Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells

Background Much attention has been paid to the regulatory role of microRNA (miRNA) in insulin resistance. Nevertheless, how miR-140-5p regulates insulin resistance remains unclear. In this research, we aim to investigate the roles of miR-140-5p in insulin resistance. Methods qRT-PCR is used to analyze the expression level of miR-140-5p in insulin-resistant HepG2 cells. Glucose consumption and glucose uptake are detected to study the effect of miR-140-5p knockdown in insulin-resistant HepG2 cells and miR-140-5p overexpression in HepG2 cells. Bioinformatic analysis, luciferase reporter assay and confirmatory experiments are applied to identify the target gene bound with miR-140-5p and study the effect of miR-140-5p on the downstream substrates of target genes. Rescue experiments have verified the roles of miR-140-5p and target gene in glucose metabolism. Results The expression level of miR-140-5p was upregulated in insulin-resistant HepG2 cells and was significantly correlated with cellular glucose metabolism. Functionally, miR-140-5p overexpression induced impairment of glucose consumption and glucose uptake. Besides, bioinformatics analysis indicated that glycogen synthetase (GYS1) and protein phosphatase 1 catalytic subunit gamma (PPP1CC) were the target genes of miR-140-5p. Western blotting and qRT-PCR results revealed a negative correlation between GYS1, PPP1CC and miR-140-5p. The glycogen detection results showed that miR140-5p inhibited the production of the downstream substrates of the target gene. Rescue experiments showed that inhibition of GYS1 or PPP1CC partially enhanced the insulin-resistant effects of miR-140-5p knockdown in insulin-resistant HepG2 cells. Conclusion miR-140-5p overexpression augments the development of insulin resistance and miR-140-5p may be served as a therapeutic target of metabolic diseases.
Nested Case–Control Study of Corin Combined with sFlt-1/PLGF in Predicting the Risk of Preeclampsia

Background Preeclampsia (PE), a serious pregnancy disorder, is responsible for maternal and fetal mortality worldwide. At present, numerous candidate biomarkers have been studied to predict PE. Objective To explore the role of Corin in PE risk prediction and then evaluate the predictive ability of soluble vascular endothelial growth factor receptor-1 (sFlt-1), placenta growth factor (PLGF), and sFlt-1/PLGF after the addition of Corin. Methods A total of 135 pregnant women from Affiliated Hospital of Shandong University of Traditional Chinese Medicine participated in this study in their first trimester. A nested case–control study was conducted and all subjects were divided into PE groups (n=46) and controls (n=89). The levels of PLGF, sFlt-1, sFlt-1/PLGF ratio, and Corin of the two groups at 12–16 weeks of gestation were measured and analyzed. Receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the predictive ability of various biomarkers. Results The concentrations of sFlt-1, sFlt-1/PLGF, and Corin in PE group were significantly higher than that in controls, while the concentration of PLGF in the PE group was lower. The area under curve (AUC) of sFlt-1, PLGF and sFlt-1/PLGF for predicting PE was 0.786, 0.719 and 0.866, respectively. Combined with Corin, the prediction ability of the above biomarkers could be improved to 0.876, 0.847, and 0.897, respectively. Corin in combination with sFlt-1/PLGF resulted in improvements with 12.6% being reclassified and a resulting NRI of 0.142 (0.020~0.263) and IDI of 0.087 (0.037~0.137). Conclusion The addition of Corin to sFlt-1, PLGF and sFlt-1/PLGF can improve the ability of each marker to predict PE risk. Corin in combination with sFlt-1/PLGF can be used as ideal markers to identify the pregnant women who subsequently develop PE, which will help in risk stratification and better therapeutic management.
ETOILE: Real-World Evidence of 24 Months of Ranibizumab 0.5 mg in Patients with Visual Impairment Due to Diabetic Macular Edema

