Sports Med. 2025 Apr 21. doi: 10.1007/s40279-025-02217-2. Online ahead of print.

ABSTRACT

BACKGROUND: In response to exercise, protein kinases and signaling networks are engaged to blunt homeostatic threats generated by acute contraction-induced increases in skeletal muscle energy and oxygen demand, as well as serving roles in the adaptive response to chronic exercise training to blunt future disruptions to homeostasis. High-intensity interval training (HIIT) is a time-efficient exercise modality that induces superior or similar health-promoting skeletal muscle and whole-body adaptations compared with prolonged, moderate-intensity continuous training (MICT). However, the skeletal muscle signaling pathways underlying HIIT's exercise intensity-specific adaptive responses are unknown.

OBJECTIVE: We mapped human muscle kinases, substrates, and signaling pathways activated/deactivated by an acute bout of HIIT versus work-matched MICT.

METHODS: In a randomized crossover trial design (Australian New Zealand Clinical Trials Registry number ACTRN12619000819123; prospectively registered 6 June 2019), ten healthy male participants (age 25.4 ± 3.2 years; BMI 23.5 ± 1.6 kg/m2; V ˙ O 2 max 37.9 ± 5.2 ml/kg/min, mean values ± SD) completed a single bout of HIIT and MICT cycling separated by ≥ 10 days and matched for total work (67.9 ± 10.2 kJ) and duration (10 min). Mass spectrometry-based phosphoproteomic analysis of muscle biopsy samples collected before, during (5 min), and immediately following (10 min) each exercise bout, to map acute temporal signaling responses to HIIT and MICT, identified and quantified 14,931 total phosphopeptides, corresponding to 8509 phosphorylation sites.

RESULTS: Bioinformatic analyses uncovered exercise intensity-specific signaling networks, including > 1000 differentially phosphorylated sites (± 1.5-fold change; adjusted P < 0.05; ≥ 3 participants) after 5 min and 10 min HIIT and/or MICT relative to rest. After 5 and 10 min, 92 and 348 sites were differentially phosphorylated by HIIT, respectively, versus MICT. Plasma lactate concentrations throughout HIIT were higher than MICT (P < 0.05), and correlation analyses identified > 3000 phosphosites significantly correlated with lactate (q < 0.05) including top functional phosphosites underlying metabolic regulation.

CONCLUSIONS: Collectively, this first global map of the work-matched HIIT versus MICT signaling networks has revealed rapid exercise intensity-specific regulation of kinases, substrates, and pathways in human skeletal muscle that may contribute to HIIT's skeletal muscle adaptations and health-promoting effects. Preprint: The preprint version of this work is available on medRxiv, https://doi.org/10:1101/2024.07.11.24310302 .

PMID:40257739 | DOI:10.1007/s40279-025-02217-2

Eur J Nucl Med Mol Imaging. 2025 Apr 21. doi: 10.1007/s00259-025-07287-y. Online ahead of print.

ABSTRACT

AIM: To assess the ability of [18F]F-fluciclovine-PET/CT to stage muscle invasive bladder cancer (MIBC) before radical cystectomy.

METHODS: This single-site prospective pilot study enrolled patients with MIBC and T2-T4, N0 disease on CT/MRI slated to undergo radical cystectomy (RC). Dynamic and static [18F]F-fluciclovine-PET/CT images were acquired. Clinical readers assessed for confirmation of the primary bladder lesion on imaging and the presence of pelvic nodal metastases. Findings were compared to pathology at RC. Kinetic parameters from dynamic PET/CT were compared across bladder lesions of different clinical stages.

