bluuebunny/crossref_metadata_2025_split huggingface dataset:
PbMADS49 Regulates Lignification During Stone Cell Development in ‘Dangshansuli’ (Pyrus bretschneideri) Fruit
Authors: Meng Dandan , Liu Xin , Cao Yunpeng , Cai Yongping , Duan Jinsheng 
Published: February 2025

ABSTRACTLignified stone cell content is one of the critical factors affecting ‘Dangshansuli’ fruit quality. The function of MADS‐box transcription factors in regulating lignin biosynthesis in pear fruit is still less. In this study, PbMADS49 gene silencing inhibited the lignin biosynthesis and stone cell secondary wall development of pear fruit mainly through reducing the expression levels of lignin monomer polymerisation key enzymes (PbPRX33 and PbPRX45). PbMADS49 was a transcriptional repressor inhibiting its transcription by binding to the CArG element in the target gene promoter. Combined with the co‐expression network and promoter cis‐acting element analysis, we hypothesised that PbMADS49 positively regulates the transcription of PbPRX33 through PbWRKY63. The gene silencing effect of homologous genes PbPRX33‐1 and PbPRX33‐2 was consistent with PbMADS49, and PbPRX33‐2 was more significant than PbPRX33‐1. This study shows that PbMADS49 is a positive regulator of stone cell lignification, providing new insights into the development mechanism of pear stone cells.
Camp Wonder Provides Short‐Term Health‐Related Quality of Life Benefits for Participants With Chronic Skin Disease
Authors: Woodward Mani K. , Seshadri Rishi , Healy Thatcher , Leitenberger Sabra , Dhossche Julie 
Published: February 2025

ABSTRACTIntroductionChronic skin diseases in children can significantly impair their quality of life (QOL) due to physical discomfort and psychosocial challenges. Disease‐focused summer camps, like Camp Wonder (CW), offer a supportive environment for children to engage in activities and build friendships, potentially improving their QOL.MethodsThis prospective cohort study evaluated the short‐term QOL benefits of CW as measured by the Children's Dermatology Life Quality Index (CDLQI). Data were collected from 58 camp participants aged 8–17 years. The CDLQI was administered on the first and last days of CW. The paired sample t‐test was used to compare pre‐camp and post‐camp CDLQI scores. A multiple linear regression analysis examined predictors of QOL improvement, including age, diagnosis category, sex, and initial CDLQI severity.ResultsCW participants showed significant improvements in total CDLQI scores (mean change = −3.8 points, p < 0.0001) and in all constituent domains. Participants with “very large” initial QOL impacts experienced an average reduction of 8.4 points, while those with “extremely large” impacts had a reduction of 15.3 points relative to the reference group. Age, sex, and diagnosis were not significant predictors of QOL changes.ConclusionCW provides significant short‐term QOL benefits, particularly for children with severe impairments due to chronic skin disease. These findings suggest that summer camp experiences may be useful as part of a comprehensive care strategy, especially for pediatric patients with severe QOL impacts.
SLC13A5 plays an essential role in the energy shift to oxidative phosphorylation in cisplatin‐resistant mesothelioma stem cells
Authors: Kato‐Shinomiya Marie , Sugino Hirokazu , Wang Lei , Saito Yusuke , He Jintao , Tanei Zen‐ichi , Oda Yoshitaka , Tanikawa Satoshi , Tanino Mishie , Gong Jian Ping , Tsuda Masumi , Tanaka Shinya 
Published: February 2025

