Curr Biol. 2025 Jul 22:S0960-9822(25)00860-7. doi: 10.1016/j.cub.2025.06.072. Online ahead of print.

ABSTRACT

In multicellular organisms, the shape of an organ is robust to unpredictable fluctuations. When parts of an organ are removed or damaged, it is often capable of regeneration, restoring its original shape. A central question is how restoration of shape occurs as the collective behavior of individual cells. Here, we use the plant root as an experimental system, surgically removing the tip that contains the organizing center and investigating how it restores its tapered shape. We discover that the transient activation of growth conflicts, which creates specific cell geometries following injury, is vital to this restoration. Using a combination of experimental approaches and computational modeling, we show that non-uniform growth among neighboring cell files generates conflicts, reshaping cuboidal cells into rhomboidal forms. These rhomboidal cells undergo anisotropic growth and establish an atypical diagonal division plane, both of which can be explained by elementary rules of microtubule dynamics. The resulting daughter cells, in turn, guide the growing cell files along an inclined path to restore the tapered morphology. Our findings reveal a two-step process: first, the activation of conflicting growth patterns to generate specific cell shapes, and second, the reorientation of cell division and growth in response to these shapes, recreating the tip-focused cell files that facilitate tapering. This previously unrecognized shape-forming mechanism reveals how local cell geometries, driven by growth conflicts, guide self-organized morphogenesis in plant wound repair.

PMID:40712581 | DOI:10.1016/j.cub.2025.06.072

Spectrochim Acta A Mol Biomol Spectrosc. 2025 Jul 21;344(Pt 2):126729. doi: 10.1016/j.saa.2025.126729. Online ahead of print.

ABSTRACT

Compounds containing the pyridopyrimidine core have attracted significant interest due to their promising biological properties and potential for medical applications. However, they represent an unexplored area in cellular imaging. Herein, a new class of aggregation-induced emission (AIE) fluorophores based on the pyrido[2,3-d]pyrimidine scaffold has been developed. We synthesized a small series of derivatives, which were evaluated for their spectroscopic properties in various solvents, considering fluorescence quantum yields, fluorescence lifetimes, and their decay components. Importantly, the physicochemical parameters were also evaluated in a MeOH/H2O environment, suggesting the possible behavior of the derivatives in the cellular environment. Our analyses revealed the excellent photophysical properties of the ET06 compound, which exhibited enhanced fluorescence as a result of increasing water content, retaining significant Stokes shifts. An in-depth characterization of the molecular mechanism of fluorescence formation was linked to an aggregation-induced blue-shifted emission effect (AIBSE). TD-DFT calculations showed the existence of different spatial conformational states of ET06 in the single molecule state and aggregated states in at sandwich arrangement. Molecular conformational and energy changes in the ground and excited states, which had a significant effect on fluorescence emission in water-containing media, were also discussed. Finally, biological studies revealed negligible cytotoxicity of ET06 against cancer and normal cells. High fluorescence intensity in cells and a possible affinity and tendency to accumulate in mitochondria and lysosomes were also confirmed. These findings provide valuable insights into the molecular behavior and properties of pyrido[2,3-d]pyrimidines, boosting the landscape for designing new fluorescent probes for bioimaging.

PMID:40712481 | DOI:10.1016/j.saa.2025.126729

Proc Natl Acad Sci U S A. 2025 Jul 29;122(30):e2426341122. doi: 10.1073/pnas.2426341122. Epub 2025 Jul 25.

