Recent ucipharmsci items

Electroacupuncture improves cognitive function and neuropsychiatric symptoms in breast cancer survivors: a pilot randomized controlled trial

Fri, 24 Apr 2026 00:00:00 +0000

BACKGROUND: We conducted a randomized, double-blinded pilot trial to compare the impact of two electroacupuncture (EA) regimens on co-occurring neuropsychiatric symptoms among breast cancer survivors (BCS). METHODS: BCS who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly EA to target either neuropsychiatric-specific (nEA) or non-neuropsychiatric-specific (sEA) acupoints. Primary endpoints were the within-group pre-post effect sizes (Glass's Δ) in symptom severities, adjusted for multiple comparisons (p-adjusted). Outcomes were assessed using neurocognitive tests (CANTAB®), PROs (FACT-Cog, MFSI-SF, EORTC QLQ-C30), plasma biomarkers, and neuroimaging. Responders were defined by reliable change index (for objective cognition) or MCID (for PROs). RESULTS: Thirty-five were recruited, with 30 (86%) completing all sessions. The mean (±SD) age was 58.2 (±12.2) years, and 86% reported co-occurring symptoms. Following...

How custom polymerases are driving innovation in synthetic biology

Wed, 22 Apr 2026 00:00:00 +0000

Polymerases are the molecular machines of information transfer, yet their natural catalytic repertoire is largely restricted to DNA, RNA, and a limited set of chemically modified analogs. In response to this constraint, custom polymerases have emerged as powerful tools in the synthetic biology toolbox. Advances in polymerase engineering are unlocking access to RNA polymers generated by primer-extension rather than a promoter driven process as well as synthetic genetic polymers with unnatural backbone structures, collectively termed xeno-nucleic acids (XNAs). In this review, we highlight examples of how custom polymerases are redefining the chemical boundaries of genetic function and driving innovation across the fields of synthetic biology, biotechnology, and molecular medicine.

Sexual dimorphism shapes renal metabolic adaptation to a ketogenic diet.

Wed, 8 Apr 2026 00:00:00 +0000

While kidneys are essential for maintaining systemic metabolic homeostasis and exhibit sexual dimorphism, the effects of sex and environmental factors, such as diet, on renal metabolism remain unclear. Using kidney-specific arteriovenous (AV) metabolomics, in vivo isotope tracing, and transcriptomics, we discover profound sex differences in kidney metabolic reprogramming under ketogenic diet (KD) in C57BL/6J mice. Tissue metabolomics shows the accumulation of aldosterone and acylcarnitines exclusively in female kidneys under a normal chow (NC) diet, suggesting basal sex differences in sodium and fatty acid metabolism. Under KD, AV metabolomics reveals that only female kidneys activate ketogenesis and gluconeogenesis, supported by transcriptional sex differences in related rate-limiting enzymes and transporters. Given the widespread public and clinical interest in KD for treating epilepsy, metabolic disorders, and cancers, our findings underscore the importance of considering sex...

A periplasmic protein complex mediates arabinofuranosyltransferase activity and intrinsic drug resistance in Mycobacterium tuberculosis

Mon, 6 Apr 2026 00:00:00 +0000

The intrinsic drug resistance of Mycobacterium tuberculosis (Mtb) is a major barrier to effective tuberculosis (TB) treatment and is largely due to its complex, impermeable cell envelope. We identified a periplasmic protein complex comprising FecB and Rv3035 that is essential for maintaining envelope integrity and mediating intrinsic multidrug resistance in Mtb. FecB interacts with Rv3035, forming a stable heterodimer that associates with the cell envelope biosynthesis protein AftB. We report the structures of Rv3035 alone and in complex with FecB and identify critical residues for complex formation and function. Coessentiality and genetic interaction analyses support a functional link between FecB, Rv3035, and AftB, an arabinofuranosyltransferase that synthesizes arabinogalactan and lipoarabinomannan. Loss of FecB or Rv3035 disrupted AftB-mediated arabinan synthesis, suggesting that these proteins support AftB's enzymatic activity. FecB is required for Mtb virulence in...

