bluuebunny/crossref_metadata_2025 huggingface dataset:
CD8+ Regulatory T Cells Induced by Peptide Vaccination Ameliorates Experimental Model of Membranous Nephropathy
Authors: Chung Edmund Y. M. , Wang Yuan Min , Shaw Karli , Ronning Emily , Wang Ya , Zhang Geoff Yu , Hu Min , Keung Karen , McCarthy Hugh J. , Harris David C. H. , Stephen Alexander
Published: February 2025

Aim

CD8+ regulatory T cells (Tregs) are cross‐protective across multiple animal models of autoimmunity. Recently, specific peptides from a yeast‐peptide‐major histocompatibility complex library that expanded CD8+ Tregs in murine experimental multiple sclerosis were reported. Whether these peptides also expand CD8+ Tregs and protect against Heymann nephritis (HN), an experimental model of membranous nephropathy is unknown. We aimed to assess the efficacy of peptide vaccination to induce CD8+ Tregs in HN.

Methods

Lewis rats were immunised with Fx1A/complete Freund's adjuvant to induce HN and received peptide vaccination 1 week before (prevention vaccination) or 1 week after disease induction (treatment vaccination). To understand whether the effect of peptide vaccination was mediated by CD8+ Tregs, we adoptively transferred CD8+ T cells 1 week after peptide vaccination into HN rats.

Results

Prevention vaccination, but not treatment vaccination, significantly reduced anti‐Fx1A autoantibody levels and serum creatinine. Both prevention and treatment vaccination reduced histological kidney injury. mRNA expression of Helios, the major CD8+ Treg transcription factor, was upregulated in both the spleen and kidney with prevention vaccination and in the kidney with treatment vaccination. Adoptive transfer of CD8+ T cells after peptide vaccination significantly reduced serum creatinine, proteinuria, histological kidney injury, anti‐Fx1A autoantibody levels, germinal centre formation, and mRNA expression of markers of T follicular helper cells (Bcl6, interleukin‐21), T helper 1 cells (interferon‐γ, Tbet) and T helper 17 cells (interleukin‐6, interleukin‐17).

Conclusions

Peptide vaccination induces CD8+ Tregs that ameliorate induction of experimental membranous nephropathy which may represent a further peripheral regulation of autoimmunity.
Polyploidization leads to salt stress resilience via ethylene signaling in citrus plants
Authors: Song Xin , Zhang Miao , Wang Ting‐Ting , Duan Yao‐Yuan , Ren Jie , Gao Hu , Fan Yan‐Jie , Xia Qiang‐Ming , Cao Hui‐Xiang , Xie Kai‐Dong , Wu Xiao‐Meng , Zhang Fei , Zhang Si‐Qi , Huang Ying , Boualem Adnane , Bendahmane Abdelhafid , Tan Feng‐Quan , Guo Wen‐Wu
Published: February 2025

Polyploidization is a common occurrence in the evolutionary history of flowering plants, significantly contributing to their adaptability and diversity. However, the molecular mechanisms behind these adaptive advantages are not well understood.

Through comprehensive phenotyping of diploid and tetraploid clones from Citrus and Poncirus genera, we discovered that genome doubling significantly enhances salt stress resilience. Epigenetic and transcriptomic analyses revealed that increased ethylene production in the roots of tetraploid plants was associated with hypomethylation and enhanced chromatin accessibility of the ACO1 gene. This increased ethylene production activates the transcription of reactive oxygen species scavenging genes and stress‐related hormone biosynthesis genes. Consequently, tetraploid plants exhibited superior root functionality under salt stress, maintaining improved cytosolic K+/Na+ homeostasis.

To genetically validate the link between salt stress resilience and ACO1 expression, we generated overexpression and knockout lines, confirming the central role of ACO1 expression regulation following genome doubling in salt stress resilience.

Our work elucidates the molecular mechanisms underlying the role of genome doubling in stress resilience. We also highlight the importance of chromatin dynamics in fine‐tuning ethylene gene expression and activating salt stress resilience pathways, offering valuable insights into plant adaptation and crop genome evolution.
Factor Models With Sparse Vector Autoregressive Idiosyncratic Components
Authors: Krampe Jonas , Margaritella Luca
Published: February 2025

We reconcile dense and sparse modelling by exploiting the positive aspects of both. We employ a high‐dimensional, approximate static factor model and assume the idiosyncratic term follows a sparse vector autoregressive model (VAR). The estimation is articulated in two steps: (i) factors and loadings are estimated via principal component analysis (PCA); (ii) a sparse VAR is estimated via the lasso on the estimated idiosyncratic components from (i). Step (ii) allows to model cross‐sectional and time dependence left after the factors estimation. We prove the consistency of this approach as the time and cross‐sectional dimensions diverge. In (ii), sparsity is allowed to be very general: approximate, row‐wise, and growing with the sample size. However, the estimation error of (i) needs to be accounted for. Instead of simply plugging‐in the standard rates derived for the PCA estimation of the factors in (i), we derive a refined expression of the error, which enables us to derive tighter rates for the lasso in (ii). We discuss applications on forecasting & factor‐augmented regression and present an empirical application on macroeconomic forecasting using the Federal Reserve Economic Data ‐ Monthly Database (FRED‐MD).
Generation of suspension cell cultures with high syringin content and anti‐inflammatory activity through overexpressing glycotransferase SiUGT72BZ2 in Saussurea involucrata
Authors: Xu Yue , Cao Yingping , Tie Fangfang , Kong Xiuya , Liu Yuchen , Zhang Yaru , Guan Wenna , Hu Na , Wang Honglun , Qin Xiaochun , Wu Zhenying , Fu Chunxiang
Published: February 2025

