Neurology. 2025 May 27;104(10):e213592. doi: 10.1212/WNL.0000000000213592. Epub 2025 Apr 24.

ABSTRACT

BACKGROUND AND OBJECTIVES: Coffee intake is linked to a reduced risk of Parkinson disease (PD), but whether this effect is mediated by gut microbiota and metabolomic changes remains unclear. This study examines PD-associated metabolomic shifts, caffeine metabolism, and their connection to gut microbiome alterations in a multicenter study.

METHODS: We conducted an untargeted serum metabolomic assay using liquid chromatography with high-resolution mass spectrometry on an exploratory cohort recruited from National Taiwan University Hospital (NTUH). A targeted metabolomic assay focusing on caffeine and its 12 downstream metabolites was conducted and validated in an independent cohort from University Malaya Medical Centre (UMMC). In the exploratory cohort, the association of each caffeine metabolite with gut microbiota changes was investigated by metagenomic shotgun sequencing. A clustering-based approach was used to correlate microbiome changes with plasma caffeine metabolite level and clinical severity. Body mass index, antiparkinsonism medication use, and dietary habits (including coffee and tea intake) were recorded.

RESULTS: Sixty-three patients with PD and 54 controls from NTUH formed the exploratory cohort while 36 patients with PD and 20 controls from UMMC served as an validation cohort to replicate the plasma caffeine findings. A total of 5,158 metabolites were detected from untargeted metabolomic analysis, with 3,131 having high confidence for analysis. Compared with controls, the abundance of 56 metabolites was significantly higher and that of 7 metabolites was significantly lower (adjusted p < 0.05 and log2 fold change >1) in patients with PD. Caffeine metabolism was significantly lower in patients with PD (p = 0.0013), and serum levels of caffeine and its metabolites negatively correlated with motor severity (p < 0.01). Targeted metabolomic analysis confirmed reduced levels of caffeine and its metabolites, including theophylline, paraxanthine, 1,7-dimethyluric acid, and 5-acetylamino-6-amino-3-methyluracil, in patients with PD; these findings were replicated in the validation cohort (p < 0.05). A clustering approach found that 56 microbiome species enriched in patients with PD negatively correlated with caffeine and its metabolites paraxanthine and theophylline (both p < 0.05), notably Clostridium sp000435655, Acetatifactor sp900066565, Oliverpabstia intestinalis, and Ruminiclostridium siraeum.

DISCUSSION: This study identifies PD-related changes in microbial-caffeine metabolism compared with controls. Our findings offer insights for future functional research on caffeine-microbiome interactions in PD.

PMID:40273394 | DOI:10.1212/WNL.0000000000213592

ACS Appl Bio Mater. 2025 Apr 24. doi: 10.1021/acsabm.5c00307. Online ahead of print.

ABSTRACT

In public health emergencies or in resource-constrained settings, laboratory-based diagnostic methods, such as RT-qPCR, need to be complemented with accurate, rapid, and accessible approaches to increase testing capacity, as this will translate into better outcomes in disease prevention and management. Here, we develop an original nucleic acid detection platform by leveraging CRISPR-Cas9 and lateral flow immunochromatography technologies. In combination with an isothermal amplification that runs with a biotinylated primer, the system exploits the interaction between the CRISPR-Cas9 R-loop formed upon targeting a specific nucleic acid and a fluorescein-labeled probe to generate a visual readout on a lateral flow device. Our method enables rapid, sensitive detection of nucleic acids, achieving a limit of 1-10 copies/μL in 1 h at a low temperature. We validated the efficacy of the method by using clinical samples of patients infected with SARS-CoV-2. Compared with other assays, it operates with more accessible molecular elements and showcases a robust signal-to-noise ratio. Moreover, multiplexed detection was demonstrated using primers labeled with biotin and digoxigenin, achieving the simultaneous identification of target genes on lateral flow devices with two test lines. We successfully detected SARS-CoV-2 and Influenza A (H1N1) in spiked samples, highlighting the potential of the method for multiplexed diagnostics of respiratory viruses. All in all, this represents a versatile and manageable platform for point-of-care testing, thereby supporting better patient outcomes and enhanced pandemic preparedness.

PMID:40273314 | DOI:10.1021/acsabm.5c00307

Gigascience. 2025 Jan 6;14:giaf028. doi: 10.1093/gigascience/giaf028.

