bluuebunny/crossref_metadata_2025 huggingface dataset:
Red Flags Suggesting Cardiac Transthyretin Amyloidosis (ATTR) in Clinical Practice
Authors: Galuszka Oskar M. , Stämpfli Simon F.
Published: April 2023

Abstract: Cardiac wtATTR is caused by extracellular deposition of misfolded proteins in the heart. It mostly affects elderly men and is still clearly underdiagnosed. Recognizing red flags suggesting wtATTR is key for a timely diagnosis, enabling the patient to profit from effective therapies. If general practitioners suspect cardiac amyloidosis, it is crucial to rapidly exclude AL-amyloidosis by immunoelectrophoresis, immunofixation as well as light-chain assay, because AL-amyloidosis needs urgent hematologic therapy. After that, the patient should be referred to the cardiologist for further assessment.
Welche Motive für körperliche Aktivität verfolgen jüngere und ältere Personen bei der Nutzung von Aktivitätstrackern?
Authors: Estorff Isabell , Notthoff Nanna
Published: April 2023

Zusammenfassung: Das Aktivitätsniveau ist vor allem im höheren Erwachsenenalter recht niedrig. Aktivitätstracker stellen eine Möglichkeit dar, diesem Trend entgegenzuwirken und zu einem gesundheitsförderlichen, aktiven Lebensstil zu motivieren. In dieser Studie wird untersucht, inwiefern sich die Motive für körperliche Aktivität bei der Nutzung von Aktivitätstrackern zwischen jungen und älteren Erwachsenen unterscheiden. 337 Personen (jüngere: 27 ± 4.2 Jahre, ältere: 62 ± 6.6 Jahre, 58 % Frauen) nahmen dazu an einer Online-Befragung teil. Erfasst wurde die Zustimmung zu vier übergeordneten Motivausprägungen für körperliche Aktivität bei der Nutzung eines Aktivitätstrackers (soziale Unterstützung, Wissenserwerb zur Selbstoptimierung, Gesunderhaltung und Prävention, Gamification). Anders als angenommen, verfolgen ältere Menschen nicht signifikant stärker Motive der sozialen Unterstützung als jüngere Erwachsene. Bei der Entwicklung von Technologien zum Aktivitätstracking für ältere Menschen erscheint es sinnvoll, das Aufzeichnen der Daten an die eher gesundheitlichen Bedürfnisse dieser Altersgruppe anzupassen, da die Gesunderhaltung als bedeutsamstes Motiv hervorging.
Sex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort
Authors: Kommaddi Reddy Peera , Verma Aditi , Muniz-Terrera Graciela , Tiwari Vivek , Chithanathan Keerthana , Diwakar Latha , Gowaikar Ruturaj , Karunakaran Smitha , Malo Palash Kumar , Graff-Radford Neill R. , Day Gregory S. , Laske Christoph , Vöglein Jonathan , Nübling Georg , Ikeuchi Takeshi , Kasuga Kensaku ,   the Dominantly Inherited Alzheimer Network (DIAN), Ravindranath Vijayalakshmi
Published: April 2023

Women carry a higher burden of Alzheimer’s disease (AD) compared to men, which is not accounted entirely by differences in lifespan. To identify the mechanisms underlying this effect, we investigated sex-specific differences in the progression of familial AD in humans and inAPPswe/PS1ΔE9mice. Activity dependent protein translation and associative learning and memory deficits were examined inAPPswe/PS1ΔE9mice and wild-type mice. As a human comparator group, progression of cognitive dysfunction was assessed in mutation carriers and non-carriers from DIAN (Dominantly Inherited Alzheimer Network) cohort. FemaleAPPswe/PS1ΔE9mice did not show recall deficits after contextual fear conditioning until 8 months of age. Further, activity dependent protein translation and Akt1-mTOR signaling at the synapse were impaired in male but not in female mice until 8 months of age. OvariectomizedAPPswe/PS1ΔE9mice displayed recall deficits at 4 months of age and these were sustained until 8 months of age. Moreover, activity dependent protein translation was also impaired in 4 months old ovariectomizedAPPswe/PS1ΔE9mice compared with sham femaleAPPswe/PS1ΔE9mice. Progression of memory impairment differed between men and women in the DIAN cohort as analyzed using linear mixed effects model, wherein men showed steeper cognitive decline irrespective of the age of entry in the study, while women showed significantly greater performance and slower decline in immediate recall (LOGIMEM) and delayed recall (MEMUNITS) than men. However, when the performance of men and women in several cognitive tasks (such as Wechsler’s logical memory) are compared with the estimated year from expected symptom onset (EYO) we found no significant differences between men and women. We conclude that in familial AD patients and mouse models, females are protected, and the onset of disease is delayed as long as estrogen levels are intact.
Long non-coding RNA maternally expressed gene 3, miR-125a-5p, CXCL13, and NF-kB in patients with immune thrombocytopenia
Authors: Naguib Mervat , El Sawy Shereen , Rashed Laila , AlHelf Maha , Abdelgwad Marwa
Published: April 2023