RESULTS: The study enrolled sixteen patients (median age: 73 years, range: 57-88 years, 11 males, 5 females), twelve receiving neoadjuvant chemotherapy before RC. There was high specificity amongst all three readers for detecting lymph node metastases (overall specificity: 0.91, 95%CI: 0.81-1.00) with good overall agreement rate with pathology (0.67, 95%CI: 0.44-0.83). The overall PPV for all readers for identifying node-positive disease was 0.4 (95%CI: 0-1.00), and the overall sensitivity was 0.13 (95%CI: 0-0.44). The overall PPV for detecting the primary tumor was 0.69 (95%CI: 0.47-0.88), and the sensitivity was 0.89 (95%CI: 0.78-1.00), with NPV and specificity being 0.70 (95%CI: 0.33, 1.00) and 0.39 (95%CI: 0.33, 0.50), respectively. Compartmental analysis of the primary bladder tumor revealed that k1 and vb parameters significantly differentiated between low (pT0-pT1) and high (pT2-pT4) risk disease (p < 0.05). Immunohistochemical assessment showed no significant correlation of tumor [18F]F-fluciclovine uptake nor kinetic parameter with amino acid transporter expression.

CONCLUSIONS: [18F]F-fluciclovine demonstrates good specificity and agreement rate for MIBC staging, with sensitivity like CT/MRI. Kinetic parameters such as k1 was able to delineate higher-stage ( ≥ = pT2) primary lesions. Heterogeneous amino acid transporter expression can be seen across lesions. Further studies are warranted to understand [18F]F-fluciclovine PET/CT use in the context of other imaging modalities in this disease.

CLINICAL TRIAL REGISTRATION: NCT04018053 Registered 2/26/2020.

PMID:40257614 | DOI:10.1007/s00259-025-07287-y

Arch Razi Inst. 2024 Aug 1;79(4):695-700. doi: 10.32592/ARI.2024.79.4.695. eCollection 2024 Aug.

ABSTRACT

Chronic kidney disease (CKD), also called chronic kidney failure, is increasingly recognized as a global public health problem in the entire world. It is characterized by slow, progressive, and irreversible loss in kidney physiology. Today, the prevalence of CKD is increasing dramatically. CKD can affect almost every organ system, including the cardiovascular system. Many treatments have been attempted for CKD, such as renal transplantation, hemodialysis (HD), and peritoneal dialysis (PD). At the end stage of CKD, HD is the most widely used therapy throughout the world. However, these options can decrease volume expansion and uremic solute retention and also increase patient survival. Furthermore, there are certain complications associated with the use of these methods. Previous studies have reported that the main side effects are headaches, muscle cramps, abdominal pain, hypotension, hypertension, vomiting, and constipation. Therefore, the investigation for better and more convenient dialysis techniques should continue, as well as the search for a better material to enhance the clearance of nitrogenous waste products from the body. The intestine has a significant effect on the clearance of nitrogenous waste products from the body, making it a potentially appropriate site for CKD management. The potential mechanism of the intestinal dialysis technique is that it can absorb excess fluids, uremic toxins, and electrolytes within the gastrointestinal (GI) tract and exert them in the feces before they can be absorbed into the blood. In the present review, we will focus on different absorbents as a conservative treatment to remove uremic waste metabolites from the GI tract for the improvement of kidney function in CKD.

PMID:40256591 | PMC:PMC12004044 | DOI:10.32592/ARI.2024.79.4.695

RSC Med Chem. 2025 Apr 17. doi: 10.1039/d5md00086f. Online ahead of print.

