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Effects of pre-oxidation temperature and air volume on oxidation thermogravimetric and functional group change of lignite

PLoS ONE Baoshan Jia, Zihao Chai, Wanting Zhao et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0316705

To investigate the impact of the oxidation temperature and variations in airflow conditions on coal spontaneous combustion characteristics, pre-oxidized coal samples were prepared using a programmed temperature rise method. Synchronous thermal analysis experiments and Fourier transform infrared spectroscopy were conducted to explore changes in the thermal effects and functional group content of the coal samples, respectively. The results indicate that variations in pre-oxidation conditions primarily in fluence the activation temperature and maximum weight loss temperature of the coal samples, while exerting a lesser impact on the critical temperature and ignition point. Variations in air volume conditions predominantly affect the content of Ar-C-O- and -CH2 & -CH3 in the oxygen-containing functional group region. The trend of the average activation energy within a conversion rate range of 0.2 to 0.6 of pre-oxidized coal samples changing with the increased of pre-oxidation temperature under the air flow conditions of 25mL/min and 50mL/min is consistent, but opposite to that under the air flow conditions of 100mL/min and 200mL/min. Compared to raw coal, under an airflow rate of 50 mL/min and when oxidized to 110°C, the coal sample exhibits an increase in the content of OH…OH, accompanied by reductions in the critical temperature, activation temperature, ignition point, and maximum weight loss temperature to varying degrees, thereby rendering it more susceptible to oxidative spontaneous combustion.

The origin of color categories

Proceedings of the National Academy of Sciences Daniel J. Garside, Audrey L. Y. Chang, Hannah M. Selwyn et al. Jan 07, 2025 DOI: 10.1073/pnas.2400273121

To what extent does concept formation require language? Here, we exploit color to address this question and ask whether macaque monkeys have color concepts evident as categories. Macaques have similar cone photoreceptors and central visual circuits to humans, yet they lack language. Whether Old World monkeys such as macaques have consensus color categories is unresolved, but if they do, then language cannot be required. If macaques do not have color categories, then color categories in humans are unlikely to derive from innate properties of visual encoding and likely to depend on cognitive abilities such as language that differ between monkeys and humans. We tested macaques by adapting a match-to-sample paradigm used in humans to uncover color categories from errors in matches, and we analyzed the data using computational simulations that assess the possibility of unrecognized distortions in the perceptual uniformity of color space. The results provide evidence that humans have consensus cognitive color categories and macaques do not. One animal showed evidence for a private color category, demonstrating that monkeys have the capacity to form color categories even if they do not form consensus color categories. Taken together, the results imply that consensus color categories in humans, for which there is ample evidence, must depend upon language or other cognitive abilities.

The role of mitochondrial dysfunction in the cytotoxic synergistic effect of gemcitabine and arsenic on breast cancer

PLoS ONE Farshid Maleki, Somayeh Handali, Mohsen Rezaei Jan 07, 2025 DOI: 10.1371/journal.pone.0312424

Breast cancer is the most common type of cancer in women worldwide. A common approach to cancer treatment in clinical practice is to use a combination of drugs to enhance the anticancer activity of drugs while reducing their side effects. In this regard, we evaluated the effectiveness of combined treatment with gemcitabine (GCB) and arsenic (ATO) and how they affect the cell death pathway in cancer cells. Cytotoxic activity of drugs individually or combined against MDA-MB-231 and MCF-7 was performed by MTT method and isobolographic analysis was used to determine the interaction between these factors. The combination of ATO and GCB showed synergistic anti-cancer activity (CI < 1) in both cancer cell lines. The combination of ATO and GCB induced sub-G1 phase arrest, apoptosis and death rates in MCF-7 and MDA-MB-231 cells. The apoptotic response induced by the combination of GCB and ATO was dependent on caspase 3/7. Combined treatment with mitochondrial membrane potential (MMP) reduction and increased reactive oxygen species (ROS) production caused mitochondrial dysfunction. Co-treatment significantly reduced catalase (CAT) activity in both cancer cells compared to the control group and cells treated with each monotherapy. A significant decrease in cellular GSH was observed in cancer cells treated with ATO and GCB. In addition, migration and invasion were significantly reduced in breast cancer cells treated with the combination of ATO and GCB compared to cells treated with ATO and GCB. In conclusion, the combined treatment of ATO and GCB synergistically increased the anti-cancer activity, and these findings provide an effective approach for the treatment of breast cancer. To the best of our knowledge, this is the first study showing promising results for combination therapy with ATO and GCB in breast cancer.

