bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox-induced controllable engineering of MnO2-MnxCo3-xO4 interface to boost catalytic oxidation of ethane
Authors: Wang Haiyan , Wang Shuang , Liu Shida , Dai Yiling , Jia Zhenghao , Li Xuejing , Liu Shuhe , Dang Feixiong , Smith Kevin J. , Nie Xiaowa , Hou Shuandi , Guo Xinwen
Published: May 2024

Multicomponent oxides are intriguing materials in heterogeneous catalysis, and the interface between various components often plays an essential role in oxidations. However, the underlying principles of how the hetero-interface affects the catalytic process remain largely unexplored. Here we report a unique structure design of MnCoOx catalysts by chemical reduction, specifically for ethane oxidation. Part of the Mn ions incorporates with Co oxides to form spinel MnxCo3-xO4, while the rests stay as MnO2 domains to create the MnO2-MnxCo3-xO4 interface. MnCoOx with Mn/Co ratio of 0.5 exhibits an excellent activity and stability up to 1000 h under humid conditions. The synergistic effects between MnO2 and MnxCo3-xO4 are elucidated, in which the C2H6 tends to be adsorbed on the interfacial Co sites and subsequently break the C-H bonds on the reactive lattice O of MnO2 layer. Findings from this study provide valuable insights for the rational design of efficient catalysts for alkane combustion.
Experimental demonstration of an on-chip p-bit core based on stochastic magnetic tunnel junctions and 2D MoS2 transistors
Authors: Daniel John , Sun Zheng , Zhang Xuejian , Tan Yuanqiu , Dilley Neil , Chen Zhihong , Appenzeller Joerg
Published: May 2024

Probabilistic computing is a computing scheme that offers a more efficient approach than conventional complementary metal-oxide–semiconductor (CMOS)-based logic in a variety of applications ranging from optimization to Bayesian inference, and invertible Boolean logic. The probabilistic bit (or p-bit, the base unit of probabilistic computing) is a naturally fluctuating entity that requires tunable stochasticity; by coupling low-barrier stochastic magnetic tunnel junctions (MTJs) with a transistor circuit, a compact implementation is achieved. In this work, by combining stochastic MTJs with 2D-MoS2 field-effect transistors (FETs), we demonstrate an on-chip realization of a p-bit building block displaying voltage-controllable stochasticity. Supported by circuit simulations, we analyze the three transistor-one magnetic tunnel junction (3T-1MTJ) p-bit design, evaluating how the characteristics of each component influence the overall p-bit output. While the current approach has not reached the level of maturity required to compete with CMOS-compatible MTJ technology, the design rules presented in this work are valuable for future experimental implementations of scaled on-chip p-bit networks with reduced footprint.
Sustained bacterial N2O reduction at acidic pH
Authors: He Guang , Chen Gao , Xie Yongchao , Swift Cynthia M. , Ramirez Diana , Cha Gyuhyon , Konstantinidis Konstantinos T. , Radosevich Mark , Löffler Frank E.
Published: May 2024

Nitrous oxide (N2O) is a climate-active gas with emissions predicted to increase due to agricultural intensification. Microbial reduction of N2O to dinitrogen (N2) is the major consumption process but microbial N2O reduction under acidic conditions is considered negligible, albeit strongly acidic soils harbor nosZ genes encoding N2O reductase. Here, we study a co-culture derived from acidic tropical forest soil that reduces N2O at pH 4.5. The co-culture exhibits bimodal growth with a Serratia sp. fermenting pyruvate followed by hydrogenotrophic N2O reduction by a Desulfosporosinus sp. Integrated omics and physiological characterization revealed interspecies nutritional interactions, with the pyruvate fermenting Serratia sp. supplying amino acids as essential growth factors to the N2O-reducing Desulfosporosinus sp. Thus, we demonstrate growth-linked N2O reduction between pH 4.5 and 6, highlighting microbial N2O reduction potential in acidic soils.
Macro-scale relationship between body mass and timing of bird migration
Authors: Wang Xiaodan , Somveille Marius , Dokter Adriaan M. , Cao Wenhua , Cheng Chuyu , Liu Jiajia , Ma Zhijun
Published: May 2024