ABSTRACT

Overexpression of histone deacetylase 6 (HDAC6) is implicated in tumorigenesis, invasion, migration, survival, apoptosis, and growth of various malignancies, making it a promising target for cancer treatment. Building on our previous work, we report a novel series of tetrahydro-β-carboline-piperazinedione derivatives as HDAC6 inhibitors. Structural modifications were introduced at the 6-aryl group, with the m-bromophenyl derivative (9c) emerging as the most potent HDAC6 inhibitor, exhibiting an IC50 of 7 nM. Compound 9c demonstrated robust growth inhibitory activity across 60 cancer cell lines from the NCI panel, with a mean GI50 of 2.64 μM and a GI50 below 5 μM for nearly all tested lines, while exhibiting significantly lower cytotoxicity towards non-tumor cell lines. The triple-negative breast cancer cell line MDA-MB-231 was selected for further investigation of 9c's cellular effects. 9c selectively increased the acetylation of non-histone α-tubulin in MDA-MB-231 cells, confirming its HDAC6 selectivity. Furthermore, 9c effectively induced apoptosis, caused apoptotic sub-G1 phase accumulation, upregulated pro-apoptotic caspase-3, and downregulated anti-apoptotic Bcl-2. Notably, 9c reduced the expression of programmed death-ligand 1 (PD-L1), a key immune checkpoint protein that enables tumor cells to evade immune surveillance, highlighting its potential role in enhancing anti-tumor immunity. In addition, 9c inhibited phosphorylated extracellular signal-regulated kinase (ERK)1/2, a central signaling pathway that drives cell proliferation, survival, and migration, further highlighting its significance in suppressing tumor progression and growth. In migration assays, 9c impaired cell motility, achieving 80% gap closure inhibition in a wound-healing assay. Collectively, these findings underline compound 9c as a highly promising candidate for the treatment of triple-negative breast cancer, with the added benefits of PD-L1 and ERK inhibition for potential synergy in enhancing anti-tumor immunity and reducing tumor cell proliferation.

PMID:40256307 | PMC:PMC12004265 | DOI:10.1039/d5md00086f

Bioinform Adv. 2025 Feb 6;5(1):vbaf017. doi: 10.1093/bioadv/vbaf017. eCollection 2025.

ABSTRACT

SUMMARY: Influencing the behavior of a Boolean network involves applying perturbations, which, in standard deterministic Boolean networks, is equivalent to modifying the update rules. Nevertheless, manipulating update functions to make a Boolean network exhibit the desired dynamics is challenging, as it requires extensive knowledge of the rationale behind the logical equations. Moreover, modifying logical rules can inadvertently alter essential functional and behavioral characteristics of the network. An alternative approach is to incorporate a set of parameters into the logical functions of Boolean networks. With such methods, one can alter the behavior of the network without needing detailed knowledge of the logical functions. We developed pastboon, an R package to simulate parameterized stochastic Boolean networks using three parameterization methods. This package enables researchers to study the phenotypic effects of various perturbations on Boolean network models describing cellular processes, which find valuable applications in systems biology.

AVAILABILITY AND IMPLEMENTATION: pastboon is freely available on the R CRAN repository at https://cran.r-project.org/package=pastboon, and its source code can be accessed on GitHub at https://github.com/taherimo/pastboon.

PMID:40255969 | PMC:PMC12007881 | DOI:10.1093/bioadv/vbaf017

Curr Res Microb Sci. 2025 Mar 27;8:100382. doi: 10.1016/j.crmicr.2025.100382. eCollection 2025.

ABSTRACT

Isoprene, a biogenic volatile compound emitted largely by plants, can form greenhouse gases when it reacts with atmospheric radicals. A significant amount of isoprene is absorbed into soil and can be degraded by soil microorganisms, but our understanding of the microbial biodegradation of isoprene in tropical ecosystems remains limited. This study investigated isoprene degradation by soil microbes indigenous to a tropical evergreen forest, focusing on those associated with coffee and tea plants grown as integrated crops and their genome characteristics in relation to their biodegradation capabilities. Following a 96-hour incubation with 7.2 × 10⁵ parts per billion by volume (ppbv) of isoprene, soil samples exhibited degradation levels ranging from 11.95 % to 36.54 %. From these soils, bacterial isolates belonging to the genera Rhodococcus and Gordonia (Actinomycetota) were recovered. These isolates demonstrated high isoprene biodegradation activity (50.3 %-69.1 % over seven days) and carried the isoA gene associated with isoprene metabolism. According to genome analysis, the organization of genes in the iso cluster was homologous, and the encoded amino acid sequences were highly similar to those of previously known isoprene-degrading members of the same genera. These findings emphasized the contribution of these widespread isoprene-degrading bacterial genera in the biodegradation of isoprene and the role of their isoprene monooxygenases in modulating atmospheric isoprene flux.

PMID:40255246 | PMC:PMC12008541 | DOI:10.1016/j.crmicr.2025.100382

OMICS. 2025 Apr 21. doi: 10.1089/omi.2025.0031. Online ahead of print.

