Miracle-dz/UniFAR-FTUs huggingface dataset:
Long non-coding RNA KCNQ1OT1 facilitates the progression of cervical cancer and tumor growth through modulating miR-296-5p/HYOU1 axis

ABSTRACT Literature reports that lncRNA KCNQ1OT1 is markedly up-regulated in cervical cancer (CC) tissues and cell lines, and KCNQ1OT1 can promote the proliferation and metastasis of CC cells. This current work was designed to investigate the molecular mechanism underlying the participation of KCNQ1OT1 in CC progression. Herein, RT-qPCR was utilized for determining the levels of KCNQ1OT1, miR-296-5p and HYOU1 in clinical tumor tissue specimens and CC cell lines. Then, starBase predicted the complementary binding sites of KCNQ1OT1 and miR-296-5p or miR-296-5p and HYOU1. Dual-luciferase reporter assay/RIP assay validated the interplays among KCNQ1OT1/miR-296-5p/HYOU1. In addition, CCK-8, wound healing and transwell assays were employed to assess the proliferative, migrative and invasive properties of CC cells. Moreover, nude mice xenograft model was established by subcutaneously injection with SiHa cells in order to validate the precise functions of KCNQ1OT1/miR-296-5p/HYOU1 axis in CC in vivo. Besides, Immunohistochemical staining examined Ki-67 expression in xenograft tumors and western blotting analysis detected expressions of MMP2/9 and Wnt/β-catenin signaling pathway in CC cells and xenograft tumors. Elevated KCNQ1OT1 and HYOU1 as well as reduced miR-296-5p were observed in clinical tumor tissue specimens and CC cell lines. Results revealed that upregulation of miR-296-5p counteracted the enhancing effects of overexpressed KCNQ1OT1 on the proliferative, migrative and invasive abilities of CC cells. Additionally, HYOU1 overexpression abolished the suppressing effects of silenced KCNQ1OT1 on the malignant behaviors of CC cells and tumor growth. To conclude, KCNQ1OT1 could aggravate the malignant behaviors of CC and facilitate tumor growth through modulating miR-296-5p/HYOU1 axis.
Microenvironment‐Responsive Prodrug‐Induced Pyroptosis Boosts Cancer Immunotherapy

The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency.
Combination therapy with PD-1 blockade and radiofrequency ablation for recurrent hepatocellular carcinoma: a propensity score matching analysis

Abstract Background This study aimed to evaluate whether combined therapy with PD-1 blockade (anti-PD-1) and radiofrequency ablation (RFA) is superior to RFA monotherapy for recurrent hepatocellular carcinoma (HCC). Methods A total of 127 patients who underwent anti-PD-1 plus RFA treatment (n = 41) or RFA alone (n = 86) for recurrent HCC were included in this retrospective study. A matched cohort comprising 40 patients from each group was selected after propensity score matching analysis. Clinical data including post-RFA HCC recurrence (primary endpoint), overall survival (OS) (secondary endpoint), adverse events, and toxic effects were retrospectively analyzed. Results The 1-year recurrence-free survival rates for the anti-PD-1 plus RFA and RFA groups were 32.5% and 10.0% after propensity score matching. There were statistically significant differences between the two groups in terms of the recurrence-free survival rate (p = 0.001) and OS rate (p = 0.016). Tumor number, tumor-node metastasis (TNM) stage, antiviral therapy, and anti-PD-1 treatment were demonstrated to be important factors associated with 1-year recurrence-free survival probability by univariate and multivariate analyses. Univariate and multivariate analyses demonstrated that tumor number, TNM stage and anti-PD-1 treatment were significant prognostic factors for OS. RFA treatment-related adverse events included pleural effusions that require drainage and a mild or moderate increase in body temperature. Grade 3 or higher events related to anti-PD-1 treatment occurred in 12.8% (6) of patients and were infrequent. Conclusions Combination therapy with anti-PD-1 plus RFA was superior to RFA alone in improving survival in patients with recurrent HCC. Graphical Abstract
The Surgeon’s Role in Inducing and Controlling Motion Errors During Intraocular Membrane Peeling Procedures

Objectives: To understand the surgeon’s role in inducing and correcting movement inaccuracies during intraocular membrane peeling procedures. Materials and Methods: Optical sensors were used to record movement errors during actuation at the distal tip of 23-gauge pneumatic forceps both when the handle was handheld and when fixed with no human contact. Movements were also recorded at the proximal part of the forceps shaft (near the sclerotomy site) and compared to movement recorded at the distal end. The root mean square (RMS) and range values of the signals obtained from the sensors were calculated before and after applying high (7-13 Hz) and low (<5 Hz) frequency filters. Results: Comparison of RMS and range values of movement errors at the distal end of the forceps during actuation when the forceps handle was fixed and handheld showed that without human contact, these values were significantly lower in the X axis at all frequencies and in the Z axis at high frequencies compared to handheld (p<0.05), while there were no significant differences in the Y axis. Comparison of values from the distal and proximal ends of the forceps showed that when the forceps were fixed, RMS and range values were significantly higher for movement errors at the distal end compared to the proximal end at all frequencies (p<0.05). There was significant positive correlation between the extent of actuation and the RMS and range values for high-frequency movement errors but not low-frequency errors in all three axes with the fixed pneumatic handle (r=0.21-0.51, p<0.05). Conclusion: Surgeon- and non-surgeon-related errors are apparent in all axes, but skilled surgeons correct these errors through visual feedback, resulting in better correction in the visible planes. Sclerotomy sites provide a pivoting and stabilizing point for the shaft of the forceps and it is likely that skilled surgeons make use of the sclerotomy point to dampen motion errors, a skill worth teaching to beginners.
Identifying immune subtypes of uterine corpus endometrial carcinoma and a four-paired-lncRNA signature with immune-related lncRNAs

Uterine corpus endometrial carcinoma (UCEC) is the third most frequent gynecological malignancies in the female reproductive system. Long non-coding RNAs (lncRNAs) are closely involved in tumor progression. This study aimed to develop an immune subtyping system and a prognostic model based on lncRNAs for UCEC. Paired lncRNAs and non-negative matrix factorization were applied to identify immune subtypes. Enrichment analysis was conducted to assess functional pathways, immune-related genes, and cells. Univariate and multivariate Cox regression analysis were performed to analyze the relation between lncRNAs and overall survival (OS). A prognostic model was constructed and optimized by least absolute shrinkage and selection operator (LASSO) and Akaike information criterion (AIC). Two immune subtypes (C1 and C2) and four paired-prognostic lncRNAs closely associated with overall survival were identified. Some immune features, sensitivity of chemotherapy and immunotherapy, and the relation with immune escape showed variations between two subtypes. A nomogram established based on prognostic model and clinical features was effective in OS prediction. The immune subtyping system based on lncRNAs and the four-paired-lncRNA signature was predictive of UCEC prognosis and can facilitate personalized therapies such as immunotherapy or RNA-based therapy for UCEC patients.
Turgor loss point and vulnerability to xylem embolism predict species‐specific risk of drought‐induced decline of urban trees

ABSTRACT Increasing frequency and severity of drought events is posing risks to trees' health, including those planted in urban settlements. Drought‐induced decline of urban trees negatively affects ecosystem services of urban green spaces and implies cost for maintenance and removal of plants. We aimed at identifying physiological traits that can explain and predict the species‐specific vulnerability to climate change in urban habitats. We assessed the relationships between long‐term risk of decline of different tree species in a medium‐sized town and their key indicators of drought stress tolerance, i.e. turgor loss point (TLP) and vulnerability to xylem embolism (P 50). Starting from 2012, the study area experienced several summer seasons with positive anomalies of temperature and negative anomalies of precipitation. This trend was coupled with increasing percentages of urban trees showing signs of crown die‐back and mortality. The species‐specific risk of decline was higher for species with less negative TLP and P 50 values. The relationship between species‐specific risk of climate change‐induced decline of urban trees and key physiological indicators of drought tolerance confirms findings obtained in natural forests and highlights that TLP and P 50 are useful indicators for species selection for tree plantation in towns, to mitigate negative impacts of climate change.
Iteratively Reweighted Minimax-Concave Penalty Minimization for Accurate Low-rank Plus Sparse Matrix Decomposition