The main aim of this study was to assess the expression level of circulating long non-coding RNA maternally expressed gene 3 (lncRNA-MEG3), microRNA (miR-125a-5P), the chemokine C-X-C motif ligand13 (CXCL13), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in immune thrombocytopenia (ITP) cases and to study its relation to the disease severity and treatment response. This case-control study included 45 patients newly diagnosed as ITP and 45 healthy subjects. We assessed complete blood count, antinuclear antibodies, hepatitis B and C virus serology, lncRNA-MEG3, miR-125a-5P, and CXCL13 expression in serum by real-time PCR and NF-kb protein by ELISA. In ITP patients compared to control, lncRNA-MEG3 was significantly increased, and miRNA-125a-5P was decreased, and this was associated with higher CXCL13 and NF-kB levels (P < 0.001, for all).There was a significant negative correlation between platelet count and lncRNA-MEG3, CXCL13, and NF-kb, while a positive correlation with miR-125a-5p in ITP patients. Patients who responded to steroids had significantly higher miR-125a-5p (P = 0.016) and significantly lower lncRNA-MEG3 (P < 0.001), CXCL13 (P = 0.005), and NF-kb (p = 0.002). Based on the ROC curves, lncRNA-MEG3 displayed the highest area under the curve (AUC) in the identification of organ bleeding (AUC = 0.805), the response to steroids (AUC = 0.853), and the need for splenectomy (AUC = 0.75).
Superfluid response of an atomically thin gate-tuned van der Waals superconductor
Authors: Jarjour Alexander , Ferguson G. M. , Schaefer Brian T. , Lee Menyoung , Loh Yen Lee , Trivedi Nandini , Nowack Katja C.
Published: April 2023

A growing number of two-dimensional superconductors are being discovered in the family of exfoliated van der Waals materials. Due to small sample volume, the superfluid response of these materials has not been characterized. Here, we use a local magnetic probe to directly measure this key property of the tunable, gate-induced superconducting state in MoS2. We find that the backgate changes the transition temperature non-monotonically whereas the superfluid stiffness at low temperature and the normal state conductivity monotonically increase. In some devices, we find direct signatures in agreement with a Berezinskii-Kosterlitz-Thouless transition, whereas in others we find a broadened onset of the superfluid response. We show that the observed behavior is consistent with disorder playing an important role in determining the properties of superconducting MoS2. Our work demonstrates that magnetic property measurements are within reach for superconducting devices based on exfoliated sheets and reveals that the superfluid response significantly deviates from simple BCS-like behavior.
The RNA-binding protein landscapes differ between mammalian organs and cultured cells
Authors: Perez-Perri Joel I. , Ferring-Appel Dunja , Huppertz Ina , Schwarzl Thomas , Sahadevan Sudeep , Stein Frank , Rettel Mandy , Galy Bruno , Hentze Matthias W.
Published: April 2023

System-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes of cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) of mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo enhanced RNA interactome capture (eRIC) to characterize the RNA-bound proteomes of three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) of these had formerly not been identified in cultured cells, with more than 100 being metabolic enzymes. Remarkably, RBP activity differs between organs independent of RBP abundance, suggesting organ-specific levels of control. Similarly, we identify systematic differences in RNA binding between animal organs and cultured cells. The pervasive RNA binding of enzymes of intermediary metabolism in organs points to tightly knit connections between gene expression and metabolism, and displays a particular enrichment for enzymes that use nucleotide cofactors. We describe a generically applicable refinement of the eRIC technology and provide an instructive resource of RBPs active in intact mammalian organs, including the brain.
Peripersonal encoding of forelimb proprioception in the mouse somatosensory cortex
Authors: Alonso Ignacio , Scheer Irina , Palacio-Manzano Mélanie , Frézel-Jacob Noémie , Philippides Antoine , Prsa Mario
Published: April 2023

Conscious perception of limb movements depends on proprioceptive neural responses in the somatosensory cortex. In contrast to tactile sensations, proprioceptive cortical coding is barely studied in the mammalian brain and practically non-existent in rodent research. To understand the cortical representation of this important sensory modality we developed a passive forelimb displacement paradigm in behaving mice and also trained them to perceptually discriminate where their limb is moved in space. We delineated the rodent proprioceptive cortex with wide-field calcium imaging and optogenetic silencing experiments during behavior. Our results reveal that proprioception is represented in both sensory and motor cortical areas. In addition, behavioral measurements and responses of layer 2/3 neurons imaged with two-photon microscopy reveal that passive limb movements are both perceived and encoded in the mouse cortex as a spatial direction vector that interfaces the limb with the body’s peripersonal space.
Single-shot isotropic differential interference contrast microscopy
Authors: Wang Xinwei , Wang Hao , Wang Jinlu , Liu Xingsi , Hao Huijie , Tan You Sin , Zhang Yilei , Zhang He , Ding Xiangyan , Zhao Weisong , Wang Yuhang , Lu Zhengang , Liu Jian , Yang Joel K. W. , Tan Jiubin , Li Haoyu , Qiu Cheng-Wei , Hu Guangwei , Ding Xumin
Published: April 2023