ABSTRACT

We introduce RWRtoolkit, a multiplex generation, exploration, and statistical package built for R and command-line users. RWRtoolkit enables the efficient exploration of large and highly complex biological networks generated from custom experimental data and/or from publicly available datasets, and is species agnostic. A range of functions can be used to find topological distances between biological entities, determine relationships within sets of interest, search for topological context around sets of interest, and statistically evaluate the strength of relationships within and between sets. The command-line interface is designed for parallelization on high-performance cluster systems, which enables high-throughput analysis such as permutation testing. Several tools in the package have also been made available for use in reproducible workflows via the KBase web application.

PMID:40272882 | DOI:10.1093/gigascience/giaf028

Probiotics Antimicrob Proteins. 2025 Apr 24. doi: 10.1007/s12602-025-10549-8. Online ahead of print.

ABSTRACT

The rise of antimicrobial-resistant infections highlights the need for novel therapeutic strategies. Class IIb microcins, a subclass of ribosomally synthesized bacteriocins, play a significant role in modulating bacterial communities by targeting iron acquisition systems in competitive environments, such as the gastrointestinal tract. In this study, we describe and characterize Ec W, a novel class IIb microcin from Escherichia coli strain NCTC10444. This strain is the first known to harbor two homologs of the class IIb microcin biosynthesis cluster and to encode four class IIb microcins in its genome. Sequence analysis revealed that Ec W shows similarity to class IIb microcin Gq W, extending the known repertoire of this microcin class to 18. Heterologous expression and inhibition assays demonstrated potent antimicrobial activity of Ec W against numerous enteric pathogens from the Enterobacteriaceae family, including drug-resistant and hypervirulent strains of E. coli and Klebsiella pneumoniae. These findings suggest that Ec W holds substantial promise as an antimicrobial agent, providing a potential alternative to traditional antibiotics for combating multidrug-resistant pathogens. This study emphasizes the importance of exploring microcins as a novel strategy to tackle the growing threat of infections caused by multidrug-resistant bacteria.

PMID:40272760 | DOI:10.1007/s12602-025-10549-8

Inflamm Res. 2025 Apr 24;74(1):69. doi: 10.1007/s00011-025-02036-1.

ABSTRACT

BACKGROUND: Due to the possible influence of inflammation and gut microbiota in cancers.

METHODS: Fc gamma receptor IIb deficient (FcGRIIb-/-) and cyclic GMP-AMP synthase deficient (cGAS-/-) mice, the model with hyperinflammation and hypo-inflammation, respectively, were subcutaneously injected with MC38 cells (a murine colon cancer cell line).

RESULTS: As such, the tumor burdens were most prominent in cGAS-/- mice, while FcGRIIb-/- mice demonstrated the least tumor sizes compared with wild-type (WT). Intra-tumoral mononuclear cells of FcGRIIb-/- (hematoxylin and eosin staining) were more prominent than other groups with the most dominant CD86-positive cells (mostly M1 proinflammatory macrophages) and the least CD206-positive cells (mostly M2 anti-inflammatory macrophages). While fecal microbiome analysis demonstrated a subtle difference among mouse strains with tumors at 24 days post-cancer injection, serum cytokines (TNF-α, IL-6, IL-1α, IFN-β, IFN-γ, IL-23, IL-12p70, GM-CSF, IL-27, and IL-17A) (fluorescence-encoded bead multiplex assay) and the expansion of immune cells in the spleens of FcGRIIb-/- mice (flow cytometry) were more prominent than others. With bone marrow-derived macrophages, prominent M1 (LPS) and M2 polarization (IL4 and cancer supernatant) in FcGRIIb-/- and cGAS-/- macrophages, respectively, were demonstrated using polymerase chain reaction and flow cytometry. The most prominent tumoricidal activity (percentage of F4/80-negative flexible780 viable dye-positive cells using flow cytometry) of LPS-stimulated FcGRIIb-/- macrophages compared with other groups supported dominant pro-inflammatory characteristics of FcGRIIb-/- macrophages.

CONCLUSIONS: In conclusion, the protective and promoting effects of FcGRIIb-/- and cGAS-/- mice, respectively, against cancers are partly related to macrophage functions with a subtle correlation to fecal microbiota, and FcGRIIb inhibitors and cGAS enhancers might be helpful for cancer adjuvant treatment.