Low-rank plus sparse matrix decomposition (LSD) is an important problem in computer vision and machine learning. It has been solved using convex relaxations of the matrix rank and l0-pseudo-norm, which are the nuclear norm and l1-norm, respectively. Convex approximations are known to result in biased estimates, to overcome which, nonconvex regularizers such as weighted nuclear-norm minimization and weighted Schatten p-norm minimization have been proposed. However, works employing these regularizers have used heuristic weight-selection strategies. We propose weighted minimax-concave penalty (WMCP) as the nonconvex regularizer and show that it admits an equivalent representation that enables weight adaptation. Similarly, an equivalent representation to the weighted matrix gamma norm (WMGN) enables weight adaptation for the low-rank part. The optimization algorithms are based on the alternating direction method of multipliers technique. We show that the optimization frameworks relying on the two penalties, WMCP and WMGN, coupled with a novel iterative weight update strategy, result in accurate low-rank plus sparse matrix decomposition. The algorithms are also shown to satisfy descent properties and convergence guarantees. On the applications front, we consider the problem of foreground-background separation in video sequences. Simulation experiments and validations on standard datasets, namely, I2R, CDnet 2012, and BMC 2012 show that the proposed techniques outperform the benchmark techniques.
Citrus heat shock transcription factor CitHsfA7-mediated citric acid degradation in response to heat stress.

Heat stress is a major abiotic stress for plants which can generate a range of biochemical and genetic responses. In "Ponkan" mandarin fruit, Hot Air Treatment (HAT) accelerates the degradation of citric acid. However, the transcriptional regulatory mechanisms of citrate degradation in response to HAT remain to be elucidated. Here, seventeen heat shock transcription factor sequences were isolated and dual-luciferase assays were employed to investigate whether the encoded proteins that could trans-activate the promoters of key genes in the GABA shunt, involved in citrate metabolism. We identified four heat shock transcription factors (CitHsfA7, CitHsfA3, CitHsfA4b and CitHsfA8) which showed trans-activation effects on CitAco3, CitIDH3 and CitGAD4, respectively. Transient expression of the CitHsfs in citrus fruits indicated that CitHsfA7 was the only factor that resulted in a significant lowering of the citric acid content, and these results were confirmed by a virus-induced gene silencing system (VIGS). Sub-cellar localization showed that CitHsfA7 is located in the nucleus and is capable of binding directly to a putative HSE in the CitAco3 promoter and enhance its expression. We proposed that the induction of CitHsfA7 transcript level contributes to citric acid degradation in citrus fruit, via modulation of CitAco3 in response to HAT. This article is protected by copyright. All rights reserved.
Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Objective This meta-analysis was conducted to investigate the relationship between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis (RA) susceptibility. Methods Eligible studies were retrieved from PubMed, Embase, and Web of Science. The fixed- or random-effects model was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) on the basis of heterogeneity. Results Overall, 11 studies containing 4019 RA patients and 4137 controls were included in this meta-analysis. The results suggested a significant association between the IL-17A rs2275913 polymorphism and RA susceptibility in the overall population (allelic model A vs. G: OR = 0.89, 95%CI: 0.83–0.95; heterozygote model GA vs. GG: OR = 0.87, 95%CI: 0.78–0.96; homozygote model AA vs. GG: OR = 0.82, 95%CI: 0.71–0.96; dominant model GA + AA vs. GG: OR = 0.86, 95%CI: 0.78–0.94). In the subgroup analyses, the IL-17A rs2275913 polymorphism was significantly associated with RA risk in Europeans (allelic model A vs. G: OR = 0.87, 95%CI: 0.78–0.97; heterozygote model GA vs. GG: OR = 0.79, 95%CI: 0.68–0.93; dominant model GA + AA vs. GG: OR = 0.79, 95%CI: 0.68–0.92), but not in Africans or Americans. Conclusion This study suggests that the IL-17A rs2275913 polymorphism is significantly associated with RA susceptibility in Europeans. INPLASY registration number: INPLASY202170056.
The preliminary effects of moderate aerobic training on cognitive function in people with TBI and significant memory impairment: a proof-of-concept randomized controlled trial