Differential interference contrast (DIC) microscopy allows high-contrast, low-phototoxicity, and label-free imaging of transparent biological objects, and has been applied in the field of cellular morphology, cell segmentation, particle tracking, optical measurement and others. Commercial DIC microscopy based on Nomarski or Wollaston prism resorts to the interference of two polarized waves with a lateral differential offset (shear) and axial phase shift (bias). However, the shear generated by these prisms is limited to the rectilinear direction, unfortunately resulting in anisotropic contrast imaging. Here we propose an ultracompact metasurface-assisted isotropic DIC (i-DIC) microscopy based on a grand original pattern of radial shear interferometry, that converts the rectilinear shear into rotationally symmetric along radial direction, enabling single-shot isotropic imaging capabilities. The i-DIC presents a complementary fusion of typical meta-optics, traditional microscopes and integrated optical system, and showcases the promising and synergetic advancements in edge detection, particle motion tracking, and label-free cellular imaging.
Targeting neuronal lysosomal dysfunction caused by β-glucocerebrosidase deficiency with an enzyme-based brain shuttle construct
Authors: Gehrlein Alexandra , Udayar Vinod , Anastasi Nadia , Morella Martino L. , Ruf Iris , Brugger Doris , von der Mark Sophia , Thoma Ralf , Rufer Arne , Heer Dominik , Pfahler Nina , Jochner Anton , Niewoehner Jens , Wolf Luise , Fueth Matthias , Ebeling Martin , Villaseñor Roberto , Zhu Yanping , Deen Matthew C. , Shan Xiaoyang , Ehsaei Zahra , Taylor Verdon , Sidransky Ellen , Vocadlo David J. , Freskgård Per-Ola , Jagasia Ravi
Published: April 2023

Mutations in glucocerebrosidase cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Therapies to restore the enzyme’s function in the brain hold great promise for treating the neurological implications. Thus, we developed blood-brain barrier penetrant therapeutic molecules by fusing transferrin receptor-binding moieties to β-glucocerebrosidase (referred to as GCase-BS). We demonstrate that these fusion proteins show significantly increased uptake and lysosomal efficiency compared to the enzyme alone. In a cellular disease model, GCase-BS rapidly rescues the lysosomal proteome and lipid accumulations beyond known substrates. In a mouse disease model, intravenous injection of GCase-BS leads to a sustained reduction of glucosylsphingosine and can lower neurofilament-light chain plasma levels. Collectively, these findings demonstrate the potential of GCase-BS for treating GBA1-associated lysosomal dysfunction, provide insight into candidate biomarkers, and may ultimately open a promising treatment paradigm for lysosomal storage diseases extending beyond the central nervous system.
Antimicrobial exposure is associated with decreased survival in triple-negative breast cancer
Authors: Ransohoff Julia D. , Ritter Victor , Purington Natasha , Andrade Karen , Han Summer , Liu Mina , Liang Su-Ying , John Esther M. , Gomez Scarlett L. , Telli Melinda L. , Schapira Lidia , Itakura Haruka , Sledge George W. , Bhatt Ami S. , Kurian Allison W.
Published: April 2023

Antimicrobial exposure during curative-intent treatment of triple-negative breast cancer (TNBC) may lead to gut microbiome dysbiosis, decreased circulating and tumor-infiltrating lymphocytes, and inferior outcomes. Here, we investigate the association of antimicrobial exposure and peripheral lymphocyte count during TNBC treatment with survival, using integrated electronic medical record and California Cancer Registry data in the Oncoshare database. Of 772 women with stage I-III TNBC treated with and without standard cytotoxic chemotherapy – prior to the immune checkpoint inhibitor era – most (654, 85%) used antimicrobials. Applying multivariate analyses, we show that each additional total or unique monthly antimicrobial prescription is associated with inferior overall and breast cancer-specific survival. This antimicrobial-mortality association is independent of changes in neutrophil count, is unrelated to disease severity, and is sustained through year three following diagnosis, suggesting antimicrobial exposure negatively impacts TNBC survival. These results may inform mechanistic studies and antimicrobial prescribing decisions in TNBC and other hormone receptor-independent cancers.
Thermal sensitivity of metabolic rate mirrors biogeographic differences between teleosts and elasmobranchs
Authors: Watanabe Yuuki Y. , Payne Nicholas L.
Published: April 2023

