bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the molecular mechanism of iguratimod act on SLE using network pharmacology and molecular docking analysis
Authors: Zeng Huiqiong , Chen Shuai , Lu Xiaoping , Yan Zhenbo 
Published: September 2022

Objective: Iguratimod (IGU) is a novel small disease-modifying compound widely used in Asia for the treatment of rheumatic diseases. IGU is a methane sulfonanilide. We applied network pharmacology to investigate the pharmacological mechanisms of IGU act on SLE.Methods: We used PharmMapper, UniProt, and OMIM databases to screen the potential targets of IGU, and the SLE-related disease targets were predicted. Hub target genes among the intersections of the potential targets (IGU) and related genes (SLE) were validated using the PPI network generated by the String database. GO and KEGG enrichment analyses were carried out using the David online platform. Finally, the molecular docking of hub targets and their corresponding compounds were completed through AutoDock Vina and PyMOL software for visualization.Result: A total of 292 potential targets of IGU, 6501 related disease targets of SLE, and 114 cross targets were screened from the aforementioned database. Network topology analysis identified 10 hub targets, such as CASP3, AKT1, EGFR, MMP9, and IGF1. GO enrichment analysis mainly focuses on the negative regulation of the apoptotic process and signal transduction. KEGG enrichment analysis illustrated that the PI3K-AKT signaling pathway, MAPK signaling pathway, and FoxO signaling pathway might play a significant role in the pharmacological mechanisms of IGU act on SLE. Molecular docking confirmed that the IGU ligand had strong binding activity to the hub targets.Conclusion: This study based on network pharmacology and molecular docking validation preliminarily revealed the protein targets affected by IGU acting on SLE through, and explored potential therapeutic mechanism role of IGU in SLE treatment by multi pathways.
Design feature combinations effects of running shoe on plantar pressure during heel landing: A finite element analysis with Taguchi optimization approach
Authors: Yang Zihan , Cui Chuyi , Wan Xianglin , Zheng Zhiyi , Yan Songhua , Liu Hui , Qu Feng , Zhang Kuan 
Published: September 2022

Large and repeated impacts on the heel during running are among the primary reasons behind runners’ injuries. Reducing plantar pressure can be conducive to reducing running injury and improving running performance and is primarily achieved by modifying the design parameters of running shoes. This study examines the effect of design parameters of running shoes (i.e., heel-cup, insole material, midsole material, and insole thickness) on landing peak plantar pressure and determines the combination of different parameters that optimize cushion effects by employing the Taguchi method. We developed the foot–shoe finite element (FE) model through reverse engineering. Model assembly with different design parameters was generated in accordance with the Taguchi method orthogonal table. The effectiveness of the model was verified using the static standing model in Ansys. The significance and contribution of different design parameters, and the optimal design to reduce plantar pressure during landing, were determined using the Taguchi method. In the descending order of percentage contribution was a conforming heel-cup (53.18%), insole material (25.89%), midsole material (7.81%), and insole thickness (2.69%). The more conforming heel-cup (p &lt; 0.001) and softer insole (p = 0.001) reduced the heel pressure during landing impact. The optimal design of running shoe in this study was achieved with a latex insole, a 6 mm insole thickness, an Asker C-45 hardness midsole, and a 100% conforming heel-cup. The conforming heel-cup and the insole material significantly affected the peak plantar pressure during heel landing. The implementation of a custom conforming heel-cup is imperative for relieving high plantar pressure for long-distance heel-strike runners.
Increased atherosclerotic plaque in AOC3 knock-out in ApoE−/− mice and characterization of AOC3 in atherosclerotic human coronary arteries
Authors: Filip Anna , Taleb Soraya , Bascetin Rümeyza , Jahangiri Mohammad , Bardin Matthieu , Lerognon Cindy , Fève Bruno , Lacolley Patrick , Jalkanen Sirpa , Mercier Nathalie 
Published: September 2022