Pseudogap in electron-doped cuprates: Strong correlation leading to band splitting

Proceedings of the National Academy of Sciences Masafumi Horio, Shiro Sakai, Hakuto Suzuki et al. Jan 07, 2025 DOI: 10.1073/pnas.2406624122

The pseudogap phenomena have been a long-standing mystery of the cuprate high-temperature superconductors. The pseudogap in the electron-doped cuprates has been attributed to band folding due to antiferromagnetic (AFM) long-range order or short-range correlation. We performed an angle-resolved photoemission spectroscopy study of the electron-doped cuprates Pr 1.3− x La 0.7 Ce x CuO 4 showing spin-glass, disordered AFM behaviors, and superconductivity at low temperatures and, by measurements with fine momentum cuts, found that the gap opens on the unfolded Fermi surface rather than the AFM Brillouin zone boundary. The gap did not show a node, following the full symmetry of the Brillouin zone, and its magnitude decreased from the zone-diagonal to ( π ,0) directions, opposite to the hole-doped case. These observations were reproduced by cluster dynamical-mean-field-theory calculation, which took into account electron correlation precisely within a (CuO 2 ) 4 cluster. The present experimental and theoretical results are consistent with the mechanism that electron or hole doping into a Mott insulator creates an in-gap band that is separated from the upper or lower Hubbard band by the pseudogap.

Factors associated with the delay in diagnosis of extrapulmonary tuberculosis at the patient and health system level: A study from a rural setting in India

PLoS ONE Shoaib Hassan, Reza Yaesoubi, Ole Bjørgaas Helle Magnus et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0316273

Background With the proportion of tuberculosis cases that are extrapulmonary tuberculosis (EPTB) increasing in recent years, understanding and addressing factors contributing to the prolonged time to diagnosis (TTD) of EPTB patients is vital. Methods We enrolled presumptive EPTB patients for a cohort study from 2018–2020 in Ujjain, India. Based on a structured questionnaire, the patients were interviewed for socio-demographic and clinical information, including previously visited health facilities (HF) for this illness. We analysed patients’ TTD, healthcare access, and referral pathways. Findings EPTB (54%) and non-TB (58%) patients visited dispensaries during their first visit to a formal HF. Patients visited multiple HFs, including dispensaries (54%) and regional hospitals (32%), during 1–4 visits but did not receive an appropriate diagnosis. Less than 2% of the patients accessed private HFs. Most of the adult EPTB (83%) and non-TB (76%) patients were self-referred to our study site, where they were diagnosed. Our statistical models highlighted low-middle income groups, longer distances and longer travel time to HFs, and potentially less-empowered occupations as housewives with a prolonged TTD. Patients with a longer wait, including travel time, had a shorter TTD. Conclusion We found individual, societal-level, and structural barriers to healthcare access and utilisation and their association with diagnostic delay among adult and paediatric EPTB patients.