The snow lotus species Saussurea involucrata (Kar. & Kir.) Sch.Bip., an endangered traditional Chinese herb, belongs to a genus of the Asteraceae family. Syringin present in S. involucrata stands as one of the predominant bioactive compounds. However, the biosynthetic pathway of syringin remains largely elusive. Here, S. involucrata suspension cell culture was subjected to methyl jasmonate (MeJA) treatment, which stimulated the synthesis of syringin, increasing its content by up to 3.9‐fold. Comparative transcriptome analysis revealed that genes involved in syringin biosynthesis were generally upregulated in response to MeJA. Furthermore, two candidate UDP‐glycosyltransferase genes, SiUGT72BZ2 and SiUGT72CY1, were identified through phylogenetic tree and expression profiling analyses. Overexpression of SiUGT72BZ2 (BZ2_OE) and SiUGT72CY1 (CY1_OE) in S. involucrata suspension cell cultures led to 15.2‐ and 5.9‐fold higher syringin levels than empty vector control cultures, respectively. Notably, upregulation of SiUGT72BZ2 enhanced the biosynthesis of coniferin as well. In contrast, only trace amounts of coniferin were present in control and CY1_OE cell cultures. Subsequent anti‐inflammatory assays using lipopolysaccharide (LPS)‐stimulated RAW264.7 cells demonstrated that the extracts from these cell cultures possessed remarkable anti‐inflammatory properties. Most strikingly, the BZ2_OE cultures exhibited superior anti‐inflammatory effects compared to the control and CY1_OE. In conclusion, our research has not only identified the key enzymes in syringin synthesis but also, through genetic engineering, has generated novel cell culture resources enriched with syringin and coniferin, and enhanced anti‐inflammatory activities, highlighting the potential of S. involucrata cell culture as an alternative for wild snow lotus resources.
Impact of Dietary Habits, Physical Activity, and Perceived Health Status on Health‐Related Quality of Life by Household Characteristics of Patients With Chronic Diseases: The Korea Community Health Survey (KCHS)
Authors: Kang Soyean , Sagong Hae , Lee Juyoung
Published: February 2025

Background

Modern societies are seeing a steady rise in individuals living alone. This study examines the impact of dietary habits, physical activity, and perceived health status on the health‐related quality of life (QoL) of adults aged 40 and older with chronic diseases, comparing living‐alone households to multi‐person households.

Methods

Data from the 2022 Korean Community Health Survey, including 65,861 respondents, were analyzed. The analysis utilized the Rao‐Scott χ2 test, independent t‐test, and multiple logistic regression with a complex sample design to assess differences in variables affecting QoL by household type.

Results

Individuals living alone were more likely to be female, older, less educated, economically inactive, divorced or separated, and have lower household incomes compared to those in multi‐person households. Physical activity, perceived health status, and QoL were higher in multi‐person households. Although all variables influenced QoL in multi‐person households, nutritional labeling awareness and frequency of physical activity showed no significant association with QoL in living‐alone households.

Conclusion

Living‐alone households with chronic diseases face notable demographic disparities. Additional research is needed to understand why nutritional labeling awareness and physical activity frequency do not significantly affect QoL in this group. The influence of mental health warrants further investigation to guide targeted interventions.
Nitrogen Deficiency Accelerates Rice Leaf Senescence Through ABA Signaling and Sugar Metabolic Shifts
Authors: Asad Muhmmad Asad Ullah , Guan Xianyue , Zhang Yan , Zhou Lujian , Bartas Martin , Ullah Najeeb , Zhou Weijun , Cheng Fangmin
Published: February 2025

Nitrogen (N) deficiency is one of the critical factors that induce leaf senescence by integrating with abscisic acid (ABA) metabolism, which results in a shortened leaf photosynthetic period and markedly lowered grain yield. However, the metabolic pathway by which ABA signaling participates in the regulation of senescence‐associated change in sugar metabolism and its relationship with N allocation in plant tissues are not well understood. In this paper, the effect of supply level on leaf C/N allocation and its relation to ABA signalling, sugar metabolism, and N assimilation were investigated by using two rice genotypes subjected to four N treatments. Results indicated that N‐deficiency markedly induced PYR1‐like (PYL) expression and ABA biosynthesis, consequently leading to the activation of ABA signaling. The increased ABA concentration in leaf tissues triggered the catabolic pathways of sugar and N metabolisms, resulting in the reduced photosynthetic pigments and intensified oxidative damage in N‐deficient leaves. ABA signaling induced by N‐deficiency upregulates the expression of senescence‐associated genes (SAGs) and C/N allocation by mediating several senescence‐promoting factors, such as NAC, bZIP, and WRKY TFs, along with the suppression of PP2Cs. Therefore, N‐deficiency impairs chlorophyll biosynthesis and triggers chlorophyll degradation to accelerate the timing and rate of leaf senescence. This metabolic network could provide helpful information for understanding the regulatory mechanism of leaf senescence in relation to sugar signaling, N‐assimilation and N‐use efficiency.
ECT8, an mRNA m6A reader, enhances salt stress tolerance by modulating mRNA stability in Arabidopsis
Authors: Nguyen Thi Kim Hang , Amara Umme , Kang Hunseung
Published: February 2025

N6‐methyladenosine (m6A), the most prevalent modification found in eukaryotic mRNAs, is recognized and interpreted by m6A‐binding proteins called m6A readers.