Clarifying migration timing and its link with underlying drivers is fundamental to understanding the evolution of bird migration. However, previous studies have focused mainly on environmental drivers such as the latitudes of seasonal distributions and migration distance, while the effect of intrinsic biological traits remains unclear. Here, we compile a global dataset on the annual cycle of migratory birds obtained by tracking 1531 individuals and 177 populations from 186 species, and investigate how body mass, a key intrinsic biological trait, influenced timings of the annual cycle using Bayesian structural equation models. We find that body mass has a strong direct effect on departure date from non-breeding and breeding sites, and indirect effects on arrival date at breeding and non-breeding sites, mainly through its effects on migration distance and a carry-over effect. Our results suggest that environmental factors strongly affect the timing of spring migration, while body mass affects the timing of both spring and autumn migration. Our study provides a new foundation for future research on the causes of species distribution and movement.
IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis
Authors: Jiang Dadi , Guo Youming , Wang Tianyu , Wang Liang , Yan Yuelong , Xia Ling , Bam Rakesh , Yang Zhifen , Lee Hyemin , Iwawaki Takao , Gan Boyi , Koong Albert C.
Published: May 2024

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α’s endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is evolutionarily conserved. Genetic deficiency and pharmacological inhibition of IRE1α have similar effects in inhibiting ferroptosis and reducing renal ischemia–reperfusion injury in mice. Our findings reveal a previously unidentified role of IRE1α to regulate ferroptosis and suggests inhibition of IRE1α as a promising therapeutic strategy to mitigate ferroptosis-associated pathological conditions.
The origin of exceptionally large ductility in molybdenum alloys dispersed with irregular-shaped La2O3 nano-particles
Authors: Chen Yujie , Fang Yan , Cheng Pengming , Ke Xiaoxing , Zhang Manchen , Zou Jiawei , Ding Jun , Zhang Bozhao , Gu Lin , Zhang Qinghua , Liu Gang , Yu Qian
Published: May 2024

Molybdenum and its alloys are known for their superior strength among body-centered cubic materials. However, their widespread application is hindered by a significant decrease in ductility at lower temperatures. In this study, we demonstrate the achievement of exceptional ductility in a Mo alloy containing rare-earth La2O3 nanoparticles through rotary-swaging, a rarity in Mo-based materials. Our analysis reveals that the large ductility originates from substantial variations in the electronic density of states, a characteristic intrinsic to rare-earth elements. This characteristic can accelerate the generation of oxygen vacancies, facilitating the amorphization of the oxide-matrix interface. This process promotes vacancy absorption and modification of dislocation configurations. Furthermore, by inducing irregular shapes in the La2O3 nanoparticles through rotary-swaging, incoming dislocations interact with them, creating multiple dislocation sources near the interface. These dislocation sources act as potent initiators at even reduced temperatures, fostering diverse dislocation types and intricate networks, ultimately enhancing dislocation plasticity.
CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials
Authors: Segal Neil H. , Melero Ignacio , Moreno Victor , Steeghs Neeltje , Marabelle Aurelien , Rohrberg Kristoffer , Rodriguez-Ruiz Maria E. , Eder Joseph P. , Eng Cathy , Manji Gulam A. , Waterkamp Daniel , Leutgeb Barbara , Bouseida Said , Flinn Nick , Das Thakur Meghna , Elze Markus C. , Koeppen Hartmut , Jamois Candice , Martin-Facklam Meret , Lieu Christopher H. , Calvo Emiliano , Paz-Ares Luis , Tabernero Josep , Argilés Guillem
Published: May 2024

Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. Here we evaluated cibisatamab for advanced CEA-positive solid tumours in two open-label Phase 1 dose-escalation and -expansion studies: as a single agent with or without obinutuzumab in S1 (NCT02324257) and with atezolizumab in S2 (NCT02650713). Primary endpoints were safety, dose finding, and pharmacokinetics in S1; safety and dose finding in S2. Secondary endpoints were anti-tumour activity (including overall response rate, ORR) and pharmacodynamics in S1; anti-tumour activity, pharmacodynamics and pharmacokinetics in S2. S1 and S2 enrolled a total of 149 and 228 patients, respectively. Grade ≥3 cibisatamab-related adverse events occurred in 36% of S1 and 49% of S2 patients. The ORR was 4% in S1 and 7% in S2. In S2, patients with microsatellite stable colorectal carcinoma (MSS-CRC) given flat doses of cibisatamab and atezolizumab demonstrated an ORR of 14%. In S1 and S2, 40% and 52% of patients, respectively, developed persistent anti-drug antibodies (ADAs). ADA appearance could be mitigated by obinutuzumab-pretreatment, with 8% of patients having persistent ADAs. Overall, cibisatamab warrants further exploration in immunotherapy combination strategies for MSS-CRC.
Inverted device architecture for high efficiency single-layer organic light-emitting diodes with imbalanced charge transport
Authors: Tan Xiao , Dou Dehai , Chua Lay-Lay , Png Rui-Qi , Congrave Daniel G. , Bronstein Hugo , Baumgarten Martin , Li Yungui , Blom Paul W. M. , Wetzelaer Gert-Jan A. H.
Published: May 2024