ABSTRACT This single-blinded RCT investigated cognitive effects of aerobic exercise in persons with TBI-related memory impairment. Five participants . were randomly assigned to 12-weeks of either supervised moderate intensity aerobic cycling or an active control. Outcome measures included neuropsychological assessments and structural neuroimaging (MRI,). The exercise group demonstrated greater improvements on auditory verbal learning (RAVLT; d=1.54) and processing speed (SDMT; d=1.58). The exercise group showed larger increases in volume of the left hippocampus (d=1.49) and right thalamus (d=1.44). These pilot data suggest that 12-weeks of moderate intensity aerobic cycling may improve memory and processing speed in those with TBI-related memory impairments.
Pseudo Pelger-Huët anomalies as potential biomarkers for acute exposure radiation dose in rhesus macaques (Macaca mulatta)

Abstract Purpose The potential for malicious use of radiation, or radiation accidents could potentially lead to acute, high radiation doses to the public. Following acute accidental exposure to high doses of radiation, medical intervention is pivotal to the survivability of the patient, and the sooner the appropriate measures are taken the better the odds for survival. Early estimates of acute accidental radiation doses can be determined via biomarkers such as dicentric chromosome analysis or scenario reconstruction using computer software. However, both take valuable time and can be expensive. Increased frequencies of abnormal neutrophils in peripheral blood, referred to as pseudo Pelger-Huët anomalies (PPHAs), have been shown to be potential biomarkers of radiation exposure in several scenarios, including the 1958 Y-12 criticality accident and the radium dial painters. PPHAs are potentially a faster and cheaper quantitative biomarker for radiation exposure, and here they were evaluated in acutely exposed rhesus macaques. Methods and materials Peripheral blood smears from acutely exposed rhesus macaques were evaluated for the percentage of neutrophils that displayed the PPHA morphology using light microscopy. Irradiated animals received 0 to 8.5 Gy total body radiation using one of two strategies: (1) linear accelerator-produced 6 MV photons delivered at 80 cGy/minute; or (2) Cobalt 60-produced gamma irradiation delivered at 60 cGy/min. Zero dose animals were used to determine a baseline percentage of PPHAs, and blood smears taken periodically throughout the lifetime of exposed animals post-irradiation were used to determine the persistence and biokinetics of PPHAs. Results The baseline prevalence of the PPHA in rhesus macaques was determined to be 0.58 ± 0.46%. The dose-response curve with doses ranging from 0 Gy to 8.5 Gy (LD90/30) displayed a strong positive correlation between PPHA percentage and acute radiation dose (R 2 of 0.88 p = 3.62 × 10−22). Statistically significant differences were found when animals were separated into dose cohorts of 0, 4, 6.4–6.5, and 8–8.5 Gy. The biokinetics model utilized only 4 Gy exposures and blood smears taken periodically over 3.1 years post-irradiation. PPHA morphology increases quickly following irradiation and appears stable over 3.1 years post-irradiation. Conclusion PPHA morphology was confirmed to be present in rhesus macaques, a dose-response relationship was constructed, and it is stable over 3 years post-irradiation. This study demonstrates that PPHA analysis can be a fast and cheap method of biodosimetry. Future studies will work to determine the accuracy of dose determination and lower limits of detection.
Electron-deficient TVT unit-based D–A polymer donor for high-efficiency thick-film OSCs

