Cancer Immunol Res. 2025 Mar 14:OF1-OF20. doi: 10.1158/2326-6066.CIR-24-0151. Online ahead of print.

ABSTRACT

Immunotherapies have had unprecedented success in the treatment of multiple cancer types, albeit with variable response rates. Unraveling the complex network of immune cells within the tumor microenvironment (TME) may provide additional insights to enhance antitumor immunity and improve clinical response. Many studies have shown that NK cells or innate lymphoid cells (ILC) have regulatory capacity. Here, we identified CD103 as a marker that was found on CD56+ cells that were associated with a poor proliferative capacity of tumor-infiltrating lymphocytes in culture. We further demonstrated that CD103+CD56+ ILCs isolated directly from tumors represented a distinct ILC population that expressed unique surface markers (such as CD49a and CD101), transcription factor networks, and transcriptomic profiles compared with CD103-CD56+ NK cells. Using single-cell multiomic and spatial approaches, we found that these CD103+CD56+ ILCs were associated with CD8+ T cells with reduced expression of granzyme B. Thus, this study identifies a population of CD103+CD56+ ILCs with potentially inhibitory functions that are associated with a TME that includes CD8+ T cells with poor antitumor activity. Further studies focusing on these cells may provide additional insights into the biology of an inhibitory TME.

PMID:40084939 | DOI:10.1158/2326-6066.CIR-24-0151

J Proteome Res. 2025 Mar 14. doi: 10.1021/acs.jproteome.4c01020. Online ahead of print.

ABSTRACT

We describe a new release of the Candida albicans PeptideAtlas proteomics spectral resource (build 2024-03), providing a sequence coverage of 79.5% at the canonical protein level, matched mass spectrometry spectra, and experimental evidence identifying 3382 and 536 phosphorylated serine and threonine sites with false localization rates of 1% and 5.3%, respectively. We provide a tutorial on how to use the PeptideAtlas and associated tools to access this information. The C. albicans PeptideAtlas summary web page provides "Build overview", "PTM coverage", "Experiment contribution", and "Data set contribution" information. The protein and peptide information can also be accessed via the Candida Genome Database via hyperlinks on each protein page. This allows users to peruse identified peptides, protein coverage, post-translational modifications (PTMs), and experiments that identify each protein. Given the value of understanding the PTM landscape in the sequence of each protein, a more detailed explanation of how to interpret and analyze PTM results is provided in the PeptideAtlas of this important pathogen. Candida albicans PeptideAtlas web page: https://db.systemsbiology.net/sbeams/cgi/PeptideAtlas/buildDetails?atlas_build_id=578.

PMID:40084908 | DOI:10.1021/acs.jproteome.4c01020

Bio Protoc. 2025 Mar 5;15(5):e5223. doi: 10.21769/BioProtoc.5223. eCollection 2025 Mar 5.

ABSTRACT

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. According to 2020 reports, globally, 2.2 million cases are reported every year, with the mortality number being as high as 1.8 million patients. To study NSCLC, systems biology offers mathematical modeling as a tool to understand complex pathways and provide insights into the identification of biomarkers and potential therapeutic targets, which aids precision therapy. Mathematical modeling, specifically ordinary differential equations (ODEs), is used to better understand the dynamics of cancer growth and immunological interactions in the tumor microenvironment. This study highlighted the dual role of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS/STING) pathway's classical involvement in regulating type 1 interferon (IFN I) and pro-inflammatory responses to promote tumor regression through senescence and apoptosis. Alternative signaling was induced by nuclear factor kappa B (NF-κB), mutated tumor protein p53 (p53), and programmed death-ligand1 (PD-L1), which lead to tumor growth. We identified key regulators in cancer progression by simulating the model and validating it with the following model estimation parameters: local sensitivity analysis, principal component analysis, rate of flow of metabolites, and model reduction. Integration of multiple signaling axes revealed that cGAS-STING, phosphoinositide 3-kinases (PI3K), and Ak strain transforming (AKT) may be potential targets that can be validated for cancer therapy. Key features • Procedures for the reconstruction of a robust and steady-state mathematical model with respective analysis in order to provide mechanistic insights. • The dynamic mathematical model allows an understanding of the multifaceted dual roles of cGAS-STING in NSCLC promotion and inhibition. • The inherent statistical tool in systems biology provides a novel immunotherapeutic target.

