bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnoses
Authors: Cathey Amber L. , Nguyen Vy K. , Colacino Justin A. , Woodruff Tracey J. , Reynolds Peggy , Aung Max T.
Published: September 2023

Background

Some hormonally active cancers have low survival rates, but a large proportion of their incidence remains unexplained. Endocrine disrupting chemicals may affect hormone pathways in the pathology of these cancers.

Objective

To evaluate cross-sectional associations between per- and polyfluoroalkyl substances (PFAS), phenols, and parabens and self-reported previous cancer diagnoses in the National Health and Nutrition Examination Survey (NHANES).

Methods

We extracted concentrations of 7 PFAS and 12 phenols/parabens and self-reported diagnoses of melanoma and cancers of the thyroid, breast, ovary, uterus, and prostate in men and women (≥20 years). Associations between previous cancer diagnoses and an interquartile range increase in exposure biomarkers were evaluated using logistic regression models adjusted for key covariates. We conceptualized race as social construct proxy of structural social factors and examined associations in non-Hispanic Black, Mexican American, and other Hispanic participants separately compared to White participants.

Results

Previous melanoma in women was associated with higher PFDE (OR:2.07, 95% CI: 1.25, 3.43), PFNA (OR:1.72, 95% CI: 1.09, 2.73), PFUA (OR:1.76, 95% CI: 1.07, 2.89), BP3 (OR: 1.81, 95% CI: 1.10, 2.96), DCP25 (OR: 2.41, 95% CI: 1.22, 4.76), and DCP24 (OR: 1.85, 95% CI: 1.05, 3.26). Previous ovarian cancer was associated with higher DCP25 (OR: 2.80, 95% CI: 1.08, 7.27), BPA (OR: 1.93, 95% CI: 1.11, 3.35) and BP3 (OR: 1.76, 95% CI: 1.00, 3.09). Previous uterine cancer was associated with increased PFNA (OR: 1.55, 95% CI: 1.03, 2.34), while higher ethyl paraben was inversely associated (OR: 0.31, 95% CI: 0.12, 0.85). Various PFAS were associated with previous ovarian and uterine cancers in White women, while MPAH or BPF was associated with previous breast cancer among non-White women.

Impact Statement

Biomarkers across all exposure categories (phenols, parabens, and per- and poly- fluoroalkyl substances) were cross-sectionally associated with increased odds of previous melanoma diagnoses in women, and increased odds of previous ovarian cancer was associated with several phenols and parabens. Some associations differed by racial group, which is particularly impactful given the established racial disparities in distributions of exposure to these chemicals. This is the first epidemiological study to investigate exposure to phenols in relation to previous cancer diagnoses, and the first NHANES study to explore racial/ethnic disparities in associations between environmental phenol, paraben, and PFAS exposures and historical cancer diagnosis.
Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings
Authors: Ogunlana Lois , Kaur Divjot , Shaw Liam P , Jangir Pramod , Walsh Timothy , Uphoff Stephan , MacLean R C
Published: September 2023

Antibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be maintained in the absence of continual antibiotic exposure. Here we investigate this problem in the context of mcr-1, a globally disseminated gene that confers resistance to colistin, an agricultural antibiotic that is used as a last resort for the treatment of multi-drug resistant infections. Here we show that regulatory evolution has fine-tuned the expression of mcr-1, allowing E. coli to reduce the fitness cost of mcr-1 while simultaneously increasing colistin resistance. Conjugative plasmids have transferred low-cost/high-resistance mcr-1 alleles across an incredible diversity of E. coli strains, further stabilising mcr-1 at the species level. Regulatory mutations were associated with increased mcr-1 stability in pig farms following a ban on the use of colistin as a growth promoter that decreased colistin consumption by 90%. Our study shows how regulatory evolution and plasmid transfer can combine to stabilise resistance and limit the impact of reducing antibiotic consumption.
Area-level inequalities in the provision of NHS orthodontic care in England from 2016 to 2019
Authors: Al-Hammadi Zinab , Ravaghi Vahid , Hill Kirsty , Morris Alexander J.
Published: September 2023

Objective To investigate geographic inequalities in the provision of NHS orthodontic care in England at the area level.

Methods NHS dental activity data were analysed for the three financial years April 2016 to March 2019. The measures used were units of dental activity (UDA), units of orthodontic activity (UOA) and commencement of orthodontic treatment. Two orthodontic activity indices were created to assess relative volumes of care. Deprivation was measured using the index of multiple deprivations. Slope and relative inequality indices were used to assess inequality.

Results Nearly 12.4 million UOA and 572,987 courses of treatment in England were reported under NHS arrangements in the three years studied. There were significant variations in the rates of UOA (0-716) and UDA (148-918) provided per 100 children (0-17 years) at the local authority level. The variation was not associated with deprivation at the local authority level.

