bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential oil extracted from Quzhou Aurantii Fructus prevents acute liver failure through inhibiting lipopolysaccharide-mediated inflammatory response
Authors: Lan Tian , Wang Wen , Huang De-Lian , Zeng Xi-Xi , Wang Xiao-Xiao , Wang Jian , Tong Yu-Hua , Mao Zhu-Jun , Wang Si-Wei
Published: October 2023

Quzhou Aurantii Fructus (QAF) has a long history as a folk medicine and food for the treatment of liver diseases. While our earlier study provided evidence of hepatoprotective properties contained within the flavonoids and limonins constituents in QAF, the potential preventative effects afforded by essential oil components present within QAF remains enigmatic. In this study, we prepared Quzhou Aurantii Fructus essential oil (QAFEO) and confirmed its anti-inflammatory effects on liver inflammation through experimentation on lipopolysaccharide and D-galactosamine (LPS/D-GalN) induced acute liver failure (ALF) mouse models. Using RNA-sequence (RNA-seq) analysis, we found that QAFEO prevented ALF by systematically blunting the pathways involved in response to LPS and toll-like receptor signaling pathways. QAFEO effectively suppressed the phosphorylation of tank-binding kinase 1 (TBK1), TGF-beta activated kinase 1 (TAK1), interferon regulatory factor 3 (IRF3), and the activation of mitogen activated kinase-like protein (MAPK) and nuclear factor-kappa B (NF-κB) pathways in vivo and in vitro. Importantly, QAFEO substantially reduced myeloid differentiation primary response gene 88 (MyD88)- toll-like receptor 4 (TLR4) interaction levels. Moreover, 8 compounds from QAFEO could directly bind to REAL, TAK1, MyD88, TBK1, and IRF3. Taken together, the results of our study support the notion that QAFEO exerts a hepatoprotective effect through inhibiting LPS-mediated inflammatory response.

Graphical abstract
Humanoid Intelligent Display Platform for Audiovisual Interaction and Sound Identification
Authors: Wang Yang , Gao Wenli , Yang Shuo , Chen Qiaolin , Ye Chao , Wang Hao , Zhang Qiang , Ren Jing , Ning Zhijun , Chen Xin , Shao Zhengzhong , Li Jian , Liu Yifan , Ling Shengjie
Published: October 2023

This study proposes a rational strategy for the design, fabrication and system integration of the humanoid intelligent display platform (HIDP) to meet the requirements of highly humanized mechanical properties and intelligence for human–machine interfaces. The platform's sandwich structure comprises a middle light-emitting layer and surface electrodes, which consists of silicon elastomer embedded with phosphor and silk fibroin ionoelastomer, respectively. Both materials are highly stretchable and resilient, endowing the HIDP with skin-like mechanical properties and applicability in various extreme environments and complex mechanical stimulations. Furthermore, by establishing the numerical correlation between the amplitude change of animal sounds and the brightness variation, the HIDP realizes audiovisual interaction and successful identification of animal species with the aid of Internet of Things (IoT) and machine learning techniques. The accuracy of species identification reaches about 100% for 200 rounds of random testing. Additionally, the HIDP can recognize animal species and their corresponding frequencies by analyzing sound characteristics, displaying real-time results with an accuracy of approximately 99% and 93%, respectively. In sum, this study offers a rational route to designing intelligent display devices for audiovisual interaction, which can expedite the application of smart display devices in human–machine interaction, soft robotics, wearable sound-vision system and medical devices for hearing-impaired patients.
Improving the Social Connectedness of Older Adults Through Digital Social Gaming - A Pilot Study
Authors: Janssen Jeroen H. M. , van Es V. E. , Châtel Bas D. L. , Tieben Rob , Deen Menno , Olde Rikkert Marcel G. M. , Peeters G. M. E. E.
Published: October 2023

Background

Digital social interventions for older adults have become increasingly important due to their flexibility and potential to reduce loneliness. Digital games provide easy and fun interaction possibilities but need more exploration.

Methods

Using a mixed-methods design, we piloted a chat-based mobile application (PhotoSnake) designed to elicit social connectedness. Participants joined two in-person workshops two weeks apart and a focus group afterwards. They filled in a demographics and loneliness questionnaire pre- and post-intervention, and we collected anonymous in-app data.

Results

At baseline, participants (N = 15) were 74 years old, moderately lonely (Median = 2.0), partnered (40%), retired (93%), and living independently alone (53%) or with others (47%). Loneliness did not change over time. They valued the in-person workshops to get to know each other. Participants enjoyed playing the game for a few days but felt it lacked sufficient variation to persist gameplay. Furthermore, the in-app interaction mainly focused on the game and was perceived as too superficial to be meaningful.