Many wide-gap organic semiconductors exhibit imbalanced electron and hole transport, therefore efficient organic light-emitting diodes require a multilayer architecture of electron- and hole-transport materials to confine charge recombination to the emissive layer. Here, we show that even for emitters with imbalanced charge transport, it is possible to obtain highly efficient single-layer organic light emitting diodes (OLEDs), without the need for additional charge-transport and blocking layers. For hole-dominated emitters, an inverted single-layer device architecture with ohmic bottom-electron and top-hole contacts moves the emission zone away from the metal top electrode, thereby more than doubling the optical outcoupling efficiency. Finally, a blue-emitting inverted single-layer OLED based on thermally activated delayed fluorescence is achieved, exhibiting a high external quantum efficiency of 19% with little roll-off at high brightness, demonstrating that balanced charge transport is not a prerequisite for highly efficient single-layer OLEDs.
Nuclear actin structure regulates chromatin accessibility
Authors: Sen Buer , Xie Zhihui , Thomas Michelle D. , Pattenden Samantha G. , Howard Sean , McGrath Cody , Styner Maya , Uzer Gunes , Furey Terrence S. , Rubin Janet
Published: May 2024

Polymerized β-actin may provide a structural basis for chromatin accessibility and actin transport into the nucleus can guide mesenchymal stem cell (MSC) differentiation. Using MSC, we show that using CK666 to inhibit Arp2/3 directed secondary actin branching results in decreased nuclear actin structure, and significantly alters chromatin access measured with ATACseq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which enhances nuclear actin structure. In addition, nuclear visualization shows Arp2/3 inhibition decreases pericentric H3K9me3 marks. CytoD, alternatively, induces redistribution of H3K27me3 marks centrally. Such alterations in chromatin landscape are consistent with differential gene expression associated with distinctive differentiation patterns. Further, knockdown of the non-enzymatic monomeric actin binding protein, Arp4, leads to extensive chromatin unpacking, but only a modest increase in transcription, indicating an active role for actin-Arp4 in transcription. These data indicate that dynamic actin remodeling can regulate chromatin interactions.
Late-stage benzenoid-to-troponoid skeletal modification of the cephalotanes exemplified by the total synthesis of harringtonolide
Authors: Wiesler Stefan , Sennari Goh , Popescu Mihai V. , Gardner Kristen E. , Aida Kazuhiro , Paton Robert S. , Sarpong Richmond
Published: May 2024

Skeletal modifications enable elegant and rapid access to various derivatives of a compound that would otherwise be difficult to prepare. They are therefore a powerful tool, especially in the synthesis of natural products or drug discovery, to explore different natural products or to improve the properties of a drug candidate starting from a common intermediate. Inspired by the biosynthesis of the cephalotane natural products, we report here a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners — representing the reverse of the proposed biosynthesis (i.e., a contra-biosynthesis approach). Computational evaluation of our designed transformation prompted us to investigate a Büchner–Curtius–Schlotterbeck reaction of a p-quinol methylether, which ultimately results in the synthesis of harringtonolide in two steps from cephanolide A, which we had previously prepared. Additional computational studies reveal that unconventional selectivity outcomes are driven by the choice of a Lewis acid and the nucleophile, which should inform further developments of these types of reactions.
Structure and genome editing of type I-B CRISPR-Cas
Authors: Lu Meiling , Yu Chenlin , Zhang Yuwen , Ju Wenjun , Ye Zhi , Hua Chenyang , Mao Jinze , Hu Chunyi , Yang Zhenhuang , Xiao Yibei
Published: May 2024

Type I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Their ability to cause long fragment deletions have led to increasing interests in eukaryotic genome editing. While the Cascade structures of all other six type I systems have been determined, the structure of the most evolutionarily conserved type I-B Cascade is still missing. Here, we present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition, and local conformational changes of the effector complex upon R-loop formation. Remarkably, a loop of Cas5 directly intercalated into the major groove of the PAM and facilitated PAM recognition. We further characterized the genome editing profiles of this I-B Cascade-Cas3 in human CD3+ T cells using mRNA-mediated delivery, which led to unidirectional 4.5 kb deletion in TRAC locus and achieved an editing efficiency up to 41.2%. Our study provides the structural basis for understanding target DNA recognition by type I-B Cascade and lays foundation for harnessing this system for long range genome editing in human T cells.
Current advances and future trends of hormesis in disease
Authors: Wan Yantong , Liu Jinxi , Mai Yiyin , Hong Yinghao , Jia Zixuan , Tian Guijie , Liu Yunzhuo , Liang Huaping , Liu Jinghua
Published: May 2024

