bluuebunny/crossref_metadata_2025 huggingface dataset:
Celastrol suppresses human pancreatic cancer via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2
Authors: Zhou Yang , Zhuang Haoran , Liu Yuxiang , Yin Jing , Wei Xiaoying , Qiu Yue , Tian Zhen , Miao Tingyu , Chen Jing , Li Peifen , Xu Xiao , Wu Wenjuan , Li Huanan , Shen Weigan
Published: December 2023

Background

Celastrol has been revealed to exhibit anticancer pharmacological activity, however, the molecular mechanisms of celastrol involved in pancreatic cancer remain to be further elucidated. The present study was to illustrate whether celastrol suppresses pancreatic cancer through modulating RNA m6A modification.

Methods

Effect of celastrol treatment on the malignant phenotypes of pancreatic cancer cells was evaluated by CCK-8 assay, EdU assay, colony formation assay, flow cytometry analysis and subcutaneous xenograft experiments. RNA sequencing (RNA-seq) analysis was carried out to analyze the genes differentially expressed in celastrol-treated pancreatic cancer cells. RT-qPCR, Western blotting and immunohistochemistry were employed to evaluate the expression of the indicated genes. RNA dot blot and quantification of total RNA m6A modification assays, MeRIP-qPCR assay, RIP-qPCR assay, RNA stability and protein stability assays were applied to evaluate the regulatory mechanism of celastrol treatment in pancreatic cancer cells.

Results

We demonstrated that celastrol suppressed cell proliferation and induced cell cycle arrest and apoptosis of pancreatic cancer cells in vitro, and decreased tumor growth in vivo. Specifically, Bcl-2, Claspin, METTL3 and YTHDF3 were identified as the potential targets of celastrol treatment in pancreatic cancer cells. Moreover, our results indicated that celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin and Bcl-2 mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells.

Conclusion

Our study highlighted a novel mechanism underlying celastrol-induced cellular proliferation inhibition and apoptosis in pancreatic cancer cells via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2.
Moisture-Electric–Moisture-Sensitive Heterostructure Triggered Proton Hopping for Quality-Enhancing Moist-Electric Generator
Authors: Yang Ya’nan , Wang Jiaqi , Wang Zhe , Shao Changxiang , Han Yuyang , Wang Ying , Liu Xiaoting , Sun Xiaotong , Wang Liru , Li Yuanyuan , Guo Qiang , Wu Wenpeng , Chen Nan , Qu Liangti
Published: December 2023

Moisture-enabled electricity (ME) is a method of converting the potential energy of water in the external environment into electrical energy through the interaction of functional materials with water molecules and can be directly applied to energy harvesting and signal expression. However, ME can be unreliable in numerous applications due to its sluggish response to moisture, thus sacrificing the value of fast energy harvesting and highly accurate information representation. Here, by constructing a moisture-electric–moisture-sensitive (ME-MS) heterostructure, we develop an efficient ME generator with ultra-fast electric response to moisture achieved by triggering Grotthuss protons hopping in the sensitized ZnO, which modulates the heterostructure built-in interfacial potential, enables quick response (0.435 s), an unprecedented ultra-fast response rate of 972.4 mV s−1, and a durable electrical signal output for 8 h without any attenuation. Our research provides an efficient way to generate electricity and important insight for a deeper understanding of the mechanisms of moisture-generated carrier migration in ME generator, which has a more comprehensive working scene and can serve as a typical model for human health monitoring and smart medical electronics design.
Enhanced Redox Electrocatalysis in High-Entropy Perovskite Fluorides by Tailoring d–p Hybridization
Authors: Li Xudong , Qiang Zhuomin , Han Guokang , Guan Shuyun , Zhao Yang , Lou Shuaifeng , Zhu Yongming
Published: December 2023

High-entropy catalysts featuring exceptional properties are, in no doubt, playing an increasingly significant role in aprotic lithium-oxygen batteries. Despite extensive effort devoted to tracing the origin of their unparalleled performance, the relationships between multiple active sites and reaction intermediates are still obscure. Here, enlightened by theoretical screening, we tailor a high-entropy perovskite fluoride (KCoMnNiMgZnF3-HEC) with various active sites to overcome the limitations of conventional catalysts in redox process. The entropy effect modulates the d-band center and d orbital occupancy of active centers, which optimizes the d–p hybridization between catalytic sites and key intermediates, enabling a moderate adsorption of LiO2 and thus reinforcing the reaction kinetics. As a result, the Li–O2 battery with KCoMnNiMgZnF3-HEC catalyst delivers a minimal discharge/charge polarization and long-term cycle stability, preceding majority of traditional catalysts reported. These encouraging results provide inspiring insights into the electron manipulation and d orbital structure optimization for advanced electrocatalyst.
Exploring the Cation Regulation Mechanism for Interfacial Water Involved in the Hydrogen Evolution Reaction by In Situ Raman Spectroscopy
Authors: You Xueqiu , Zhang Dongao , Zhang Xia-Guang , Li Xiangyu , Tian Jing-Hua , Wang Yao-Hui , Li Jian-Feng
Published: December 2023