ABSTRACT

Environmental causes of intrauterine growth restriction (IUGR) remain poorly characterized. Here, we compare germ-free (GF) and conventionally raised (CONV-R) mice to assess the effects of the gut microbiota on placental/fetal development at embryonic day (E)11.5 (end of placentation) and E17.5 (near term). Pregnancy- and microbiota-associated changes in gene expression occur along the gut, including those related to angiogenesis, while bacterial composition and fermentation activity remain stable. Placental weights at E11.5 and fetal weights at E17.5 are significantly reduced in GF animals. Compared to CONV-R dams, the GF maternal decidua exhibits similar vascular histomorphometric features at E11.5 and E17.5, and numbers of uterine NK-cells (effectors of vascular remodeling) at E11.5. In contrast, angiogenesis is disturbed in the GF fetal-derived placental compartment (junctional and/or labyrinth zones) at E11.5, as judged by i) increased levels of proangiogenic proteins (angiopoietin-2, FGF-2, follistatin, SDF-1, VEGF-A, VEGF-C); ii) increased levels of phos-VEGFR2 and phos-p38-MAPK yet reduction in phos-ERK1/2; and iii) reduced expression of junctional zone glycoprotein genes associated with angiogenesis and fetal growth, resulting in reduced endothelial cell density at the labyrinth zone at E17.5. Colonization of GF mice before pregnancy with cecal microbiota from CONV-R animals rescues fetal growth and altered transcriptomic, proteomic, and immunohistochemical features in the fetal GF placental compartment. Single-nucleus RNA-sequencing demonstrated increased expression of mitochondrial and ribosomal-associated oxidative stress genes in endothelial cell clusters in the GF fetal placental compartment (E11.5, E17.5), mimicking oxidative stress signatures in human IUGR. These results provide a rationale for seeking microbial targets for treating/preventing IUGR.

PMID:40711921 | DOI:10.1073/pnas.2426341122

J Gen Virol. 2025 Jul;106(7). doi: 10.1099/jgv.0.002114.

ABSTRACT

In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV.

PMID:40711908 | DOI:10.1099/jgv.0.002114

J Am Soc Nephrol. 2025 Jul 25. doi: 10.1681/ASN.0000000805. Online ahead of print.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a prevalent clinical syndrome with insufficient kidney function. Keratin 20 (KRT20), a component of intermediate filaments, is widely recognized as a biomarker of kidney tubular injury, yet its exact function in kidney disease remains uncertain.

METHODS: RNA sequencing data from a mouse model of ischemia/reperfusion-induced AKI were analyzed to assess KRT20 transcript levels. The effect of specific Krt20 knockout in renal proximal tubule cells (Krt20PTKO) was subsequently examined in two distinct AKI mouse models. Luciferase reporter assays and ChIP-PCR was used to identify transcription factors regulating KRT20 expression, while immunoprecipitation followed by mass spectrometry elucidated the downstream targets of KRT20. Additionally, the clinical significance of KRT20 and peroxiredoxin 2 (PRDX2) was evaluated in patients with acute tubular necrosis.

RESULTS: KRT20 was significantly upregulated in renal proximal tubule cells during the early phase of AKI, preceding the induction of KIM1 expression. This upregulation was mediated by Fosb in both ischemia/reperfusion and cisplatin-induced AKI models. Renal proximal tubule cells-specific knockout of Krt20 exacerbated the kidney injury during AKI. Mechanistically, KRT20 protected against AKI by sequestering PRDX2, an antioxidant protein, and inhibiting the exosomal secretion of PRDX2, eventually preventing ferroptosis in kidney tubular cells. Further analysis revealed that ALG-2-interacting protein X (Alix) facilitated PRDX2 exosomal release, while KRT20 competed with Alix for binding to the N-terminal domain of PRDX2, thereby retaining PRDX2 intracellularly. Finally, the expression levels of KRT20 and PRDX2 were correlated with kidney injury severity and kidney function decline in clinical samples.

CONCLUSIONS: These findings indicate that KRT20 was upregulated in the early stages of AKI, serving to protect kidney tubule cells by sequestering PRDX2 and inhibiting ferroptosis.

PMID:40711819 | DOI:10.1681/ASN.0000000805

Discov Oncol. 2025 Jul 25;16(1):1404. doi: 10.1007/s12672-025-03030-z.