An expanded reference catalog of translated open reading frames for biomedical research.

Fri, 3 Apr 2026 00:00:00 +0000

Non-canonical (i.e. unannotated) open reading frames (ncORFs) have until recently been omitted from reference genome annotations, despite evidence of their translation, limiting their incorporation into biomedical research. To address this, in 2022, we initiated the TransCODE consortium and built the first community-driven consensus catalog of human ncORFs, which was openly distributed to the research community via Ensembl-GENCODE. While this catalog represented a starting point for reference ncORF annotation, major technical and scientific issues remained. In particular, this initial catalog had no standardized framework to judge the evidence of translation for individual ncORFs. Here, we present an expanded and refined catalog of the human reference annotation of ncORFs. By incorporating more datasets and by lifting constraints on ORF length and start codon, we define a comprehensive set of 28 359 ncORFs that is nearly four times the size of the previous catalog. Furthermore,...

Xeno-nucleic acids support formation of Ag(I)-mediated duplexes and silver nanoclusters

Thu, 12 Mar 2026 00:00:00 +0000

The expanded backbone chemistries of xeno-nucleic acids (XNAs) hold significant promise for emerging areas of synthetic biology and nanomaterials, but metal-mediated XNA interactions remain largely unexplored. Here, we use a combination of circular dichroism spectroscopy and mass spectrometry to show that XNAs can form Ag+-mediated duplex structures resembling their DNA counterparts. XNAs with a range of different backbone compositions are found to stabilize photoluminescent silver nanoclusters with spectral properties that can be tuned based on their respective backbone chemistry. The resistance of silver nanoclusters to nuclease digestion is also compared for DNA and XNAs. These results show that XNA backbone chemistry provides a new tool beyond nucleobase sequence for controlling and expanding the properties of nucleic acid-stabilized silver nanoclusters and metal-mediated DNA duplexes.

Iran: Attacking injured protestors and healthcare workers violates medical neutrality

Wed, 11 Mar 2026 00:00:00 +0000

Iran: Attacking injured protestors and healthcare workers violates medical neutrality

Diversity in Structure and Function: How Cyanobacterial Metallophores Reveal a Broadening Perspective of Microbial Metal-Chelators.

Wed, 25 Feb 2026 00:00:00 +0000

Cyanobacteria are known for their rich secondary metabolome with a long history of research directed toward the industrial and pharmaceutical applications of their natural products. Cyanobacterial metallophores (metal-chelating molecules), however, are understudied relative to metallophores from other phyla despite evidence suggesting that genes for metallophore biosynthesis are well-represented in cyanobacterial genomes. Many of the characterized cyanobacterial metallophores are formed from hybrid biosynthetic pathways and feature mixed coordinating functional groups, leading to enhanced structural and functional diversity. The few characterized metallophore families have intriguing properties including promiscuity of metal binding, photoreactivity, and amphiphilicity that are yet to be fully explored. Research suggests that these compounds are ecologically relevant and could guide community dynamics by controlling the availability of iron, detoxifying copper, and allelopathically...

A simple compound prioritization method for drug discovery considering multi-target binding.

Tue, 17 Feb 2026 00:00:00 +0000

Active learning is an emerging paradigm used to help accelerating drug discovery, but most prior applications seek solely to optimize potency, whereas multiple properties influence a compounds utility as a drug candidate. We introduce a method for multiobjective ligand optimization, which is able to efficiently handle distinct molecular properties that are expensive to compute, such as binding affinities with respect to multiple protein targets. We validate this protocol retrospectively using docking scores, showing an improved retrieval of the top 0.04-0.4% binders from the dataset with our method compared to greedy acquisition, owing to a better distribution of the compute budget between different properties. Our results also suggest that fitting individual properties separately leads to a better rank correlation of the resulting predictions. This workflow addresses the needs of pharmaceutical research for improving the efficiency of hit-to-lead and lead optimization by considering...