Environmental temperature affects physiological functions, representing a barrier for the range expansions of ectothermic species. To understand the link between thermal physiology and biogeography, a key question is whether among-species thermal sensitivity of metabolic rates is mechanistically constrained or buffered through physiological remodeling over evolutionary time. The former conception, the Universal Temperature Dependence hypothesis, predicts similar among- and within-species thermal sensitivity. The latter conception, the Metabolic Cold Adaptation hypothesis, predicts lower among-species thermal sensitivity than within-species sensitivity. Previous studies that tested these hypotheses for fishes overwhelmingly investigated teleosts with elasmobranchs understudied. Here, we show that among-species thermal sensitivity of resting metabolic rates is lower than within-species sensitivity in teleosts but not in elasmobranchs. Further, species richness declines with latitude more rapidly in elasmobranchs than in teleosts. Metabolic Cold Adaptation exhibited by teleosts might underpin their high diversity at high latitudes, whereas the inflexible thermal sensitivity approximated by Universal Temperature Dependence of elasmobranchs might explain their low diversity at high latitudes.
Diffusive excitonic bands from frustrated triangular sublattice in a singlet-ground-state system
Authors: Gao Bin , Chen Tong , Wu Xiao-Chuan , Flynn Michael , Duan Chunruo , Chen Lebing , Huang Chien-Lung , Liebman Jesse , Li Shuyi , Ye Feng , Stone Matthew B. , Podlesnyak Andrey , Abernathy Douglas L. , Adroja Devashibhai T. , Duc Le Manh , Huang Qingzhen , Nevidomskyy Andriy H. , Morosan Emilia , Balents Leon , Dai Pengcheng
Published: April 2023

Magnetic order in most materials occurs when magnetic ions with finite moments arrange in a particular pattern below the ordering temperature. Intriguingly, if the crystal electric field (CEF) effect results in a spin-singlet ground state, a magnetic order can still occur due to the exchange interactions between neighboring ions admixing the excited CEF levels. The magnetic excitations in such a state are spin excitons generally dispersionless in reciprocal space. Here we use neutron scattering to study stoichiometric Ni2Mo3O8, where Ni2+ions form a bipartite honeycomb lattice comprised of two triangular lattices, with ions subject to the tetrahedral and octahedral crystalline environment, respectively. We find that in both types of ions, the CEF excitations have nonmagnetic singlet ground states, yet the material has magnetic order. Furthermore, CEF spin excitons from the tetrahedral sites form a dispersive diffusive pattern around the Brillouin zone boundary, likely due to spin entanglement and geometric frustrations.
Near-atomic architecture of Singapore grouper iridovirus and implications for giant virus assembly
Authors: Zhao Zhennan , Huang Youhua , Liu Congcong , Zhu Dongjie , Gao Shuaixin , Liu Sheng , Peng Ruchao , Zhang Ya , Huang Xiaohong , Qi Jianxun , Wong Catherine C. L. , Zhang Xinzheng , Wang Peiyi , Qin Qiwei , Gao George F.
Published: April 2023

Singapore grouper iridovirus (SGIV), one of the nucleocytoviricota viruses (NCVs), is a highly pathogenic iridovirid. SGIV infection results in massive economic losses to the aquaculture industry and significantly threatens global biodiversity. In recent years, high morbidity and mortality in aquatic animals have been caused by iridovirid infections worldwide. Effective control and prevention strategies are urgently needed. Here, we present a near-atomic architecture of the SGIV capsid and identify eight types of capsid proteins. The viral inner membrane-integrated anchor protein colocalizes with the endoplasmic reticulum (ER), supporting the hypothesis that the biogenesis of the inner membrane is associated with the ER. Additionally, immunofluorescence assays indicate minor capsid proteins (mCPs) could form various building blocks with major capsid proteins (MCPs) before the formation of a viral factory (VF). These results expand our understanding of the capsid assembly of NCVs and provide more targets for vaccine and drug design to fight iridovirid infections.
Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders
Authors: Eide Per Kristian , Lashkarivand Aslan , Pripp Are , Valnes Lars Magnus , Hovd Markus Herberg , Ringstad Geir , Blennow Kaj , Zetterberg Henrik
Published: April 2023

Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-β (Aβ40 and Aβ42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.
An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters
Authors: Deng Shaofeng , Liu Ying , Tam Rachel Chun-Yee , Chen Pin , Zhang Anna Jinxia , Mok Bobo Wing-Yee , Long Teng , Kukic Anja , Zhou Runhong , Xu Haoran , Song Wenjun , Chan Jasper Fuk-Woo , To Kelvin Kai-Wang , Chen Zhiwei , Yuen Kwok-Yung , Wang Pui , Chen Honglin
Published: April 2023

Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
Authors: Mao Mao , Qu Xiaoli , Zhang Yabo , Gu Bingsong , Li Chen , Liu Rongzhi , Li Xiao , Zhu Hui , He Jiankang , Li Dichen
Published: April 2023

Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.
Collagen breaks at weak sacrificial bonds taming its mechanoradicals
Authors: Rennekamp Benedikt , Karfusehr Christoph , Kurth Markus , Ünal Aysecan , Monego Debora , Riedmiller Kai , Gryn’ova Ganna , Hudson David M. , Gräter Frauke
Published: April 2023

Collagen is a force-bearing, hierarchical structural protein important to all connective tissue. In tendon collagen, high load even below macroscopic failure level creates mechanoradicals by homolytic bond scission, similar to polymers. The location and type of initial rupture sites critically decide on both the mechanical and chemical impact of these micro-ruptures on the tissue, but are yet to be explored. We here use scale-bridging simulations supported by gel electrophoresis and mass spectrometry to determine breakage points in collagen. We find collagen crosslinks, as opposed to the backbone, to harbor the weakest bonds, with one particular bond in trivalent crosslinks as the most dominant rupture site. We identify this bond as sacrificial, rupturing prior to other bonds while maintaining the material’s integrity. Also, collagen’s weak bonds funnel ruptures such that the potentially harmful mechanoradicals are readily stabilized. Our results suggest this unique failure mode of collagen to be tailored towards combatting an early onset of macroscopic failure and material ageing.
Glucose depletion enables Candida albicans mating independently of the epigenetic white-opaque switch
Authors: Guan Guobo , Tao Li , Li Chao , Xu Ming , Liu Ling , Bennett Richard J. , Huang Guanghua
Published: April 2023