ABSTRACT

Network medicine considers the interconnectedness of human diseases and their underlying molecular substrates. In this context, sarcoidosis and pulmonary hypertension (PH) have long been thought of as distinct diseases, but there is growing evidence of shared molecular mechanisms. This study reports on common differentially expressed genes (DEGs), regulatory elements, and pathways between the two diseases. Publicly available transcriptomic datasets for sarcoidosis (GSE157671) and PH (GSE236251) were retrieved from the Gene Expression Omnibus database. DEGs were identified using GEO2R, followed by pathway enrichment and gene interaction analyses via GeneMANIA and STRING. Importantly, a total of 13 common DEGs were identified between sarcoidosis and PH, with 7 upregulated and 6 downregulated genes. The SMAD2/3 nuclear pathway was a shared enriched pathway, suggesting a role in fibrosis and immune regulation. There were also divergences between sarcoidosis and PH. For example, gene set enrichment analysis indicated significant associations of the IFN-gamma signaling pathway with sarcoidosis and the TNF-alpha signaling with PH. miRNA network analysis identified hsa-miR-34a-5p, hsa-let-7g-5p, and hsa-miR-19a-3p as key shared regulators linked to common genes in both sarcoidosis and PH. Finally, DGIdb analysis revealed potential therapeutic candidates targeting these genes in both diseases. This study contributes to the field of drug design and discovery from a network medicine standpoint. The shared molecular links uncovered between sarcoidosis and PH in this study point to several potential biomarkers and therapeutic targets. Further experimental validation and translational medical research are called for diagnostics and drugs, which can effectively and safely help the clinical management of both diseases.

PMID:40255202 | DOI:10.1089/omi.2025.0031

Anal Chem. 2025 Apr 21. doi: 10.1021/acs.analchem.4c06796. Online ahead of print.

NO ABSTRACT

PMID:40254992 | DOI:10.1021/acs.analchem.4c06796

Brief Bioinform. 2025 Mar 4;26(2):bbaf174. doi: 10.1093/bib/bbaf174.

ABSTRACT

Encoding spatially resolved transcriptomics (SRT) data serves to identify the biological semantics of RNA expression within the tissue while preserving spatial characteristics. Depending on the analytical scenario, one may focus on different contextual structures of tissues. For instance, anatomical regions reveal consistent patterns by focusing on spatial homogeneity, while elucidating complex tumor micro-environments requires more expression heterogeneity. However, current spatial encoding methods lack consideration of the tissue context. Meanwhile, most developed SRT technologies are still limited in providing exact patterns of intact tissues due to limitations such as low resolution or missed measurements. Here, we propose STForte, a novel pairwise graph autoencoder-based approach with cross-reconstruction and adversarial distribution matching, to model the spatial homogeneity and expression heterogeneity of SRT data. STForte extracts interpretable latent encodings, enabling downstream analysis by accurately portraying various tissue contexts. Moreover, STForte allows spatial imputation using only spatial consistency to restore the biological patterns of unobserved locations or low-quality cells, thereby providing fine-grained views to enhance the SRT analysis. Extensive evaluations of datasets under different scenarios and SRT platforms demonstrate that STForte is a scalable and versatile tool for providing enhanced insights into spatial data analysis.

PMID:40254832 | DOI:10.1093/bib/bbaf174

Ann Clin Microbiol Antimicrob. 2025 Apr 20;24(1):27. doi: 10.1186/s12941-025-00793-9.

ABSTRACT

BACKGROUND: Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.

METHODS: A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.

RESULTS: The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.

CONCLUSIONS: This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.

PMID:40254579 | DOI:10.1186/s12941-025-00793-9

J Neuroendocrinol. 2025 Apr 20:e70033. doi: 10.1111/jne.70033. Online ahead of print.

