bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2
Authors: Liu Zheng , Lee Pyung-Gang , Krez Nadja , Lam Kwok-ho , Liu Hao , Przykopanski Adina , Chen Peng , Yao Guorui , Zhang Sicai , Tremblay Jacqueline M. , Perry Kay , Shoemaker Charles B. , Rummel Andreas , Dong Min , Jin Rongsheng
Published: April 2023

Botulinum neurotoxin E (BoNT/E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. Here we determined the co-crystal structures of the receptor-binding domain of BoNT/E (HCE) in complex with its neuronal receptor synaptic vesicle glycoprotein 2A (SV2A) and a nanobody that serves as a ganglioside surrogate. These structures reveal that the protein-protein interactions between HCE and SV2 provide the crucial location and specificity information for HCE to recognize SV2A and SV2B, but not the closely related SV2C. At the same time, HCE exploits a separated sialic acid-binding pocket to mediate recognition of an N-glycan of SV2. Structure-based mutagenesis and functional studies demonstrate that both the protein-protein and protein-glycan associations are essential for SV2A-mediated cell entry of BoNT/E and for its potent neurotoxicity. Our studies establish the structural basis to understand the receptor-specificity of BoNT/E and to engineer BoNT/E variants for new clinical applications.
A unifying criterion of the boiling crisis
Authors: Zhang Limiao , Wang Chi , Su Guanyu , Kossolapov Artyom , Matana Aguiar Gustavo , Seong Jee Hyun , Chavagnat Florian , Phillips Bren , Rahman Md Mahamudur , Bucci Matteo
Published: April 2023

We reveal and justify, both theoretically and experimentally, the existence of a unifying criterion of the boiling crisis. This criterion emerges from an instability in the near-wall interactions of bubbles, which can be described as a percolation process driven by three fundamental boiling parameters: nucleation site density, average bubble footprint radius and product of average bubble growth time and detachment frequency. Our analysis suggests that the boiling crisis occurs on a well-defined critical surface in the multidimensional space of these parameters. Our experiments confirm the existence of this unifying criterion for a wide variety of boiling surface geometries and textures, two boiling regimes (pool and flow boiling) and two fluids (water and liquid nitrogen). This criterion constitutes a simple mechanistic rule to predict the boiling crisis, also providing a guiding principle for designing boiling surfaces that would maximize the nucleate boiling performance.
Transcription factor binding site orientation and order are major drivers of gene regulatory activity
Authors: Georgakopoulos-Soares Ilias , Deng Chengyu , Agarwal Vikram , Chan Candace S. Y. , Zhao Jingjing , Inoue Fumitaka , Ahituv Nadav
Published: April 2023

The gene regulatory code and grammar remain largely unknown, precluding our ability to link phenotype to genotype in regulatory sequences. Here, using a massively parallel reporter assay (MPRA) of 209,440 sequences, we examine all possible pair and triplet combinations, permutations and orientations of eighteen liver-associated transcription factor binding sites (TFBS). We find that TFBS orientation and order have a major effect on gene regulatory activity. Corroborating these results with genomic analyses, we find clear human promoter TFBS orientation biases and similar TFBS orientation and order transcriptional effects in an MPRA that tested 164,307 liver candidate regulatory elements. Additionally, by adding TFBS orientation to a model that predicts expression from sequence we improve performance by 7.7%. Collectively, our results show that TFBS orientation and order have a significant effect on gene regulatory activity and need to be considered when analyzing the functional effect of variants on the activity of these sequences.
Nickel/biimidazole-catalyzed electrochemical enantioselective reductive cross-coupling of aryl aziridines with aryl iodides
Authors: Wang Yun-Zhao , Wang Zhen-Hua , Eshel Inbal L. , Sun Bing , Liu Dong , Gu Yu-Cheng , Milo Anat , Mei Tian-Sheng
Published: April 2023

Here, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affordingβ-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover. Mechanistic studies suggest a radical pathway is involved in the ring opening of aziridines. The statistical analysis serves to compare the different design requirements for photochemically and electrochemically mediated reactions under this type of mechanistic manifold.
Para-hydrodynamics from weak surface scattering in ultraclean thin flakes
Authors: Wolf Yotam , Aharon-Steinberg Amit , Yan Binghai , Holder Tobias
Published: April 2023

Electron hydrodynamics typically emerges in electron fluids with a high electron–electron collision rate. However, new experiments with thin flakes of WTe2 have revealed that other momentum-conserving scattering processes can replace the role of the electron–electron interaction, thereby leading to a novel, so-called para-hydrodynamic regime. Here, we develop the kinetic theory for para-hydrodynamic transport. To this end, we consider a ballistic electron gas in a thin three-dimensional sheet where the momentum-relaxing (lmr) and momentum-conserving (lmc) mean free paths are decreased due to boundary scattering from a rough surface. The resulting effective mean free path of the in-plane components of the electronic flow is then expressed in terms of microscopic parameters of the sheet boundaries, predicting that a para-hydrodynamic regime with lmr ≫ lmc emerges generically in ultraclean three-dimensional materials. Using our approach, we recover the transport properties of WTe2 in the para-hydrodynamic regime in good agreement with existing experiments.
Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases
Authors: Zelnik Iris D. , Mestre Beatriz , Weinstein Jonathan J. , Dingjan Tamir , Izrailov Stav , Ben-Dor Shifra , Fleishman Sarel J. , Futerman Anthony H.
Published: April 2023