The EVOLUTIONARILY CONSERVED C‐TERMINAL REGION (ECT) proteins have increasingly been identified as m6A readers in plants. A recent study has demonstrated that the loss‐of‐function ect8 mutant is sensitive to salt stress by enhancing the stability of negative salt stress regulators in Arabidopsis (Arabidopsis thaliana). In this study, we generated and analyzed the ECT8‐overexpressing transgenic Arabidopsis plants to further explore the function of ECT8 in salt stress response. The electrophoretic mobility shift assay in vitro showed that ECT8 binds to the m6A‐modified synthetic RNAs, preferring UGUm6AA and UACm6AGA motifs over the GGm6ACU motif. Contrary to the ect8 mutant exhibiting salt hypersensitivity by enhancing the stability of salt stress negative regulators, the ECT8‐overexpressing transgenic Arabidopsis plants displayed salt tolerance by increasing the stability and expression levels of salt stress positive regulators. Moreover, RNA‐immunoprecipitation assay demonstrated that ECT8 binds to the m6A‐modified salt stress‐responsive mRNAs in planta. Collectively, our current and previous findings highlight that ECT8‐mediated stabilization and destabilization of the genes encoding salt stress positive or negative regulators, respectively, contribute to the salt stress tolerance of Arabidopsis.
Simulation model to estimate the burden of disease due to hepatitis E virus in Dutch pig meat and cost‐effectiveness of control measures
Authors: Focker M. , van Wagenberg C. P. A. , van Asseldonk M. A. P. M. , Boxman I. L. A. , Hakze ‐ van der Honing R. W. , van Asselt E. D.
Published: February 2025

Hepatitis E virus (HEV) can lead to liver disease in humans. In the Netherlands, the consumption of pig meat is thought to be the main contributor to the total burden of disease caused by HEV. In this study, the number of cases and lost disability‐adjusted‐life‐years (DALYs) due to HEV in pig meat were estimated by simulating HEV through the pig supply chain, including the farm, transport, lairage, slaughtering, processing, and consumption stages. The first four stages were modeled using a susceptible‐exposed‐infected‐recovered (SEIR) model. For the last two stages, pig meat and liver products were divided into six product categories commonly consumed by Dutch consumers. Depending on the product category, different ways of heating and storing, leading to the reduction of infectious HEV genome copies, were assumed. Furthermore, the model was challenged by four selected control options at the pig farm: the cleaning of driving boards, the use of predatory flies, the use of rubber mats, and the vaccination of finishing pigs. Finally, the cost‐effectiveness of these control measures was estimated by estimating the costs per avoided DALY. For the baseline situation, it was estimated that HEV in pig meat would lead to 70 cases and 21 DALYs per year. All control measures led to a decreased number of DALYs, with vaccination leading to the largest decrease: five DALYs per year. However, the costs per avoided DALY ranged from €0.5 to €7.5 million, making none of the control measures cost‐effective unless the control measures are also effective against other pathogens.
Evaluation of T‐cell repertoire by flow cytometric analysis in primary immunodeficiencies with DNA repair defects
Authors: Karaaslan Betul Gemici , Demirkale Zeynep Hizli , Turan Isilay , Aydemir Sezin , Meric Zeynep , Taskin Zuleyha , Kilinc Ozgur Can , Burtecene Nihan , Topcu Birol , Yucel Esra , Aydogmus Cigdem , Cokugras Haluk , Kiykim Ayca
Published: February 2025

The group of patients with DNA‐repair‐defects increases susceptibility to infections due to impaired repertoire diversity. In this context, we aimed to investigate the TCRvβ‐repertoire by flow cytometric analysis and its correlation with clinical entities in a group of IEI patients with DNA repair defects. Peripheral lymphocyte subset and TCRvβ‐repertoire analyses were performed by flow cytometric analysis. The aim was to explore the changing TCR‐Vβ‐repertoire that can predict some clinical entities by investigating the repertoire using flow‐cytometric‐analysis‐based TCR‐Vβ and its interaction with clinical entities in a group of IEI patients with DNA repair defects. TCR‐repertoire of the patients with DNA‐repair‐defects and healthy controls was analysed with flow‐cytometer. The potential of flow‐cytometric analysis of the TCR repertoire as a practical and easily accessible clinical prediction method was investigated. Thirty‐nine‐IEI patients with DNA‐repair‐defects and 15 age‐matched healthy‐controls were included in this study. Peripheral lymphocyte subset and TCR‐Vβ repertoire analyses were performed by flow cytometry. Compared to the control group, 9 out of 24 clones (37.5%) exhibited a statistically significant reduction, while only 3 clones showed a statistically significant increase (p < 0.05). Preferential use of vβ‐genes was associated with some clinical entities. Lower TCR‐vβ‐9 and TCR‐vβ23, higher TCR‐vβ7.2 were found in the patients with pneumonia (n = 13) (p = 0.018, p = 0.044 p = 0.032). AT patients with pneumonia had lower TCR‐vβ‐9 clone than patients without pneumonia (p = 0.008). Skewed proliferation of most TCR‐vβ clones was seen DNA‐repair‐defects, especially AT. In addition, this study showed that preferential use of TCR‐vβ genes could be predictive for some clinical entities.
Between space, relational sociology, and Lefebvre's critique of modernity: An understanding of relational spatiality in trans‐actional perspective
Authors: Fu Yongxuan
Published: February 2025