The human fungal pathogen Candida albicans can switch stochastically and heritably between a “white” phase and an “opaque” phase. Opaque cells are the mating-competent form of the species, whereas white cells are thought to be essentially “sterile”. Here, we report that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating. The relative expression levels of pheromone-sensing and mating-associated genes (including STE2/3, MFA1, MFα1, FIG1, FUS1, and CEK1/2) are increased under glucose depletion conditions, while expression of mating repressors TEC1 and DIG1 is decreased. Cph1 and Tec1, factors that act downstream of the pheromone MAPK pathway, play opposite roles in regulating white cell mating as TEC1 deletion or CPH1 overexpression promotes white cell mating. Moreover, inactivation of the Cph1 repressor Dig1 increases white cell mating ~4000 fold in glucose-depleted medium relative to that in the presence of glucose. Our findings reveal that the white-to-opaque epigenetic switch may not be a prerequisite for sexual mating in C. albicans in nature.
Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens
Authors: Wang Rui , Shu Xian , Zhao Huiwei , Xue Qiong , Liu Chao , Wu Aici , Cheng Feiyue , Wang Lingyun , Zhang Yihan , Feng Jie , Wu Nannan , Li Ming
Published: April 2023

CreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targeting several essential RNA molecules that are required to initiate protein synthesis. CreA guides the CRISPR effector to transcriptionally repress CreT. We further demonstrate a proof-of-concept antimicrobial strategy named ATTACK, which AssociaTes TA and CRISPR-Cas to Kill multidrug resistant (MDR) pathogens. In this design, CRISPR-Cas is programed to target antibiotic resistance gene(s) to selectively kill MDR pathogens or cure their resistance, and when CRISPR-Cas is inactivated or suppressed by unwanted genetic or non-genetic events/factors, CreTA triggers cell death as the last resort. Our data highlight the diversity of RNA toxins coevolving with CRISPR-Cas, and illuminate a combined strategy of CRISPR and TA antimicrobials to ‘ATTACK’ MDR pathogens.
Forensic characteristics of 4866 violent injury cases in Sichuan Province, China
Authors: Zhang Shilin , Wang Wei , Wei Mengxuan , Luo Yu , Long Wu , Li Lincong , Jiang Chunyue , Zhu Tao , Lin Xia , Jin Bo
Published: April 2023

To evaluate the characteristics of violent injury cases in Sichuan Province, China. Overall, 4866 violent injury cases in Sichuan province, China from 2014 to 2017 were included. The injury evaluation report was used to classify and summarize the injury information, case and injury characteristics, and to describe the characteristics for each risk factor. The majority of cases were males (n = 3851, 79.14%), aged 20–60 (n = 3867, 79.47%), and living in rural areas (n = 3094, 65.55%). Many cases occurred in public areas (n = 3351, 74.19%) and in the evening (n = 1005, 29.49%). Passion was the main motive for the violent injuries (n = 2098, 82.11%) and the main types of injuries were those to the brain, face, and auricula (n = 3075, 63.21%). Blunt instruments (n = 2951, 64.86%) were most commonly used to inflict injury, and the injury evaluation determined that the majority of injuries were simple (n = 2669, 54.85%) and slight (n = 1685, 34.63%). For cases resulting from passion and money, blunt instruments were more commonly used, while sharp instruments were more commonly used for injuries resulting from emotion and revenge (p < 0.05). Compared with grievous injuries, public and entertainment areas and the use of blunt instruments were risk factors for slight injuries. The use of blunt instruments was a risk factor for simple injuries. The cases of violent injury in the Sichuan Province of China have certain characteristics and causes. In order to reduce the frequency of such cases, corresponding intervention measures should be actively conducted at the identified high risk places, times, and populations.
Chemical composition and repellent activity of essential oils of Tithonia diversifolia (Asteraceae) leaves against the bites of Anopheles coluzzii
Authors: Akeumbiwo Tchumkam Cédric , Kojom Foko Loick Pradel , Ndo Cyrille , Essangui Same Estelle , Cheteug Nguetsa Glwadys , Eya’Ane Meva François , Ayong Lawrence , Eboumbou Moukoko Carole Else
Published: April 2023

