bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing
Authors: Arora Nisha , Hazra Jagadish P. , Roy Sandip , Bhati Gaurav K. , Gupta Sarika , Yogendran K. P. , Chaudhuri Abhishek , Sagar Amin , Rakshit Sabyasachi
Published: February 2024

Tip-links in the inner ear convey force from sound and trigger mechanotransduction. Here, we present evidence that tip-links (collectively as heterotetrameric complexes of cadherins) function as force filters during mechanotransduction. Our force-clamp experiments reveal that the tip-link complexes show slip-ideal-slip bond dynamics. At low forces, the lifetime of the tip-link complex drops monotonically, indicating slip-bond dynamics. The ideal bond, rare in nature, is seen in an intermediate force regime where the survival of the complex remains constant over a wide range. At large forces, tip-links follow a slip bond and dissociate entirely to cut-off force transmission. In contrast, the individual tip-links (heterodimers) display slip-catch-slip bonds to the applied forces. While with a phenotypic mutant, we showed the importance of the slip-catch-slip bonds in uninterrupted hearing, our coarse-grained Langevin dynamics simulations demonstrated that the slip-ideal-slip bonds emerge as a collective feature from the slip-catch-slip bonds of individual tip-links.
Porous borders at the wild-crop interface promote weed adaptation in Southeast Asia
Authors: Li Lin-Feng , Pusadee Tonapha , Wedger Marshall J. , Li Ya-Ling , Li Ming-Rui , Lau Yee-Ling , Yap Soo-Joo , Jamjod Sansanee , Rerkasem Benjavan , Hao Yan , Song Beng-Kah , Olsen Kenneth M.
Published: February 2024

High reproductive compatibility between crops and their wild relatives can provide benefits for crop breeding but also poses risks for agricultural weed evolution. Weedy rice is a feral relative of rice that infests paddies and causes severe crop losses worldwide. In regions of tropical Asia where the wild progenitor of rice occurs, weedy rice could be influenced by hybridization with the wild species. Genomic analysis of this phenomenon has been very limited. Here we use whole genome sequence analyses of 217 wild, weedy and cultivated rice samples to show that wild rice hybridization has contributed substantially to the evolution of Southeast Asian weedy rice, with some strains acquiring weed-adaptive traits through introgression from the wild progenitor. Our study highlights how adaptive introgression from wild species can contribute to agricultural weed evolution, and it provides a case study of parallel evolution of weediness in independently-evolved strains of a weedy crop relative.
Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn
Authors: Liebhoff Anna-Maria , Venkataraman Thiagarajan , Morgenlander William R. , Na Miso , Kula Tomasz , Waugh Kathleen , Morrison Charles , Rewers Marian , Longman Randy , Round June , Elledge Stephen , Ruczinski Ingo , Langmead Ben , Larman H. Benjamin
Published: February 2024

We investigate a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To cover large antigenic spaces, we develop Dolphyn, a method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn compresses the size of a peptide library by 78% compared to traditional tiling, increasing the antibody-reactive peptides from 10% to 31%. We find that the immune system develops antibodies to human gut bacteria-infecting viruses, particularly E.coli-infecting Myoviridae. Cost-effective PhIP-Seq libraries designed with Dolphyn enable the assessment of a wider range of proteins in a single experiment, thus facilitating the study of the gut-immune axis.
Photocured room temperature phosphorescent materials from lignosulfonate
Authors: Guo Hongda , Cao Mengnan , Liu Ruixia , Tian Bing , Liu Shouxin , Li Jian , Li Shujun , Strehmel Bernd , James Tony D. , Chen Zhijun
Published: February 2024

Photocured room temperature phosphorescent (RTP) materials hold great potential for practical applications but are scarcely reported. Here, we develop photocured RTP materials (P-Lig) using a combination of lignosulfonate, acrylamide, and ionic liquid (1-ethyl-3-methylimidazolium bromide). With this design, lignosulfonate simultaneously serves as RTP chromophore and photoinitiator. Specifically, lignosulfonate in the ionic liquid generates radicals to polymerize the acrylamide upon UV irradiation. The resulting lignosulfonate is automatically confined in an as-formed crosslinked matrix to provide RTP. As such RTP with an emission lifetime of ~110 ms is observed from the confined lignosulfonate in P-Lig. Additionally, energy transfer occur between P-Lig and Rhodamine B (RhB), triggering red afterglow emission when P-Lig is in situ loaded with RhB (P-Lig/RhB). As a demonstration of potential applications, the P-Lig and P-Lig/RhB are used as photocured RTP coatings and RTP inks for fabricating 3D materials and for information encryption.
Large dynamics of a phase separating arginine-glycine-rich domain revealed via nuclear and electron spins
Authors: Sicoli Giuseppe , Sieme Daniel , Overkamp Kerstin , Khalil Mahdi , Backer Robin , Griesinger Christian , Willbold Dieter , Rezaei-Ghaleh Nasrollah
Published: February 2024