Until now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2. Together with molecular dynamics simulations, we propose a pathway by which substrates might be delivered to the ceramide synthases.
DNA-binding mechanism and evolution of replication protein A
Authors: Madru Clément , Martínez-Carranza Markel , Laurent Sébastien , Alberti Alessandra C. , Chevreuil Maelenn , Raynal Bertrand , Haouz Ahmed , Le Meur Rémy A. , Delarue Marc , Henneke Ghislaine , Flament Didier , Krupovic Mart , Legrand Pierre , Sauguet Ludovic
Published: April 2023

Replication Protein A (RPA) is a heterotrimeric single stranded DNA-binding protein with essential roles in DNA replication, recombination and repair. Little is known about the structure of RPA in Archaea, the third domain of life. By using an integrative structural, biochemical and biophysical approach, we extensively characterize RPA from Pyrococcus abyssi in the presence and absence of DNA. The obtained X-ray and cryo-EM structures reveal that the trimerization core and interactions promoting RPA clustering on ssDNA are shared between archaea and eukaryotes. However, we also identified a helical domain named AROD (Acidic Rpa1 OB-binding Domain), and showed that, in Archaea, RPA forms an unanticipated tetrameric supercomplex in the absence of DNA. The four RPA molecules clustered within the tetramer could efficiently coat and protect stretches of ssDNA created by the advancing replisome. Finally, our results provide insights into the evolution of this primordial replication factor in eukaryotes.
Achieving volatile potassium promoted ammonia synthesis via mechanochemistry
Authors: Kim Jong-Hoon , Dai Tian-Yi , Yang Mihyun , Seo Jeong-Min , Lee Jae Seong , Kweon Do Hyung , Lang Xing-You , Ihm Kyuwook , Shin Tae Joo , Han Gao-Feng , Jiang Qing , Baek Jong-Beom
Published: April 2023

Potassium oxide (K2O) is used as a promotor in industrial ammonia synthesis, although metallic potassium (K) is better in theory. The reason K2O is used is because metallic K, which volatilizes around 400 °C, separates from the catalyst in the harsh ammonia synthesis conditions of the Haber-Bosch process. To maximize the efficiency of ammonia synthesis, using metallic K with low temperature reaction below 400 °C is prerequisite. Here, we synthesize ammonia using metallic K and Fe as a catalyst via mechanochemical process near ambient conditions (45 °C, 1 bar). The final ammonia concentration reaches as high as 94.5 vol%, which was extraordinarily higher than that of the Haber-Bosch process (25.0 vol%, 450 °C, 200 bar) and our previous work (82.5 vol%, 45 °C, 1 bar).
High-harmonic generation from a flat liquid-sheet plasma mirror
Authors: Kim Yang Hwan , Kim Hyeon , Park Seong Cheol , Kwon Yongjin , Yeom Kyunghoon , Cho Wosik , Kwon Taeyong , Yun Hyeok , Sung Jae Hee , Lee Seong Ku , Luu Tran Trung , Nam Chang Hee , Kim Kyung Taec
Published: April 2023

High-harmonic radiation can be generated when an ultra-intense laser beam is reflected from an over-dense plasma, known as a plasma mirror. It is considered a promising technique for generating intense attosecond pulses in the extreme ultraviolet and X-ray wavelength ranges. However, a solid target used for the formation of the over-dense plasma is completely damaged by the interaction. Thus, it is challenging to use a solid target for applications such as time-resolved studies and attosecond streaking experiments that require a large amount of data. Here we demonstrate that high-harmonic radiation can be continuously generated from a liquid plasma mirror in both the coherent wake emission and relativistic oscillating mirror regimes. These results will pave the way for the development of bright, stable, and high-repetition-rate attosecond light sources, which can greatly benefit the study of ultrafast laser-matter interactions.
A massively parallel screening platform for converting aptamers into molecular switches
Authors: Yoshikawa Alex M. , Rangel Alexandra E. , Zheng Liwei , Wan Leighton , Hein Linus A. , Hariri Amani A. , Eisenstein Michael , Soh H. Tom
Published: April 2023

Aptamer-based molecular switches that undergo a binding-induced conformational change have proven valuable for a wide range of applications, such as imaging metabolites in cells, targeted drug delivery, and real-time detection of biomolecules. Since conventional aptamer selection methods do not typically produce aptamers with inherent structure-switching functionality, the aptamers must be converted to molecular switches in a post-selection process. Efforts to engineer such aptamer switches often use rational design approaches based on in silico secondary structure predictions. Unfortunately, existing software cannot accurately model three-dimensional oligonucleotide structures or non-canonical base-pairing, limiting the ability to identify appropriate sequence elements for targeted modification. Here, we describe a massively parallel screening-based strategy that enables the conversion of virtually any aptamer into a molecular switch without requiring any prior knowledge of aptamer structure. Using this approach, we generate multiple switches from a previously published ATP aptamer as well as a newly-selected boronic acid base-modified aptamer for glucose, which respectively undergo signal-on and signal-off switching upon binding their molecular targets with second-scale kinetics. Notably, our glucose-responsive switch achieves ~30-fold greater sensitivity than a previously-reported natural DNA-based switch. We believe our approach could offer a generalizable strategy for producing target-specific switches from a wide range of aptamers.
Species invasiveness and community invasibility of North American freshwater fish fauna revealed via trait-based analysis
Authors: Su Guohuan , Mertel Adam , Brosse Sébastien , Calabrese Justin M.
Published: April 2023