ABSTRACT

Mucin 1 (MUC1) is a type-I transmembrane glycoprotein, ranked as the second most promising cancer antigen for therapeutic development by the National Cancer Institute. Recently, MUC1 has gained significant attention as a therapeutic target in cancer immunotherapy. Thus, understanding MUC1-regulated signaling is essential for advancing therapeutic strategies. Since existing pathway repositories lack a comprehensive MUC1 signaling map, we constructed one by manually annotating experimentally validated signaling events from 115 articles following NetPath annotation criteria. Considering the topology of annotated molecules, a pathway map was developed using the PathVisio software. This pathway map is a valuable resource cataloguing 209 molecules and 690 signaling events, of which 395 events are unique. The catalogued reactions include 118 enzyme catalysis events, 133 molecular associations, 132 gene regulation events, 216 protein expressions, 49 activation/inhibition and 42 protein translocation events. MUC1 signaling pathway showed significant cross-talk with Wnt/β-catenin, NF-κB, PI3K-AKT, and MAPK signaling. The aberrant expression of MUC1 is associated with proliferation, metastasis, angiogenesis and invasion in various cancers, such as breast, lung, pancreatic, colon, oral, prostate, ovarian, and gastric cancers. Moreover, it also regulates the proliferation and function of immune cells, including myeloid-derived suppressor cells, tumour-associated macrophages, dendritic cells, CD4 + T-cells and CD8 + T-cells. This pathway map may serve as a valuable reference for understanding MUC1-driven oncogenic and immunomodulatory mechanisms, providing insights for developing novel therapeutic strategies for cancer treatment.

PMID:40711726 | DOI:10.1007/s12672-025-03030-z

ISME J. 2025 Jul 25:wraf136. doi: 10.1093/ismejo/wraf136. Online ahead of print.

ABSTRACT

The Indri indri is a critically endangered lemur species that has not successfully been maintained or bred under human care. Investigating this lemur's virtually unexplored gut microbiome will deepen our understanding of the species' health determinants and inform conservation efforts. Through metagenomic assembly and integration into an updated reference database, we found the I. indri faecal microbiome remains largely uncultivated (cultivated species representing <0.1% relative abundance) and is largely specific to this primate species. After reconstructing 342 metagenome-assembled genomes encompassing 48 candidate species from a total of 22 samples (18 of which newly sequenced), we substantially improved microbiome mappability to 85% on average and found evidence for a proportionally large core microbiome. Social group membership emerged as the main determinant of both their taxonomic and functional gut microbiome composition. Using strain-level profiling, we detected extensive microbiome transmission within social groups, suggesting physical interaction is key in promoting microbiome acquisition. Strain sharing rates were highest between mothers and their offspring. Intergroup strain sharing was minimal and inversely correlated with geographical distance, aligning with the rare intergroup interactions and stable territory occupancy coupled with ongoing habitat fragmentation. No evidence of microbiome acquisition through geophagy was detected. These findings underscore the profound influence of social structure on microbiome transmission and composition in I. indri, and highlight the importance of considering social dynamics into research and conservation strategies.

PMID:40709814 | DOI:10.1093/ismejo/wraf136

Elife. 2025 Jul 25;13:RP101327. doi: 10.7554/eLife.101327.

ABSTRACT

In the last decade, activity-dependent strategies for labeling multiple immediate early gene ensembles in mice have generated unprecedented insight into the mechanisms of memory encoding, storage, and retrieval. However, few strategies exist for brain-wide mapping of multiple ensembles, including their overlapping population, and none incorporate capabilities for downstream network analysis. Here, we introduce a scalable workflow to analyze traditionally coronally sectioned datasets produced by activity-dependent tagging systems. Intrinsic to this pipeline is simple multi-ensemble atlas registration and statistical testing in R (SMARTTR), an R package which wraps mapping capabilities with functions for statistical analysis and network visualization, and support for import of external datasets. We demonstrate the versatility of SMARTTR by mapping the ensembles underlying the acquisition and expression of learned helplessness (LH), a robust stress model. Applying network analysis, we find that exposure to inescapable shock (IS), compared to context training, results in decreased centrality of regions engaged in spatial and contextual processing and higher influence of regions involved in somatosensory and affective processing. During LH expression, the substantia nigra emerges as a highly influential region that shows a functional reversal following IS, indicating a possible regulatory function of motor activity during helplessness. We also report that IS results in a robust decrease in reactivation activity across a number of cortical, hippocampal, and amygdalar regions, indicating suppression of ensemble reactivation may be a neurobiological signature of LH. These results highlight the emergent insights uniquely garnered by applying our analysis approach to multiple ensemble datasets and demonstrate the strength of our workflow as a hypothesis-generating toolkit.