PMID:40084069 | PMC:PMC11896782 | DOI:10.21769/BioProtoc.5223

Front Immunol. 2025 Feb 27;16:1530053. doi: 10.3389/fimmu.2025.1530053. eCollection 2025.

ABSTRACT

OBJECTIVE: To observe the inhibitory effect and potential mechanism of Yiqi Huayu Jiedu Decoction (YHJD) on liver metastasis of colorectal cancer (CRC).

METHODS: We compared the changes of liver weight and liver index before and after YHJD treatment in CRC liver metastasis mouse models. HE staining was employed to observe the pathological changes in mouse liver tissue sections. Flow cytometry was used to analyze the number and marker of neutrophils treated with YHJD. Transcriptomics, proteomics, and multiplex cytokine array analyses were conducted to further verify the role of YHJD on CXCL1. Differential gene analysis was performed to further explore the mechanism by which YHJD inhibits liver metastasis of CRC.

RESULTS: Animal studies demonstrated that YHJD reduces liver metastases. Flow cytometry results revealed that YHJD promotes N1 neutrophils in liver. Combining multi-omics and multiple cytokine arrays, we observed a significant increase in the expression of CXCL1 in the liver and plasma. GO and KEGG enrichment analyses indicated that YHJD may regulate the chemotaxis of neutrophils to inhibit the liver metastasis of CRC by participating in the regulation of cell adhesion molecule binding, adhesion protein binding, and multiple metabolic pathways.

CONCLUSIONS: YHJD inhibits CRC liver metastasis by upregulating CXCL1, thereby promoting N1 neutrophil chemotaxis towards the liver, and concurrently raising the expression of N1 neutrophil markers.

PMID:40083557 | PMC:PMC11903724 | DOI:10.3389/fimmu.2025.1530053

J Public Health Afr. 2025 Feb 25;16(1):690. doi: 10.4102/jphia.v16i1.690. eCollection 2025.

ABSTRACT

BACKGROUND: Human immunodeficiency viruses (HIV) and acquired immunodeficiency syndrome (AIDS) remain a global public health problem. Other sexually transmitted infections (STIs) are aggravating factors.

AIM: This study aimed to assess the prevalence and identify new cases of HIV and STIs, as well as their associated risk factors.

SETTING: Political insecurity in the northern regions of Cameroon has led to population displacement, weakening an already fragile health system.

METHODS: A cohort of 684 consenting participants from the north and far north were enrolled in 2021 and followed up in 2022. Socio-demographic variables and risk behaviours were collected. Anti-HIV Ab, hepatitis B surface antigen, Treponema pallidum haemagglutination tests were performed. The data were analysed using Epi Info 7.5.2. The associations between variables were evaluated using the Chi-square test with a 95% confidence interval.

RESULTS: The new cases of HIV rate and overall prevalence were 1.63% (95% confidence interval [CI]: 0.83% - 2.41%) and 3.8% (95% CI: 2.01% - 3.97%), respectively. New HIV cases increased from 0.27% (2017, Demographic and Health Survey [DHS]) to 1.63%. The prevalence of syphilis and hepatitis B was 1.03% (95% CI: 0.98% - 1.09%) and 4.56% (95% CI: 4.51% - 4.66%), respectively. Factors associated with HIV included religion (p = 0.027), unprotected sex (p = 0.006), sex with a sex worker (p = 0.00009), and co-infection with syphilis and hepatitis B (p = 0.033). New HIV infections may also be associated with population displacement.

CONCLUSION: HIV infection, syphilis and hepatitis B are on the rise in the Northern Cameroon.

CONTRIBUTION: Future HIV prevention strategies should consider population displacement and HIV-associated infections such as hepatitis B and syphilis in order to secure achievements in HIV programme and further curb the burden of these infections in the country.