Multiplexed bioluminescence microscopy via phasor analysis

Thu, 12 Feb 2026 00:00:00 +0000

Bioluminescence imaging with luciferase–luciferin pairs is a well-established technique for visualizing biological processes across tissues and whole organisms. Applications at the microscale, by contrast, have been hindered by a lack of detection platforms and easily resolved probes. We addressed this limitation by combining bioluminescence with phasor analysis, a method commonly used to distinguish spectrally similar fluorophores. We built a camera-based microscope equipped with special optical filters to directly assign phasor locations to unique luciferase–luciferin pairs. Six bioluminescent reporters were easily resolved in live cells, and the readouts were quantitative and instantaneous. Multiplexed imaging was also performed over extended time periods. Bioluminescent phasor further provided direct measures of resonance energy transfer in single cells, setting the stage for dynamic measures of cellular and molecular features. The merger of bioluminescence with phasor analysis...

The impact of patient personality traits on adherence to tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia

Wed, 11 Feb 2026 00:00:00 +0000

Abstract Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion oncoprotein and treated with oral tyrosine kinase inhibitors (TKIs), which have significantly improved long-term survival. However, sustained therapeutic response is closely tied to patient adherence, with suboptimal adherence linked to inferior molecular and clinical outcomes. Despite known barriers to adherence, including side effects, cost, and disease-related distress, little is known about the role of patient personality traits in influencing adherence behavior, particularly among patients with CML. To address this gap, we conducted a prospective pilot study evaluating the relationship between patient personality traits, medication adherence, and quality of life among individuals with CML receiving TKI therapy. Subjects were recruited from the University of California, Irvine Chao Family Comprehensive Cancer Center and the CML Buster Foundation national patient network....

NLRP10 engages oxidized DNA through a Schiff-base mechanism and dissociates from NLRP3 upon inflammasome activation.

Sat, 31 Jan 2026 00:00:00 +0000

Mitochondrial DNA release into the cytosol is a critical event in innate immune activation, often acting as a damage-associated molecular pattern (DAMP) that triggers inflammasome assembly. Here, we demonstrate that NLRP3 is involved in the release of D-loop mtDNA into the cytosol. We further show that NLRP3 interacts with NLRP10. NLRP10-mediated oxidized DNA cleavage involves a Schiff base intermediate and is inhibited by small molecules known to inhibit glycosylases. These findings support a model where NLRP10 interaction with oxidized DNA may contribute to long-term senescence secretory phenotype and modulate inflammasome activation. Our study highlights a novel mechanism by which NLRP10 can respond to mitochondrial stress signals to influence innate immunity and suggests therapeutic potential for targeting these interactions in inflammatory diseases.

The quality and safety of Rhodiola rosea supplements on the U.S. market: An analysis of biomarkers, heavy metals, and pesticide residues.

Fri, 23 Jan 2026 00:00:00 +0000

Rhodiola rosea supplements have become popular in the U.S., with a $3.4 billion market and an annual growth of about 10% in sales in the past few years. While the health benefits of this plant have been evaluated in many scientific studies, the potential differences in quality of these botanical products on the U.S. market have not been studied in detail. Using reversed-phase ultra-performance liquid chromatography, we determined the concentrations of the biomarker molecules, rosavins and salidroside, in a small but representative sample of R. rosea dietary supplement products commercially available in the U.S. Concentrations of rosavins and salidroside ranged from 0.01% to 3.08% and 0.07% to 2.91%, respectively, including substantial aberrations from advertised biomarker amounts. One product showed an undisclosed likely addition of synthetic salidroside. We also assessed heavy metal contaminations via inductively coupled plasma mass spectrometry and pesticide contents by gas...