Although the ongoing Lefebvre renaissance has recently generated interest in many areas of sociology, contemporary relational sociology has not specifically considered Lefebvre's potential contribution to it. The article introduces a concept of relational spatiality based on the epistemology of relational sociology by reconsidering Lefebvre's inquiry into modernity and space. The article first briefly explains Lefebvre's epistemological critique of modernity, including everyday life and space, and then constructs the relational spatiality by combining Lefebvre with the relational and processual viewpoints of relational sociology. The article accordingly characterizes relational spatiality by combining Lefebvre's critique of “abstract space” as a crucial case with the de‐reification of relational sociology. At last, we further explore the trans‐actional perspective of relational sociology to motivate the deep relationalist understanding of space. From the “inter‐actional” premise to “trans‐actional” processes, relational spatiality reveals and avoids the underlying abstract purification, substantialism, and dualism in the analysis and cognition of space. We hope to lead sociologists to recognize that space involves a relational‐sociological concept constantly produced, functioned, and emerging through iterative trans‐actions rather than an objective entity or geographical premise waiting to be influenced by society, demonstrating the possibility of a spatial epistemology based on relational sociology.
Seizures and Lung Lesions in a Solid Organ Transplant Recipient: Bringing Things Together
Authors: Roberts Matthew B. , Coussement Julien , Lebeaux David , Coates P. Toby , Clemente Wanessa Trindade
Published: February 2025

A 28‐year‐old male presented to an Australian hospital with sudden‐onset headache and seizure following a kidney transplant for end‐stage renal disease due to IgA nephropathy. Clinical approach to the cases and management of the diagnosed disease are discussed.
Genome editing, an opportunity to revive soybean cultivation in Europe
Authors: Monfort Manon , Buitink Julia , Roeber Frank , Nogué Fabien
Published: February 2025

Soybean (Glycine max Merr.) is the world's most important oilseed crop and its ability to fix atmospheric nitrogen makes it a cornerstone of sustainable agriculture. Despite its importance, Europe relies heavily on imports, leading to environmental and economic vulnerabilities. To address these challenges, the European Union has implemented policies to boost local soybean production, emphasizing sustainable practices and reduced dependency on imports. However, conventional breeding methods are time‐consuming and may not keep pace with the rapid environmental and consumer habit changes. Genome‐editing technologies, such as CRISPR‐Cas, offer precise and efficient tools for developing soybean varieties tailored to European conditions. These technologies can enhance traits related to precocity, stress responses, yield and quality that are essential for adapting to climate change and promoting ecological sustainability. This review explores the integration of genome editing (GE) in soybean breeding, highlighting its potential in advancing the agroecological transition in Europe. By having a clear regulation and enhancing breeding efforts, GE can significantly contribute to developing resilient and sustainable soybean varieties, fostering a competitive and environmentally friendly European agriculture.
Systolic and diastolic dysfunction is exacerbated by age and spinal cord injury in male and female mice with central nervous system serotonin deficiency
Authors: Qiu Qingchao , Komnenov Dragana , Hali Mirabela , Chung Charles S. , Mueller Patrick J. , Rossi Noreen F. , Kuhn Donald M. , Mateika Jason H.
Published: February 2025

The present study was designed to explore whether the depletion of serotonin (5‐HT) in the central nervous system (CNS5‐HT) leads to systolic and diastolic dysfunction and whether this dysfunction is exacerbated by sex, age and spinal cord injury. Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female tryptophan hydroxylase 2 knockout (TPH2−/−) and wild‐type (TPH2+/+) mice with intact spinal cords, as well as in C2  spinal cord hemisected young TPH2−/− and TPH2+/+ mice. In addition, lumbar sympathetic nervous system activity was recorded in elderly male and female intact TPH2−/− and TPH2+/+ mice. Systolic and diastolic dysfunction was evident in young TPH2−/− mice, including a higher left ventricular mass (P < 0.001), left ventricular outflow parameters (e.g. peak velocity) and E/A (P < 0.001). Reductions in ejection fraction and fractional shortening were also evident (P < 0.001), although stroke volume and cardiac output were maintained. The assessed dysfunction was exacerbated by age and spinal cord injury, resulting in reductions in cardiac output (P ≤ 0.01). The dysfunction was accompanied by increases in sympathetic burst height (P = 0.038) and incidence (P = 0.001). Reductions in CNS5‐HT are coupled to systolic and diastolic dysfunction, which is exacerbated by age and spinal cord injury. This dysfunction is coupled to increases in sympathetic nervous system activity in elderly mice. Our findings are an initial step toward determining whether reductions in CNS5‐HT are a unifying mechanism that links central sleep apnoea, sympathoexcitation and heart failure in intact and spinal cord injured individuals.

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Key points

Reductions in central nervous system serotonin (CNS5‐HT) may contribute to systolic and diastolic dysfunction. This dysfunction may be linked to increases in sympathetic nervous system activity and exacerbated by sex, age and spinal cord injury.

Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female intact TPH2+/+ and TPH2−/− mice, as well as in C2 spinal cord hemisected young mice. Lumbar sympathetic nervous system activity was also recorded in elderly male and female intact TPH2+/+ and TPH2−/− mice.

Systolic and diastolic dysfunction was evident in young TPH2−/− mice. This dysfunction was exacerbated by age and spinal cord injury. The cardiac dysfunction was accompanied by increases in lumbar sympathetic nervous system activity.

