Peer-reviewed journals are a critical part of the scientific landscape. While the so-called “publish or perish” model may not be perfect, publishing in a peer-reviewed journals does have its benefits. Most importantly, peer review ensures your research can be replicated—a core tenant of scientific research and discoveries. Publishing, especially in an open-access journal, allows others to find your work, build upon your findings, and ultimately push the field forward for the greater good.
In that spirit of sharing, Labcompare has compiled a list of recently published peer-reviewed articles from high-impact, open-access journals. Whether the journal article is in your field or not, read or share an article to help strengthen the web of reproducible scientific research.
1. Whole-genome sequencing of 490,640 UK Biobank participants
Published August 6 in Nature
Whole-genome sequencing provides an unbiased and complete view of the human genome and enables the discovery of genetic variation without the technical limitations of other genotyping technologies. Here we report on whole-genome sequencing of 490,640 UK Biobank participants, building on previous genotyping effort. This advance deepens our understanding of how genetics associates with disease biology and further enhances the value of this open resource for the study of human biology and health. Coupling this dataset with rich phenotypic data, we surveyed within- and cross-ancestry genomic associations and identified novel genetic and clinical insights. Although most associations with disease traits were primarily observed in individuals of European ancestries, strong or novel signals were also identified in individuals of African and Asian ancestries. With the improved ability to accurately genotype structural variants and exonic variation in both coding and UTR sequences, we strengthened and revealed novel insights relative to whole-exome sequencing analyses. This dataset, representing a large collection of whole-genome sequencing data that is available to the UK Biobank research community, will enable advances of our understanding of the human genome, facilitate the discovery of diagnostics and therapeutics with higher efficacy and improved safety profile, and enable precision medicine strategies with the potential to improve global health.
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2. A closed-loop bioelectronic patch for intelligent blood pressure management
Published August 5 in Science Advances
Cardiovascular diseases remain a leading cause of mortality due to passive and delayed drug interventions. This study introduces an intelligent blood pressure management system (BPMS) for real-time monitoring and adaptive intervention through a closed-loop framework integrating sensors, control circuits, and microneedle electrodes. A hierarchical microneedle architecture, featuring gold nanoparticle (Au NP) electrocatalysts and copper-nitrogen–doped carbon nanoribbon (Cu-NC NB) nanozymes, selectively catalyzes the in situ generation of nitric oxide (NO) for vasodilation. To enhance NO delivery, an electroosmotic flow (EOF) mechanism extends the diffusion range up to 4 millimeters through a porous microneedle (PMN) array, enabling effective vascular penetration. In vivo studies in rabbits and pigs confirm that BPMS dynamically regulates NO release in response to fluctuating blood pressure, achieving real-time hemodynamic control. This work pioneers a closed-loop strategy for continuous blood pressure monitoring and on-demand vasodilation, offering a transformative approach to the intelligent management of cardiovascular diseases.
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3. Cryosectioning-enhanced super-resolution microscopy for single-protein imaging across cells and tissues
Published August 7 in PNAS
DNA-points accumulation for imaging in nanoscale topography (DNA-PAINT) enables nanoscale imaging with virtually unlimited multiplexing and molecular counting. Here, we address challenges, such as variable imaging performance and target accessibility, that can limit its broader applicability. Specifically, we enhance its capacity for robust single-protein imaging and molecular counting by optimizing the integration of total internal reflection fluorescence microscopy with physical sectioning, in particular, Tokuyasu cryosectioning. Our method, tomographic and kinetically enhanced DNA-PAINT (tkPAINT), achieves 3 nm localization precision across diverse samples, enhanced imager binding, and improved cellular integrity. tkPAINT can facilitate molecular counting with DNA-PAINT inside the nucleus, as demonstrated through its quantification of the in situ abundance of RNA Polymerase II in both HeLa cells as well as mouse tissues. Anticipating that tkPAINT could become a versatile tool for the exploration of biomolecular organization and interactions across cells and tissues, we also demonstrate its capacity to support multiplexing, multimodal targeting of proteins and nucleic acids, and three-dimensional (3D) imaging.
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4. Modular Synthetic Platform for the Elaboration of Fragments in Three Dimensions for Fragment-Based Drug Discovery
Published July 30 in the Journal of the American Chemical Society
Fragment-based drug discovery (FBDD) is a key strategy employed in the hit-to-lead phase of pharmaceutical development. The rate-limiting step of this process is often identifying and optimizing synthetic chemistry suitable for fragment elaboration, especially in three dimensions (3-D). To address this limitation, we herein present a modular platform for the systematic and programmable elaboration of two-dimensional (2-D) fragment hits into lead-like 3-D compounds, utilizing nine bifunctional building blocks that explore a range of vectors in 3-D. The building blocks comprise (i) rigid sp3-rich bicyclic cyclopropane-based structures to fix the vectors and (ii) two synthetic handles─a protected cyclic amine and a cyclopropyl N-methyliminodiacetic acid (MIDA) boronate. To validate our approach, we present (i) multigram-scale synthesis of each 3-D building block; (ii) Suzuki-Miyaura cross-coupling reactions of the cyclopropyl BMIDA functionality with aryl bromides; and (iii) N-functionalization (via commonplace medicinal chemistry toolkit reactions) of arylated products to deliver 3-D lead-like compounds. Each building block accesses a distinct 3-D exit vector, as shown by analysis of the lowest energy conformations of lead-like molecules using RDKit, and by X-ray crystallography of pyrimidine methanesulfonamide derivatives. Since the synthetic methodology is established in advance of fragment screening and utilizes robust chemistry, the elaboration of fragment hits in 3-D for biochemical screening can be achieved rapidly. To provide proof-of-concept, starting from the drug Ritlecitinib, the development of inhibitors of Janus kinase 3 (JAK3) around a putative pyrrolopyrimidine 2-D fragment hit was explored, streamlining the discovery of a novel and selective JAK3 inhibitor with IC50 = 69 nM.
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5. OmicsTweezer: A distribution-independent cell deconvolution model for multi-omics Data
Published on July 16 in Cell Genomics
Cell deconvolution estimates cell type proportions from bulk omics data, enabling insights into tissue microenvironments and disease. However, practical applications are often hindered by batch effects between bulk data and referenced single-cell data, a challenge that is frequently overlooked. To address this discrepancy, we developed OmicsTweezer, a distribution-independent cell deconvolution model. By integrating optimal transport with deep learning, OmicsTweezer aligns simulated and real data in a shared latent space, effectively mitigating data shifts and inter-omics distribution differences. OmicsTweezer is versatile, capable of deconvolving bulk RNA-seq, bulk proteomics, and spatial transcriptomics. Extensive evaluations on simulated and real-world datasets demonstrate its robustness and accuracy. Furthermore, applications in prostate and colon cancer showcase OmicsTweezer’s ability to identify biologically meaningful cell types. As a unified deconvolution framework for multi-omics data, OmicsTweezer offers an efficient and powerful tool for studying disease microenvironments.
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