Genes Encoding Multiple Modulators of the Immune Response Are Methylated in the Prostate Tumor Microenvironment of African Americans

Thu, 15 Jan 2026 00:00:00 +0000

Background/Objectives: Prostate cancer (PCa) is diagnosed at an earlier median age, more advanced stage, and has worse clinical outcomes in African American (AA) men compared to European Americans (EA). Methods: To investigate the role of aberrant DNA methylation in tumor-adjacent stroma (TAS), methyl binding domain sequencing (MBD-seq) was performed on AA (n = 17) and EA (n = 15) PCa patients. This was independently confirmed using the long interspersed nuclear element-1 (LINE-1) assay. Pathway analysis was performed on statistically significantly differentially methylated genes for AA and EA TAS. DNA methylation profiles of primary cultured AA and EA carcinoma-associated fibroblasts (CAFs) were compared with AA and EA TAS. AA and EA CAFs were treated with demethylating agent 5-Azacytidine (5-AzaC). Results: AA TAS exhibited higher global DNA methylation than EA TAS (p-value < 0.001). Of the 3268 differentially methylated regions identified...

Obstetric Outcomes With Second-Generation Long-Acting Injectable Versus Oral Antipsychotics.

Wed, 14 Jan 2026 00:00:00 +0000

Objective: The purpose of this study is to evaluate obstetric outcomes in pregnant women who received second-generation long-acting injectable antipsychotics (LAIAs) compared to a control group who received second-generation oral antipsychotics. Methods: This was a retrospective study utilizing a global cohort of 148 health care organizations grouped into a network within the TriNetX database. Pregnant patients of any trimester were grouped into 2 cohorts: (1) exposure to long-acting aripiprazole, risperidone, paliperidone, or olanzapine (n=2,082) and (2) exposure to the corresponding oral formulations (n=31,376) and propensity matched. The primary outcome was the occurrence of one of the following obstetric complications: gestational diabetes, preeclampsia, eclampsia, or a newly diagnosed hypertensive disorder. Cesarean section rates were also assessed. Results: After propensity matching, each cohort yielded 2,025 patients. No intergroup differences were...

Allele-specific knockdown by an engineered DNAzyme capable of RNase H1 evasion.

Sat, 10 Jan 2026 00:00:00 +0000

DNA enzymes (DNAzymes) offer an attractive therapeutic approach for targeting disease-associated mutations in mRNA transcripts, but face limitations in development due to unintended engagement by RNase H1. Although chemical optimization has led to designs with improved catalytic activity, strategies to mitigate RNase H1 recognition remain underexplored. Here, we report the incorporation of threose nucleic acid (TNA) into the backbone architecture of the 10-23 DNAzyme variant known as Dz46. Substitution of the dC3 position in the catalytic loop with TNA increases activity, whereas installation of two TNA residues in the binding arm abrogates competition by RNase H1. The resulting enzyme enables allele-specific knockdown of an oncogenic KRAS mutation in mammalian cells and facilitates general knockdown of PCSK9 and GATA3 targets. Together, these results demonstrate the utility of TNA as a chemical tool for enhancing DNAzyme performance and evading RNase H1 activity in cells.

Total synthesis of asperdinones B, C, D, E and terezine D

Sat, 27 Dec 2025 00:00:00 +0000

The total synthesis of new members of prenylated indole alkaloids exhibiting α-glucosidase activity is described. Asperdinones B, C, D, and E are characterized by the presence of a (3R)-3-indolylmethylbenzodiazepine-2,5-dione unit at C-3 of C4-C7 prenylated indoles. Methods of direct and indirect prenylation of indole and tryptophan were explored. Different approaches were adopted for the functionalization of C4-C7 prenylindoles at C-3 using Negishi cross-coupling methods. The asperdinones are among the rare tryptophan-derived indole alkaloids which appear to have undergone epimerization due to genetic alteration of specific gene clusters that code for a (3R) configuration.

A resource to empirically establish drug exposure records directly from untargeted metabolomics data

Mon, 15 Dec 2025 00:00:00 +0000

Despite extensive efforts, extracting medication exposure information from clinical records remains challenging. To complement this approach, here we show the Global Natural Product Social Molecular Networking (GNPS) Drug Library, a tandem mass spectrometry (MS/MS) based resource designed for drug screening with untargeted metabolomics. This resource integrates MS/MS references of drugs and their metabolites/analogs with standardized vocabularies on their exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data, supporting flexible summarization at multiple ontology levels to align with different research goals. We demonstrate its application by stratifying participants in a human immunodeficiency virus (HIV) cohort based on detected drug exposures. We uncover drug-associated alterations in microbiota-derived N-acyl lipids that are not captured when stratifying...

