Search Results (175)

The BeiDou-3 Navigation Satellite System (BDS-3) precise point positioning (PPP) service through the B2b signal (PPP-B2b) leverages precise correction data disseminated by satellites to eliminate or mitigate key error sources, including satellite orbit errors, clock biases, and ionospheric delays, thereby enabling high-precision timing and positioning. This paper investigates the disparities in time comparison and positioning capabilities associated with the PPP-B2b signals transmitted by the BDS-3 Geostationary Earth Orbit (GEO) satellites (C59 and C61). Three stations in the Asia–Pacific region were selected to establish two time comparison links. The study evaluated the time transfer accuracy of PPP-B2b signals by analyzing orbit and clock corrections from BDS-3 GEO satellites C59 and C61. Using multi-GNSS final products (GBM post-ephemeris) as a reference, the performance of PPP-B2b-based time comparison was assessed. The results indicate that while both satellites achieve comparable time transfer accuracy, C59 demonstrates superior stability and availability compared to C61. Additionally, five stations from the International GNSS Service (IGS) and the International GNSS Monitoring and Assessment System (iGMAS) were selected to assess the positioning accuracy of PPP-B2b corrections transmitted by BDS-3 GEO satellites C59 and C61. Using IGS/iGMAS weekly solution positioning results as a reference, the analysis demonstrates that PPP-B2b enables centimeter-level static positioning and decimeter-level simulated kinematic positioning. Furthermore, C59 achieves higher positioning accuracy than C61. Full article

Transcriptomic profiling has shown that exposure to PM_2.5, a common air pollutant, can modulate gene expression, which has been linked to negative health effects and diseases. However, there are few population-based cohort studies on the association between PM_2.5 exposure and specific gene set expression. In this study, we used an unbiased transcriptomic profiling approach to examine gene expression in a mouse model exposed to PM_2.5 and to identify PM_2.5-responsive genes. The gene expressions were further validated in both the human cell lines and a population-based cohort study. Two cohorts of healthy older adults (aged ≥ 65 years) were recruited from regions characterized by differing levels of PM_2.5. Logistic regression and decision tree algorithms were then utilized to construct predictive models for PM_2.5 exposure based on these gene expression profiles. Our results indicated that the expression of five genes (FAM102B, PPP2R1B, OXR1, ITGAM, and PRP38B) increased with PM_2.5 exposure in both cell-based assay and population-based cohort studies. Furthermore, the predictive models demonstrated high accuracy in classifying high-and-low PM_2.5 exposure, potentially supporting the integration of gene biomarkers into public health practices. Full article

Rectal carcinoma (RC) represents approximately 30% of all colorectal carcinomas (CRC) and is considered a distinct clinical entity. Vascular invasion (VI) is recognized as an independent predictor of poor outcomes in RC. In this study, we applied bioinformatics methods to identify gene pathways most likely associated with VI in rectal carcinoma. As ADAMTS8 showed statistically significant negative relations with the VI in RC patients, we further analyzed its top co-dependent genes—DNAL4, EVI2B, PPP1R35, PTGR3, RPL21, SOX4, and ZNF3—for the experimentally proven molecular modulators. We identified a total of 23 compounds from the Comparative Toxicogenomics Database based on previously reported data for all eight target genes. The search was expanded to include additional chemical agents by structure similarity using the PubChem database, which revealed 9661 additional compounds. These were subsequently used for molecular interaction analysis against target proteins co-expressed with, or associated with, ADAMTS8 in RC with VI. Ultimately, we identified four high-affinity compounds—cyanoginosin LR, doxorubicin, benzo[a]pyrene, and dibenzo(a,e)pyrene—that interacted with all target proteins. These compounds show potential for further assessment of their role in modulating processes related to vascular invasion, which is a strong negative predictor of RC outcomes. Full article