PMID:40083464 | PMC:PMC11905195 | DOI:10.4102/jphia.v16i1.690

Aging Cell. 2025 Mar 13:e70043. doi: 10.1111/acel.70043. Online ahead of print.

ABSTRACT

The lymphatic vasculature plays essential roles in fluid balance, immunity, and lipid transport. Chronic, low-grade inflammation in peripheral tissues develops when lymphatic structure or function is impaired, as observed during aging. While aging has been associated with a broad range of heart pathophysiology, its effect on cardiac lymphatic vasculature has not been characterized. Here, we analyzed cardiac lymphatics in aged 20-month-old mice versus young 2-month-old mice. Aged hearts showed reduced lymphatic vascular density, more dilated vessels, and increased inflammation and fibrosis in peri-lymphatic zones. As exercise has shown benefits in several different models of age-related heart disease, we further investigated the effects of aerobic training on cardiac lymphatics. Eight weeks of voluntary wheel running attenuated age-associated adverse remodeling of the cardiac lymphatics, including reversing their dilation, increasing lymph vessel density and branching, and reducing perilymphatic inflammation and fibrosis. Intravital lymphangiography demonstrated improved cardiac lymphatic flow after exercise training. Our findings illustrate that aging leads to cardiac lymphatic dysfunction, and that exercise can improve lymphatic health in aged animals.

PMID:40083143 | DOI:10.1111/acel.70043

FEMS Yeast Res. 2025 Mar 13:foaf011. doi: 10.1093/femsyr/foaf011. Online ahead of print.

ABSTRACT

The formation of hyphae is one of the most crucial virulence traits the human pathogenic fungus Candida albicans possesses. The assessment of hyphal length in response to various stimuli, such as exposure to human serum, provides valuable insights into the adaptation strategies of C. albicans to the host environment. Despite the increasing high-throughput capacity live-cell imaging and data generation, the accurate analysis of hyphal growth has remained a laborious, error-prone, and subjective manual process. We developed an analysis pipeline utilizing the open-source visual programming language JIPipe to overcome the limitations associated with manual analysis of hyphal growth. By comparing our automated approach with manual analysis, we refined the strategies to achieve accurate differentiation between yeast cells and hyphae. The automated method enables length measurements of individual hyphae, facilitating a time-efficient, high-throughput, and user-friendly analysis. By utilizing this JIPipe analysis approach, we obtained insights into the filamentation behavior of two C. albicans strains when exposed to human serum albumin (HSA), the most abundant protein in human serum. Our findings indicate that despite the known role of HSA in stimulating fungal growth, it reduces filamentous growth. The implementation of our automated JIPipe analysis approach for hyphal growth represents a long-awaited and time-efficient solution to meet the demand of high-throughput data generation. This tool can benefit different research areas investigating the virulence aspects of C. albicans.

PMID:40082735 | DOI:10.1093/femsyr/foaf011

EMBO J. 2025 Mar 13. doi: 10.1038/s44318-025-00408-1. Online ahead of print.

ABSTRACT

The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following the overproduction of protein components, recent cryo-EM structures showed symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit the degradation of membrane-embedded substrates. Here, we present structures of native protein complexes, in which HflK/C instead forms an asymmetric nautilus-shaped assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. Consistent with this nautilus-like structure, proteomic assays suggest that HflK/C enhances FtsH degradation of certain membrane-embedded substrates. Membrane curvature in our FtsH•HflK/C complexes is opposite that of surrounding membrane regions, a property that correlates with lipid scramblase activity and possibly with FtsH's function in the degradation of membrane-embedded proteins.

PMID:40082723 | DOI:10.1038/s44318-025-00408-1

Nat Aging. 2025 Mar 13. doi: 10.1038/s43587-025-00816-2. Online ahead of print.