Tithonia diversifolia is widely used in African traditional medicine for the treatment of a large number of ailments and disorders, including malaria. In the present study, we evaluated the repellent activity of essential oils (EO) of this plant against Anopheles coluzzii, a major vector of malaria in Africa. Fresh leaves of T. diversifolia were used to extract EO, which were used to perform repellency assays in the laboratory and in the field using commercially available N,N-Diethyl-meta-toluamide (DEET) and Cymbopogon (C.) citratus EO as positive controls and vaseline as negative control. The repellency rates and durations of protection of the human volunteers involved were used as measures of repellent activity. Chemical composition of the T. diversifolia EO was established further by gas chromatography coupled with mass spectrometry. The moisture content and oil yield were 81% and 0.02% respectively. A total of 29 compounds in the T. diversifolia EO was identified, with d-limonene (20.1%), α-Copaene (10.3%) and o-Cymene (10.0%) as the most represented. In field studies, the mean time of protection against mosquito bites was significantly lower in T. diversifolia EO-treated volunteers compared to treatments with C. citratus EO (71 min versus 125 min, p = 0.04), but significantly higher when compared with the non-treated volunteers (71 min vs 0.5 min, p = 0.03). The same pattern was found in laboratory repellency assays against A. coluzzii. In contrast, repulsion rates were statistically similar between T. diversifolia EO and positive controls. In conclusion, the study suggests promising repellent potential of leaves of T. diversifolia EO against A. coluzzii.
Cosmic time calibrator for wireless sensor network
Authors: Tanaka Hiroyuki K. M.
Published: April 2023

Time synchronization of sensor nodes is critical for optimal operation of wireless sensor networks (WSNs). Since clocks incorporated into each node tend to drift, recurrent corrections are required. Most of these correction schemes involve clients periodically receive RF timing signals from a time server. However, an RF-based scheme is prone to glitches or failure unless operating in a region with almost entirely unobstructed space; hence it only operates well in a limited range of environments. For example, GPS requires open-sky environments. Moreover, the precision of land-based RF schemes is limited to a few micro seconds. In this work, we report on a more versatile and new type of recurrent clock resynchronization scheme called cosmic time calibrator (CTC) and its development and testing. CTC utilizes cosmic-ray muon signals instead of RF signals. Muons are penetrative and continuously precipitating onto the Earth’s surface, and they tend to travel linearly through encountered matter at approximately the speed of light in vacuum. Therefore, muons themselves can periodically transfer the precise timing information from node to node; hence, the performance of the inter-nodal communication device such as Wi-Fi or Bluetooth is minimized/unnecessary for an online/offline WSN analysis. The experimental results have indicated that a resynchronization frequency and precision of 60 Hz and ± 4.3 ns (S.D.) can be achieved. Modelling work of the WSN-based structural health monitoring of aerospace structures has shown that CTC can contribute to the development of new critical and useful applications of WSN in a wider range of environments.
5-methyladenosine regulators play a crucial role in development of chronic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis
Authors: Zhou Yiyi , Hu Zhenli , Sun Qinying , Dong Yuchao
Published: April 2023

5-methyladenosine (m5C) modification regulates gene expression and biological functions in oncologic areas. However, the effect of m5C modification in chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remains unknown. Expression data for 12 significant m5C regulators were obtained from the interstitial lung disease dataset. Five candidate m5C regulators, namely tet methylcytosine dioxygenase 2, NOP2/Sun RNA methyltransferase 5, Y-box binding protein 1, tRNA aspartic acid methyltransferase 1, and NOP2/Sun RNA methyltransferase 3 were screened using random forest and nomogram models to predict risks of pulmonary fibrosis. Next, we applied the consensus clustering method to stratify the samples with different m5C patterns into two groups (cluster A and B). Finally, we calculated immune cell infiltration scores via single-sample gene set enrichment analysis, then compared immune cell infiltration, related functions as well as the expression of programmed cell death 1 (PD-1, PDCD1) and programmed death protein ligand-1 (PD-L1, CD274) between the two clusters. Principal component analysis of m5C-related scores across the 288 samples revealed that cluster A had higher immune-related expression than B. Notably, T helper cell (Th) 2 type cytokines and Th1 signatures were more abundant in clusters A and B, respectively. Our results suggest that m5C is associated with and plays a crucial role in development of pulmonary fibrosis. These m5C patterns could be potential biomarkers for identification of CHP and IPF, and guide future development of immunotherapy or other new drugs strategies for pulmonary fibrosis.
Self-assembling bilayer wiring with highly conductive liquid metal and insulative ion gel layers
Authors: Murakami Koki , Isano Yuji , Asada Juri , Usami Natsuka , Isoda Yutaka , Takano Tamami , Matsuda Ryosuke , Ueno Kazuhide , Fuchiwaki Ohmi , Ota Hiroki
Published: April 2023