Green genes from blue greens: challenges and solutions to unlocking the potential of cyanobacteria in drug discovery

Tue, 9 Dec 2025 00:00:00 +0000

Cyanobacteria are prolific producers of biologically active compounds that are important in influencing ecology, behavior of interacting organisms, and as leads in drug discovery efforts. Here we discuss the challenges faced by all natural product researchers, especially those that focus on cyanobacteria, and then describe progress that has been made in these areas. We also propose some solutions, paths forward, and thoughts for consideration on these challenges.

Molecules to medicine: advances in metabolomics for natural product drug discovery

Wed, 3 Dec 2025 00:00:00 +0000

Recent advances in metabolomics are accelerating natural product (NP) drug discovery. NPs possess diverse biological relevance and comprise a significant portion of our modern pharmacopeia. We highlight studies from the past two years with innovative discovery techniques, ranging from small sample analyses to large-scale data-driven approaches. We focus on nuclear magnetic resonance- and mass spectrometry-based metabolomics for their broad use and greatest advancements in the field. We highlight strategies that utilize computational tools to enable prioritization of samples based on structural novelty, cross-referencing structural data with bioactivity, and the development of innovative annotation techniques that surpass common library matching methods. We also look at the trajectory of metabolomic discovery of NPs over the last decade to inform how these platforms may further evolve. The goal is to enhance the likelihood and improve the efficiency of discovering NPs with pharmaceutical...

Evaluation of integrative oncology modalities for symptom management: a MASCC/SIO global survey

Fri, 7 Nov 2025 00:00:00 +0000

BackgroundWith growing evidence pointing towards the potential of integrative oncology modalities (IOM) in addressing cancer and cancer-treatment related symptoms, research on IOM utilization and implementation is warranted. This study examines global stakeholder perspectives on integrative oncology (IO) utilization for supportive cancer care.MethodsMembers of the Multinational Association of Supportive Care in Cancer (MASCC) and the Society for Integrative Oncology (SIO) completed a survey on the utilization of IOM for supportive cancer care. Descriptive statistics were used to assess demographic data, IOM usage patterns, IOM education, and financial considerations for utilizing IOM.ResultsAmong 344 participants representing eight geographical regions, 70% reported having utilized or recommended IOM and 79% perceived IOM to be underutilized in cancer supportive care. Acupuncture (48%), exercise classes (39%), nutrition (38%), breathing/yoga (38%) and personalized exercise (38%)...

Incidence and predictors of immune checkpoint inhibitor treatment–related cognitive impairment in a racial and ethnic diverse population

Tue, 4 Nov 2025 00:00:00 +0000

IntroductionImmune checkpoint inhibitors (ICI) have revolutionized cancer therapy in recent years. In addition to rejuvenating anti-cancer immunity, ICI may cause immune dysregulation, impacting homeostasis, including brain functions. Thus, the association of ICI with cognitive function needs further investigation. Using NIH’s PROMIS system, this study investigates self-reported cognitive impairment within a diverse cohort of ICI-treated patients. Additionally, we explore risk factors influencing self-reported cognitive function, including concurrent symptoms and racial/ethnic background.MethodsThis was a prospective, longitudinal study conducted between July 2021 and June 2023. Included patients were ≥ 18 years old, newly diagnosed with cancer, and scheduled to receive ICI therapy. Serial patient-reported outcomes (PROs) were collected from self-reported patient surveys at therapy initiation and while receiving treatment. Clinically significant cognitive impairment was defined...

Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke

Fri, 17 Oct 2025 00:00:00 +0000

The integrity of adherens and tight junctions is critical for blood-brain barrier (BBB) function in the healthy brain. Disassembly of cell junctions due to degradation of adherens and tight junction-associated proteins leads to acute BBB dysfunction after ischemic stroke, but the mechanisms of this process are not fully understood. Using genetic studies in mice coupled with histopathological analysis of the brains after ischemic stroke, we demonstrate that endothelial cell deletion of Rab7a, a small GTPase crucial for protein degradation through the endolysosomal system, reduces acute BBB leakage and improves neuronal health in mice after ischemic stroke by reducing the degradation of select adherens and tight junction proteins, and preserving the structural morphology of tight junctions at both confocal and electron microscopy level. Two pro-inflammatory cytokines, TNFα and IL1β, that are known to trigger disruption of paracellular barrier properties in primary brain endothelial...

