Understanding the impacts of street greening patterns and wind directions on the dispersion of fine particles.

Inappropriate planting patterns can increase pollutant concentrations and threaten human health. This study examined three greening patterns (trees, trees + hedges, and hedges) using the ENVI-met model to evaluate the different effects of various planting patterns on PM2.5 dispersion within an idealized 3D street canyon under three typical wind directions. Results showed that street greenbelts alter the PM2.5 concentration field within canyons, and the horizontal and vertical distribution characteristics of PM2.5 under different wind directions were significantly different. The arbor-hedge vegetation structure showed the highest total vegetation deposition amount due to larger canopy volumes while hedges have better deposition amounts per unit volume due to their proximity to emission sources. Additionally, this research selected the averaged relative difference in PM2.5 concentration (ARDC) indicator to assess the influence of different green scenarios on the dispersion of PM2.5 concentrations. Wind direction and planting patterns jointly affect the dispersion of PM2.5 in canyons, and the ARDC varied from -4.39 % to 105.36 %. Unilateral-trees on the windward side or two rows of hedges may be the optimal vegetation layout by trade-off with other services. ARDC was significantly correlated (p < 0.01) with most of the 3D green indicators. These results could provide effective suggestions for optimizing the layout of greenbelts in street canyons to improve air quality.

A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis.

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

Unilateral Plyometric Jump Training Shows Significantly More Effective than Bilateral Training in Improving Both Time to Stabilization and Peak Landing Force in Single-Leg Lend and Hold Test: A Randomized Multi-Arm Study Conducted Among Young Male Basketball Players.

Enhancing peak landing forces and ensuring faster stabilization in the lower limbs during jumping activities can significantly improve performance and decrease the risk of injury among basketball players. This study aimed to compare the effects of unilateral (uPJT) and bilateral plyometric jump training (bPJT) programs on various performance measures, including countermovement jump (CMJ), squat jump (SJ), and single-leg land and hold (SLLH) test outcomes, assessed using force plates. A randomized multi-arm study design was employed, comprising two experimental groups (n = 25; uPJT and n = 25; bPJT) and one control group (n = 25), conducted with youth male regional-level basketball players (16.3 ± 0.6 years old). Participants underwent assessment twice, both before and after an 8-week intervention training period. The uPJT program exclusively involved plyometric drills (e.g., vertical jump exercises; horizontal jump exercises) focusing on single-leg exercises, whereas the bPJT program utilized drills involving both legs simultaneously. The outcomes analyzed included CMJ peak landing force, CMJ peak power, SJ peak force, SJ maximum negative displacement, SLLH time to stabilization, and SLLH peak landing force. The control group exhibited significantly greater SLLH time to stabilization compared to both the uPJT (p < 0.001) and bPJT (p < 0.030) groups. Additionally, time to stabilization was also significantly higher in bPJT than in uPJT (p = 0.042). Comparisons between groups in regards SLLH peak landing force after intervention revealed that the value was significantly smaller in uPJT than in bPJT (p = 0.043) and control (p < 0.001). In the remaining outcomes of CMJ and SJ, both uPJT and bPJT showed significant improvement compared to the control group (p > 0.05), although there was no significant difference between them. In conclusion, our study suggests that utilizing uPJT is equally effective as bPJT in enhancing performance in bilateral jump tests. However, it significantly outperforms bPJT in improving time to stabilization and peak landing forces during single-leg land and hold test. uPJT could be advantageous not for maximizing performance but also for potentially decreasing injury risk by enhancing control and balance during single-leg actions, which are common in basketball.

Combination of Channel Reordering Strategy and Dual CNN-LSTM for Epileptic Seizure Prediction Using Three iEEG Datasets.