Conclusion

This study helps design future digital interventions by showing the importance of in-person contact for engagement and meaningfulness. Players do not automatically label in-game interaction as valuable, and game design should focus on aiding players in creating personal interaction moments.
Enhancing seismic performance of buckling-restrained brace frames equipped with innovative bracing systems
Authors: Mohebi Benyamin , Sartipi Mohammad , Kazemi Farzin
Published: October 2023

Nowadays, to improve the performance of conventional bracing systems, in which, buckling in the pressure loads is the main disadvantage, the buckling-restrained brace (BRB) is introduced as a solution. In this study, the performance of the BRB system was improved with innovative lateral-resisting systems of double-stage yield buckling-restrained brace (DYB), and a combination of DYB improved with shape memory alloy (SMA) materials (DYBSMA). The proposed systems have been verified and implemented in the 2- to 12-story elevation steel buckling-restrained brace frames (BRBFs). To evaluate their effects on the seismic performance, two types of analysis including nonlinear dynamic analysis (NDA) and incremental dynamic analysis (IDA) were performed considering design-based earthquakes (DBE) and maximum considered earthquakes (MCE) levels for far-field ground motions. The results showed that the BRB system in all BRBFs had the highest values of residual drift ratio (RDRMed) demands, while implementing innovative DYBSMA can considerably reduce the values of RDRMed compared to other lateral-resisting systems. In addition, under MCE level, the BRB-DYBSMA system had lower values of the interstory drift ratio (IDRMed) and RDRMed demands (e.g., the IDRMed reduced by 79.67% and 18.5% compared to BRB and DYB systems, respectively), and can be introduced as the best lateral-resisting system. Therefore, the proposed BRB-DYBSMA system can effectively reduce the IDRMed and RDRMed demands, as result, higher performance levels can be achieved, as well as, the collapse probability occurrence over 1 and 50 years impressively decreased.
Application of processing maps and numerical modelling for identification of parameters and limitations of hot forging process of 80MnSi8-6 steel
Authors: Wojtaszek Marek , Lisiecki Łukasz , Łukaszek-Sołek Aneta , Korpała Grzegorz , Zyguła Krystian , Śleboda Tomasz , Jabłońska Magdalena Barbara , Prahl Ulrich
Published: October 2023

The processing maps developed by dynamic material modelling (DMM) method are now widely used in the design of hot forming processes. However, this applies to those processes that are relatively fast or are carried out under isothermal conditions, when it is possible to maintain the deformation parameters within the processing window. In the case of multi-stage free forging, the temperature successively decreases during subsequent operations and is increased during inter-process reheating. Under such conditions, processing maps in direct form are not applicable. The proposed solution is to implement the data obtained by the DMM method into calculations carried out by the finite element method (FEM). This approach leads to obtain the distributions of DMM parameters in the volume of the feedstock at successive forging stages. Selected results of a combined DMM/FEM analysis of a multi-stage hot forging process of 80MnSi8-6 steel are presented. The starting data for the analysis were the flow curves of this material, determined from compression tests. The processing maps were developed and processing windows were determined. The results of the DMM analysis were verified by microstructure observations. Data from the DMM analysis were implemented into QForm software using LUA scripts. An integrated FEM/DMM numerical analysis of the process of a multi-step hot free forging of an example product was performed. The geometry of the tools and a sequence of operations were developed. The distributions of the DMM parameters and the hot deformation activation energy in the forging volume after successive forging sequences were analyzed.
Literature and Natural Theology in Early Modern England
Authors: Calloway Katherine
Published: October 2023

Guiding readers through the diverse forms of natural theology expressed in seventeenth-century English literature, Katherine Calloway reveals how, in ways that have not yet been fully recognized, authors such as Donne, Herbert, Vaughan, Cavendish, Hutchinson, Milton, Marvell, and Bunyan describe, promote, challenge, and even practice natural theology in their poetic works. She simultaneously improves our understanding of an important and still-influential intellectual movement and deepens our appreciation of multiple major literary works. “Natural theology,” as it was popularly understood, changed dramatically in England over the seventeenth century, from the application of natural light to divine things to a newer, more brittle, understanding of the enterprise as the exclusive use of reason and observation to prove theological conclusions outside of any context of faith. These poets profoundly complicate the story, collectively demonstrating that some forms of natural theology lend themselves to poetry or imaginative literature rather than prose.
Corporate Networks and Business Groups in Egypt, 1924–1948: Economic Necessity or Entrepreneurial Dynamism
Authors: Beniamin Akram , Wilson John F. , Abdelrehim Neveen
Published: October 2023