Liquid-liquid phase separation is the key process underlying formation of membrane-less compartments in cells. A highly dynamic cellular body with rapid component exchange is Cajal body (CB), which supports the extensive compositional dynamics of the RNA splicing machinery, spliceosome. Here, we select an arginine-glycine (RG)-rich segment of coilin, the major component of CB, establish its RNA-induced phase separation, and through combined use of nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) probes, interrogate its dynamics within the crowded interior of formed droplets. Taking advantage of glycine-based singlet-states, we show that glycines retain a large level of sub-nanoseconds dynamics inside the coilin droplets. Furthermore, the continuous-wave (CW) and electron-electron dipolar (PELDOR) and electron-nucleus hyperfine coupling EPR data (HYSCORE) support the RNA-induced formation of dynamic coilin droplets with high coilin peptide concentrations. The combined NMR and EPR data reveal the high dynamics of the RG-rich coilin within droplets and suggest its potential role in the large dynamics of CBs.
Quantifying the adaptive landscape of commensal gut bacteria using high-resolution lineage tracking
Authors: Wong Daniel P. G. H. , Good Benjamin H.
Published: February 2024

Gut microbiota can adapt to their host environment by rapidly acquiring new mutations. However, the dynamics of this process are difficult to characterize in dominant gut species in their complex in vivo environment. Here we show that the fine-scale dynamics of genome-wide transposon libraries can enable quantitative inferences of these in vivo evolutionary forces. By analyzing >400,000 lineages across four human Bacteroides strains in gnotobiotic mice, we observed positive selection on thousands of cryptic variants — most of which were unrelated to their original gene knockouts. The spectrum of fitness benefits varied between species, and displayed diverse tradeoffs over time and in different dietary conditions, enabling inferences of their underlying function. These results suggest that within-host adaptations arise from an intense competition between numerous contending variants, which can strongly influence their emergent evolutionary tradeoffs.
Extracting accurate materials data from research papers with conversational language models and prompt engineering
Authors: Polak Maciej P. , Morgan Dane
Published: February 2024

There has been a growing effort to replace manual extraction of data from research papers with automated data extraction based on natural language processing, language models, and recently, large language models (LLMs). Although these methods enable efficient extraction of data from large sets of research papers, they require a significant amount of up-front effort, expertise, and coding. In this work, we propose the method that can fully automate very accurate data extraction with minimal initial effort and background, using an advanced conversational LLM. consists of a set of engineered prompts applied to a conversational LLM that both identify sentences with data, extract that data, and assure the data’s correctness through a series of follow-up questions. These follow-up questions largely overcome known issues with LLMs providing factually inaccurate responses. can be applied with any conversational LLMs and yields very high quality data extraction. In tests on materials data, we find precision and recall both close to 90% from the best conversational LLMs, like GPT-4. We demonstrate that the exceptional performance is enabled by the information retention in a conversational model combined with purposeful redundancy and introducing uncertainty through follow-up prompts. These results suggest that approaches similar to , due to their simplicity, transferability, and accuracy are likely to become powerful tools for data extraction in the near future. Finally, databases for critical cooling rates of metallic glasses and yield strengths of high entropy alloys are developed using .
Heterogeneity of synaptic connectivity in the fly visual system
Authors: Cornean Jacqueline , Molina-Obando Sebastian , Gür Burak , Bast Annika , Ramos-Traslosheros Giordano , Chojetzki Jonas , Lörsch Lena , Ioannidou Maria , Taneja Rachita , Schnaitmann Christopher , Silies Marion
Published: February 2024

Visual systems are homogeneous structures, where repeating columnar units retinotopically cover the visual field. Each of these columns contain many of the same neuron types that are distinguished by anatomic, genetic and – generally – by functional properties. However, there are exceptions to this rule. In the 800 columns of the Drosophila eye, there is an anatomically and genetically identifiable cell type with variable functional properties, Tm9. Since anatomical connectivity shapes functional neuronal properties, we identified the presynaptic inputs of several hundred Tm9s across both optic lobes using the full adult female fly brain (FAFB) electron microscopic dataset and FlyWire connectome. Our work shows that Tm9 has three major and many sparsely distributed inputs. This differs from the presynaptic connectivity of other Tm neurons, which have only one major, and more stereotypic inputs than Tm9. Genetic synapse labeling showed that the heterogeneous wiring exists across individuals. Together, our data argue that the visual system uses heterogeneous, distributed circuit properties to achieve robust visual processing.
Smart touchless human–machine interaction based on crystalline porous cages
Authors: Wang Jinrong , Lin Weibin , Chen Zhuo , Nikolaeva Valeriia O. , Alimi Lukman O. , Khashab Niveen M.
Published: February 2024

The rise of touchless technology, driven by the recent pandemic, has transformed human-machine interaction (HMI). Projections indicate a substantial growth in the touchless technology market, nearly tripling from $13.6 billion in 2021 to an estimated $37.6 billion by 2026. In response to the pandemic-driven shift towards touchless technology, here we show an organic cage-based humidity sensor with remarkable humidity responsiveness, forming the basis for advanced touchless platforms in potential future HMI systems. This cage sensor boasts an ultrafast response/recovery time (1 s/3 s) and exceptional stability (over 800 cycles) across relative humidity (RH) changes from 11% to 95%. The crystal structure’s 3D pore network and luxuriant water-absorbing functional groups both inside and outside of the cage contribute synergistically to superior humidity sensing. Demonstrating versatility, we showcase this cage in smart touchless control screens and touchless password managers, presenting cost-effective and easily processable applications of molecularly porous materials in touchless HMI.
Directive giant upconversion by supercritical bound states in the continuum
Authors: Schiattarella Chiara , Romano Silvia , Sirleto Luigi , Mocella Vito , Rendina Ivo , Lanzio Vittorino , Riminucci Fabrizio , Schwartzberg Adam , Cabrini Stefano , Chen Jiaye , Liang Liangliang , Liu Xiaogang , Zito Gianluigi
Published: February 2024