Compared to high-cost hardware-based Global Navigation Satellite System (GNSS) positioning techniques, smartphone-based precise positioning technology plays an important role in applications such as the Internet of Things (IoT). Since Google released the Nougat version of Android in 2016, this has provided a new method for achieving high-accuracy positioning solutions with a smartphone. However, two factors are limiting smartphone-based high-accuracy applications, namely, real-time precise orbit/clock products without the internet and the quality-adaptive precise point positioning (PPP) model. To overcome these two factors, we introduce BDS PPP-B2b orbit/clock corrections and a hybrid weight function (based on C/N₀ and satellite elevation) into smartphone real-time PPP. To validate the performance of such a method, two sets of field tests were arranged to collect the smartphone’s GNSS measurements and PPP-B2b orbit/clock corrections. The results illustrated that the hybrid weight function led to 5.13%, 18.00%, and 15.15% positioning improvements compared to the results of the C/N₀-dependent model in the east, north, and vertical components, and it exhibited improvements of 71.10%, 72.53%, and 53.93% compared to the results of the satellite-elevation-angle-dependent model. Moreover, the mixed-frequency measurement PPP model could also provide positioning improvements of about 14.63%, 19.99%, and 9.21%. On average, the presented smartphone PPP model can bring about 76.64% and 59.84% positioning enhancements in the horizontal and vertical components. Full article

Since 2020, the BDS-3 has been providing real-time corrections via the B2b signal, enabling users in China and its neighboring regions to achieve kinematic positioning accuracy at the decimeter level. The rapid geometric changes of Low-Earth-Orbit (LEO) satellites facilitate the rapid resolution of phase ambiguities and accelerate the convergence of Precise Point Positioning (PPP). Therefore, this study proposes an LEO-enhanced BDS-3 PPP-B2b positioning model. Firstly, a novel BDS-3 PPP model accounting for satellite clock bias characteristics is proposed, and experimental validation confirms its efficacy. Subsequently, an LEO-enhanced BDS-3 PPP model is developed. Finally, the positioning performance is rigorously evaluated using combined LEO simulation observations and BDS-3 observations. The results indicate that, compared with the traditional PPP model, the new model yields an average convergence time of 25.1 min for experiments where the convergence criterion is jointly satisfied, representing a 35.6% improvement in convergence speed, while maintaining the same positioning accuracy after convergence. When augmented with LEO satellites, the convergence time of the BDS-3 PPP-B2b solution is reduced to less than 2 min. Furthermore, when more than three LEO satellites are available, the mean convergence time is shortened to within 1 min. Full article

Background: Colonic diverticulosis is a common condition, particularly in the elderly population. While dietary habits, obesity, smoking, and physical inactivity contribute to its pathogenesis, emerging evidence highlights a genetic predisposition affecting extracellular matrix (ECM) remodeling, inflammation, and connective tissue integrity. The aim of this systematic review was to summarize genetic determinants of colonic diverticulosis. Methods: The PubMed^® database was searched for original studies in humans. The inclusion criteria were named genetic factor and confirmed diverticulosis. Patients with diverticulitis and diverticular diseases were excluded from this review. Results: Out of 137 publications, 10 articles met the inclusion criteria: six large association studies (GWAS) and four cross-sectional studies. The genes regulating ECM turnover, including TIMP1, MMP3, and MMP9, are involved in diverticulosis development. The TIMP1 (rs4898) T allele has been associated with increased susceptibility, potentially due to its role in ECM remodeling. Similarly, MMP3 (rs3025058) and MMP9 (rs3918242) polymorphisms contribute to altered collagen degradation. The COL3A1 (rs3134646) variant coding modified collagen type III may promote diverticular formation. Other genes, such as ARHGAP15 (rs4662344, rs6736741), affect cytoskeletal dynamics. Identified in GWAS studies, gene candidates may be grouped into blood group and immune system-related genes (ABO, HLA-DQA1, HLA-H, OAS1, TNFSF13, FADD), extracellular matrix and connective tissue genes (COL6A1, COLQ, EFEMP1, ELN, HAS2, TIMP2), signaling and cell communication (BMPR1B, WNT4, RHOU, PHGR1, PCSK5), nervous system and neurodevelopment (BDNF, CACNB2, GPR158, SIRT1, SCAPER, TRPS1), metabolism and transporters (SLC25A28, SLC35F3, RBKS, PPP1R14A, PPP1R16B), lipids and cholesterol (LDAH, LYPLAL1, STARD13), transcription and gene regulation (ZBTB4, UBTF, TNRC6B), apoptosis (FADD, PIAS1), and poorly characterized genes (C1TNF7, ENSG00000224849, ENSG00000251283, LINC01082, DISP2, SNX24, THEM4, UBL4B, UNC50, WDR70, SREK1IP1). Conclusions: There are a number of gene variants that probably predispose to colonic diverticulosis. Detailed characterization of the multigene background of diverticulosis will enable appropriate therapeutic or preventive interventions in the future. Full article

