bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy
Authors: Chen Ying-Chen , Lu Bing-Ze , Shu Yu-Chen , Sun Yuan-Ting 
Published: January 2022

AimsDiabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM).MethodsKtrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).ResultsIn all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs.ConclusionsThis study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.
Numerical Analysis of a New Type of Dishwasher Pump for Different Rotation Speeds of the Volute
Authors: Ning Chao , Li Yalin , Huang Ping , Xu Hui , Zheng Feng 
Published: January 2022

The interaction between impeller and volute produces a complex and unsteady water flow. It involves the interference of the non-uniform flow (such as the impeller’s jet wake and a secondary flow). In this paper, the transient flow in a new type of dishwasher pump is investigated numerically. In addition, pressure measurements are used to validate the numerical method, and the simulation results agree well with the experiment. Three schemes, 0 rpm (revolutions per minute)/30 rpm/60 rpm, of volute speeds are investigated. Multiple monitoring points are set at different positions of the new dishwasher pump to record pressure-pulse signals. In addition, frequency signals are obtained using a Fast Fourier Transform, which is then used to analyze the effect of the volute tongue and the outflow of the impeller. The radial force on the principal axis is recorded, and the schemes with different rotation speeds of volute are compared. The results show that the volute speed has only a small effect on the pump performance. In addition, the speed of the volute mainly affects the flow field in the transition section located between impeller and volute. The difference of the flow field in the impeller depends on the relative position between the impeller and the volute. The time domain curve for the pressure pulse is periodic, and there is a deviation between the peak for the schemes in the outflow region. In the frequency domain, the characteristic frequency equals the blade passing frequency. In the outflow region, the effect of the volute speeds increases with increasing volute speed. For the radial force, the rotating volute strengthens the fluctuation of the radial force, which affects the operational stability of the pump. The shape of the vector distribution is most regular for the 30 rpm scheme, which indicates that the stability of the pump is the highest. This paper can be used to improve both the control and selection of volute speeds.
Hsa-miR-557 Inhibits Osteosarcoma Growth Through Targeting KRAS
Authors: Qiao Zhi , Li Jinfeng , Kou Hongwei , Chen Xiangrong , Bao Deming , Shang Guowei , Chen Songfeng , Ji Yanhui , Cheng Tian , Wang Yisheng , Liu Hongjian 
Published: January 2022

Objective: Osteosarcoma is the most common malignancy in the skeletal system; studies showed an important role of miRNAs in tumorigenesis, indicating miRNAs as possible therapeutic molecules. This study found abnormal hsa-miR-557 expression levels in osteosarcoma and tried to explore the potential function and the mechanism.Methods: Differential expression genes of osteosarcoma were analyzed using GSE28423 from the GEO database. Survival analysis of miRNAs was conducted with data obtained from the TARGET-OS database. STRING and miRDIP were used to predict target genes of hsa-miR-557; KRAS was then verified using dual-luciferase reporter assay. Expression of genes was detected by qPCR, and levels of proteins were detected by Western blot. The proliferation ability of cells was detected by CCK-8 and cell cycle analysis. Tumor formation assay in nude mice was used to detect the influence of osteosarcoma by hsa-miR-557 in vivo.Results: Analysis from the GEO and TARGET databases found 12 miRNAs that are significantly related to the osteosarcoma prognosis, 7 downregulated (hsa-miR-140-3p, hsa-miR-564, hsa-miR-765, hsa-miR-1224-5p, hsa-miR-95, hsa-miR-940, and hsa-miR-557) and 5 upregulated (hsa-miR-362-3p, hsa-miR-149, hsa-miR-96, hsa-miR-744, and hsa-miR-769-5p). CCK-8 analysis and cell cycle analysis found that hsa-miR-557 could significantly inhibit the proliferation of osteosarcoma cells. The tumor formation assay in nude mice showed that tumor sizes and weights were inhibited by hsa-miR-557 transfection. Further studies also proved that hsa-miR-557 could target the 3′UTR of KRAS and modulate phosphorylation of downstream proteins.Conclusion: This study showed that hsa-miR-557 could inhibit osteosarcoma growth both in vivo and in vitro, by modulating KRAS expression.
Prenatal Cadmium Exposure Alters Proliferation in Mouse CD4+ T Cells via LncRNA Snhg7
Authors: McCall Jamie L. , Varney Melinda E. , Rice Emily , Dziadowicz Sebastian A. , Hall Casey , Blethen Kathryn E. , Hu Gangqing , Barnett John B. , Martinez Ivan 
Published: January 2022

ObjectivePrenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring affecting coding and non-coding genes. Recent studies have shown that long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we investigated the role of long non-coding RNA small nucleolar RNA host gene 7 (lncSnhg7) in T cell proliferation.MethodsRNA sequencing was used to analyze the expression of lncRNAs in splenic CD4+ T cells with and without CD3/CD28 stimulation. Next, T cells isolated from offspring exposed to control or Cd water throughout mating and gestation were analyzed with and without stimulation with anti-CD3/CD28 beads. Quantitative qPCR and western blotting were used to detect RNA and protein levels of specific genes. Overexpression of a miR-34a mimic was achieved using nucleofection. Apoptosis was measured using flow cytometry and luminescence assays. Flow cytometry was also used to measure T cell proliferation in culture. Finally, lncSnhg7 was knocked down in splenic CD4+ T cells with lentivirus to assess its effect on proliferation.ResultsWe identified 23 lncRNAs that were differentially expressed in stimulated versus unstimulated T cells, including lncSnhg7. LncSnhg7 and a downstream protein, GALNT7, are upregulated in T cells from offspring exposed to Cd during gestation. Overexpression of miR-34a, a regulator of lncSnhg7 and GALNT7, suppresses GALNT7 protein levels in primary T cells, but not in a mouse T lymphocyte cell line. The T cells isolated from Cd-exposed offspring exhibit increased proliferation after activation in vitro, but Treg suppression and CD4+ T cell apoptosis are not affected by prenatal Cd exposure. Knockdown on lncSnhg7 inhibits proliferation of CD4+ T cells.ConclusionPrenatal Cd exposure alters the expression of lncRNAs during T cell activation. The induction of lncSnhg7 is enhanced in splenic T cells from Cd offspring resulting in the upregulation of GALNT7 protein and increased proliferation following activation. miR-34a overexpression decreased GALNT7 expression and knockdown of lncSnhg7 inhibited proliferation suggesting that the lncSnhg7/miR-34a/GALNT7 is an important pathway in primary CD4+ T cells. These data highlight the need to understand the consequences of environmental exposures on lncRNA functions in non-cancerous cells as well as the effects in utero.
Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus
Authors: Kleer Jessica S. , Rabatscher Pascal A. , Weiss Jessica , Leonardi Joel , Vogt Severin B. , Kieninger-Gräfitsch Andrea , Chizzolini Carlo , Huynh-Do Uyen , Ribi Camillo , Trendelenburg Marten 
Published: January 2022

ObjectiveIn patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.MethodsFirst, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP®microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.ResultsThe epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p &lt; 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.ConclusionIn this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.
LncRNA GAS5/miR-137 Is a Hypoxia-Responsive Axis Involved in Cardiac Arrest and Cardiopulmonary Cerebral Resuscitation
Authors: Jing Wang , Tuxiu Xie , Xiaobing Long , Guijun Jiang , Lulu Kang , Jie Jiang , Lu Ye , Liying Zhan , Xiaoxing Xiong , Jingjun Lyu 
Published: January 2022

BackgroundCardiac arrest/cardiopulmonary resuscitation (CA/CPR) represents one of the devastating medical emergencies and is associated with high mortality and neuro-disability. Post-cardiac arrest syndrome (PCAS) is mechanistically ascribed to acute systemic ischemia/reperfusion(I/R) injury. The lncRNA/microRNA/mRNA networks have been found to play crucial roles in the pathogenesis of the hypoxia-responsive diseases. Nonetheless, the precise molecular mechanisms by which lncRNA/miRNA/mRNA axes are involved in the astrocyte–microglia crosstalk in CA/CPR have not been fully elucidated.MethodsWe collected and purified the exosomes from the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. On the basis of microarray analysis, bioinformatic study, and luciferase activity determination, we speculated that lncRNA GAS5/miR-137 is implicated in the astrocyte–microglia crosstalk under the insult of systemic I/R injury. The regulation of lncRNA GAS5/miR-137 on INPP4B was examined by cellular transfection in OGD/R cell culture and by lateral ventricle injection with miR-137 agomir in CA/CPR mice model. Flow cytometry and immunofluorescence staining were performed to detect the microglial apoptosis, M1/M2 phenotype transformation, and neuroinflammation. Neurological scoring and behavior tests were conducted in CA/CPR group, with miR-137 agomir lateral-ventricle infusion and in their controls.ResultsIn all the micRNAs, miR-137 was among the top 10 micRNAs that experienced greatest changes, in both the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. Bioinformatic analysis revealed that miR-137 was sponged by lncRNA GAS5, targeting INPP4B, and the result was confirmed by Luciferase activity assay. qRT-PCR and Western blotting showed that lncRNA GAS5 and INPP4B were over-expressed whereas miR-137 was downregulated in the blood of CA/CPR patients, OGD/R-stimulated astrocytes, and brain tissue of CA/CPR mice. Silencing lncRNA GAS5 suppressed INPP4B expression, but over-expression of miR-137 negatively modulated its expression. Western blotting exhibited that PI3K and Akt phosphorylation was increased when lncRNA GAS5 was silenced or miR-137 was over-expressed. However, PI3K and Akt phosphorylation was notably suppressed in the absence of miR-137, almost reversing their phosphorylation in the silencing lncRNA GAS5 group. Then we found that GAS5 siRNA or miR-137 mimic significantly increased cell viability and alleviated apoptosis after OGD/R injury. Furthermore, over-expression of miR-137 attenuated microglial apoptosis and neuroinflammation in CA/CPR mice model, exhibiting significantly better behavioral tests after CA/CPR.ConclusionLncRNA GAS5/miR-137 may be involved in the astrocyte–microglia communication that inhibits PI3K/Akt signaling activation via regulation of INPP4B during CA/CPR.
l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats
Authors: Mao Xiangbing , Sun Rui , Wang Qingxiang , Chen Daiwen , Yu Bing , He Jun , Yu Jie , Luo Junqiu , Luo Yuheng , Yan Hui , Wang Jianping , Wang Huifen , Wang Quyuan 
Published: January 2022