Protein dynamics underlies strong temperature dependence of heat receptors

Proceedings of the National Academy of Sciences Andrew Njagi Mugo, Ryan Chou, Feng Qin Jan 07, 2025 DOI: 10.1073/pnas.2406318121

Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals. Despite intensive studies, however, the nature of the temperature sensor domain in these channels remains elusive. By direct calorimetry of TRPV1 proteins, we have recently provided a proof of principle that temperature sensing by ion channels may diverge from the conventional allosterity theory; rather it is intimately linked to inherent thermal instability of channel proteins. Here, we tackle the generality of the hypothesis and provide key molecular pieces of evidence on the coupling of thermal transitions in the channels. We show that while wild-type channels possess a single concerted thermal transition peak, the chimera, in which strong temperature dependence becomes disrupted, results in multitransition peaks, and the activation enthalpies are accordingly reduced. The data show that the coupling with protein unfolding drives up the energy barrier of activation, leading to a strong temperature dependence of opening. Furthermore, we pinpoint the proximal N-terminus of the channels as a linchpin in coalescing different parts of the channels into concerted activation. Thus, we suggest that coupled interaction networks in proteins underlie the strong temperature dependence of temperature receptors.

Solar radiation model and optimization of asymmetric large-span externally insulated plastic greenhouses

PLoS ONE Chuanqing Wang, Kai Liu, Hongyu Ma et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0309734

To improve the light environment of asymmetric large-span externally insulated plastic greenhouses, a solar radiation model that considers the projection path equations of the insulation quilts and validated the model was established. The model was employed to investigate the impact of different heights, spans, and north lighting projection lengths on the greenhouses’ light environment. The results revealed that ground radiation interception, a key component of winter lighting, was most influenced by height, followed by span, and least influenced by the projection length of the north lighting roof. Additionally, ground radiation spatial uniformity was most affected by height, followed by the projection length of the north lighting roof, and least influenced by span. The optimization objectives for solar radiation were set to maximize solar radiation interception and minimize the coefficient of variation. The optimal structural parameters for the asymmetric large-span externally insulated plastic greenhouse were determined using the NSGA-II method and the entropy weight-TOPSIS method: the height of 6.97 m, and the projection length of north lighting roof is 7.44 m for a greenhouse with a span of 20.00 m. Compared to the initial greenhouse, the optimized design enhances both radiation interception performance and ensures uniform light distribution. These results offer valuable theoretical guidance for greenhouse construction.

Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe <i>Eubacterium limosum</i>

Proceedings of the National Academy of Sciences Saisuki Putumbaka, Gerrit J. Schut, Michael P. Thorgersen et al. Jan 07, 2025 DOI: 10.1073/pnas.2411809121

Eubacterium limosum is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by E. limosum has not been explored. We show that E. limosum growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by E. limosum is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.

The ambiguous role of partially protected marine protected areas in Australia: Results from a systematic literature review

PLoS ONE Genevieve A. C. Phillips, Emily Ogier, Ian Dutton et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0307324

Marine protected areas (MPAs) are an important tool in helping to protect biodiversity in the oceans. Recent ratification of the Kunming-Montreal Global Biodiversity Framework (GBF) has ensured that globally we are committed to effectively protecting 30% of the world’s oceans by 2030, in MPAs. In Australia there is considerable interest in the potential benefits that partially protected areas (PPAs) may provide. However, a consistent definition of a PPA is currently lacking, and urgently needed to conduct quantitative analyses of PPAs. We conducted a systematic literature review to understand the current knowledge surrounding PPAs and their potential benefits. We define a PPA, characterise PPA implementation in Australia, and present results for the outcomes of PPAs in terms of ecological, economic, and social indicators. Our review suggests that although 45% of Australia’s marine environment is within MPAs, 61% of MPAs provide only partial protection. The Northern Territory (100%), New South Wales (81%), and Queensland (79.8%) have the highest percentage of MPAs that are partially protected, compared to Tasmania which has the smallest percentage of partially protected MPAs (13.12%). Tasmania also has the smallest percentage cover of MPAs (6.49% state waters). Most PPA management plans did not contain quantifiable Key Performance Indicators (KPIs) to be able to effectively monitor the progress of these PPAs against the stated outcomes. We find the benefits of PPAs to be ambiguous: PPAs generally provide benefits when compared to ‘open’ ocean, however this is not a consistent result. There are no PPAs that provide greater overall benefits when compared to fully protected MPAs. Only one state (South Australia) and the Commonwealth (Australian Marine Parks) are collecting publicly available baseline data to facilitate quantitative monitoring of PPAs. Contrary to fisheries management, there were no plans of action if the declared MPAs and PPAs failed to meet their declared objectives and goals. Some PPAs within Australia appear to be incompatible with conservation priorities according to the recent “MPA Guide” classification framework. This study highlights the need for clearer management rationale and plans for PPAs in Australia, as these comprise the majority of MPAs in Australia’s Exclusive Economic Zone.