PMID:40709549 | DOI:10.7554/eLife.101327

ArXiv [Preprint]. 2025 Jul 14:arXiv:2507.10714v1.

ABSTRACT

Stochastic Petri Nets (SPNs) are an increasingly popular tool of choice for modeling discrete-event dynamics in areas such as epidemiology and systems biology, yet their parameter estimation remains challenging in general and in particular when transition rates depend on external covariates and explicit likelihoods are unavailable. We introduce a neural-surrogate (neural-network--based approximation of the posterior distribution) framework that predicts the coefficients of known covariate-dependent rate functions directly from noisy, partially observed token trajectories. Our model employs a lightweight 1D Convolutional Residual Network trained end-to-end on Gillespie-simulated SPN realizations, learning to invert system dynamics under realistic conditions of event dropout. During inference, Monte Carlo dropout provides calibrated uncertainty bounds together with point estimates. On synthetic SPNs with 20% missing events, our surrogate recovers rate-function coefficients with an RMSE = 0.108 and substantially runs faster than traditional Bayesian approaches. These results demonstrate that data-driven, likelihood-free surrogates can enable accurate, robust, and real-time parameter recovery in complex, partially observed discrete-event systems.

PMID:40709304 | PMC:PMC12288651

GEN Biotechnol. 2024 Aug;3(4):196-206. doi: 10.1089/genbio.2024.0014. Epub 2024 Aug 16.

ABSTRACT

The dissatisfaction within the postdoctoral training phase has led to the drastic reduction in the number of U.S. citizens pursuing postdoctoral positions within the biological and biomedical sciences fields. Even more so, there is an obvious disparity in not only the recruitment but the retention among underrepresented groups to pursue careers as academic scientists. The proposed social-ecological model and National Institute of Health advisory committee suggests reforming the postdoctoral training phase to overcome these downward trends and disparities. Importantly, some programs like the Stanford Propel Postdoctoral Program were integrating this framework and recommendations without knowledge that they would be released 2 years later. The goal of the Propel Program is to provide social, cohort, financial, and institutional support to diverse cohorts of postdoctoral trainee to diversify the professoriate. Within this piece, several of the Propel scholars come together to provide their perspectives on how the Propel Program has benefited their postdoctoral training experience.

PMID:40709103 | PMC:PMC12288851 | DOI:10.1089/genbio.2024.0014

Bioinform Adv. 2025 Jun 27;5(1):vbaf153. doi: 10.1093/bioadv/vbaf153. eCollection 2025.

ABSTRACT

MOTIVATION: The latest generation of deep learning-based structure prediction methods enable accurate modelling of most proteins and many complexes. However, preparing inputs for the locally installed software is not always straightforward, and the results of local runs are not always presented in an ideally accessible fashion. Furthermore, it is not yet clear whether the latest tools perform equivalently for all types of target.

RESULTS: ABCFold facilitates the use of AlphaFold 3, Boltz-1, and Chai-1 with a standardized input to predict atomic structures, with Boltz-1 and Chai-1 being installed on runtime (if required). MSAs can be generated internally using either the JackHMMER MSA search within AlphaFold 3, or with the MMseqs2 API. Alternatively, users can provide their own custom MSAs. This therefore allows AlphaFold 3 to be installed and run without downloading the large databases needed for JackHMMER. There are also straightforward options to use templates, including custom templates. Results from all packages are treated in a unified fashion, enabling easy comparison of results from different methods. A variety of visualization options are available which include information on steric clashes.

AVAILABILITY AND IMPLEMENTATION: ABCFold is coded in Python and JavaScript. All scripts and associated documentation are available from https://github.com/rigdenlab/ABCFold or https://pypi.org/project/ABCFold/.

