bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased FGF19 and FGF21: possible underlying common pathogenic mechanism of metabolic and cognitive dysregulation in depression
Authors: Tang Mimi , Cheng Shuqiao , Wang Lu , Tang Hui , Liu Ting , Zhao Tingyu , Dang Ruili 
Published: May 2023

BackgroundAccumulating studies suggested that major depressive disorder (MDD) was closely related to metabolic syndrome (MetS). Important endogenous regulators fibroblast growth factors (FGFs) 19 and 21 were also reported to participate in psychiatric disorders. This study aimed to investigate the role of FGF19 and FGF21 in MDD and to explore the possible pathogenic mechanism of metabolic and cognitive dysregulation in depression.MethodsA total of 59 MDD patients and 55 healthy control participants were recruited. The serum levels of FGF19 and FGF21 and lipid profiles were measured by means of enzymatic methods. Cognitive function was measured by repeatable battery for the assessment of neuropsychological status (RBANS) scores. The gene expression of PGC-1α and FNDC5 was determined by quantitative polymerase chain reaction (PCR).ResultsWe found that plasma FGF19 and FGF21 levels were significantly decreased in patients with MDD. Meanwhile, triglyceride (TG) was significantly elevated and PGC-1α was significantly downregulated in MDD patients. Correlation analyses showed negative associations between TG and FGF19 levels. As for cognitive performance, both FGF19 and FGF21 levels were positively correlated with immediate memory. However, FGF19 levels were negatively correlated with language, and FGF21 levels were also negatively correlated with attention and delayed memory. Additionally, negative associations were found between FGF19 levels and PGC-1α. FGF21 levels were positively associated with PGC-1α and negatively associated with FNDC5.ConclusionThis study elucidated the role of FGF19 and FGF21 in MDD. MDD patients were confirmed to have metabolic and cognitive dysregulation, and this abnormality was linked to the decreased concentrations of FGF19 and FGF21 through the PGC-1α/FNDC5 pathway. Our results showed that the alterations of FGF19 and FGF21 levels may be a common pathogenic mechanism of metabolic and cognitive disturbances in patients with MDD.
Causal associations between insulin-like growth factor 1 and vitamin D levels: a two-sample bidirectional Mendelian randomization study
Authors: Gou Zhaoyang , Li Fan , Qiao Fengzhen , Maimaititusvn Gulinuer , Liu Fang 
Published: May 2023

BackgroundInsulin-like growth factor 1 (IGF-1) plays a vital role in the attainment and maintenance of bone mass throughout life and is closely related to the stature of children. 25-Hydroxyvitamin D (25-OHD) is an intermediate of vitamin D (Vit D) metabolism and a key indicator of Vit D nutritional status. Multiple studies have revealed that IGF-1 levels undergo a non-significant increase after Vit D supplementation. Here, we analyzed the causal and reverse causal relationships between 25-OHD and IGF-1 levels using Mendelian randomization (MR).MethodsTwo-sample MR was used to estimate an unconfounded bidirectional causal relationship between the level of IGF-1 and those of Vit D and 25-OHD. Single nucleotide polymorphisms (SNPs) were filtered from genome-wide association studies (GWAS) after a comprehensive search of the Integrative Epidemiology Unit GWAS database. Several MR methods were employed, including inverse-variance weighted (IVW) method, and a sensitivity analysis was undertaken to detect whether pleiotropy or heterogeneity biased the MR results.ResultsGenetically predicted IGF-1 was found to have a causal association with Vit D and serum 25-OHD levels, where Vit D and serum 25-OHD levels increased with increasing IGF-1 concentrations (Vit D: IVW β:0.021, 95% CI: 0.005–0.036, p = 7.74 × 10–3; 25-OHD: IVW β: 0.041, 95% CI: 0.026–0.057, p = 2.50 × 10–7). A reverse causal effect was also found, indicating Vit D and serum 25-OHD have a positive causal relationship with IGF-1 (Vit D: IVW β:0.182, 95% CI: 0.061–0.305, p = 3.25 × 10–3; 25-OHD: IVW β: 0.057, 95% CI = 0.017–0.096, p = 4.73 × 10–3). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept p = 5.1 × 10–5, 25-OHD intercept p = 6.4 × 10–4 in forward analysis; Vit D intercept p = 6.6 × 10–4, 25-OHD intercept p = 1.9 × 10–3 in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.ConclusionThe results of the MR analysis provide evidence that IGF-1 has positive causal and reverse causal relationships with Vit D and serum 25-OHD, respectively, in European populations. Our findings also provide guidance for the prevention and treatment of short stature and other related diseases.
Optimal treatment strategy for hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer patients with 1–2 suspicious axillary lymph node metastases on breast magnetic resonance imaging: upfront surgery vs. neoadjuvant chemotherapy
Authors: Lee Seung Eun , Ahn Sung Gwe , Ji Jung Hwan , Kook Yoonwon , Jang Ji Soo , Baek Seung Ho , Jeong Joon , Bae Soong June 
Published: May 2023

