bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblast regulates angiogenesis in assembled oral cancer organoid: A possible role of NNMT
Authors: Holkom Mohammed , Yang Xiao , Li Rui , Chen Yang , Zhao Hui , Shang Zhengjun 
Published: April 2024

AbstractObjectiveTumour angiogenesis is affected by various cell types in the tumour microenvironment (TME), including cancer cells and cancer‐associated fibroblasts (CAFs). Here, an assembled organoid model was generated to investigate the mechanism by which the TME regulates angiogenesis in oral squamous cell carcinoma (OSCC).Materials and MethodsSecretion of vascular endothelial growth factor‐A (VEGFA) was analysed to compare the proangiogenic properties of OSCC cells and corresponding CAFs. Cell aggregates consisting of endothelial cells (ECs), CAFs and cancer cells were generated to construct assembled organoids. Nicotinamide N‐methyltransferase (NNMT) was pharmacologically or genetically inhibited to block the activation of CAFs. ATAC‐seq was employed to test the transcriptional network of fibroblasts overexpressing NNMT.ResultsCompared with cancer cells, CAFs secreted more VEGFA. Coculture with CAFs more effectively promoted the sprouting of ECs. Blockade of CAF activation via inhibition of NNMT drastically reduced the expression of CD31 in the assembled organoids. Overexpression of NNMT enhanced the transcription of genes related to angiogenesis in fibroblasts. Specifically, NNMT orchestrated the enrichment of the transcription factor JUNB at the promoter of VEGFA.ConclusionsWe clarify that stromal NNMT enables the steady reproduction of angiogenesis in assembled oral cancer organoids, providing a novel target for exploiting antiangiogenic therapy.
Macrophage‐derived exosomes rescue the TNF‐ɑ‐suppressed osteo‐/cementogenic differentiation of hPDLCs
Authors: Deng Yifei , Xiao Junhong , Huang Xin , Cao Zhengguo 
Published: April 2024

AbstractObjectiveInflammatory stimuli compromise the differentiation potency of human periodontal ligament cells (hPDLCs). Macrophage‐derived exosomes (M‐Exo) play a role in several aspects of cellular activity. This study investigated how M‐Exo contributes to the osteo‐/cementogenic differentiation of hPDLCs under inflammation and the mechanism involved.MethodsM‐Exo was identified by transmission electron microscopy, western blotting (WB), and dynamic light scattering. The internalization of M‐Exo by hPDLCs was observed. After M‐Exo treatment, the osteo‐/cementogenic markers were detected by RT‐qPCR and WB, and alkaline phosphatase (ALP) activity by ALP staining. Tumor necrosis factor alpha (TNF‐ɑ) was applied to simulate inflammation. The rescue effect of M‐Exo on TNF‐ɑ‐suppressed differentiation was validated. The p38 MAPK pathway activity was tested and a specific inhibitor was applied to explore the mechanism.ResultsM‐Exo was successfully isolated, identified and internalized by hPDLCs. M‐Exo enhanced the osteo‐/cementogenic differentiation of hPDLCs, as indicated by upregulated osteo‐/cementogenic markers and elevated ALP activity. Moreover, TNF‐ɑ inhibited the differentiation capabilities of hPDLCs, on which M‐Exo showed a rescue effect. M‐Exo activated the p38 MAPK pathway and SB203580 attenuated its promotion effect.ConclusionThis study showed that M‐Exo ameliorated the TNF‐ɑ‐suppressed osteo‐/cementogenic differentiation of hPDLCs partly through the p38 MAPK pathway.
Impact of preoperative haemoglobin, albumin, lymphocyte, and platelet score on oral cancer prognosis
Authors: Ito Yu , Abe Atsushi , Hayashi Hiroki 
Published: April 2024