Our findings are an initial step toward determining whether reductions in CNS5‐HT is a unifying mechanism that links central sleep apnoea, sympathoexcitation and heart failure in intact and spinal cord injured individuals.
The Eclipse
Authors: Vallelly Neil
Published: February 2025

‘It is the only democracy in the Middle East’—this is a standard refrain about Israel. Some stand by it; others refute it. Many argue that Benjamin Netanyahu has been eroding democratic values in Israel over the last decade; others insist that so-called Israeli democracy is premised on the oppression and killing of Palestinians, which thus undermines the universalist principles of liberal democracy. While many disagree on Israel’s democratic credentials, what underpins these debates is an implicit understanding of democracy as an inherently pacifying political and social system, one that has ‘if not banished brutality and physical violence, then [it has] at least brought them under control’. Violence is not necessarily external to democracy, but something that democratic societies have learned to manage through a variety of political, social, and legal institutions.
Effect of WC particle size on the microstructural evolution and wear resistance of laser cladding Inconel 718/WC-12Co composite coating
Authors: Liu Yu , Jin Haiquan , Li Guohui , Wang Zhaofeng , Liang Hui , Zhang Dongdong
Published: February 2025

The Cr-Zr-Cu copper alloy is widely used to manufacture mold for continuous casting. The proper coating can avoid the mold's failure under the condition of a high-temperature and friction environment. Three kinds of Inconel 718/WC-12Co coatings (micro-, nano-, and micro-nano-WC particles) were prepared on the surface of the copper alloy by laser. The phases, microstructure, and elemental distribution of L1–L3 coatings were observed and analyzed by x-ray diffractometer, scanning electron microscope, and energy dispersive spectrometer. The properties of L1–L3 coatings were tested by a Vickers hardness tester and friction and wear testing machine. The results show that the main phases are γ-Ni, M3W3C, MC, W0.15Ni0.85, and W2C in the L1–L3 coatings. In the L1 coating, there is an obvious phenomenon of WC agglomeration. In the L2 coating, there are many columnar, dendritic compounds, and “fish-bone” crystals with small size due to the addition of nanoparticles. In the L3 coating, the structure is scattered due to the uneven distribution of compounds. The average values of L1–L3 coatings' microhardness are 709.6, 851.9, and 600.1 HV0.5, respectively. The L2 coating has the maximum average microhardness. When the experimental temperature is 400 °C during the friction and wear test, the wear rates of L1–L3 coatings are 3.29, 1.89, and 2.83 × 10−4 mm3 N−1 mm−1, respectively. The L2 coating has the minimum wear rate due to the smaller grain size, denier microstructure, and “fish-bone” structure.
Passive acoustic measurements of air temperature at various altitudes
Authors: Yue Yan , Qi Zhi-Mei , Qiao Tao , Wang Junbo , Cai Rong
Published: February 2025

Acoustic thermometry is a fast, noncontact temperature measurement method that does not require heat exchange and, thus, is suitable for real-time monitoring of changes in air temperature at high altitudes where the thin air is not conducive to establishing thermal equilibrium. In this work, real-time measurements of air temperature at altitudes of up to 5200 m were achieved using a passive acoustic thermometer, which is an acoustic Fabry–Perot resonator (AFPR), consisting of an electret condenser microphone and an acoustic waveguide. The resonant frequency (fR) of the AFPR as a linear function of the mode order number (m) is measured using ambient white noise instead of external sound source, and the air temperature is determined based on the slope of the fR versus m curve. The surface air temperature changes in Beijing and the Kashgar Plateau were measured in real time over more than 15 h using the AFPR. By mounting the AFPR on a tethered balloon, the continuous monitoring of air temperature during liftoff and descent of the balloon was tested. The average deviation between the results simultaneously measured with the AFPR and commercial electronic thermometer was less than 0.5 °C, which verified the reliability of the AFPR-based passive acoustic thermometry.
A Randomized Crossover Trial on the Effects of Cadence on Calf Raise Test Outcomes: Cadence Does Matter
Authors: Hébert-Losier Kim , Fernandez Ma. Roxanne , Athens Josie , Kubo Masayoshi , O’Neill Seth
Published: February 2025

The calf raise test (CRT) is commonly used to assess triceps surae muscle-tendon unit function. Often, a metronome set to 60 beats/min (30 repetitions/min) is used to set the cadence of calf raise repetitions, but studies report using cadences ranging from 30 to 120 beats/min. We investigated the effect of cadence on CRT outcomes, accounting for the potential confounders of sex, age, body mass index, and physical activity. Thirty-six healthy individuals (50% female) performed single-leg calf raise repetitions to volitional exhaustion in 3 randomized cadence conditions, 7 days apart: 30, 60, and 120 beats/min. Repetitions, total vertical displacement, total work, peak height, and peak power were recorded using the validated Calf Raise application. Cadence significantly affected all CRT outcomes (P ≤ .008), except repetitions (P = .200). Post hoc analysis revealed 60 beats/min resulted in significantly greater total vertical displacement and work than 30 and 120 beats/min. Peak height was greater at 60 and 120 than 30 beats/min, and peak power was greater at 120 beats/min. Males generated greater work and peak power (P ≤ .001), whereas individuals with greater body mass index completed less repetitions (P = .008), achieved lower total vertical displacements (P = .003), and generated greater peak power (P = .005). CRT cadence is important to consider when interpreting CRT outcomes and comparing data between studies.
Physical Activity Barriers and Facilitators for Older Women With Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Tortosa-Martinez Juan , Martinez-Canales Celeste , Sanchis-Soler Gema , Beltran-Carrillo Vicente J.
Published: February 2025