ABSTRACT

Evidence from both clinical and preclinical studies indicates that females experience a faster progression to drug addiction and more severe addiction-related health effects compared with males. Estradiol (E2) plays a critical role in these sex differences. Recently, we demonstrated that E2 significantly exacerbates adverse health effects, such as respiratory distress and weight loss, in ovariectomized (OVX) female rats during withdrawal from extended-access fentanyl self-administration. To uncover the mechanisms behind E2-enhanced toxicity, we investigated proteomic changes in the plasma of fentanyl-withdrawn OVX rats under both E2 and non-E2 presentation conditions.Plasma samples were collected following extended-access fentanyl self-administration during protracted withdrawal, when adverse health effects were most pronounced. Using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) we conducted proteomic analysis in OVX rats comparing the effect of fentanyl withdrawal, with or without E2, to drug-naïve control rats.We found a significant effect of fentanyl withdrawal on plasma proteomes within OVX rats. Fentanyl withdrawal was associated with a significant change in 15 plasma proteins including B-factor, properdin (Cfb), apolipoprotein E (ApoE), complement 4, precursor (C4), C-reactive protein (Crp), zinc-alpha-2-glycoprotein precursor (Azgp1), and serine peptidase inhibitor 3L (Serinpa3l). The addition of E2 was associated with enhanced proteomic changes. Bioinformatic gene ontology enrichment analysis indicates that fentanyl withdrawal can disrupt the expression of proteins associated with immunity, lipid transport, and components of the extracellular matrix. We identify protein changes in plasma that may contribute to adverse health outcomes in females, with and without E2, during fentanyl withdrawal. These findings support the development of targeted strategies addressing health risks during opioid use disorder in women.

PMID:40254411 | DOI:10.1111/jne.70033

Cancer Lett. 2025 Apr 18:217733. doi: 10.1016/j.canlet.2025.217733. Online ahead of print.

ABSTRACT

Inflammation is a widely recognized key contributor to KRAS-driven lung adenocarcinoma (LUAD). Tumor-associated macrophages (TAM) are an integral part of the tumor microenvironment and create a supportive niche that sustains inflammation-driven tumorigenesis. In the present study, we unravel a dual role of sphingosine kinase 1 (SPHK1) in KRAS-driven LUAD. While SPHK1 promotes tumorigenesis in in vitro experimental models, it paradoxically suppresses tumorigenesis in in vivo models of KRAS-mutated LUAD. Mechanistically, tumor-intrinsic loss of SPHK1 leads to disrupted lipid homeostasis, increased inflammation and infiltration by TAM, ultimately driving tumor progression. Thus, our study suggests that clinically targeting the SPHK1/S1P axis could potentially result in increased tumor progression, possibly by rewiring the tumor microenvironment toward a more inflammatory and pro-tumorigenic state.

PMID:40254091 | DOI:10.1016/j.canlet.2025.217733

Mol Cell Proteomics. 2025 Apr 18:100974. doi: 10.1016/j.mcpro.2025.100974. Online ahead of print.

ABSTRACT

Relative quantitation, used by most MS-based proteomics laboratories to determine protein fold-changes, requires samples being processed and analyzed together for best comparability through minimizing batch differences. This limits the adoption of MS-based proteomics in population-wide studies, and the detection of subtle but relevant changes in heterogeneous samples. Absolute quantitation circumvents these limitations and enables comparison of results across laboratories, studies, and longitudinally. However, high costs of the essential stable isotope labeled (SIL) standards prevents widespread access and limits the number of quantifiable proteins. Our new approach, called "SysQuan", repurposes SILAC mouse tissues/biofluids as system-wide internal standards for matched human samples to enable absolute quantitation of, theoretically, two-thirds of the human proteome using 157,086 shared tryptic peptides, of which 73,901 with lysine on the c-terminus. We demonstrate that SysQuan enables quantification of 70% and 31% of the liver and plasma proteomes, respectively. We demonstrate for 14 metabolic proteins that abundant SIL mouse tissues enable cost-effective reverse absolute quantitation in, theoretically, 1000s of human samples. Moreover, 10,000s of light/heavy doublets in untargeted SysQuan datasets enable unique post-acquisition absolute quantitation. SysQuan empowers researchers to replace relative quantitation with affordable absolute quantitation at scale, making data comparable across laboratories, diseases and tissues, enabling completely novel study designs and increasing reusability of data in repositories.