AbstractObjectiveTo evaluate the preoperative haemoglobin, albumin, lymphocyte, and platelet score as a prognostic indicator in oral squamous cell carcinoma treated by radical surgery.Subjects and MethodsPatients (83 men, 32 women; 65.80 ± 11.47 years) who underwent radical surgery between 2012 and 2022 were included. Factors affecting overall survival and disease‐free survival according to the haemoglobin, albumin, lymphocyte, and platelet score were examined. Patients were categorised into low‐ and high‐score groups using optimal cut‐off values obtained from receiver operating characteristic curve analysis.ResultsThe low‐score group had poorer overall and disease‐free survival (p < 0.001 each). Multivariate analysis identified alcohol consumption (hazard ratio [HR], 3.83; 95% confidence interval [CI]: 1.56–9.41, p = 0.003); vascular invasion (HR, 3.97; 95% CI: 1.60–9.85, p = 0.003); and the haemoglobin, albumin, lymphocyte, and platelet score (HR, 0.39; 95% CI: 0.20–0.78, p = 0.007) as independent prognostic factors for overall survival and vascular (HR, 3.66; 95% CI: 1.79–7.50, p < 0.001) and lymphovascular (HR, 2.44; 95% CI: 1.36–4.41, p = 0.003) invasion as independent prognostic factors for disease‐free survival.ConclusionThe preoperative haemoglobin, albumin, lymphocyte, and platelet score may be a significant prognostic factor for patients with oral squamous cell carcinoma undergoing radical surgery.
HOW DO YOU SOLVE A PROBLEM LIKE NAILS? A NEW, MULTI‐PERIOD METHODOLOGY AND TYPOLOGY FOR RECORDING IRON NAILS
Authors: Manby Katie J B 
Published: April 2024

SummaryThis paper sets out new recommendations for recording structural iron nails. Despite their ubiquity, iron nails have received limited analytical and interpretative attention and recording practices are highly variable. Too often current recording is time‐consuming and costly without providing meaningful information. This paper proposes a new recording methodology, developed through analysis of the Roman structural nail assemblage from the MHI A14 Cambridge‐Huntingdon excavations alongside experiments in nail shaping, with wider context provided by medieval and post‐medieval assemblages from the City of London. This approach includes a new nail typology, recommendations for bulk recording of basic details for whole assemblages (using counts and typologies), alongside detailed recording (shank morphology and further metric data) for certain nail groups. Shank morphology is a particularly important aspect proposed here, being indicative of how nails were used in antiquity.
Physiological and molecular responses in phosphorus‐hyperaccumulating Polygonum species to high phosphorus exposure
Authors: Ye Daihua , Xie Min , Liu Tao , Huang Huagang , Zhang Xizhou , Yu Haiying , Zheng Zicheng , Wang Yongdong , Tang Yu , Li Tingxuan 
Published: April 2024

AbstractPhosphorus (P)‐hyperaccumulators for phytoextraction from P‐polluted areas generally show rapid growth and accumulate large amounts of P without any toxicity symptom, which depends on a range of physiological processes and gene expression patterns that have never been explored. We investigated growth, leaf element concentrations, P fractions, photosynthetic traits, and leaf metabolome and transcriptome response in amphibious P‐hyperaccumulators, Polygonum hydropiper and P. lapathifolium, to high‐P exposure (5 mmol L−1), with 0.05 mmol L−1 as the control. Under high‐P exposure, both species demonstrated good growth, allocating more P to metabolite P and inorganic P (Pi) accompanied by high potassium and calcium. The expression of a cluster of unigenes associated with photosynthesis was maintained or increased in P. lapathifolium, explaining the increase in net photosynthetic rate and the rapid growth under high‐P exposure. Metabolites of trehalose metabolism, including trehalose 6‐phosphate and trehalose, were sharply increased in both species by the high‐P exposure, in line with the enhanced expression of associated unigenes, indicating that trehalose metabolic pathway was closely related to high‐P tolerance. These findings elucidated the physiological and molecular responses involved in the photosynthesis and trehalose metabolism in P‐hyperaccumulators to high‐P exposure, and provides potential regulatory pathways to improve the P‐phytoextraction capability.
SlCathB2 as a negative regulator mediates a novel regulatory pathway upon high‐temperature stress response in tomato
Authors: Wen Junqin , Zhou Rong , Jiang Fangling , Chen Zheng , Sun Mintao , Li Haolong , Wu Zhen 
Published: April 2024