While biological invasions are recognized as a major threat to global biodiversity, determining non-native species’ abilities to establish in new areas (species invasiveness) and the vulnerability of those areas to invasions (community invasibility) is challenging. Here, we use trait-based analysis to profile invasive species and quantify the community invasibility for >1,800 North American freshwater fish communities. We show that, in addition to effects attributed to propagule pressure caused by human intervention, species with higher fecundity, longer lifespan and larger size tend to be more invasive. Community invasibility peaks when the functional distance among native species was high, leaving unoccupied functional space for the establishment of potential invaders. Our findings illustrate how the functional traits of non-native species determining their invasiveness, and the functional characteristics of the invaded community determining its invasibility, may be identified. Considering those two determinants together will enable better predictions of invasions.
Modalities of group A streptococcal prevention and treatment and their economic justification
Authors: Cannon Jeffrey W. , Wyber Rosemary
Published: April 2023

Infection by group A Streptococcus (Strep A) results in a diverse range of clinical conditions, including pharyngitis, impetigo, cellulitis, necrotising fasciitis, and rheumatic heart disease. In this article, we outline the recommended strategies for Strep A treatment and prevention and review the literature for economic evaluations of competing treatment and prevention strategies. We find that most economic evaluations focus on reducing the duration of illness or risk of rheumatic fever among people presenting with sore throat through diagnostic and/or treatment strategies. Few studies have evaluated strategies to reduce the burden of Strep A infection among the general population, nor have they considered the local capacity to finance and implement strategies. Evaluation of validated costs and consequences for a more diverse range of Strep A interventions are needed to ensure policies maximise patient outcomes under budget constraints. This should include attention to basic public health strategies and emerging strategies such as vaccination.
Efficient evolution of human antibodies from general protein language models
Authors: Hie Brian L. , Shanker Varun R. , Xu Duo , Bruun Theodora U. J. , Weidenbacher Payton A. , Tang Shaogeng , Wu Wesley , Pak John E. , Kim Peter S.
Published: April 2023

Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings.
A shared neural basis underlying psychiatric comorbidity
Authors: Xie Chao , Xiang Shitong , Shen Chun , Peng Xuerui , Kang Jujiao , Li Yuzhu , Cheng Wei , He Shiqi , Bobou Marina , Broulidakis M. John , van Noort Betteke Maria , Zhang Zuo , Robinson Lauren , Vaidya Nilakshi , Winterer Jeanne , Zhang Yuning , King Sinead , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Bromberg Uli , Büchel Christian , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Ittermann Bernd , Lemaître Hervé , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Fröhner Juliane H. , Schmidt Ulrike , Sinclair Julia , Smolka Michael N. , Stringaris Argyris , Walter Henrik , Whelan Robert , Desrivières Sylvane , Sahakian Barbara J. , Robbins Trevor W. , Schumann Gunter , Jia Tianye , Feng Jianfeng ,   IMAGEN Consortium,   STRATIFY/ESTRA Consortium, van Noort Betteke Maria ,   ZIB Consortium
Published: April 2023

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the STRATIFY & ESTRA Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities.
Computational complexity drives sustained deliberation
Authors: Hong Tao , Stauffer William R.
Published: April 2023

Economic deliberations are slow, effortful and intentional searches for solutions to difficult economic problems. Although such deliberations are critical for making sound decisions, the underlying reasoning strategies and neurobiological substrates remain poorly understood. Here two nonhuman primates performed a combinatorial optimization task to identify valuable subsets and satisfy predefined constraints. Their behavior revealed evidence of combinatorial reasoning—when low-complexity algorithms that consider items one at a time provided optimal solutions, the animals adopted low-complexity reasoning strategies. When greater computational resources were required, the animals approximated high-complexity algorithms that search for optimal combinations. The deliberation times reflected the demands created by computational complexity—high-complexity algorithms require more operations and, concomitantly, the animals deliberated for longer durations. Recurrent neural networks that mimicked low- and high-complexity algorithms also reflected the behavioral deliberation times and were used to reveal algorithm-specific computations that support economic deliberation. These findings reveal evidence for algorithm-based reasoning and establish a paradigm for studying the neurophysiological basis for sustained deliberation.
Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience
Authors: Udeochu Joe C. , Amin Sadaf , Huang Yige , Fan Li , Torres Eileen Ruth S. , Carling Gillian K. , Liu Bangyan , McGurran Hugo , Coronas-Samano Guillermo , Kauwe Grant , Mousa Gergey Alzaem , Wong Man Ying , Ye Pearly , Nagiri Ravi Kumar , Lo Iris , Holtzman Julia , Corona Carlo , Yarahmady Allan , Gill Michael T. , Raju Ravikiran M. , Mok Sue-Ann , Gong Shiaoching , Luo Wenjie , Zhao Mingrui , Tracy Tara E. , Ratan Rajiv R. , Tsai Li-Huei , Sinha Subhash C. , Gan Li
Published: April 2023