OBJECTIVE: Intracranial electroencephalogram (iEEG) signals are generally recorded using multiple channels, and channel selection is therefore a significant means in studying iEEG-based seizure prediction. For n channels, 2n-1 channel cases can be generated for selection. However, by this means, an increase in n can cause an exponential increase in computational consumption, which may result in a failure of channel selection when n is too large. Hence, it is necessary to explore reasonable channel selection strategies under the premise of controlling computational consumption and ensuring high classification accuracy. Given this, we propose a novel method of channel reordering strategy combined with dual CNN-LSTM for effectively predicting seizures. METHOD: First, for each patient with n channels, interictal and preictal iEEG samples from each single channel are input into the CNN-LSTM model for classification. Then, the F1-score of each single channel is calculated, and the channels are reordered in descending order according to the size of F1-scores (channel reordering strategy). Next, iEEG signals with an increasing number of channels are successively fed into the CNN-LSTM model for classification again. Finally, according to the classification results from n channel cases, the channel case with the highest classification rate is selected. RESULTS: Our method is evaluated on the three iEEG datasets: the Freiburg, the SWEC-ETHZ and the American Epilepsy Society Seizure Prediction Challenge (AES-SPC). At the event-based level, the sensitivities of 100%, 100% and 90.5%, and the false prediction rates (FPRs) of 0.10/h, 0/h and 0.47/h, are achieved for the three datasets, respectively. Moreover, compared to an unspecific random predictor, our method also shows a better performance for all patients and dogs from the three datasets. At the segment-based level, the sensitivities-specificities-accuracies-AUCs of 88.1%-94.0%-93.5%-0.9101, 99.1%-99.7%-99.6%-0.9935, and 69.2%-79.9%-78.2%-0.7373, are attained for the three datasets, respectively. CONCLUSION: Our method can effectively predict seizures and address the challenge of an excessive number of channels during channel selection.

Human yolk sac-derived innate lymphoid-biased multipotent progenitors emerge prior to hematopoietic stem cell formation.

Hematopoietic stem cell (HSC)-independent lymphopoiesis has been elucidated in murine embryos. However, our understanding regarding human embryonic counterparts remains limited. Here, we demonstrated the presence of human yolk sac-derived lymphoid-biased progenitors (YSLPs) expressing CD34, IL7R, LTB, and IRF8 at Carnegie stage 10, much earlier than the first HSC emergence. The number and lymphopoietic potential of these progenitors were both significantly higher in the yolk sac than the embryo proper at this early stage. Importantly, single-cell/bulk culture and CITE-seq have elucidated the tendency of YSLP to differentiate into innate lymphoid cells and dendritic cells. Notably, lymphoid progenitors in fetal liver before and after HSC seeding displayed distinct transcriptional features, with the former closely resembling those of YSLPs. Overall, our data identified the origin, potential, and migratory dynamics of innate lymphoid-biased multipotent progenitors in human yolk sac before HSC emergence, providing insights for understanding the stepwise establishment of innate immune system in humans.

Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis.

Alternative polyadenylation (APA) is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites (PASs). APA is involved in lymphocyte activation; however, its role throughout the entire differentiation trajectory remains elusive. Here, we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells (HSPCs) to terminally differentiated lymphocytes. This analysis covered 19973 cells of 12 clusters from five lineages (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, and plasmacytoid dendritic cells). A total of 2364 genes exhibited differential 3'UTR PAS usage, and 3021 genes displayed differential intronic cleavage during lymphoid differentiation. We observed a global trend of 3'UTR shortening during lymphoid differentiation. Nevertheless, specific events of both 3'UTR shortening and lengthening were also identified within each cluster. The APA patterns delineated three differentiation stages: HSPCs, precursor cells, and mature cells. Moreover, we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes (TCF7 and NFATC2IP), immune function-related genes (BCL2, CD5, CD28, GOLT1B, and TMEM59), and protein ubiquitination-related genes (UBE2G1, YPEL5, and SUMO3). These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.

Microdosing Plyometric Training Enhances Jumping Performance, Reactive Strength Index, and Acceleration among Youth Soccer Players: A Randomized Controlled Study Design.

Microdosing can facilitate better accommodation to the training stimulus while aligning with the scheduling needs of teams. In this study, the effectiveness of microdosing exposure was investigated by comparing the effects of microdosing plyometric jump training (microPJT) with those of regular plyometric jump training (regPJT) and a control group not exposed to plyometric training. The comparison focused on the effects on jumping performance, reactive strength index (RSI), and acceleration over a 10-meter distance. Fifty-two male youth soccer players (16.3 ± 0.6 years old) from under-17 teams participated in a randomized controlled study, with interventions lasting 8 weeks. Assessments were conducted twice, before and after the intervention, measuring squat jump (SJ), countermovement jump (CMJ), RSI during drop jumps, and acceleration in a 10-meter sprint test. The regPJT group completed 34 bilateral jumps and 48 unilateral jumps per week over two weekly sessions, totaling 82 jumps. Conversely, the microPJT group performed 17 bilateral jumps and 24 unilateral jumps weekly over 4 sessions week, totaling 41 jumps. Significant interactions between groups and time were observed concerning SJ (p < 0.001; η2= 0.282), CMJ (p < 0.001; η2= 0.368), RSI (p < 0.001; η2= 0.400) and 10-m sprint time (p < 0.001; η2 = 0.317). Between-group analysis indicated that both the microPJT (p < 0.001) and regPJT (p < 0.001) groups exhibited significant better results compared to the control group in post-intervention evaluation of SJ, CMJ, RSI and 10-m sprint time, while no significant differences were found between experimental groups (p > 0.050). In conclusion, this study has revealed that both microPJT and regPJT are equally effective in enhancing jumping performance and acceleration time in soccer players. This suggests that a smaller training volume, distributed more frequently across the week, can effectively induce improvements in soccer players.