PMID:40272597 | DOI:10.1007/s00011-025-02036-1

Clin Chem. 2025 Apr 24:hvaf043. doi: 10.1093/clinchem/hvaf043. Online ahead of print.

ABSTRACT

BACKGROUND: In 2009, the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines established standards for the design, execution, and reporting of quantitative PCR (qPCR) in research. The expansion of qPCR into numerous new domains has driven the development of new reagents, methods, consumables, and instruments, requiring revisions to best practices that are tailored to the evolving complexities of contemporary qPCR applications.

CONTENT: Transparent, clear, and comprehensive description and reporting of all experimental details are necessary to ensure the repeatability and reproducibility of qPCR results. These revised MIQE guidelines reflect recent advances in qPCR technology, offering clear recommendations for sample handling, assay design, and validation, along with guidance on qPCR data analysis. Instrument manufacturers are encouraged to enable the export of raw data to facilitate thorough analyses and re-evaluation by manuscript reviewers and interested researchers. The guidelines emphasize that quantification cycle (Cq) values should be converted into efficiency-corrected target quantities and reported with prediction intervals, along with detection limits and dynamic ranges for each target, based on the chosen quantification method. Additionally, best practices for normalization and quality control are outlined and reporting requirements have been clarified and streamlined. The aim is to encourage researchers to provide all necessary information without undue burden, thereby promoting more rigorous and reproducible qPCR research.

SUMMARY: Building on the collaborative efforts of an international team of researchers, we present updates, simplifications, and new recommendations to the original MIQE guidelines, designed to maintain their relevance and applicability in the context of emerging technologies and evolving qPCR applications.

PMID:40272429 | DOI:10.1093/clinchem/hvaf043

Nucleic Acids Res. 2025 Apr 22;53(8):gkaf329. doi: 10.1093/nar/gkaf329.

ABSTRACT

Inverted repeats are repetitive elements that can form hairpin and cruciform structures. They are linked to genomic instability; however, they also have various biological functions. Their distribution differs markedly across taxonomic groups in the tree of life, and they exhibit high polymorphism due to their inherent genomic instability. Advances in sequencing technologies and declined costs have enabled the generation of an ever-growing number of complete genomes for organisms across taxonomic groups in the tree of life. However, a comprehensive database encompassing inverted repeats across diverse organismal genomes has been lacking. We present invertiaDB, the first comprehensive database of inverted repeats spanning multiple taxa, featuring repeats identified in the genomes of 118 101 organisms across all major taxonomic groups. For each organism, we derived inverted repeats with arm lengths of at least 10 bp, spacer lengths up to 8 bp, and no mismatches in the arms. The database currently hosts 34 330 450 inverted repeat sequences, serving as a centralized, user-friendly repository to perform searches and interactive visualizations, and download existing inverted repeat data for independent analysis. invertiaDB is implemented as a web portal for browsing, analyzing, and downloading inverted repeat data. invertiaDB is publicly available at https://invertiadb.netlify.app/homepage.html.

PMID:40272360 | DOI:10.1093/nar/gkaf329

Microscopy (Oxf). 2025 Apr 24:dfaf020. doi: 10.1093/jmicro/dfaf020. Online ahead of print.

ABSTRACT

Genome-wide profiling of gene expression levels in cells, such as transcriptomics and proteomics, is a powerful experimental approach in modern biology, allowing not only efficient exploration of the genetic elements responsible for biological phenomena of interest, but also characterization of the global constraints behind plastic phenotypic changes of cells that accompany large-scale remodeling of omics profiles. To understand how individual cells change their molecular profiles to achieve specific phenotypic changes in phenomena such as differentiation, cancer metastasis and adaptation, it is crucial to characterize the dynamics of cellular phenotypes and omics profiles simultaneously at the single-cell level. Especially in the last decade, significant technical progress has been made in the in situ identification of omics profiles of cells on the microscope. However, most approaches still remain destructive and cannot unravel the post-measurement dynamics. In recent years, Raman spectroscopy-based methods for omics inference have emerged, allowing the characterization of genome-wide molecular profile dynamics in living cells. In this review, we give a brief overview of the recent development of imaging-based omics profiling methods. We then present the approach to infer omics profiles from single-cell Raman spectra. Since Raman spectra can be obtained from living cells in a non-destructive and non-staining manner, this method may open the door to live-cell omics.