Objectives: The objective of this qualitative study was to analyze the barriers and facilitators for the practice of physical activity (PA) perceived by older women with Mild Cognitive Impairment and Alzheimer disease. Methods: Semistructured interviews were conducted with 22 female participants and 22 matching family members. Data were analyzed with a conventional content analysis. Results: The barriers for PA identified in this study need to be interpreted from an intersectional perspective, since these participants remained in a particular situation of vulnerability due to not only being Mild Cognitive Impairment/Alzheimer disease participants, but also women and older adults. The main barriers identified were health problems, feelings of insecurity and helplessness in their out-home activities, reliance on the social network, and lack of PA culture and exercise knowledge. The main facilitators were the perceived benefits of PA, social support, currently having more free time, and the doctor’s advice of doing PA. Conclusions: Based on the results, recommendations for promoting PA in this population include the following: (a)  Promote a more constructive and positive conception of aging, gender roles, and cognitive impairment; (b) provide knowledge about the benefits of PA for this population; and (c) out-home PA with a social component could enhance the positive effects of PA, but exercise at home guided by a qualified professional could be an alternative for being active for those who suffer more from insecurity or dependence.
Large closed-basin lakes sustainably supplied phosphate during the origins of life
Authors: Walton Craig R. , Hao Jihua , Schönbächler Maria , Shorttle Oliver
Published: February 2025

The origin of life on Earth required a supply of phosphorus (P) for the synthesis of universal biomolecules. Closed lakes may have accumulated high P concentrations on early Earth. However, it is not clear whether prebiotic P uptake in such settings would then have been sustainable. We show that large closed-basin lakes can combine high P concentrations at steady state with extremely high rates of biological productivity. Our case study is Mono Lake in California, which has close to 1 millimolar dissolved P at steady state despite extremely high rates of biological productivity, in contrast to smaller closed basins where life is scarce. Hence, large closed-basin lakes offer an environment where high rates of prebiotic P productivity can plausibly coexist with high steady-state P concentrations. Such lakes should have readily formed on the heavily cratered and volcanically active surface of early Earth.
Exchange-selective excitation pulses for dynamic magnetic resonance
Authors: Lindale Jacob R. , Warren Warren S.
Published: February 2025

Coherent evolution is punctuated by dynamical processes such as chemical exchange, conformational transformation, or site hopping in many important problems ranging from biomolecular function to ion trap quantum computation. One well-explored example is nuclear magnetic resonance (NMR) spectroscopy, where experimental development is grounded in decades-old theory, but structural dynamics are not easily integrated into this picture. Here, we introduce an approach that selectively excites NMR resonances that undergo chemical exchange while suppressing the signal arising from nondynamic components of the system. We show that for exchange rates spanning more than four orders of magnitude, one can still selectively excite spins undergoing exchange while suppressing static resonances. Generalizing this approach, to selectively excite (or selectively preserve) only members of an ensemble that have undergone exchange or rearrangement, has the potential to improve the analytical power of many spectroscopic techniques.
Intratumoral antigen-presenting cell activation by a nanovesicle for the concurrent tertiary lymphoid structure de novo neogenesis
Authors: Cheng Ran , Li Sucheng , Ma Xianbin , Zhuang Wanru , Lei Yao , He Jiaqi , Liang Chao , Nie Weidong , Xie Hai-Yan
Published: February 2025

Tertiary lymphoid structures (TLSs) usually lead to significantly improved clinical benefits in immunotherapy but are rarely observed within native tumors. The current approaches are difficult in effectively inducing TLS formation, let alone fully exploiting its anticancer efficacy. Here, a biomimetic nanovesicle (ADU-S@M1) is constructed to target tumors and then to produce abundant activated antigen-presenting cells (APCs) in situ by polarizing the tumor-associated macrophages toward M1 phenotype and promoting dendritic cell maturation. These activated APCs effectively initiate the TLS de novo neogenesis by acting as lymphoid tissue inducer cells that secrete lymphotoxin α and tumor necrosis factor α while normalizing the intratumoral vasculatures. In addition, they induce robust in situ adaptive immune responses by presenting the antigens released from the M1 cell–destroyed tumors and transporting them to the nearby TLS. Therefore, the development of tumors in mice, especially immune-cold tumors, was efficiently prevented, providing a promising strategy for promoting cancer immunotherapy.
Disabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viability
Authors: Kollenstart Leonie , Biran Alva , Alcaraz Nicolas , Reverón-Gómez Nazaret , Solis-Mezarino Victor , Völker-Albert Moritz , Jenkinson Fion , Flury Valentin , Groth Anja
Published: February 2025