AbstractMesothelioma is a highly aggressive tumor affecting an increasing number of patients worldwide. Owing to the poor clinical outcomes associated with current therapies, the development of novel therapies that target cancer stem cells (CSCs) is desirable. Here, we examined the applicability of our previously established hydrogel‐based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) ‐like cells. Human mesothelioma cell lines cultured on hydrogels presented increased expression of pan‐stem cell markers and acquired spheroid formation and early tumorigenicity, suggesting that MesoSC‐like cells are highly malignant. Microarray analysis demonstrated that the expression of SLC13A5, a citrate transporter involved in TCA cycle, was significantly induced in the resulting MesoSC‐like cells. The overexpression of SLC13A5 resulted in a metabolic shift toward oxidative phosphorylation, increased phosphorylation of ERK and YAP, and increased SOX2 expression, leading to increased cisplatin resistance. scRNA‐seq database analysis revealed that clinical mesothelioma samples contained a small number of SLC13A5‐expressing cells. Our findings suggest that the hydrogel‐based CSC generation method is also effective for human mesothelioma cells and that SLC13A5 may contribute to MesoSC survival. The new properties of MesoSCs revealed in this study may provide clues for establishing future treatments.
Associations Between Snoring, Body Mass Index and Coronary Artery Diseases: Observational and Mendelian Randomization Study in Asia
Authors: Zhu Yunqing , Lan Yongbing , Lv Jun , Sun Dianjianyi , Pei Pei , Yang Ling , Millwood Iona Y. , Walters Robin G. , Chen Yiping , Du Huaidong , Wang Jian , Yang Xiaoming , Stevens Rebecca , Chen Junshi , Chen Zhengming , Li Liming , Yu Canqing ,   the China Kadoorie Biobank Collaborative Group
Published: February 2025

ABSTRACTBackground and ObjectivePrevious observational studies reported a complex relationship between snoring and coronary artery disease (CAD). We aimed to estimate the causal associations between snoring and CAD among East Asian people, and the effects independent of BMI.MethodsBased on 497,250 adults from China Kadoorie Biobank (CKB), we performed a conventional prospective analysis between snoring and CAD outcomes, using the multivariable Cox regression. We also leveraged genome‐wide association (GWAS) summary statistics of snoring and BMI from CKB (n = 100,626, 47,208 snorers) and CAD outcomes from Biobank of Japan (BBJ, 5891–25,892 cases, 142,336–168,186 controls). Single‐variable and multivariable two‐sample bi‐directional Mendelian randomization (MR) analyses were performed.ResultsDuring a median follow‐up of 12.32 years, 48,997 participants developed CAD. Snoring and habitual snoring were associated with incident CAD and myocardial infarction (MI), habitual snoring was also associated with stable angina pectoris (SAP). The HRs (95% CIs) of habitual snoring were 1.06 (1.04, 1.08), 1.06 (1.04, 1.08) and 1.14 (1.03, 1.25). The associations remained among non‐adiposity participants. Genetically predicted habitual snoring was associated with CAD and MI, the corresponding IVW‐ORs (95% CIs) were 1.09 (1.005, 1.19) and 1.15 (1.05, 1.25). Further adjusted BMI, habitual snoring retained independent effects on MI and CAD, and showed impact on SAP (1.09 [1.01, 1.17]). No reverse associations were observed between CADs on snoring traits.ConclusionHabitual snoring elevated the risks of total CAD, MI and SAP. The causal associations were independent of BMI. These findings indicated that snoring intervention might contribute to the decrease of CAD risk among Asians.
Exploring ABI5 regulation: Post‐translational control and cofactor interactions in ABA signaling
Authors: Du Chang , Bai Haiyan , Yan Yujie , Liu Yurui , Wang Xiangying , Zhang Zhonghui 
Published: February 2025

SUMMARYAbscisic acid insensitive 5 (ABI5) is a pivotal transcription factor in abscisic acid (ABA) signaling, playing an essential role in plant growth and responses to abiotic stress. This key regulator is subject to multifaceted regulation, especially on post‐translational mechanisms. Recent research has shed light on the post‐translational regulation of ABI5, encompassing both post‐translational modifications (PTMs) and the modulation of its transcriptional activity. In this review, we provide a comprehensive overview of the current knowledge surrounding the post‐translational regulation of ABI5, along with the influence of various cofactors on its transcriptional activity and protein stability. The potential biological roles of PTMs of ABI5 in the context of ABA signaling and plant stress responses are also explored. As ABI5 is one of the most extensively studied proteins in the context of plant ABA signaling and environmental stress responses, a sophisticated and precise understanding of the regulatory mechanisms that govern ABI5 is not only beneficial for its application in genetic engineering but also helpful for our exploration in the fundamental principles of post‐translational regulation.
Lysine acetylation modulates drought stress responses in birch (Betula platyphylla) through metabolic and transcriptional pathway regulation
Authors: Sun Shilin , Han Xue , Wang Jiayi , Liu Mingshuang , Wu Siqi , Wu Di , Wang Yucheng 
Published: February 2025