Conclusions There were significant disparities in the provision of NHS orthodontic treatment at the local authority level, but this was not associated with area-level measures of deprivation. Inequality in the uptake of orthodontic care may not be due to area-level disparities in service provision.
KLF4 regulates skeletal muscle development and regeneration by directly targeting P57 and Myomixer
Authors: Cai Shufang , Wang Xiaoyu , Xu Rong , Liang Ziyun , Zhu Qi , Chen Meilin , Lin Zhuhu , Li Chenggan , Duo Tianqi , Tong Xian , Li Enru , He Zuyong , Liu Xiaohong , Chen Yaosheng , Mo Delin
Published: September 2023

Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger-containing transcription factor that regulates diverse cellular processes such as cell proliferation, apoptosis, and differentiation. Our previous study showed that KLF4 expression is upregulated in skeletal muscle ontogeny during embryonic development in pigs, suggesting its importance for skeletal muscle development and muscle function. We revealed here that KLF4 plays a critical role in skeletal muscle development and regeneration. Specific knockout of KLF4 in skeletal muscle impaired muscle formation further affecting physical activity and also defected skeletal muscle regeneration. In vitro, KLF4 was highly expressed in proliferating myoblasts and early differentiated cells. KLF4 knockdown promoted myoblast proliferation and inhibited myoblast fusion, while its overexpression showed opposite results. Mechanically, in proliferating myoblasts, KLF4 inhibits myoblast proliferation through regulating cell cycle arrest protein P57 by directly targeting its promoter; while in differentiated myoblasts, KLF4 promotes myoblast fusion by transcriptionally activating Myomixer. Our study provides mechanistic information for skeletal muscle development, reduced muscle strength and impaired regeneration after injury and unveiling the mechanism of KLF4 in myogenic regulation.
Probing three-dimensional mesoscopic interfacial structures in a single view using multibeam X-ray coherent surface scattering and holography imaging
Authors: Chu Miaoqi , Jiang Zhang , Wojcik Michael , Sun Tao , Sprung Michael , Wang Jin
Published: September 2023

Visualizing surface-supported and buried planar mesoscale structures, such as nanoelectronics, ultrathin-film quantum dots, photovoltaics, and heterogeneous catalysts, often requires high-resolution X-ray imaging and scattering. Here, we discovered that multibeam scattering in grazing-incident reflection geometry is sensitive to three-dimensional (3D) structures in a single view, which is difficult in conventional scattering or imaging approaches. We developed a 3D finite-element-based multibeam-scattering analysis to decode the heterogeneous electric-field distribution and to faithfully reproduce the complex scattering and surface features. This approach further leads to the demonstration of hard-X-ray Lloyd’s mirror interference of scattering waves, resembling dark-field, high-contrast surface holography under the grazing-angle scattering conditions. A first-principles calculation of the single-view holographic images resolves the surface patterns’ 3D morphology with nanometer resolutions, which is critical for ultrafine nanocircuit metrology. The holographic method and simulations pave the way for single-shot structural characterization for visualizing irreversible and morphology-transforming physical and chemical processes in situ or operando.
Chemical evolution of primordial salts and organic sulfur molecules in the asteroid 162173 Ryugu
Authors: Yoshimura Toshihiro , Takano Yoshinori , Naraoka Hiroshi , Koga Toshiki , Araoka Daisuke , Ogawa Nanako O. , Schmitt-Kopplin Philippe , Hertkorn Norbert , Oba Yasuhiro , Dworkin Jason P. , Aponte José C. , Yoshikawa Takaaki , Tanaka Satoru , Ohkouchi Naohiko , Hashiguchi Minako , McLain Hannah , Parker Eric T. , Sakai Saburo , Yamaguchi Mihoko , Suzuki Takahiro , Yokoyama Tetsuya , Yurimoto Hisayoshi , Nakamura Tomoki , Noguchi Takaaki , Okazaki Ryuji , Yabuta Hikaru , Sakamoto Kanako , Yada Toru , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Yogata Kasumi , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Yoshikawa Makoto , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Nakazawa Satoru , Watanabe Sei-ichiro , Tsuda Yuichi , Tachibana Shogo ,   Hayabusa2-initial-analysis SOM team, Hamase Kenji , Furusho Aogu , Fukushima Kazuhiko , Aoki Dan , Glavin Daniel P. , McLain Hannah L. , Elsila Jamie E. , Graham Heather V. , Eiler John M. , Ruf Alexander , Orthous-Daunay Francois-Regis , Wolters Cédric , Isa Junko , Vuitton Véronique , Thissen Roland , Sugahara Haruna , Mita Hajime , Furukawa Yoshihiro , Chikaraishi Yoshito , Morita Mayu , Onose Morihiko , Kabashima Fumie , Fujishima Kosuke , Sato Hajime , Sasaki Kazunori , Kano Kuniyuki , Nomura Shin-ichiro M. , Aoki Junken , Yamazaki Tomoya , Kimura Yuki
Published: September 2023