PMID:40708869 | PMC:PMC12287924 | DOI:10.1093/bioadv/vbaf153

APL Bioeng. 2025 Jul 23;9(3):036107. doi: 10.1063/5.0246495. eCollection 2025 Sep.

ABSTRACT

Lens-free digital in-line holography (LDIH) provides a large field-of-view at micrometer-scale resolution, making it a promising tool for high-throughput cellular analysis. However, the complexity of diffraction images (holograms) produced by LDIH presents challenges for human interpretation and requires time-consuming computational reconstruction, often leading to artifacts and information loss. To address these issues, we present HoloNet, a novel deep learning architecture specifically designed for direct analysis of diffraction images in cellular diagnostics. Tailored to the unique characteristics of diffraction images, HoloNet captures multi-scale features, enabling it to outperform conventional convolutional neural networks in recognizing well-defined regions within complex holograms. HoloNet classifies breast cancer cell types with high precision and quantifies molecular marker intensities using raw diffraction images of cells stained with ER/PR and HER2. Additionally, HoloNet has proven effective in transfer learning applications, accurately classifying breast cancer cell lines and discovering previously unidentified subtypes through unsupervised learning. By integrating computational imaging with deep learning, HoloNet offers a robust solution to the challenges of holographic data analysis, significantly improving the accuracy and explainability of cellular diagnostics.

PMID:40708806 | PMC:PMC12289329 | DOI:10.1063/5.0246495

CNS Neurosci Ther. 2025 Jul;31(7):e70535. doi: 10.1111/cns.70535.

ABSTRACT

AIMS: Albiflorin, a key compound from Paeonia lactiflora, has shown therapeutic potential in neuropsychiatric and neurodegenerative disorders (NPDs and NDDs), especially depression and Alzheimer's disease (AD). This review aimed to summarize its pharmacological effects, mechanisms, pharmacokinetics, and therapeutic prospects.

DISCUSSION: Albiflorin exhibits multi-target actions, including modulation of monoamine neurotransmitters, inhibition of neuroinflammation, and enhancement of neuroplasticity. In AD, it reduces Aβ accumulation, improves mitochondrial function, and activates MAPK/ERK and Nrf2/HO-1 signaling pathways. In depression, it restores phospholipid and tryptophan metabolism, regulates HPA axis function, and increases BDNF expression. Albiflorin crosses the blood-brain barrier (BBB) and may act indirectly via the gut-brain axis through its metabolite benzoic acid. Though brain concentrations are low, its pharmacological effects remain significant. Albiflorin also shows potential benefits in conditions like cerebral ischemia and hypoxic-ischemic brain injury. Toxicological data indicate low systemic toxicity and good safety margins in vivo and in vitro.

CONCLUSIONS: Albiflorin demonstrates promising therapeutic potential for NPDs and NDDs via multi-pathway regulation. However, further studies are needed to optimize brain delivery, understand gut microbiota interactions, and confirm efficacy through clinical trials. The advancement of formulation strategies and pharmacokinetic research will be considered key to achieving clinical translation.

PMID:40708436 | DOI:10.1111/cns.70535

Birth Defects Res. 2025 Aug;117(8):e2514. doi: 10.1002/bdr2.2514.

ABSTRACT

BACKGROUND: Dexamethasone (DEX) is used during pregnancies at risk of early delivery or congenital adrenal hyperplasia. DEX exposure is also known to cause placental damage. Although placental cytokines/chemokines protect the fetus and regulate placental development, few studies have examined placental cytokine/chemokine transcript levels in DEX-dosed pregnant mice.

METHODS: To examine this, quantitative PCR and histological analysis in humanized mice were performed. Mice were injected once daily for five consecutive days with DEX (5 mg/kg) or saline (0.9%) via the tail vein on gestation days (GDs) 10-14, respectively (n = 3-5). All mice were intravenously injected with human immunoglobulin G (2 mg/kg) on GD14.