Hormesis, an adaptive response, occurs when exposure to low doses of a stressor potentially induces a stimulatory effect, while higher doses may inhibit it. This phenomenon is widely observed across various organisms and stressors, significantly advancing our understanding and inspiring further exploration of the beneficial effects of toxins at doses both below and beyond traditional thresholds. This has profound implications for promoting biological regulation at the cellular level and enhancing adaptability throughout the biosphere. Therefore, conducting bibliometric analysis in this field is crucial for accurately analyzing and summarizing its current research status. The results of the bibliometric analysis reveal a steady increase in the number of publications in this field over the years. The United States emerges as the leading country in both publication and citation numbers, with the journal Dose–Response publishing the highest number of papers in this area. Calabrese E.J. is a prominent person with significant contributions and influence among authors. Through keyword co-occurrence and trend analysis, current hotspots in this field are identified, primarily focusing on the relationship between hormesis, oxidative stress, and aging. Analysis of highly cited references predicts that future research trends may center around the relationship between hormesis and stress at different doses, as well as exploring the mechanisms and applications of hormesis. In conclusion, this review aims to visually represent hormesis-related research through bibliometric methods, uncovering emerging patterns and areas of focus within the field. It provides a summary of the current research status and forecasts trends in hormesis-related research.
Assessing the suitability of desalination techniques for hydraulic barriers
Authors: Rosentreter Hanna , Walther Marc , Lerch André
Published: May 2024

Seawater intrusion is a worldwide increasing challenge, which lowers the freshwater availability by salination of fresh groundwater resources in coastal areas. The abstraction-desalination-recharge (ADR) methodology can combat seawater intrusion, whereby desalination is hereby the key factor for the overall efficiency of aquifer remediation. Which desalination technique is suitable within ADR depends on several factors and was not discussed before. We use a multi-criteria decision analysis and cost analysis to compare nanofiltration, reverse osmosis, electrodialysis, and (membrane) capacitive deionization and show for three case scenarios which desalination technique is most suitable within ADR. Overall, electrodialysis, nanofiltration, and reverse osmosis have shown the best utility value for saline groundwater salinity of 1–10 g L−1, whereby electrodialysis is more suitable for lower salinities. The lowest desalination costs are calculated for nanofiltration and reverse osmosis with 0.3–0.6 € m−3 depending on specific energy costs. Even capacitive deionisation can be a suitable alternative for low, slightly saline groundwater (1 g L−1) if the technology readiness level and a lifetime of electrodes increase and material costs decrease. These new insights provide a data analysis, costs, and decision support for desalination which are needed for the holistic approach to counteract seawater intrusion.
Response of tropical forest productivity to seasonal drought mediated by potassium and phosphorus availability
Authors: Manu Raphael , Iddris Najeeb Al-Amin , Corre Marife D. , Aleeje Alfred , Mwanjalolo Majaliwa J. G. , van Straaten Oliver , Veldkamp Edzo
Published: May 2024

Tropical forest productivity is increasingly reported to be nutrient limited, which may affect its response to seasonal droughts. Yet experimental evidence on nutrient limitation from Afrotropical forests remains rare. We conducted an ecosystem-scale, full factorial nitrogen (N)–phosphorus (P)–potassium (K) addition experiment in a moist forest in Uganda to investigate nutrient controls on fine litter production and foliar chemistry. The eight factorial treatments were replicated four times in 32 plots of 40 × 40 m each. During the three-year nutrient additions, we found K and P limitations on leaf litter production, exhibiting strong links to ecosystem responses to seasonal drought. Specifically, leaf litterfall consistently decreased in dry seasons with K additions, whereas P additions caused a reduction only during prolonged drought in the first year. Leaf litterfall was not significantly affected by N additions. Furthermore, K additions delayed the timing of leaf litterfall peak, underscoring the crucial role of K in regulating stomatal aperture and signalling during water-stress conditions and suggesting a prolonged leaf lifespan. Foliar N increased with N and P additions whereas K was the most resorbed nutrient. We conclude that the productivity and resilience of tropical forests, particularly under drier conditions, may depend on terrestrial K and P availability.
Arresting failure propagation in buildings through collapse isolation
Authors: Makoond Nirvan , Setiawan Andri , Buitrago Manuel , Adam Jose M.
Published: May 2024