PMID:40271815 | DOI:10.1093/jmicro/dfaf020

Nucleic Acids Res. 2025 Apr 24:gkaf335. doi: 10.1093/nar/gkaf335. Online ahead of print.

ABSTRACT

The Bakta command line application is widely used and one of the most established tools for bacterial genome annotation. It balances comprehensive annotation with computational efficiency via alignment-free sequence identifications. However, the usage of command line software tools and the interpretation of result files in various formats might be challenging and pose technical barriers. Here, we present the recent updates on the Bakta web server, a user-friendly web interface for conducting and visualizing annotations using Bakta without requiring command line expertise or local computing resources. Key features include interactive visualizations through circular genome plots, linear genome browsers, and searchable data tables facilitating the interpretation of complex annotation results. The web server generates standard bioinformatics outputs (GFF3, GenBank, EMBL) and annotates diverse genomic features, including coding sequences, non-coding RNAs, small open reading frames (sORFs), and many more. The development of an auto-scaling cloud-native architecture and improved database integration led to substantially faster processing times and higher throughputs. The system supports FAIR principles via extensive cross-reference links to external databases, including RefSeq, UniRef, and Gene Ontology. Also, novel features have been implemented to foster sharing and collaborative interpretation of results. The web server is freely available at https://bakta.computational.bio.

PMID:40271661 | DOI:10.1093/nar/gkaf335

iScience. 2025 Mar 26;28(5):112167. doi: 10.1016/j.isci.2025.112167. eCollection 2025 May 16.

ABSTRACT

Dormant lung adenocarcinoma (LUAD) cells in the bone microenvironment can re-emerge as metastatic disease through osteoclast interactions. Using a 3D dormancy model and a mouse bone metastasis model, this study reveals that arachidonic acid (AA) is the initiating molecule transferred from osteoclasts to dormant LUAD cells, triggering their activation. Dormant LUAD cells uptake AA through CD36, which activates the PPARγ-ANGPTL4 pathway and activates tumor cells. There is a dose-response relationship in the activation effect of AA, and inhibiting AA metabolism prevents this reactivation. The study also finds that the serum levels of AA and ANGPTL4 are significantly elevated in patients with clinical bone metastases compared to those without. This research confirms that osteoclasts transmit AA via the CD36-PPARγ-ANGPTL4 axis to activate dormant LUAD cells, suggesting that AA and ANGPTL4 may serve as valuable biomarkers and potential clinical applications in treatment and prediction of LUAD bone metastasis.

PMID:40271019 | PMC:PMC12018030 | DOI:10.1016/j.isci.2025.112167

Front Immunol. 2025 Apr 9;16:1509805. doi: 10.3389/fimmu.2025.1509805. eCollection 2025.

ABSTRACT

INTRODUCTION: Uveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.

METHODS: In this study, we conducted an integrative systems biology analysis of blood transcriptome data from 169 non-infectious uveitis patients (56 isolated uveitis, 113 systemic disease-associated uveitis) and 82 healthy controls.

RESULTS: Modular co-expression analysis identified distinct cytokine signaling networks, emphasizing interleukin and interferon pathways. A meta-analysis revealed 110 differentially expressed genes (metaDEGs) in isolated uveitis and 91 in systemic disease-associated uveitis, predominantly linked to immune responses. The Interferome database confirmed a predominance of type I and II IFN signatures in both groups. Pathway enrichment analysis highlighted inflammatory responses, including cytokine production (IL-8, IL1-β, IFN-γ, β, and α) and toll-like receptor signaling (TLR4, TLR7, TLR8, CD180). Principal component analysis emphasized the IFN signature's discriminative power, particularly in systemic disease-associated uveitis. Machine learning identified IFN-associated genes as robust predictors, while linear discriminant analysis pinpointed CCR2, CD180, GAPT, and PTGS2 as key risk factors in isolated uveitis and CA1, SIAH2, and PGS in systemic disease-associated uveitis.

CONCLUSION: These findings highlight IFN-driven imune dysregulation and potential molecular targets for precision therapies in uveitis.

PMID:40270958 | PMC:PMC12014655 | DOI:10.3389/fimmu.2025.1509805

Front Public Health. 2025 Apr 9;13:1459060. doi: 10.3389/fpubh.2025.1459060. eCollection 2025.