Photonic bound states in the continuum (BICs), embedded in the spectrum of free-space waves1,2 with diverging radiative quality factor, are topologically non-trivial dark modes in open-cavity resonators that have enabled important advances in photonics3,4. However, it is particularly challenging to achieve maximum near-field enhancement, as this requires matching radiative and non-radiative losses. Here we propose the concept of supercritical coupling, drawing inspiration from electromagnetically induced transparency in near-field coupled resonances close to the Friedrich–Wintgen condition2. Supercritical coupling occurs when the near-field coupling between dark and bright modes compensates for the negligible direct far-field coupling with the dark mode. This enables a quasi-BIC field to reach maximum enhancement imposed by non-radiative loss, even when the radiative quality factor is divergent. Our experimental design consists of a photonic-crystal nanoslab covered with upconversion nanoparticles. Near-field coupling is finely tuned at the nanostructure edge, in which a coherent upconversion luminescence enhanced by eight orders of magnitude is observed. The emission shows negligible divergence, narrow width at the microscale and controllable directivity through input focusing and polarization. This approach is relevant to various physical processes, with potential applications for light-source development, energy harvesting and photochemical catalysis.
Twisted-layer boron nitride ceramic with high deformability and strength
Authors: Wu Yingju , Zhang Yang , Wang Xiaoyu , Hu Wentao , Zhao Song , Officer Timothy , Luo Kun , Tong Ke , Du Congcong , Zhang Liqiang , Li Baozhong , Zhuge Zewen , Liang Zitai , Ma Mengdong , Nie Anmin , Yu Dongli , He Julong , Liu Zhongyuan , Xu Bo , Wang Yanbin , Zhao Zhisheng , Tian Yongjun
Published: February 2024

Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1–5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.
Progressive unanchoring of Antarctic ice shelves since 1973
Authors: Miles Bertie W. J. , Bingham Robert G.
Published: February 2024

Mass loss of the Antarctic Ice Sheet has been driven primarily by the thinning of the floating ice shelves that fringe the ice sheet1, reducing their buttressing potential and causing land ice to accelerate into the ocean2. Observations of ice-shelf thickness change by satellite altimetry stretch back only to 1992 (refs. 1,3–5) and previous information about thinning remains unquantified. However, extending the record of ice-shelf thickness change is possible by proxy, by measuring the change in area of the surface expression of pinning points—local bathymetric highs on which ice shelves are anchored6. Here we measure pinning-point change over three epochs spanning the periods 1973–1989, 1989–2000 and 2000−2022, and thus by proxy infer changes to ice-shelf thickness back to 1973–1989. We show that only small localized pockets of ice shelves were thinning between 1973 and 1989, located primarily in the Amundsen Sea Embayment and the Wilkes Land coastline. Ice-shelf thinning spreads rapidly into the 1990s and 2000s and is best characterized by the proportion of pinning points reducing in extent. Only 15% of pinning points reduced from 1973 to 1989, before increasing to 25% from 1989 to 2000 and 37% from 2000 to 2022. A continuation of this trend would further reduce the buttressing potential of ice shelves, enhancing ice discharge and accelerating the contribution of Antarctica to sea-level rise.
B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4
Authors: Afzali Ali Maisam , Nirschl Lucy , Sie Christopher , Pfaller Monika , Ulianov Oleksii , Hassler Tobias , Federle Christine , Petrozziello Elisabetta , Kalluri Sudhakar Reddy , Chen Hsin Hsiang , Tyystjärvi Sofia , Muschaweckh Andreas , Lammens Katja , Delbridge Claire , Büttner Andreas , Steiger Katja , Seyhan Gönül , Ottersen Ole Petter , Öllinger Rupert , Rad Roland , Jarosch Sebastian , Straub Adrian , Mühlbauer Anton , Grassmann Simon , Hemmer Bernhard , Böttcher Jan P. , Wagner Ingrid , Kreutzfeldt Mario , Merkler Doron , Pardàs Irene Bonafonte , Schmidt Supprian Marc , Buchholz Veit R. , Heink Sylvia , Busch Dirk H. , Klein Ludger , Korn Thomas
Published: February 2024

Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which the water-channel protein AQP4 is the target antigen1. The immunopathology in neuromyelitis optica is largely driven by autoantibodies to AQP42. However, the T cell response that is required for the generation of these anti-AQP4 antibodies is not well understood. Here we show that B cells endogenously express AQP4 in response to activation with anti-CD40 and IL-21 and are able to present their endogenous AQP4 to T cells with an AQP4-specific T cell receptor (TCR). A population of thymic B cells emulates a CD40-stimulated B cell transcriptome, including AQP4 (in mice and humans), and efficiently purges the thymic TCR repertoire of AQP4-reactive clones. Genetic ablation of Aqp4 in B cells rescues AQP4-specific TCRs despite sufficient expression of AQP4 in medullary thymic epithelial cells, and B-cell-conditional AQP4-deficient mice are fully competent to raise AQP4-specific antibodies in productive germinal-centre responses. Thus, the negative selection of AQP4-specific thymocytes is dependent on the expression and presentation of AQP4 by thymic B cells. As AQP4 is expressed in B cells in a CD40-dependent (but not AIRE-dependent) manner, we propose that thymic B cells might tolerize against a group of germinal-centre-associated antigens, including disease-relevant autoantigens such as AQP4.
Targeted protein degradation via intramolecular bivalent glues
Authors: Hsia Oliver , Hinterndorfer Matthias , Cowan Angus D. , Iso Kentaro , Ishida Tasuku , Sundaramoorthy Ramasubramanian , Nakasone Mark A. , Imrichova Hana , Schätz Caroline , Rukavina Andrea , Husnjak Koraljka , Wegner Martin , Correa-Sáez Alejandro , Craigon Conner , Casement Ryan , Maniaci Chiara , Testa Andrea , Kaulich Manuel , Dikic Ivan , Winter Georg E. , Ciulli Alessio
Published: February 2024