AbstractHigh‐temperature stress (HS) is a major abiotic stress that affects the yield and quality of plants. Cathepsin B‐like protease 2 (CathB2) has been reported to play a role in developmental processes and stress response, but its involvement in HS response has not been identified. Here, overexpression, virus‐induced gene silencing (VIGS)and RNA‐sequencing analysis were performed to uncover the functional characteristics of SlCathB2‐1 and SlCathB2‐2 genes for HS response in tomato. The results showed that overexpression of SlCathB2‐1 and SlCathB2‐2 resulted in reduced heat tolerance of tomato to HS while silencing the genes resulted in enhanced heat tolerance. RNA‐sequencing analysis revealed that the heat shock proteins (HSPs) exhibited higher expression in WT than in SlCathB2‐1 and SlCathB2‐2 overexpression lines. Furthermore, the possible molecular regulation mechanism underlying SlCathB2‐1 and SlCathB2‐2‐mediated response to HS was investigated. We found that SlCathB2‐1 and SlCathB2‐2 negatively regulated antioxidant capacity by regulating a set of genes involved in antioxidant defence and reactive oxygen species (ROS) signal transduction. We also demonstrated that SlCathB2‐1 and SlCathB2‐2 positively regulated ER‐stress‐induced PCD (ERSID) by regulating unfolded protein response (UPR) gene expression. Furthermore, SlCathB2‐1 and SlCathB2‐2 interacting with proteasome subunit beta type‐4 (PBA4) was identified in the ERSID pathway using yeast two‐hybrid (Y2H) analysis and bimolecular fluorescence complementation (BiFC) screening. Overall, the study identified both SlCathB2‐1 and SlCathB2‐2 as new negative regulators to HS and presented a new HS response pathway. This provided the foundation for the construction of heat‐tolerant molecular mechanisms and breeding strategies aiming to improve the thermotolerance of tomato plants.
Characterization of a CrPME indicates its possible role in determining vindoline accumulation in Catharanthus roseus leaves
Authors: Singh Pooja , Yadav Seema , Shah Saumya , Shanker Karuna , Sundaresan Velusamy , Shukla Ashutosh K. 
Published: April 2024

AbstractThe leaf‐specific Catharanthus roseus alkaloid, vindoline, is the major bottleneck precursor in the production of scarce and costly anticancer bisindoles (vincristine and vinblastine). The final steps of its biosynthesis and storage occur in the laticifers. Earlier, we have shown that vindoline content is directly related to laticifer number. Pectin remodeling enzymes, like pectin methylesterase (PME), are known to be involved in laticifer development. A search in the croFGD yielded a leaf‐abundant CrPME isoform that co‐expressed with a few vindoline biosynthetic genes. Full‐length cloning, tissue‐specific expression profiling, and in silico analysis of CrPME were carried out. It was found to possess all the specific characteristics of a typical plant PME. Transient silencing (through VIGS) and overexpression of CrPME in C. roseus indicated a direct relationship between its expression and vindoline content. Comparative analysis of transcript abundance and enzyme activity in three familial C. roseus genotypes differing significantly in their vindoline content and laticifer count (CIM‐Sushil > Dhawal > Nirmal) also corroborated the positive relationship of CrPME expression with vindoline content. This study highlights the possible role of CrPME, a cell wall remodeling enzyme, in modulating laticifer‐associated secondary metabolism.
Use of thermography in the long‐term evaluation of scrotal surface temperature and its impact on seminal quality in stallions
Authors: Freitas M. L. , Viana J. H. M. , Dode M. A. N. , Braga T. R. C. , de Oliveira R. A. 
Published: April 2024

AbstractScrotal surface thermography is a non‐invasive method for assessing testicular thermoregulation in stallions; however, few studies have explored the application of this technique concerning the thermal physiology of equine reproductive systems. This study aimed to evaluate the consistency of testicular thermoregulation in stallions over a year using thermography to measure the scrotal surface temperature (SST). Moreover, we assessed the best region for measuring the surface body temperature compared with the SST. Ten light‐breed stallions were used in the experiment. Thermographic images of the scrotal and body surfaces (neck and abdomen) were captured. Fresh, cooled and frozen–thawed semen samples were evaluated to verify the impact of thermoregulation on semen quality. Testicular thermoregulation was maintained throughout the year in stallions amidst changes in the external temperature, as evidenced by the weak correlation between the SST and ambient temperature. A lower correlation was observed between the environmental temperature and body surface temperature (BTS) obtained from the abdomen (BTS‐A; R = .4772; p < .0001) than with that obtained from the neck (BTS‐N; R = .7259; p < .0001). Moreover, both BTS‐A and SST were simultaneously captured in a single image. The consistent quality of the fresh, cooled and frozen semen suggests efficient thermoregulation in stallions throughout the year.
One Size Does Not Fit All: Idiographic Computational Models Reveal Individual Differences in Learning and Meta‐Learning Strategies
Authors: Haile Theodros M. , Prat Chantel S. , Stocco Andrea 
Published: April 2024