IntroductionAmine oxidase copper containing 3 (AOC3) displays adhesion between leukocytes and endothelial cells and enzymatic functions. Given its controversial role in atherogenesis, we proposed to investigate the involvement of AOC3 in the formation of atherosclerotic plaques in ApoE−/−AOC3−/− mice and human coronary arteries.MethodsLesions, contractile markers, and AOC3 were studied in aortic tissues from 15- and 25-week-old mice and different stages of human coronary atherosclerotic arteries by immunohistochemistry (IHC) and/or western blot. Human VSMCs, treated or not with LJP1586, an AOC3 inhibitor, were used to measure differentiation markers by qPCR. AOC3 co-localization with specific cell markers was studied by using confocal microscopy in mice and human samples.ResultsAt 15 weeks old, the absence of AOC3 was associated with increased lesion size, α-SMA, and CD3 staining in the plaque independently of a cholesterol modification. At 25 weeks old, advanced plaques were larger with equivalent staining for α-SMA while CD3 increased in the media from ApoE−/−AOC3−/− mice. At both ages, the macrophage content of the lesion was not modified. Contractile markers decreased whereas MCP-1 appeared augmented only in the 15-week-old ApoE−/−AOC3. AOC3 is mainly expressed by mice and human VSMC is slightly expressed by endothelium but not by macrophages.ConclusionAOC3 knock-out increased atherosclerotic plaques at an early stage related to a VSMC dedifferentiation associated with a higher T cells recruitment in plaques explained by the MCP-1 augmentation. This suggests that AOC3 may have an important role in atherosclerosis independent of its canonical inflammatory effect. The dual role of AOC3 impacts therapeutic strategies using pharmacological regulators of SSAO activity.
Reference values of normal abdominal aortic areas in Chinese population measured by contrast-enhanced computed tomography
Authors: Wang Xiang , Jin Shasha , Wang Qing , Liu Jiawei , Li Fei , Chu Haiwei , Zheng Dexing , Zhang Xiaolong , Ding Jianrong , Pan Jingli , Zhao Wenjun 
Published: September 2022

ObjectiveTo generate reference values of the normal areas of the abdominal aorta at various levels among Chinese people and to explore the factors that may promote the expansion of the abdominal aorta.MethodsThe areas of normal abdominal aortas were gauged at various levels based on inner-to-inner measurements in 1,066 Chinese adult patients (&gt;18 years) without the abdominal aortic disease. The areas of subphrenic abdominal, suprarenal abdominal, infrarenal abdominal, and distal abdominal aortas were measured. The demographic and clinical characteristics were collected into a specifically designed electronic database. Multivariable linear regression was used to analyze the potential risk factors promoting the expansion of the abdominal aorta.ResultsIn males, the median areas of the subphrenic abdominal aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and distal abdominal aorta were 412.1, 308.0, 242.2, and 202.2 mm2, respectively. In females, the median areas of the subphrenic abdominal aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and distal abdominal aorta were 327.7, 243.4, 185.4, and 159.6 mm2, respectively. The areas of the abdominal aorta at different levels were larger in males than in females and increased with age. Multiple linear stepwise regression analysis showed that the subphrenic abdominal aortic area was significantly related to age (β = 0.544, p &lt; 0.001), sex (β = 0.359, p &lt; 0.001), and hypertension (β = 0.107, p &lt; 0.001). Suprarenal abdominal aortic area was related to age (β = 0.398, p &lt; 0.001), sex (β = 0.383, p &lt; 0.001), history of smoking (β = 0.074, p = 0.005), and hypertension (β = 0.111, p &lt; 0.001). The infrarenal abdominal aortic area was correlated with age (β = 0.420, p &lt; 0.001), sex (β = 0.407, p &lt; 0.001), and history of smoking (β = 0.055, p = 0.036). The distal abdominal aortic area was correlated with age (β = 0.463, p &lt; 0.001), sex (β = 0.253, p &lt; 0.001), and hypertension (β = 0.073, p = 0.013).ConclusionThe abdominal aortic areas at different levels were larger in males than in females. Aging, hypertension, and smoking prompt the expansion of abdominal aorta.
Comparative effects of different types of cardioplegia in cardiac surgery: A network meta-analysis
Authors: Tan Jia , Bi Siwei , Li Jingyi , Gu Jun , Wang Yishun , Xiong Jiyue , Yu Xiang , Du Lei 
Published: September 2022