An open, integrated platform for multiplexed bioluminescence microscopy

Wed, 1 Oct 2025 00:00:00 +0000

We report an imaging package to democratize all-in-one bioluminescence and fluorescence microscopy. The platform comprises three tools: PhasorViewer, a visualization suite to design experiments and identify optimal probe combinations; PhasorScope, an open-source, cost-effective microscopy framework to upgrade conventional microscopes; and PhasorAnalysis, a dedicated, user-friendly analysis pipeline to quantify phasor imaging data. We demonstrate the utility of the platform for multiplexed, simultaneous fluorescence and bioluminescence imaging with readily accessible optical reporters.

Antibodies raised against a structurally defined Aβ oligomer mimic protect human iPSC neurons from Aβ toxicity at sub-stoichiometric concentrations

Mon, 15 Sep 2025 00:00:00 +0000

Anti-Aβ antibodies are important tools for identifying structural features of aggregates of the Aβ peptide and are used in many aspects of Alzheimer's disease (AD) research. Our laboratory recently reported the generation of a polyclonal antibody, pAb2AT-L, that is moderately selective for oligomeric Aβ over monomeric and fibrillar Aβ and recognizes the diffuse peripheries of Aβ plaques in AD brain tissue but does not recognize the dense fibrillar plaque cores. This antibody was generated against 2AT-L, a structurally defined Aβ oligomer mimic composed of three Aβ-derived β-hairpins arranged in a triangular fashion and covalently stabilized with three disulfide bonds. In the current study, we set out to determine if pAb2AT-L is neuroprotective against toxic aggregates of Aβ and found that pAb2AT-L protects human iPSC-derived neurons from Aβ42-mediated toxicity at molar ratios as low as 1:100 antibody to Aβ42, with a ratio of 1:25 almost completely rescuing cell viability. Few...

Advancing Binding Affinity Calculations: A Non-Equilibrium Simulations Approach for Calculation of Relative Binding Free Energies in Systems with Trapped Waters

Sat, 30 Aug 2025 00:00:00 +0000

The formation of protein-ligand complexes involves displacement of water molecules that were previously occupying the protein's binding site. In some cases, however, some water molecules may not be displaced by the ligand's binding, and they can stabilize the complex by mediating the interactions between the ligand and the protein. A relative binding free energy (RBFE) calculation between two ligands, one of which binds to the protein with an intermediate water while the other displaces the water, can yield wrong results if the water fails to rearrange itself within the simulation timescale. Enhanced sampling methods have previously been used to address the sampling of such "trapped" waters, inserting or deleting waters in the protein's binding site during ligand transformation. While sometimes effective, the enhanced sampling methods typically require long simulation times to converge and may lead to differences in RBFE estimates (i.e., hysteresis) based on initial water placement....

Cyanobacteria Join the Kahalalide Conversation: Genome and Metabolite Evidence for Structurally Related Peptides

Thu, 28 Aug 2025 00:00:00 +0000

Kahalalide F is a cyclic depsipeptide with notable anticancer properties, initially discovered from the green alga Bryopsis sp. and its molluscan predator Elysia rufescens. Recent studies have pinpointed a bacterial endosymbiont of the green alga, Candidatus Endobryopsis kahalalidefaciens, as the true producer of kahalalide F. In the present work, we characterize a closely related kahalalide F analog, kahalalide Z₅, from the marine cyanobacterium Limnoraphis sp. collected in the Las Perlas Islands, Panama, and propose the structures of several related compounds by detailed MS analysis. To uncover novel metabolites and prioritize them for targeted isolation from this organism, we employed a robust metabolomics strategy combining LC-MS/MS with SMART NMR and DeepSAT, artificial intelligence platforms trained to infer chemical structures from ¹H-¹³C HSQC NMR data. This integrated approach annotated a compound with structural...