Pathological hallmarks of Alzheimer’s disease (AD) precede clinical symptoms by years, indicating a period of cognitive resilience before the onset of dementia. Here, we report that activation of cyclic GMP–AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of Cgas in mice with tauopathy diminished the microglial IFN-I response, preserved synapse integrity and plasticity and protected against cognitive impairment without affecting the pathogenic tau load. cGAS ablation increased, while activation of IFN-I decreased, the neuronal MEF2C expression network linked to cognitive resilience in AD. Pharmacological inhibition of cGAS in mice with tauopathy enhanced the neuronal MEF2C transcriptional network and restored synaptic integrity, plasticity and memory, supporting the therapeutic potential of targeting the cGAS–IFN–MEF2C axis to improve resilience against AD-related pathological insults.
Estimating GRACE terrestrial water storage anomaly using an improved point mass solution
Authors: Ferreira Vagner , Yong Bin , Montecino Henry , Ndehedehe Christopher E. , Seitz Kurt , Kutterer Hansjörg , Yang Kun
Published: April 2023

The availability of terrestrial water storage anomaly (TWSA) data from the Gravity Recovery and Climate Experiment (GRACE) supports many hydrological applications. Five TWSA products are operational and publicly available, including three based on mass concentration (mascon) solutions and two based on the synthesis of spherical harmonic coefficients (SHCs). The mascon solutions have advantages regarding the synthesis of SHCs since the basis functions are represented locally rather than globally, which allows geophysical data constraints. Alternative new solutions based on SHCs are, therefore, critical and warranted to enrich the portfolio of user-friendly TWSA data based on different algorithms. TWSA data based on novel processing protocols is presented with a spatial re-sampling of 0.25 arc-degrees covering 2002–2022. This approach parameterizes the improved point mass (IPM) and adopts the synthesized residual gravitational potential as observations. The assay indicates that the proposed Hohai University (HHU-) IPM TWSA data reliably agree with the mascon solutions. The presented HHU-IPM TWSA data set would be instrumental in regional hydrological applications, particularly enabling improved assessment of regional water budgets.
A novel visual illusion paradigm provides evidence for a general factor of illusion sensitivity and personality correlates
Authors: Makowski Dominique , Te An Shu , Kirk Stephanie , Liang Ngoi Zi , Chen S. H. Annabel
Published: April 2023

Visual illusions are a gateway to understand how we construct our experience of reality. Unfortunately, important questions remain open, such as the hypothesis of a common factor underlying the sensitivity to different types of illusions, as well as of personality correlates of illusion sensitivity. In this study, we used a novel parametric framework for visual illusions to generate 10 different classic illusions (Delboeuf, Ebbinghaus, Rod and Frame, Vertical-Horizontal, Zöllner, White, Müller-Lyer, Ponzo, Poggendorff, Contrast) varying in strength, embedded in a perceptual discrimination task. We tested the objective effect of the illusions on errors and response times, and extracted participant-level performance scores (n=250) for each illusion. Our results provide evidence in favour of a general factor underlying the sensitivity to different illusions (labelled Factor i). Moreover, we report a positive link between illusion sensitivity and personality traits such as Agreeableness, Honesty-Humility, and negative relationships with Psychoticism, Antagonism, Disinhibition, and Negative Affect.
CBCT-based synthetic CT generated using CycleGAN with HU correction for adaptive radiotherapy of nasopharyngeal carcinoma
Authors: Jihong Chen , Kerun Quan , Kaiqiang Chen , Xiuchun Zhang , Yimin Zhou , penggang Bai
Published: April 2023

This study aims to utilize a hybrid approach of phantom correction and deep learning for synthesized CT (sCT) images generation based on cone-beam CT (CBCT) images for nasopharyngeal carcinoma (NPC). 52 CBCT/CT paired images of NPC patients were used for model training (41), validation (11). Hounsfield Units (HU) of the CBCT images was calibrated by a commercially available CIRS phantom. Then the original CBCT and the corrected CBCT (CBCT_cor) were trained separately with the same cycle generative adversarial network (CycleGAN) to generate SCT1 and SCT2. The mean error and mean absolute error (MAE) were used to quantify the image quality. For validations, the contours and treatment plans in CT images were transferred to original CBCT, CBCT_cor, SCT1 and SCT2 for dosimetric comparison. Dose distribution, dosimetric parameters and 3D gamma passing rate were analyzed. Compared with rigidly registered CT (RCT), the MAE of CBCT, CBCT_cor, SCT1 and SCT2 were 346.11 ± 13.58 HU, 145.95 ± 17.64 HU, 105.62 ± 16.08 HU and 83.51 ± 7.71 HU, respectively. Moreover, the average dosimetric parameter differences for the CBCT_cor, SCT1 and SCT2 were 2.7% ± 1.4%, 1.2% ± 1.0% and 0.6% ± 0.6%, respectively. Using the dose distribution of RCT images as reference, the 3D gamma passing rate of the hybrid method was significantly better than the other methods. The effectiveness of CBCT-based sCT generated using CycleGAN with HU correction for adaptive radiotherapy of nasopharyngeal carcinoma was confirmed. The image quality and dose accuracy of SCT2 were outperform the simple CycleGAN method. This finding has great significance for the clinical application of adaptive radiotherapy for NPC.
Initial development and testing of an exhaled microRNA detection strategy for lung cancer case–control discrimination
Authors: Shi Miao , Han Weiguo , Loudig Olivier , Shah Chirag D. , Dobkin Jay B. , Keller Steven , Sadoughi Ali , Zhu Changcheng , Siegel Robert E. , Fernandez Maria Katherine , DeLaRosa Lizett , Patel Dhruv , Desai Aditi , Siddiqui Taha , Gombar Saurabh , Suh Yousin , Wang Tao , Hosgood H. Dean , Pradhan Kith , Ye Kenny , Spivack Simon D.
Published: April 2023