Several catastrophic building collapses1–5 occur because of the propagation of local-initial failures6,7. Current design methods attempt to completely prevent collapse after initial failures by improving connectivity between building components. These measures ensure that the loads supported by the failed components are redistributed to the rest of the structural system8,9. However, increased connectivity can contribute to collapsing elements pulling down parts of a building that would otherwise be unaffected10. This risk is particularly important when large initial failures occur, as tends to be the case in the most disastrous collapses6. Here we present an original design approach to arrest collapse propagation after major initial failures. When a collapse initiates, the approach ensures that specific elements fail before the failure of the most critical components for global stability. The structural system thus separates into different parts and isolates collapse when its propagation would otherwise be inevitable. The effectiveness of the approach is proved through unique experimental tests on a purposely built full-scale building. We also demonstrate that large initial failures would lead to total collapse of the test building if increased connectivity was implemented as recommended by present guidelines. Our proposed approach enables incorporating a last line of defence for more resilient buildings.
GLP-1-directed NMDA receptor antagonism for obesity treatment
Authors: Petersen Jonas , Ludwig Mette Q. , Juozaityte Vaida , Ranea-Robles Pablo , Svendsen Charlotte , Hwang Eunsang , Kristensen Amalie W. , Fadahunsi Nicole , Lund Jens , Breum Alberte W. , Mathiesen Cecilie V. , Sachs Luisa , Moreno-Justicia Roger , Rohlfs Rebecca , Ford James C. , Douros Jonathan D. , Finan Brian , Portillo Bryan , Grose Kyle , Petersen Jacob E. , Trauelsen Mette , Feuchtinger Annette , DiMarchi Richard D. , Schwartz Thue W. , Deshmukh Atul S. , Thomsen Morten B. , Kohlmeier Kristi A. , Williams Kevin W. , Pers Tune H. , Frølund Bente , Strømgaard Kristian , Klein Anders B. , Clemmensen Christoffer
Published: May 2024

The N-methyl-d-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis1. Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease. GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects neuroplasticity in the hypothalamus and brainstem. Importantly, targeting of MK-801 to GLP-1 receptor-expressing brain regions circumvents adverse physiological and behavioural effects associated with MK-801 monotherapy. In summary, our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for safe and effective obesity treatment.
Wavefunction matching for solving quantum many-body problems
Authors: Elhatisari Serdar , Bovermann Lukas , Ma Yuan-Zhuo , Epelbaum Evgeny , Frame Dillon , Hildenbrand Fabian , Kim Myungkuk , Kim Youngman , Krebs Hermann , Lähde Timo A. , Lee Dean , Li Ning , Lu Bing-Nan , Meißner Ulf-G. , Rupak Gautam , Shen Shihang , Song Young-Ho , Stellin Gianluca
Published: May 2024

Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1–3to quantum chemistry4–6and from atomic and molecular systems7–9to nuclear physics10–14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.
Comparing built-up area datasets to assess urban exposure to coastal hazards in Europe
Authors: Bonatz Hedda , Reimann Lena , Vafeidis Athanasios T.
Published: May 2024

Information on urban land use, beyond the urban-rural dichotomy, can improve the assessment of potential impacts of coastal hazards by refining estimates of damages and supporting adaptation planning. However, the lack of a consistent definition of “urban” in previous studies has led to exposure estimates that vary considerably. Here, we explore the sensitivity of exposed population and built-up area in four settlement types, defined by four different built-up area datasets. We find large differences in the exposed population of up to 65% (127 million people) in the “Urban” class. The exposure estimates are highly sensitive to the density thresholds used to distinguish the settlement types, with a difference in exposed urban population of up to 53.5 million people when the threshold varies by 10%. We attribute the high sensitivity of the exposure estimates to the varying definitions of built-up area of the underlying datasets. We argue that the definition of urban land is crucial for coastal impact assessments and make recommendations for the use of the analyzed datasets.
Proteomics profiling of the honeybee parasite Tropilaelaps mercedesae across post-embryonic development
Authors: Wei Qiaohong , Wu Jiangli , Liu Fengying , Sun Jiajing , Kang Weipeng , Zhao Meijiao , Wang Feng , Zhang Chenhuan , Xu Shufa , Han Bin
Published: May 2024