Integrating climate and physical constraints into assessments of net capture from direct air capture facilities

Proceedings of the National Academy of Sciences Patrick Shorey, Ahmed Abdulla Jan 07, 2025 DOI: 10.1073/pnas.2410824121

Limiting climate change to targets enshrined in the Paris Agreement will require both deep decarbonization of the energy system and the deployment of carbon dioxide removal at potentially large scale (gigatons of annual removal). Nations are pursuing direct air capture to compensate for inertia in the expansion of low-carbon energy systems, decarbonize hard-to-abate sectors, and address legacy emissions. Global assessments of this technology have failed to integrate factors that affect net capture and removal cost, including ambient conditions like temperature and humidity, as well as emission factors of electricity and natural gas systems. We present an integrated assessment of the global deployment potential of this technology. Employing a chemical process model, climate data, grid emission factors, and fugitive methane emission factors, we predict critical performance metrics, including carbon dioxide capture rates, and water-, energy-, and emissions-intensity of capture. Our results support investors and policy makers as they site facilities and develop credible policy instruments to support expansion.

Optimization design and application of library face recognition access control system based on improved PCA

PLoS ONE Na Lin, Yan Ding, Yulei Tan Jan 07, 2025 DOI: 10.1371/journal.pone.0313415

The application of face recognition technology in Library Access Control System (LACS) has an important impact on improving the security and management efficiency of the library. However, the traditional face recognition methods have some limitations in the face of complex environmental conditions such as illumination and posture change. To solve this problem, an improved method combining the Aggregating Spatial Embeddings for Face Recognition (ASEF) algorithm and Principal Component Analysis (PCA) is proposed. The PCA algorithm is optimized by introducing beta prior and full probability Bayesian model. In addition, the research also integrates K-means Clustering Algorithm (KA) to further improve the accuracy and efficiency of face recognition. The experiment showed that the improved PCA method had an average recognition rate of 92.6%, an average recognition speed of 0.40s, and higher accuracy compared to other related methods, reaching 96%. In practical applications, the system quickly and accurately completes the identification of personnel entry and exit, and improves the efficiency and security of library access management.

Genesis and regulation of C-terminal cyclic imides from protein damage

Proceedings of the National Academy of Sciences Wenqing Xu, Zhenguang Zhao, Matthew Su et al. Jan 07, 2025 DOI: 10.1073/pnas.2415976121

C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail. Here, we characterize the primary and secondary structures of peptides and proteins that promote intrinsic formation of C-terminal cyclic imides in comparison to deamidation, a related form of protein damage. Extrinsic effects from solution properties and stressors on the cellular proteome additionally promote C-terminal cyclic imide formation on proteins like glutathione synthetase that are susceptible to aggregation if the protein damage products are not removed by CRBN. This systematic investigation provides insight into the regions of the proteome that are prone to these unexpectedly frequent modifications, the effects of this form of protein damage on protein stability, and the biological role of CRBN.