By providing fresh insights into the development of Egyptian corporate networks and business groups between the early 1920s and late 1940s, this article extends the geographical ambit of an expanding field of study. Data from contemporaneous sources were analyzed through social network analysis techniques, in the search for an improved understanding of both the nature of and motivations behind networking in Egypt. In conducting this exercise, this article assesses the success with which the state acted to stimulate local entrepreneurship in its search for greater economic independence. By linking the Egyptian case to a wider literature on corporate networks, the article reveals similarities with other cases of how developing economies responded to the challenges of that era.
Radiofrequency ice dielectric measurements at Summit Station, Greenland
Authors: Aguilar Juan Antonio , Allison Patrick , Besson Dave , Bishop Abby , Botner Olga , Bouma Sjoerd , Buitink Stijn , Cataldo Maddalena , Clark Brian A. , Couberly Kenny , Curtis-Ginsberg Zach , Dasgupta Paramita , de Kockere Simon , de Vries Krijn D. , Deaconu Cosmin , DuVernois Michael A. , Eimer Anna , Glaser Christian , Hallgren Allan , Hallmann Steffen , Hanson Jordan Christian , Hendricks Bryan , Henrichs Jakob , Heyer Nils , Hornhuber Christian , Hughes Kaeli , Karg Timo , Karle Albrecht , Kelley John L. , Korntheuer Michael , Kowalski Marek , Kravchenko Ilya , Krebs Ryan , Lahmann Robert , Latif Uzair , Mammo Joseph , Marsee Matthew J. , Meyers Zachary S. , Michaels Kelli , Mulrey Katharine , Muzio Marco , Nelles Anna , Novikov Alexander , Nozdrina Alisa , Oberla Eric , Oeyen Bob , Plaisier Ilse , Punsuebsay Noppadol , Pyras Lilly , Ryckbosch Dirk , Scholten Olaf , Seckel David , Seikh Mohammad Ful Hossain , Smith Daniel , Stoffels Jethro , Southall Daniel , Terveer Karen , Toscano Simona , Tosi Delia , Van Den Broeck Dieder J. , van Eijndhoven Nick , Vieregg Abigail G. , Vischer Janna Z. , Welling Christoph , Williams Dawn R. , Wissel Stephanie , Young Robert , Zink Adrian
Published: October 2023

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60

$\to$

–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
High-dose cholecalciferol supplementation to obese infertile men is sufficient to reach adequate vitamin D status
Authors: Holt Rune , Jorsal Mads Joon , Yahyavi Sam Kafai , Qin Simeng , Juul Anders , Jørgensen Niels , Blomberg Jensen Martin
Published: October 2023

Obesity is associated with low vitamin D status, and the optimal supplement and dosage of cholecalciferol (vitamin D3) or calcidiol (25OHD) for individuals with obesity have been debated. We aimed to determine the effect of high-dose vitamin D3 supplementation on achieving adequate vitamin D levels among infertile men with normal weight v. obesity. Here, we present secondary end points from a single-centre, double-blinded, randomised clinical trial, comprising 307 infertile men randomised to active or placebo treatment for 150 days. Men in the active group initially received an oral bolus of 300 000 mg of vitamin D3, followed by daily supplementation with 1400 mg of vitamin D3 and 500 mg of calcium. Baseline BMI was listed as a predefined subgroup. At baseline, serum 25OHD was significantly higher in men with normal weight (BMI < 25 kg/m2) compared with men with overweight (BMI 25–30 kg/m2) and obesity (BMI > 30 kg/m2) (48 nmol/l v. 45 nmol/l and 39 nmol/l, respectively; P = 0·024). After the intervention, men with normal weight, overweight and obesity treated with vitamin D3 had a significantly higher serum 25OHD compared with corresponding placebo-treated men (BMI < 25 kg/m2: 92 nmol/l v. 53 nmol/l, BMI = 25–30 kg/m2: 87 nmol/l v. 49 nmol/l and BMI > 30 kg/m2: 85 nmol/l v. 48 nmol/l; P < 0·001 for all, respectively). In conclusion, we show that high-dose vitamin D3 supplementation to infertile men with obesity and low vitamin D status is sufficient to achieve adequate serum 25OHD levels.
Day-to-day affect fluctuations in adults with childhood trauma history: a two-week ecological momentary assessment study
Authors: Kuzminskaite Erika , Vinkers Christiaan H. , Smit Arnout C. , van Ballegooijen Wouter , Elzinga Bernet M. , Riese Harriëtte , Milaneschi Yuri , Penninx Brenda W.J.H.
Published: October 2023

Background

Childhood trauma (CT) may increase vulnerability to psychopathology through affective dysregulation (greater variability, autocorrelation, and instability of emotional symptoms). However, CT associations with dynamic affect fluctuations while considering differences in mean affect levels across CT status have been understudied.

Methods

346 adults (age = 49.25 ± 12.55, 67.0% female) from the Netherlands Study of Depression and Anxiety participated in ecological momentary assessment. Positive and negative affect (PA, NA) were measured five times per day for two weeks by electronic diaries. Retrospectively-reported CT included emotional neglect and emotional/physical/sexual abuse. Linear regressions determined associations between CT and affect fluctuations, controlling for age, sex, education, and mean affect levels.

Results

Compared to those without CT, individuals with CT reported significantly lower mean PA levels (Cohen'sd= −0.620) and higher mean NA levels (d= 0.556) throughout the two weeks. CT was linked to significantly greater PA variability (d= 0.336), NA variability (d= 0.353), and NA autocorrelation (d= 0.308), with strongest effects for individuals reporting higher CT scores. However, these effects were entirely explained by differences in mean affect levels between the CT groups. Findings suggested consistency of results in adults with and without lifetime depressive/anxiety disorders and across CT types, with sexual abuse showing the smallest effects.