PMID:40254065 | DOI:10.1016/j.mcpro.2025.100974

Sci Data. 2025 Apr 19;12(1):665. doi: 10.1038/s41597-025-04973-2.

ABSTRACT

Tackling the current global biodiversity crisis requires large-scale spatially accurate biodiversity data to rapidly assess knowledge gaps and set conservation priorities. Obtaining such data is often challenging because surveying biodiversity across broad spatial scales requires massive logistical and economic efforts. Here, we provide high-resolution (0.81 to 81 km2, depending on species ecology) habitat suitability raster maps for all 225 widespread breeding bird species in Italy. Maps were generated by means of species distribution models based on ~2.5 million spatially accurate (≤1 km-scale) and expert-validated occurrence records. Occurrence data were collected during the breeding seasons 2010-2016 by over 3000 skilled observers, mostly through the Ornitho.it web platform, with the aim of realizing the second Atlas of Breeding Birds in Italy, released in 2022. These raster maps will be useful to ecologists, conservation scientists and practitioners for investigating broad spatial patterns in avian diversity and identifying conservation priorities. We discuss potential applications of this dataset for inferring the composition of ecological communities and species distributions at the Italian scale.

PMID:40253483 | DOI:10.1038/s41597-025-04973-2

Nat Commun. 2025 Apr 19;16(1):3718. doi: 10.1038/s41467-025-58982-1.

ABSTRACT

Tissue-resident immune cells such as innate lymphoid cells (ILC) are known to reside in the parenchymal compartments of tissues and modulate local immune protection. Here we use intravascular cell labeling, parabiosis and multiplex 3D imaging to identify a population of group 3 ILCs in mice that are present within the intravascular space of lung blood vessels (vILC3). vILC3s are distributed broadly in alveolar capillary beds from which inhaled pathogens enter the lung parenchyma. By contrast, conventional ILC3s in tissue parenchyma are enriched in lymphoid clusters in proximity to large veins. In a mouse model of pneumonia, Pseudomonas aeruginosa infection results in rapid vILC3 expansion and production of chemokines including CCL4. Blocking CCL4 in vivo attenuates neutrophil recruitment to the lung at the early stage of infection, resulting in prolonged inflammation and delayed bacterial clearance. Our findings thus define the intravascular space as a site of ILC residence in mice, and reveal a unique immune cell population that interfaces with tissue alarmins and the circulating immune system for timely host defense.

PMID:40253407 | DOI:10.1038/s41467-025-58982-1

Virol J. 2025 Apr 19;22(1):107. doi: 10.1186/s12985-025-02727-5.

ABSTRACT

To be successful, a virus must maintain high between-host transmissibility while also effectively adapting within hosts. The impact of these potentially conflicting demands on viral genetic diversity and adaptation remains largely unexplored. These modes of adaptation can induce uncorrelated selection, bring mutations that enhance certain fitness aspects at the expense of others to high freqency, and contribute to the maintenance of genetic variation. The vast wealth of SARS-CoV-2 genetic data gathered from within and across hosts offers an unparalleled opportunity to test the above hypothesis. By analyzing a large set of SARS-CoV-2 sequences (~ 2 million) collected from early 2020 to mid-2021, we found that high frequency mutations within hosts are sometimes detrimental during between-host transmission. This highlights potential inverse selection pressures within- versus between-hosts. We also identified a group of nonsynonymous changes likely maintained by pleiotropy, as their frequencies are significantly higher than neutral expectation, yet they have never experienced clonal expansion. Analyzing one such mutation, spike M1237I, reveals that spike I1237 boosts viral assembly but reduces in vitro transmission, highlighting its pleiotropic effect. Though they make up about 2% of total changes, these types of variants represent 37% of SARS-CoV-2 genetic diversity. These mutations are notably prevalent in the Omicron variant from late 2021, hinting that pleiotropy may promote positive epistasis and new successful variants. Estimates of viral population dynamics, such as population sizes and transmission bottlenecks, assume neutrality of within-host variation. Our demonstration that these changes may affect fitness calls into question the robustness of these estimates.