Survival machine learning methods for mortality prediction after heart transplantation in the contemporary era

PLoS ONE Lathan Liou, Elizabeth Mostofsky, Laura Lehman et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0313600

Although prediction models for heart transplantation outcomes have been developed previously, a comprehensive benchmarking of survival machine learning methods for mortality prognosis in the most contemporary era of heart transplants following the 2018 donor heart allocation policy change is warranted. This study assessed seven statistical and machine learning algorithms–Lasso, Ridge, Elastic Net, Cox Gradient Boost, Extreme Gradient Boost Linear, Extreme Gradient Boost Tree, and Random Survival Forests in a post-policy cohort of 7,160 adult heart-only transplant recipients in the Scientific Registry of Transplant Recipients (SRTR) database who received their first transplant on or after October 18, 2018. A cross-validation framework was designed in mlr. Model performance was also compared in a seasonally-matched pre-policy cohort. In the post-policy cohort, Random Survival Forests and Cox Gradient Boost had the highest performances with C-indices of 0.628 and 0.627. The relative importance of some predictive variables differed between the pre-policy and post-policy cohorts, such as the absence of ECMO in the post-policy cohort. Survival machine learning models provide reasonable prediction of 1-year posttransplant mortality outcomes and continual updating of prediction models is warranted in the contemporary era.

Mechanism-guided engineering of a minimal biological particle for genome editing

Proceedings of the National Academy of Sciences Wayne Ngo, Julia Peukes, Alisha Baldwin et al. Jan 07, 2025 DOI: 10.1073/pnas.2413519121

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization. Here, we show that Cas9 RNP nuclear delivery is independent of the native lentiviral capsid structure. Instead, EDV-mediated genome editing activity corresponds directly to the number of nuclear localization sequences on the Cas9 enzyme. EDV structural analysis using cryo-electron tomography and small molecule inhibitors guided the removal of ~80% of viral residues, creating a minimal EDV (miniEDV) that retains full RNP delivery capability. MiniEDVs are 25% smaller yet package equivalent amounts of Cas9 RNPs relative to the original EDVs and demonstrated increased editing in cell lines and therapeutically relevant primary human T cells. These results show that virally derived particles can be streamlined to create efficacious genome editing delivery vehicles with simpler production and manufacturing.

Integrative metabolomics and transcriptomics profiling reveals differential expression of flavonoid synthesis in Ophiopogon japonicus (L. f.) Ker-Gawl. in adaptation to drought

PLoS ONE Tingting Cheng, Juan Lin, Xia Zhou et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0313580

Drought is one of the consequences of climate change that severely affects plant growth and development. Ophiopogon japonicus (L. f.) Ker-Gawl. (Chinese name: Chuanmaidong, abbreviated as CMD) is a commonly used herbaceous plant whose growth and development are strongly affected by drought. Here, we comprehensively analyzed the transcriptomic and metabolic responses of two CMD varieties (EP and CP) to drought stress. CP utilized a small number of differentially expressed genes to regulate a greater number of differential metabolites compared to EP, suggesting that it may be more drought tolerant. In addition, integrated transcriptome and metabolome analyses revealed that transcription factors such as WRKY, TIFY, and C2H2 regulate flavonoid synthesis in CMD. These findings provide ideas for in-depth analysis of the mechanism of CMD against drought stress, and provide a theoretical basis for breeding high-quality drought-tolerant varieties.

Structural insight into sodium ion pathway in the bacterial flagellar stator from marine <i>Vibrio</i>

Proceedings of the National Academy of Sciences Tatsuro Nishikino, Norihiro Takekawa, Jun-ichi Kishikawa et al. Jan 07, 2025 DOI: 10.1073/pnas.2415713122

Many bacteria swim in liquid or swarm on surface using the flagellum rotated by a motor driven by specific ion flow. The motor consists of the rotor and stator, and the stator converts the energy of ion flow to mechanical rotation. However, the ion pathway and the mechanism of stator rotation coupled with specific ion flow are still obscure. Here, we determined the structures of the sodium-driven stator of Vibrio , namely PomAB, in the presence and absence of sodium ions and the structure with its specific inhibitor, phenamil, by cryo-electron microscopy. The structures and following functional analysis revealed the sodium ion pathway, the mechanism of ion selectivity, and the inhibition mechanism by phenamil. We propose a model of sodium ion flow coupled with the stator rotation based on the structures. This work provides insights into the molecular mechanisms of ion specificity and conversion of the electrochemical potential into mechanical functions.