Interfacial water molecules are the most important participants in the hydrogen evolution reaction (HER). Hence, understanding the behavior and role that interfacial water plays will ultimately reveal the HER mechanism. Unfortunately, investigating interfacial water is extremely challenging owing to the interference caused by bulk water molecules and complexity of the interfacial environment. Here, the behaviors of interfacial water in different cationic electrolytes on Pd surfaces were investigated by the electrochemistry, in situ core–shell nanostructure enhanced Raman spectroscopy and theoretical simulation techniques. Direct spectral evidence reveals a red shift in the frequency and a decrease in the intensity of interfacial water as the potential is shifted in the positively direction. When comparing the different cation electrolyte systems at a given potential, the frequency of the interfacial water peak increases in the specified order: Li+  < Na+  < K+  < Ca2+  < Sr2+. The structure of interfacial water was optimized by adjusting the radius, valence, and concentration of cation to form the two-H down structure. This unique interfacial water structure will improve the charge transfer efficiency between the water and electrode further enhancing the HER performance. Therefore, local cation tuning strategies can be used to improve the HER performance by optimizing the interfacial water structure.
Self-Assembly of Binderless MXene Aerogel for Multiple-Scenario and Responsive Phase Change Composites with Ultrahigh Thermal Energy Storage Density and Exceptional Electromagnetic Interference Shielding
Authors: Zhu Chuanbiao , Hao Yurong , Wu Hao , Chen Mengni , Quan Bingqing , Liu Shuang , Hu Xinpeng , Liu Shilong , Ji Qinghong , Lu Xiang , Qu Jinping
Published: December 2023

The severe dependence of traditional phase change materials (PCMs) on the temperature-response and lattice deficiencies in versatility cannot satisfy demand for using such materials in complex application scenarios. Here, we introduced metal ions to induce the self-assembly of MXene nanosheets and achieve their ordered arrangement by combining suction filtration and rapid freezing. Subsequently, a series of MXene/ K+/paraffin wax (PW) phase change composites (PCCs) were obtained via vacuum impregnation in molten PW. The prepared MXene-based PCCs showed versatile applications from macroscale technologies, successfully transforming solar, electric, and magnetic energy into thermal energy stored as latent heat in the PCCs. Moreover, due to the absence of binder in the MXene-based aerogel, MK3@PW exhibits a prime solar–thermal conversion efficiency (98.4%). Notably, MK3@PW can further convert the collected heat energy into electric energy through thermoelectric equipment and realize favorable solar–thermal–electric conversion (producing 206 mV of voltage with light radiation intensity of 200 mw cm−2). An excellent Joule heat performance (reaching 105 °C with an input voltage of 2.5 V) and responsive magnetic–thermal conversion behavior (a charging time of 11.8 s can achieve a thermal insulation effect of 285 s) for contactless thermotherapy were also demonstrated by the MK3@PW. Specifically, as a result of the ordered arrangement of MXene nanosheet self-assembly induced by potassium ions, MK3@PW PCC exhibits a higher electromagnetic shielding efficiency value (57.7 dB) than pure MXene aerogel/PW PCC (29.8 dB) with the same MXene mass. This work presents an opportunity for the multi-scene response and practical application of PCMs that satisfy demand of next-generation multifunctional PCCs.
Purpose-driven oral examination: insights from doctoral viva examiners
Authors: Tan Wee Chun
Published: December 2023

Despite the importance of the PhD viva in assessing the quality of doctoral research, how examiners approach the PhD viva remains underexplored in the Global South. This study fills this gap by investigating the conceptions of doctoral examiners in Malaysia, shedding light on how they approach the PhD viva and what they believe its key purposes are. Through qualitative thematic analysis of interviews with twelve examiners, this study reveals that examiners place a significant emphasis on the quality of the research thesis, empower candidates to demonstrate mastery of the research subject, initiate dialogue for research engagement, and foster socialisation within the disciplinary community. The study contributes to the conceptualisation of the purposes of the PhD viva, encompassing gatekeeping, empowerment, dialogue, and enculturation, which can provide valuable guidance for examiner practices. The implications of these findings are discussed, highlighting the facilitative role of examiners in the examination process.
Application of laser cleaning technology on metal cultural relics
Authors: Qian Runling , Wang Qiang , Niu Wenjuan , Zhang Hongzhi , Wei Cheng
Published: December 2023