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P &lt;0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P &lt;0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P &lt;0.05), shortened colonic length (P &lt;0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P &lt;0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P &lt;0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P &lt;0.05), DAI (P &lt;0.05), colonic length and enterocyte apoptosis (P &lt;0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P &lt;0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.
Novel Findings of Retinal and Choroidal Features Utilizing Optical Coherence Tomography Angiography Analysis in Patients With Autoimmune Posterior Uveitis
Authors: Shen Junhui , Kong Jinfeng , Chen Si , Liu Xin , Teng Yan , Wu Hailan , Wang Lijuan , Wu Manman , Su Zhaoan , Feng Lei 
Published: January 2022

Purpose: To analyze the quantitative parameters acquired by optical coherence tomography angiography (OCTA) in patients with autoimmune posterior uveitis.Methods: OCTA images of 65 eyes affected with uveitis and 65 normal control (NC) eyes were obtained. The central macular thickness (CMT), retinal thicknesses, foveal avascular zone (FAZ) area, foveal density 300 μm (FD300), and vascular density (VD) were compared among acute uveitic eyes, chronic uveitic eyes, and NC eyes. VDs were evaluated in the choriocapillaris, outer retina, optic disk, whole and parafovea superficial capillary plexus (SCP), and whole and parafovea deep capillary plexus (DCP). Correlation analysis was used to analyze the relationship between LogMAR best-corrected visual acuity (BCVA) and quantitative parameters from OCTA.Results: Compared with NC eyes, the CMT and retinal thicknesses were increased significantly in eyes with uveitis (p &lt; 0.05, respectively). No significant difference was observed in the FAZ area. FD300, VDs in the optic disk, SCP, and DCP both in whole image and parafovea, choriocapillaris were significantly decreased in uveitis eyes (p &lt; 0.05, respectively) compared with NC eyes, only the acute group had decreased VD of the outer retina and choriocapillaris compared with the NC group (p &lt; 0.05). Moreover, quantitative parameters of OCTA showed a significant correlation with LogMAR BCVA in the patients with uveitis. Whole VD DCP was the best predictive factor for BCVA in the patients with uveitis.Conclusion: Quantitative measurement by OCTA is a promising strategy for objective assessment of autoimmune posterior uveitis.
High-Frequency Repetitive Transcranial Magnetic Stimulation Over the Left Dorsolateral Prefrontal Cortex Shortly Alleviates Fatigue in Patients With Multiple System Atrophy: A Randomized Controlled Trial
Authors: Pan Jing , Mi Tao-Mian , Ma Jing-Hong , Sun Hong , Chan Piu 
Published: January 2022