SUMMARYAcetylation modifies protein subcellular localization, stability, enzymatic activity, and protein–protein and protein‐DNA interactions, playing a crucial role in mediating protein function. However, research on non‐histone acetylation remains limited. This study investigates changes in lysine acetylation (Kac) in proteins of birch (Betula platyphylla) in response to drought using 4D label‐free quantitative lys‐acetylproteome analysis. We identified a total of 15 064 acetylated peptides across 4393 proteins, with 2486 Kac sites exhibiting significant changes: 246 prteins showed increased Kac levels, while 1406 displayed reductions. Notably, proteins associated with metabolic pathways, such as nucleotide sugar biosynthesis, proteasome, glutamate decarboxylase and the tricarboxylic acid (TCA) cycle, were significantly impacted. The alterations in Kac levels correlated with various KEGG pathways, suggesting that acetylation plays a regulatory role in drought response mechanisms. Furthermore, we identified specific acetylation sites in transcription factors (TFs), highlighting their involvement in this process. Functional validation demonstrated that mutations in Kac sites of five randomly selected TFs resulted in significant changes in drought tolerance, emphasizing the critical role of lysine acetylation in modulating stress responses. Overall, our findings indicate that Kac modification serves as a key regulatory mechanism in birch adaptation to drought stress, influencing both metabolic processes and transcriptional regulation.
On volume and surface area of parallel sets. II. Surface measures and (non)differentiability of the volume
Authors: Rataj Jan , Winter Steffen 
Published: February 2025

AbstractWe prove that at differentiability points of the volume function of a compact set (associating to the volume of the ‐parallel set of ), the surface area measures of ‐parallel sets of converge weakly to the surface area measure of the ‐parallel set as . We further study the question which sets of parallel radii can occur as sets of nondifferentiability points of the volume function of some compact set. We provide a full characterization for dimensions and 2.
Minimizing Running Load via Gentle Heel Strike Techniques: A Gait Modification Study
Authors: Shen Wei , Hou Zongchen , Wheeler Patrick C. , Fong Daniel T.P. 
Published: February 2025

Introduction: Running overuse injuries are among the most common running-related musculoskeletal injuries. Modifying gait has been recognized as an effective strategy for preventing running overuse injuries. This study investigates whether gentle heel strike (GHS) running decreases the impact loading rate during 30-minute runs in healthy participants. Methods: In this prospective cohort interventional study, 20 male participants underwent gait modification in a controlled laboratory setting, with the goal of reducing heel impact through real-time visual feedback. Comprehensive measurements, including plantar contact, force, pressure, and detailed kinetic and kinematic analyses, were employed to assess changes in gait dynamics. Results: GHS significantly shifted plantar pressure, reducing heel forces and increasing forefoot load. Mean heel force decreased by 0.32 (0.1) body weight (BW) and heel pressure reduced by 0.1 kPa/BW. Although peak vertical ground reaction force and anterior–posterior ground reaction force did not change significantly across the entire stance phase, early stance vertical ground reaction force (7%–12% of the gait cycle) was reduced, leading to the disappearance of the vertical impact peak. Vertical impact peak dropped from 1.45 (0.23) to 1.27 (0.25) BW. Significant reductions were also seen in the vertical instantaneous loading rate, which decreased from 68.32 (14.20) to 46.77 (13.95) BW/s, and the vertical average loading rate, which fell from 54.96 (14.38) to 38.84 (12.62) BW/s (P < .001). Discussion: GHS has the potential to modify running mechanics by redistributing plantar pressure and diminishing heel impact force. This reduction in heel impact force could lead to a change in landing pattern anteriorly and a decrease in loading rates, potentially reducing the risk of running overuse injuries. Conclusion: Visual biofeedback-guided GHS is feasible in healthy participants, and it effectively reduces the loading rate during running for 30 minutes.
An Examination of Physical Education Technology Courses in Physical Education Teacher Education
Authors: Cox Dannon G. , Krause Jennifer M. , O’Neil Kason , Brooks Collin 
Published: February 2025