ObjectiveTo compare the outcomes of four types of cardioplegia during cardiac surgery: del Nido (DN), blood cardioplegia (BC), histidine-tryptophan-ketoglutarate (HTK) and St. Thomas.MethodsRandomized controlled trials (RCTs) and observational cohort studies from 2005 to 2021 were identified in PubMed, Embase, and Cochrane databases. Data were extracted for the primary endpoint of perioperative mortality as well as the following secondary endpoints: atrial fibrillation, renal failure, stroke, use of an intra-aortic balloon pump, re-exploration, intensive care unit stay and hospital stay. A network meta-analysis comparing all four types of cardioplegia was performed, as well as direct meta-analysis comparing pairs of cardioplegia types.ResultsData were extracted from 18 RCTs and 49 observational cohort studies involving 18,191 adult patients (55 studies) and 1,634 children (12 studies). Among adult patients, risk of mortality was significantly higher for HTK (1.89, 95% CI 1.10, 3.52) and BC (RR 1.73, 95% CI 1.22, 2.79) than for DN. Risk of atrial fibrillation was significantly higher for BC (RR 1.41, 95% CI 1.09, 1.86) and DN (RR 1.51, 95% CI 1.15, 2.03) than for HTK. Among pediatric patients, no significant differences in endpoints were observed among the four types of cardioplegia.ConclusionsThis network meta-analysis suggests that among adult patients undergoing cardiac surgery, DN may be associated with lower perioperative mortality than HTK or BC, while risk of atrial fibrillation may be lower with HTK than with BC or DN.
Interacting municipal-level anthropogenic and ecological disturbances drive changes in Neotropical forest carbon storage
Authors: Toro Giselle , Otero Maria Paula , Clerici Nicola , Szantoi Zoltan , González-González Andrés , Escobedo Francisco J. 
Published: September 2022

Deforestation is a documented driver of biodiversity loss and ecosystem services in the tropics. However, less is known on how interacting regional and local-level anthropogenic and ecological disturbances such as land use activities, human populations, and armed conflict affect carbon storage and emissions in Neotropical forests. Therefore, we explored how local-scale, socio-ecological drivers affect carbon dynamics across space and time in a region in Colombia characterized by deforestation, land use cover (LULC) changes, and armed conflict. Specifically, using available municipal level data from a period of armed conflict (2009–2012), spatiotemporal analyses, and multivariate models, we analyzed the effects of a suite of socio-ecological drivers (e.g., armed conflict, illicit crops, human population, agriculture, etc.) on deforestation and carbon storage-emission dynamics. We found that about 0.4% of the initial forest cover area was converted to other LULC types, particularly pastures and crops. Gross C storage emissions were 4.14 Mt C, while gross carbon sequestration was 1.43 Mt C; primarily due to forest regeneration. We found that livestock ranching, illegal crop cultivation, and rural population were significant drivers of deforestation and carbon storage changes, while the influential role of armed conflict was less clear. However, temporal dynamics affected the magnitude of LULC effects and deforestation on carbon storage and emissions. The approach and findings can be used to better inform medium to long-term local and regional planning and decision-making related to forest conservation and ecosystem service policies in Neotropical forests experiencing disturbances related to global change and socio-political events like armed conflict.
Characterization of PM2.5-bound trace elements, source apportionment, and assessment of associated human health risks during summer and winter in Greater Noida, the National Capital Region of India
Authors: Kumar Vishnu , Yadav Mudit , Behera Sailesh N. 
Published: September 2022

To examine the trends of particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) and its elemental constituents during two distinct seasons at a site away from the city center of Delhi and the National Capital Region (Delhi-NCR) of India, this unique study aimed at the development of source-receptor-effect linkages. This research paper presents results of occurrence, long-range transport (LRT), source apportionment, and human health impact assessment of 24 PM2.5-bound trace elements (Al, Ba, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, K, Li, Mg, Mn, Na, Ni, Pb, S, Se, Si, Te, Tl, Zn, and Zr). The concentration of PM2.5 during winter (296 ± 45 μg/m3) was significantly higher than in summer (114 ± 48 μg/m3) and exceeded 24 h Indian standard on most of the measurement days. The seasonal concentration ratios (winter/summer) of individual elements varied from 1.7 (Si) to 5.9 (Tl). The backward trajectory of air masses showed that transboundary transport of pollutants occurred in the downwind direction during winter, indicating that this remote site was affected by transported particulates and local activities. The principal component analysis–absolute principal component score (PCA-APCS) model confirmed five significant sources, vehicles (22.3%), soil/road dust (23.1%), coal combustion (20.9%), open burning (13.8%), and other industries (10.2%) responsible for particulate emission. The results from the multiple path particle dosimetry model (MPPD) showed higher deposition of particulates in the human respiratory system occurred during winter (44%) than in summer (40%). The elements with crustal sources of origin had a higher deposition fraction in the head region (0.27 for Si) compared to elements of anthropogenic sources (0.13 for Li). The excess lifetime carcinogenic risk (ELCR) under winter episodic events increased significantly at 128 × 10−6 compared to the summer non-episodic period at 41 × 10−6.
Development of an exosome-related and immune microenvironment prognostic signature in colon adenocarcinoma
Authors: Cui Guoliang , Wang Can , Liu Jinhui , Shon Kinyu , Gu Renjun , Chang Cheng , Ren Lang , Wei Fei , Sun Zhiguang 
Published: September 2022

Background: The correlation between exosomes and the tumor immune microenvironment has been proved to affect tumorigenesis and progression of colon adenocarcinoma (COAD). However, it remained unclear whether exosomes had an impact on the prognostic indications of COAD patients.Methods: Expression of exosome-related genes (ERGs) and clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The ERGs associated with prognosis were identified and exosome-related prognostic signature was constructed. Patients in two risk groups were classified according to the risk score calculation formula: Risk score = 1.0132 * CCKBR + 0.2416 * HOXC6 + 0.7618 * POU4F1. The expression of three ERGs was investigated by qRT-PCR. After that, we developed a nomogram predicting the likelihood of survival and verified its predictive efficiency. The differences of tumor immune microenvironment, immune cell infiltration, immune checkpoint and sensitivity to drugs in two risk groups were analyzed.Results: A prognostic signature was established based on the three ERGs (CCKBR, HOXC6, and POU4F1) and patients with different risk group were distinguished. Survival analysis revealed the negative associated of risk score and prognosis, ROC curve analyses showed the accuracy of this signature. Three ERGs expression was investigated by qRT-PCR in three colorectal cancer cell lines. Moreover, risk score was positively correlated with tumor mutational burden (TMB), immune activities, microsatellite instability level, the expression of immune checkpoint genes. Meanwhile, the expression level of three ERGs and the risk score were markedly related with the sensitive response to chemotherapy.Conclusion: The novel signature composed of three ERGs with precise predictive capabilities can be used to predict prognosis and provide a promising therapeutic target for improving the efficacy of immunotherapy.
Benzophenone-3 and antinuclear antibodies in U.S. adolescents and adults ages 12-39 years
Authors: Parks Christine G. , Meier Helen C. S. , Jusko Todd A. , Wilkerson Jesse , Miller Frederick W. , Sandler Dale P. 
Published: September 2022