The International Bureau of Weights and Measures (BIPM) currently mainly uses GPS time transfer for the calculation of UTC. In order to enhance the reliability of the time links, the common-view (CV) and Precise Point Positioning (PPP) time transfer performance of the dual-frequency ionosphere-free combination for BRUX-SPT0, NIST-USN7, and BRUX-USN7 links was evaluated, including GPS (P1 & P2), Galileo (E1 & E5a), and BDS-3 (B1I & B3I, B1I & B2a, B1C & B3I, B1C & B2a). The experimental results show that the precision and average frequency stability (AFT) of BDS-3 B1C & B2a CV and PPP links are better than those of BDS-3 B1I & B3I, B1I & B2a, and B1C & B3I links. Compared to the GPS P1 & P2 and BDS-3 B1C & B2a CV links, the Galileo E1 & E5a links have the highest precision. In addition, the precision of GPS PPP links outperforms the BDS-3 and Galileo links. The short-term FT (frequency stability) of GPS PPP links is better than that of BDS-3 B1C & B2a PPP links. When the average time is greater than 4.3 h, however, the BDS-3 B1C & B2a PPP link’s AFT is significantly improved compared with the Galileo PPP links. Full article

Background: Macrocephaly can be a component manifestation of several monogenic conditions, in association with intellectual disability/developmental delay (ID/DD) behaviour abnormalities, including autism spectrum disorders (ASD), and variable additional features. On the other hand, idiopathic ASD can present with developmental delay and macrocephaly. Methods: We carried out a retrospective analysis of a cohort of 78 patients who were tested from February 2017 to December 2024 by high-throughput sequencing of a panel of 27 genes (ABCC9, AKT1, AKT2, AKT3, BRWD3, DIS3L2, DNMT3A, EZH2, GPC3, GPC4, HERC1, MED12, MTOR, NFIA, NFIX, NSD1, PDGFRB, PIK3CA, PIK3R1, PIK3R2, PPP2R1A, PPP2R5D, PTEN, RAB39B, RNF135, SETD2, and TBC1D7) because of neurodevelopmental impairment, including ID/DD, ASD/behaviour abnormalities associated with macrocephaly, mimicking to a large extent idiopathic ASD. Results: Pathogenic variants leading to the diagnosis of monogenic conditions were detected in 22 patients (28%), including NSD1 (2), PTEN (16), and PPP2R5D (4). Distinctive of the PTEN-associated phenotype were true macrocephaly (100%), ASD or behaviour abnormalities (92%), mild/borderline ID (79%), and no facial dysmorphisms. Typical of the PPP2R5D-associated phenotype were relative macrocephaly (75%), a few unspecific peculiar facial characteristics (50%), and a more variable presentation of the neurodevelopmental phenotype. Conclusions: Pathogenic variants in PTEN and PPP2R5D are the most recurrent gene mutations in a patient-oriented procedure for the genetic diagnosis of apparently idiopathic ASD and behaviour abnormalities associated with macrocephaly. The clinical applicability of the presented diagnostic strategy is discussed. Full article

Congenital developmental abnormalities in piglets, such as intersex and aproctia, adversely affect survival rates, growth performance, and genetic breeding efficiency in pig populations. To elucidate their genetic basis, we performed a genome-wide association study (GWAS) on 1030 Large White pigs. We combined 50 K SNP chip data with SWIM-based genotype imputation to enhance the resolution of genetic variation detection, followed by MLM analysis. Our results identified 53 significant SNPs, with 52 associated with intersex and 1 with aproctia. Key candidate genes included MAD1L1, ID4, EFNA5, and PPP1R16B for intersex and ARNT2 for aproctia. Functional enrichment analysis highlighted pathways related to gonadal development (e.g., progesterone-mediated oocyte maturation) and embryonic morphogenesis. Collectively, the identification of these SNPs and candidate genes advances our understanding of the genetic architecture of intersex and aproctia in piglets. These findings provide actionable insights for optimizing genetic breeding strategies and improving health management in Large White pig production, with potential implications for reducing economic losses caused by congenital disorders. Full article