Samples from the carbonaceous asteroid (162173) Ryugu provide information on the chemical evolution of organic molecules in the early solar system. Here we show the element partitioning of the major component ions by sequential extractions of salts, carbonates, and phyllosilicate-bearing fractions to reveal primordial brine composition of the primitive asteroid. Sodium is the dominant electrolyte of the salt fraction extract. Anions and NH4+ are more abundant in the salt fraction than in the carbonate and phyllosilicate fractions, with molar concentrations in the order SO42− > Cl− > S2O32− > NO3− > NH4+. The salt fraction extracts contain anionic soluble sulfur-bearing species such as Sn-polythionic acids (n < 6), Cn-alkylsulfonates, alkylthiosulfonates, hydroxyalkylsulfonates, and hydroxyalkylthiosulfonates (n < 7). The sulfur-bearing soluble compounds may have driven the molecular evolution of prebiotic organic material transforming simple organic molecules into hydrophilic, amphiphilic, and refractory S allotropes.
Microcavity phonoritons – a coherent optical-to-microwave interface
Authors: Kuznetsov Alexander Sergeevich , Biermann Klaus , Reynoso Andres Alejandro , Fainstein Alejandro , Santos Paulo Ventura
Published: September 2023

Optomechanical systems provide a pathway for the bidirectional optical-to-microwave interconversion in (quantum) networks. These systems can be implemented using hybrid platforms, which efficiently couple optical photons and microwaves via intermediate agents, e.g. phonons. Semiconductor exciton-polariton microcavities operating in the strong light-matter coupling regime offer enhanced coupling of near-infrared photons to GHz phonons via excitons. Furthermore, a new coherent phonon-exciton-photon quasiparticle termed phonoriton, has been theoretically predicted to emerge in microcavities, but so far has eluded observation. Here, we experimentally demonstrate phonoritons, when two exciton-polariton condensates confined in a μm-sized trap within a phonon-photon microcavity are strongly coupled to a confined phonon which is resonant with the energy separation between the condensates. We realize control of phonoritons by piezoelectrically generated phonons and resonant photons. Our findings are corroborated by quantitative models. Thus, we establish zero-dimensional phonoritons as a coherent microwave-to-optical interface.
Intracellular Fusobacterium nucleatum infection attenuates antitumor immunity in esophageal squamous cell carcinoma
Authors: Li Yiqiu , Xing Shan , Chen Fangfang , Li Qifan , Dou Shuheng , Huang Yuying , An Jun , Liu Wanli , Zhang Ge
Published: September 2023

Currently, the influence of the tumor microbiome on the effectiveness of immunotherapy remains largely unknown. Intratumoural Fusobacterium nucleatum (Fn) functions as an oncogenic bacterium and can promote tumor progression in esophageal squamous cell carcinoma (ESCC). Our previous study revealed that Fn is a facultative intracellular bacterium and that its virulence factor Fn-Dps facilitates the intracellular survival of Fn. In this study, we find that Fn DNA is enriched in the nonresponder (NR) group among ESCC patients receiving PD-1 inhibitor and that the serum antibody level of Fn is significantly higher in the NR group than in the responder (R) group. In addition, Fn infection has an opposite impact on the efficacy of αPD-L1 treatment in animals. Mechanistically, we confirm that Fn can inhibit the proliferation and cytokine secretion of T cells and that Fn-Dps binds to the PD-L1 gene promoter activating transcription factor-3 (ATF3) to transcriptionally upregulate PD-L1 expression. Our results suggest that it may be an important therapeutic strategy to eradicate intratumoral Fn infection before initiating ESCC immunotherapies.
Heterostructure particles enable omnidispersible in water and oil towards organic dye recycle
Authors: Song Yongyang , Zhou Jiajia , Zhu Zhongpeng , Li Xiaoxia , Zhang Yue , Shen Xinyi , O’Reilly Padraic , Li Xiuling , Liang Xinmiao , Jiang Lei , Wang Shutao
Published: September 2023