ABSTRACT

Nowadays, heavy metal (HM) contamination and their ecological risk in coastal sediments are global issues. This research provides insight into the heavy metals' contamination, source apportionment, and potential ecological risks in the surface sediments of the Xiang-Shan wetland in Taiwan, which is undergoing rapid economic development, mainly by the semiconductor industries. The levels of twelve metals and total organic matter (TOM) were measured in 44 samples of surface sediment during the spring and winter seasons of 2022. Subsequently, the single and comprehensive pollution indices were assessed. The findings showed that the average of HM contents exhibited a descending sequence of Al > Fe > Mn > Zn > Co > Ga > Cr > Cu > In > Ni > Pb = Cd during both seasons. The E f , I geo , and PI showed that the majority of sediment samples were uncontaminated to heavily contaminated by Fe, Al, Zn, Cu, Mn, Cr, Ni, Co and Ga, and extremely contaminated by In. Moreover, PLI and mC deg unveiled that the surface sediments of DJ, OB, and KY stations were strongly or extremely polluted. PERI revealed that the sediment shows minimal to moderate ecological risk. The findings of multivariate analyses suggested that Fe, Al, Cu, Zn, and Ni derived from natural sources, while Ga, In, Co, Cr, and Mn originated from both anthropogenic and natural origins. Hence, it is critical that HM contamination, particularly Co, In, and Ga, be continuously monitored in the study area. Our data provide significant insights for more effective prevention and evaluation of HM contamination in the aquatic-sedimentary ecosystems of Taiwan.

PMID:40270744 | PMC:PMC12014647 | DOI:10.3389/fpubh.2025.1459060

MicroPubl Biol. 2025 Apr 8;2025. doi: 10.17912/micropub.biology.001567. eCollection 2025.

ABSTRACT

We examined the effects of X-ray irradiation on Xenopus laevis , focusing on pre- and post-fertilization exposure. We applied X-ray doses of 10, 50, 100, 250, and 500 Gy. Fifty percent of the 360 eggs irradiated at 250 Gy failed to fertilize, while fertilized eggs developed normally until the gastrula stage. Doses ranging from 10 to 250 Gy caused developmental anomalies. High mortality rates were observed at doses of 100 to 500 Gy. Post-fertilization irradiation at 50 to 100 Gy resulted in 100% lethality, while exposure to 10 Gy led to only 13% lethality, although both exposure levels produced similar types of developmental anomalies compared to pre-fertilization irradiation. This study highlights how the timing and intensity of exposure critically affect embryo viability, especially during the sensitive stages of fertilization and gastrulation. We establish the necessary and sufficient dosage to further investigate the molecular mechanisms of X-ray damage to DNA and protein.

PMID:40270682 | PMC:PMC12015645 | DOI:10.17912/micropub.biology.001567

Front Mol Biosci. 2025 Apr 9;12:1557835. doi: 10.3389/fmolb.2025.1557835. eCollection 2025.

ABSTRACT

The human protein kinome is a group of over 500 therapeutically relevant kinases. Exemplified by over 10,000 phosphorylated sites reported in global phosphoproteomes, kinases are also highly regulated by phosphorylation. Currently, 1008 phosphorylated sites in 273 kinases are associated with their regulation of activation/inhibition, and a few in 30 kinases are associated with altered activity. Phosphorylated sites in 196 kinases are related to other molecular functions such as localization and protein interactions. Over 8,000 phosphorylated sites, including all those in 517 kinases are unassigned to any functions. This imposes a significant bias and challenge for the effective analysis of global phosphoproteomics datasets. Hence, we derived a set of stably and frequently detected phosphorylated sites (representative phosphorylated sites) across diverse experimental conditions annotated in the PhosphoSitePlus database and presumed them to be relevant to the human kinase regulatory network. Analysis of these representative phosphorylated sites led to the classification of 449 kinases into four distinct categories (kinases with phosphorylated sites apportioned (PaKD) and enigmatic (PeKD), and those with predominantly within kinase domain (PiKD) and outside kinase domain (PoKD)). Knowledge-based functional analysis and sequence conservation across the family/subfamily identified phosphorylated sites unique to specific kinases that could contribute to their unique functions. This classification of representative kinase phosphorylated sites enhance our understanding of prioritized validation and provides a novel framework for targeted phosphorylated site enrichment approaches. Phosphorylated sites in kinases associated with dysregulation in diseases were frequently located outside the kinase domain, and suggesting their regulatory roles and opportunities for phosphorylated site-directed therapeutic approaches.