Acoustic Side Channel Attack Against DNA Synthesis Machines: Poster Abstract

Thu, 14 Aug 2025 00:00:00 +0000

Synthetic DNA molecules play an essential role in genomics research and are a promising, high-capacity data storage medium. Currently, researchers use automated DNA synthesizers to custom-build sequences of oligonucleotides (short DNA strands) using the nucleobases: Adenine (A), Guanine (G), Cytosine (C), and Thymine (T). Research laboratories invest large amounts of capital to engineer unique oligonucleotide sequences. In our work, we demonstrate the vulnerability of commonly used DNA synthesizers to acoustic side-channel attacks, where confidentiality can be breached to steal precious DNA sequences. We introduce a novel methodology to reverse engineer the acoustic noise generated by the DNA synthesizer and extract the type and order of the nucleobases delivered to the output. To the best of our knowledge, this is the first work which highlights the possibility of physical-to-cyber attacks in DNA synthesis technologies.

The XNA alphabet

Fri, 18 Jul 2025 00:00:00 +0000

Inspired by nature, chemists have spent the last 50 years systematically designing and synthesizing a vast array of sugar-modified nucleic acids, so-called xenonucleic acids (XNAs), collectively forming what we now describe as the XNA alphabet. Within the alphabet, systems can be categorized into two major groups: those capable of interacting with natural nucleic acids and those that do not cross-pair with DNA or RNA. The sugar component of XNAs plays a crucial role in defining their conformational space, which, in turn, influences their hybridization properties and potential applications across biotechnology and synthetic biology. This review provides an overview of sugar-modified XNA systems developed to date as well as the geometric parameters and physicochemical principles that have enhanced our understanding of XNA conformational behavior, particularly in relation to their orthogonality to (i.e. inability to cross-pair with) natural nucleic acids. These insights are essential...

Where positivity meets specificity: A designer peptide as a novel pore blocker of the voltage-gated potassium channel Kv1.5

Thu, 17 Jul 2025 00:00:00 +0000

Where positivity meets specificity: A designer peptide as a novel pore blocker of the voltage-gated potassium channel Kv1.5

Microglia Support Both the Singular Form of LTP Expressed by the Lateral Perforant Path and Episodic Memory

Wed, 16 Jul 2025 00:00:00 +0000

We report here that microglia exert a surprisingly discrete but functionally critical influence on synaptic plasticity in the mouse hippocampus. Treatment of adult male mice with colony-stimulating factor 1 receptor antagonist PLX5622 (PLX), with resultant depletion of forebrain microglia, did not disturb basal synaptic transmission at four synaptic connections in the hippocampus. Long-term potentiation (LTP) was also intact for three of these sites, but the singular, endocannabinoid-dependent form of LTP expressed by lateral perforant path (LPP) input to the dentate gyrus (DG) was severely impaired. The LPP-LTP defect occurred in conjunction with a pronounced increase in DG (but not neocortical) levels of 2-arachidonoylglycerol (2-AG), the retrograde (spine-to-terminal) endocannabinoid messenger that initiates LPP-LTP. Despite this, concentrations of the 2-AG synthetic enzyme diacylglycerol lipase were not affected by PLX treatment. Synaptic levels of the cannabinoid type 1 receptor,...

Enabling pan-repository reanalysis for big data science of public metabolomics data

Tue, 15 Jul 2025 00:00:00 +0000

Public untargeted metabolomics data is a growing resource for metabolite and phenotype discovery; however, accessing and utilizing these data across repositories pose significant challenges. Therefore, here we develop pan-repository universal identifiers and harmonized cross-repository metadata. This ecosystem facilitates discovery by integrating diverse data sources from public repositories including MetaboLights, Metabolomics Workbench, and GNPS/MassIVE. Our approach simplified data handling and unlocks previously inaccessible reanalysis workflows, fostering unmatched research opportunities.

In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures