bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO
Authors: de la Fuente-Alonso Andrea , Toral Marta , Alfayate Alvaro , Ruiz-Rodríguez María Jesús , Bonzón-Kulichenko Elena , Teixido-Tura Gisela , Martínez-Martínez Sara , Méndez-Olivares María José , López-Maderuelo Dolores , González-Valdés Ileana , Garcia-Izquierdo Eusebio , Mingo Susana , Martín Carlos E. , Muiño-Mosquera Laura , De Backer Julie , Nistal J. Francisco , Forteza Alberto , Evangelista Arturo , Vázquez Jesús , Campanero Miguel R. , Redondo Juan Miguel
Published: May 2021

Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.
Observation of ordered organic capping ligands on semiconducting quantum dots via powder X-ray diffraction
Authors: Calvin Jason J. , Kaufman Tierni M. , Sedlak Adam B. , Crook Michelle F. , Alivisatos A. Paul
Published: May 2021

Powder X-ray diffraction is one of the key techniques used to characterize the inorganic structure of colloidal nanocrystals. The comparatively low scattering factor of nuclei of the organic capping ligands and their propensity to be disordered has led investigators to typically consider them effectively invisible to this technique. In this report, we demonstrate that a commonly observed powder X-ray diffraction peak around $$q=1.4{\AA}^{-1}$$
q
=
1.4

Å

−
1

observed in many small, colloidal quantum dots can be assigned to well-ordered aliphatic ligands bound to and capping the nanocrystals. This conclusion differs from a variety of explanations ascribed by previous sources, the majority of which propose an excess of organic material. Additionally, we demonstrate that the observed ligand peak is a sensitive probe of ligand shell ordering. Changes as a function of ligand length, geometry, and temperature can all be readily observed by X-ray diffraction and manipulated to achieve desired outcomes for the final colloidal system.
Asymmetric cell division shapes naive and virtual memory T-cell immunity during ageing
Authors: Borsa Mariana , Barandun Niculò , Gräbnitz Fabienne , Barnstorf Isabel , Baumann Nicolas S. , Pallmer Katharina , Baumann Samira , Stark Dominique , Balaz Miroslav , Oetiker Nathalie , Wagen Franziska , Wolfrum Christian , Simon Anna Katharina , Joller Nicole , Barral Yves , Spörri Roman , Oxenius Annette
Published: May 2021

Efficient immune responses rely on heterogeneity, which in CD8+ T cells, amongst other mechanisms, is achieved by asymmetric cell division (ACD). Here we find that ageing, known to negatively impact immune responses, impairs ACD in murine CD8+ T cells, and that this phenotype can be rescued by transient mTOR inhibition. Increased ACD rates in mitotic cells from aged mice restore the expansion and memory potential of their cellular progenies. Further characterization of the composition of CD8+ T cells reveals that virtual memory cells (TVM cells), which accumulate during ageing, have a unique proliferation and metabolic profile, and retain their ability to divide asymmetrically, which correlates with increased memory potential. The opposite is observed for naive CD8+ T cells from aged mice. Our data provide evidence on how ACD modulation contributes to long-term survival and function of T cells during ageing, offering new insights into how the immune system adapts to ageing.
Taxonomic signatures of cause-specific mortality risk in human gut microbiome
Authors: Salosensaari Aaro , Laitinen Ville , Havulinna Aki S. , Meric Guillaume , Cheng Susan , Perola Markus , Valsta Liisa , Alfthan Georg , Inouye Michael , Watrous Jeramie D. , Long Tao , Salido Rodolfo A. , Sanders Karenina , Brennan Caitriona , Humphrey Gregory C. , Sanders Jon G. , Jain Mohit , Jousilahti Pekka , Salomaa Veikko , Knight Rob , Lahti Leo , Niiranen Teemu
Published: May 2021

The collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.
Macrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models
Authors: Saito Makoto , Itoh Yasushi , Yasui Fumihiko , Munakata Tsubasa , Yamane Daisuke , Ozawa Makoto , Ito Risa , Katoh Takayuki , Ishigaki Hirohito , Nakayama Misako , Shichinohe Shintaro , Yamaji Kenzaburo , Yamamoto Naoki , Ikejiri Ai , Honda Tomoko , Sanada Takahiro , Sakoda Yoshihiro , Kida Hiroshi , Le Thi Quynh Mai , Kawaoka Yoshihiro , Ogasawara Kazumasa , Tsukiyama-Kohara Kyoko , Suga Hiroaki , Kohara Michinori
Published: May 2021

Most anti-influenza drugs currently used, such as oseltamivir and zanamivir, inhibit the enzymatic activity of neuraminidase. However, neuraminidase inhibitor-resistant viruses have already been identified from various influenza virus isolates. Here, we report the development of a class of macrocyclic peptides that bind the influenza viral envelope protein hemagglutinin, named iHA. Of 28 iHAs examined, iHA-24 and iHA-100 have inhibitory effects on the in vitro replication of a wide range of Group 1 influenza viruses. In particular, iHA-100 bifunctionally inhibits hemagglutinin-mediated adsorption and membrane fusion through binding to the stalk domain of hemagglutinin. Moreover, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models. This study shows the potential for developing cyclic peptides that can be produced more efficiently than antibodies and have multiple functions as next-generation, mid-sized biomolecules.
Selective and noncovalent targeting of RAS mutants for inhibition and degradation
Authors: Teng Kai Wen , Tsai Steven T. , Hattori Takamitsu , Fedele Carmine , Koide Akiko , Yang Chao , Hou Xuben , Zhang Yingkai , Neel Benjamin G. , O’Bryan John P. , Koide Shohei
Published: May 2021

Activating mutants of RAS are commonly found in human cancers, but to date selective targeting of RAS in the clinic has been limited to KRAS(G12C) through covalent inhibitors. Here, we report a monobody, termed 12VC1, that recognizes the active state of both KRAS(G12V) and KRAS(G12C) up to 400-times more tightly than wild-type KRAS. The crystal structures reveal that 12VC1 recognizes the mutations through a shallow pocket, and 12VC1 competes against RAS-effector interaction. When expressed intracellularly, 12VC1 potently inhibits ERK activation and the proliferation of RAS-driven cancer cell lines in vitro and in mouse xenograft models. 12VC1 fused to VHL selectively degrades the KRAS mutants and provides more extended suppression of mutant RAS activity than inhibition by 12VC1 alone. These results demonstrate the feasibility of selective targeting and degradation of KRAS mutants in the active state with noncovalent reagents and provide a starting point for designing noncovalent therapeutics against oncogenic RAS mutants.
Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation
Authors: Mijnheer Gerdien , Lutter Lisanne , Mokry Michal , van der Wal Marlot , Scholman Rianne , Fleskens Veerle , Pandit Aridaman , Tao Weiyang , Wekking Mark , Vervoort Stephin , Roberts Ceri , Petrelli Alessandra , Peeters Janneke G. C. , Knijff Marthe , de Roock Sytze , Vastert Sebastiaan , Taams Leonie S. , van Loosdregt Jorg , van Wijk Femke
Published: May 2021

Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations.
Scalable recombinase-based gene expression cascades
Authors: Kim Tackhoon , Weinberg Benjamin , Wong Wilson , Lu Timothy K.
Published: May 2021

Temporal modulation of the expression of multiple genes underlies complex complex biological phenomena. However, there are few scalable and generalizable gene circuit architectures for the programming of sequential genetic perturbations. Here, we describe a modular recombinase-based gene circuit architecture, comprising tandem gene perturbation cassettes (GPCs), that enables the sequential expression of multiple genes in a defined temporal order by alternating treatment with just two orthogonal ligands. We use tandem GPCs to sequentially express single-guide RNAs to encode transcriptional cascades that trigger the sequential accumulation of mutations. We build an all-in-one gene circuit that sequentially edits genomic loci, synchronizes cells at a specific stage within a gene expression cascade, and deletes itself for safety. Tandem GPCs offer a multi-tiered cellular programming tool for modeling multi-stage genetic changes, such as tumorigenesis and cellular differentiation.
Sugar transporters enable a leaf beetle to accumulate plant defense compounds
Authors: Yang Zhi-Ling , Nour-Eldin Hussam Hassan , Hänniger Sabine , Reichelt Michael , Crocoll Christoph , Seitz Fabian , Vogel Heiko , Beran Franziska
Published: May 2021

Many herbivorous insects selectively accumulate plant toxins for defense against predators; however, little is known about the transport processes that enable insects to absorb and store defense compounds in the body. Here, we investigate how a specialist herbivore, the horseradish flea beetle, accumulates glucosinolate defense compounds from Brassicaceae in the hemolymph. Using phylogenetic analyses of coleopteran major facilitator superfamily transporters, we identify a clade of glucosinolate-specific transporters (PaGTRs) belonging to the sugar porter family.PaGTRsare predominantly expressed in the excretory system, the Malpighian tubules. Silencing ofPaGTRs leads to elevated glucosinolate excretion, significantly reducing the levels of sequestered glucosinolates in beetles. This suggests thatPaGTRs reabsorb glucosinolates from the Malpighian tubule lumen to prevent their loss by excretion. Ramsay assays corroborated the selective retention of glucosinolates by Malpighian tubules ofP. armoraciaein situ. Thus, the selective accumulation of plant defense compounds in herbivorous insects can depend on the ability to prevent excretion.
Hierarchical communication of chirality for aromatic oligoamide sequences
Authors: Zhang Jiajia , Luo Dan , Ma Chunmiao , Huang Lu , Gan Quan
Published: May 2021

The communication of chirality at a molecular and supramolecular level is the fundamental feature capable of transmitting and amplifying chirality information. Yet, the limitation of one-step communication mode in many artificial systems has precluded the ability of further processing the chirality information. Here, we report the chirality communication of aromatic oligoamide sequences within the interpenetrated helicate architecture in a hierarchical manner, specifically, the communication is manipulated by three sequential steps: (i) coordination, (ii) concentration, and (iii) ion stimulus. Such approach enables the information to be implemented progressively and reversibly to different levels. Furthermore, the chiral information on the side chains can be accumulated and transferred to the helical backbones of the sequences, resulting in that one of ten possible diastereoisomers of the interpenetrated helicate is finally selected. The circular dichroism experiments with a mixture of chiral and achiral ligands demonstrate a cooperative behavior of these communications, leading to amplification of chiral information.
Integration of machine learning and genome-scale metabolic modeling identifies multi-omics biomarkers for radiation resistance
Authors: Lewis Joshua E. , Kemp Melissa L.
Published: May 2021

Resistance to ionizing radiation, a first-line therapy for many cancers, is a major clinical challenge. Personalized prediction of tumor radiosensitivity is not currently implemented clinically due to insufficient accuracy of existing machine learning classifiers. Despite the acknowledged role of tumor metabolism in radiation response, metabolomics data is rarely collected in large multi-omics initiatives such as The Cancer Genome Atlas (TCGA) and consequently omitted from algorithm development. In this study, we circumvent the paucity of personalized metabolomics information by characterizing 915 TCGA patient tumors with genome-scale metabolic Flux Balance Analysis models generated from transcriptomic and genomic datasets. Metabolic biomarkers differentiating radiation-sensitive and -resistant tumors are predicted and experimentally validated, enabling integration of metabolic features with other multi-omics datasets into ensemble-based machine learning classifiers for radiation response. These multi-omics classifiers show improved classification accuracy, identify clinical patient subgroups, and demonstrate the utility of personalized blood-based metabolic biomarkers for radiation sensitivity. The integration of machine learning with genome-scale metabolic modeling represents a significant methodological advancement for identifying prognostic metabolite biomarkers and predicting radiosensitivity for individual patients.
Structural visualization of transcription activated by a multidrug-sensing MerR family regulator
Authors: Yang Yang , Liu Chang , Zhou Wei , Shi Wei , Chen Ming , Zhang Baoyue , Schatz David G. , Hu Yangbo , Liu Bin
Published: May 2021

Bacterial RNA polymerase (RNAP) holoenzyme initiates transcription by recognizing the conserved –35 and –10 promoter elements that are optimally separated by a 17-bp spacer. The MerR family of transcriptional regulators activate suboptimal 19–20 bp spacer promoters in response to myriad cellular signals, ranging from heavy metals to drug-like compounds. The regulation of transcription by MerR family regulators is not fully understood. Here we report one crystal structure of a multidrug-sensing MerR family regulator EcmrR and nine cryo-electron microscopy structures that capture the EcmrR-dependent transcription process from promoter opening to initial transcription to RNA elongation. These structures reveal that EcmrR is a dual ligand-binding factor that reshapes the suboptimal 19-bp spacer DNA to enable optimal promoter recognition, sustains promoter remodeling to stabilize initial transcribing complexes, and finally dissociates from the promoter to reverse DNA remodeling and facilitate the transition to elongation. Our findings yield a comprehensive model for transcription regulation by MerR family factors and provide insights into the transition from transcription initiation to elongation.
Ternary nickel–tungsten–copper alloy rivals platinum for catalyzing alkaline hydrogen oxidation
Authors: Qin Shuai , Duan Yu , Zhang Xiao-Long , Zheng Li-Rong , Gao Fei-Yue , Yang Peng-Peng , Niu Zhuang-Zhuang , Liu Ren , Yang Yu , Zheng Xu-Sheng , Zhu Jun-Fa , Gao Min-Rui
Published: May 2021

Operating fuel cells in alkaline environments permits the use of platinum-group-metal-free (PGM-free) catalysts and inexpensive bipolar plates, leading to significant cost reduction. Of the PGM-free catalysts explored, however, only a few nickel-based materials are active for catalyzing the hydrogen oxidation reaction (HOR) in alkali; moreover, these catalysts deactivate rapidly at high anode potentials owing to nickel hydroxide formation. Here we describe that a nickel–tungsten–copper (Ni5.2WCu2.2) ternary alloy showing HOR activity rivals Pt/C benchmark in alkaline electrolyte. Importantly, we achieved a high anode potential up to 0.3 V versus reversible hydrogen electrode on this catalyst with good operational stability over 20 h. The catalyst also displays excellent CO-tolerant ability that Pt/C catalyst lacks. Experimental and theoretical studies uncover that nickel, tungsten, and copper play in synergy to create a favorable alloying surface for optimized hydrogen and hydroxyl bindings, as well as for the improved oxidation resistance, which result in the HOR enhancement.
Identification of poly(ADP-ribose) polymerase 9 (PARP9) as a noncanonical sensor for RNA virus in dendritic cells
Authors: Xing Junji , Zhang Ao , Du Yong , Fang Mingli , Minze Laurie J. , Liu Yong-Jun , Li Xian Chang , Zhang Zhiqiang
Published: May 2021

Innate immune cells are critical in protective immunity against viral infections, involved in sensing foreign viral nucleic acids. Here we report that the poly(ADP-ribose) polymerase 9 (PARP9), a member of PARP family, serves as a non-canonical sensor for RNA virus to initiate and amplify type I interferon (IFN) production. We find knockdown or deletion of PARP9 in human or mouse dendritic cells and macrophages inhibits type I IFN production in response to double strand RNA stimulation or RNA virus infection. Furthermore, mice deficient for PARP9 show enhanced susceptibility to infections with RNA viruses because of the impaired type I IFN production. Mechanistically, we show that PARP9 recognizes and binds viral RNA, with resultant recruitment and activation of the phosphoinositide 3-kinase (PI3K) and AKT3 pathway, independent of mitochondrial antiviral-signaling (MAVS). PI3K/AKT3 then activates the IRF3 and IRF7 by phosphorylating IRF3 at Ser385 and IRF7 at Ser437/438 mediating type I IFN production. Together, we reveal a critical role for PARP9 as a non-canonical RNA sensor that depends on the PI3K/AKT3 pathway to produce type I IFN. These findings may have important clinical implications in controlling viral infections and viral-induced diseases by targeting PARP9.
N-aryl pyrido cyanine derivatives are nuclear and organelle DNA markers for two-photon and super-resolution imaging
Authors: Uno Kakishi , Sugimoto Nagisa , Sato Yoshikatsu
Published: May 2021

Live cell imaging using fluorescent DNA markers are an indispensable molecular tool in various biological and biomedical fields. It is a challenge to develop DNA probes that avoid UV light photo-excitation, have high specificity for DNA, are cell-permeable and are compatible with cutting-edge imaging techniques such as super-resolution microscopy. Herein, we present N-aryl pyrido cyanine (N-aryl-PC) derivatives as a class of long absorption DNA markers with absorption in the wide range of visible light. The high DNA specificity and membrane permeability allow the staining of both organelle DNA as well as nuclear DNA, in various cell types, including plant tissues, without the need for washing post-staining. N-aryl-PC dyes are also highly compatible with a separation of photon by lifetime tuning method in stimulated emission depletion microscopy (SPLIT-STED) for super-resolution imaging as well as two-photon microscopy for deep tissue imaging, making it a powerful tool in the life sciences.
A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation
Authors: Kang Sisi , Yang Mei , He Suhua , Wang Yueming , Chen Xiaoxue , Chen Yao-Qing , Hong Zhongsi , Liu Jing , Jiang Guanmin , Chen Qiuyue , Zhou Ziliang , Zhou Zhechong , Huang Zhaoxia , Huang Xi , He Huanhuan , Zheng Weihong , Liao Hua-Xin , Xiao Fei , Shan Hong , Chen Shoudeng
Published: May 2021

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.
Marine ice-cliff instability modeling shows mixed-mode ice-cliff failure and yields calving rate parameterization
Authors: Crawford Anna J. , Benn Douglas I. , Todd Joe , Åström Jan A. , Bassis Jeremy N. , Zwinger Thomas
Published: May 2021

Marine ice-cliff instability could accelerate ice loss from Antarctica, and according to some model predictions could potentially contribute >1 m of global mean sea level rise by 2100 at current emission rates. Regions with over-deepening basins >1 km in depth (e.g., the West Antarctic Ice Sheet) are particularly susceptible to this instability, as retreat could expose increasingly tall cliffs that could exceed ice stability thresholds. Here, we use a suite of high-fidelity glacier models to improve understanding of the modes through which ice cliffs can structurally fail and derive a conservative ice-cliff failure retreat rate parameterization for ice-sheet models. Our results highlight the respective roles of viscous deformation, shear-band formation, and brittle-tensile failure within marine ice-cliff instability. Calving rates increase non-linearly with cliff height, but runaway ice-cliff retreat can be inhibited by viscous flow and back force from iceberg mélange.
Superconducting diode effect via conformal-mapped nanoholes
Authors: Lyu Yang-Yang , Jiang Ji , Wang Yong-Lei , Xiao Zhi-Li , Dong Sining , Chen Qing-Hu , Milošević Milorad V. , Wang Huabing , Divan Ralu , Pearson John E. , Wu Peiheng , Peeters Francois M. , Kwok Wai-Kwong
Published: May 2021

A superconducting diode is an electronic device that conducts supercurrent and exhibits zero resistance primarily for one direction of applied current. Such a dissipationless diode is a desirable unit for constructing electronic circuits with ultralow power consumption. However, realizing a superconducting diode is fundamentally and technologically challenging, as it usually requires a material structure without a centre of inversion, which is scarce among superconducting materials. Here, we demonstrate a superconducting diode achieved in a conventional superconducting film patterned with a conformal array of nanoscale holes, which breaks the spatial inversion symmetry. We showcase the superconducting diode effect through switchable and reversible rectification signals, which can be three orders of magnitude larger than that from a flux-quantum diode. The introduction of conformal potential landscapes for creating a superconducting diode is thereby proven as a convenient, tunable, yet vastly advantageous tool for superconducting electronics. This could be readily applicable to any superconducting materials, including cuprates and iron-based superconductors that have higher transition temperatures and are desirable in device applications.
An fMRI study of scientists with a Ph.D. in physics confronted with naive ideas in science
Authors: Allaire-Duquette Geneviève , Brault Foisy Lorie-Marlène , Potvin Patrice , Riopel Martin , Larose Marilyne , Masson Steve
Published: May 2021

A central challenge in developing conceptual understanding in science is overcoming naive ideas that contradict the content of science curricula. Neuroimaging studies reveal that high school and university students activate frontal brain areas associated with inhibitory control to overcome naive ideas in science, probably because they persist despite scientific training. However, no neuroimaging study has yet explored how persistent naive ideas in science are. Here, we report brain activations of 25 scientists with a Ph.D. in physics assessing the scientific value of naive ideas in science. Results show that scientists are slower and have lower accuracy when judging the scientific value of naive ideas compared to matched control ideas. fMRI data reveals that a network of frontal brain regions is more activated when judging naive ideas. Results suggest that naive ideas are likely to persist, even after completing a Ph.D. Advanced experts may still rely on high order executive functions like inhibitory control to overcome naive ideas when the context requires it.
Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative
Authors: Prowle John R. , Forni Lui G. , Bell Max , Chew Michelle S. , Edwards Mark , Grams Morgan E. , Grocott Michael P. W. , Liu Kathleen D. , McIlroy David , Murray Patrick T. , Ostermann Marlies , Zarbock Alexander , Bagshaw Sean M. , Bartz Raquel , Bell Samira , Bihorac Azra , Gan Tong J. , Hobson Charles E. , Joannidis Michael , Koyner Jay L. , Levett Denny Z. H. , Mehta Ravindra L. , Miller Timothy E. , Mythen Michael G. , Nadim Mitra K. , Pearse Rupert M. , Rimmele Thomas , Ronco Claudio , Shaw Andrew D. , Kellum John A.
Published: May 2021

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.
Facile isolation and analysis of sporopollenin exine from bee pollen
Authors: Hegedüs Kristóf , Fehér Csaba , Jalsovszky István , Kristóf Zoltán , Rohonczy János , Vass Elemér , Farkas Attila , Csizmadia Tamás , Friedbacher Gernot , Hantz Peter
Published: May 2021

We present facile methods to obtain purified sporopollenin exine capsules, and provide mass balances for classical and novel purification procedures. An ionic liquid, tetrabutyl phosphonium hydroxide turned out to be the most effective in removing the intine wall. The sporopollenin capsules were investigated by fluorescent microscopy, AFM, solid-state NMR and infrared Raman spectroscopy. The latter two methods showed that sunflower and rape exines have different proportions of O-aliphatic and aromatic constituents. Purified exine capsules were coated with functionalized fluorophores. The procedures presented in this paper could contribute to further spread of the applications of this hollow, and chemically highly resistant material.
Stochastic light concentration from 3D to 2D reveals ultraweak chemi- and bioluminescence
Authors: Khaoua Ibtissame , Graciani Guillaume , Kim Andrey , Amblard François
Published: May 2021

For countless applications in science and technology, light must be concentrated, and concentration is classically achieved with reflective and refractive elements. However, there is so far no efficient way, with a 2D detector, to detect photons produced inside an extended volume with a broad or isotropic angular distribution. Here, with theory and experiment, we propose to stochastically transform and concentrate a volume into a smaller surface, using a high-albedo Ulbricht cavity and a small exit orifice through cavity walls. A 3D gas of photons produced inside the cavity is transformed with a 50% number efficiency into a 2D Lambertian emitting orifice with maximal radiance and a much smaller size. With high-albedo quartz-powder cavity walls ($$\rho =99.94\%$$

ρ
=
99.94
%

), the orifice area is $$1/(1-\rho )\approx 1600$$

1
/
(
1
-
ρ
)
≈
1600

times smaller than the walls’ area. When coupled to a detectivity-optimized photon-counter ($$\mathcal{D}=0.015\,{\text{photon}}^{-1}\,{\text{s}}^{1/2}\text{ cm}$$

D
=
0.015

photon

-
1

s

1
/
2

cm

) the detection limit is $$110\;{\text{photon}}\;{\text{s}}^{ - 1} \;{\text{L}}^{ - 1}$$

110

photon

s

-
1

L

-
1

. Thanks to this unprecedented sensitivity, we could detect the luminescence produced by the non-catalytic disproportionation of hydrogen peroxide in pure water, which has not been observed so far. We could also detect the ultraweak bioluminescence produced by yeast cells at the onset of their growth. Our work opens new perspectives for studying ultraweak luminescence, and the concept of stochastic 3D/2D conjugation should help design novel light detection methods for large samples or diluted emitters.
Sex and body mass index dependent associations between serum 25-hydroxyvitamin D and pulse pressure in middle-aged and older US adults
Authors: Kwak Jung Hyun , Choi Yoon-Hyeong
Published: May 2021

High pulse pressure (PP) is a valid indicator of arterial stiffness. Many studies have reported that vitamin D concentration is inversely associated with vascular stiffening. This association may differ depending on sex and body mass index (BMI). This study investigated the associations between vitamin D and PP and evaluated whether these associations differ according to sex and BMI, using data for individuals aged ≥ 50 years from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were used as biomarkers of vitamin D levels. High PP was defined as ≥ 60 mmHg. Total 25(OH)D concentrations were dose-dependently associated with lower odds ratios (ORs) for high PP (p-trend = 0.01), after controlling for sociodemographic, behavioral, and dietary factors. When stratified by sex, there was a dose-dependent association between total 25(OH)D concentrations and lower risk of high PP (p-trend < 0.001) in females, but not in males. When stratified by BMI, there was a dose-dependent association between total 25(OH)D concentrations and lower risk of high PP (p-trend < 0.001) in non-overweight subjects, but not in overweight subjects. Improving the vitamin D status could delay elevation of PP and vascular stiffening in female and non-overweight subjects.
UVB protective effects of Sargassum horneri through the regulation of Nrf2 mediated antioxidant mechanism
Authors: Han Eui Jeong , Kim Seo-Young , Han Hee-Jin , Kim Hyun-Soo , Kim Kil-Nam , Fernando Ilekuttige Priyan Shanura , Madusanka Disanayake Mudiyanselage Dinesh , Dias Mawalle Kankanamge Hasitha Madhawa , Cheong Sun Hee , Park Sang Rul , Han Young Seok , Lee Kyounghoon , Ahn Ginnae
Published: May 2021

The present study aimed to evaluate the protective effect of a methanol extract of Sargassum horneri (SHM), which contains 6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one (HTT) and apo-9′-fucoxanthinone, against ultraviolet B (UVB)-induced cellular damage in human keratinocytes and its underlying mechanism. SHM significantly improved cell viability of UVB-exposed human keratinocytes by reducing the generation of intracellular reactive oxygen species (ROS). Moreover, SHM inhibited UVB exposure-induced apoptosis by reducing the formation of apoptotic bodies and the populations of the sub-G1 hypodiploid cells and the early apoptotic cells by modulating the expression of the anti- and pro-apoptotic molecules, Bcl-2 and Bax, respectively. Furthermore, SHM inhibited NF-κB p65 activation by inducing the activation of Nrf2/HO-1 signaling. The cytoprotective and antiapoptotic activities of SHM are abolished by the inhibition of HO-1 signaling. In further study, SHM restored the skin dryness and skin barrier disruption in UVB-exposed human keratinocytes. Based to these results, our study suggests that SHM protects the cells against UVB-induced cellular damages through the Nrf2/HO-1/NF-κB p65 signaling pathway and may be potentially useful for the prevention of UVB-induced skin damage.
Haplotype-resolved genome assembly enables gene discovery in the red palm weevil Rhynchophorus ferrugineus
Authors: Dias Guilherme B. , Altammami Musaad A. , El-Shafie Hamadttu A. F. , Alhoshani Fahad M. , Al-Fageeh Mohamed B. , Bergman Casey M. , Manee Manee M.
Published: May 2021

The red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae) is an economically-important invasive species that attacks multiple species of palm trees around the world. A better understanding of gene content and function in R. ferrugineus has the potential to inform pest control strategies and thereby mitigate economic and biodiversity losses caused by this species. Using 10x Genomics linked-read sequencing, we produced a haplotype-resolved diploid genome assembly for R. ferrugineus from a single heterozygous individual with modest sequencing coverage ($$\sim$$
∼
62x). Benchmarking against conserved single-copy Arthropod orthologs suggests both pseudo-haplotypes in our R. ferrugineus genome assembly are highly complete with respect to gene content, and do not suffer from haplotype-induced duplication artifacts present in a recently published hybrid assembly for this species. Annotation of the larger pseudo-haplotype in our assembly provides evidence for 23,413 protein-coding loci in R. ferrugineus, including over 13,000 predicted proteins annotated with Gene Ontology terms and over 6000 loci independently supported by high-quality Iso-Seq transcriptomic data. Our assembly also includes 95% of R. ferrugineus chemosensory, detoxification and neuropeptide-related transcripts identified previously using RNA-seq transcriptomic data, and provides a platform for the molecular analysis of these and other functionally-relevant genes that can help guide management of this widespread insect pest.
Importance of $${{d}}_{{{xy}}}$$ orbital and electron correlation in iron-based superconductors revealed by phase diagram for 1111-system
Authors: Kawashima Tsuyoshi , Miyasaka Shigeki , Tsuji Hirokazu , Yamamoto Takahiro , Uekubo Masahiro , Takemori Akira , Lai Kwing To , Tajima Setsuko
Published: May 2021

The structural flexibility at three substitution sites in LaFeAsO enabled investigation of the relation between superconductivity and structural parameters over a wide range of crystal compositions. Substitutions of Nd for La, Sb or P for As, and F or H for O were performed. All these substitutions modify the local structural parameters, while the F/H-substitution also changes band filling. It was found that the superconducting transition temperature $$T_{\text{c}}$$

T
c

is strongly affected by the pnictogen height $$h_{Pn}$$

h

Pn

from the Fe-plane that controls the electron correlation strength and the size of the $$d_{xy}$$

d

xy

hole Fermi surface (FS). With increasing $$h_{Pn}$$

h

Pn

, weak coupling BCS superconductivity switches to the strong coupling non-BCS one where electron correlations and the $$d_{xy}$$

d

xy

hole FS may be important.
Utilization of urea and chicken litter biochar to improve rice production
Authors: Maikol Nathaniel , Haruna Ahmed Osumanu , Maru Ali , Asap Audrey , Medin Simon
Published: May 2021

The use of N fertilizers on tropical acid soils is increasing because of their low native fertility. Chicken litter biochar was used to improve N use efficiency and rice yield. The objective of this study was to determine the effects of chicken litter biochar on selected chemical properties of a tropical acid soil under rice (MR219) cultivation. Treatments evaluated were in this study were as follows: (1) T1, soil only, (2) T2, existing recommended fertilization, (3) T3, chicken litter biochar alone, and (4) T4, chicken litter biochar + existing recommended fertilization. Plant and soil analyses were conducted using standard procedures. The use of chicken litter biochar increased soil pH, total carbon, total P, available P, total N, and exchangeable N. Also, this practice decreased soil total acidity and exchangeable Al3+. Compared with T2, T4 significantly increased Crop Recovery Efficiency and Agronomic Recovery Efficiency of N. This resulted in a significant increase in the grain yield (11 t ha−1) of MR219 (Malaysia hybrid rice) for T4 compared with the existing rice grain yield of 5.9 t ha−1(T2). Moreover, application of chicken litter biochar (5 t ha−1) to tropical acid soil suggested that N application can be reduced to 26.67%, 30.03%, 30.15%, and 14.15% of the recommended rates by MADA on days 10, 30, 50, and 70 after transplanting, respectively. Chicken litter biochar can improve the chemical properties of tropical acid soils and rice (MR219) grain yield.
Comparison of sample types from white-tailed deer (Odocoileus virginianus) for DNA extraction and analyses
Authors: Edson Jessie , Brown Justin , Miller William L. , Walter W. David
Published: May 2021

Collection of biological samples for DNA is necessary in a variety of disciplines including disease epidemiology, landscape genetics, and forensics. Quantity and quality of DNA varies depending on the method of collection or media available for collection (e.g., blood, tissue, fecal). Blood is the most common sample collected in vials or on Whatman Flinders Technology Associates (FTA) cards with short- and long-term storage providing adequate DNA for study objectives. The focus of this study was to determine if biological samples stored on Whatman FTA Elute cards were a reasonable alternative to traditional DNA sample collection, storage, and extraction. Tissue, nasal swabs, and ocular fluid were collected from white-tailed deer (Odocoileus virginianus). Tissue samples and nasal swabs acted as a control to compare extraction and DNA suitability for microsatellite analysis for nasal swabs and ocular fluid extracted from FTA Elute cards. We determined that FTA Elute cards improved the extraction time and storage of samples and that nasal swabs and ocular fluid containing pigmented fluid were reasonable alternatives to traditional tissue DNA extractions.
DNA repair proteins may differentiate papillary thyroid cancer from chronic lymphocytic thyroiditis and nodular colloidal goiter
Authors: Evren Bahri , Yılmaz Sami , Karadağ Neşe , Sertkaya Ayşe Çıkım , Topaloğlu Ömercan , Kılınç Faruk
Published: May 2021

Malignant thyroid lesions are the most common malignancy of the endocrine glands with increasing rates in the last two decades. Papillary thyroid cancer is the most common thyroid malignancy. In our study, we aimed to quantitatively evaluate the levels of DNA repair proteins MSH2, MLH1, MGMT, which are representative blocks of patients diagnosed with papillary carcinoma, chronic thyroiditis, or colloidal goiter. Total or subtotal thyroidectomy material of 90 patients diagnosed with papillary carcinoma, nodular colloidal goiter, or chronic thyroiditis between 2009 and 2012 were retrospectively evaluated. Tissue samples obtained from paraffin blocks were stained with MGMT, MSH2, MLH1 proteins and their immunohistochemistry was evaluated. Prepared sections were examined qualitatively by an impartial pathologist and a clinician, taking into account the staining method under the trinocular light microscope. Although there was no statistically significant difference in MGMT, MSH2, MLH1, follicular cell positivity, staining intensity, and immunoreactivity values, papillary carcinoma cases showed a higher rate of follicular cell positivity, and this difference was more pronounced between papillary carcinoma and colloidal goiter. In the MSH2 follicular cell positivity evaluation, the difference between chronic thyroiditis and colloidal goiter was significant (p = 0.023). The difference between chronic thyroiditis and colloidal goiter was significant in the MSH2 staining intensity evaluation (p = 0.001). The difference between chronic thyroiditis and colloidal goiter was significant in MLH1 immunoreactivity evaluation (p = 0.012). Papillary carcinoma cases were demonstrated by nuclear staining only for MSH2 and MLH1 proteins as opposed to hyperplastic nodules. The higher levels of expression of DNA repair genes in malignant tumors compared to benign tumors are attributed to the functional activation of DNA repair genes. Further studies are needed for DNA repair proteins to be a potential test in the development and progression of thyroid cancer.
Safety measures for COVID-19 do not compromise the outcomes of patients undergoing primary percutaneous coronary intervention: a single center retrospective study
Authors: Guan Xiaonan , Zhang Jianjun , Li Yanbing , Ma Ning
Published: May 2021

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting nearly 170 countries/regions and millions of patients worldwide. Patients with acute myocardial infarction (AMI) still need to be treated at percutaneous coronary intervention (PCI) centers with relevant safety measures. This retrospective study was conducted to assess the therapeutic outcomes of PCI performed under the safety measures and normal conditions. AMI patients undergoing PCI between January 24 to April 30, 2020 were performed under safety measures for COVID-19. Patients received pulmonary computed tomography (CT) and underwent PCI in negative pressure ICU. Cardiac catheterization laboratory (CCL) staff and physicians worked with level III personal protection. Demographic and clinical data, such as door-to-balloon (DTB) time, operation time, complications for patients in this period (COVID-19 group) and the same period in 2019 (2019 group) were retrieved and analyzed. COVID-19 and 2019 groups had 37 and 96 patients, respectively. There was no significant difference in age, gender, BMI and comorbidity between the two groups. DTB time and operation time were similar between the two groups (60.0 ± 12.39 vs 58.83 ± 12.85 min, p = 0.636; 61.46 ± 9.91 vs 62.55 ± 10.72 min, p = 0.592). Hospital stay time in COVID-19 group was significantly shorter (6.78 ± 2.14 vs 8.85 ± 2.64 days, p < 0.001). The incidences of malignant arrhythmia and Takotsubo Syndrome in COVID-19 group were higher than 2019 group significantly (16.22% vs 5.21%, p = 0.039; 10.81% vs 1.04% p = 0.008). During hospitalization and 3-month follow-up, the incidence of major adverse cardiovascular events and mortality in the two groups were statistically similar (35.13% vs 14.58%, p = 0.094; 16.22% vs 8.33%, p = 0.184). The risk of major adverse cardiac events (MACE) was associated with cardiogenic shock (OR, 11.53; 95% CI, 2.888–46.036; p = 0.001), malignant arrhythmias (OR, 7.176; 95% CI, 1.893–27.203; p = 0.004) and advanced age (≥ 75 years) (OR, 6.718; 95% CI, 1.738–25.964; p = 0.006). Cardiogenic shock (OR, 17.663; 95% CI, 5.5–56.762; p < 0.001) and malignant arrhythmias (OR, 4.659; 95% CI, 1.481–14.653; p = 0.008) were also associated with death of 3 months. Our analysis showed that safety measures undertaken in this hospital, including screening of COVID-19 infection and use of personal protection equipment for conducting PCI did not compromise the surgical outcome as compared with PCI under normal condition, although there were slight increases in incidence of malignant arrhythmia and Takotsubo Syndrome.
Surgical outcomes of localization using indocyanine green fluorescence in breast conserving surgery: a prospective study
Authors: Lee Eun-Gyeong , Kim Seok-Ki , Han Jai Hong , Lee Dong-Eun , Jung So-Youn , Lee Seeyoun
Published: May 2021

We investigated localization and safe resection margins for breast cancer patients undergoing breast conserving surgery (BCS) using ultrasound-guided indocyanine green fluorescence (ICG-F) marking. From April 2016 to March 2019, we prospectively enrolled 114 patients who underwent BCS using US-guided ICG-F marking and we compared these results with 300 patients who underwent BCS using US-guided skin marking from January 2012 to December 2016. Clinical features, identification rates, status of resection margins, and re-operation rates were analyzed. The ICG-F identification rate was 100% (114/114). The mean approach time for resection of the lesion ICG-F using group was about 13 min. The positive rate of frozen resection margins was 10.5% using ICG-F and 25.0% using sono-guided skin marking (p < 0.01). The rate of additional intraoperative resection was significantly lower in the ICG-F marking group compared to that in the sono-guided skin marking group (8.8% vs. 23.3%, p < 0.01). The rate of final positive resection margins was 3.5% in the ICG-F using group and 14.7% in the sono-guided skin marking group (p < 0.01). The rate of re-operation was 4.4% in the ICG-F using group and 4% in the sono-guided group (p = 0.79). At follow-up after the operation using ICG-F, no complications occurred. Using ICG-F during BCS could be a safe, sophisticated method for localization.