Purpose To evaluate the real-world effectiveness of intravitreal ranibizumab 0.5 mg (Lucentis) in improving visual acuity (VA) in adults with decreased VA due to diabetic macular edema (DME). Patients and Methods Real-world prospective observational 24-month study. Ranibizumab-naïve patients (n=116) were enrolled, treated and followed up according to investigators’ usual procedures. Outcomes included change from baseline to month 24 in best-corrected VA (BCVA; primary outcome), central retinal thickness (CRT), treatment exposure and safety. Results Overall, 62.9% of patients completed the study per protocol, 68.6% completed the induction phase (first three injections one month apart). On average, patients had 12.5 ophthalmologist visits and 5.74 injections in year 1, decreasing to 4.6 visits and 1.94 injections in year 2. Mean baseline BCVA was 58.4 letters, mean gain at M24 was +6.08 letters (95% CI: 2.95, 9.21). Gains were higher for patients who completed induction, and for patients who did not switch treatment. Mean CRT improved by 149.17 μm at M24. There were no new safety signals. BCVA variation of ≥6 letters by M3 was predictive of BCVA gains at M24 (p=0.007), as was hypertension medication at baseline (p=0.022). Conclusion Real-world ranibizumab treatment improved VA in DME patients, despite fewer injections than recommended.
Can Plasma α-Synuclein Help Us to Differentiate Parkinson’s Disease from Essential Tremor?

Background: Studies have revealed controversial results regarding the diagnostic accuracy of plasma α-synuclein levels in patients with Parkinson’s disease (PD). This study was aimed to analyze the diagnostic accuracy of plasma α-synuclein in PD versus healthy controls and patients with essential tremor (ET). Methods: In this cross-sectional study, we included de novo (n = 19) and advanced PD patients [OFF (n = 33), and On (n = 35) states], patients with ET (n = 19), and controls (n = 35). The total plasma α-synuclein levels were determined using an ELISA sandwich method. We performed adjusted multivariate regression analysis to estimate the association of α-synuclein levels with group conditions [controls, ET, and de novo, OFF and ON-PD]. We studied the diagnostic accuracy of plasma α-synuclein using the area under the curve (AUC). Results: The plasma α-synuclein levels were higher in controls compared to PD and ET (p < 0.0001), discriminating de novo PD from controls (AUC = 0.74, 95% CI 0.60–0.89), with a trend towards in advanced PD (OFF state) from ET (AUC = 0.69, 95% CI 0.53–0.84). Conclusions: This is the first study examining and comparing plasma α-synuclein levels in ET vs. PD and controls. Preliminary findings suggest that plasma α-synuclein levels might help to discriminate de novo and advanced PD from controls and ET.
Pulsed Electric Field (PEF) Enhances Iron Uptake by the Yeast Saccharomyces cerevisiae

The aim of the study was to investigate the influence of a pulsed electric field (PEF) on the level of iron ion accumulation in Saccharomyces cerevisiae cells and to select PEF conditions optimal for the highest uptake of this element. Iron ions were accumulated most efficiently when their source was iron (III) nitrate. When the following conditions of PEF treatment were used: voltage 1500 V, pulse width 10 μs, treatment time 20 min, and a number of pulses 1200, accumulation of iron ions in the cells from a 20 h-culture reached a maximum value of 48.01 mg/g dry mass. Application of the optimal PEF conditions thus increased iron accumulation in cells by 157% as compared to the sample enriched with iron without PEF. The second derivative of the FTIR spectra of iron-loaded and -unloaded yeast cells allowed us to determine the functional groups which may be involved in metal ion binding. The exposure of cells to PEF treatment only slightly influenced the biomass and cell viability. However, iron-enriched yeast (both with or without PEF) showed lower fermentative activity than a control sample. Thus obtained yeast biomass containing a high amount of incorporated iron may serve as an alternative to pharmacological supplementation in the state of iron deficiency.
Hierarchical Topology-Based Cluster Representation for Scalable Evolutionary Multiobjective Clustering