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disorder with limited therapeutic options, particularly for refractory discoid lupus (DLE), which often results in scarring and atrophy. Recent studies have identified miR-31, miR-485-3p, and miR-885-5p as key regulators of inflammation, apoptosis, and fibrosis in CLE skin lesions. This research investigates a novel topical miRNA therapy using DDC642 elastic liposomes to target these pathways in CLE. DDC642 liposomes were complexed with miRNAs (anti-miR-31, anti-miR-485-3p, pre-miR-885-5p) and characterized through dynamic light scattering and Cryo-TEM. Cytotoxicity, cellular penetration, and therapeutic efficacy were evaluated in primary keratinocytes, PBMCs, and immune 3D-skin organoids. miRNA lipoplexes were successfully synthesized with optimized particle size, surface charge, and encapsulation efficiency. These lipoplexes exhibited effective cellular penetration and low cytotoxicity. Anti-miR-31 lipoplexes reduced miR-31 and NF-κB levels while increasing STK40 and PPP6C expression. Pre-miR-885-5p lipoplexes elevated miR-885-5p levels and downregulated PSMB5 and NF-κB in keratinocytes. While anti-miR-485-3p lipoplexes reduced T-cell activation markers. Anti-miR-31 and pre-miR-885-5p lipoplexes successfully modulated inflammatory pathways in 3D-skin CLE models. miRNA lipoplexes represent promising candidates for pioneering topical genetic therapies for CLE. Further studies, including animal models, are necessary to validate and optimize these findings. Full article

The BeiDou global navigation satellite system (BDS-3) and Galileo systems both broadcast satellite signals on five frequencies, which can form many observation combinations with dual-frequency ionospheric-free (DFIF) precise point positioning (PPP). This study analyzes the PPP static and kinematic performance of a total of eight different DFIF combinations, including BDS-3’s B1C/B2a, B1C/B3I, B1I/B2b, and B1I/B3I and Galileo’s E1/E5, E1/E6, E1/E5a, and E1/E5b combinations. A 10-day dataset from 60 Multi-GNSS Experiment (MGEX) stations was adopted. The root mean square error (RMSE) of the PPP was tested in the north, east, and up (NEU), horizontal (H), and three-dimensional (3D) components. The PPP accuracy of BDS-3 was comparable with that of Galileo. Both BDS-3 and Galileo signals allow for independent PPP processing both in static and kinematic modes. When the 3D error was used as the evaluation criterion, the order of the combinations in which the positioning accuracy gradually deteriorated was as follows: E1/E5, B1C/B3I, B1I/B2b, E1/E6, B1I/B3I, E1/E5b, E1/E5a, and B1C/B2a; The 3D RMSE values for the best combination, E1/E5, and the worst combination, B1C/B2a, were 1.06 cm and 1.43 cm, respectively; the positioning accuracies of all combinations remained at the level of 1 cm in static mode. In kinematic mode, the order of the combinations in which the PPP accuracy gradually deteriorated was as follows: E1/E5, E1/E5a, E1/E5b, B1I/B2b, B1I/B3I, B1C/B2a, B1C/B3I, and E1/E6. The 3D RMSE values for the best combination, E1/E5, and the worst combination, B1C/B2a, were 3.89 cm and 1.95 cm, respectively. The best results could be achieved with the E1/E5 combination, which outperforms the worst combination, E1/E6, by about 1 cm. Full article

Pulmonary fibrosis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of death in patients with COVID-19. β-catenin, a key molecule in the Wnt/β-catenin signaling pathway, has been shown to be involved in the development of pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis, silicosis). In this study, we developed a SARS-CoV-2-infected A549-hACE2 cell model to evaluate the efficacy of the A549-hACE2 monoclonal cell line against SARS-CoV-2 infection. The A549-hACE2 cells were then subjected to either knockdown or overexpression of the effector β-catenin, and the modified cells were subsequently infected with SARS-CoV-2. Additionally, we employed transcriptomics and raw letter analysis approaches to investigate other potential effects of β-catenin on SARS-CoV-2 infection. We successfully established a model of cellular fibrosis induced by SARS-CoV-2 infection in lung-derived cells. This model can be utilized to investigate the molecular biological mechanisms and cellular signaling pathways associated with virus-induced lung fibrosis. The results of our mechanistic studies indicate that β-catenin plays a significant role in lung fibrosis resulting from SARS-CoV-2 infection. Furthermore, the inhibition of β-catenin mitigated the accumulation of mesenchymal stroma in A549-hACE2 cells. Additionally, β-catenin knockdown was found to facilitate multi-pathway crosstalk following SARS-CoV-2 infection. The fact that β-catenin overexpression did not exacerbate cellular fibrosis may be attributed to the activation of PPP2R2B. Full article