BackgroundIt is unclear whether upfront surgery or neoadjuvant chemotherapy is appropriate for first treatment in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with 1–2 suspicious axillary lymph node (ALN) metastases on preoperative breast magnetic resonance imaging (MRI).MethodWe identified 282 patients with HR+HER2- breast cancer and 1–2 suspicious ALN metastases on baseline breast MRI (147 received upfront surgery; 135 received neoadjuvant chemotherapy). We evaluated the predictive clinicopathological factors for pN2-3 in the adjuvant setting and axillary pathologic complete response (pCR) in the neoadjuvant setting.ResultsLymphovascular invasion (LVI)-positive and clinical tumors &gt;3 cm were significantly associated with pN2-3 in patients who received upfront surgery. The pN2-3 rate was 9.3% in patients with a clinical tumor ≤ 3 cm and LVI-negative versus 34.7% in the others (p &lt; 0.001). The pN2-3 rate in patients with a clinical tumor ≤ 3 cm and LVI-negative and in the others were 9.3% versus 34.7% in all patients (p &lt; 0.001), 10.7% versus 40.0% (p = 0.033) in patients aged &lt; 50 years, and 8.5% versus 31.0% in patients aged ≥ 50 years (p &lt; 0.001), respectively. In the neoadjuvant setting, patients with tumor-infiltrating lymphocytes (TILs) ≥ 20% had a higher axillary pCR than those with TILs &lt; 20% (46.7% vs. 15.3%, p &lt; 0.001). A similar significant finding was also observed in patients &lt; 50 years.ConclusionsUpfront surgery may be preferable for patients aged ≥ 50 years with a clinical tumor &lt; 3 cm and LVI-negative, while neoadjuvant chemotherapy may be preferable for those aged &lt; 50 years with TILs ≥ 20%.
On determining the mechanical nociceptive threshold in pigs: a reliability study
Authors: Rettore Andreis Felipe , Mørch Carsten Dahl , Jensen Winnie , Meijs Suzan 
Published: May 2023

BackgroundA pressure algometer is a valuable tool for assessing the mechanical nociceptive threshold (MNT) in clinical pain studies. Recent research has turned to large animal models of pain because of the closer anatomy and physiology to humans. Although the reliability and usefulness of the MNT have been extensively validated in humans, similar data from large animals is still sparse.ObjectiveTherefore, the aim of the current study was to evaluate the reliability (within- and between-session) of MNT in the forelimb of pigs using a pressure algometer.MethodsNine animals were used (23–40 kg), and MNTs were measured at both the right and left limbs at three different sessions, with three repetitions per session. The intraclass correlation coefficient (ICC) was used as a metric for relative reliability. The standard error of measurement (SEM) and coefficient of variation (CV) was used to assess absolute reliability. Systematic bias was also evaluated.ResultsThe average ICC was found to be 0.71 and 0.45 for the between-session and within-session, respectively. CV ranged from 17.9% to 20.5%, with a grand average of 19.1%. The grand average SEM was 249.5 kPa (16.6%). No systematic differences were found for the MNT between sessions, which suggests that there was no habituation to the stimulus.ConclusionThe reliability indices obtained in this study are comparable to results obtained in other species or anatomical regions and substantiate the use of the pressure algometer as a valuable tool to investigate the nociceptive system in pigs and translation to the human nociceptive withdrawal reflex.
Angiopoietin-like protein 3: a novel potential biomarker for nephrotic syndrome in children
Authors: Wen Fujie , Liu Junchao , Dai Rufeng , Hong Sha , Ji Baowei , Liu Jiaojiao , Zhang Jun , Han Xinli , Lv Qianying , Liu Jialu , Shen Qian , Xu Hong 
Published: May 2023

BackgroundAngiopoietin-like 3 (ANGPTL3) is a secretory glycoprotein. It has been demonstrated that ANGPTL3 level was upregulated in minimal change nephrotic syndrome (MCNS) kidney tissues. Subsequently, our group found that ANGPTL3 level was closely correlated with nephropathy in vivo and in vitro. Hence, whether ANGPTL3 level could be correlated with the proteinuria level, and assessment of disease severity of nephrotic syndrome (NS) remained to be investigated. This study aimed to analyzed the correlation between the levels of ANGPTL3 in serum and urine of patients with nephrotic syndrome and proteinuria, and assessed the severity of the patients' disease. In future clinical translation, the level of ANGPTL3 in serum, urine will be used as a biomarker to better predict the development of nephrotic syndrome.MethodsA total of 200 NS patients and 80 healthy controls (age, 1–18 years) were admitted to our institution between 2021 and 2022. The etiology of NS included primary nephrotic syndrome (PNS, n = 144) and NS with other causes (n = 56). A total of 280 serum samples and 244 urinary samples were collected to determine ANGPTL3 level using enzyme-linked immunosorbent assay (ELISA).ResultsSerum ANGPTL3 and urinary ANGPTL3/Cre were remarkably elevated in NS patients compared with those in healthy controls. Furthermore, serum ANGPTL3 and urinary ANGPTL3/Cre were significantly correlated with proteinuria level. Additionally, multivariate linear regression analysis demonstrated that serum ALB was independently correlated with serum ANGPTL3 and PRO/CR was independently correlated with urinary ANGPTL3/Cre in NS patients.ConclusionSerum ANGPTL3 and urinary ANGPTL3/Cre showed a promising performance in the diagnosis of NS, and served as novel potential noninvasive biomarkers to assess disease severity of NS. Further exploration of the role of ANGPTL3 level may shed a new light on the treatment of NS.
Acacetin exerts antitumor effects on gastric cancer by targeting EGFR
Authors: Zhang Guangtao , Dong Jiahuan , Lu Lu , Liu Yujing , Hu Dan , Wu Yuanmin , Zhao Aiguang , Xu Hanchen 
Published: May 2023

Background: Gastric cancer (GC) is a common malignant tumor with a poor prognosis. Combination treatments may prolong the survival of patients with GC. Acacetin, which is a flavonoid, exerts potent inhibitory effects on several types of cancer cells; however, the mechanisms of action remain poorly understood.Methods: Network pharmacology and RNA sequencing were used to predict the targets of acacetin, which were then verified by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking. The biological functions of acacetin in MKN45 and MGC803 cells were investigated using TUNEL assays, crystal staining and colony formation assays. The pathways affected by acacetin were verified through reverse experiments. The in vivo antitumor efficacy of acacetin was assessed in a subcutaneous xenotransplanted tumor model.Results: In this study, we identified EGFR from more than a dozen predicted targets as a protein that directly binds to acacetin. Moreover, acacetin affected the level of phosphorylated EGFR. In vitro, acacetin promoted the apoptosis of GC cells. Importantly, EGFR agonists reversed the inhibitory effects of acacetin on the STAT3 and ERK pathways. In vivo, acacetin decreased the protein levels of pEGFR in tumors, resulting in increased GC xenograft tumor regression without obvious toxicity.Conclusion: Our findings highlight EGFR as one of the direct targets of acacetin in GC cells. Acacetin inhibited the phosphatase activity of EGFR in vitro and in vivo, which played a role in the antitumor effects of acacetin. These studies provide new evidence for the use of acacetin as a potential reagent for the treatment of GC.
Cost-effectiveness analysis of toripalimab plus chemotherapy as the first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) without EGFR or ALK driver mutations from the Chinese perspective
Authors: Zhou Kexun , Shu Pei , Zheng Hanrui , Li Qiu 
Published: May 2023

Objectives: The results of a CHOICE-1 study demonstrated the superior efficacy of toripalimab (anti-PD-1 antibody) plus chemotherapy for patients with advanced non–small cell lung cancer (NSCLC), with a manageable safety profile. This study was performed to evaluate the economic value of this treatment for this patient population from the Chinese payer’s perspective.Materials and methods: Basic data were derived from the CHOICE-1 study. Markov models were developed to simulate the process of advanced NSCLC, including the progression-free survival (PFS), progressive disease (PD), and death in intention-to-treat (ITT) populations, as well as patients with squamous or non-squamous NSCLC. The cost was obtained from the local institution, and the value of utilities referred to previous studies. Monte Carlo simulations were performed to depict the probabilistic scatter plots of the incremental cost-effectiveness ratio (ICER) and acceptability curves, aiming to address the uncertainty of model inputs.Results: Compared with standard chemotherapy, toripalimab plus chemotherapy yields an ICER of $21,563 per quality-adjusted life year (QALY) in the ITT population. For patients with squamous NSCLC, comparing the combined therapy with chemotherapy led to an ICER of $18,369 per QALY, while the ICER was $24,754 per QALY in patients with non-squamous NSCLC. With the threshold of willingness to pay we set ($37,653 per QALY), toripalimab plus chemotherapy was cost-effective in these patient populations.Conclusion: For patients with advanced NSCLC, toripalimab plus chemotherapy was an optimal choice as first-line treatment, regardless of histology.
A novel glycyrrhizin acid-coated stent reduces neointimal formation in a rabbit iliac artery model
Authors: Teng Shuai , Zhu Zhaowei , Li Yang , Hu Xinqun , Fang Zhenfei , Liu Zhenjiang , Zhou Shenghua 
Published: May 2023

Introduction: Most drug-eluting stents (DESs) inhibit intimal hyperplasia but impair re-endothelialization. This study aimed to evaluate in vivo strut coverage and neointimal growth in a new glycyrrhizin acid (GA)-eluting stent.Methods: New Zealand White rabbits (n = 20) with atherosclerotic plaques were randomly divided into three groups based on implanted iliac artery stents: bare-metal stents (BMSs), rapamycin-eluting stents, and GA-eluting stents. After the in vivo intravascular ultrasound (IVUS) assessment at 28 days, the vessels were harvested for scanning electron microscopy (SEM) and histology. After 4 weeks of follow-up, the stent and external elastic lamina (EEL) areas were compared among the groups.Results: The rapamycin- or GA-eluting stents significantly reduced the neointimal area compared with BMSs, though GA-eluting stents had the lowest reduction. There were more uncovered struts for rapamycin-eluting stents than those for GA-eluting stents and bare-metal stents. The endothelial nitric oxide synthase (eNOS) expression in GA-eluting stents was much higher than that in BMSs and rapamycin-eluting stents, even though the endothelial coverage between struts was equivalent between BMSs and GA-eluting stents. Moreover, GA-eluting stents markedly promoted re-endothelialization and improved arterial healing compared to rapamycin-eluting stents in a rabbit atherosclerotic model.Conclusion: In conclusion, the novel GA-coated stent used in this study inhibited intimal hyperplasia and promoted re-endothelialization.
Size regulation of the lateral organ initiation zone and its role in determining cotyledon number in conifers
Authors: Holloway David M. , Saunders Rebecca , Wenzel Carol L. 
Published: May 2023

IntroductionUnlike monocots and dicots, many conifers, particularly Pinaceae, form three or more cotyledons. These are arranged in a whorl, or ring, at a particular distance from the embryo tip, with cotyledons evenly spaced within the ring. The number of cotyledons, nc, varies substantially within species, both in clonal cultures and in seed embryos. nc variability reflects embryo size variability, with larger diameter embryos having higher nc. Correcting for growth during embryo development, we extract values for the whorl radius at each nc. This radius, corresponding to the spatial pattern of cotyledon differentiation factors, varies over three-fold for the naturally observed range of nc. The current work focuses on factors in the patterning mechanism that could produce such a broad variability in whorl radius. Molecularly, work in Arabidopsis has shown that the initiation zone for leaf primordia occurs at a minimum between inhibitor zones of HD-ZIP III at the shoot apical meristem (SAM) tip and KANADI (KAN) encircling this farther from the tip. PIN1-auxin dynamics within this uninhibited ring form auxin maxima, specifying primordia initiation sites. A similar mechanism is indicated in conifer embryos by effects on cotyledon formation with overexpression of HD-ZIP III inhibitors and by interference with PIN1-auxin patterning.MethodsWe develop a mathematical model for HD-ZIP III/KAN spatial localization and use this to characterize the molecular regulation that could generate (a) the three-fold whorl radius variation (and associated nc variability) observed in conifer cotyledon development, and (b) the HD-ZIP III and KAN shifts induced experimentally in conifer embryos and in Arabidopsis.ResultsThis quantitative framework indicates the sensitivity of mechanism components for positioning lateral organs closer to or farther from the tip. Positional shifting is most readily driven by changes to the extent of upstream (meristematic) patterning and changes in HD-ZIP III/KAN mutual inhibition, and less efficiently driven by changes in upstream dosage or the activation of HD-ZIP III. Sharper expression boundaries can also be more resistant to shifting than shallower expression boundaries.DiscussionThe strong variability seen in conifer nc (commonly from 2 to 10) may reflect a freer variation in regulatory interactions, whereas monocot (nc = 1) and dicot (nc = 2) development may require tighter control of such variation. These results provide direction for future quantitative experiments on the positional control of lateral organ initiation, and consequently on plant phyllotaxy and architecture.
Genomic insights into genetic diversity and local adaptation of a dominant desert steppe feather grass, Stipa breviflora Griseb.
Authors: Yan Dongqing , Liu Jiamei , Fan Yanyan , Lian Zhi , Dang Zhenhua , Niu Jianming 
Published: May 2023

Investigating the genetic mechanisms of local adaptation is critical to understanding how species adapt to heterogeneous environments. In the present study, we analyzed restriction site-associated DNA sequencing (RADseq) data in order to explore genetic diversity, genetic structure, genetic differentiation, and local adaptation of Stipa breviflora. In total, 135 individual plants were sequenced and 25,786 polymorphic loci were obtained. We found low genetic diversity (He = 0.1284) within populations of S. breviflora. Four genetic clusters were identified along its distribution range. The Mantel test, partial Mantel test, and multiple matrix regression with randomization (MMRR) indicate that population differentiation was caused by both geographic distance and environmental factors. Through the FST outlier test and environmental association analysis (EAA), 113 candidate loci were identified as putatively adaptive loci. RPK2 and CPRF1, which are associated with meristem maintenance and light responsiveness, respectively, were annotated. To explore the effects of climatic factors on genetic differentiation and local adaptation of S. breviflora, gradient forest (GF) analysis was applied to 25,786 single nucleotide polymorphisms (SNPs) and 113 candidate loci, respectively. The results showed that both temperature and precipitation affected the genetic differentiation of S. breviflora, and precipitation was strongly related to local adaptation. Our study provides a theoretical basis for understanding the local adaptation of S. breviflora.
Relationship among positive self-esteem, physical literacy, and physical activity in college students: a study of a mediation model
Authors: She Xi , Gao Tian-Yu , Ma Rui-Si , Tang Di , Zhong Hua , Dong He-Ling 
Published: May 2023

BackgroundIn light of the substantial decline in physical activity during college years, this study aims to examine the relationship between positive self-esteem, physical literacy, and physical activity in order to investigate the mechanisms for improving physical activity in college students and to provide a foundation for future interventions.MethodsA cross-sectional study design was employed in this study. A total of 5,184 Participants, aged between 17 and 21 years (M = 18.97, SD = 1.10), completed the Positive Version of Rosenberg Self-esteem Scales, Perceived Physical Literacy Instruments, and the International Physical Activity Questionnaires. A mediation model was utilized to explore the associations among the three concepts.ResultsThe three regression models were as follows: Physical literacy = 18.03 + 0.98 *Self-esteem, Physical activity = 43.23 + 0.16 *Self-esteem, and Physical activity = 28.18 + 0.11 *Physical literacy. Positive self-esteem, physical literacy, and physical activity were significantly linked with each other. Physical literacy mediated 26.93% of the effect, indicating a partial mediator in the relationship between positive self-esteem and physical activity.ConclusionThe mediating effect of physical literacy on the relationship between positive self-esteem and physical activity was identified. Our findings support the development of positive self-esteem and physical literacy in college physical education curricula as part of an overall program to address students’ physical inactivity at school and in the future. This study provides a new intervention perspective for improving physical inactivity in college students.