Targeted protein degradation is a pharmacological modality that is based on the induced proximity of an E3 ubiquitin ligase and a target protein to promote target ubiquitination and proteasomal degradation. This has been achieved either via proteolysis-targeting chimeras (PROTACs)—bifunctional compounds composed of two separate moieties that individually bind the target and E3 ligase, or via molecular glues that monovalently bind either the ligase or the target1–4. Here, using orthogonal genetic screening, biophysical characterization and structural reconstitution, we investigate the mechanism of action of bifunctional degraders of BRD2 and BRD4, termed intramolecular bivalent glues (IBGs), and find that instead of connecting target and ligase in trans as PROTACs do, they simultaneously engage and connect two adjacent domains of the target protein in cis. This conformational change ‘glues’ BRD4 to the E3 ligases DCAF11 or DCAF16, leveraging intrinsic target–ligase affinities that do not translate to BRD4 degradation in the absence of compound. Structural insights into the ternary BRD4–IBG1–DCAF16 complex guided the rational design of improved degraders of low picomolar potency. We thus introduce a new modality in targeted protein degradation, which works by bridging protein domains in cis to enhance surface complementarity with E3 ligases for productive ubiquitination and degradation.
Research on the ratio of similar materials in water-absorbent mudstone based on fuzzy mathematics
Authors: Zeng Chunlin , Zhou Yuejin , Xiaoding Xu
Published: February 2024

To determine the suitability and credibility of similar water-absorbent mudstone materials in model experiments, the prototype mudstone parameter similarity index was determined based on the similarity theory. Similar materials use cement and Plaster as binders and quartz sand as aggregate. The sensitivity of similar indicators of similar materials to control factors was analyzed through range statistics. Multiple regression analysis was used to establish the quantitative relationship between each control factor and similar indicators. Finally, the optimal matching scheme was refined through the combination of fuzzy mathematics and analytic hierarchy process. The results show that the physical and mechanical property indicators of similar materials with different proportions have a wide distribution range, and under certain similar conditions, they can meet the requirements of rock model tests with different properties. The aggregate-binder ratio is a direct indicator of material density, elastic modulus, and compressive strength. The main controlling factors, material density, elastic modulus, and compressive strength all increase with the decrease in aggregate-binder ratio. The cement-plaster ratio is the main control factor of material water absorption, and the water absorption gradually decreases with the increase of the cement-plaster ratio. The formula obtained through linear analysis can better represent the changing trend and distribution characteristics of various parameters of similar materials with the aggregate-binder ratio and cement-plaster ratio, and initially optimize the proportioning scheme of similar materials. Use fuzzy mathematics to evaluate the membership degree of each parameter index of similar materials, and the optimal ratio scheme was further determined to improve the credibility of later model experiments.
Integrating artificial intelligence in osteosarcoma prognosis: the prognostic significance of SERPINE2 and CPT1B biomarkers
Authors: Qu Haishun , Jiang Jie , Zhan Xinli , Liang Yunxiao , Guo Quan , Liu Peifeng , Lu Ling , Yang Yanwei , Xu Weicheng , Zhang Yitian , Lan Shaohang , Chen Zeshan , Lu Yuanhong , Ou Yufu , Qin Yijue
Published: February 2024

The principal aim of this investigation is to identify pivotal biomarkers linked to the prognosis of osteosarcoma (OS) through the application of artificial intelligence (AI), with an ultimate goal to enhance prognostic prediction. Expression profiles from 88 OS cases and 396 normal samples were procured from accessible public databases. Prognostic models were established using univariate COX regression analysis and an array of AI methodologies including the XGB method, RF method, GLM method, SVM method, and LASSO regression analysis. Multivariate COX regression analysis was also employed. Immune cell variations in OS were examined using the CIBERSORT software, and a differential analysis was conducted. Routine blood data from 20,679 normal samples and 437 OS cases were analyzed to validate lymphocyte disparity. Histological assessments of the study's postulates were performed through immunohistochemistry and hematoxylin and eosin (HE) staining. AI facilitated the identification of differentially expressed genes, which were utilized to construct a prognostic model. This model discerned that the survival rate in the high-risk category was significantly inferior compared to the low-risk cohort (p < 0.05). SERPINE2 was found to be positively associated with memory B cells, while CPT1B correlated positively with CD8 T cells. Immunohistochemical assessments indicated that SERPINE2 was more prominently expressed in OS tissues relative to adjacent non-tumorous tissues. Conversely, CPT1B expression was elevated in the adjacent non-tumorous tissues compared to OS tissues. Lymphocyte counts from routine blood evaluations exhibited marked differences between normal and OS groups (p < 0.001). The study highlights SERPINE2 and CPT1B as crucial biomarkers for OS prognosis and suggests that dysregulation of lymphocytes plays a significant role in OS pathogenesis. Both SERPINE2 and CPT1B have potential utility as prognostic biomarkers for OS.
Hepa-ToxMOA: a pathway-screening method for evaluating cellular stress and hepatic metabolic-dependent toxicity of natural products
Authors: Park Se-Myo , Choi Mi-Sun , Kim Soojin , Jegal Hyun , Han Hyoung-Yun , Chun Hyang Sook , Kim Sang Kyum , Oh Jung-Hwa
Published: February 2024