ABSTRACT

Neuroinflammation including interleukin (IL)-12/IL-23-signaling is central to Alzheimer's disease (AD) pathology. Inhibition of p40, a subunit of IL-12/IL-23, attenuates pathology in AD-like mice; however, its signaling mechanism and expression pattern remained elusive. Here we show that IL-12 receptors are predominantly expressed in neurons and oligodendrocytes in AD-like APPPS1 mice and in patients with AD, whereas IL-23 receptor transcripts are barely detectable. Consistently, deletion of the IL-12 receptor in neuroectodermal cells ameliorated AD pathology in APPPS1 mice, whereas removal of IL-23 receptors had no effect. Genetic ablation of IL-12 signaling alone reverted the loss of mature oligodendrocytes, restored myelin homeostasis, rescued the amyloid-β-dependent reduction of parvalbumin-positive interneurons and restored phagocytosis-related changes in microglia of APPPS1 mice. Furthermore, IL-12 protein expression was increased in human AD brains compared to healthy age-matched controls, and human oligodendrocyte-like cells responded profoundly to IL-12 stimulation. We conclude that oligodendroglial and neuronal IL-12 signaling, but not IL-23 signaling, are key in orchestrating AD-related neuroimmune crosstalk and that IL-12 represents an attractive therapeutic target in AD.

PMID:40082619 | DOI:10.1038/s43587-025-00816-2

Metabolomics. 2025 Mar 13;21(2):40. doi: 10.1007/s11306-025-02228-0.

ABSTRACT

BACKGROUND: Advancements in the research of intracellular metabolome have the potential to affect our understanding of biological processes. The applications and findings of intracellular metabolome analysis are useful in understanding cellular pathways, microbial interactions, and the detection of secreted metabolites and their functions.

AIM OF REVIEW: This work focuses on the analysis of intracellular metabolomes in microorganisms. The techniques used for analyzing the intracellular metabolomes including metabolomics approaches such as mass spectrometry, nuclear magnetic resonance, liquid chromatography, and gas chromatography are discussed.

KEY SCIENTIFIC CONCEPTS OF REVIEW: Challenges such as sample preparation, data analysis, metabolite extraction, sample storage and collection, and processing techniques were investigated, as they can highlight emerging technologies and advancements in metabolome analysis, future applications in drug discovery, personalized medicine, systems biology, and the limitations and challenges in studying the metabolome of microorganisms.

PMID:40082321 | DOI:10.1007/s11306-025-02228-0

Trends Cell Biol. 2025 Mar 12:S0962-8924(25)00040-6. doi: 10.1016/j.tcb.2025.02.006. Online ahead of print.

ABSTRACT

Aging is a dynamic process that is driven by cellular damage and disruption of homeostatic gene regulatory networks (GRNs). Traditional studies often focus on individual genes, but understanding their interplay is key to unraveling the mechanisms of aging. This review explores the gene circuits that influence longevity and highlights the role of feedback loops in maintaining cellular balance. The SIR2-HAP circuit in yeast serves as a model to explore how mutual inhibition between pathways influences aging trajectories and how engineering stable fixed points or oscillations within these circuits can extend lifespan. Feedback loops crucial for maintaining homeostasis are also reviewed, and we highlight how their destabilization accelerates aging. By leveraging systems and synthetic biology, strategies are proposed that may stabilize these loops within single cells, thereby enhancing their resilience to aging-related damage.

PMID:40082090 | DOI:10.1016/j.tcb.2025.02.006

J Microbiol Biotechnol. 2025 Mar 13;35:e2411058. doi: 10.4014/jmb.2411.11058.

ABSTRACT

Polyethylene (PE) is among the most widely used synthetic plastics globally, serving as an essential material in daily life and numerous industries, such as packaging for bottles and food, as well as in the production of toys and pipes. PE is used for various purposes owing to its high durability and low production costs, leading to a steadily increasing demand. However, PE waste is a significant contributor to environmental pollution, posing serious threats to marine and soil ecosystems. Therefore, the efficient decomposition of PE, a synthetic polymer known for its resistance to degradation, using bacteria offers a sustainable and effective method for reusing PE. In this study, we isolated a novel species of Kosakonia, designated Kosakonia cowanii JNU01, from a landfill site, capable of biodegrading PE. K. cowanii JNU01 exhibited the highest cell growth rate in media containing PE, indicating its effectiveness in decomposing PE for use as a sole carbon source in its metabolic pathway. Treatment of PE with K. cowanii JNU01 resulted in the emergence of new chemical functional groups, including hydroxyl, carboxyl, amide, and ether groups, within the inert hydrocarbon structure. Analysis of the PE film treated with K. cowanii JNU01 revealed considerable physical degradation on the film's surface. Additionally, various metabolites released from PE by K. cowanii JNU01 were identified. These findings suggest that K. cowanii JNU01 proves to be an effective candidate bacterium for PE degradation.