PMID:40270594 | PMC:PMC12015135 | DOI:10.3389/fmolb.2025.1557835

Bioact Mater. 2025 Apr 14;50:246-272. doi: 10.1016/j.bioactmat.2025.04.008. eCollection 2025 Aug.

ABSTRACT

We produced a microstructured, electroconductive and nano-functionalized drug eluting cardiac patch (MENDEP) designed to attract endogenous precursor cells, favor their differentiation and counteract adverse ventricular remodeling in situ. MENDEP showed mechanical anisotropy and biaxial strength comparable to porcine myocardium, reduced impedance, controlled biodegradability, molecular recognition ability and controlled drug release activity. In vitro, cytocompatibility and cardioinductivity were demonstrated. Migration tests showed the chemoattractive capacity of the patches and conductivity assays showed unaltered cell-cell interactions and cell beating synchronicity. MENDEP was then epicardially implanted in a rat model of ischemia/reperfusion (I/R). Histological, immunofluorescence and biomarker analysis indicated that implantation did not cause damage to the healthy myocardium. After I/R, MENDEP recruited precursor cells into the damaged myocardium and triggered their differentiation towards the vascular lineage. Under the patch, the myocardial tissue appeared well preserved and cardiac gap junctions were correctly distributed at the level of the intercalated discs. The fibrotic area measured in the I/R group was partially reduced in the patch group. Overall, these results demonstrate that MENDEP was fully retained on the epicardial surface of the left ventricle over 4-week implantation period, underwent progressive vascularization, did not perturb the healthy myocardium and showed great potential in repairing the infarcted area.

PMID:40270551 | PMC:PMC12017858 | DOI:10.1016/j.bioactmat.2025.04.008

J Diabetes. 2025 Apr;17(4):e70090. doi: 10.1111/1753-0407.70090.

ABSTRACT

AIM: Circulating Gremlin 2 (Grem2) has recently been linked to human obesity, but its role in type 2 diabetes (T2D) remains unclear. This study aims to explore the association of circulating Grem2 with β-cell function.

METHODS: A post hoc analysis was conducted using data from three clinical trials, in which all participants underwent the oral glucose tolerance test (OGTT). Circulating Grem2 levels were measured at 0, 1, and 2 h during the OGTT. In Trial 1, Grem2 levels were compared between participants with T2D (n = 59) and without T2D (n = 119). We further examined changes in Grem2 levels in response to oral antidiabetic drugs in participants with T2D in Trial 2 (n = 67) and calorie restriction in participants with prediabetes in Trial 3 (n = 231). The relationship between Grem2 levels and β-cell function was analyzed across all trials.

RESULTS: Fasting and 1-h Grem2 levels were lower in participants with T2D compared with those without T2D (728 ± 25 vs. 649 ± 31 pg/mL, p = 0.020; 631 ± 26 vs. 537 ± 31 pg/mL, p = 0.007). Fasting Grem2 levels were restored after antidiabetic treatment (550 ± 12 vs. 575 ± 12 pg/mL, p = 0.019), and 1-h Grem2 levels increased following calorie restriction (1118 ± 89 vs. 1144 ± 90 vs. 1253 ± 89 pg/mL, p for trend = 0.002). The 1-h Grem2 levels were positively associated with β-cell function assessed by the oral disposition index and HOMA-β.

CONCLUSION: Reduced circulating Grem2 levels are associated with impaired β-cell function in T2D, and could be restored through antidiabetic interventions.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01959984, NCT01758471, NCT03856762.

PMID:40270326 | DOI:10.1111/1753-0407.70090

Plant Physiol. 2025 Mar 28;197(4):kiaf107. doi: 10.1093/plphys/kiaf107.

ABSTRACT

Elevated temperatures resulting from climate change adversely affect natural and crop ecosystems, necessitating the development of heat-tolerant crops. Here, we established a framework to precisely identify protein phosphorylation sites associated with varying temperature sensitivities in wheat (Triticum aestivum). We identified specific kinases primarily associated with particular temperatures, but our results also suggest a striking overlap between cold and heat signaling. Furthermore, we propose that the phosphorylation state of a specific set of proteins may represent a signature for heat stress tolerance. These findings can potentially aid in the identification of targets for breeding or genome editing to enhance the sub- and supra-optimal temperature tolerance of crops.