Background: Fatigue is a common symptom in patients with Multiple system atrophy (MSA), but effective treatments remain elusive. The present study aims to investigate whether high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) could relieve fatigue in patients with MSA.Methods: This is a single-center, randomized and double-blind trial. Twenty-two patients with MSA and fatigue were randomly allocated to receive 10 sessions of either active (N = 11) or sham (N = 11) 10 Hz rTMS over the left DLPFC. The participants were assessed at baseline (T0), after the last session of treatment (T1), and at 2-week (T2), and 4-week (T3) follow-up timepoints. The primary outcomes were Fatigue Severity Scale-9 (FSS-9) scores, with Unified Multiple System Atrophy Rating Scale (UMSARS), 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) as secondary outcomes.Results: Two-way repeated ANOVAs revealed significant group × time interactions for FSS-9 scores (p &lt; 0.001), HAMD-17 scores (p = 0.01), HAMA scores (p = 0.01), and UMRSA part II (p = 0.05). Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FSS-9 and UMRSA part II scores at T1 and T2, but not at T3, and also in HAMD-17 and HAMA scores at T1, T2, and T3. No significant improvement was found in the sham group.Conclusion: High-frequency rTMS over the left DLPFC could provide short-term improvements for alleviating fatigue in patients with MSA, but the beneficial effects last no more than 4 weeks.
Social Isolation and Associated Factors in Chinese Adults With Epilepsy: A Cross-Sectional Study
Authors: Zhong Rui , Zhang Hanyu , Chen Qingling , Guo Xin , Han Yujian , Lin Weihong 
Published: January 2022

Objective: We aimed to determine the prevalence of social isolation and associated factors among adults with epilepsy in northeast China.Methods: A cohort of consecutive patients with epilepsy (PWE) from the First Hospital of Jilin University (Changchun, China) was recruited. Demographic and clinical data for each patient were collected during a face-to-face interview. Social isolation was measured using the Berkman-Syme Social Network Index (SNI), and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Quality of Life in Epilepsy Inventory (QOLIE-31) were also administered. Multivariate logistic regression analyses were used to determine the factors associated with social isolation in PWE.Results: A total of 165 patients were included in the final analysis. The mean SNI score was 2.56 (SD: 1.19), and 35 patients (21.2%) were socially isolated. In multivariate logistic regression analysis, higher depressive symptom levels (OR = 1.15, 95% CI: 1.003–1.318, P = 0.045) and poorer quality of life (OR = 0.967, 95% CI: 0.935–0.999, P = 0.047) emerged as independent factors associated with social isolation in PWE.Conclusion: Social isolation is common and occurs in approximately one-fifth of PWE. Social isolation is significantly associated with depressive symptoms and poor quality of life in PWE. Patients need to be encouraged to actively integrate with others and reduce social isolation, which may help improve their quality of life.
Differential Effects of One Meal per Day in the Evening on Metabolic Health and Physical Performance in Lean Individuals
Authors: Meessen Emma C. E. , Andresen Håvard , van Barneveld Thomas , van Riel Anne , Johansen Egil I. , Kolnes Anders J. , Kemper E. Marleen , Olde Damink Steven W. M. , Schaap Frank G. , Romijn Johannes A. , Jensen Jørgen , Soeters Maarten R. 
Published: January 2022

Background: Generally, food intake occurs in a three-meal per 24 h fashion with in-between meal snacking. As such, most humans spend more than ∼ 12–16 h per day in the postprandial state. It may be reasoned from an evolutionary point of view, that the human body is physiologically habituated to less frequent meals. Metabolic flexibility (i.e., reciprocal changes in carbohydrate and fatty acid oxidation) is a characteristic of metabolic health and is reduced by semi-continuous feeding. The effects of time-restricted feeding (TRF) on metabolic parameters and physical performance in humans are equivocal.Methods: To investigate the effect of TRF on metabolism and physical performance in free-living healthy lean individuals, we compared the effects of eucaloric feeding provided by a single meal (22/2) vs. three meals per day in a randomized crossover study. We included 13 participants of which 11 (5 males/6 females) completed the study: age 31.0 ± 1.7 years, BMI 24.0 ± 0.6 kg/m2 and fat mass (%) 24.0 ± 0.6 (mean ± SEM). Participants consumed all the calories needed for a stable weight in either three meals (breakfast, lunch and dinner) or one meal per day between 17:00 and 19:00 for 11 days per study period.Results: Eucaloric meal reduction to a single meal per day lowered total body mass (3 meals/day –0.5 ± 0.3 vs. 1 meal/day –1.4 ± 0.3 kg, p = 0.03), fat mass (3 meals/day –0.1 ± 0.2 vs. 1 meal/day –0.7 ± 0.2, p = 0.049) and increased exercise fatty acid oxidation (p &lt; 0.001) without impairment of aerobic capacity or strength (p &gt; 0.05). Furthermore, we found lower plasma glucose concentrations during the second half of the day during the one meal per day intervention (p &lt; 0.05).Conclusion: A single meal per day in the evening lowers body weight and adapts metabolic flexibility during exercise via increased fat oxidation whereas physical performance was not affected.