Ga-based liquid metals (LMs) are expected to be suitable for wiring highly deformable devices because of their high electrical conductivity and stable resistance to extreme deformation. Injection and printed wiring, and wiring using LM–polymer composites are the most popular LM wiring approaches. However, additional processing is required to package the wiring after LM patterning, branch and interrupt wiring shape, and ensure adequate conductivity, which results in unnecessary wiring shape changes and increased complexity of the wiring methods. In this study, we propose an LM–polymer composite comprising LM particles and ion gel as a flexible matrix material with low viscosity and specific gravity before curing. Moreover, the casting method is used for wire patterning, and the material is cured at room temperature to ensure that the upper insulative layer of the ion gel self-assembles simultaneously with the formation of LM wiring in the lower layer. High conductivity and low resistance change rate of the formed wiring during deformation are achieved without an activation process. This ion gel–LM bilayer wiring can be used for three-dimensional wiring by stacking. Furthermore, circuits fabricated using ion gel–LM bilayer wiring exhibit stable operation. Therefore, the proposed method can significantly promote the development of flexible electronic devices.
Heat transport in inclined flow towards a rotating disk under MHD
Authors: Mahmud K. , Duraihem Faisal Z. , Mehmood R. , Sarkar S. , Saleem S.
Published: April 2023

Flow towards a rotating disk is of highly practical significance in numerous engineering applications such as Turbine disks, rotary type machine systems and many more. In light of this, the current work is an attempt to explore MHD oblique flow towards a rotating disk. Hydromagnetic effects in addition to heat transfer is taken into consideration. The flow governing Partial Differential Equations are altered to a system to coupled non-linear Ordinary Differential Equations through scaling group of transformations which afterwards are tackled using Shooting Algorithm. The impact of obliqueness parameter γ, rotation ratio parameter $$\alpha$$
α
and magnetic field parameter M on 2-dimensional and 3-dimensional stream contours are presented. Location of the shear center varies with magnetic field parameter. Heat flow at the disk surface boosts with magnet field parameter M and rotation ratio parameter $$\alpha$$
α
.
Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest
Authors: Vítovcová Barbora , Skarková Veronika , Havelek Radim , Soukup Jiří , Pande Ananya , Caltová Kateřina , Rudolf Emil
Published: April 2023

Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of GBM cells. FLU exerted its effect by affecting microtubule structure and our results also suggest that FLU influences tubulins expression to a certain degree. Moreover, FLU effects decreased activation of STAT3 and also partially inhibited its expression, leading to upregulation of p53 signaling pathway and subsequent cell cycle arrest at G2/M phase as well as caspase-dependent cell death in GBM cells. These results suggest FLU as a promising agent to be used in GBM treatment and prompting further testing of its effects on GBM.
Location-based collective distress using large-scale biosignals in real life for walkable built environments
Authors: Kim Jinwoo , Nirjhar Ehsanul Haque , Lee Hanwool , Chaspari Theodora , Lee Chanam , Ham Youngjib , Winslow Jane Futrell , Ahn Changbum R.
Published: April 2023

Biosignals from wearable sensors have shown great potential for capturing environmental distress that pedestrians experience from negative stimuli (e.g., abandoned houses, poorly maintained sidewalks, graffiti, and so forth). This physiological monitoring approach in an ambulatory setting can mitigate the subjectivity and reliability concerns of traditional self-reported surveys and field audits. However, to date, most prior work has been conducted in a controlled setting and there has been little investigation into utilizing biosignals captured in real-life settings. This research examines the usability of biosignals (electrodermal activity, gait patterns, and heart rate) acquired from real-life settings to capture the environmental distress experienced by pedestrians. We collected and analyzed geocoded biosignals and self-reported stimuli information in real-life settings. Data was analyzed using spatial methods with statistical and machine learning models. Results show that the machine learning algorithm predicted location-based collective distress of pedestrians with 80% accuracy, showing statistical associations between biosignals and the self-reported stimuli. This method is expected to advance our ability to sense and react to not only built environmental issues but also urban dynamics and emergent events, which together will open valuable new opportunities to integrate human biological and physiological data streams into future built environments and/or walkability assessment applications.
Discovery and systematic assessment of early biomarkers that predict progression to severe COVID-19 disease
Authors: Hufnagel Katrin , Fathi Anahita , Stroh Nadine , Klein Marco , Skwirblies Florian , Girgis Ramy , Dahlke Christine , Hoheisel Jörg D. , Lowy Camille , Schmidt Ronny , Griesbeck Anne , Merle Uta , Addo Marylyn M. , Schröder Christoph
Published: April 2023

Background

The clinical course of COVID-19 patients ranges from asymptomatic infection, via mild and moderate illness, to severe disease and even fatal outcome. Biomarkers which enable an early prediction of the severity of COVID-19 progression, would be enormously beneficial to guide patient care and early intervention prior to hospitalization.

Methods

Here we describe the identification of plasma protein biomarkers using an antibody microarray-based approach in order to predict a severe cause of a COVID-19 disease already in an early phase of SARS-CoV-2 infection. To this end, plasma samples from two independent cohorts were analyzed by antibody microarrays targeting up to 998 different proteins.

Results

In total, we identified 11 promising protein biomarker candidates to predict disease severity during an early phase of COVID-19 infection coherently in both analyzed cohorts. A set of four (S100A8/A9, TSP1, FINC, IFNL1), and two sets of three proteins (S100A8/A9, TSP1, ERBB2 and S100A8/A9, TSP1, IFNL1) were selected using machine learning as multimarker panels with sufficient accuracy for the implementation in a prognostic test.

