bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of diabetes mellitus on left ventricular function and remodeling in hypertensive patients with heart failure with reduced ejection fraction: assessment with 3.0 T MRI feature tracking
Authors: Zhang Ge , Shi Ke , Yan Wei-Feng , Li Xue-Ming , Li Yuan , Guo Ying-Kun , Yang Zhi-Gang 
Published: May 2022

Abstract
Background
Heart failure with reduced ejection fraction (HFrEF) is a major health burden worldwide with high morbidity and mortality. Comorbidities of HFrEF complicate treatment and lead to poor prognosis, among which hypertension (HTN) and diabetes mellitus (DM) are common and frequently cooccur. DM was found to have additive effects on cardiac function and structure in hypertensive patients, while its effects on the HFrEF cohort in the context of HTN remain unclear.

Methods
A total of 171 patients with HFrEF were enrolled in our study, consisting of 51 HFrEF controls, 72 hypertensive HFrEF patients (HTN-HFrEF [DM−]) and 48 hypertensive HFrEF patients with comorbid DM (HTN-HFrEF [DM+]). Cardiac MRI-derived left ventricular (LV) strains, including global radial (GRPS), circumferential (GCPS) and longitudinal (GLPS) peak strain, and remodeling parameters were measured and compared among groups. The determinants of impaired LV function and LV remodeling in HFrEF patients were investigated by multivariable linear regression analyses.

Results
Despite a similar LV ejection fraction, patients in the HTN-HFrEF (DM+) and HTN-HFrEF (DM−) groups showed a higher LV mass index and LV remodeling index than those in the HFrEF control group (all p < 0.05). Compared with the HTN-HFrEF (DM−) and HFrEF control groups, the HTN-HFrEF (DM+) group exhibited the most severe GLPS impairment (p < 0.001). After adjustment for covariates in HFrEF patients, DM was found to be an independent determinant of impaired LV strains in all three directions (GRPS [β = − 0.189; p = 0.011], GCPS [β = 0.217; p = 0.005], GLPS [β = 0.237; p = 0.002]). HTN was associated with impaired GLPS (β = 0.185; p = 0.016) only. However, HTN rather than DM was associated with LV remodeling in HFrEF patients in the multivariable regression analysis (p < 0.05).

Conclusions
DM aggravated LV longitudinal dysfunction in hypertensive HFrEF patients without further changes in LV remodeling, indicating that HFrEF patients with comorbid HTN and DM may have a hidden high-risk phenotype of heart failure that requires more advanced and personalized management.
Tetraspanin 7 promotes osteosarcoma cell invasion and metastasis by inducing EMT and activating the FAK-Src-Ras-ERK1/2 signaling pathway
Authors: Shao Shijie , Piao Lianhua , Guo Liwei , Wang Jiangsong , Wang Luhui , Wang Jiawen , Tong Lei , Yuan Xiaofeng , Zhu Junke , Fang Sheng , Wang Yimin 
Published: May 2022

Abstract
Background
Tetraspanins are members of the 4-transmembrane protein superfamily (TM4SF) that function by recruiting many cell surface receptors and signaling proteins into tetraspanin-enriched microdomains (TEMs) that play vital roles in the regulation of key cellular processes including adhesion, motility, and proliferation. Tetraspanin7 (Tspan7) is a member of this superfamily that plays documented roles in hippocampal neurogenesis, synaptic transmission, and malignant transformation in certain tumor types. How Tspan7 influences the onset or progression of osteosarcoma (OS), however, remains to be defined. Herein, this study aimed to explore the relationship between Tspan7 and the malignant progression of OS, and its underlying mechanism of action.

Methods
In this study, the levels of Tspan7 expression in human OS cell lines were evaluated via qRT-PCR and western blotting. The effect of Tspan7 on proliferation was examined using CCK-8 and colony formation assays, while metastatic role of Tspan7 was assessed by functional assays both in vitro and in vivo. In addition, mass spectrometry and co-immunoprecipitation were performed to verify the interaction between Tspan7 and β1 integrin, and western blotting was used to explore the mechanisms of Tspan7 in OS progresses.

Results
We found that Tspan7 is highly expressed in primary OS tumors and OS cell lines. Downregulation of Tspan7 significantly suppressed OS growth, metastasis, and attenuated epithelial-mesenchymal transition (EMT), while its overexpression had the opposite effects in vitro. Furthermore, it exhibited reduced OS pulmonary metastases in Tspan7-deleted mice comparing control mice in vivo. Additionally, we proved that Tspan7 interacted with β1 integrin to facilitate OS metastasis through the activation of integrin-mediated downstream FAK-Src-Ras-ERK1/2 signaling pathway.

Conclusion
In summary, this study demonstrates for the first time that Tspan7 promotes OS metastasis via interacting with β1 integrin and activating the FAK-Src-Ras-ERK1/2 pathway, which could provide rationale for a new therapeutic strategy for OS.
Dietary fiber and prevalence of abdominal aortic calcification in the United States (from the national health and nutrition examination survey data [2013–2014])
Authors: Sun YuJiao , Zhang HuanRui , Tian Wen 
Published: May 2022

Abstract
Background
Abdominal aortic calcification (AAC) is recognized as a valuable predictor of cardiovascular diseases (CVDs). Dietary fiber is strongly correlated with CVDs. However, the effect of dietary fiber on AAC in the population is not well understood.

Objective
To assess the relationship between dietary fiber intake and AAC in the US adult population.

Methods
A total of 2671 individuals with both dietary fiber intake and AAC score data were enrolled from the 2013–2014 National Health and Nutrition Examination Survey (NHANES), a cross-sectional health examination in the US. Multinomial logistic regression was used to calculate the odds ratio (OR), with 95% confidence interval (CI). To reveal the relationship between dietary fiber intake and AAC, restricted cubic spline was also applied.

Results
Out of the total participants, 241 (9%) had severe AAC and 550 (20%) had mild-moderate AAC. Multinomial logistic regression indicated that higher intake of dietary fiber was associated with lower risk of severe AAC, but not with lower risk of mild-moderate AAC. For every one standard deviation increase (9.4 g/day) in dietary fiber intake, the odds of severe AAC were reduced by 28% [OR 0.72 (95% CI, 0.57–0.90), p = 0.004], after adjusting for confounding factors. Dose–response relationship revealed that dietary fiber intake was negatively correlated with severe AAC (p for linear < 0.001, p for nonlinear = 0.695).

Conclusions
Dietary fiber intake was negatively associated with severe AAC, and showed a dose–response relationship in US adults.
Effects of Benzo[a]pyrene-DNA adducts, dietary vitamins, folate, and carotene intakes on preterm birth: a nested case–control study from the birth cohort in China
Authors: Zhao Nan , Wu Weiwei , Cui Shiwei , Li Haibin , Feng Yongliang , Guo Ling , Zhang Yawei , Wang Suping 
Published: May 2022

AbstractBackgroundPolycyclic aromatic hydrocarbons (PAHs) and its DNA adducts has been suggested to increase the risk of preterm birth (PB). Yet, few studies have been conducted to investigate this association, and the role of dietary nutrients intakes including vitamins, folate, and carotene during pre- and post-conception on this association has not been studied.MethodsBuilding upon a birth cohort in Taiyuan China, we conducted a nested case control study including 83 PB and 82 term births. Benzo[a]pyrene (BaP)-DNA adducts were measured by an improved LC-MC/MC analytic method. Dietary nutrient intakes were estimated from food frequency questionnaire using the Chinese Standard Tables of Food Consumption. Multivariable logistic regression model was used to examine the associations.ResultsIncreased risk of PB was observed as per interquartile increase in maternal BaP-DNA adduct level (OR = 1.27, 95%CI 0.95–1.67). Compared to low level (below mean) of maternal adducts, high level (above mean) of adducts was associated with the risk of PB (OR = 2.05, 95%CI 1.05–4.01). After stratified by dietary nutrients intakes, high adducts levels were associated with approximately 2–fourfold times increases in risk of PB among women with low vitamin A, C, E, folate, and carotene intakes during pre- and/or post-conception. Stronger stratified associations were consistently seen during preconception. Similar patterns were observed after additional adjustment for supplementation.ConclusionsOur study supports the hypothesis that high level of maternal PAHs exposure was significantly associated with increased risk of PB, and provides the first evidence that dietary vitamins, carotene, and folate intake levels may modify this association during different pregnancy windows. Our findings are relevant to identify recommendation for environment management and prenatal nutrition regarding pregnant women and newborns. Further investigation in other populations is warranted.
Conductive nanocomposite hydrogel and mesenchymal stem cells for the treatment of myocardial infarction and non-invasive monitoring via PET/CT
Authors: Zhu Ke , Jiang Dawei , Wang Kun , Zheng Danzha , Zhu Ziyang , Shao Fuqiang , Qian Ruijie , Lan Xiaoli , Qin Chunxia 
Published: May 2022

Abstract
Background
Injectable hydrogels have great promise in the treatment of myocardial infarction (MI); however, the lack of electromechanical coupling of the hydrogel to the host myocardial tissue and the inability to monitor the implantation may compromise a successful treatment. The introduction of conductive biomaterials and mesenchymal stem cells (MSCs) may solve the problem of electromechanical coupling and they have been used to treat MI. In this study, we developed an injectable conductive nanocomposite hydrogel (GNR@SN/Gel) fabricated by gold nanorods (GNRs), synthetic silicate nanoplatelets (SNs), and poly(lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA). The hydrogel was used to encapsulate MSCs and 68Ga3+ cations, and was then injected into the myocardium of MI rats to monitor the initial hydrogel placement and to study the therapeutic effect via 18F-FDG myocardial PET imaging.

Results
Our data showed that SNs can act as a sterically stabilized protective shield for GNRs, and that mixing SNs with GNRs yields uniformly dispersed and stabilized GNR dispersions (GNR@SN) that meet the requirements of conductive nanofillers. We successfully constructed a thermosensitive conductive nanocomposite hydrogel by crosslinking GNR@SN with PLGA2000-PEG3400-PLGA2000, where SNs support the proliferation of MSCs. The cation-exchange capability of SNs was used to adsorb 68Ga3+ to locate the implanted hydrogel in myocardium via PET/CT. The combination of MSCs and the conductive hydrogel had a protective effect on both myocardial viability and cardiac function in MI rats compared with controls, as revealed by 18F-FDG myocardial PET imaging in early and late stages and ultrasound; this was further validated by histopathological investigations.

Conclusions
The combination of MSCs and the GNR@SN/Gel conductive nanocomposite hydrogel offers a promising strategy for MI treatment.

Graphical Abstract
ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling
Authors: Liu Junzhao , Wu Zuohong , Liu Yadong , Zhan Zhu , Yang Liping , Wang Can , Jiang Qinqin , Ran Haitao , Li Pan , Wang Zhigang 
Published: May 2022

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-β (TGF-β), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-β expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation.ResultsWe synthesized DMF-loaded ROS-responsive DSPE-TK-PEG@DMF liposomes (DTP@DMF NPs). DTP@DMF NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while DTP@DMF NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that DTP@DMF NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-β and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, DTP@DMF NPs treatment presented enhanced antifibrotic effect. DTP@DMF NPs also had a prolonged residence time in the lung as well as excellent biocompatibility.ConclusionsDTP@DMF NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.Graphical Abstract
Two-photon responsive porphyrinic metal-organic framework involving Fenton-like reaction for enhanced photodynamic and sonodynamic therapy
Authors: Duan Wenyao , Li Bo , Zhang Wen , Li Jiaqi , Yao Xin , Tian Yupeng , Zheng Jun , Li Dandan 
Published: May 2022

AbstractDesigning new oxygenation nanomaterials by oxygen-generating or oxygen-carrying strategies in hypoxia-associated anti-tumor therapy is a high priority target yet challenge. In this work, we fabricated a nanoplatform involving Fenton-like reaction, Pd@MOF-525@HA, to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy. Thereinto, the porphyrinic MOF-525 can produce singlet oxygen (1O2) via light or ultrasonic irradiation for photodynamic and sonodynamic therapy. Notably, the well-dispersed Pd nanocubes within MOF-525 can convert H2O2 into O2 to mitigate the hypoxic environment for enhanced therapy outcome. Moreover, the two-photon activity and cancer cell specific targeting capability of Pd@MOF-525@HA gave rise to deeper tissue penetration and near-infrared light-induced fluorescence imaging to achieve precise guidance for cancer therapy. This work provides a feasible way in designing new oxygenation nanomaterials to relieve tumor hypoxia for enhanced cancer treatment.
Graphical Abstract
Three birds with one stone: co-encapsulation of diclofenac and DL-menthol for realizing enhanced energy deposition, glycolysis inhibition and anti-inflammation in HIFU surgery
Authors: Wu Haitao , Zhou Hu , Zhang Wenjie , Jin Ping , Shi Qianqian , Miao Zhaohua , Wang Hua , Zha Zhengbao 
Published: May 2022

AbstractDespite attracting increasing attention in clinic, non-invasive high-intensity focused ultrasound (HIFU) surgery still commonly suffers from tumor recurrence and even matastasis due to the generation of thermo-resistance in non-apoptotic tumor cells and adverse therapy-induced inflammation with enhanced secretion of growth factors in irradiated region. In this work, inspired by the intrinsic property that the expression of thermo-resistant heat shock proteins (HSPs) is highly dependent with adenosine triphosphate (ATP), dual-functionalized diclofenac (DC) with anti-inflammation and glycolysis-inhibition abilities was successfully co-encapsulated with phase-change dl-menthol (DLM) in poly(lactic-co-glycolic acid) nanoparticles (DC/DLM@PLGA NPs) to realize improved HIFU surgery without causing adverse inflammation. Both in vitro and in vivo studies demonstrated the great potential of DC/DLM@PLGA NPs for serving as an efficient synergistic agent for HIFU surgery, which can not only amplify HIFU ablation efficacy through DLM vaporization-induced energy deposition but also simultaneously sensitize tumor cells to hyperthermia by glycolysis inhibition as well as diminished inflammation. Thus, our study provides an efficient strategy for simultaneously improving the curative efficiency and diminishing the harmful inflammatory responses of clinical HIFU surgery.
Graphical Abstract
Association of inflammatory markers with cerebral small vessel disease in community-based population
Authors: Jiang Lingling , Cai Xueli , Yao Dongxiao , Jing Jing , Mei Lerong , Yang Yingying , Li Shan , Jin Aoming , Meng Xia , Li Hao , Wei Tiemin , Wang Yongjun , Pan Yuesong , Wang Yilong 
Published: May 2022