RESULTS: No statistically significant changes in maternal body weights by GD 12, absolute or relative placental weights in the dosed group were observed compared to concurrent controls. Fetal weights in the DEX-dosed group were lower than in concurrent controls, and statistically significant changes were observed on GD 18. Necrosis/apoptosis of cytotrophoblasts in the placenta's labyrinth zone was observed in the DEX-dosed dams. The placental transcript levels of interferon lambda receptor 1, interleukin 6, and C-X-C motif chemokine ligand 10 (Cxcl10) were higher in the DEX-dosed than the control group on GDs 15 and 16; the difference of Cxcl10 transcript level was statistically significant (p = 0.016) on GD 16.

CONCLUSIONS: Cxcl10 is overexpressed during DEX-induced placental damage in the mouse models, suggesting it as a potential biomarker of placental damage. Further studies are needed to confirm Cxcl10 changes during placental damage induced by other placental toxicants.

PMID:40708190 | DOI:10.1002/bdr2.2514

Biotechnol Biofuels Bioprod. 2025 Jul 24;18(1):81. doi: 10.1186/s13068-025-02684-9.

ABSTRACT

Plant specialised metabolism generates a vast array of compounds with significant potential across agriculture, medicine, cosmetics, and the food industry. A key challenge lies in optimising their production in the plant, as these compounds are often present in trace amounts in a complex metabolic cocktail. Given their high economic value, extensive efforts have been made to elucidate their biosynthetic pathways and pinpoint key regulatory and enzymatic targets. This knowledge has been applied for metabolic engineering to enhance the carbon flux towards metabolites of interest, thereby broadening the utility of plants as a source of high-value compounds. This review examines different metabolic engineering strategies employed today using the phenylpropanoid pathway as a case study and highlights the potential of integrating plant and microbial research to drive cross-disciplinary innovation.

PMID:40708042 | DOI:10.1186/s13068-025-02684-9

Genome Biol. 2025 Jul 24;26(1):220. doi: 10.1186/s13059-025-03680-w.

ABSTRACT

Advances in single-cell technology enable large-scale generation of omics data, promising for clarifying gene regulatory networks governing different cell type/states. Nonetheless, prevailing methods fail to account for universal and reusable regulatory modules in GRNs, which are fundamental underpinnings of cell type landscape. We introduce cRegulon to infer regulatory modules by modeling combinatorial regulation of transcription factors based on diverse GRNs from single-cell multi-omics data. Through benchmarking and applications using simulated datasets and real datasets, cRegulon outperforms existing approaches in identifying TF combinatorial modules as regulatory units and annotating cell types. cRegulon offers new insights and methodology into combinatorial regulation.

PMID:40707940 | DOI:10.1186/s13059-025-03680-w

Discov Oncol. 2025 Jul 24;16(1):1403. doi: 10.1007/s12672-025-03272-x.

ABSTRACT

BACKGROUND: Microbial lung infections may promote development of lung cancer through overlapping molecular mechanisms. This analysis aimed to identify a co-regulated peripheral blood gene signature in lung adenocarcinoma (LUAD) and microbial lung infections.

METHODS: A total of 403 peripheral blood transcriptomic profiles from five GEO test datasets-two LUAD (GSE39345, GSE103527) and three infection-related (GSE40012, GSE65682, GSE103119)-were analyzed using the limma package. Differentially expressed genes (DEGs) were defined by|log2FC| >1 and p < 0.05. Two additional GEO datasets (GSE42826 and GSE42830), comprising 30 blood samples (16 LUAD, 14 lung infection), served as validation sets. Shared DEGs were subjected to KEGG and GO enrichment analyses. Protein-protein interaction (PPI) networks were constructed in Cytoscape, and the top 10 hub genes were identified. Expression data of hub genes were compared between validation LUAD and lung infection samples using the Mann-Whitney U test, followed by linear regression and Pearson correlation to confirm co-regulation. Immune cell infiltration was assessed using xCell deconvolution algorithm.