In the process of DNA replication, the first steps in restoring the chromatin landscape involve parental histone recycling and new histone deposition. Disrupting histone recycling to either the leading or lagging strand induces asymmetric histone inheritance, affecting epigenome maintenance and cellular identity. However, the order and kinetics of these effects remain elusive. Here, we use inducible mutants to dissect the early and late consequences of impaired histone recycling. Simultaneous disruption of both leading (POLE4) and lagging strand (MCM2-2A) recycling pathways impairs the transmission of parental histones to newly synthesized DNA, releasing some parental histones to the soluble pool. Subsequently, H3K27me3 accumulates aberrantly during chromatin restoration in a manner preceding gene expression changes. Loss of histone inheritance and the ensuing chromatin restoration defects alter gene expression in embryonic stem cells and challenge differentiation programs and cell viability. Our findings demonstrate the importance of efficient transmission of histone-based information during DNA replication for maintaining chromatin landscapes, differentiation potential, and cellular viability.
A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment
Authors: Gao Xin , Hu Yichen , Zhang Yingfei , Huang Yanyan , Zhang Guanxin , Zhang Xiao , Zhou Yongsheng , Zhang Deqing
Published: February 2025

Osteoporosis and bone injury healing in elderly patients are major medical challenges, often exacerbated by the accumulation of senescent cells. Herein, we show that TPE-Gal, which contains a tetraphenylethene unit and a galactose moiety, offers a promising molecular therapy designed to light up and eliminate senescent cells through a hydrolysis reaction catalyzed by β-galactosidase, an enzyme overexpressed in senescent cells. The reaction produces TPE-OH, which, in turn, increases reactive oxygen species levels within the senescent cells, leading to noninflammatory apoptosis of senescent cells. This targeted clearance mechanism helps to alleviate osteoporosis symptoms and promotes bone injury healing. Moreover, apoptotic vesicles, which are generated during the process, are partly phagocytosed by macrophages, mimicking physiological metabolic processes. This study opens new avenues for addressing bone health issues through the designed bioclearance of senescent cells, aligning with the body’s natural pathways for maintaining homeostasis.
Rift-inversion orogens are potential hot spots for natural H
2
generation
Authors: Zwaan Frank , Brune Sascha , Glerum Anne C. , Vasey Dylan A. , Naliboff John B. , Manatschal Gianreto , Gaucher Eric C.
Published: February 2025

Naturally occurring hydrogen gas (H
2
) represents a potential source of clean energy. A promising mechanism for large-scale natural H
2
generation is serpentinization of exhumed mantle material. We study this serpentinization-related H
2
generation during rifting and subsequent rift-inversion orogen development using numerical geodynamic models. Serpentinization-related H
2
generation is best known from rifted margins and spreading ridges. However, because orogens are colder than rift environments, conditions for serpentinization and natural H
2
generation are considerably better in orogenic settings: We find that yearly H
2
generation capacity from serpentinization in the overriding mantle wedge during rift inversion may be up to 20 times larger than during rifting. Moreover, suitable reservoirs and seals required for economic H
2
accumulations to form are readily available in rift-inversion orogens but are likely absent during bulk serpentinization in rift settings. Together with indications of ongoing natural H
2
generation in the Balkans and Pyrenees, our model results provide a first-order motivation for natural H
2
exploration in rift-inversion orogens.
Bioengineered protein nanocarrier facilitating siRNA escape from lysosomes for targeted RNAi therapy in glioblastoma
Authors: Jin Yiliang , Zhang Baoli , Li Jianru , Guo Zhenxi , Zhang Chen , Chen Xuehui , Ma Long , Wang Zhuoran , Yang Haiyin , Li Yong , Weng Yuhua , Huang Yuanyu , Yan Xiyun , Fan Kelong
Published: February 2025

RNA interference (RNAi) represents a promising gene-specific therapy against tumors. However, its clinical translation is impeded by poor performance of lysosomal escape and tumor targeting. This challenge is especially prominent in glioblastoma (GBM) therapy, necessitating the penetration of the blood-brain barrier (BBB). Leveraging the intrinsic tumor-targeting and BBB traversing capability of human H-ferritin, we designed a series of ferritin variants with positively charged cavity and truncated carboxyl terminus, termed tHFn(+). These nanocarriers respond to weak acid and disassemble in endosomal compartments, exposing the internal positive charges to facilitate the lysosomal escape of loaded small interfering RNA (siRNA). Functioning as universal siRNA nanocarriers, tHFn(+) significantly enhanced the uptake of different siRNAs and suppressed gene expressions associated with GBM progression. Furthermore, tHFn(+) traversed the BBB and targeted glioma in vivo by binding to its receptors (e.g., transferrin receptor 1). tHFn(+)-delivered siRNAs exhibited exceptional therapeutic effects against glioma in vivo, advancing RNAi therapeutics beyond GBM for the treatment of various diseases.
Noninvasive characterization of oocyte deformability in microconstrictions
Authors: Barbier Lucie , Bulteau Rose , Rezaei Behnam , Panier Thomas , Letort Gaëlle , Labrune Elsa , Verlhac Marie-Hélène , Vernerey Franck , Campillo Clément , Terret Marie-Emilie
Published: February 2025

Oocytes naturally present mechanical defects that hinder their development after fertilization. Thus, in the context of assisted reproduction, oocyte selection based on their mechanical properties has great potential to improve the quality of the resulting embryos and the success rate of these procedures. However, using mechanical properties as a quantifiable selective criterion requires robust and nondestructive measurement tools. This study developed a constriction-based microfluidic device that monitors the deformation of mouse oocytes under controlled pressure. The device can distinguish mechanically aberrant oocyte groups from healthy control ones. On the basis of a mathematical model, we propose that deformability measurements infer both oocyte tension and elasticity, elasticity being the most discriminating factor in our geometry. Despite force transmission during oocyte deformation, no long-term damage was observed. This noninvasive characterization of mouse oocyte deformability in microconstrictions allows for a substantial advance in assessing the mechanical properties of mammalian oocytes and has potential application as a quantifiable selective criterion in medically assisted reproduction.
Flexible circuit-free system via passive modulated ultrasound for wireless thoracic pressure monitoring
Authors: Wang Muyao , Jia Lu , Jia Xinyuan , Li Haicheng , Feng Xue
Published: February 2025