Tropilaelaps mercedesae, an ectoparasitic mite of honeybees, is currently a severe health risk to Apis mellifera colonies in Asia and a potential threat to the global apiculture industry. However, our understanding of the physiological and developmental regulation of this pest remains significantly insufficient. Using ultra-high resolution mass spectrometry, we provide the first comprehensive proteomic profile of T. mercedesae spanning its entire post-embryonic ontogeny, including protonymphs, deutonymphs, mature adults, and reproductive mites. Consequently, a total of 4,422 T. mercedesae proteins were identified, of which 2,189 proteins were significantly differentially expressed (FDR < 0.05) throughout development and maturation. Our proteomic data provide an important resource for understanding the biology of T. mercedesae, and will contribute to further research and effective control of this devastating honeybee pest.
POSoligo software for in vitro gene synthesis
Authors: Tong Yingying , Sun Jie , Chen Yang , Yi Changhua , Wang Hua , Li Caixin , Dai Nana , Yang Guanghua
Published: May 2024

Oligonucleotide synthesis is vital for molecular experiments. Bioinformatics has been employed to create various algorithmic tools for the in vitro synthesis of nucleotides. The main approach to synthesizing long-chain DNA molecules involves linking short-chain oligonucleotides through ligase chain reaction (LCR) and polymerase chain reaction (PCR). Short-chain DNA molecules have low mutation rates, while LCR requires complementary interfaces at both ends of the two nucleic acid molecules or may alter the conformation of the nucleotide chain, leading to termination of amplification. Therefore, molecular melting temperature, length, and specificity must be considered during experimental design. POSoligo is a specialized offline tool for nucleotide fragment synthesis. It optimizes the oligonucleotide length and specificity based on input single-stranded DNA, producing multiple contiguous long strands (COS) and short patch strands (POS) with complementary ends. This process ensures free 5′- and 3′-ends during oligonucleotide synthesis, preventing secondary structure formation and ensuring specific binding between COS and POS without relying on stabilizing the complementary strands based on Tm values. POSoligo was used to synthesize the linear RBD sequence of SARS-CoV-2 using only one DNA strand, several POSs for LCR ligation, and two pairs of primers for PCR amplification in a time- and cost-effective manner.
Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development
Authors: da Silva Ohana Leticia Tavares , da Silva Maria Karolaynne , Rodrigues-Neto Joao Firmino , Santos Lima Joao Paulo Matos , Manzoni Vinicius , Akash Shopnil , Fulco Umberto Laino , Bourhia Mohammed , Dawoud Turki M. , Nafidi Hiba-Allah , Sitotaw Baye , Akter Shahina , Oliveira Jonas Ivan Nobre
Published: May 2024

Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ($$\beta$$
β
-defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.
Low-adhesion culture selection for human iPS cell-derived cardiomyocytes
Authors: Kikuchi Tetsutaro , Matsuura Katsuhisa , Shimizu Tatsuya
Published: May 2024

Despite progress in generating cardiomyocytes from pluripotent stem cells, these populations often include non-contractile cells, necessitating cardiomyocyte selection for experimental purpose. This study explores a novel cardiomyocyte enrichment mechanism: low-adhesion culture selection. The cardiac cells derived from human induced pluripotent stem cells were subjected to a coating-free low-adhesion culture using bovine serum albumin and high molecular weight dextran sulfate. This approach effectively increased the population of cardiac troponin T-positive cardiomyocytes. Similar results were obtained with commercially available low-adhesion culture dishes. Subsequently, we accessed the practicality of selection of cardiomyocytes using this phenomenon by comparing it with established methods such as glucose-free culture and selection based on puromycin resistance genes. The cardiomyocytes enriched through low-adhesion culture selection maintained autonomous pulsation and responsiveness to beta-stimuli. Moreover, no significant differences were observed in the expression of genes related to subtype commitment and maturation when compared to other selection methods. In conclusion, cardiomyocytes derived from pluripotent stem cells were more low-adhesion culture resistant than their accompanying non-contractile cells, and low-adhesion culture is an alternative method for selection of pluripotent stem cell-derived cardiomyocytes.
Prediction of treatment response after stereotactic radiosurgery of brain metastasis using deep learning and radiomics on longitudinal MRI data
Authors: Cho Se Jin , Cho Wonwoo , Choi Dongmin , Sim Gyuhyeon , Jeong So Yeong , Baik Sung Hyun , Bae Yun Jung , Choi Byung Se , Kim Jae Hyoung , Yoo Sooyoung , Han Jung Ho , Kim Chae-Yong , Choo Jaegul , Sunwoo Leonard
Published: May 2024