Metal cultural relics are witnesses to the development of human history and civilization, containing rich value and connotation. Metal cultural relics have existed in the natural environment for hundreds and thousands of years and are facing severe corrosion problems, urgently requiring protection. Cleaning is the primary task of protection for metal cultural relics. Laser cleaning technology has attracted the interest of cultural relics scholars because of non-abrasive, non-contact, high efficiency and applicability to various materials. In order to enhance the understanding and application of laser cleaning technology on metal cultural relics, this paper provides a comprehensive review of the research advancements regarding the history and mechanism of laser cleaning technology, the corrosion mechanism of different metal cultural relics (copper relics, iron relics, silver relics, gold relics), as well as the application achievements of laser cleaning for metal cultural relics. The present study discusses the key problems and the development prospects of laser cleaning technology of metal cultural relics. Ultimately, the article will provide new ideas for the research and practice for the cleaning and protection of metal cultural relics.
Persistence and the Sheaf-Function Correspondence
Authors: Berkouk Nicolas
Published: December 2023

The sheaf-function correspondence identifies the group of constructible functions on a real analytic manifold M with the Grothendieck group of constructible sheaves on M. When M is a finite dimensional real vector space, Kashiwara-Schapira have recently introduced the convolution distance between sheaves of

$\mathbf {k}$

-vector spaces on M. In this paper, we characterize distances on the group of constructible functions on a real finite dimensional vector space that can be controlled by the convolution distance through the sheaf-function correspondence. Our main result asserts that such distances are almost trivial: they vanish as soon as two constructible functions have the same Euler integral. We formulate consequences of our result for Topological Data Analysis: there cannot exist nontrivial additive invariants of persistence modules that are continuous for the interleaving distance.
Lubrication dynamics of a settling plate
Authors: Wilkinson Andrew , Pradas Marc , Wilkinson Michael
Published: December 2023

If a flat, horizontal, plate settles onto a flat surface, it is known that the gap

$h$

decreases with time

$t$

as a power law:

$h\sim t^{-1/2}$

. We consider what happens if the plate is not initially horizontal, and/or the centre of mass is not symmetrically positioned: does one edge contact the surface in finite time, or does the plate approach the horizontal without making contact? The dynamics of this system is analysed and shown to be remarkably complex. We find that, depending upon the initial position of the plate and the position of the centre of force, the plate might either make contact in finite time or settle progressively without ever making contact. Our results show an excellent agreement between analytical exact solutions, asymptotic solutions and numerical studies of the lubrication equations.
Insights into the flame transitions and flame stabilization mechanisms in a freely falling burning droplet encountering a co-flow
Authors: Vadlamudi Gautham , Aravind Akhil , Basu Saptarshi
Published: December 2023

The present study investigates the flame dynamics of a contactless burning fuel droplet under free fall subjected to a co-flow. The dynamic external relative flow established due to co-flow and droplet acceleration results in a series of droplet flame transitions. Different flame structures were observed, including a wake flame, reversed wake flame and enveloped flame. Following ignition, the droplet is allowed to fall through the central tube of a co-flow arrangement, and, at its exit, the droplet flame encounters the co-flow. The wake flame, which was established based on the droplet's instantaneous velocity of descent, encounters the abrupt relative velocity jump due to the co-flow. This causes the droplet flame to go through various transitions as it approaches equilibrium with the surrounding flow. Once it equilibrates, the droplet flame evolves in response to the instantaneous relative flow velocity. The droplet flame evolves by altering both its shape and the stabilization mechanism. Two stabilization mechanisms were identified for the droplet wake flame: edge-flame stabilization and bluff-body stabilization. The stabilization mechanism for different flame structures and the transition events have been theoretically analysed, and the relation between flame shape evolution and flow velocity has been determined based on the flow-field characteristics at the corresponding Re (Reynolds number) range. Furthermore, these correlations are employed in a mathematical formulation based on the spring–mass analogy, which predicts the droplet flame evolution after encountering the co-flow, including all the transition events.
Path curvature enhances the flow-induced vibrations of a cylinder without structural restoring force
Authors: Bourguet Rémi
Published: December 2023

A cylinder immersed in a current and free to translate along a circular arc is considered to investigate the impact of path curvature on the flow-induced vibrations (FIV) occurring without structural restoring force. Path curvature magnitude (

$\kappa$

, inverse of path radius non-dimensionalized by the body diameter

$D$

) is varied from

$0$

(transverse rectilinear path) to

$20$

, over a wide range of values of the structure to displaced fluid mass ratio,

$m^\star \in [0.05,10]$

. The exploration is carried out numerically at subcritical and postcritical values of the Reynolds number (

$Re$

, based on

$D$

and the inflow velocity), i.e. below and above the critical value

$47$

for the onset of flow unsteadiness when the body is fixed, up to

$100$

. Path curvature triggers a desynchronized regime of the flow–body system in addition to the synchronized regime typical of vortex-induced vibrations, and alters the composition of fluid forcing. The most prominent effect uncovered here is, however, a global enhancement of FIV, with three principal results: (i) vibrations and flow unsteadiness are found to arise at lower subcritical

$Re$

along a curved path, down to

$19.5$

versus

$31$

for

$\kappa =0$

; (ii) the

$m^\star$

range where substantial responses develop is considerably extended and encompasses the entire interval under study, which contrasts with the narrow band of low