For detecting field carcinogenesis non-invasively, early technical development and case–control testing of exhaled breath condensate microRNAs was performed. In design, human lung tissue microRNA-seq discovery was reconciled with TCGA and published tumor-discriminant microRNAs, yielding a panel of 24 upregulated microRNAs. The airway origin of exhaled microRNAs was topographically “fingerprinted”, using paired EBC, upper and lower airway donor sample sets. A clinic-based case–control study (166 NSCLC cases, 185 controls) was interrogated with the microRNA panel by qualitative RT-PCR. Data were analyzed by logistic regression (LR), and by random-forest (RF) models. Feasibility testing of exhaled microRNA detection, including optimized whole EBC extraction, and RT and qualitative PCR method evaluation, was performed. For sensitivity in this low template setting, intercalating dye-based URT-PCR was superior to fluorescent probe-based PCR (TaqMan). In application, adjusted logistic regression models identified exhaled miR-21, 33b, 212 as overall case–control discriminant. RF analysis of combined clinical + microRNA models showed modest added discrimination capacity (1.1–2.5%) beyond clinical models alone: all subjects 1.1% (p = 8.7e−04)); former smokers 2.5% (p = 3.6e−05); early stage 1.2% (p = 9.0e−03), yielding combined ROC AUC ranging from 0.74 to 0.83. We conclude that exhaled microRNAs are qualitatively measureable, reflect in part lower airway signatures; and when further refined/quantitated, can potentially help to improve lung cancer risk assessment.
A comparative analysis of lipoprotein transport proteins: LolA and LolB from Vibrio cholerae and LolA from Porphyromonas gingivalis
Authors: Jaiman Deepika , Nagampalli Raghavendra , Persson Karina
Published: April 2023

In Gram-negative bacteria, N-terminal lipidation is a signal for protein trafficking from the inner membrane (IM) to the outer membrane (OM). The IM complex LolCDE extracts lipoproteins from the membrane and moves them to the chaperone LolA. The LolA-lipoprotein complex crosses the periplasm after which the lipoprotein is anchored to the OM. In γ-proteobacteria anchoring is assisted by the receptor LolB, while a corresponding protein has not been identified in other phyla. In light of the low sequence similarity between Lol-systems from different phyla and that they may use different Lol components, it is crucial to compare representative proteins from several species. Here we present a structure–function study of LolA and LolB from two phyla: LolA from Porphyromonas gingivalis (phylum bacteroidota), and LolA and LolB from Vibrio cholerae (phylum proteobacteria). Despite large sequence differences, the LolA structures are very similar, hence structure and function have been conserved throughout evolution. However, an Arg-Pro motif crucial for function in γ-proteobacteria has no counterpart in bacteroidota. We also show that LolA from both phyla bind the antibiotic polymyxin B whereas LolB does not. Collectively, these studies will facilitate the development of antibiotics as they provide awareness of both differences and similarities across phyla.
Forensic application of epidermal expression of HSP27 and HSP70 for the determination of wound vitality in human compressed neck skin
Authors: Zhang Siying , Ishida Yuko , Ishigami Akiko , Nosaka Mizuho , Kuninaka Yumi , Yasuda Haruki , Kofuna Ayumi , Matsuki Jumpei , Osako Miyu , Zhang Wei , Kimura Akihiko , Furukawa Fukumi , Kondo Toshikazu
Published: April 2023

Estimating the age and vitality of human skin wounds is essential in forensic practice, and the use of immunohistochemical parameters in this regard remains a challenge. Heat shock proteins (HSPs) are evolutionarily conserved universal proteins that protect biological systems from various types of stress. However, its importance in forensic pathology for determining wound activation in neck compression skin remains unclear. The expression of HSP27 and HSP70 in neck skin samples was immunohistochemically examined to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 45 cases of neck compression (hanging, 32 cases; strangulation, 10 cases; manual strangulation, 2 cases; other, 1 case) during forensic autopsies; intact skin from the same individual was used as a control. HSP27 expression was detected in 17.4% of keratinocytes in the intact skin samples. In the compressed region, the frequency of HSP27 expression in keratinocytes was 75.8%, which was significantly higher than that in intact skin. Similarly, HSP70 expression was 24.8% in intact skin samples and 81.9% in compressed skin samples, significantly higher in compressed skin than in intact skin samples. This increase in case compression cases may be due to the cell defence role of HSPs. From a forensic pathology perspective, the immunohistochemical examination of HSP27 and HSP70 expression in neck skin could be considered a valuable marker for diagnosing traces of antemortem compression.
Effect of Laminaria digitata dietary inclusion and CAZyme supplementation on blood cells, serum metabolites and hepatic lipids and minerals of weaned piglets
Authors: Ribeiro David M. , Pinto Rui M. A. , Lopes Paula A. , Pestana José M. , Alfaia Cristina M. , Costa Mónica M. , Carvalho Daniela F. P. , Mourato Miguel P. , de Almeida André M. , Freire João P. B. , Prates José A. M.
Published: April 2023