Evolutionary multiobjective clustering (MOC) algorithms have shown promising potential to outperform conventional single-objective clustering algorithms, especially when the number of clusters $k$ is not set before clustering. However, the computational burden becomes a tricky problem due to the extensive search space and fitness computational time of the evolving population, especially when the data size is large. This article proposes a new, hierarchical, topology-based cluster representation for scalable MOC, which can simplify the search procedure and decrease computational overhead. A coarse-to-fine-trained topological structure that fits the spatial distribution of the data is utilized to identify a set of seed points/nodes, then a tree-based graph is built to represent clusters. During optimization, a bipartite graph partitioning strategy incorporated with the graph nodes helps in performing a cluster ensemble operation to generate offspring solutions more effectively. For the determination of the final result, which is underexplored in the existing methods, the usage of a cluster ensemble strategy is also presented, whether $k$ is provided or not. Comparison experiments are conducted on a series of different data distributions, revealing the superiority of the proposed algorithm in terms of both clustering performance and computing efficiency.
An updated meta-analysis of partial splenic embolization versus splenectomy in the treatment of hypersplenism due to cirrhosis

Abstract Objective To evaluate the efficacy and safety of partial splenic embolization (PSE) versus splenectomy (SP) for hypersplenism. Material and methods Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Science and Technology Periodical Database (VIP) databases were systematically searched to identify all relevant studies. Stratified meta-analysis was also conducted to control the influence of confounding factors on the research results Results Twenty-three studies comparing PSE with SP involving a total of 1849 hypersplenism patients were selected. Postoperative increased level of platelet (PLT) [mean difference (MD) = −65.51; 95% confidence interval (CI), −81.33 to −41.69; p < . 00001] were better in SP than in PSE; however, PSE was associated with less operation time (MD = −53.47; 95% CI, −65.01 to −41.94; p < .00001), less intraoperative blood loss (MD = −61.58; 95% CI, −80.35 to −42.82; p < .00001), shorter hospital stay (MD = −2.98;95% CI, −4.07 to −1.88; p < .00001) and lower complication rate [odds ratio (OR) = 0.53; 95% CI, 0.32 to 0.90; p = . 02] compared with the SP. Meanwhile, there was no significant difference in postoperative increased level of white blood cells (WBC) (MD = −1.02; 95% CI, −2.16 to 0.11; p = .08) and postoperative increased level of hemoglobin (HB) (MD = −4.09; 95% CI, −14.06 to 5.88; p = .42) between PSE and SP group. Conclusion PSE had similar efficacy with SP in improving postoperative PLT, WBC, and HB levels. Moreover, PSE had the advantages of less trauma and fewer complications as well as faster recovery when compared with SP. Therefore, we tended to be cautious about SP and considered that patients with hypersplenism might benefit more from PSE.
The stability of R-spine defines RAF inhibitor resistance: A comprehensive analysis of oncogenic BRAF mutants with in-frame insertion of αC-β4 loop

The stabilized R-spine of oncogenic BRAF mutants impairs RAF inhibitor association and confers drug resistance. Although targeting BRAF mutants with RAF inhibitors has achieved promising outcomes in cancer therapy, drug resistance remains a remarkable challenge, and underlying molecular mechanisms are not fully understood. Here, we characterized a previously unknown group of oncogenic BRAF mutants with in-frame insertions (LLRins506 or VLRins506) of αC-β4 loop. Using structure modeling and molecular dynamics simulation, we found that these insertions formed a large hydrophobic network that stabilizes R-spine and thus triggers the catalytic activity of BRAF. Furthermore, these insertions disrupted BRAF dimer interface and impaired dimerization. Unlike BRAF(V600E), these BRAF mutants with low dimer affinity were strongly resistant to all RAF inhibitors in clinic or clinical trials, which arises from their stabilized R-spines. As predicted by molecular docking, the stabilized R-spines in other BRAF mutants also conferred drug resistance. Together, our data indicated that the stability of R-spine but not dimer affinity determines the RAF inhibitor resistance of oncogenic BRAF mutants.
A noninvasive diagnostic model for significant liver fibrosis in patients with chronic hepatitis B based on CHI3L1 and routine clinical indicators.