Conclusions

Individuals with CT show greater affective dysregulation during the two-week monitoring of emotional symptoms, likely due to their consistently lower PA and higher NA levels. It is essential to consider mean affect level when interpreting the impact of CT on affect dynamics.
The long history of shortening: a diachronic analysis of abbreviation practices from the fifteenth to the twenty-first century
Authors: HONKAPOHJA ALPO , MARCUS IMOGEN
Published: October 2023

This article investigates continuities and changes in abbreviation practices from late Middle English to twenty-first-century digital platforms. Adopting a diachronic perspective and lexicological framework, it quantitatively analyses frequency patterns across fifteenth-century memoranda, letters and administrative receipts, seventeenth-century letters and depositions, late nineteenth-century letters, early twentieth-century letters and a subcorpus of WhatsApp instant messages dating from 2018–19. It then presents analyses of the frequencies of various abbreviation forms, such as clippings, and abbreviated lexemes, such as their use for names, over time. The article then provides a qualitative analysis of these lexeme categories over the centuries, with a focus on specific examples. Major changes to overall abbreviation density across time are identified. The forms of abbreviation also go through major change, but the types of lexemes that are abbreviated stay more consistent over time. For example, abbreviations being used for closed-class function words such astheandthatare dominant from the earliest data we have looked at to the present day. Overall, the study demonstrates how situating new media abbreviation practices within a historical continuum can enhance our understanding of them.
Dietary inflammatory potential is associated with higher odds of hepatic steatosis in US adults: a cross-sectional study
Authors: Yang Hu , Zhang Tengfei , Song Wen , Peng Zhaohong , Zhu Yu , Huang Yong , Li Xiude , Zhang Zhuang , Tang Min , Yang Wanshui
Published: October 2023

Objective:

Inflammation plays a critical role in the progression of chronic liver diseases, and diet can modulate inflammation. Whether an inflammatory dietary pattern is associated with higher risk of hepatic steatosis or fibrosis remains unclear. We aimed to investigate the associations between inflammatory dietary pattern and the odds of hepatic steatosis and fibrosis.

Design:

In this nationwide cross-sectional study, diet was measured using two 24-h dietary recalls. Empirical dietary inflammatory pattern (EDIP) score was derived to assess the inflammatory potential of usual diet, which has been validated to highly predict inflammation markers in the study population. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were derived from FibroScan to define steatosis and fibrosis, respectively.

Setting:

US National Health and Nutrition Examination Survey.

Participants:

4171 participants aged ≥18 years.

Results:

A total of 1436 participants were diagnosed with S1 steatosis (CAP ≥ 274 dB/m), 255 with advanced fibrosis (LSM ≥ 9·7 kPa). Compared with those in the lowest tertile of EDIP-adherence scores, participants in the highest tertile had 74 % higher odds of steatosis (OR: 1·74, 95 % CI (1·26, 2·41)). Such positive association persisted among never drinkers, or participants who were free of hepatitis B and/or C. Similarly, EDIP was positively associated with CAP in multivariate linear model (P< 0·001). We found a non-significant association of EDIP score with advanced fibrosis or LSM (P= 0·837).

Conclusions:

Our findings suggest that a diet score that is associated with inflammatory markers is associated with hepatic steatosis. Reducing or avoiding pro-inflammatory diets intake might be an attractive strategy for fatty liver disease prevention.
Combining Stochastic Parameterized Reduced‐Order Models With Machine Learning for Data Assimilation and Uncertainty Quantification With Partial Observations
Authors: Mou Changhong , Smith Leslie M. , Chen Nan
Published: October 2023

A hybrid data assimilation algorithm is developed for complex dynamical systems with partial observations. The method starts with applying a spectral decomposition to the entire spatiotemporal fields, followed by creating a machine learning model that builds a nonlinear map between the coefficients of observed and unobserved state variables for each spectral mode. A cheap low‐order nonlinear stochastic parameterized extended Kalman filter (SPEKF) model is employed as the forecast model in the ensemble Kalman filter to deal with each mode associated with the observed variables. The resulting ensemble members are then fed into the machine learning model to create an ensemble of the corresponding unobserved variables. In addition to the ensemble spread, the training residual in the machine learning‐induced nonlinear map is further incorporated into the state estimation, advancing the diagnostic quantification of the posterior uncertainty. The hybrid data assimilation algorithm is applied to a precipitating quasi‐geostrophic (PQG) model, which includes the effects of water vapor, clouds, and rainfall beyond the classical two‐level QG model. The complicated nonlinearities in the PQG equations prevent traditional methods from building simple and accurate reduced‐order forecast models. In contrast, the SPEKF forecast model is skillful in recovering the intermittent observed states, and the machine learning model effectively estimates the chaotic unobserved signals. Utilizing the calibrated SPEKF and machine learning models under a moderate cloud fraction, the resulting hybrid data assimilation remains reasonably accurate when applied to other geophysical scenarios with nearly clear skies or relatively heavy rainfall, implying the robustness of the algorithm for extrapolation.
Hurricane Harvey Filled Houston with Sediment
Authors: Besl J.
Published: October 2023