Conclusions

Using these biomarkers, patients at high risk of developing a severe or critical disease may be selected for treatment with specialized therapeutic options such as neutralizing antibodies or antivirals. Early therapy through early stratification may not only have a positive impact on the outcome of individual COVID-19 patients but could additionally prevent hospitals from being overwhelmed in potential future pandemic situations.
Orientation order of a nonpolar molecular fluid compressed into a nanosmall space
Authors: Wang Dan , Lippmann Milena , Gäding Johannes , Ehnes Anita , Novikov Dmitri , Meißner Robert , Seeck Oliver H.
Published: April 2023

Simulation and X-ray experiments indicate confinement induce orientational ordering of the non-polar molecules in the vicinity of the interfaces.
Modification of sulfonated poly(arylene ether nitrile) proton exchange membranes by poly(ethylene-co-vinyl alcohol)
Authors: Liu Hao , Dong Tiandu , Zhou Mingzheng , Zhang Zetian , Li Yunxi , Lu Chuanrui , Liu Yichen , Zhao Shengqiu , Zheng Shuhong , Meng Zihan , Tang Haolin
Published: April 2023

The modification of the physicochemical properties of sulfonated poly(arylene ether nitrile) (SPAEN) proton exchange membranes was demonstrated by poly(ethylene-co-vinyl alcohol) (EVOH) doping (named SPAEN-x%).
On-line monitoring of a recirculating-flow fluorescent capillary system for exploring the interaction mechanism of carbon dots/metal ions
Authors: Luo Ya-Xiong , Li Qiao-Jing , Li Yong-Sheng , Gao Xiu-Feng
Published: April 2023

The interaction mechanism of CDs with metal ions was explored by using fluorescence kinetics.
Microwave-assisted carbon-confined iron nanoparticles for steering CO2 hydrogenation to heavy hydrocarbons
Authors: Guo Lisheng , Ai Peipei , Gao Xinhua , Wu Hao , Wang Xianbiao , Kugue Yasuharu , Liang Jiaming , Gao Weizhe , Guo Xiaoyu , Sun Jian , Sun Song , Tsubaki Noritatsu
Published: April 2023

The key to efficient thermocatalytic conversion of CO2 lies in the rational design of catalysts.
Recent progress of cocatalysts loaded on carbon nitride for selective photoreduction of CO2to CH4
Authors: Guo Rui-Tang , Zhang Zhen-Rui , Xia Cheng , Li Chu-Fan , Pan Wei-Guo
Published: April 2023

This review summarizes the theory and application of cocatalyst/g-C3N4composite photocatalysts in the selective reduction of CO2to CH4.
The influence of dysfunctional actin on polystyrene-nanotube-mediated mRNA nanoinjection into mammalian cells
Authors: Yoh Hao Zhe , Chen Yaping , Shokouhi Ali-Reza , Thissen Helmut , Voelcker Nicolas H. , Elnathan Roey
Published: April 2023

PSNT replicated from SiNT were used as a nanoinjection platform for mRNA delivery into mammalian cells. The study showed that functional actin plays an important role in PSNT-mediated delivery especially during the initial cell interfacing period.
A photoluminescence assay with a portable device for rapid, sensitive and selective detection of europium and terbium
Authors: Bhowmik Dipankar , Maitra Uday
Published: April 2023

This work highlights the development of a paper-based photoluminescent sensor for the detection of europium and terbium.
The role of analyte concentration in accelerated reaction rates in evaporating droplets
Authors: Chen Casey J. , Williams Evan R.
Published: April 2023

Reactant concentration increases in evaporating droplets, leading to an apparent reaction acceleration up to 10 million fold, and this effect is a significant factor in reaction acceleration in droplets where volume is not carefully controlled.
A multi‐stage model for bird's eye view prediction based on stereo‐matching model and RGB‐D semantic segmentation
Authors: Rao Zhongyu , Cai Yingfeng , Wang Hai , Chen Long , Li Yicheng
Published: April 2023

Bird's‐Eye‐View (BEV) map is a powerful and detailed scene representation for intelligent vehicles that provides both the location and semantic information about nearby objects from a top‐down perspective. BEV map generation is a complex multi‐stage task, and the existing methods typically perform poorly for distant scenes. Thus, the authors introduce a novel multi‐stage model that infers to obtain more accurate BEV map. First, the authors propose the Adaptive Aggregation with Stereo Mixture Density (AA‐SMD) model, which is an improved stereo matching model that eliminates bleeding artefacts and provides more accurate depth estimation. Next, the authors employ the RGB‐Depth (RGB‐D) semantic segmentation model to improve the semantic segmentation performance and connectivity of their model. The depth map and semantic segmentation maps are then combined to create an incomplete BEV map. Finally, the authors propose a Multi Strip Pooling Unet (MSP‐Unet) model with a hierarchical multi‐scale (HMS) attention and strip pooling (SP) module to improve prediction with BEV generation. The authors evaluate their model with a Car Learn to Act (CARLA)‐generated synthetic dataset. The experiment results demonstrate that the authors’ model generates a highly accurate representation of the surrounding environment achieving a state‐of‐the‐art result of 61.50% Mean Intersection‐over‐Union (MIoU) across eight classes.