Purpose: This study explored how physical education-specific technology courses within physical education teacher education (PETE) programs address students’ Technological, Pedagogical, and Content Knowledge (TPACK), given that successful technology integration in PETE remains unclear. Method: A case study design was used to examine six PETE programs’ physical education-specific technology courses within the United States. Semistructured interviews with course instructors and course materials (e.g., syllabi, assignments) were inductively analyzed to explore how they addressed TPACK components and PETE technology standards. Results: All courses addressed varying components of TPACK and PETE technology standards. Additional thematic analysis showed that all courses encouraged (a) hands-on practical experience, (b) technology exploration, (c) empowering teachers, and (d) digital citizenship advocacy. Discussion: PETE programs currently with or those considering a physical education-specific course should ensure they enhance students’ TPACK by specifically addressing technology use in lesson planning, lesson delivery, assessment, and advocacy in program and course experiences.
Longitudinal analysis of rhesus macaque metabolome during acute SIV infection reveals disruption in broad metabolite classes
Authors: Hudson Andrew , Wu Peng , Kroll Kyle W. , Hueber Brady , Woolley Griffin , Shi Pixu , Reeves R. Keith 
Published: February 2025

ABSTRACT

Persons living with HIV experience significant metabolic dysregulation, frequently resulting in immune and other cellular dysfunction. However, our understanding of metabolism and its relationship to immunity in the context of HIV remains incompletely understood, especially as it relates to the acute and early chronic phases of HIV infection. Herein, we employed mass spectrometry and a simian immunodeficiency virus (SIV)-infected rhesus macaque model to characterize changes in over 500 plasma metabolites throughout SIV infection. This broad metabolomic approach recapitulated known pathogenic signatures of HIV, such as a perturbed tryptophan/kynurenine ratio, but also identified novel metabolic changes. We observed a general decrease in plasma amino acid concentrations, with the notable exceptions of elevated aspartate and glutamate. Acute infection was marked by a transient increase in lactate dehydrogenase activity, indicating a shift toward anaerobic metabolism. Indoleamine 2,3-dioxygenase activity, defined by the kynurenine/tryptophan ratio, was significantly increased in both acute and chronic phases and strongly correlated with viral load. These results provide a comprehensive characterization of metabolic fluctuations during early lentiviral infection, furthering our understanding of the crucial interplay between metabolism and immune response. Our findings highlight systemic metabolic consequences of infection and provide potential targets for therapeutic intervention or biomarkers of disease progression.

IMPORTANCE
Despite significant advances in antiretroviral therapy and pre-exposure prophylaxis, HIV remains a global challenge. Understanding the underlying immune mechanisms is critical for improving HIV control and therapeutic development. Cellular metabolism represents a crucial yet underappreciated area of immune system function. Metabolite availability and metabolic pathway preferences directly influence the functional response capacity of immune cells and are highly dysregulated during HIV infection. To further the understanding of metabolic impacts of HIV infection, we utilized cutting-edge mass spectrometry-based metabolome interrogation to measure over 500 metabolites using an acute simian immunodeficiency virus infection model in rhesus macaques. Our comprehensive analysis provides insights into the dynamic metabolic landscape throughout early infection, revealing both known and novel metabolic signatures. These findings enhance our understanding of the complex interplay between metabolism and immunity in lentiviral infections, potentially informing new strategies for early detection, prevention, and treatment of HIV.
Synergistic action of mucoactive drugs and phages against
Pseudomonas aeruginosa
and
Klebsiella pneumoniae
Authors: Sui Bingrui , Li Xiaoyu , Li Na , Tao Yang , Wang Lili , Xu Yongping , Hou Yumin , Hu Bijie , Tan Demeng 
Published: February 2025