The storm’s record-setting rains moved an equally impressive amount of sediment and elevated the risk and expense of absorbing all that muck.
Sands on Meridiani Planum, Mars
Authors: Kozakiewicz J. , Kania M. , Salata D. , Nowak L.
Published: October 2023

The analyses of 184 sediment targets and more than 70,000 individual grains revealed that along the Opportunity rover traverse there are four distinct fractions of deposits related to different geomorphological settings: (a) dust mixed with very fine sand is common behind topographical obstacles, (b) fine sands are deposited in depressions, (c) very coarse sands occur in coarse‐grained ripple fields, and (d) gravel dominates at the rims of craters and on bedrock as lag deposits. Medium size sands were not observed on the plains, but they can be trapped in relatively large craters, where they form dunes and are within coarse‐grained ripples and transverse aeolian ridges (TARs). The fine sands show no regional variations in chemical composition and granulometry, as these sands are easily transported by wind. The very coarse sands vary in composition and shape between the plains and the Endeavour crater rim as their sources are local and their transport distances are short. On the plains, the gravel and the coarse sands are enriched in iron and characterized by higher roundness than the grains from the Endeavour crater rim. The source of iron‐rich, rounded grains on the plains are hematite spherules that are eroded out of Burns formation rocks. The smallest, the best sorted, and the least rounded coarse sand samples are found on coarse‐grained ripple crests. They are mainly composed of spherule fragments and their low roundness indicates shorter transport path lengths than those of grains transported in the past when coarse‐grained ripples migrated.
Coevolution between marine Aeromonas and phages reveals temporal trade-off patterns of phage resistance and host population fitness
Authors: Xu Zhenhe , Ding Zihan , Shi Lijia , Xie Yuzhen , Zhang Yuanxing , Wang Zhuang , Liu Qin
Published: October 2023

Coevolution of bacteria and phages is an important host and parasite dynamic in marine ecosystems, contributing to the understanding of bacterial community diversity. On the time scale, questions remain concerning what is the difference between phage resistance patterns in marine bacteria and how advantageous mutations gradually accumulate during coevolution. In this study, marine Aeromonas was co-cultured with its phage for 180 days and their genetic and phenotypic dynamics were measured every 30 days. We identified 11 phage resistance genes and classified them into three categories: lipopolysaccharide (LPS), outer membrane protein (OMP), and two-component system (TCS). LPS shortening and OMP mutations are two distinct modes of complete phage resistance, while TCS mutants mediate incomplete resistance by repressing the transcription of phage genes. The co-mutation of LPS and OMP was a major mode for bacterial resistance at a low cost. The mutations led to significant reductions in the growth and virulence of bacterial populations during the first 60 days of coevolution, with subsequent leveling off. Our findings reveal the marine bacterial community dynamics and evolutionary trade-offs of phage resistance during coevolution, thus granting further understanding of the interaction of marine microbes.
Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury
Authors: Liu Ting-tao , Shi Xin , Hu Hong-wei , Chen Ju-ping , Jiang Qin , Zhen Yun-Fang , Cao Cong , Liu Xue-wu , Liu Jian-gang
Published: October 2023

The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and β-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.
JMJD5 inhibits lung cancer progression by facilitating EGFR proteasomal degradation
Authors: Shen Jing , Liu Guiling , Qi Hongyan , Xiang Xueping , Shao Jimin
Published: October 2023

Aberrant activation of epidermal growth factor receptor (EGFR) signaling is closely related to the development of non-small cell lung cancer (NSCLC). However, targeted EGFR therapeutics such as tyrosine kinase inhibitors (TKIs) face the challenge of EGFR mutation-mediated resistance. Here, we showed that the reduced JmjC domain-containing 5 (JMJD5) expression is negatively associated with EGFR stability and NSCLC progression. Mechanically, JMJD5 cooperated with E3 ligase HUWE1 to destabilize EGFR and EGFR TKI-resistant mutants for proteasomal degradation, thereby inhibiting NSCLC growth and promoting TKI sensitivity. Furthermore, we identified that JMJD5 can be transported into recipient cells via extracellular vesicles, thereby inhibiting the growth of NSCLC. Together, our findings demonstrate the tumor-suppressive role of JMJD5 in NSCLC and suggest a putative therapeutic strategy for EGFR-related NSCLC by targeting JMJD5 to destabilize EGFR.
Ketamine evoked disruption of entorhinal and hippocampal spatial maps
Authors: Masuda Francis Kei , Aery Jones Emily A. , Sun Yanjun , Giocomo Lisa M.
Published: October 2023

Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine’s impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal’s spatial position, as mice navigated virtual reality and real world environments. Ketamine acutely increased firing rates, degraded cell-pair temporal firing-rate relationships, and altered oscillations, leading to longer-term remapping of spatial representations. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings demonstrate ketamine-induced dysfunction of the MEC-hippocampal circuit at the single cell, local-circuit population, and network levels, connecting previously demonstrated physiological effects of ketamine on spatial cognition to alterations in the spatial navigation circuit.
UV-B irradiation-activated E3 ligase GmILPA1 modulates gibberellin catabolism to increase plant height in soybean
Authors: Sun Jiaqi , Huang Shiyu , Lu Qing , Li Shuo , Zhao Shizhen , Zheng Xiaojian , Zhou Qian , Zhang Wenxiao , Li Jie , Wang Lili , Zhang Ke , Zheng Wenyu , Feng Xianzhong , Liu Baohui , Kong Fanjiang , Xiang Fengning
Published: October 2023