$m^\star$

identified for

$\kappa =0$

; (iii) the vibrations are amplified,

$+45\,\%$

relative to the peak amplitude measured along a rectilinear path at

$Re =100$

.
Reengineering of interbank networks
Authors: Leventides John , Poulios Costas , Livada Maria , Giannikos Ioannis
Published: December 2023

We investigate the reengineeering of interbank networks with a specific focus on capital increase. We consider a scenario where all other components of the network’s infrastructure remain stable (a practical assumption for short-term situations). Our objective is to assess the impact of raising capital on the network’s robustness and to address the following key aspects. First, given a predefined target for network robustness, our aim is to achieve this goal optimally, minimizing the required capital increase. Second, in cases where a total capital increase has been determined, the central challenge lies in distributing this increase among the banks in a manner that maximizes the stability of the network. To tackle these challenges, we begin by developing a comprehensive theoretical framework. Subsequently, we formulate an optimization model for the network’s redesign. Finally, we apply this framework to practical examples, highlighting its applicability in real-world scenarios.
Slow positron production and storage for the ASACUSA-Cusp experiment
Authors: Murtagh D.J. , Amsler C. , Breuker H. , Bumbar M. , Chesnevskaya S. , Costantini G. , Ferragut R. , Giammarchi M. , Gligorova A. , Gosta G. , Higaki H. , Hunter E.D. , Killian C. , Kraxberger V. , Kuroda N. , Lanz A. , Leali M. , Maero G. , Malbrunot C. , Mascagna V. , Matsuda Y. , Mäckel V. , Migliorati S. , Nanda A. , Nowak L. , Parnefjord Gustafsson F. , Rheinfrank S. , Romé M. , Simon M.C. , Tajima M. , Toso V. , Ulmer S. , Venturelli L. , Weiser A. , Widmann E. , Wolz T. , Yamazaki Y. , Zmeskal J.
Published: December 2023

The ASACUSA (atomic spectroscopy and collisions using slow antiprotons) Cusp experiment requires the production of dense positron plasmas with a high repetition rate to produce a beam of antihydrogen. In this work, details of the positron production apparatus used for the first observation of the antihydrogen beam, and subsequent measurements, are described in detail. This apparatus replaced the previous compact trap design resulting in an improvement in the positron accumulation rate by a factor of

$52\pm 3$

.
The egg ribonuclease SjCP1412 accelerates liver fibrosis caused by Schistosoma japonicum infection involving damage-associated molecular patterns (DAMPs)
Authors: Li Qi-Feng , Li Yi-Xin , Yang Ying-Ying , Dong Pan-Pan , Mei Cong-Jin , Lu Ju-Lu , Zhang Jian-Feng , Hua Hai-Yong , Xiong Chun-Rong , Yu Chuan-Xin , Song Li-Jun , Yang Kun
Published: December 2023

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.
Rethinking pedagogic identities for Key Stage 3 general classroom music teacher education: an autoethnographic study
Authors: Axtell Ian James
Published: December 2023

My role as a university-based, general classroom music teacher educator in England has become unclear, exacerbated by policies that have undermined the field of classroom music in schools and the role of universities in teacher education. Using self-critical inquiry enacted as critically reflexive autoethnography, I interrogated my professional practice to rethink my pedagogic identity. Theoretical perspectives, drawn from Bernstein and Bourdieu, were used to chart my shifting identity. This paper introduces a theorised model to illustrate a range of pedagogic identities for Key Stage 3 (KS3) general classroom music teacher education.
The syntactic status of V-final conjunct clauses in Old English: the role of priming
Authors: CICHOSZ ANNA
Published: December 2023

This study is a corpus-based investigation of the use of the V-final (VF) order in Old English conjunct (or coordinate) clauses. The aim of the analysis is to determine which of the two hypotheses formulated in earlier studies of the subject finds more convincing data support in the available corpora of Old English. According to one interpretation, conjunct clauses are a subtype of main clauses, and the VF order is used in both groups to signal continuation in discourse, especially with punctual, dynamic and relatively heavy verbs. Under the other view, VF conjunct clauses are syntactically subordinate, with the coordinating conjunction blocking verb movement like a complementiser. The present study shows that while both hypotheses are descriptively adequate, the main mechanism responsible for the use of the VF order in conjunct clauses is syntactic priming, with the VF order activated by a trigger clause (usually subordinate) and spreading to the following conjunct clause(s), which often results in long chains of subsequent VF clauses.
Effects of Wind Shear and Aerosol Conditions on the Organization of Precipitating Marine Stratocumulus Clouds
Authors: Jeong Jong‐Hoon , Witte Mikael K. , Smalley Mark
Published: December 2023