Seaweeds, such as Laminaria digitata, are a sustainable alternative to conventional feedstuffs for weaned piglet diets, improving their health and mitigating environmental impacts. L. digitata has a complex cell wall that can be difficult for monogastrics to digest. However, carbohydrate-active enzymes (CAZymes) such as Rovabio® Excel AP and alginate lyase can help break down these polysaccharides and render intracellular nutrients more accessible. This study aimed to evaluate the impact of 10% L. digitata feed inclusion and CAZyme supplementation on piglet blood cells, serum metabolites, liver lipid and mineral profiles. Forty weaned piglets were randomly assigned to one of four diets (n = 10 each): a control diet, 10% L. digitata (LA), 10% L. digitata + 0.005% Rovabio® Excel AP (LAR), and 10% L. digitata + 0.01% alginate lyase (LAL). After two weeks of trial, animals were slaughtered and liver and blood serum samples taken for analysis. The results showed that the LA and LAL diets increased blood lymphocytes, IgG and IgM, and decreased serum lipids, improving both cellular and humoral immune response and cardiovascular health. Dietary CAZymes reversed the anti-inflammatory and hematopoietic effects. Additionally, cortisol levels were reduced with seaweed inclusion compared to the control diet (P < 0.001). In the liver, total n-3 PUFA and n-6/n-3 ratio were increased and decreased, respectively, due to eicosapentaenoic acid and α-linolenic acid accumulation (P < 0.001). However, total liver mineral content was incorporated to a lesser extent with the combined seaweed and enzyme diets (P < 0.001), potentially indicating a negative effect on mineral bioavailability. Overall, results suggest that a 10% L. digitata inclusion can effectively improve piglet health by reducing stress during weaning, without the need for dietary CAZymes.
Identification and pathogenicity analysis of leaf brown spot of Juglans regia in China
Authors: Wang Feihu , Liu Chao , Zeng Qian , Zhou Yijie , Liu Feng , Xu Xiulan , Yang Hanbo , Liu Yinggao , Yang Chunlin
Published: April 2023

English walnut (Juglans regia), has high economic and ecological value. As an important tree species for eliminating poverty, it is planted in many Provinces of China. In 2021, new pathogenic fungi were observed in English walnut in Guangyuan City, Sichuan Province, China. The initial symptom of leaf infection is that the leaves are covered with small black spots, which gradually expand into larger brown spots. Most of the spots appeared at the edges of the leaves, and yellow whorls were observed at the junction between the spots and the healthy leaves. The pathogenic fungi were isoalted form collecting disease samples and purified by single-spore culturing. In vitro and field experiments showed that the pathogen could cause brown spots on walnut leaves. The inoculation experiment showed that the symptoms in the field experiment were the same as those observed on the spot; however, slight differences were observed in the in vitro experiment. Ten isolates were obtained from walnut leaves with brown spot symptoms, and these were further characterized based on morphology and DNA sequencing. ITS (internal transcribed spacer), LSU (large sub-unit rDNA), rpb2 (second largest subunit of RNA polymerase) and tub2 (beta-tubulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. The isolate was identified as Nothophoma quercina by morphological and polygene analyses. As far as we are aware, the brown spots on walnut leaves caused by N. quercina is the first report of its kind.
Spatial distribution characteristics of plumes induced by femtosecond laser ablation of silicon in vacuum
Authors: Chen Zhandong , Ning Hua , Zhang Xiulan
Published: April 2023

The spatial distribution characteristics of plumes induced by femtosecond laser ablation of silicon in vacuum are studied by using spectroscopy. The plume spatial distribution clearly shows two zones with different characteristics. The center of the first zone is at a distance of approximately 0.5 mm from the target. Silicon ionic radiation, recombination radiation, and bremsstrahlung mainly occur in this zone, causing an exponential decay with a decay constant of approximately 0.151–0.163 mm. The second zone with a greater area, whose center is at a distance of approximately 1.5 mm from the target, follows the first zone. In this zone, the radiation from silicon atoms and electron-atom collisions dominates, leading to an allometric decay with an allometric exponent of approximately − 1.475 to − 1.376. In the second zone, the electron density spatial distribution is approximately arrowhead-shaped, which is potentially induced by collisions between ambient molecules and the particles in front of the plume. These results indicate that both the recombination effect and expansion effect play important roles and compete with each other in plumes. The recombination effect is dominant near the silicon surface, causing exponential decay. As the distance increases, the electron density decreases exponentially by recombination, causing a more intense expansion effect.
Dramatic, durable response to therapy in gBRCA2-mutated pancreas neuroendocrine carcinoma: opportunity and challenge
Authors: Keane Fergus , Bajwa Raazi , Selenica Pier , Park Wungki , Roehrl Michael H. , Reis-Filho Jorge S. , Mandelker Diana , O’Reilly Eileen M.
Published: April 2023