PMID:40253323 | DOI:10.1186/s12985-025-02727-5

Brain Stimul. 2025 Apr 17:S1935-861X(25)00090-7. doi: 10.1016/j.brs.2025.04.009. Online ahead of print.

NO ABSTRACT

PMID:40252968 | DOI:10.1016/j.brs.2025.04.009

N Biotechnol. 2025 Apr 17:S1871-6784(25)00041-X. doi: 10.1016/j.nbt.2025.04.003. Online ahead of print.

ABSTRACT

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most mutated oncogene in human cancers, found in approximately 30% of tumors. These mutations primarily consist of single-base missense alterations in codon G12. While extensive efforts have focused on developing allele-specific inhibitors for KRAS mutations, mutation-specific antibodies (Abs) remain largely unexplored, with only a few research-use-only catalog Abs available. In this study, we employed the proprietary Epivolve technology to develop site-directed monoclonal Abs (mAbs) that target KRAS oncogenic driver mutation KRAS G12D. These site-directed mAbs demonstrate high binding affinity, with equilibrium dissociation constants (KD) in the nanomolar range, showing over 1,000-fold greater affinity for KRAS G12D compared to wild-type KRAS. Western blot analyses using both purified KRAS protein variants and tumor cell lines harboring G12D mutations confirmed the high specificity of these mAbs. Furthermore, immunocytochemistry revealed co-localization of the site-directed mAbs with endogenously expressed KRAS in cancer cells bearing G12D mutations. The validated high affinity and specificity of these site-directed mAbs highlight their potential for diagnostic applications and therapeutic development targeting KRAS driver mutations.

PMID:40252917 | DOI:10.1016/j.nbt.2025.04.003

J Insect Physiol. 2025 Apr 17:104813. doi: 10.1016/j.jinsphys.2025.104813. Online ahead of print.

ABSTRACT

Natural selection has favoured the incorporation of ions, including transition metals, in materials of various biological structures susceptible to mechanical fracture to enhance their failure and wear resistance. With regards to insects, only a few taxa have been investigated. The objective of this study was to analyse the biomechanical properties of the ovipositor in a damselfly Calopteryx splendens Harris, 1780 (Odonata, Zygoptera, Calopterygidae) through nanoindentation and to ascertain the elemental composition gradient within the cuticle using energy-dispersive X-ray spectroscopy. This research represents the first report indicating that the damselfly ovipositor exhibits a gradient in the mechanical properties of the cuticle, with Young's modulus ranging from approximately 3.0 to 7.0 GPa and hardness from 0.1 to 0.3 GPa. These properties are shown to highly correlate with the contents of copper and magnesium, both of which increase in the distal direction. The results also suggests that the mechanical properties of the cuticle are significantly influenced by the degree of sclerotization revealed by confocal laser scanning microscopy. These findings propose that the material properties of the ovipositor cuticle in C. splendens may have adapted to enhance piercing capability and to reduce the risk of structural failure during insertion of eggs in plant substrates.

PMID:40252915 | DOI:10.1016/j.jinsphys.2025.104813

Cell Host Microbe. 2025 Apr 15:S1931-3128(25)00126-X. doi: 10.1016/j.chom.2025.03.015. Online ahead of print.

ABSTRACT

The gut microbiome plays a crucial role in modulating human immunity. Previously, we reported that antibiotic-induced microbiome perturbation affects influenza vaccine responses, depending on pre-existing immunity levels. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on both primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration reduced the gut bacterial load, with a long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced (1) an enhanced pro-inflammatory signature early after vaccination, (2) a shift in the balance of vaccine-specific T-helper 1 (Th1) to T-follicular-helper response toward Th1 phenotype, and (3) profound alterations in metabolites, particularly in secondary bile acids in the blood. By integrating multi-omics datasets, we generated a multiscale, multi-response network that revealed key regulatory nodes, including the microbiota, secondary bile acids, and humoral immunity to vaccination.

PMID:40252648 | DOI:10.1016/j.chom.2025.03.015