ABSTRACT

N
-acetylcysteine (NAC) and ambroxol hydrochloride (AMB) are commonly prescribed alongside antibiotics to alleviate sputum retention in lower respiratory tract infections, which are often caused by bacterial pathogens. With the rising threat of antibiotic resistance, phage therapy has emerged as a promising alternative alongside. However, no studies have explored the potential interactions between phages and these mucoactive agents despite their frequent concurrent use during phage therapy. Therefore, investigating the potential synergy and its subsequent impact on phage infection dynamics could enhance clinical strategies for treating bacterial infections with phages. Our study utilized
Pseudomonas aeruginosa
strain ZS-PA-35 and
Klebsiella pneumoniae
strain Kp36, alongside their respective phages, to investigate their interactions in the presence of NAC or AMB. Our findings indicate that, under specific conditions, these mucoactive agents can function as adjuvants to lytic phages, enhancing bacterial susceptibility to phage infection and facilitating subsequent phage proliferation. Our study revealed that these synergistic interactions are strongly influenced by the physiological characteristics of the phages, the surrounding microenvironments, and the physiology of host tissues, as varying outcomes of phage-host interactions were observed among different phages and across distinct media. Taken together, our results emphasize the complexity of interactions between phages and NAC or AMB, underscoring the need for caution when using combination treatments.

IMPORTANCE

N
-acetylcysteine (NAC) and ambroxol hydrochloride (AMB) are used in medical treatment of patients with acute and chronic bronchitis. Often, the choice of NAC or AMB is empirically determined by physicians. However, the potential impact of combining NAC or AMB with phage therapy remains unclear. To address this gap, a comprehensive understanding of their interplay is crucial to determine any potential synergistic effects. This study aims to elucidate how NAC or AMB influence phages targeting different receptors, thereby affecting their antibacterial activity against
Pseudomonas aeruginosa
and
Klebsiella pneumoniae
. Our results suggest that, under certain conditions, NAC or AMB provides an adjuvant effect by rendering the cells more susceptible to phage infection. These results contribute to advancing our understanding of the clinical combination of mucoactive agents and phage therapy, offering insights for optimizing treatment efficacy.
Targeted delivery of antitubercular drugs using glucan lipid particles
Authors: Jaecklein Eleni , Papavinasasundaram Kadamba , Ostroff Gary R. , Sassetti Christopher , Soto Ernesto R. 
Published: February 2025

ABSTRACT

Simpler, safer, and faster chemotherapeutic regimens for tuberculosis and other respiratory mycobacterial infections are an urgent need. Many current therapies suffer from suboptimal drug exposure and dose-limiting systemic adverse effects, challenges that could be addressed via controlled delivery of drugs to the primary site of infection. We sought to address this need by designing a flexible formulation platform that targets drugs to the lung macrophages that concentrate at infectious foci. Our approach is based on an encapsulation strategy in which drugs or specifically designed prodrugs are captured in the hydrophobic core of a glucan-lipid particle (GLP). We show chemically diverse antimycobacterial drugs can be efficiently and stably encapsulated within GLP and that these microparticles can be engineered to release drugs upon low pH or reducing conditions that occur upon phagocytosis by macrophages. Encapsulated formulations of clofazimine, isoniazid, and linezolid retain activity against intracellular
Mycobacterium tuberculosis
(Mtb) in an
ex vivo
model, demonstrating efficient drug delivery and release. Intranasal administration of GLP-clofazimine to
Mtb
-infected mice effectively concentrates the drug in the lung and reduces bacterial burden, whereas GLP-delivered linezolid was systemically distributed and failed to inhibit bacterial growth in the lung. This work establishes GLPs as a promising platform for targeted antibiotic delivery to the lung and also illustrates pharmacokinetic parameters that must be considered in future development.

IMPORTANCE
Tuberculosis (TB) causes an estimated 10.8 million cases each year and remains one of the leading causes of infectious death. Effective treatment is complicated due to the lengthy drug regimen required to prevent relapse and treatment failure. A primary challenge is delivering drugs effectively to lung granulomas, where TB bacteria can persist. Here, we developed yeast-derived glucan lipid microparticles (GLPs) as a novel delivery system to efficiently encapsulate and deliver TB drugs directly to lung tissue via intranasal administration. Of the formulations evaluated, GLP-encapsulated clofazimine achieved increased lung drug levels and reduced bacterial burden in TB-infected mice. The use of GLPs offers a promising approach to improve TB treatment by enabling targeted drug delivery to infection sites within the lungs.