Implantable medical devices (IMDs) provide effective medical solutions for diverse health care applications. Electrical circuits are crucial for implantable devices due to the requirement of intended functions, such as communication with external devices. Circuits have several risks, such as biocompatibility issues, power limitations, or size constraints. In this work, we propose a passive modulated ultrasound (PMU) principle for IMDs and develop a circuit-free ultrasonic system (CUS) for thoracic pressure monitoring. The PMU principle can passively modulate monitored physiological signals into ultrasound pulses without using electrical circuits or power supply. The size of the developed CUS is only 2.5 millimeters in radius and 850 micrometers in height. Animal experiments demonstrated that the CUS, with a high sensitivity (−22.96 millivolts per kilopascal), can monitor thoracic pressure to assist in diagnosing different heart diseases, including cardiac arrest and myocardial infarction. The PMU provides a human-friendly wireless sensing and communication strategy for IMDs, which promotes advancements in health care applications within the human body.
Sequence-dependent scale for translocon-mediated insertion of interfacial helices in membranes
Authors: Grau Brayan , Kormos Rian , Bañó-Polo Manuel , Chen Kehan , García-Murria María J. , Hajredini Fatlum , Sánchez del Pino Manuel M. , Jo Hyunil , Martínez-Gil Luis , von Heijne Gunnar , DeGrado William F. , Mingarro Ismael
Published: February 2025

Biological membranes consist of a lipid bilayer studded with integral and peripheral membrane proteins. Most α-helical membrane proteins require protein-conducting insertases known as translocons to assist in their membrane insertion and folding. While the sequence-dependent propensities for a helix to either translocate through the translocon or insert into the membrane have been codified into numerical hydrophobicity scales, the corresponding propensity to partition into the membrane interface remains unrevealed. By engineering diagnostic glycosylation sites around test peptide sequences inserted into a host protein, we devised a system that can differentiate between water-soluble, surface-bound, and transmembrane (TM) states of the sequence based on its glycosylation pattern. Using this system, we determined the sequence-dependent propensities for transfer from the translocon to a TM, interfacial, or extramembrane space and compared these propensities with the corresponding probability distributions determined from the sequences and structures of experimentally determined proteins.
The Rise of Algae promoted eukaryote predation in the Neoproterozoic benthos
Authors: Mills Daniel B. , Vuillemin Aurèle , Muschler Katharina , Coskun Ömer K. , Orsi William D.
Published: February 2025

The proliferation of marine algae in the Neoproterozoic Era is thought to have stimulated the ecology of predatory microbial eukaryotes. To test this proposal, we introduced algal particulate matter (APM) to marine sediments underlying a modern marine oxygen minimum zone with bottom-water oxygen concentrations approximating those of the late Neoproterozoic water column. We found that under anoxia, APM significantly stimulated microbial eukaryote gene expression, particularly genes involved in anaerobic energy metabolism and phagocytosis, and increased the relative abundance of 18
S
rRNA from known predatory clades. We additionally confirmed that APM promoted the reproduction of benthic foraminifera under anoxia with higher-than-expected net growth efficiencies. Overall, our findings suggest that algal biomass exported to the Neoproterozoic benthos stimulated the ecology of benthic predatory protists under anoxia, thereby creating more modern food webs by enhancing the transfer of fixed carbon and energy to eukaryotes occupying higher trophic levels, including the earliest benthic metazoans.
Highly agile flat swimming robot
Authors: Hartmann Florian , Baskaran Mrudhula , Raynaud Gaetan , Benbedda Mehdi , Mulleners Karen , Shea Herbert
Published: February 2025

Navigating and exploring the surfaces of bodies of water allow swimming robots to perform a range of measurements while efficiently communicating and harvesting energy from the Sun. Such environments are often highly unstructured and cluttered with plant matter, animals, and debris, which require robots to move swiftly. We report a fast (5.1 centimeters per second translation and 195 degrees per second rotation), centimeter-scale swimming robot with high maneuverability and autonomous untethered operation. Locomotion is enabled by a pair of soft, millimeter-thin, undulating pectoral fins, in which traveling waves are electrically excited to generate propulsion. The actuators, robot design, and power supply are codesigned to enable high-performance locomotion in a scaled-down system. A single soft electrohydraulic actuator per side generates the traveling wave. A compact and lightweight power supply enables untethered operation, made possible by decreasing the operating voltage of the electrohydraulic actuators to below 500 volts and their power consumption to 35 milliwatts. By an experimental study and by modeling, we determined optimum dimensions and operating conditions across designs and size scales. The robots navigate through narrow spaces and through grassy plants and push objects weighing more than 16 times their body weight. Such robots can allow exploration of complex environments as well as continuous measurement of plant and water parameters for aquafarming.
A democratized bimodal model of research for soft robotics: Integrating slow and fast science
Authors: Obayashi Nana , Howard David , Walker Kyle L. , Jørgensen Jonas , Gepner Maks , Sameoto Dan , Stokes Adam , Iida Fumiya , Hughes Josie
Published: February 2025

A shift toward a democratized, bimodal model of research would allow soft robotics to realize its full potential.