Poorly differentiated pancreatic neuroendocrine tumors (PDNEC), are a subtype of pancreatic cancer encompassing both small cell and large cell neuroendocrine carcinoma subtypes, and are characterized as distinct in terms of biology and prognosis compared to the more common pancreatic adenocarcinoma. Until recently, there has been a paucity of data on the genomic features of this cancer type. We describe a male patient diagnosed with PDNEC and extensive metastatic disease in the liver at diagnosis. Genomic analysis demonstrated a germline pathogenic variant in BRCA2 with somatic loss-of-heterozygosity of the BRCA2 wild-type allele. Following a favorable response to platinum-based chemotherapy (and the addition of immunotherapy), the patient received maintenance therapy with olaparib, which resulted in a further reduction on follow-up imaging (Fig. 1). After seventeen months of systemic control with olaparib, the patient developed symptomatic central nervous system metastases, which harboured a BRCA2 reversion mutation. No other sites of disease progression were observed. Herein, we report an exceptional outcome through the incorporation of a personalized management approach for a patient with a pancreatic PDNEC, guided by comprehensive genomic sequencing.
Considerations for integrating wearables into the everyday healthcare practice
Authors: Powell Dylan , Godfrey Alan
Published: April 2023

Wearable technologies are becoming ever more popular as suggested tools for use in modern medicine. Studies evidence their growing pragmatism and provision of objective data for a more informative and personalised approach to patient care. Yet many wearables are one dimensional, despite the underlying technology being common across a large array of tools. That is primarily due to the accompanying software, unmodifiable or black box-based scripts that generally lack accessibility or modification, meaning wearables may often get discarded. Use of wearables for sustainable healthcare needs careful consideration.
Search for large topological gaps in atomic spin chains on proximitized superconducting heavy-metal layers
Authors: Beck Philip , Nyári Bendegúz , Schneider Lucas , Rózsa Levente , Lászlóffy András , Palotás Krisztián , Szunyogh László , Ujfalussy Balázs , Wiebe Jens , Wiesendanger Roland
Published: April 2023

One-dimensional systems comprising s-wave superconductivity with meticulously tuned magnetism realize topological superconductors hosting Majorana modes whose stability is determined by the gap size. However, for atomic spin chains on superconductors, the effect of the substrate’s spin-orbit coupling on the topological gap is largely unexplored. Here, we introduce an atomic layer of the heavy metal gold on a niobium surface combining strong spin-orbit coupling and a large superconducting gap with a high crystallographic quality, enabling the assembly of defect-free iron chains using a scanning tunneling microscope tip. Scanning tunneling spectroscopy experiments and density functional theory calculations reveal ungapped Yu–Shiba–Rusinov bands in the ferromagnetic chain despite the heavy substrate. By artificially imposing a spin spiral state, the calculations indicate minigap opening and zero-energy edge state formation. The methodology enables a material screening of heavy-metal layers on elemental superconductors for ideal systems hosting Majorana edge modes protected by large topological gaps.
Omnipresent authigenic calcite distorts Arctic radiocarbon chronology
Authors: Wollenburg Jutta Erika , Matthiessen Jens , Vogt Christoph , Nehrke Gernot , Grotheer Hendrik , Wilhelms-Dick Dorothee , Geibert Walter , Mollenhauer Gesine
Published: April 2023

As calcareous foraminifera precipitate their shells from the surrounding water mass, they are the basis of most marine radiocarbon chronologies and paleo-proxies. Nevertheless, post-mortem alteration of shells, especially addition of authigenic calcite, impact proxy records. In the Arctic Ocean, authigenic calcite overgrowth on foraminifera has been attributed to hydrocarbon release, with a single report on 13C-enriched authigenic calcite, indicating a different carbon source. Here, we use comparative radiocarbon, carbon and oxygen isotope measurements to show that this 13C-enriched authigenic calcite impacts a large proportion of Holocene and the majority of last glacial planktonic foraminifera in the Arctic Basin. This authigenic precipitated calcite is 14C-depleted, so overgrowth results in invariably older 14C-ages. We show that, in comparison with published data, the true chronology of Arctic basin sediments can deviate by more than 10,000 years in critical parts of the last deglaciation and that stable oxygen and carbon isotopes, as likely all calcite-based proxy-records are affected with potential implications for paleoclimate models.
Copper(ii) defect-cubane water oxidation electrocatalysts: from molecular tetramers to oxidic nanostructures
Authors: Adiyeri Saseendran Devi Prasad , Fischer Jörg W. A. , Müller Lea , Abbott Daniel F. , Mougel Victor , Jeschke Gunnar , Triana Carlos A. , Patzke Greta R.
Published: April 2023

We introduce a bio-inspired copper cubane-type water oxidation catalyst, and we track its transformations and electrocatalytically active species with comprehensive in situ and post-catalytic techniques.
Competition between side-chain interactions dictates 2D polymer stacking order
Authors: Oanta Alexander K. , Pelkowski Chloe E. , Strauss Michael J. , Dichtel William R.
Published: April 2023