In the field of drug discovery, natural products have emerged as therapeutic agents for diseases such as cancer. However, their potential toxicity poses significant obstacles in the developing effective drug candidates. To overcome this limitation, we propose a pathway-screening method based on imaging analysis to evaluate cellular stress caused by natural products. We have established a cellular stress sensing system, named Hepa-ToxMOA, which utilizes HepG2 cells expressing green fluorescent protein (GFP) fluorescence under the control of transcription factor response elements (TREs) for transcription factors (AP1, P53, Nrf2, and NF-κB). Additionally, to augment the drug metabolic activity of the HepG2 cell line, we evaluated the cytotoxicity of 40 natural products with and without S9 fraction-based metabolic activity. Our finding revealed different activities of Hepa-ToxMOA depending on metabolic or non-metabolic activity, highlighting the involvement of specific cellular stress pathways. Our results suggest that developing a Hepa-ToxMOA system based on activity of drug metabolizing enzyme provides crucial insights into the molecular mechanisms initiating cellular stress during liver toxicity screening for natural products. The pathway-screening method addresses challenges related to the potential toxicity of natural products, advancing their translation into viable therapeutic agents.
Insulin and IGF-1 have both overlapping and distinct effects on CD4+ T cell mitochondria, metabolism, and function
Authors: Kiernan Kaitlin , Alwarawrah Yazan , Nichols Amanda G. , Danzaki Keiko , MacIver Nancie J.
Published: February 2024

Insulin and insulin-like growth factor 1 (IGF-1) are metabolic hormones with known effects on CD4+ T cells through insulin receptor (IR) and IGF-1 receptor (IGF-1R) signaling. Here, we describe specific and distinct roles for these hormones and receptors. We have found that IGF-1R, but not IR, expression is increased following CD4+ T cell activation or following differentiation toward Th17 cells. Although both insulin and IGF-1 increase the metabolism of CD4+ T cells, insulin has a more potent effect. However, IGF-1 has a unique role and acts specifically on Th17 cells to increase IL-17 production and Th17 cell metabolism. Furthermore, IGF-1 decreases mitochondrial membrane potential and mitochondrial reactive oxygen species (mROS) in Th17 cells, providing a cytoprotective effect. Interestingly, both IR and IGF-1R are required for this effect of IGF-1 on mitochondria, which suggests that the hybrid IR/IGF-1R may be required for mediating the effect of IGF-1 on mitochondrial membrane potential and mROS production.
External validation of the rCAST for patients after in-hospital cardiac arrest: a multicenter retrospective observational study
Authors: Ishii Junki , Nishikimi Mitsuaki , Kikutani Kazuya , Kyo Michihito , Ohki Shingo , Ota Kohei , Fujino Mitsuhiro , Sakuraya Masaaki , Ohshimo Shinichiro , Shime Nobuaki
Published: February 2024

No established predictive or risk classification tool exists for the neurological outcomes of post-cardiac arrest syndrome (PCAS) in patients with in-hospital cardiac arrest (IHCA). This study aimed to investigate whether the revised post-cardiac arrest syndrome for therapeutic hypothermia score (rCAST), which was developed to estimate the prognosis of PCAS patients with out-of-hospital cardiac arrest (OHCA), was applicable to patients with IHCA. A retrospective, multicenter observational study of 140 consecutive adult IHCA patients admitted to three intensive care units. The area under the receiver operating characteristic curves (AUCs) of the rCAST for poor neurological outcome and mortality at 30 days were 0.88 (0.82–0.93) and 0.83 (0.76–0.89), respectively. The sensitivity and specificity of the risk classification according to rCAST for poor neurological outcomes were 0.90 (0.83–0.96) and 0.67 (0.55–0.79) for the low, 0.63 (0.54–0.74) and 0.67 (0.55–0.79) for the moderate, and 0.27 (0.17–0.37) and 1.00 (1.00–1.00) for the high-severity grades. All 22 patients classified with a high-severity grade showed poor neurological outcomes. The rCAST showed excellent predictive accuracy for neurological prognosis in patients with PCAS after IHCA. The rCAST may be useful as a risk classification tool for PCAS after IHCA.
Endothelium-related biomarkers enhanced prediction of kidney support therapy in critically ill patients with non-oliguric acute kidney injury
Authors: Salmito Francisco Thiago Santos , Mota Sandra Mara Brasileira , Holanda Francisco Márcio Tavares , Libório Santos Leticia , Silveira de Andrade Luana , Meneses Gdayllon Cavalcante , Lopes Nicole Coelho , de Araújo Leticia Machado , Martins Alice Maria Costa , Libório Alexandre Braga
Published: February 2024