PHI-1, encoded by PPP1R14B, regulates cellular protein phosphatase-1 (PP1) signaling and has emerged as both a biomarker and therapeutic target. Initially identified as a phospholipase-neighboring gene (PNG), PHI-1 is now known for its phosphorylation-dependent inhibition of PP1 holoenzymes, with bi-directional roles depending on its expression levels. Under physiological conditions, PHI-1 selectively regulates PP1 activity to maintain cellular homeostasis, whereas its pathological upregulation promotes oncogenic pathways, stabilizes tumor-promoting proteins, and modulates immune responses. This article explores PHI-1’s emerging role as a pan-cancer biomarker in parallel with emphasizing its physiological functions in signaling networks, smooth muscle contraction, cytoskeletal dynamics, and selective proteostasis. The mechanistic insights highlight PHI-1’s potential in precision oncology, offering opportunities for developing diagnostics and therapies that target its conditional functions. Full article

In 2020, BDS-3 began broadcasting high-precision positioning correction products through B2b signals, effectively addressing the limitations of ground-based augmentation. However, challenges such as the “south wall effect” from geostationary orbit (GEO) satellites, issues of data (IOD) mismatch, and signal priority conflicts often result in interruptions and anomalies during real-time positioning with the B2b service. This paper proposes a continuous B2b-PPP (B2b signal-based Precise Point Positioning) model that incorporates signal-in-space range error (SISRE) residuals and predictions for B2b orbits and clock corrections to achieve seamless, high-precision continuous positioning. In our experiments, we first analyze the characteristics of B2b SISRE for both BDS-3 and GPS. We then evaluate the positioning accuracy of several models, B2b-PPP, EB2b-PPP, PB2b-PPP, EB2bS-PPP, and PB2bS-PPP, through simulated and real dynamic experiments. Here, ‘E’ indicates the direct utilization of the previous observation corrections from B2b before the signal interruption, ‘P’ represents B2b prediction products, and ‘S’ signifies the incorporation of the SISRE residuals. The results show that EB2b-PPP exhibits significant deviations as early as 10 min into a B2b signal interruption. Both PB2b-PPP and EB2bS-PPP demonstrate comparable performances, with PB2bS-PPP emerging as the most effective method. Notably, in real dynamic experiments, PB2bS-PPP maintains positioning accuracy in the E/N directions like B2b-PPP, even after 40 min of signal interruption, ensuring continuous and stable positioning upon signal restoration. This achievement significantly enhances the capability for high-precision continuous positioning based on B2b signals. Full article

The BeiDou Navigation Satellite System (BDS) offers orbit and clock corrections through the B2b signal, enabling Precise Point Positioning (PPP) without relying on ground communication networks. This capability supports applications such as aerial and maritime mapping. However, achieving high precision during the convergence period remains challenging, particularly for missions with short observation durations. To address this, we analyze the performance of PPP over short periods using PPP-B2b products and propose using the backward smoothing method to enhance the accuracy during the convergence period. Evaluation of the accuracy of PPP-B2b products shows that the orbit and clock accuracy of the BDS surpass those of GPS. Specifically, the BDS achieves orbit accuracies of 0.059 m, 0.178 m, and 0.186 m in the radial, along-track, and cross-track components, respectively, with a clock accuracy within 0.13 ns. The hourly static PPP achieves 0.5 m and 0.1 m accuracies with convergence times of 4.5 and 25 min at a 50% proportion, respectively. Nonetheless, 7.07% to 23.79% of sessions fail to converge to 0.1 m due to the limited availability of GPS and BDS corrections at certain stations. Simulated kinematic PPP requires an additional 1–4 min to reach the same accuracy as the static PPP. Using the backward smoothing method significantly enhances accuracy, achieving 0.024 m, 0.046 m, and 0.053 m in the north, east, and up directions, respectively. For vehicle-based positioning, forward PPP can achieve a horizontal accuracy better than 0.5 m within 4 min; however, during the convergence period, positioning errors may exceed 1.5 m and 3.0 m in the east and up direction. By applying the smoothing method, horizontal accuracy can reach better than 0.2 m, while the vertical accuracy can improve to better than 0.3 m. Full article