Dispersion of colloidal particles in water or oil is extensively desired for industrial and environmental applications. However, it often strongly depends on indispensable assistance of chemical surfactants or introduction of nanoprotrusions onto the particle surface. Here we demonstrate the omnidispersity of hydrophilic-hydrophobic heterostructure particles (HL-HBPs), synthesized by a surface heterogeneous nanostructuring strategy. Photo-induced force microscopy (PiFM) and adhesion force images both indicate the heterogeneous distribution of hydrophilic domains and hydrophobic domains on the particle surface. These alternating domains allow HL-HBPs to be dispersed in various solvents with different polarity and boiling point. The HL-HBPs can efficiently adsorb organic dyes from water and release them into organic solvents within several seconds. The surface heterogeneous nanostructuring strategy provides an unconventional approach to achieve omnidispersion of colloidal particles beyond surface modification, and the omnidispersible HL-HBPs demonstrate superior capability for dye recycle merely by solvent exchange. These omnidispersible HL-HBPs show great potentials in industrial process and environmental protection.
High-fidelity parametric beamsplitting with a parity-protected converter
Authors: Lu Yao , Maiti Aniket , Garmon John W. O. , Ganjam Suhas , Zhang Yaxing , Claes Jahan , Frunzio Luigi , Girvin Steven M. , Schoelkopf Robert J.
Published: September 2023

Fast, high-fidelity operations between microwave resonators are an important tool for bosonic quantum computation and simulation with superconducting circuits. An attractive approach for implementing these operations is to couple these resonators via a nonlinear converter and actuate parametric processes with RF drives. It can be challenging to make these processes simultaneously fast and high fidelity, since this requires introducing strong drives without activating parasitic processes or introducing additional decoherence channels. We show that in addition to a careful management of drive frequencies and the spectrum of environmental noise, leveraging the inbuilt symmetries of the converter Hamiltonian can suppress unwanted nonlinear interactions, preventing converter-induced decoherence. We demonstrate these principles using a differentially-driven DC-SQUID as our converter, coupled to two high-Q microwave cavities. Using this architecture, we engineer a highly-coherent beamsplitter and fast (~100 ns) swaps between the cavities, limited primarily by their intrinsic single-photon loss. We characterize this beamsplitter in the cavities’ joint single-photon subspace, and show that we can detect and post-select photon loss events to achieve a beamsplitter gate fidelity exceeding 99.98%, which to our knowledge far surpasses the current state of the art.
Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase
Authors: Piniello Beatriz , Macías-León Javier , Miyazaki Shun , García-García Ana , Compañón Ismael , Ghirardello Mattia , Taleb Víctor , Veloz Billy , Corzana Francisco , Miyagawa Atsushi , Rovira Carme , Hurtado-Guerrero Ramon
Published: September 2023

Soluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic complexes. Here, we report structures of binary and ternary NGT complexes of Aggregatibacter aphrophilus NGT (AaNGT), revealing an essential dyad of basic/acidic residues located in the N-terminal all α-domain (AAD) that intimately recognizes the Thr residue within the conserved motif Asn0-X+1-Ser/Thr+2. Poor substrates and inhibitors such as UDP-galactose and UDP-glucose mimetics adopt non-productive conformations, decreasing or impeding catalysis. QM/MM simulations rationalize these results, showing that AaNGT follows a SN2 reaction mechanism in which the acceptor asparagine uses its imidic form for catalysis and the UDP-glucose phosphate group acts as a general base. These findings provide key insights into the mechanism of NGTs and will facilitate the design of structure-based inhibitors to treat diseases caused by non-typeable H. influenzae or other Gram-negative bacteria.
Natural plant growth and development achieved in the IPK PhenoSphere by dynamic environment simulation
Authors: Heuermann Marc C. , Knoch Dominic , Junker Astrid , Altmann Thomas
Published: September 2023

In plant science, the suboptimal match of growing conditions hampers the transfer of knowledge from controlled environments in glasshouses or climate chambers to field environments. Here we present the PhenoSphere, a plant cultivation infrastructure designed to simulate field-like environments in a reproducible manner. To benchmark the PhenoSphere, the effects on plant growth of weather conditions of a single maize growing season and of an averaged season over three years are compared to those of a standard glasshouse and of four years of field trials. The single season simulation proves superior to the glasshouse and the averaged season in the PhenoSphere: The simulated weather regime of the single season triggers plant growth and development progression very similar to that observed in the field. Hence, the PhenoSphere enables detailed analyses of performance-related trait expression and causal biological mechanisms in plant populations exposed to weather conditions of current and anticipated future climate scenarios.
Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality
Authors: Dong Shengzhang , Dimopoulos George
Published: September 2023

Ae. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disruption by CRISPR/Cas9-based Ago2 knockout impaired the mosquitoes’ ability to degrade arbovirus RNA leading to hyper-infection accompanied by cell lysis and tissue damage. Ago2 disruption impaired DNA repair mechanisms and the autophagy pathway by altering histone abundance. This compromised DNA repair and removal of damaged cellular organelles and dysfunctional aggregates promoted mosquito death. We also report that hyper-infection of Ago2 knockout mosquitoes stimulated a broad-spectrum antiviral immunity, including apoptosis, which may counteract infection. Taken together, our studies reveal novel roles for Ago2 in protecting mosquitoes from arbovirus infection and associated death.
Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection
Authors: Ullah Tomalika R. , Johansen Matt D. , Balka Katherine R. , Ambrose Rebecca L. , Gearing Linden J. , Roest James , Vivian Julian P. , Sapkota Sunil , Jayasekara W. Samantha N. , Wenholz Daniel S. , Aldilla Vina R. , Zeng Jun , Miemczyk Stefan , Nguyen Duc H. , Hansbro Nicole G. , Venkatraman Rajan , Kang Jung Hee , Pang Ee Shan , Thomas Belinda J. , Alharbi Arwaf S. , Rezwan Refaya , O’Keeffe Meredith , Donald William A. , Ellyard Julia I. , Wong Wilson , Kumar Naresh , Kile Benjamin T. , Vinuesa Carola G. , Kelly Graham E. , Laczka Olivier F. , Hansbro Philip M. , De Nardo Dominic , Gantier Michael P.
Published: September 2023

TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to these responses is unknown. Here we find that the small molecule idronoxil inhibits TBK1/IKKε signalling through destabilisation of TBK1/IKKε protein complexes. Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation.
Light-enhanced molecular polarity enabling multispectral color-cognitive memristor for neuromorphic visual system
Authors: Lee Jongmin , Jeong Bum Ho , Kamaraj Eswaran , Kim Dohyung , Kim Hakjun , Park Sanghyuk , Park Hui Joon
Published: September 2023

An optoelectronic synapse having a multispectral color-discriminating ability is an essential prerequisite to emulate the human retina for realizing a neuromorphic visual system. Several studies based on the three-terminal transistor architecture have shown its feasibility; however, its implementation with a two-terminal memristor architecture, advantageous to achieving high integration density as a simple crossbar array for an ultra-high-resolution vision chip, remains a challenge. Furthermore, regardless of the architecture, it requires specific material combinations to exhibit the photo-synaptic functionalities, and thus its integration into various systems is limited. Here, we suggest an approach that can universally introduce a color-discriminating synaptic functionality into a two-terminal memristor irrespective of the kinds of switching medium. This is possible by simply introducing the molecular interlayer with long-lasting photo-enhanced dipoles that can adjust the resistance of the memristor at the light-irradiation. We also propose the molecular design principle that can afford this feature. The optoelectronic synapse array having a color-discriminating functionality is confirmed to improve the inference accuracy of the convolutional neural network for the colorful image recognition tasks through a visual pre-processing. Additionally, the wavelength-dependent optoelectronic synapse can also be leveraged in the design of a light-programmable reservoir computing system.
Whole-genome screens reveal regulators of differentiation state and context-dependent migration in human neutrophils
Authors: Belliveau Nathan M. , Footer Matthew J. , Akdoǧan Emel , van Loon Aaron P. , Collins Sean R. , Theriot Julie A.
Published: September 2023

Neutrophils are the most abundant leukocyte in humans and provide a critical early line of defense as part of our innate immune system. We perform a comprehensive, genome-wide assessment of the molecular factors critical to proliferation, differentiation, and cell migration in a neutrophil-like cell line. Through the development of multiple migration screen strategies, we specifically probe directed (chemotaxis), undirected (chemokinesis), and 3D amoeboid cell migration in these fast-moving cells. We identify a role for mTORC1 signaling in cell differentiation, which influences neutrophil abundance, survival, and migratory behavior. Across our individual migration screens, we identify genes involved in adhesion-dependent and adhesion-independent cell migration, protein trafficking, and regulation of the actomyosin cytoskeleton. This genome-wide screening strategy, therefore, provides an invaluable approach to the study of neutrophils and provides a resource that will inform future studies of cell migration in these and other rapidly migrating cells.
Experimental confirmation of driving pressure boosting and smoothing for hybrid-drive inertial fusion at the 100-kJ laser facility
Authors: Yan Ji , Li Jiwei , He X. T. , Wang Lifeng , Chen Yaohua , Wang Feng , Han Xiaoying , Pan Kaiqiang , Liang Juxi , Li Yulong , Guan Zanyang , Liu Xiangming , Che Xingsen , Chen Zhongjing , Zhang Xing , Xu Yan , Li Bin , He Minqing , Cai Hongbo , Hao Liang , Liu Zhanjun , Zheng Chunyang , Dai Zhensheng , Fan Zhengfeng , Qiao Bin , Li Fuquan , Jiang Shaoen , Yu M. Y. , Zhu Shaoping
Published: September 2023