PMID:40081902 | DOI:10.4014/jmb.2411.11058

J Mol Biol. 2025 Mar 11:169087. doi: 10.1016/j.jmb.2025.169087. Online ahead of print.

ABSTRACT

I started my faculty career in 1981 at the UW-Madison in the Department of Bacteriology and moved to the University of California, San Francisco in 1993, where I am a Professor in the Departments of Microbiology and Immunology and Cell and Tissue Biology. In this article, I first review my contributions to understanding the molecular biology of bacterial transcriptional apparatus and the global role of alternative sigmas (σs), a major pillar of bacterial transcriptional control. I then discuss my role in spearheading the development of bacterial systems biology, specifically to the genome-wide phenotyping approaches necessary for rapid understanding of gene function and the molecular basis of pathway connections across the bacterial universe.

PMID:40081792 | DOI:10.1016/j.jmb.2025.169087

J Affect Disord. 2025 Mar 11:S0165-0327(25)00370-2. doi: 10.1016/j.jad.2025.03.032. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies have linked branched-chain amino acids (BCAAs) metabolism with the risk of major depressive disorder (MDD). However, it is unclear whether associations of plasma BCAA levels with MDD are causal or driven by reverse causality.

METHODS: Mendelian randomization (MR) was used to investigate the causal association of genetically determined BCAA levels with the risk of MDD. The large genome-wide association study (GWAS) datasets on plasma BCAA levels (n = 115,051) were obtained from the UK Biobank. The summary GWAS dataset for MDD was obtained from the Psychiatric Genomics Consortium (n = 1,035,760). We applied the inverse variance-weighted (IVW) method to explore the causal relationships between BCAA levels and MDD, followed by multiple pleiotropy and heterogeneity tests.

RESULTS: Our results demonstrated that genetically determined circulating total BCAAs (odds ratio (OR): 1.05, 95 % confidence interval (CI): 1.01-1.10, P = 0.016), leucine (OR: 1.06, 95 % CI: 1.02-1.11, P = 7.22 × 10-3), and isoleucine (OR: 1.08, 95 % CI: 1.01-1.16, P = 0.032) levels were associated with an increased risk of MDD. There was suggestive evidence supporting the causal effect of valine levels on MDD (OR: 1.04, 95 % CI: 1.00-1.08, P = 0.075). Bidirectional MR analysis did not provide evidence of reverse causality.

CONCLUSIONS: We report evidence supporting the causal role of BCAAs in the development of MDD. This study offers new insights into the mechanisms and treatment of MDD.

PMID:40081595 | DOI:10.1016/j.jad.2025.03.032

Metab Eng. 2025 Mar 11:S1096-7176(25)00033-3. doi: 10.1016/j.ymben.2025.03.003. Online ahead of print.

ABSTRACT

Microbial poly(3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyvalerate), abbreviated as P(3HB-4HB-3HV) or P34HBHV, is a flexible polyhydroxyalkanoate (PHA) material ranging from softness to elasticity depending on the ratios of various monomers. Halomonas bluephagenesis, as the chassis of the next generation industrial biotechnology (NGIB) able to grow contamination free under open unsterile conditions. The resulting recombinants of H. bluephagenesis became capable of efficiently synthesizing P34HBHV utilizing glucose as the sole carbon source. Engineered H. bluephagenesis H1 (encoding ogdA, sucD, 4hbD, orfZ, scpA and scpB in chromosomes) transformed with a plasmid containing PHA synthesis genes phaC and phaA and its derivative H29 produced up to 92% P(3HB-co-8.85%4HB-co-8.47%3HV) and 72% P(3HB-co-13.21%4HB-co-11.97%3HV) in cell dry weight (CDW), respectively, in shake flasks. In bioreactor cultivation, H. bluephagenesis H39 constructed by integrating the 4hbD, phaC and phaA genes into the genome of H. bluephagenesis H1 achieved 95 g/L CDW with 69% P(3HB-co-10.49%4HB-co-3.54%3HV), while H. bluephagenesis H43, further optimized with lpxM deletion, reached 73 g/L CDW with 78% P(3HB-co-10.35%4HB-co-4.54%3HV) in a 100 L bioreactor. For the first time, H. bluephagenesis was successfully engineered to generate stable and hyperproductive derivative strains for pilot production of P(3HB-4HB-3HV) with customizable monomer ratios from glucose as the sole carbon source.