Effects of different speed-accuracy instructions on perception in psychology experiments: evidence from event-related potential and oscillation.

Introduction: In cognitive behavioral experiments, we often asked participants to make judgments within a deadline. However, the most common instruction of "do the task quickly and accurately" does not highlight the importance of the balance between being fast and accurate. Methods: Our research aimed to explore how instructions about speed or accuracy affect perceptual process, focus on event-related potentials (ERPs) and event-related oscillations (EROs) of two brain responses for visual stimuli, known as P1 and N1. Additionally, we compared the conventional analysis approach with principal component analysis (PCA) based methods to analyze P1 and N1 ERP amplitude and ERO power. Results: The results showed that individuals instructed to respond quickly had lower P1 amplitude and alpha ERO than those who prioritized accuracy, using the PCA-based approach. However, these two groups had no differences between groups in the N1 theta band using both methods. The traditional time-frequency analysis method could not detect any ERP or ERO distinctions between groups due to limitations in detecting specific components in time or frequency domains. That means PCA is effective in separating these components. Discussion: Our findings indicate that the instructions given regarding speed and accuracy impact perceptual process of subjects during cognitive behavioral experiments. We suggest that future researchers should choose their instructions carefully, considering the purpose of study.

Higher final speed in 30-15 intermittent fitness tests correlates with soccer's locomotor demands, not heart rate responses in small-sided soccer games.

This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.32 years, with 3.4 ± 1.1 years of experience, voluntarily participated in the study. These players belonged to two regional-level tier 2 teams (trained/developmental). In the initial week of observation, the 30-15 Intermittent Fitness Test was implemented to measure the final velocity (VIFT) achieved by the players. Subsequently, the 5v5 format of play was conducted twice a week over two consecutive weeks, during which heart rate responses and locomotor demands were measured. The Pearson product-moment correlation test revealed a significant correlation between VIFT and the total distance covered during the 5v5 format (r = 0.471 [95% CI: 0.093; 0.721], p = 0.015). Conversely, small and non-significant correlations were identified between VIFT and mean heart rate (r = 0.280 [95% CI: - 0.126; 0.598]; p = 0.166), VIFT and peak heart rate (r = 0.237 [95% CI: - 0.170; 0.569]; p = 0.243), as well as VIFT and high-speed running (r = 0.254 [95% CI: - 0.153; 0.580]; p = 0.211). Players with higher VIFT demonstrated a significantly greater total distance, with a large effect size (+ 6.64%; p = 0.015; d = 1.033), compared to those with lower VIFT. Our findings suggest that improved performance in VIFT may lead to covering more distance in 5v5 matches. However, the lack of significant associations between VIFT and heart rate levels during SSGs suggests that they are not strongly correlated, possibly because VIFT is more closely linked to locomotor profile. As a practical implication, coaches may consider organizing players during SSGs based on their VIFT if the goal is to standardize locomotor demands.

Ultrasound-assisted complex enzyme extraction, structural characterization, and biological activity of polysaccharides from Ligustrum robustum.

Ligustrum robustum is one of the traditional teas in China with a long history of drinking and medicinal use. Through Response surface optimization, the yield of polysaccharides extracted by ultrasonic-assisted complex enzyme (UAE-EN) method was increased to 14.10 ±â€¯0.56 %. Neutral homogeneous polysaccharide (LRNP) and acidic homogeneous polysaccharide (LRAP-1, LRAP-2, LRAP-3) from L. robustum were purified. The molecular weights of them were 5894, 4256, 4621 and 3915 Da. LRNP was composed of glucose (Glc), galactose (Gal), arabinose (Ara) with molar percentage of 24.97, 42.38 and 30.80. Structure analysis revealed that the backbone of LRNP consisted of 1,5-linked α-Araf, 1,4-linked ß-Galp, 1,6-linked ß-Galp, and 1,4-linked ß-Glcp with the branches of 1,2-linked α-Araf, 1,3-linked α-Araf, 1,3-linked ß-Glcp and 1,6-linked ß-Galp residues, some terminal residues of α-Araf, ß-Glcp and α-Galp were also included. In vitro experiments showed that the four polysaccharides possessed excellent antioxidant, antitumor and hypoglycemic activities. LRNP possessed the protective effect against oxidative stress. The studies provide a basis for further exploitation of L. robustum.