In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43–50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6–4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8–4.0 and 3.5–3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.
Epitaxial growth of metal-organic framework nanosheets into single-crystalline orthogonal arrays
Authors: Zou Yingying , Liu Chao , Zhang Chaoqi , Yuan Ling , Li Jiaxin , Bao Tong , Wei Guangfeng , Zou Jin , Yu Chengzhong
Published: September 2023

Construction of two-dimensional nanosheets into three-dimensional regular structures facilitates the mass transfer and exploits the maximum potential of two-dimensional building blocks in applications such as catalysis. Here, we report the synthesis of metal-organic frameworks with an orthogonal nanosheet array. The assembly involves the epitaxial growth of single crystalline metal-organic framework nanosheets with a naturally non-preferred facet exposure as the shell on a cubic metal-organic framework as the core. The nanosheets, despite of two typical shapes and crystallographic orientations, also form a single crystalline orthogonally arrayed framework. The density and size of nanosheets in the core-shell-structured composite metal-organic frameworks can be well adjusted. Moreover, metal-organic frameworks with a single composition and hollow orthogonal nanosheet array morphology can be obtained. Benefiting from the unusual facet exposure and macroporous structure, the designed structure exhibits improved electrocatalytic oxygen evolution activity compared to conventional nanosheets.
Structure of human drug transporters OATP1B1 and OATP1B3
Authors: Ciută Anca-Denise , Nosol Kamil , Kowal Julia , Mukherjee Somnath , Ramírez Ana S. , Stieger Bruno , Kossiakoff Anthony A. , Locher Kaspar P.
Published: September 2023

The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug elimination from the human body. Polymorphic variants of these transporters can cause reduced drug clearance and adverse drug effects such as statin-induced rhabdomyolysis, and co-administration of OATP substrates can lead to damaging drug-drug interaction. Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity.
A GPU-based computational framework that bridges neuron simulation and artificial intelligence
Authors: Zhang Yichen , He Gan , Ma Lei , Liu Xiaofei , Hjorth J. J. Johannes , Kozlov Alexander , He Yutao , Zhang Shenjian , Kotaleski Jeanette Hellgren , Tian Yonghong , Grillner Sten , Du Kai , Huang Tiejun
Published: September 2023

Biophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such a process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs with 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience tasks. We investigate how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines. Furthermore, we provide a brief discussion on the potential of DeepDendrite for AI, specifically highlighting its ability to enable the efficient training of biophysically detailed models in typical image classification tasks.
Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice
Authors: Ha Pin , Kwak Jin Hee , Zhang Yulong , Shi Jiayu , Tran Luan , Liu Timothy Pan , Pan Hsin-Chuan , Lee Samantha , Kim Jong Kil , Chen Eric , Shirazi-Fard Yasaman , Stodieck Louis S. , Lin Andy , Zheng Zhong , Dong Stella Nuo , Zhang Xinli , Wu Benjamin M. , Ting Kang , Soo Chia
Published: September 2023

Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).
Non-adaptive measurement-based quantum computation on IBM Q
Authors: Mackeprang Jelena , Bhatti Daniel , Barz Stefanie
Published: September 2023

We test the quantumness of IBM’s quantum computer IBM Quantum System One in Ehningen, Germany. We generate generalised n-qubit GHZ states and measure Bell inequalities to investigate the n-party entanglement of the GHZ states. The implemented Bell inequalities are derived from non-adaptive measurement-based quantum computation (NMQC), a type of quantum computing that links the successful computation of a non-linear function to the violation of a multipartite Bell-inequality. The goal is to compute a multivariate Boolean function that clearly differentiates non-local correlations from local hidden variables (LHVs). Since it has been shown that LHVs can only compute linear functions, whereas quantum correlations are capable of outputting every possible Boolean function it thus serves as an indicator of multipartite entanglement. Here, we compute various non-linear functions with NMQC on IBM’s quantum computer IBM Quantum System One and thereby demonstrate that the presented method can be used to characterize quantum devices. We find a violation for a maximum of seven qubits and compare our results to an existing implementation of NMQC using photons.
Pollinator-dependent crops significantly contribute to diets and reduce household nutrient deficiencies in sub-Saharan Africa
Authors: Mulungu Kelvin , Tekelewold Hailemariam , Abro Zewdu , Sevgan Subramanian , Muriithi Beatrice , Ecuru Julius , Beesigamukama Dennis , Kassie Menale
Published: September 2023

Recent literature highlights the potential of animal pollinator-dependent (PD) crops in enhancing food and nutrition security, although there is a lack of detailed household-level estimates. In this study, we investigate the nutrient composition, productivity, and contribution of PD and pollinator-independent (PI) crops to household nutrition in four sub-Saharan African (SSA) countries. We also evaluate the impact of reallocating resources from PI crops to PD crops on nutrient deficiencies, utilizing nationally representative panel data from three waves and over 30,000 household-year observations. Our findings reveal that PD crops exhibit higher micronutrient content per unit, albeit with lower macronutrient content compared to PI crops. PI crops have higher yield of calories per hectare while PD crops have higher vitamin A yield per hectare. However, protein and iron yield for PD and PI crops varies across countries. PI crops predominantly contribute to macronutrients and iron, while PD crops significantly contribute to vitamin A production. Our econometric results demonstrate that increasing the cultivation of PD crops relative to PI crops reduces the prevalence of nutrient deficiencies and increases crop income without compromising macronutrients production. This suggests that greater investment in PD crop production can be an integral approach to achieving nutrition security in SSA.
Floquet space exploration for the dual-dressing of a qubit
Authors: Fregosi Alessandro , Marinelli Carmela , Gabbanini Carlo , Bevilacqua Giuseppe , Biancalana Valerio , Arimondo Ennio , Fioretti Andrea
Published: September 2023

The application of a periodic nonresonant drive to a system allows the Floquet engineering of effective fields described by a broad class of quantum simulated Hamiltonians. The Floquet evolution is based on two different elements. The first one is a time-independent or stroboscopic evolution with an effective Hamiltonian corresponding to the quantum simulation target. The second element is the time evolution at the frequencies of the nonresonant driving and of its harmonics, denoted as micromotion. We examine experimentally and theoretically the harmonic dual-dressing Floquet engineering of a cold atomic two-level sample. Our focus is the dressing operation with small bare energies and large Rabi frequencies, where frequencies and amplitudes of the stroboscopic/micromotion time evolutions are comparable. At the kHz range of our dressed atom oscillations, we probe directly both the stroboscopic and micromotion components of the qubit global time evolution. We develop ad-hoc monitoring tools of the Floquet space evolution. The direct record of the time evolution following a pulsed excitation demonstrates the interplay between the two components of the spin precession in the Floquet space. From the resonant pumping of the dressed system at its evolution frequencies, Floquet eigenenergy spectra up to the fifth order harmonic of the dressing frequency are precisely measured as function of dressing parameters. Dirac points of the Floquet eigenenergies are identified and, correspondingly, a jump in the dynamical phase shift is measured. The stroboscopic Hamiltonian eigenfrequencies are measured also from the probe of the micromotion sidebands.These monitoring tools are appropriate for quantum simulation/computation investigations. Our results evidence that the stroboscopic phase shift of the qubit wavefunction contains an additional information that opens new simulation directions.
Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment
Authors: Doleschal Bernhard , Taghizadeh Hossein , Webersinke Gerald , Piringer Gudrun , Schreil Georg , Decker Jörn , Aichberger Karl J. , Kirchweger Patrick , Thaler Josef , Petzer Andreas , Schmitt Clemens A. , Prager Gerald W. , Rumpold Holger
Published: September 2023

Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFStargeted/PFSpre-chemotherapy) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.
Simple dihydropyridine-based colorimetric chemosensors for heavy metal ion detection, biological evaluation, molecular docking, and ADMET profiling
Authors: Hamada Wafaa M. , El-Nahass Marwa N. , Noser Ahmed A. , Fayed Tarek A. , El-Kemary Maged , Salem Maha M. , Bakr Eman A.
Published: September 2023

In this study, two novel chemosensors containing dihydropyridine fragment namely; (2E, 2Eʹ)-1,1ʹ-(2,6-dimethyl-1,4-dihydropyridine-3,5-diyl)bis(3-(4-(dimethylamino)phenyl)prop-2-en-1-one) (1), (2E,2E',4E,4E')-1,1ʹ -(2,6-dimethyl-1,4-dihydropyridine-3,5-diyl)bis(5-(4-(dimethylamino)phenyl)penta-2,4-dien-1-one) (2) have been synthesized and characterized. The solvatochromic behavior was explored in different solvents of various polarities. The visual detection, as well as UV–Vis and fluorescence measurements were carried out to explore the colorimetric and optical sensing properties of the investigated chemosensors towards various metal ions such as Al3+, Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Mg2+, Hg2+ and Zn2+. The chemosensors 1 and 2 have strong detecting abilities, with excellent sensitivity and selectivity for Cu2+ and Fe3+, respectively, over the other metal ions. The chemosensors were totally reversible upon addition of EDTA to the formed complexes and displayed a turn on–off-on fluorescence response based on an effect of chelation-quenching fluorescence. The antioxidant activities of the investigated chemosensors were assessed. They were examined in-silico for their capacity to block the Akt signaling pathway, which is involved in cancer proliferation with interpreting their pharmacokinetics aspects. Furthermore, in-vitro antitumor evaluation against a panel of cancer cell lines for the investigated chemosensors has been examined. Conclusively, chemosensor 1 was more effective at scavenging free radicals and as an anticancer agent and could be exploited as a therapeutic candidate for cancer therapy than chemosensor 2 due to its potential inhibition of Akt protein.
Impact on quality of life with affirmative feedback on weight loss after gastrectomy
Authors: Lee Seung Soo , Chung Ho Young , Kwon Oh Kyoung
Published: September 2023

This study investigated the feasibility of improving post-gastrectomy satisfaction/quality of life (QoL) of gastric cancer survivors by readjusting their expectations through patient interviews. Weight loss after gastric cancer surgery is common, and a change in the departmental policy helped in providing cancer survivors with an alternative interpretation of lost weight. Under the new policy, a group of patients who were preoperatively overweight or obese were provided with affirmative feedback, despite their postoperative weight loss. The European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 and -STO22 were used to assess the QoL. The postoperative 1-year QoL was compared before (control) and after policy changes (affirmative-feedback group) in preoperatively overweight (or obese) patients who lost weight. Despite the weight loss, the affirmative-feedback group exhibited a higher percentage of “less worried” responses (90.4%) on low body weight concerns as compared to the control group (76.5%; P = 0.037). Significant QoL advantages were also observed in the affirmative-feedback group on multiple scales (global health status/QoL, nausea/vomiting, diarrhea, dysphagia, dry mouth, and body image). Patient interviews with affirmative feedback on weight loss improved weight satisfaction and QoL in gastric cancer survivors who lost weight.
Environmental and geographical conditions influence color, physical properties, and physiochemical composition of pomegranate fruits
Authors: Ghasemi-Soloklui Ali Akbar , Kordrostami Mojtaba , Gharaghani Ali
Published: September 2023

The highest quality pomegranate necessitates a tropical or subtropical environment for proper growth and development. This study evaluated two pomegranate cultivars including Rabab Poost Ghermez Neyriz (RPGN) and Makhmal Malas Shahreza (MMS) for physical traits, biochemical properties, and juice quality in their native locations as well as other warm and arid regions during two growing seasons (2019–2020 and 2020–2021) in Iran. The results showed that cultivars with the maximum redness (a*) were more likely to originate in cooler climates, and the cultivar’s responses to changing climates were also different. According to pomegranate characteristics, cultivars in different regions had different fruit, aril, and skin weights. According to these findings, pomegranate fruits cultivated in other climates than the origin climate have a smaller edible fraction. The findings also demonstrate that pomegranate fruits cultivated in mountain climates have more significant biochemical parameters such as total phenol, anthocyanin content, antioxidant capacity, and vitamin C than those produced in desert environment settings. The increased titratable acidity (TA), total soluble solids (TSS), and pH values of pomegranates produced in origin climate than the warm environment; thus, suggest that changes in pomegranate cultivar origin had a clear impact on fruit juice quality. Environmental factors, such as wind speed, altitude, and annual precipitation, had a significant correlation with a* skin, TSS, fruit weight, aril weight, edible portion, pH, TA, phenol, antioxidants, and anthocyanin content.
PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma
Authors: Wartewig Tim , Daniels Jay , Schulz Miriam , Hameister Erik , Joshi Abhinav , Park Joonhee , Morrish Emma , Venkatasubramani Anuroop V. , Cernilogar Filippo M. , van Heijster Frits H. A. , Hundshammer Christian , Schneider Heike , Konstantinidis Filippos , Gabler Judith V. , Klement Christine , Kurniawan Henry , Law Calvin , Lee Yujin , Choi Sara , Guitart Joan , Forne Ignasi , Giustinani Jérôme , Müschen Markus , Jain Salvia , Weinstock David M. , Rad Roland , Ortonne Nicolas , Schilling Franz , Schotta Gunnar , Imhof Axel , Brenner Dirk , Choi Jaehyuk , Ruland Jürgen
Published: September 2023

The PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The highest frequencies of PDCD1 deletions are detected in advanced disease, predicting inferior prognosis. However, the tumor-suppressive mechanisms of PD-1 signaling remain unknown. Here, using tractable mouse models for T-NHL and primary patient samples, we demonstrate that PD-1 signaling suppresses T cell malignancy by restricting glycolytic energy and acetyl coenzyme A (CoA) production. In addition, PD-1 inactivation enforces ATP citrate lyase (ACLY) activity, which generates extramitochondrial acetyl-CoA for histone acetylation to enable hyperactivity of activating protein 1 (AP-1) transcription factors. Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1-mutated T-NHL and identify PD-1 as regulator of AP-1 activity.