RESULTS: Ninety-three significant DEGs were shared between LUAD and infection datasets, including 40 upregulated and 53 downregulated genes. Eight hub genes showed consistent differential expression in both LUAD and lung infection: BCL6, CD163, S100A12 (upregulated); and FLT3LG, RPL13, RPL14, RPL22, RPS4X (downregulated), of which BCL6, S100A12, FLT3LG, RPL13, RPL14, RPL22 and RPS4X were significantly co-regulated (R2 >0.8, p < 0.001) and correlated (p < 0.05). Immune profiling revealed that upregulated genes were associated with immunosuppressive cells such as Tregs and M2 macrophages, while downregulated genes were positively correlated with antitumor immune cell infiltration including CD8+ T cells and M1 macrophages. Consistent immune, stroma and microenvironment scores were observed between LUAD and lung infection.

CONCLUSION: This analysis identified a blood-based 7-gene signature shared between LUAD and microbial lung infections, associated with immunosuppressive microenvironment features, suggesting a potential link between infection-driven inflammation and tumor-promoting immune modulation.

PMID:40707667 | DOI:10.1007/s12672-025-03272-x

Nat Commun. 2025 Jul 24;16(1):6831. doi: 10.1038/s41467-025-62099-w.

ABSTRACT

Induced proximity by molecular glues refers to strategies that leverage the recruitment of proteins to facilitate their modification, regulation or degradation. As prospective design of molecular glues remains challenging, unbiased discovery methods are necessary to discover new chemical targets. Here we establish a high throughput affinity proteomics workflow leveraging E3 ligase activity-impaired CRBN-DDB1ΔB in cell lysates for the unbiased identification of molecular glue targets. By mapping the interaction landscape of CRBN-binding molecular glues, we unveil 298 protein targets and demonstrate the utility of enrichment methods for identifying targets overlooked by established methods. We use a computational workflow to estimate target confidence and perform biochemical and structural validation of uncharacterized neo-substrates. We further identify a lead compound for the previously untargeted non-zinc finger PPIL4 through a biochemical screen. Our study provides a comprehensive inventory of targets chemically recruited to CRBN and delivers a robust and scalable workflow for identifying drug-induced protein interactions in cell lysates.

PMID:40707481 | DOI:10.1038/s41467-025-62099-w

Nat Commun. 2025 Jul 24;16(1):6487. doi: 10.1038/s41467-025-61483-w.

ABSTRACT

Trichomonas vaginalis, the causative agent of the venereal disease trichomoniasis, infects men and women globally and is associated with serious outcomes during pregnancy, increased risk of HIV-1 infection, and cancers of the human reproductive tract. Species of trichomonad parasitize a range of hosts in addition to humans, including birds, livestock, and pets. Genetic analysis of trichomonads recovered from columbid birds has provided evidence that they undergo frequent host-switching, and that a spillover event from columbids likely gave rise to T. vaginalis in humans. Here we describe a comparative genomics study of seven trichomonad species, generating chromosome-scale reference genomes for T. vaginalis and its avian sister species Trichomonas stableri, and assemblies of five other species that infect birds and mammals. Human-infecting trichomonad lineages have undergone recent and convergent genome size expansions compared to their avian sister species, a result of extensive repeat expansions specifically of multicopy gene families and transposable elements, with genetic drift likely a driver due to relaxed selection. Trichomonads are thought to have independently host-switched twice from birds to mammals/humans. We identify gene functions implicated in the transition, including host tissue adherence and phagocytosis, extracellular vesicle formation, and CAZyme virulence factors, which are all associated with pathogenesis phenotypes.

PMID:40707449 | DOI:10.1038/s41467-025-61483-w

Fungal Biol. 2025 Aug;129(5):101590. doi: 10.1016/j.funbio.2025.101590. Epub 2025 May 6.

ABSTRACT

The Fifth International Symposium on Fungal Stress (ISFUS) brought together in Brazil many of the leaders in the field of fungal stress responses, from fourteen countries, for four days of outstanding science ranging from basic research to studies with agricultural, medical, industrial, and environmental significance. In addition to the excellent oral and poster presentations, the Symposium organisers ensured that all participants had ample opportunity to engage, socialise, and network to exchange ideas and share research. The conference was enhanced by the world-class venue near Iguazu Falls, probably the greatest natural phenomenon in South America.

PMID:40707112 | DOI:10.1016/j.funbio.2025.101590