BACKGROUND In consideration of the limitations of liver biopsy, the past years have seen a great advance in the application of noninvasive indices in assessing liver fibrosis. However, the accuracies of the existing indices to determine liver fibrosis in patients with chronic hepatitis B (CHB) are still unsatisfactory. Here, we established a noninvasive diagnostic model for assessing significant liver fibrosis (SLF) in CHB patients based on serum chitinase 3-like 1 (CH3L1) and routine clinical indicators. METHODS The clinical data of 337 CHB patients treated at Xiamen Hospital of Traditional Chinese Medicine from December 1, 2019, to September 30, 2020, were collected in this cross-sectional study. All the enrolled cases were randomly divided into a training cohort (n=270) and a validation cohort (n=67). The training cohort was further divided into a non-significant liver fibrosis (NSLF) group (stages S0-S1; n=189; used as the control group) and an SLF group (stage S2-S4; n=81) based on the Scheuer scoring system. Univariate and multivariate logistic regression analyses were performed to screen for independent predictors of SLF in CHB patients and to establish a diagnostic model. RESULTS The results of univariate and multivariate logistic regression analysis showed that CHI3L1, AFP and PLT were independent predictors of SLF in CHB patients, and the diagnostic model was established as follows: CHI3L1/AFP/PLT (CAP) = 0.600 × CHI3L1/upper limit of normal (ULN) + 0.252 × AFP/ULN - 1.424 × PLT/lower limit of normal (LLN) - 1.223. The area under the receiver operating characteristic (AUROC) of this model for the diagnosis of SLF in the training cohort and the validation cohort was 0.805 and 0.819, respectively, showing no statistically significant difference (P>0.05), and the AUROC for the diagnosis of SLF in the whole cohort was significantly higher than those of other noninvasive markers including aspartate transaminase to platelet ratio index (APRI), fibrosis 4 score (FIB-4) and CHI3L1 (all P<0.05). CONCLUSIONS The newly established model has a good diagnostic efficacy for SLF in CHB patients and is superior to other noninvasive markers including APRI, FIB-4, and CHI3L1. Thus, it can be used as a noninvasive diagnostic index for liver fibrosis in CHB patients.
Resemblance in Physical Activity in Families with Children in Time Segments during the Week: The Lolland–Falster Health Study

ABSTRACT Purpose Evidence of shared physical activity (PA) habits within families is inconsistent. The present study aimed at examining intrafamily resemblance in PA during different time segments of the week. Method This cross-sectional study used data from the Danish household-based population study Lolland–Falster Health Study. We assessed time spent in various PA intensities and behaviors using a dual-accelerometer system (Axivity AX3). At least one parent and one child per household provided data for a minimum of three weekdays and one weekend day. We analyzed three time segments: early weekdays, late weekdays, and weekends. A linear mixed model regression analysis was used to estimate intraclass correlation coefficients (ICC) of the total family, parent–child dyads, siblings, and parent–parent dyads for PA outcomes, adjusting for sex, age, parental education, and the interaction between sex and age. Results We included 774 parents (57.9% female, 42.8 ± 7 yr) and 802 children (54.2% girls, 11.1 ± 4.3 yr) nested within 523 families. The clustering among the total family was stronger during late weekdays (ICC = 0.11–0.31) and weekends (ICC = 0.14–0.29) than during early weekdays (ICC = 0.02–0.19). We found stronger clustering among siblings (ICC = 0.08–0.47) and between parents (ICC = 0.02–0.52) than between parents and children (ICC < 0.01–0.37). Generally, the clustering was strongest for light PA, and among PA behaviors, walking showed the highest resemblance across all subgroups. Conclusion Initiatives to promote children’s PA that involve parent or sibling coparticipation may focus on the time segment and activity types with the highest resemblance. For the family as a whole, promoting walking or limiting sedentary activities may be a potential target for interventions during late weekdays and weekends. Trial registration: Clinicaltrials.gov (NCT02482896).
The tobacco phosphatidylethanolamine‐binding protein NtFT4 simultaneously improves vitality, growth, and protein yield in human cells