PMID:40270188 | DOI:10.1093/plphys/kiaf107

Biol Sex Differ. 2025 Apr 23;16(1):28. doi: 10.1186/s13293-025-00707-6.

ABSTRACT

Gonadal testosterone stimulates skeletal muscle anabolism and contributes to sexually differentiated adipose distribution through incompletely understood mechanisms. Observations in humans and animal models have indicated a major role for androgen receptor (AR) in mediating sex differences in body composition throughout the lifespan. Traditional surgical, genetic and pharmacological studies have tested systemic actions of circulating androgens, and more recent transgenic approaches have allowed for tests of AR gene function in specific androgen responsive niches contributing to body composition, including: skeletal muscle and surrounding interstitial cells, white and brown adipose, as well as trabecular and cortical bone. Less well understood is how these functions of gonadal androgens interact with exercise. Here, we summarize the understood mechanisms of action of AR and its interactions with exercise, specifically on outcomes of body composition and muscle function, and the global- and tissue-specific role of AR in regulating skeletal muscle, adipose, and bone morphology. Additionally, we describe the known effects of androgen and AR manipulation on female body composition, muscle morphology, and sport performance, while highlighting a need for greater inclusion of female subjects in human and animal muscle physiology and endocrinology research.

PMID:40269952 | DOI:10.1186/s13293-025-00707-6

J Pept Sci. 2025 Jun;31(6):e70020. doi: 10.1002/psc.70020.

ABSTRACT

Peptide-based therapeutics have gained attention in cancer treatment because of their good specificity, low toxicity, and ability to modulate immune responses. However, challenges such as enzymatic degradation and poor bioavailability limit their clinical application. Peptide-functionalized poly(lactic-co-glycolic acid) (PLGA) systems have emerged as a transformative platform in cancer therapy that offers unique advantages, including enhanced stability, sustained release, and precise delivery of therapeutic agents. This review highlights the synergistic integration of peptides with PLGA and addresses key challenges of peptide-based therapeutics. The application of peptide-functionalized PLGA systems encompasses a diverse range of strategies for cancer therapy. In chemotherapy, peptides disrupt critical tumor pathways, induce apoptosis, and inhibit angiogenesis, demonstrating their versatility in targeting various aspects of tumor progression. In immunotherapy, peptides act as antigens to stimulate robust immune responses or as immune checkpoint inhibitors to restore T cell activity, overcoming tumor immune evasion. These systems also harness the enhanced permeability and retention effect, facilitating preferential accumulation in tumor tissues while leveraging tumor microenvironment (TME)-responsive mechanisms, such as pH-sensitive or enzyme-triggered drug release, to achieve controlled, localized delivery. Collectively, peptide-functionalized PLGA systems represent a promising, versatile approach for precise cancer therapy that integrates innovative delivery strategies with highly specific, potent therapeutic agents.

PMID:40269479 | DOI:10.1002/psc.70020

Environ Microbiol Rep. 2025 Apr;17(2):e70088. doi: 10.1111/1758-2229.70088.

ABSTRACT

The Amazon rainforest has been subjected to high rates of deforestation, mostly for pasturelands, over the last few decades. This change in plant cover is known to alter the soil microbiome and the functions it mediates, but the genomic changes underlying this response are still unresolved. In this study, we used a combination of deep shotgun metagenomics complemented by a supervised machine learning approach to compare the metabolic strategies of tropical soil microbial communities in pristine forests and long-term established pastures in the Amazon. Machine learning-derived metagenome analysis indicated that microbial community structures (bacteria, archaea and viruses) and the composition of protein-coding genes were distinct in each plant cover type environment. Forest and pasture soils had different genomic diversities for the above three taxonomic groups, characterised by their protein-coding genes. These differences in metagenome profiles in soils under forests and pastures suggest that metabolic strategies related to carbohydrate and energy metabolisms were altered at community level. Changes were also consistent with known modifications to the C and N cycles caused by long-term shifts in aboveground vegetation and were also associated with several soil physicochemical properties known to change with land use, such as the C/N ratio, soil temperature and exchangeable acidity. In addition, our analysis reveals that these alterations in land use can also result in changes to the composition and diversity of the soil DNA virome. Collectively, our study indicates that soil microbial communities shift their overall metabolic strategies, driven by genomic alterations observed in pristine forests and long-term established pastures with implications for the C and N cycles.

PMID:40269473 | DOI:10.1111/1758-2229.70088