Plant height is a key agronomic trait that affects yield and is controlled by both phytohormone gibberellin (GA) and ultraviolet-B (UV-B) irradiation. However, whether and how plant height is modulated by UV-B-mediated changes in GA metabolism are not well understood. It has not been reported that the E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) is involved in the regulation of plant growth in response to environmental factors. We perform a forward genetic screen in soybean and find that a mutation in Glycine max Increased Leaf Petiole Angle1 (GmILPA1), encoding a subunit of the APC/C, lead to dwarfism under UV-B irradiation. UV-B promotes the accumulation of GmILPA1, which ubiquitinate the GA catabolic enzyme GA2 OXIDASE-like (GmGA2ox-like), resulting in its degradation in a UV-B-dependent manner. Another E3 ligase, GmUBL1, also ubiquitinate GmGA2ox-like and enhance the GmILPA1-mediated degradation of GmGA2ox-like, which suggest that GmILPA1-GmGA2ox-like module counteract the UV-B-mediated reduction of bioactive GAs. We also determine that GmILPA1 is a target of selection during soybean domestication and breeding. The deletion (Indel-665) in the promoter might facilitate the adaptation of soybean to high UV-B irradiation. This study indicates that an evolutionary GmILPA1 variant has the capability to develop ideal plant architecture with soybean cultivars.
Chemoproteomic capture of RNA binding activity in living cells
Authors: Heindel Andrew J. , Brulet Jeffrey W. , Wang Xiantao , Founds Michael W. , Libby Adam H. , Bai Dina L. , Lemke Michael C. , Leace David M. , Harris Thurl E. , Hafner Markus , Hsu Ku-Lung
Published: October 2023

Proteomic methods for RNA interactome capture (RIC) rely principally on crosslinking native or labeled cellular RNA to enrich and investigate RNA-binding protein (RBP) composition and function in cells. The ability to measure RBP activity at individual binding sites by RIC, however, has been more challenging due to the heterogenous nature of peptide adducts derived from the RNA-protein crosslinked site. Here, we present an orthogonal strategy that utilizes clickable electrophilic purines to directly quantify protein-RNA interactions on proteins through photoaffinity competition with 4-thiouridine (4SU)-labeled RNA in cells. Our photo-activatable-competition and chemoproteomic enrichment (PACCE) method facilitated detection of >5500 cysteine sites across ~3000 proteins displaying RNA-sensitive alterations in probe binding. Importantly, PACCE enabled functional profiling of canonical RNA-binding domains as well as discovery of moonlighting RNA binding activity in the human proteome. Collectively, we present a chemoproteomic platform for global quantification of protein-RNA binding activity in living cells.
Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans
Authors: Viola Cristina M. , Frittmann Orsolya , Jenkins Huw T. , Shafi Talha , De Meyts Pierre , Brzozowski Andrzej M.
Published: October 2023

The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR). This report describes the cryoEM structure of the dmIR ectodomain:DILP5 complex, revealing high structural homology between dmIR and hIR. The excess of DILP5 yields dmIR complex in an asymmetric ‘T’ conformation, similar to that observed in some complexes of human IRs. However, dmIR binds three DILP5 molecules in a distinct arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, and also underpins a better understanding of an important model organism.
Triepoxide formation by a flavin-dependent monooxygenase in monensin biosynthesis
Authors: Wang Qian , Liu Ning , Deng Yaming , Guan Yuze , Xiao Hongli , Nitka Tara A. , Yang Hui , Yadav Anju , Vukovic Lela , Mathews Irimpan I. , Chen Xi , Kim Chu-Young
Published: October 2023

Monensin A is a prototypical natural polyether polyketide antibiotic. It acts by binding a metal cation and facilitating its transport across the cell membrane. Biosynthesis of monensin A involves construction of a polyene polyketide backbone, subsequent epoxidation of the alkenes, and, lastly, formation of cyclic ethers via epoxide-opening cyclization. MonCI, a flavin-dependent monooxygenase, is thought to transform all three alkenes in the intermediate polyketide premonensin A into epoxides. Our crystallographic study has revealed that MonCI’s exquisite stereocontrol is due to the preorganization of the active site residues which allows only one specific face of the alkene to approach the reactive C(4a)-hydroperoxyflavin moiety. Furthermore, MonCI has an unusually large substrate-binding cavity that can accommodate premonensin A in an extended or folded conformation which allows any of the three alkenes to be placed next to C(4a)-hydroperoxyflavin. MonCI, with its ability to perform multiple epoxidations on the same substrate in a stereospecific manner, demonstrates the extraordinary versatility of the flavin-dependent monooxygenase family of enzymes.
Polarized microtubule remodeling transforms the morphology of reactive microglia and drives cytokine release
Authors: Adrian Max , Weber Martin , Tsai Ming-Chi , Glock Caspar , Kahn Olga I. , Phu Lilian , Cheung Tommy K. , Meilandt William J. , Rose Christopher M. , Hoogenraad Casper C.
Published: October 2023

