8L1 and MPZ for non-recurrence. Functional analyses identified intermediate filament organization and keratinization as pathways associated with specific candidate biomarkers of TNBC following C. Survival analysis using METABRIC strengthened the prognostic ability of LRP1B and TTYH1 to predict worse survival and ANXA8L1 and MPZ to predict prolonged survival, with four additional prognostic biomarkers. CONCLUSION: This study identified gene expression prognostic biomarkers for luminal and TNBC subtypes, thereby supporting personalized therapies. Further experimental validation is required to confirm these findings for clinical application. CLINICAL TRIAL REGISTRY: No.

Breast cancer↗