We developed artificial intelligence models to predict the brain metastasis (BM) treatment response after stereotactic radiosurgery (SRS) using longitudinal magnetic resonance imaging (MRI) data and evaluated prediction accuracy changes according to the number of sequential MRI scans. We included four sequential MRI scans for 194 patients with BM and 369 target lesions for the Developmental dataset. The data were randomly split (8:2 ratio) for training and testing. For external validation, 172 MRI scans from 43 patients with BM and 62 target lesions were additionally enrolled. The maximum axial diameter (Dmax), radiomics, and deep learning (DL) models were generated for comparison. We evaluated the simple convolutional neural network (CNN) model and a gated recurrent unit (Conv-GRU)-based CNN model in the DL arm. The Conv-GRU model performed superior to the simple CNN models. For both datasets, the area under the curve (AUC) was significantly higher for the two-dimensional (2D) Conv-GRU model than for the 3D Conv-GRU, Dmax, and radiomics models. The accuracy of the 2D Conv-GRU model increased with the number of follow-up studies. In conclusion, using longitudinal MRI data, the 2D Conv-GRU model outperformed all other models in predicting the treatment response after SRS of BM.
CERN-based experiments and Monte-Carlo studies on focused dose delivery with very high energy electron (VHEE) beams for radiotherapy applications
Authors: Whitmore L. , Mackay R. I. , van Herk M. , Korysko P. , Farabolini W. , Malyzhenkov A. , Corsini R. , Jones R. M.
Published: May 2024

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.
Identification of Gα12-vs-Gα13-coupling determinants and development of a Gα12/13-coupled designer GPCR
Authors: Tatsumi Manae , Cruz Christian , Kamakura Nozomi , Kuwabara Riku , Nakamura Gaku , Ikuta Tatsuya , Abrol Ravinder , Inoue Asuka
Published: May 2024

G-protein-coupled receptors (GPCRs) transduce diverse signals into the cell by coupling to one or several Gα subtypes. Of the 16 Gα subtypes in human cells, Gα12 and Gα13 belong to the G12 subfamily and are reported to be functionally different. Notably, certain GPCRs display selective coupling to either Gα12 or Gα13, highlighting their significance in various cellular contexts. However, the structural basis underlying this selectivity remains unclear. Here, using a Gα12-coupled designer receptor exclusively activated by designer drugs (DREADD; G12D) as a model system, we identified residues in the α5 helix and the receptor that collaboratively determine Gα12-vs-Gα13 selectivity. Residue-swapping experiments showed that G12D distinguishes differences between Gα12 and Gα13 in the positions G.H5.09 and G.H5.23 in the α5 helix. Molecular dynamics simulations observed that I378G.H5.23 in Gα12 interacts with N1032.39, S1693.53 and Y17634.53 in G12D, while H364G.H5.09 in Gα12 interact with Q2645.71 in G12D. Screening of mutations at these positions in G12D identified G12D mutants that enhanced coupling with Gα12 and to an even greater extent with Gα13. Combined mutations, most notably the dual Y17634.53H and Q2645.71R mutant, further enhanced Gα12/13 coupling, thereby serving as a potential Gα12/13-DREADD. Such novel Gα12/13-DREADD may be useful in future efforts to develop drugs that target Gα12/13 signaling as well as to identify their therapeutic indications.
Layout analysis of the RCEP international airline network based on hub identification using improved contribution matrix
Authors: Yang Wendong , Chi Yulin , Huang Yining , Wei Wenbin , Xu Zhengjia
Published: May 2024