Supervised Offseason Training Programs are able to mitigate the Effects of Detraining in Youth Men Soccer Players Physical Fitness: A Randomized Parallel Controlled Study.

This study aimed to analyze the effects of three off-season training programs on the aerobic capacity, countermovement jump (CMJ), and linear sprint performance of young male soccer players. The study employed a randomized multi-arm design, consisting of three experimental groups: i) a high-intensity interval training (HIIT) group; (ii) a plyometric jump training (PJT) group; and (iii) a HIIT+PJT group; and an inactive control group. Fifty-eight under-19 male soccer players (aged 17.6 ±0.6 years) were randomly assigned to participate in a 3-week offseason training program exclusively performing HIIT, PJT, or a combination of both, while the fourth group remained inactive. Players underwent assessments twice, using the Yo-Yo Intermittent Recovery Test - Level 1 (YYIRT), CMJ, and 30-meter linear sprint. Significant interactions between time and groups were found in CMJ (p<0.001), YYIRT (p<0.001), and 30-m sprint (p<0.001). Group*time interaction revealed that the control group was significantly different from HIIT (p<0.001), PJT (p<0.001), and HIIT+PJT (p<0.001) considering the CMJ. Moreover, the control group was significantly different from HIIT (p=0.037) in YYIRT. Finally, the control group was significantly different from HIIT (p=0.024), PJT (p<0.001), and HIIT+PJT (p=0.021) considering the 30-m sprint. In conclusion, off-season training programs are effective in significantly reducing declines in CMJ and sprint performance compared to maintaining training cessation. However, in the YYIRT, only HIIT seems to be significantly superior to maintaining inactivity. To mitigate aerobic performance declines, incorporating HIIT sessions twice weekly during the offseason is advisable. To enhance or maintain jump performance, integrating at least one session of PJT weekly is beneficial.

Does artistic training affect color perception? A study of ERPs and EROs in experiencing colors of different brightness.

Color is a visual cue that can convey emotions and attract attention, and there is no doubt that brightness is an important element of color differentiation. To examine the impact of art training on color perception, 44 participants were assigned to two groups-one for those with and one for those without art training-in an EEG experiment. While the participants had their electroencephalographic data recorded, they scored their emotional responses to color stimuli of different brightness levels based on the Munsell color system. The behavioral results revealed that in both groups, high-brightness colors were rated more positively than low-brightness colors. Furthermore, event-related potential results for the artist group showed that high-brightness colors enhanced P2 and P3 amplitudes. Moreover, non-artists had longer N2 latency than artists, and there was a significant Group × Brightness interaction separately for the N2 and P3 components. Simple effect analysis showed that N2 and P3 amplitudes were substantially higher for high-brightness stimuli than for lower-brightness stimuli in the artistic group, but this was not the case in the non-artist group. Additionally, evoked event-related oscillation results showed that in both groups, high-brightness stimuli also elicited large delta, theta, and alpha as well as low gamma responses. These results indicate that high-brightness color stimuli elicit more positive emotions and stronger neurological reactions and that artistic training may have a positive effect on top-down visual perception.

Internal m 6 A and m 7 G RNA modifications in hematopoietic system and acute myeloid leukemia.

ABSTRACT: Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m 6 A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m 6 A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m 6 A.

A novel pectin polysaccharide from vinegar-baked Radix Bupleuri absorbed by microfold cells in the form of nanoparticles.