This study examines how wind shear affects precipitating marine stratocumulus clouds under different cloud droplet number concentrations (Nd). We performed a series of large eddy simulations (LES) of nocturnal marine stratocumulus clouds using Cloud Model 1 (CM1). The simulations show that Nd is the dominant factor for cloud cellular organization in this cloud regime rather than wind shear. Low Nd characterizes the open cellular structure with a high in‐cloud liquid water path (LWP). When wind shear is increased, the cloud fraction tends to decrease along with LWP, suggesting the cloud top region is significantly influenced by the entrainment and mixing of dry air from the free troposphere. We also examine cold pools in open and closed cellular clouds. Open‐cell clouds produce larger and deeper cold pools compared to closed‐cell clouds. Interestingly, cold pools can exist without surface precipitation and are produced by evaporation of light precipitation (drizzle) below the cloud base with weak downdrafts. The evaporation of raindrops and drizzle play an important role in initiating new convection, particularly where colliding outflows occur downstream of the cloud. This secondary convection contributes to the development and maintenance of the cloud cellular organization and formation.
Event‐Based Recession Analysis for Estimation of Basin‐Wide Characteristic Drainage Timescale and Groundwater Storage Trends
Authors: Hameed Mehvish , Nayak Munir Ahmad , Ahanger Manzoor Ahmad
Published: December 2023

In the absence of precipitation or any other recharge source, baseflow sustains natural surface water bodies like streams and rivers. It also indicates the quality and quantity of storage in the aquifers underlying the basin. Thus, identifying and extracting baseflow is critical for most hydrological studies, for example, estimating water budget, watershed characteristics, and groundwater surface‐water interactions. Most approaches for baseflow separation are based on recession hydrographs obtained solely from streamflow observations. A few studies have used the absence of precipitation as a filter for extracting baseflows for recession analysis, but not for estimating changes in groundwater storage. We demonstrate that an accurate estimation of drainage characteristic recession timescale 𝐾 for a linear storage‐discharge relationship should be based on carefully selected individual baseflow events extracted from streamflow observations complemented with precipitation observations. The drainage/recession timescale varies with time, even for a single basin, and hence, should not be generalized to a specific range for a wide range of basins. Estimations of groundwater storage trends and aquifer characteristics from streamflow and lumped analysis can be misleading. Event‐based recession analysis yields large variations in characteristic drainage timescales for a given catchment, which appears a more realistic representation of basin‐wide aquifer characteristics that are known to vary with antecedent climate. In the Rock River basin, we find contrasting trends in the estimated groundwater storages in two selected periods, which are then attributed to the contrasting trends in annual rainfall and evapotranspiration. The approach presented here would be beneficial in investigating aquifer characteristics and storage trends.
Evolution of Parent-Targeted Interventions for Pain-Predominant Disorders of Gut–Brain Interactions: Research and Clinical Practice Considerations
Authors: Lamparyk Katherine , Stellway Jacklyn , Turnage Cathleen , Murphy Tasha B. , Echere Jovita , Levy Rona L.
Published: December 2023

Objective:

Abdominal pain-related disorders of gut–brain interaction (DGBIs) in children are best understood from a biopsychosocial model, including particular attention to the child’s environment. Interventions have begun to increasingly target parents as important agents of change in this population. The purpose of this article is to summarize the evolution of parent-targeted interventions for pediatric pain-related DGBIs and provide recommendations for application of the model to clinical practice.

Method:

A topical review of literature regarding parent-targeted interventions and related factors in the treatment of pediatric pain-related DGBIs was conducted, followed by a discussion of these findings to clinical practice settings.

Results:

A growing body of research has supported parent-targeted interventions in the treatment of pediatric pain-related DGBIs, although translation of these findings to practice settings is complicated by numerous factors. Strategies for obtaining physician buy-in and parental engagement are discussed, as are potential logistical considerations of multiple caregivers, child age, and billing considerations.

Conclusions:

There is a promising and growing evidence-base for parent-targeted interventions for pain-related DGBIs, which have not yet been widely adopted into clinical practice recommendations. Engaging all stakeholders and attending to the nuances of this approach are recommended to successfully apply parent-targeted interventions into clinical practice settings.

Implications for Impact Statement

The role of parents in treating children with pain-related disorders of gut–brain interaction (DGBIs) has been an increasing area of study. This article summarizes the research on interventions for DGBIs that focus on parents as agents of change and provides practical considerations for applying this research to clinical, “real-world” settings.
Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation
Authors: Casella Valentina , Domenjo-Vila Eva , Esteve-Codina Anna , Pedragosa Mireia , Cebollada Rica Paula , Vidal Enric , de la Rubia Ivan , López-Rodríguez Cristina , Bocharov Gennady , Argilaguet Jordi , Meyerhans Andreas
Published: December 2023