Acute kidney injury (AKI) is a common condition in hospitalized patients who often requires kidney support therapy (KST). However, predicting the need for KST in critically ill patients remains challenging. This study aimed to analyze endothelium-related biomarkers as predictors of KST need in critically ill patients with stage 2 AKI. A prospective observational study was conducted on 127 adult ICU patients with stage 2 AKI by serum creatinine only. Endothelium-related biomarkers, including vascular cell adhesion protein-1 (VCAM-1), angiopoietin (AGPT) 1 and 2, and syndecan-1, were measured. Clinical parameters and outcomes were recorded. Logistic regression models, receiver operating characteristic (ROC) curves, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for analysis. Among the patients, 22 (17.2%) required KST within 72 h. AGPT2 and syndecan-1 levels were significantly greater in patients who progressed to the KST. Multivariate analysis revealed that AGPT2 and syndecan-1 were independently associated with the need for KST. The area under the ROC curve (AUC-ROC) for AGPT2 and syndecan-1 performed better than did the constructed clinical model in predicting KST. The combination of AGPT2 and syndecan-1 improved the discrimination capacity of predicting KST beyond that of the clinical model alone. Additionally, this combination improved the classification accuracy of the NRI and IDI. AGPT2 and syndecan-1 demonstrated predictive value for the need for KST in critically ill patients with stage 2 AKI. The combination of AGPT2 and syndecan-1 alone enhanced the predictive capacity of predicting KST beyond clinical variables alone. These findings may contribute to the early identification of patients who will benefit from KST and aid in the management of AKI in critically ill patients.
Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes
Authors: Malar Dicson Sheeja , Verma Kanika , Prasanth Mani Iyer , Tencomnao Tewin , Brimson James Michael
Published: February 2024

The COVID-19 pandemic caused by the SARS-CoV-2 virus has greatly affected global health. Emerging evidence suggests a complex interplay between Alzheimer’s disease (AD), diabetes (DM), and COVID-19. Given COVID-19’s involvement in the increased risk of other diseases, there is an urgent need to identify novel targets and drugs to combat these interconnected health challenges. Lysophosphatidic acid receptors (LPARs), belonging to the G protein-coupled receptor family, have been implicated in various pathological conditions, including inflammation. In this regard, the study aimed to investigate the involvement of LPARs (specifically LPAR1, 3, 6) in the tri-directional relationship between AD, DM, and COVID-19 through network analysis, as well as explore the therapeutic potential of selected anti-AD, anti-DM drugs as LPAR, SPIKE antagonists. We used the Coremine Medical database to identify genes related to DM, AD, and COVID-19. Furthermore, STRING analysis was used to identify the interacting partners of LPAR1, LPAR3, and LPAR6. Additionally, a literature search revealed 78 drugs on the market or in clinical studies that were used for treating either AD or DM. We carried out docking analysis of these drugs against the LPAR1, LPAR3, and LPAR6. Furthermore, we modeled the LPAR1, LPAR3, and LPAR6 in a complex with the COVID-19 spike protein and performed a docking study of selected drugs with the LPAR-Spike complex. The analysis revealed 177 common genes implicated in AD, DM, and COVID-19. Protein–protein docking analysis demonstrated that LPAR (1,3 & 6) efficiently binds with the viral SPIKE protein, suggesting them as targets for viral infection. Furthermore, docking analysis of the anti-AD and anti-DM drugs against LPARs, SPIKE protein, and the LPARs-SPIKE complex revealed promising candidates, including lupron, neflamapimod, and nilotinib, stating the importance of drug repurposing in the drug discovery process. These drugs exhibited the ability to bind and inhibit the LPAR receptor activity and the SPIKE protein and interfere with LPAR-SPIKE protein interaction. Through a combined network and targeted-based therapeutic intervention approach, this study has identified several drugs that could be repurposed for treating COVID-19 due to their expected interference with LPAR(1, 3, and 6) and spike protein complexes. In addition, it can also be hypothesized that the co-administration of these identified drugs during COVID-19 infection may not only help mitigate the impact of the virus but also potentially contribute to the prevention or management of post-COVID complications related to AD and DM.
Reimagining plastics waste as energy solutions: challenges and opportunities
Authors: Tan Angie F. J. , Yu Sam , Wang Cheng , Yeoh Guan Heng , Teoh Wey Yang , Yip Alex C. K.
Published: February 2024

Recent statistics portray a stark reality, particularly highlighting the inadequate recycling measures and the consequent environmental threats, most notably in developing nations. The global ramifications of plastic pollution are elucidated, specifically focusing on the alarming accumulation in regions such as the “Great Pacific Garbage Patch” and evolving waste management practices in Southeast Asian countries. We emphasize the significance of Waste-to-Energy (W2E) and Waste-to-Fuel (W2F) technologies, e.g., pyrolysis and gasification, for converting difficult-to-recycle plastic waste into a dense-energy source. However, we identify a critical gap in current research: the emission of CO2 during these processes. This perspective spotlights emergent CO2 capture and utilization technologies, underscoring their role as a robust turnkey solution in making W2E and W2F methods more sustainable and unleashing the huge potential of using waste plastics as a dense-energy source. The scientific community is urged to develop tailored solutions for reducing CO2 emissions in plastic waste conversion processes. This approach promotes circular resource utilization and realizes the socio-economic and environmental advantages of plastic waste utilization technologies, advocating their implementation in economically disadvantaged regions.
Effects of single and multiple nucleotide mutations on loop-mediated isothermal amplification
Authors: Moehling Taylor J. , Browne Erica R. , Meagher Robert J.
Published: February 2024

Nucleotide substitutions and deletions can slow or completely inhibit nucleic acid amplification compared to unmodified control samples.
Rapid synthesis of Pt(0) motors-microscrolls on a nickel surface via H2PtCl6-induced galvanic replacement reaction
Authors: Tolstoy Valeri , Nikitin Kirill , Kuzin Aleksei , Zhu Fenyang , Li Xing , Goltsman Gregory , Gorin Dmitry , Huang Gaoshan , Solovev Alexander A. , Mei Yongfeng
Published: February 2024