PMID:40081465 | DOI:10.1016/j.ymben.2025.03.003

Metab Eng. 2025 Mar 11:S1096-7176(25)00028-X. doi: 10.1016/j.ymben.2025.02.015. Online ahead of print.

ABSTRACT

Advances in genomics technologies have generated large data sets that provide tremendous insights into the genetic diversity of taxonomic groups. However, it remains challenging to pinpoint the effect of genetic diversity on different traits without performing resource-intensive phenotyping experiments. Pan-genome-scale metabolic models (panGEMs) extend traditional genome-scale metabolic models by considering the entire reaction repertoire that enables the prediction and comparison of metabolic capabilities within a taxonomic group. Here, we systematically review the state-of-the-art methodologies for constructing panGEMs, focusing on used tools, databases, experimental datasets, and orthology relationships. We highlight the unique advantages of panGEMs compared to single-species GEMs in predicting metabolic phenotypes and in guiding the experimental validation of genome annotations. In addition, we emphasize the disparity between the available (pan-)genomic data on photosynthetic organisms and their under-representation in current (pan)GEMs. Finally, we propose a perspective for tackling the reconstruction of panGEMs for photosynthetic eukaryotes that can help advance our understanding of the metabolic diversity in this taxonomic group.

PMID:40081464 | DOI:10.1016/j.ymben.2025.02.015

Semin Liver Dis. 2025 Mar 13. doi: 10.1055/a-2516-2361. Online ahead of print.

ABSTRACT

Acute-on-chronic liver failure (ACLF) is a severe condition in patients with decompensated liver cirrhosis, marked by high short-term mortality. Recent experimental and clinical evidence has linked intestinal dysfunction to both the initiation of ACLF as well as disease outcome. This review discusses the significant role of the gut-liver axis in ACLF pathogenesis, highlighting recent advances. Gut mucosal barrier disruption, gut dysbiosis, and bacterial translocation emerge as key factors contributing to systemic inflammation in ACLF. Different approaches of therapeutically targeting the gut-liver axis via farnesoid X receptor agonists, nonselective beta receptor blockers, antibiotics, and probiotics are discussed as potential strategies mitigating ACLF progression. The importance of understanding the distinct pathophysiology of ACLF compared with other stages of liver cirrhosis is highlighted. In conclusion, research findings suggest that disruption of intestinal integrity may be an integral component of ACLF pathogenesis, paving the way for novel diagnostic and therapeutic approaches to manage this syndrome more effectively.

PMID:40081417 | DOI:10.1055/a-2516-2361

J Pharmacol Exp Ther. 2025 Feb 21;392(4):103403. doi: 10.1016/j.jpet.2025.103403. Online ahead of print.