AbstractComplex skill learning depends on the joint contribution of multiple interacting systems: working memory (WM), declarative long‐term memory (LTM) and reinforcement learning (RL). The present study aims to understand individual differences in the relative contributions of these systems during learning. We built four idiographic, ACT‐R models of performance on the stimulus‐response learning, Reinforcement Learning Working Memory task. The task consisted of short 3‐image, and long 6‐image, feedback‐based learning blocks. A no‐feedback test phase was administered after learning, with an interfering task inserted between learning and test. Our four models included two single‐mechanism RL and LTM models, and two integrated RL‐LTM models: (a) RL‐based meta‐learning, which selects RL or LTM to learn based on recent success, and (b) a parameterized RL‐LTM selection model at fixed proportions independent of learning success. Each model was the best fit for some proportion of our learners (LTM: 68.7%, RL: 4.8%, Meta‐RL: 13.25%, bias‐RL:13.25% of participants), suggesting fundamental differences in the way individuals deploy basic learning mechanisms, even for a simple stimulus‐response task. Finally, long‐term declarative memory seems to be the preferred learning strategy for this task regardless of block length (3‐ vs 6‐image blocks), as determined by the large number of subjects whose learning characteristics were best captured by the LTM only model, and a preference for LTM over RL in both of our integrated‐models, owing to the strength of our idiographic approach.
Knockout of endoplasmic reticulum‐localized molecular chaperone HSP90.7 impairs seedling development and cellular auxin homeostasis in Arabidopsis
Authors: Noureddine Jenan , Mu Bona , Hamidzada Homaira , Mok Wai Lam , Bonea Diana , Nambara Eiji , Zhao Rongmin 
Published: April 2024

SUMMARYThe Arabidopsis endoplasmic reticulum‐localized heat shock protein HSP90.7 modulates tissue differentiation and stress responses; however, complete knockout lines have not been previously reported. In this study, we identified and analyzed a mutant allele, hsp90.7‐1, which was unable to accumulate the HSP90.7 full‐length protein and showed seedling lethality. Microscopic analyses revealed its essential role in male and female fertility, trichomes and root hair development, proper chloroplast function, and apical meristem maintenance and differentiation. Comparative transcriptome and proteome analyses also revealed the role of the protein in a multitude of cellular processes. Particularly, the auxin‐responsive pathway was specifically downregulated in the hsp90.7‐1 mutant seedlings. We measured a much‐reduced auxin content in both root and shoot tissues. Through comprehensive histological and molecular analyses, we confirmed PIN1 and PIN5 accumulations were dependent on the HSP90 function, and the TAA‐YUCCA primary auxin biosynthesis pathway was also downregulated in the mutant seedlings. This study therefore not only fulfilled a gap in understanding the essential role of HSP90 paralogs in eukaryotes but also provided a mechanistic insight on the ER‐localized chaperone in regulating plant growth and development via modulating cellular auxin homeostasis.
Acute effects of MitoQ on vascular endothelial function are influenced by cardiorespiratory fitness and baseline FMD in middle‐aged and older adults
Authors: Carlini Nicholas A. , Harber Matthew P. , Fleenor Bradley S. 
Published: April 2024

AbstractA key mechanism promoting vascular endothelial dysfunction is mitochondrial‐derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function in preclinical models by lowering mtROS. However, the effects of mtROS on endothelial function in exercising and non‐exercising adults is limited. In a double‐blind, randomized, placebo‐controlled crossover study design 23 (10 M/13 F, age 62.1 ± 11.5 years) middle‐aged and older (MA/O, ≥45 years) adults were divided into two groups: exercisers (EX, n = 11) and non‐exercisers (NEX, n = 12). All participants had endothelial function (brachial artery flow‐mediated dilatation, FMDBA) measured before and ∼1 h after mitoquinone mesylate (MitoQ) (single dose, 80 mg) and placebo supplementation. A two‐way repeated measures ANOVA was used to determine the effects of MitoQ and placebo on FMDBA. Pearson correlations assessed the association between the change in FMDBA with MitoQ and baseline FMDBA and cardiorespiratory fitness (CRF). Compared with placebo, MitoQ increased FMDBA in NEX by + 2.1% (MitoQ pre: 4.9 ± 0.4 vs. post: 7.0 ± 0.4 %, P = 0.004, interaction) but not in EX (P = 0.695, interaction). MitoQ also increased endothelial function in adults with a FMDBA <6% (P < 0.0001, interaction) but not >6% (P = 0.855, interaction). Baseline FMDBA and CRF were correlated (r = 0.44, P = 0.037), whereas the change in FMDBA with MitoQ was inversely correlated with CRF (r = ‐0.66, P < 0.001) and baseline FMDBA (r = ‐0.73, P < 0.0001). The relationship between the change in FMDBA and baseline FMDBA remained correlated after adjusting for CRF (r = ‐0.55, P = 0.007). These data demonstrate that MitoQ acutely improves FMDBA in NEX and EX adults who have a baseline FMDBA <6%.
imageKey points
A key age‐related change contributing to increased cardiovascular disease (CVD) risk is vascular endothelial dysfunction due to increased mitochondrial‐derived reactive oxygen species (mtROS).
Aerobic exercise preserves endothelial function via suppression of mtROS in preclinical models but the evidence in humans is limited.
In the present study, a single dose of the mitochondria‐targeted antioxidant, mitoquinone mesylate (MitoQ), increases endothelial function in non‐exercisers with lower cardiorespiratory fitness (CRF) but not in exercisers with higher CRF.
The acute effects of MitoQ on endothelial function in middle‐aged and older adults (MA/O) are influenced by baseline endothelial function independent of CRF.
These data provide initial evidence that the acute MitoQ‐enhancing effects on endothelial function in MA/O adults are influenced, in part, via CRF and baseline endothelial function.
Integral Sliding Mode Disturbance Observer-Based Preview Repetitive Control
Authors: Lan Yonghong , Luo Zhao 
Published: April 2024