The production of biopharmaceutical proteins in mammalian cells by transient expression or stable transformation requires robust and viable cells. Cell line engineering must therefore balance improved cell growth and viability with high productivity. We tested the ability of nonmammalian phosphatidylethanolamine‐binding proteins to enhance cell proliferation in monolayers and suspension cultures. The tobacco protein NtFT4 improved the proliferation of multiple human cell lines. Viable cell density is usually impaired by efficient transfection, but we found that the number of HEK‐293TNtFT4 cells at the peak of protein expression was twice that of standard HEK‐293T cells, and the antibody yield increased by approximately one‐third. Improved growth and viability were observed in different cell lines, in different culture media, and also after transient transfection, suggesting the beneficial trait is consistent and transferable. Additional modifications could boost the productivity of high‐density HEK‐293TNtFT4 cells even further as we showed for a fluorescent marker protein and recombinant antibody expressed in monolayer cultures. The HEK‐293TNtFT4 cell line provides a new human model platform that increases cell proliferation, also achieving a fundamental improvement in recombinant protein expression.
Balancing selection maintains ancient polymorphisms at conserved enhancers for the olfactory receptor genes of a Chinese marine fish

The study of balancing selection, as a selective force maintaining adaptive genetic variation in gene pools longer than expected by drift, is currently experiencing renewed interest due to the increased availability of new data, methods of analysis, and case studies. In this investigation, evidence of balancing selection operating on conserved enhancers of the olfactory receptor (OR) genes is presented for the Chinese sleeper (Bostrychus sinensis), a coastal marine fish that is emerging as a model species for evolutionary studies in the Northwest Pacific marginal seas. Coupled with tests for Gene Ontology enrichment and transcription factor binding, population genomic data allow for the identification of an OR cluster in the sleeper with a downstream flanking region containing three enhancers that are conserved with human and other fish species. Phylogenetic and population genetic analyses indicate that the enhancers are under balancing selection as evidenced by their translineage polymorphisms, excess common alleles, and increased within‐group diversities. Age comparisons between the translineage polymorphisms and most recent common ancestors of neutral genealogies substantiate that the former are old, and thus, due to ancient balancing selection. The survival and reproduction of vertebrates depend on their sense of smell, and thereby, on their ORs. In addition to locus duplication and allelic variation of structural genes, this study highlights a third mechanism by which receptor diversity can be achieved for detecting and responding to the huge variety of environmental odorants (i.e., by balancing selection acting on OR gene expression through their enhancer variability).
Culturally modified olfactory test adapted to East‐Turkey: A comparison with Sniffin’ Sticks

Although the “Sniffin’ Sticks” test (SST) is a widely used odor test, aplicability of odor tests is limited because of the high cost of the test and the regional‐cultural differentiation of odor recognition. We aimed to evaluate our regional odor norms by applying the SST with a Modified odor test (MOT) we created for this study, and to develop a test similar to the SST, which was less expensive and probably had a higher odor definition for our region.
Folate-Conjugated Polylactic Acid-Silica Hybrid Nanoparticles as Degradable Carriers for Targeted Drug Delivery, On-Demand Release and Simultaneous Self-Clearance.

Improving the therapeutic efficacy of cancer chemotherapy and reducing the side effects in patients are appealing goals but represent critical challenges. In this work, a novel SiO2 -based nanocarrier coated with polylactic acid and folate has been fabricated to destroy tumors in vivo. Folic acid promotes the targeted intracellular delivery of drug molecules to cancer cells overexpressing the folate receptor for improving the efficacy of the therapy. The polylactic acid layer prevents the premature leakage of drug until the polylactic acid is degraded as a response to low pH and enzymes; this mechanism is designed for sustained and on-demand drug release to prevent undesired side effects. Escape of the drug molecules then triggers decomposition of the SiO2 carrier, improving its elimination from the patient. The strategy of combining the engineering flexibility of inorganic nanocarriers with the stimuli-responsive biodegradability of organic molecules will offer new directions in on-demand and sustained drug release for chemotherapy.