As the power conversion efficiencies of organic solar cells (OSCs) have been improved continuously in recent years, more attention will be paid to the industrial production and practical application of OSCs. However, there are still many problems to be solved in the process of large-scale production. Among them, reducing the costs of the materials and enhancing the film-thickness tolerance of the active layer are the two key points. Therefore, it is urgent to develop organic semiconductor materials which are easy to synthesize and suitable for the construction of high-efficiency, thick-film OSCs. In this work, we have focused on the (E)−2-[2-(thiophen-2-yl)vinyl]thiophene (TVT) unit because of its unique coplanar structure. And we noticed that TVT was mostly used as an electron-donating unit in the previous reports. However, we have modified TVT into electron-withdrawing unit by the introduction of fluorine atoms/ester groups. And two new donor–acceptor (D–A) copolymers have been obtained by combining the electron-withdrawing TVT unit with benzo[2,1-b:4,5-b′]dithiophene (BDT) unit. Among them, the polymer based on the ester modified TVT unit presents excellent photovoltaic performance by virtue of its good solubility and preferable molecular stacking mode, and the corresponding devices also show extraordinarily high-thickness tolerance. The emergence of this new electron-withdrawing TVT unit will undoubtedly further promote the development of low-cost, high-efficiency, thick-film OSCs.
Protection and safety of a repeated dosage of KI for iodine thyroid blocking during pregnancy

In case of nuclear power plant accidents resulting in the release of radioactive iodine (131I) in large amounts, a single intake of stable iodine is recommended in order to prevent 131I fixation to the thyroid gland. However, in situations of prolonged exposure to 131I (e.g. Fukushima-Daiichi natural and nuclear disaster), repetitive administration of iodine may be necessary to ensure adequate protection, with acceptable safety in vulnerable populations including pregnant women. Here we conducted toxicological studies on adult rats progeny following prolonged exposure to potassium iodide (KI) in utero. Pregnant Wistar rats were treated with 1 mg kg d−1 KI or saline water for 2 or 4 d either between gestation days gestational day (GD) GD 9–12, or GD13–16. Plasma samples from the progeny were tested 30 d post-weaning for clinical biochemistry, thyroid hormones, and anti-thyroid antibody levels. Thyroid and brain were collected for gene expression analysis. The hormonal status was similar for the mothers in all experimental conditions. In the offspring, while thyroid-stimulating hormone and anti-thyroid peroxidase (anti-TPO) antibody levels were similar in all groups, a significant increase of FT3 and FT4 levels was observed in GD9–GD10 and in GD13–GD14 animals treated for 2 d, respectively. In addition, FT4 levels were mildly decreased in 4 d treated GD13–16 individuals. Moreover, a significant decrease in the expression level of thyroid genes involved in iodide metabolism, TPO and apical iodide transporter, was observed in GD13–GD14 animals treated for 2 d. We conclude that repeated KI administration for 2–4 d during gestation did not induce strong thyroid toxicity.
Characterization of Postural Sway in Patients With Persistent Postural-Perceptual Dizziness (PPPD) Using Wearable Motion Sensors

Objective: To extend previous investigations of postural control in patients with persistent-postural perceptual dizziness (PPPD). Study Design: Case-controlled, cross-sectional, observational investigation. Setting: Tertiary care center. Patients: Fifteen patients with PPPD, 15 control volunteers. Interventions: Measurement of anterior-posterior (AP) and medial-lateral (ML) sway at the waist using wearable accelerometers during posturography; assessment of reach and gait. Main Outcome Measures: Peak-to-peak AP and ML sway displacement on the six conditions of the Sensory Organization Test (SOT); Scores on the SOT, Functional Reach Test (FRT), and Dynamic Gait Index (DGI). Results: Compared to control volunteers, patients with PPPD had significantly greater sway displacement at the waist in the AP direction in SOT conditions 3, 5, and 6 and in the ML direction in SOT conditions 2 and 4, resulting in significantly lower median equilibrium scores on the composite index and all six SOT conditions. Patients with PPPD had significantly lower scores on the FRT and DGI that were not correlated with SOT performance. AP sway in conditions 3 and 6 differentiated patients with PPPD from controls with high sensitivity (≥0.87) and specificity (≥0.87). Conclusions: This study replicated previous work showing poor SOT performance by patients with PPPD who had greater AP sway associated with visual dependence and greater ML sway in low demand conditions than controls. Patients with PPPD also performed poorer on the FRT and DGI, but lack of correlation with SOT scores suggested different mechanisms of impairment in postural control, reach, and ambulation. AP sway demonstrated potential as a diagnostic marker.