ABSTRACT

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with unclear pathological mechanisms. ADHD is treated with both stimulant and nonstimulant medications, but their therapeutic mechanisms and impact on brain metabolites are not fully understood. This study employed an untargeted metabolomics approach with liquid chromatography mass spectrometry to investigate the pathogenesis of ADHD, as well as the effects of established and novel therapeutics. We characterized the metabolomic signatures of the adgrl3.1 mutant zebrafish ADHD model and examined the impact of methylphenidate, guanfacine, atomoxetine, and 5 novel putative therapeutics identified in a prior screen, including amlodipine. Our analysis revealed that the drugs commonly affect pathways related to amino acid and lipid metabolism, specifically involving glycine, serine, threonine, phenylalanine, lysophosphatidylcholine, and sphingomyelin. This convergence on similar metabolic targets was unexpected and suggests a broader, systemic effect of ADHD therapeutics, challenging the traditional view of distinct drug mechanisms. Amlodipine exhibited metabolic effects consistent with established treatments, indicating its potential as a viable alternative or adjunct therapy. These findings provide new insights into the metabolic underpinnings of ADHD and highlight potential targets for developing improved therapeutic strategies. SIGNIFICANCE STATEMENT: This study explores the metabolic pathways affected by attention deficit hyperactivity disorder treatments using a zebrafish adgrl3.1 mutant model. Untargeted metabolomics revealed that both established and novel attention deficit hyperactivity disorder medications influence common amino acid and lipid metabolism pathways, suggesting systemic effects. Notably, amlodipine showed similar impacts as current drugs, offering promise as an alternative therapy.

PMID:40081232 | DOI:10.1016/j.jpet.2025.103403

J Phys Chem B. 2025 Mar 13. doi: 10.1021/acs.jpcb.4c08640. Online ahead of print.

ABSTRACT

The dynamic formation of (bio)molecular condensates has emerged as a key regulatory mechanism in cellular processes. Concepts from polymer physics can provide valuable insights into the underlying mechanisms and properties of these condensates. While stoichiometric interactions between chemically distinct molecules have traditionally been the primary focus for understanding and predicting the equilibrium behavior, recent attention has turned to the role of molecular diversity, particularly the interplay between molecules of similar types but varying chain lengths. To mimic such cellular conditions, we investigated the impact of molecular weight polydispersity using polyethylene glycol (PEG) and dextran (Dex) solutions through experiments and molecular simulations. Our findings reveal that polydisperse systems, which contain a higher fraction of short-chain components, exhibit a narrower two-phase region, along with reduced concentration differences and interfacial tension between the coexisting polymer-rich and polymer-poor phases. In these systems, the Dex-rich phase is enriched with longer Dex chains compared to the PEG-rich phase, with a gradual transition in chain length across their interface. However, polydispersity has no significant effects on the critical concentration and critical exponents. Finally, our study of condensation kinetics demonstrates that phase separation is not limited by the nucleation rate but instead by the diffusion-driven aggregation of polymers.

PMID:40080692 | DOI:10.1021/acs.jpcb.4c08640

ACS Synth Biol. 2025 Mar 13. doi: 10.1021/acssynbio.4c00806. Online ahead of print.

ABSTRACT

Interest in Xanthobacter species is increasing due to their unique metabolic capabilities. They can grow in both heterotrophic and fully autotrophic environments, including carbon dioxide, dinitrogen gas, and hydrogen as the sole carbon, nitrogen, and energy sources, respectively. Academic and industrial groups looking to leverage these metabolic properties are already using Xanthobacter strains for the sustainable production of food and commodities. However, only a handful of genetic parts and protocols exist in scattered genetic backgrounds, and there is an unmet need for reliable genetic engineering tools to manipulate Xanthobacter species. Here, we developed XanthoMoClo, a robust modular cloning genetic toolkit for Xanthobacter and Roseixanthobacter species and strains, providing extensive tools to transform them, manipulate their metabolism, and express genes of interest. The toolkit contains plasmid parts, such as replication origins, antibiotic selection markers, fluorescent proteins, constitutive and inducible promoters, a standardized framework to incorporate novel components into the toolkit, and a conjugation donor to transform Xanthobacter and Roseixanthobacter strains easily with no or minimal optimization. We validated these plasmid components in depth in three of the most commonly studied Xanthobacter strains: X. versatilis Py2, X. autotrophicus GZ29, and X. flavus GJ10, as well as in R. finlandensis VTT E-85241. Finally, we demonstrate robust toolkit functionality across 21 different species of Xanthobacter and Roseixanthobacter, comprising 23 strains in total. The XanthoMoClo genetic toolkit is available to the research community (through AddGene) and will help accelerate the genetic engineering of Xanthobacter to further their applications in sustainability and bioremediation efforts.

PMID:40080684 | DOI:10.1021/acssynbio.4c00806