The signing of the Regional Comprehensive Economic Partnership agreement brings new opportunities for the development of international air transportation. Faced with fierce competition, it is worth studying how hub airports should enhance competitiveness, and how low-cost carriers and full-service carriers should optimize the RCEP international airline network layout for better development. Aiming at providing suggestions for the development of hub airports, low-cost and full-service carriers in the RCEP international airline network, this paper identifies the hub airports, analyzes the layout of the RCEP international airline network, and the multi-layered characteristics based on an improved contribution matrix using data from 2010 to 2019 collected from the Official Airline Guide (OAG). This method comprehensively considers attributes of hub airports and the multi-layered characteristics of the airports and routes. The layout analysis indicates that the RCEP international transportation market presents a more open environment for competition and cooperation where base carriers are often the biggest supporters of hub construction. The multi-layered characteristics analysis reveals that low-cost carriers contribute more towards opening up new RCEP routes than full-service carriers. It is advised that carriers newly entering the RCEP international aviation transportation market and low-cost carriers dedicate to establishing new routes around their hub airports to monopolize this market and enhance their market share, whilst full-service carriers consolidate existing routes and increase route density to achieve economic benefits.
Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation
Authors: Hill Christopher J. , Phelan Marie M. , Dutton Philip J. , Busuulwa Paula , Maclean Alison , Davison Andrew S. , Drury Josephine A. , Tempest Nicola , Horne Andrew W. , Gutiérrez Eva Caamaño , Hapangama Dharani K.
Published: May 2024

A significant number of pregnancies are lost in the first trimester and 1–2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.
Laser weeding: opportunities and challenges for couch grass (Elymus repens (L.) Gould) control
Authors: Andreasen Christian , Vlassi Eleni , Salehan Najmeh
Published: May 2024

Laser weeding may contribute to less dependency on herbicides and soil tillage. Several research and commercial projects are underway to develop robots equipped with lasers to control weeds. Artificial intelligence can be used to locate and identify weed plants, and mirrors can be used to direct a laser beam towards the target to kill it with heat. Unlike chemical and mechanical weed control, laser weeding only exposes a tiny part of the field for treatment. Laser weeding leaves behind only ashes from the burned plants and does not disturb the soil. Therefore, it is an eco-friendly method to control weed seedlings. However, perennial weeds regrow from the belowground parts after the laser destroys the aerial shoots. Depletion of the belowground parts for resources might be possible if the laser continuously kills new shoots, but it may require many laser treatments. We studied how laser could be used to destroy the widespread and aggressive perennial weed Elymus repens after the rhizomes were cut into fragments. Plants were killed with even small dosages of laser energy and stopped regrowing. Generally, the highest efficacy was achieved when the plants from small rhizomes were treated at the 3-leaf stage.
Introduced species shed friends as well as enemies
Authors: Xirocostas Zoe A. , Ollerton Jeff , Peco Begoña , Slavich Eve , Bonser Stephen P. , Pärtel Meelis , Raghu S. , Moles Angela T.
Published: May 2024

Many studies seeking to understand the success of biological invasions focus on species’ escape from negative interactions, such as damage from herbivores, pathogens, or predators in their introduced range (enemy release). However, much less work has been done to assess the possibility that introduced species might shed mutualists such as pollinators, seed dispersers, and mycorrhizae when they are transported to a new range. We ran a cross-continental field study and found that plants were being visited by 2.6 times more potential pollinators with 1.8 times greater richness in their native range than in their introduced range. Understanding both the positive and negative consequences of introduction to a new range can help us predict, monitor, and manage future invasion events.
Enhancing gain and isolation of a quad-element MIMO antenna array design for 5G sub-6 GHz applications assisted with characteristic mode analysis
Authors: Khan Rabia , Sethi Waleed Tariq , Malik Waqar Ahmad , Jan Latif , Tahseen Muhammad M. , Almuhlafi Ali M. , Himdi Mohamed
Published: May 2024

This paper presents a novel quad-element array with multiple inputs and multiple outputs (MIMO) designed for 5th generation sub-6 GHz applications. The MIMO system achieves a wide impedance bandwidth, high gain, and high isolation among its components, representing significant advancements in sub-6 GHz antenna applications. The single element, an elliptical resonator with a circular slot, is fed by a 50 Ω microstrip feedline, achieves a broad characteristic bandwidth from 3.7 to 5.7 GHz with a resonant frequency of 4.33 GHz and a gain of 1.81 dBi. Characteristic Mode Analysis (CMA) was employed to elucidate the evolution phases of this design. The quad-element MIMO antenna array maintains a compact size and broadband characteristics by arranging mirrored elements on the same ground plane. Implemented on a cost-effective FR-4 substrate measuring 44 × 44 × 1.6 mm3, the recommended MIMO antenna array, enhanced with a partial ground plane and due to the introduction of a vertical strip, a high isolation of − 38.53 dB is achieved between MIMO components along with a realized gain of 3.01 dBi and a radiation efficiency of 71% in the 5G sub-6 GHz band. Noteworthy properties include high isolation, diversity gain (DG), and envelope correlation coefficient (ECC), verifying the appropriateness of the suggested MIMO scheme for 5G transmission and reception in sub-6 GHz applications.