Microglial reactivity is a pathological hallmark in many neurodegenerative diseases. During stimulation, microglia undergo complex morphological changes, including loss of their characteristic ramified morphology, which is routinely used to detect and quantify inflammation in the brain. However, the underlying molecular mechanisms and the relation between microglial morphology and their pathophysiological function are unknown. Here, proteomic profiling of lipopolysaccharide (LPS)-reactive microglia identifies microtubule remodeling pathways as an early factor that drives the morphological change and subsequently controls cytokine responses. We find that LPS-reactive microglia reorganize their microtubules to form a stable and centrosomally-anchored array to facilitate efficient cytokine trafficking and release. We identify cyclin-dependent kinase 1 (Cdk-1) as a critical upstream regulator of microtubule remodeling and morphological change in-vitro and in-situ. Cdk-1 inhibition also rescues tau and amyloid fibril-induced morphology changes. These results demonstrate a critical role for microtubule dynamics and reorganization in microglial reactivity and modulating cytokine-mediated inflammatory responses.
In situ electron paramagnetic resonance spectroscopy using single nanodiamond sensors
Authors: Qin Zhuoyang , Wang Zhecheng , Kong Fei , Su Jia , Huang Zhehua , Zhao Pengju , Chen Sanyou , Zhang Qi , Shi Fazhan , Du Jiangfeng
Published: October 2023

An ultimate goal of electron paramagnetic resonance (EPR) spectroscopy is to analyze molecular dynamics in place where it occurs, such as in a living cell. The nanodiamond (ND) hosting nitrogen-vacancy (NV) centers will be a promising EPR sensor to achieve this goal. However, ND-based EPR spectroscopy remains elusive, due to the challenge of controlling NV centers without well-defined orientations inside a flexible ND. Here, we show a generalized zero-field EPR technique with spectra robust to the sensor’s orientation. The key is applying an amplitude modulation on the control field, which generates a series of equidistant Floquet states with energy splitting being the orientation-independent modulation frequency. We acquire the zero-field EPR spectrum of vanadyl ions in aqueous glycerol solution with embedded single NDs, paving the way towards in vivo EPR.
Record ages of non-Markovian scale-invariant random walks
Authors: Régnier Léo , Dolgushev Maxim , Bénichou Olivier
Published: October 2023

How long is needed for an observable to exceed its previous highest value and establish a new record? This time, known as the age of a record plays a crucial role in quantifying record statistics. Until now, general methods for determining record age statistics have been limited to observations of either independent random variables or successive positions of a Markovian (memoryless) random walk. Here we develop a theoretical framework to determine record age statistics in the presence of memory effects for continuous non-smooth processes that are asymptotically scale-invariant. Our theoretical predictions are confirmed by numerical simulations and experimental realisations of diverse representative non-Markovian random walk models and real time series with memory effects, in fields as diverse as genomics, climatology, hydrology, geology and computer science. Our results reveal the crucial role of the number of records already achieved in time series and change our view on analysing record statistics.
Electronic Janus lattice and kagome-like bands in coloring-triangular MoTe2 monolayers
Authors: Lei Le , Dai Jiaqi , Dong Haoyu , Geng Yanyan , Cao Feiyue , Wang Cong , Xu Rui , Pang Fei , Liu Zheng-Xin , Li Fangsen , Cheng Zhihai , Wang Guang , Ji Wei
Published: October 2023

Polymorphic structures of transition metal dichalcogenides (TMDs) host exotic electronic states, like charge density wave and superconductivity. However, the number of these structures is limited by crystal symmetries, which poses a challenge to achieving tailored lattices and properties both theoretically and experimentally. Here, we report a coloring-triangle (CT) latticed MoTe2 monolayer, termed CT-MoTe2, constructed by controllably introducing uniform and ordered mirror-twin-boundaries into a pristine monolayer via molecular beam epitaxy. Low-temperature scanning tunneling microscopy and spectroscopy (STM/STS) together with theoretical calculations reveal that the monolayer has an electronic Janus lattice, i.e., an energy-dependent atomic-lattice and a Te pseudo-sublattice, and shares the identical geometry with the Mo5Te8 layer. Dirac-like and flat electronic bands inherently existing in the CT lattice are identified by two broad and two prominent peaks in STS spectra, respectively, and verified with density-functional-theory calculations. Two types of intrinsic domain boundaries were observed, one of which maintains the electronic-Janus-lattice feature, implying potential applications as an energy-tunable electron-tunneling barrier in future functional devices.
Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis
Authors: Tsuchiya Yuichi , Seki Takao , Kobayashi Kenta , Komazawa-Sakon Sachiko , Shichino Shigeyuki , Nishina Takashi , Fukuhara Kyoko , Ikejima Kenichi , Nagai Hidenari , Igarashi Yoshinori , Ueha Satoshi , Oikawa Akira , Tsurusaki Shinya , Yamazaki Soh , Nishiyama Chiharu , Mikami Tetuo , Yagita Hideo , Okumura Ko , Kido Taketomo , Miyajima Atsushi , Matsushima Kouji , Imasaka Mai , Araki Kimi , Imamura Toru , Ohmuraya Masaki , Tanaka Minoru , Nakano Hiroyasu
Published: October 2023