Pt(0) microscrolls are synthesized on Ni via galvanic replacement reaction, and corresponding catalytic motion in H2O2 solutions is demonstrated.
Leveraging Cas13a's trans-cleavage on RNA G-quadruplexes for amplification-free RNA detection
Authors: Li Tao , Chen Dongjuan , He Xiaoling , Li Zheyu , Xu Zhichen , Li Runchen , Zheng Bingxin , Hu Rui , Zhu Jiang , Li Ying , Yang Yunhuang
Published: February 2024

CRISPR-Cas13a is found to be able to trans-cleave RNA G4 and this is utilized for amplification-free RNA detection.
Reduction of CO2 in the presence of light via excited-state hydride transfer reaction in a NADPH-inspired derivative
Authors: Ostojić Bojana D. , Stanković Branislav , Đorđević Dragana S. , Schwerdtfeger Peter
Published: February 2024

Light-driven reduction of CO2 into formate by a NADPH-inspired derivative is analyzed with theoretical approach. The results show that this catalyst is a promising candidate for the photochemical reduction of CO2.
Plasmonic silver and gold nanoparticles: shape- and structure-modulated plasmonic functionality for point-of-caring sensing, bio-imaging and medical therapy
Authors: Hang Yingjie , Wang Anyang , Wu Nianqiang
Published: February 2024

Silver and gold nanoparticles have found extensive biomedical applications due to their strong localized surface plasmon resonance (LSPR) and intriguing plasmonic properties.
High-level analytical potential-energy-surface-based dynamics of the OH− + CH3CH2Cl SN2 and E2 reactions in full (24) dimensions
Authors: Nacsa András B. , Tokaji Csenge , Czakó Gábor
Published: February 2024

We report a full-dimensional ab initio analytical potential energy surface and a detailed dynamics investigation for the multi-pathway OH− + CH3CH2Cl reaction.
Synthesis of the dibenzo[b,d]azepine skeleton via a catalyst-free ring expansion domino reaction
Authors: Guo Tao , Hu Penghua , Li Jiaxin , Zhou Yujia , Zhang Panke , Zhao Yunhui , Zhu Congjun
Published: February 2024

A hitherto unreported catalyst-free ring expansion reaction of tetrahydroisoquinolines with o-alkynylarylaldehydes for the construction of the dibenzo[b,d]azepine skeleton is described.
Synthesis of glycerol carbonate using Li/Mg/K modified zeolite beta: a kinetic study
Authors: Gautam Priyanka , Barman Sanghamitra , Ali Amjad
Published: February 2024

In the present investigation, the transesterification of glycerol with dimethyl carbonate was studied in the presence of Li, Mg, and K-modified zeolite beta. Out of all the modified catalysts, Li-modified zeolite beta comes out to be the best catalyst for the synthesis of glycerol carbonate.
Design, synthesis, and evaluation of 1,4-naphthoquinone-chromene hybrids as potential anti-K562 and A549 agents
Authors: Zhang Wen-Hui , Zhang Bo , Pan Bo-Wen , Liu Xiong-Wei , Yin Zhi-Gang , Zhuo Yu-Zhou , Lei Chuan-wen , Zhou Ying
Published: February 2024

Two series of 1,4-naphthoquinone-chromone hybrids 4a (4aa–4ao) and 4b (4ba–4bq) were designed, synthesized and evaluated as antitumor agents.
Fabrication of polyaniline/waste sugarcane bagasse composite fillers for excellent anti-corrosion protective coatings
Authors: Yu Sidi , Liu Yuansong , Mo Rongcan , Li Ya , Zhou Zhongyang , Zhang Liangkun , Fan Bing , Cao Yuegang
Published: February 2024

Herein, biomass-based anti-corrosion composite fillers for water-based epoxy resin coatings, epoxy resin powder coatings, and efficient anticorrosive coatings were successfully prepared.
3D hierarchical Ti3C2Tx@NiCo2S4–RGO heterostructure hydrogels as free-standing electrodes for high-performance supercapacitors
Authors: Yin Dashu , Zhang Wenlei , Hao Shengcai
Published: February 2024

A high-energy supercapacitor device based on 3D hierarchical free-standing Ti3C2Tx@NiCo2S4–RGO heterostructure hydrogel electrodes is assembled.
Diagnosis of Mycobacterium tuberculosis using palladium–platinum bimetallic nanoparticles combined with paper-based analytical devices
Authors: Tung Cheng-Yang , Tsai Tsung-Ting , Chiu Ping-Yeh , Viter Roman , Ramanavičius Arũnas , Yu Cheng-Ju , Chen Chien-Fu
Published: February 2024

This study demonstrates that palladium–platinum bimetallic nanoparticles (Pd@Pt NPs) can be used as the nanozyme for highly sensitive Mycobacterium tuberculosis diagnosis on a multi-layer paper-based analytical device.
Nanoparticles traversing the extracellular matrix induce biophysical perturbation of fibronectin depicted by surface chemistry
Authors: Guo Xing , Yang Lin , Deng Chaofan , Ren Luyao , Li Shixin , Zhang Xianren , Zhao Jian , Yue Tongtao
Published: February 2024

In addition to the filtering and accumulation effects of the ECM on nanoparticles (NPs), NPs traversing the ECM can interact with fibronectin (Fn) to induce biophysical perturbation modulated by surface chemistry.
Plasmon-enhanced second harmonic generation of metal nanostructures
Authors: Zhang Cong-Cong , Zhang Jia-Yi , Feng Jing-Ru , Liu Si-Ting , Ding Si-Jing , Ma Liang , Wang Qu-Quan
Published: February 2024