Competition between zwitterionic electrostatic forces and alkyl stabilization directs the stacking order of two-dimensional polymer sheets and resulting materials quality.
Nitroreductase-sensitive fluorescent covalent organic framework for tumor hypoxia imaging in cells
Authors: Skorjanc Tina , Shetty Dinesh , Kumar Sushil , Makuc Damjan , Mali Gregor , Volavšek Janez , Bergant Marušič Martina , Valant Matjaz
Published: April 2023

A fluorescent covalent organic framework (COF) for imaging hypoxic conditions in tumor cells.
Rivaroxaban eutectics with improved solubility, dissolution rates, bioavailability and stability
Authors: Shaligram Parth S. , George Christy P. , Sharma Himanshu , Mahadik Kakasaheb R. , Patil Sharvil , Vanka Kumar , Arulmozhi S. , Gonnade Rajesh G.
Published: April 2023

Six acidic coformers were used to prepare eutectics of rivaroxaban (RXB), a factor Xa inhibitor. The eutectics displayed improved solubility, dissolution rate, and bioavailability of RXB, without compromising on its stability.
Structure and dynamics of dynamic covalent cross-linked PEOs and PEO/LiPF6 electrolytes: a coarse-grained simulation study
Authors: Wu Tongfei , Zhang Ping
Published: April 2023

A coarse-grained model is created for dynamic covalent cross-linked PEO16–LiPF6 with the assistance of machine learning. Based on MD simulations, the relationship between dynamic-bond reshuffling, ion transport and segmental dynamics is investigated.
Recreational drug-use as an urban source of nitrous oxide
Authors: Charoenpornpukdee Kanokrat , Stanley Kieran , Pitt Joe , Wenger Angelina , Manning Alistair , Young Dickon , Say Daniel , O'Doherty Simon
Published: April 2023

Our urban measurement found that recreational use became an unnecessary anthropogenic source of N2O, and that the UK emission inventory provided a significant underestimate of this source.
Electroorganic synthesis in aqueous solution via generation of strongly oxidizing and reducing intermediates
Authors: Hosseini Seyyedamirhossein , Beeler Joshua A. , Sanford Melanie S. , White Henry S.
Published: April 2023

Electrocatalytic reduction of S2O82− in water yields SO4˙−, which is employed for homogeneous oxidation reactions. Highly reducing CO2˙− was electrogenerated via mediated oxidation of C2O42− and utilized for various reductive reactions.
Development of Moringa oleifera as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems
Authors: Manjunath Souparnika H. , Nataraj Prabhakaran , Swamy Vikas H. , Sugur Kavya , Dey Sumit K. , Ranganathan Veena , Daniel Shyni , Leihang Zonunsiami , Sharon Veronica , Chandrashekharappa Sandeep , Sajeev Nithin , Venkatareddy Venkataramana G. , Chuturgoon Anil , Kuppusamy Gowthamarajan , Madhunapantula SubbaRao V. , Thimmulappa Rajesh K.
Published: April 2023

Pharmacological activation of nuclear factor erythroid 2 related factor 2 (NRF2) by Moringa oleifera leaves protects against environmental diseases by inhibiting oxidative and inflammatory injury.
Detection of H2S using a novel fluorescent nanoprobe in plasma and tissue samples from ASD patients and model mice
Authors: Zhang Changmei , Wang Feng , Liu Zehui , Guo Peiwen , Liang Huirong , Tian Wenru , Yang Lingyuan , Shi Yaxin , Zou Mingyang , Wu Lijie
Published: April 2023

A novel fluorescent nanoprobe was prepared to measure H2S in plasma and tissue samples from ASD patients and model mice.
Theoretical insight into the influence of different molecular design strategies on photovoltaic properties for a series of POM-based dyes applied in dye-sensitized solar cells
Authors: Gao Yu , Lu Zhi-Bin
Published: April 2023

Different molecular design strategies including introduction of a second donor or a change in π linker units.
Progress and prospectives of solution-processed kesterite absorbers for photovoltaic applications
Authors: Wang Lijing , Wang Yufei , Zhou Zhengji , Zhou Wenhui , Kou Dongxing , Meng Yuena , Qi Yafang , Yuan Shengjie , Han Litao , Wu Sixin
Published: April 2023

Solution-processed kesterite absorbers using different solvents are summarized, and the critical insights toward high-efficiency CZTSSe solar cells are presented.
Plasmon-coupled circularly polarized luminescence: generation and enhancement
Authors: Meng Dejing , Zhao Tonghan , Yang Dong , Jin Xue , Duan Pengfei
Published: April 2023

Two efficient methods to modulate circularly polarized luminescence (CPL) signals by plasmonic metal nanoparticles: amplified and induced CPL signals.
Growth mechanism study and band structure modulation of a manganese doped two-dimensional BlueP-Au network
Authors: Guo Yuxuan , Liu Chen , Liao Jiangwen , Liu Yunpeng , Qian Haijie , Xu Jinfeng , Wang Hao , Nie Kaiqi , Wang Jiaou
Published: April 2023

We introduced Mn atoms into the BlueP-Au network for the first time in an experiment and proposed a growth model. We found the band structure was modulated after Mn deposition.