Liver fibrosis results from chronic liver injury triggered by factors such as viral infection, excess alcohol intake, and lipid accumulation. However, the mechanisms underlying liver fibrosis are not fully understood. Here, we demonstrate that the expression of fibroblast growth factor 18 (Fgf18) is elevated in mouse livers following the induction of chronic liver fibrosis models. Deletion of Fgf18 in hepatocytes attenuates liver fibrosis; conversely, overexpression of Fgf18 promotes liver fibrosis. Single-cell RNA sequencing reveals that overexpression of Fgf18 in hepatocytes results in an increase in the number of Lrat+ hepatic stellate cells (HSCs), thereby inducing fibrosis. Mechanistically, FGF18 stimulates the proliferation of HSCs by inducing the expression of Ccnd1. Moreover, the expression of FGF18 is correlated with the expression of profibrotic genes, such as COL1A1 and ACTA2, in human liver biopsy samples. Thus, FGF18 promotes liver fibrosis and could serve as a therapeutic target to treat liver fibrosis.
Cloaking a qubit in a cavity
Authors: Lledó Cristóbal , Dassonneville Rémy , Moulinas Adrien , Cohen Joachim , Shillito Ross , Bienfait Audrey , Huard Benjamin , Blais Alexandre
Published: October 2023

Cavity quantum electrodynamics (QED) uses a cavity to engineer the mode structure of the vacuum electromagnetic field such as to enhance the interaction between light and matter. Exploiting these ideas in solid-state systems has lead to circuit QED which has emerged as a valuable tool to explore the rich physics of quantum optics and as a platform for quantum computation. Here we introduce a simple approach to further engineer the light-matter interaction in a driven cavity by controllably decoupling a qubit from the cavity’s photon population, effectively cloaking the qubit from the cavity. This is realized by driving the qubit with an external tone tailored to destructively interfere with the cavity field, leaving the qubit to interact with a cavity which appears to be in the vacuum state. Our experiment demonstrates how qubit cloaking can be exploited to cancel the ac-Stark shift and measurement-induced dephasing, and to accelerate qubit readout. In addition to qubit readout, applications of this method include qubit logical operations and the preparation of non-classical cavity states in circuit QED and other cavity-based setups.
ELMAS: a one-year dataset of hourly electrical load profiles from 424 French industrial and tertiary sectors
Authors: Bellinguer Kevin , Girard Robin , Bocquet Alexis , Chevalier Antoine
Published: October 2023

The combination of ongoing urban expansion and electrification of uses challenges the power grid. In such a context, information regarding customers’ consumption is vital to assess the expected load at strategic nodes over time, and to guide power system planning strategies. Comprehensive household consumption databases are widely available today thanks to the roll-out of smart meters, while the consumption of tertiary premises is seldom shared mainly due to privacy concerns. To fill this gap, the French main distribution system operator, Enedis, commissioned Mines Paris to derive load profiles of industrial and tertiary sectors for its prospective tools. The ELMAS dataset is an open dataset of 18 electricity load profiles derived from hourly consumption time series collected continuously over one year from a total of 55,730 customers. These customers are divided into 424 fields of activity, and three levels of capacity subscription. A clustering approach is employed to gather activities sharing similar temporal patterns, before averaging the associated time series to ensure anonymity.
Variable cardiac responses in rhesus macaque monkeys after discrete mediodorsal thalamus manipulations
Authors: Méndez Juan Carlos , Perry Brook A. L. , Premereur Elsie , Pelekanos Vassilis , Ramadan Tamara , Mitchell Anna S.
Published: October 2023

The control of some physiological parameters, such as the heart rate, is known to have a role in cognitive and emotional processes. Cardiac changes are also linked to mental health issues and neurodegeneration. Thus, it is not surprising that many of the brain structures typically associated with cognition and emotion also comprise a circuit—the central automatic network—responsible for the modulation of cardiovascular output. The mediodorsal thalamus (MD) is involved in higher cognitive processes and is also known to be connected to some of the key neural structures that regulate cardiovascular function. However, it is unclear whether the MD has any role in this circuitry. Here, we show that discrete manipulations (microstimulation during anaesthetized functional neuroimaging or localized cytotoxin infusions) to either the magnocellular or the parvocellular MD subdivisions led to observable and variable changes in the heart rate of female and male rhesus macaque monkeys. Considering the central positions that these two MD subdivisions have in frontal cortico-thalamocortical circuits, our findings suggest that MD contributions to autonomic regulation may interact with its identified role in higher cognitive processes, representing an important physiological link between cognition and emotion.