In this review, the basic principles of plasmon-enhanced SHG, different methods to enhance the SHG intensity of metal nanostructures, and related applications of SHG based on metal nanostructures are introduced.
Naturally occurring phytic acid: an advanced Brønsted acid catalyst for direct amination reactions of allylic alcohols
Authors: Pham Van-Can , Chavasiri Warinthorn , Radtanajiravong Lalita
Published: February 2024

Phytic acid, abundant in seeds, grains, nuts, and legumes, serves as an eco-friendly catalyst for the sustainable synthesis of allylanilines through Brønsted acid-catalysed amination reactions of allylic alcohols.
Direct chemoselective reduction of plant oils using silane catalysed by Rh(iii) complexes at ambient temperature
Authors: Prieto-Pascual Unai , Bustos Itxaso , Freixa Zoraida , Kumar Amit , Huertos Miguel A.
Published: February 2024

This work reports a new procedure for the selective reduction of plant oils to fatty alcohols. This methodology is performed under mild reaction conditions and in the absence of solvents.
Protein deuteration via algal amino acids to circumvent proton back-exchange for 1H-detected solid-state NMR
Authors: Aucharova Hanna , Klein Alexander , Gomez Sara Medina , Söldner Benedikt , Vasa Suresh K. , Linser Rasmus
Published: February 2024

Deuterated amino acids as sole carbon sources enable high-resolution proton-detected solid-state NMR of large proteins.
Active control of an electromagnetically induced transparency analogue in a coupled dual bound states in the continuum system integrated with graphene
Authors: Jiang Fan , Lu Yanxin , Chen Yihang
Published: February 2024

A novel study on actively controlling electromagnetically induced transparency-like effects in a coupled dual BIC system via graphene is reported.
Oxygen-resistant [FeFe]hydrogenases: new biocatalysis tools for clean energy and cascade reactions
Authors: Valetti Francesca , Morra Simone , Barbieri Lisa , Dezzani Sabrina , Ratto Alessandro , Catucci Gianluca , Sadeghi Sheila J. , Gilardi Gianfranco
Published: February 2024

A game-changer [FeFe]hydrogenase was studied to dissect the mechanism of oxygen resistance and learn how to protect biocatalysts for hydrogen-driven reactions.
Multivariate regression analysis of factors regulating the formation of synthetic aluminosilicate nanoparticles
Authors: Adams Faisal T. , Bauer McNeill , Levard Clément , Michel F. Marc
Published: February 2024

Statistical analysis of synthesis conditions models the formation of alumino(silicate) nanoparticles with unique morphologies and structures. Phase maps from these models illustrate the distribution of nanoparticle phases across the synthesis space.
Correction: f-Element heavy pnictogen chemistry
Authors: Du Jingzhen , Cobb Philip J. , Ding Junru , Mills David P. , Liddle Stephen T.
Published: February 2024

Correction for ‘f-Element heavy pnictogen chemistry’ by Jingzhen Du et al., Chem. Sci., 2024, 15, 13–45, https://doi.org/10.1039/D3SC05056D.
Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway
Authors: Weatherdon Laura , Stuart Kate , Cassidy Megan , de la Gándara Alberto Moreno , Okkenhaug Hanneke , Muellener Markus , Mckenzie Grahame , Cook Simon J. , Gilley Rebecca
Published: February 2024

The RAS-regulated RAF–MEK1/2–ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based screens with small molecules or genetic screens such as RNAi, CRISPR or protein interference. Here we describe cell lines that exhibit doxycycline-dependent expression KRASG12V or BRAFV600E and harbour a stably integrated EGR1:EmGFP reporter gene that can be detected by flow cytometry, high-content microscopy or immunoblotting. KRASG12V or BRAFV600E-driven EmGFP expression is inhibited by MEK1/2 or ERK1/2 inhibitors (MEKi and ERKi). BRAFi inhibit BRAFV600E-driven EmGFP expression but enhance the response to KRASG12V, recapitulating paradoxical activation of wild type RAF proteins. In addition to small molecules, expression of iDab6, encoding a RAS-specific antibody fragment inhibited KRASG12V- but not BRAFV600E-driven EmGFP expression. Finally, substitution of EmGFP for a bacterial nitroreductase gene allowed KRASG12V or BRAFV600E to drive cell death in the presence of a pro-drug, which may allow selection of pathway inhibitors that promote survival. These cell lines should prove useful for cell-based screens to identify new regulators of KRAS- or BRAF-dependent ERK1/2 signalling (drug target discovery) as well as screening or triaging ‘hits’ from drug discovery screens.
PCRLB for batch discrete‐time estimation through state decoupling
Authors: Bao Xiao‐Chuan , Luo Ji‐An
Published: February 2024

This letter aims to obtain a closed‐form performance metric using the smoothing posterior Cramér–Rao lower bound (PCRLB) for a class of direct discrete‐time kinematic models. By decoupling the state‐space model into separate position, velocity and acceleration components using an independent dynamic representation, the velocity component in the a priori distribution is converted into a position component. Based on the above derivations, the closed‐form PCRLB is developed. The effectiveness of the proposed bound is demonstrated by contrasting the proposed smoothing PCRLB with the traditional recursive PCRLB in a bearings‐only target tracking scenario.