Polysaccharides of vinegar-baked Radix Bupleuri (VBCP) have been reported to exhibit liver-targeting and immunomodulatory activities through oral administration, but the absorption behavior and mechanism of VBCPs have not been extensively studied. In this study, a novel HG type pectin polysaccharide, VBCP1-4, with a high molecular weight of 2.94 × 106 Da, was separated from VBCP. VBCP1-4 backbone was contained 1,4-α-D-GalpA, 1,4-α-D-GalpA6OMe, 1,3,4-α-D-GalpA and 1,2,4-α-D-Rhap. The branches were mainly contained 1,5-α-L-Araf, 1,3,5-α-L-Araf, t-α-L-Araf and t-α-D-Galp, which linked to the 3 position of 1,3,4-α-D-GalpA and the 4 position of 1,2,4-α-D-Rhap. VBCP1-4 could self-assemble to nanoparticles in water, with CMC values of 106.41 µg/mL, particle sizes of 178.20 ± 2.82 nm and zeta potentials of -23.19 ± 1.44 mV. The pharmacokinetic study of VBCP1-4, which detected by marking with FITC, revealed that it could be partially absorbed into the body through Peyer's patches of the ileum. In vitro absorption study demonstrated that VBCP1-4 was difficult to be absorbed by Caco-2 cell monolayer, but could be absorbed by M cells in a time and concentration dependent manner. The absorption mechanism was elucidated that VBCP1-4 entered M cells through clathrin-mediated endocytosis in the form of nanoparticles. These findings provide valuable insights into the absorption behavior of VBCP and contribute to its further development.

Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4+ and dysfunctional CD8+ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4+ T cells, while FCN3+ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3+ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3+ macrophage, cDC1 and LAMP3+ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.

The combination of IL-2 nanoparticles and Palbociclib enhances the anti-tumor immune response for colon cancer therapy.

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.

N-doped carbon dots for the determination of Al3+ and Fe3+ using aggregation-induced emission.

New portable hydrogel sensors for Al3+ and Fe3+ detection were designed based on the aggregation-induced emission (AIE) and color change of N-doped carbon dots (N-CDs). N-CDs with yellow fluorescence were prepared by a one-pot hydrothermal method from 2,5-dihydroxyterephthalic acid and acrylamide. The fluorescence of N-CDs was enhanced by Al3+ about 20 times and quenched by Fe3+. It was interesting that although Fe3+ showed obvious quenching on the fluorescence of N-CDs it did not cause a noticeable change in the fluorescence of N-CDs + Al3+. The colorless solution of N-CDs appeared blue in the presence of Fe3+ without the influence of Al3+. Therefore, the turn-on fluorometry and colorimetry systems based on N-CDs were constructed for the simultaneous detection of Al3+ and Fe3+. Furthermore, the portable sensing of Al3+ and Fe3+ was realized with the assistance of hydrogel, filter paper, cellulose acetate, and cellulose nitrate film. The proposed approach was successfully applied to the detection of Al3+ and Fe3+ in food samples and cell imaging.

Efficacy of roxadustat in maintenance hemodialysis patients with erythropoietin-hyporesponsive anemia.

OBJECTIVE: To investigate the efficacy of roxadustat in hemodialysis patients with erythropoietin (EPO) hypo-responsive anemia. MATERIALS AND METHODS: This retrospective study included 55 hemodialysis patients with erythropoietin hypo-responsive anemia at the First Affiliated Hospital of Chongqing Medical University from January to December 2020. We observed their hemoglobin (Hb) changes, inflammatory factors, and adverse reactions before and after 12 weeks of roxadustat treatment. RESULTS: Among the 55 patients, the average age was 60.75 ± 13.96 years old, and the median dialysis age was 48 months. All patients were taken off EPO and switched to roxadustat during the follow-up period. Compared with baseline, patients' Hb was significantly increased (90.64 ± 20.01 g/L, 98.52 ± 15.89 g/L, 104.34 ± 19.15 g/L, and 107.02 ± 20.54 g/L, respectively) (p < 0.05). At 12 weeks of roxadustat treatment, 34 patients (61.82%) met the target Hb levels (100 - 130 g/L). The multivariate logistic analysis showed that Hb response positively correlated with the Hb level before roxadustat treatment (p = 0.046), while responding well to roxadustat negatively correlated with blood platelet-to-lymphocyte ratio (PLR) and duration of dialysis (p = 0.029 and p = 0.046) in patients with EPO hypo-responsive anemia. CONCLUSION: Roxadustat could effectively improve anemia; the PLR and dialysis age were independent predictors of roxadustat efficacy in dialysis patients with EPO hypo-responsive anemia.

REDH: A database of RNA editome in hematopoietic differentiation and malignancy.

BACKGROUND: The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. METHODS: We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. RESULTS: We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. CONCLUSIONS: REDH is accessible at http://www.redhdatabase.com/ . This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.