Innovameter: Agent-based modeling of innovation determinants in American and European countries

PLoS ONE Arles Rodríguez, Mercedes Gaitán-Angulo, Melva Inés Gómez-Caicedo et al. Jan 07, 2025 DOI: 10.1371/journal.pone.0313756

This article discusses the dynamics of innovation in America and Europe, focusing on variables such as access to technology, education, and life expectancy. To do this, the article proposes an agent-based model called the Innovameter. The dependent variable is the Global Innovation Index. The paper focuses on data analysis through correlation analysis and multiple hierarchical regressions to determine the contribution of specific variables related to the pillars of the Global Innovation Index and indicators of the Human Development Index. After analyzing the data, an agent-based model was built to parameterize these main variables by defining two levels of abstraction: at the global level, there is the country, where birth rates, life expectancy, ICT use, and research and development are defined. At the local level, we define the individuals who have an age, years of schooling, and income. A series of experiments were conducted by selecting data from 30 countries. From the results of the experiments, a nonparametric correlation analysis was performed, and correlation indices were obtained indicating a relationship between the predicted outcomes and the outcomes in the global index. The proposed model aims to provide suggestions on how the different variables can become the norm in most of the countries studied.

Palmitoylation-dependent association with Annexin II directs hepatitis E virus ORF3 sorting into vesicles and quasi-enveloped virions

Proceedings of the National Academy of Sciences Xing Liu, Tianxu Liu, Zhen Shao et al. Jan 07, 2025 DOI: 10.1073/pnas.2418751122

Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear. Here, we demonstrate that the HEV ORF3 protein possesses an inherent capacity for self-secretion and that palmitoylation at two cysteine residues within the ORF3 N-terminal region is essential for its secretion and quasi-enveloped virus formation. We further found that only palmitoylated ORF3 proteins hijacked Annexin II for transport to the cytoskeleton and are then directed into multivesicular bodies through the nSMase-endosomal sorting complexes required for transport-III pathway for secretion. Finally, we show that infection of gerbils with HEV mutants harboring mutations at palmitoylation sites within ORF3 showed no fecal viral shedding but competent replication in the liver. Our study fills a gap in the understanding of the assembly and release of quasi-enveloped virions mediated by ORF3 and offers the potential for designing therapeutic strategies to control HEV infection.

Profile of Stefan W. Hell

Proceedings of the National Academy of Sciences Sandeep Ravindran Jan 07, 2025 DOI: 10.1073/pnas.2424369121

Modular DNA origami–based electrochemical detection of DNA and proteins

Proceedings of the National Academy of Sciences Byoung-jin Jeon, Matteo M. Guareschi, Jaimie Marie Stewart et al. Jan 07, 2025 DOI: 10.1073/pnas.2311279121

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte. Here, we demonstrate a modular electrochemical biosensor, built from DNA origami, which is easily adapted to diverse molecules by merely replacing its analyte binding domains. Instead of relying on a unique nanometer-scale movement of a single redox reporter, all sensor variants rely on the same 100-nm scale conformational change, which brings dozens of reporters close enough to a gold electrode surface that a signal can be measured via square-wave voltammetry, a standard electrochemical technique. To validate our sensor’s mechanism, we used single-stranded DNA as an analyte, and optimized the number of redox reporters and various linker lengths. Adaptation of the sensor to streptavidin and Platelet-Derived Growth Factor-BB (PDGF-BB) analytes was achieved by simply adding biotin or anti-PDGF aptamers to appropriate DNA linkers. Geometrically optimized streptavidin sensors exhibited signal gain and limit of detection markedly better than comparable reagentless electrochemical sensors. After use, the same sensors could be regenerated under mild conditions: Performance was largely maintained over four cycles of DNA strand displacement and rehybridization. By leveraging the modularity of DNA nanostructures, our work provides a straightforward route to the single-step quantification of arbitrary nucleic acids and proteins.