Abstract
Background
This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD).

Methods
A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed.

Results
At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05–1.70; cOR 1.28, 95% CI 1.02–1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00–1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25–3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14–2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16–2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08–1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20–2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04–1.39) and small vessel stroke (OR 1.21, 95% CI 1.06–1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p < 0.05).

Conclusions
This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC.
Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis
Authors: Chkioua Latifa , Amri Yessine , Saheli Chaima , Mili Wassila , Mabrouk Sameh , Chabchoub Imen , Boudabous Hela , Azzouz Wissem Ben , Turkia Hadhami Ben , Ferchichi Salima , Tebib Neji , Massoud Taieb , Ghorbel Mohamed , Laradi Sandrine 
Published: May 2022

Abstract
Background
Ocular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene. Cysteamine therapy mostly corrects the organ abnormalities.

Methods
This study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital. The Optical Coherence Tomography (OCT) of the cornea and retinal photography were used to search cystine crystals within the corneas and conjunctiva in eight Tunisian patients. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the entire CTNS gene.

Results
The studied patients were found to have cystine crystal limited anterior corneal stroma and the conjunctiva associated with retinal crystals accumulation. CTNS gene sequencing disclosed 7 mutations: three missense mutations (G308R, p.Q88K, and p.S139Y); one duplication (C.829dup), one framshift mutation (p.G258f), one splice site mutation (c.681 + 7delC) and a large deletion (20,327-bp deletion). Crystallographic structure analysis suggests that the novel mutation p.S139Y is buried in a first transmembrane helix closed to the lipid bilayer polar region, introducing a difference in hydrophobicity which could affect the hydrophobic interactions with the membrane lipids. The second novel mutation p.Q88K which is located in the lysosomal lumen close to the lipid membrane polar head region, introduced a basic amino acid in a region which tolerate only uncharged residue. The third missense mutation introduces a positive change in nonpolar tail region of the phospholipid bilayer membrane affecting the folding and stability of the protein in the lipid bilayer.

Conclusions
Our data demonstrate that impaired transport of cystine out of lysosomes is the most common, which is obviously associated with the mutations of transmembrane domains of cystinosine resulting from a total loss of its activity.
Application of gas flow headspace liquid phase micro extraction coupled with gas chromatography-mass spectrometry for determination of 4-methylimidazole in food samples employing experimental design optimization
Authors: Rafiei jam Mahdiye , Nezhadali Azizollah , Kaykhaii Massoud 
Published: May 2022

Abstract
Background
4-Methylimidazole (4-MeI) or 4-methyl-1H-imidazole, a slightly yellowish solid with molecular formula C4H6N2, is a heterocyclic compound which supposedly does not exist as a natural product and is formed when carbohydrates are heating with ammonium compounds. This compound is used in pharmaceuticals, agriculture and photography chemicals, dyes and pigments, and rubber manufacturing. In the present study, a simple and efficient sample preparation method designated gas flow headspace liquid phase microextraction (GF-HS-SDME) was employed for the extraction and preconcentration of 4-methylimidazole (4-MeI) from food and beverage samples, before its determination by gas chromatography-mass spectrometry.

Result
To investigate the optimal conditions for the extraction process in GF-HS-SDME method, factors affecting extraction, including selection of extraction solvent, vial volume, extraction solvent ratio, position of extracting solvent, drop volume, sample volume, stirring speed, temperature, extraction time, sample pH, ionic strength of the sample solution and gas flow rate were optimized by utilizing both one-variable-at-a-time method and Plackett–Burman design. The investigation of protocol was carried out by using a standard solution containing 100.0 μg L−1 of 4-MeI in deionized water.

Conclusion
In this study, a simple and green analytical method based on GF-HS-SDME was proposed for the extraction and preconcentration of 4-MeI from foodstuffs, followed by GC–MS determination. The main advantage of this method is its high preconcentration factor and fastness due to the application of an inert gas stream during microextraction.