Acute infection and chronic infection are the two most common fates of pathogenic virus infections. While several factors that contribute to these fates are described, the critical control points and the mechanisms that underlie infection fate regulation are incompletely understood. Using the acute and chronic lymphocytic choriomeningitis virus (LCMV) infection model of mice, we find that the early dynamic pattern of the IFN-I response is a differentiating trait between both infection fates. Acute-infected mice generate a 2-wave IFN-I response while chronic-infected mice generate only a 1-wave response. The underlying cause is a temporal difference in CD8 T cell-mediated killing of splenic marginal zone CD169+ macrophages. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce the 2nd IFN-I wave. This is required for subsequent immune events including induction of inflammatory macrophages, generation of effector CD8+ T cells and virus clearance. Importantly, these benefits come at a cost for the host in the form of spleen fibrosis. Due to an earlier marginal zone destruction, these ordered immune events are deregulated in chronic infection. Our findings demonstrate the critical importance of kinetically well-coordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.
Structure and dynamics of endogenous cardiac troponin complex in human heart tissue captured by native nanoproteomics
Authors: Chapman Emily A. , Roberts David S. , Tiambeng Timothy N. , Andrews Jãán , Wang Man-Di , Reasoner Emily A. , Melby Jake A. , Li Brad H. , Kim Donguk , Alpert Andrew J. , Jin Song , Ge Ying
Published: December 2023

Protein complexes are highly dynamic entities that display substantial diversity in their assembly, post-translational modifications, and non-covalent interactions, allowing them to play critical roles in various biological processes. The heterogeneity, dynamic nature, and low abundance of protein complexes in their native states present challenges to study using conventional structural biology techniques. Here we develop a native nanoproteomics strategy for the enrichment and subsequent native top-down mass spectrometry (nTDMS) analysis of endogenous cardiac troponin (cTn) complex directly from human heart tissue. The cTn complex is enriched and purified using peptide-functionalized superparamagnetic nanoparticles under non-denaturing conditions to enable the isotopic resolution of cTn complex, revealing their complex structure and assembly. Moreover, nTDMS elucidates the stoichiometry and composition of the cTn complex, localizes Ca2+ binding domains, defines cTn-Ca2+ binding dynamics, and provides high-resolution mapping of the proteoform landscape. This native nanoproteomics strategy opens a paradigm for structural characterization of endogenous native protein complexes.
Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q
Authors: Murphy Andrew J. , Cheng Changde , Williams Justin , Shaw Timothy I. , Pinto Emilia M. , Dieseldorff-Jones Karissa , Brzezinski Jack , Renfro Lindsay A. , Tornwall Brett , Huff Vicki , Hong Andrew L. , Mullen Elizabeth A. , Crompton Brian , Dome Jeffrey S. , Fernandez Conrad V. , Geller James I. , Ehrlich Peter F. , Mulder Heather , Oak Ninad , Maciezsek Jamie , Jablonowski Carolyn M. , Fleming Andrew M. , Pichavaram Prahalathan , Morton Christopher L. , Easton John , Nichols Kim E. , Clay Michael R. , Santiago Teresa , Zhang Jinghui , Yang Jun , Zambetti Gerard P. , Wang Zhaoming , Davidoff Andrew M. , Chen Xiang
Published: December 2023

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.
Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir
Authors: Pardons Marion , Cole Basiel , Lambrechts Laurens , van Snippenberg Willem , Rutsaert Sofie , Noppe Ytse , De Langhe Nele , Dhondt Annemieke , Vega Jerel , Eyassu Filmon , Nijs Erik , Van Gulck Ellen , Boden Daniel , Vandekerckhove Linos
Published: December 2023

The development of latency reversing agents that potently reactivate HIV without inducing global T cell activation would benefit the field of HIV reservoir research and could pave the way to a functional cure. Here, we explore the reactivation capacity of a lipid nanoparticle containing Tat mRNA (Tat-LNP) in CD4 T cells from people living with HIV undergoing antiretroviral therapy (ART). When combined with panobinostat, Tat-LNP induces latency reversal in a significantly higher proportion of latently infected cells compared to PMA/ionomycin (≈ 4-fold higher). We demonstrate that Tat-LNP does not alter the transcriptome of CD4 T cells, enabling the characterization of latently infected cells in their near-native state. Upon latency reversal, we identify transcriptomic differences between infected cells carrying an inducible provirus and non-infected cells (e.g. LINC02964, GZMA, CCL5). We confirm the transcriptomic differences at the protein level and provide evidence that the long non-coding RNA LINC02964 plays a role in active HIV infection. Furthermore, p24+ cells exhibit heightened PI3K/Akt signaling, along with downregulation of protein translation, suggesting that HIV-infected cells display distinct signatures facilitating their long-term persistence. Tat-LNP represents a valuable research tool for in vitro reservoir studies as it greatly facilitates the in-depth characterization of HIV reservoir cells’ transcriptome and proteome profiles.
Orbital perspective on high-harmonic generation from solids
Authors: Jiménez-Galán Álvaro , Bossaer Chandler , Ernotte Guilmot , Parks Andrew M. , Silva Rui E. F. , Villeneuve David M. , Staudte André , Brabec Thomas , Luican-Mayer Adina , Vampa Giulio
Published: December 2023