BackgroundBetween 1988 and 2012, prevalence of antinuclear antibodies (ANA) increased in the U.S., especially in adolescents and non-Hispanic Whites. Female predominance of ANA suggests a role for hormonal factors, including xenobiotic exposures that may disrupt endocrine signaling. Benzophenone-3 (BP-3) is one such chemical with increasing exposure through sunscreen use. We investigated whether urinary BP-3 levels were related to ANA in adolescents and young adults.MethodsIn a sample of 1,785 individuals ages 12-39 years in the National Health and Nutrition Examination Survey (NHANES; 2003-4, 2011-12), we examined cross-sectional associations of ANA (N=192; 3+ or 4+ at the 1:80 dilution, measured by HEp-2 immunofluorescence) with urinary BP-3, and other phenols bisphenol-A, triclosan, and parabens. Adjusted prevalence odds ratios (POR) were calculated in season-stratified models [winter (November-April) and summer (May-October)], given differences in sunscreen use and BP-3 concentrations.ResultsBP-3 concentrations (detected in &gt;98.5% of individuals) did not differ by ANA positivity in the summer (geometric mean, GM 30.6 ng/ml ANA-positive vs. 35.3 ANA-negative; GM ratio 1.15), but in winter were higher among ANA-positives (50.2 vs. 20.1 ANA-negative; GM ratio 2.50). ANA was associated with log10BP-3 in winter (POR 1.57; 95%CI 1.07-2.30 per unit increase) but not summer (0.94; 0.61, 1.44; interaction p=0.09). Triclosan, parabens, and bisphenol-A levels were unrelated to ANA overall or by season (ORs 0.64 to 1.33).ConclusionsThe association of urinary BP-3 with ANA in the winter may reflect different exposure patterns or unmeasured confounders. Findings warrant replication in prospective studies and including past and year-round exposures.
Efficacy, immunogenicity and safety of COVID-19 vaccines in older adults: a systematic review and meta-analysis
Authors: Li Zejun , Liu Shouhuan , Li Fengming , Li Yifeng , Li Yilin , Peng Pu , Li Sai , He Li , Liu Tieqiao 
Published: September 2022

BackgroundOlder adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors.MethodsRandomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456).ResultsOf the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55−89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77−96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80−4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80−96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82−93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45−99.98) and GMT (SMD 6.20, 95% CI: 2.02−10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38−1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups (p &gt; 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22).ConclusionCOVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.
Plasma-derived exosomal mRNA profiles associated with type 1 diabetes mellitus
Authors: Fan Wenqi , Pang Haipeng , Shi Xiajie , Li Jiaqi , Wang Yimeng , Luo Shuoming , Lin Jian , Yu Haibo , Xiao Yang , Li Xia , Huang Gan , Xie Zhiguo , Zhou Zhiguang 
Published: September 2022

BackgroundExosomes carry various types of transcripts, such as messenger RNAs (mRNAs), and play an important role in mediating cell-to-cell communication, thus influencing multiple physiological and pathological processes. However, the role of exosomal mRNAs in T1DM is largely unknown. Here, we aimed to identify the plasma-derived exosomal mRNA expression profiles in T1DM and to explore their potential biological functions in T1DM.Materials and MethodsPlasma-derived exosomes were isolated from 10 patients with T1DM and 10 age- and sex-matched control subjects by size exclusion chromatography methods. Transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis confirmed the presence of exosomes. The exosomal mRNAs were analyzed using the Illumina HiSeq platform. Six differentially expressed mRNAs (DEMs) were randomly selected to determine the expression level by quantitative real-time PCR (qRT−PCR) in a larger cohort (T1DM subjects N=40; control subjects N=40). The biological functions of DEMs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein−protein interaction networks were constructed to explore the potential associations among DEMs.ResultsIn total, 112 DEMs were identified in T1DM, among which 66 mRNAs were upregulated and 46 mRNAs were downregulated. Four of six candidate exosomal mRNAs were successfully validated by qRT−PCR. Bioinformatics analysis indicated that these mRNAs were most significantly involved in positive regulation by host viral transcription (GO enrichment analysis) and oxidative phosphorylation (KEGG pathway analysis).ConclusionsOur study reported the plasma-derived exosomal mRNA expression profiles of T1DM for the first time. The identified DEMs might be associated with the pathogenesis of T1DM, and some DEMs have the potential to serve as biomarkers and therapeutic targets for T1DM.