Abstract
This paper deals with the problem of integral sliding mode disturbance observer (ISDOB)-based preview repetitive control (PRC) for a class of nonlinear systems subject to external disturbances and nonlinearity. First, an ISDOB-based PRC law is presented to estimate and compensate the exogenous disturbances and nonlinearity. Next, by using a new equality constraint, a continuous-discrete two-dimensional (2D) system is established. Then, the stability of the combined controller–observer system is derived on the basis of a Lyapunov analysis, 2D system theory, and the singular-value-decomposition technique. By solving an linear matrix inequality (LMI), the gains of the controller and state observer can be obtained. Finally, two numerical examples are provided to illustrate the effectiveness and superiority of the proposed method.
Few-Shot Classification of Wafer Bin Maps Using Transfer Learning and Ensemble Learning
Authors: Kim Hyeonwoo , Yoon Heegeon , Kim Heeyoung 
Published: April 2024

Abstract
The high cost of collecting and annotating wafer bin maps (WBMs) necessitates few-shot WBM classification, i.e., classifying WBM defect patterns using a limited number of WBMs. Existing few-shot WBM classification algorithms mainly utilize meta-learning methods that leverage knowledge learned in several episodes. However, meta-learning methods require a large amount of additional real WBMs, which can be unrealistic. To help train a network with a few real-WBMs while avoiding this challenge, we propose the use of simulated WBMs to pre-train a classification model. Specifically, we employ transfer learning by pre-training a classification network with sufficient amounts of simulated WBMs and then fine-tuning it with a few real-WBMs. We further employ ensemble learning to overcome the overfitting problem in transfer learning by fine-tuning multiple sets of classification layers of the network. A series of experiments on a real-dataset demonstrate that our model outperforms the meta-learning methods that are widely used in few-shot WBM classification. Additionally, we empirically verify that transfer and ensemble learning, the two most important yet simple components of our model, reduce the prediction bias and variance in few-shot scenarios without a significant increase in training time.
Endwall Contouring for Improving Aerodynamic Performance in a High-Pressure Turbine Cascade
Authors: Du Zhengshuai , Cai Le , Chen Yingjie , Wang Songtao , Tang Hongfei , Zeng Jun 
Published: April 2024

Abstract
The endwall contouring has proven to be an effective technique in controlling the impacts of secondary flow within turbomachinery. A baseline cascade with the original axisymmetric endwall (BASE) has been redesigned with a non-axisymmetric contoured shroud endwall (EW-B1), and both configurations are investigated through experimental and numerical methods. The endwall is profiled through the B-spline surface method with the purpose of reducing the overall total pressure loss at the exit. The experimental studies involve flow field traverses at the exits of both cascades. Numerical calculations are conducted to gain a deeper understanding of the effects of endwall contouring. The numerical results exhibit good agreement with the experimental results, both in loss and flow angle. The results demonstrate a significant reduction in losses and secondary kinetic energy in EW-B1. The causes of the high-loss region and the overturning near the shroud are analyzed using computational fluid dynamics (CFD), as well as the changes in pressure fields and vortex structures within the cascade passage. The weakening of the horseshoe vortex and the radial movement of the passage vortex are confirmed to be the primary reasons for losses reduction.