High-harmonic generation in solids allows probing and controlling electron dynamics in crystals on few femtosecond timescales, paving the way to lightwave electronics. In the spatial domain, recent advances in the real-space interpretation of high-harmonic emission in solids allows imaging the field-free, static, potential of the valence electrons with picometer resolution. The combination of such extreme spatial and temporal resolutions to measure and control strong-field dynamics in solids at the atomic scale is poised to unlock a new frontier of lightwave electronics. Here, we report a strong intensity-dependent anisotropy in the high-harmonic generation from ReS2 that we attribute to angle-dependent interference of currents from the different atoms in the unit cell. Furthermore, we demonstrate how the laser parameters control the relative contribution of these atoms to the high-harmonic emission. Our findings provide an unprecedented atomic perspective on strong-field dynamics in crystals, revealing key factors to consider in the route towards developing efficient harmonic emitters.
iMUT-seq: high-resolution DSB-induced mutation profiling reveals prevalent homologous-recombination dependent mutagenesis
Authors: Bader Aldo S. , Bushell Martin
Published: December 2023

DNA double-strand breaks (DSBs) are the most mutagenic form of DNA damage, and play a significant role in cancer biology, neurodegeneration and aging. However, studying DSB-induced mutagenesis is limited by our current approaches. Here, we describe iMUT-seq, a technique that profiles DSB-induced mutations at high-sensitivity and single-nucleotide resolution around endogenous DSBs. By depleting or inhibiting 20 DSB-repair factors we define their mutational signatures in detail, revealing insights into the mechanisms of DSB-induced mutagenesis. Notably, we find that homologous-recombination (HR) is more mutagenic than previously thought, inducing prevalent base substitutions and mononucleotide deletions at distance from the break due to DNA-polymerase errors. Simultaneously, HR reduces translocations, suggesting a primary role of HR is specifically the prevention of genomic rearrangements. The results presented here offer fundamental insights into DSB-induced mutagenesis and have significant implications for our understanding of cancer biology and the development of DDR-targeting chemotherapeutics.
Strain-driven Kovacs-like memory effect in glasses
Authors: Tong Yu , Song Lijian , Gao Yurong , Fan Longlong , Li Fucheng , Yang Yiming , Mo Guang , Liu Yanhui , Shui Xiaoxue , Zhang Yan , Gao Meng , Huo Juntao , Qiao Jichao , Pineda Eloi , Wang Jun-Qiang
Published: December 2023

Studying complex relaxation behaviors is of critical importance for understanding the nature of glasses. Here we report a Kovacs-like memory effect in glasses, manifested by non-monotonic stress relaxation during two-step high-to-low strains stimulations. During the stress relaxation process, if the strain jumps from a higher state to a lower state, the stress does not continue to decrease, but increases first and then decreases. The memory effect becomes stronger when the atomic motions become highly collective with a large activation energy, e.g. the strain in the first stage is larger, the temperature is higher, and the stimulation is longer. The physical origin of the stress memory effect is studied based on the relaxation kinetics and the in-situ synchrotron X-ray experiments. The stress memory effect is probably a universal phenomenon in different types of glasses.
Behavior of glioblastoma brain tumor stem cells following a suborbital rocket flight: reaching the “edge” of outer space
Authors: Garcia Cesar A. , Suárez-Meade Paola , Brooks Mieu , Bhargav Adip G. , Freeman Michelle L. , Harvey Lawrence M. , Quinn John , Quiñones-Hinojosa Alfredo
Published: December 2023

The emerging arena of space exploration has created opportunities to study cancer cell biology in the environments of microgravity and hypergravity. Studying cellular behavior in altered gravity conditions has allowed researchers to make observations of cell function that would otherwise remain unnoticed. The patient-derived QNS108 brain tumor initiating cell line (BTIC), isolated from glioblastoma (GBM) tissue, was launched on a suborbital, parabolic rocket flight conducted by EXOS Aerospace Systems & Technologies. All biologicals and appropriate ground controls were secured post-launch and transported back to our research facility. Cells from the rocket-flight and ground-based controls were isolated from the culture containers and expanded on adherent flasks for two weeks. In vitro migration, proliferation, and stemness assays were performed. Following cell expansion, male nude mice were intracranially injected with either ground-control (GC) or rocket-flight (RF) exposed cells to assess tumorigenic capacity (n = 5 per group). Patient-derived QNS108 BTICs exposed to RF displayed more aggressive tumor growth than the GC cells in vitro and in vivo. RF cells showed significantly higher migration (p < 0.0000) and stemness profiles (p < 0.01) when compared to GC cells. Further, RF cells, when implanted in vivo in the brain of rodents had larger tumor-associated cystic growth areas (p = 0.00029) and decreased survival (p = 0.0172) as compared to those animals that had GC cells implanted.
Anomalous Nernst effect in the topological and magnetic material MnBi4Te7
Authors: Ceccardi M. , Zeugner A. , Folkers L. C. , Hess C. , Büchner B. , Marré D. , Isaeva A. , Caglieris F.
Published: December 2023

The recently discovered magnetic topological insulators (MnBi2Te4)(Bi2Te3)n, n = 0–4, are an ideal playground to study the influence of magnetic properties on band topology, giving access to diverse quantum states in a single compound. In the low temperature-antiferromagnetic state and vanishing magnetic field, the n = 1 system is a topological insulator protected by a combination of time reversal and a translation symmetries. It has been argued that, when the antiferromagnetic phase is forced to a the fully spin polarized state by the application of an external magnetic field, this system develops Weyl cones in the conduction band, which become accessible in presence of an intrinsic electronic doping. In this work, we experimentally prove the raising of field-induced Weyl state through the detection of an intrinsic anomalous Nernst effect in a bulk single crystal of MnBi4Te7.
Asking the right questions for mutagenicity prediction from BioMedical text
Authors: Acharya Sathwik , Shinada Nicolas K. , Koyama Naoki , Ikemori Megumi , Nishioka Tomoki , Hitaoka Seiji , Hakura Atsushi , Asakura Shoji , Matsuoka Yukiko , Palaniappan Sucheendra K.
Published: December 2023

Assessing the mutagenicity of chemicals is an essential task in the drug development process. Usually, databases and other structured sources for AMES mutagenicity exist, which have been carefully and laboriously curated from scientific publications. As knowledge accumulates over time, updating these databases is always an overhead and impractical. In this paper, we first propose the problem of predicting the mutagenicity of chemicals from textual information in scientific publications. More simply, given a chemical and evidence in the natural language form from publications where the mutagenicity of the chemical is described, the goal of the model/algorithm is to predict if it is potentially mutagenic or not. For this, we first construct a golden standard data set and then propose MutaPredBERT, a prediction model fine-tuned on BioLinkBERT based on a question-answering formulation of the problem. We leverage transfer learning and use the help of large transformer-based models to achieve a Macro F1 score of >0.88 even with relatively small data for fine-tuning. Our work establishes the utility of large language models for the construction of structured sources of knowledge bases directly from scientific publications.
Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women
Authors: Liu Aoxing , Akimova Evelina T. , Ding Xuejie , Jukarainen Sakari , Vartiainen Pekka , Kiiskinen Tuomo , Koskelainen Sara , Havulinna Aki S. , Gissler Mika , Lombardi Stefano , Fall Tove , Mills Melinda C. , Ganna Andrea
Published: December 2023

The percentage of people without children over their lifetime is approximately 25% in men and 20% in women. Individual diseases have been linked to childlessness, mostly in women, yet we lack a comprehensive picture of the effect of early-life diseases on lifetime childlessness. We examined all individuals born in 1956–1968 (men) and 1956–1973 (women) in Finland (n = 1,035,928) and Sweden (n = 1,509,092) to the completion of their reproductive lifespan in 2018. Leveraging nationwide registers, we associated sociodemographic and reproductive information with 414 diseases across 16 categories, using a population and matched-pair case–control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers). The strongest associations were mental–behavioural disorders (particularly among men), congenital anomalies and endocrine–nutritional–metabolic disorders (strongest among women). We identified new associations for inflammatory and autoimmune diseases. Associations were dependent on age at onset and mediated by singlehood and education. This evidence can be used to understand how disease contributes to involuntary childlessness.
Unequal climate impacts on global values of natural capital
Authors: Bastien-Olvera B. A. , Conte M. N. , Dong X. , Briceno T. , Batker D. , Emmerling J. , Tavoni M. , Granella F. , Moore F. C.
Published: December 2023

Ecosystems generate a wide range of benefits for humans, including some market goods as well as other benefits that are not directly reflected in market activity1. Climate change will alter the distribution of ecosystems around the world and change the flow of these benefits2,3. However, the specific implications of ecosystem changes for human welfare remain unclear, as they depend on the nature of these changes, the value of the affected benefits and the extent to which communities rely on natural systems for their well-being4. Here we estimate country-level changes in economic production and the value of non-market ecosystem benefits resulting from climate-change-induced shifts in terrestrial vegetation cover, as projected by dynamic global vegetation models (DGVMs) driven by general circulation climate models. Our results show that the annual population-weighted mean global flow of non-market ecosystem benefits valued in the wealth accounts of the World Bank will be reduced by 9.2% in 2100 under the Shared Socioeconomic Pathway SSP2-6.0 with respect to the baseline no climate change scenario and that the global population-weighted average change in gross domestic product (GDP) by 2100 is −1.3% of the baseline GDP. Because lower-income countries are more reliant on natural capital, these GDP effects are regressive. Approximately 90% of these damages are borne by the poorest 50% of countries and regions, whereas the wealthiest 10% experience only 2% of these losses.