Search Results (62)

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article

BeiDou navigation satellite system (BDS) precise point positioning (PPP)-B2b has significant potential for application in meteorological fields, such as standalone water vapor monitoring in depopulated area without Internet. In this study, the practical ability of water vapor monitoring using the BDS PPP-B2b service is illustrated through a continuously operated water vapor monitoring system in Wuhan, China, with a 25-day experiment in 2025. Original observations from the Global Positioning System (GPS) and BDS are collected and processed in the near real-time (NRT) mode using ephemeris from the PPP-B2b service. Precipitable water vapor PWV monitored with B2b ephemeris are evaluated with radiosonde and ERA5 reanalysis, respectively. Taking PWV from radiosonde observations as the reference, RMS of PWV based on B2b ephemeris varies from 3.71 to 4.66 mm for different satellite combinations. While those values are with a range from 3.95 to 4.55 mm when compared with ERA5 reanalysis. These values are similar to those processed with the real-time ephemeris from the China Academy of Science (CAS). In general, this study demonstrates that the practical accuracy of water vapor monitored based on the BDS PPP-B2b service can meet the basic demand for operational meteorology for the first time. This will provide a scientific reference for its wide promotion to meteorological applications in the near future. Full article

Coronary atherosclerosis (CAS) is a major cause of cardiovascular morbidity worldwide. The understanding of atherosclerosis has shifted from a cholesterol deposition disorder to an inflammation-driven disease, with anti-inflammatory therapies demonstrating clinical efficacy. Identifying inflammatory protein targets is crucial for developing targeted therapies. A proteome-wide Mendelian randomization (MR) analysis was performed to explore therapeutic targets for CAS by integrating inflammatory proteomics data from the UK-PPP (54,219 participants, 2923 proteins) and Iceland cohorts (35,559 participants, 4907 proteins) as exposures and outcome data for CAS, atherosclerosis, and carotid atherosclerosis from FinnGen. Replication MR employed meta-analysis of six proteomics datasets and CAS data from three sources, while the impact of the identified proteins on four cardiovascular diseases was also investigated. Colocalization analysis (PPH₄ > 0.9), reverse MR, and SMR were used to ensure robust causal inference. Proteome-wide MR identified 11 proteins significantly associated with CAS (p < 3.52 × 10⁻⁵), with all but CD4 linked to cardiovascular disease risk. Notably, colocalization confirmed the causal roles of PCSK9, IL6R, CELSR2, FN1, and SPARCL1 in CAS, and single-cell RNA-seq analysis revealed that five genes (TGFB1, SPARCL1, IL6R, FN1, and CELSR2) were exclusively expressed in smooth muscle cells of either coronary plaques or healthy vasculature. Druggability assessments were subsequently conducted for these targets. The three most promising targets (CELSR2, FN1, and SPARCL1), along with the other identified proteins and their biological functions, exhibit robust causal associations with CAS. FN1 and TGFB1 have the potential for drug repurposing in atherosclerosis treatment. 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

Coronavirus disease 2019 is a multi-systemic syndrome that caused a pandemic. Proteomic studies have shown changes in protein expression and interaction involved in signaling pathways related to SARS-CoV-2 infections. Protein phosphatases play a crucial role in regulating cell signaling. In this study, we assessed the potential involvement of protein phosphatases and their associated signaling pathways during SARS-CoV-2 infection by conducting a meta-analysis of proteome databases from COVID-19 patients. We identified both direct and indirect interactions between human protein phosphatases and viral proteins, as well as the expression levels and phosphorylation status of intermediate proteins. Our analyses revealed that PPP2CA and PTEN are key phosphatases involved in cell cycle and apoptosis regulation during SARS-CoV-2 infection. We also highlighted the direct involvement of PPP2CA in the cell division throughout its interaction with CDC20 protein (cell division cycle protein 20 homolog). This evidence strongly suggests that both proteins play critical roles during SARS-CoV-2 infection and represent potential targets for COVID-19 treatment. Full article

Fish body mucus plays a protective role, especially in Halobatrachus didactylus, which inhabits intertidal zones vulnerable to anthropogenic contaminants. In silico predicted bioactive peptides were identified in its body mucus, namely, EDNSELGQETPTLR (HdKTLR), DPPNPKNL (HdKNL), PAPPPPPP (HdPPP), VYPFPGPLPN (HdVLPN), and PFPGPLPN (HdLPN). These peptides were studied in vitro for bioactivities and aggregation behavior under different ionic strengths and pH values. Size exclusion chromatography revealed significant peptide aggregation at 344 mM and 700 mM ionic strengths at pH 7.0, decreasing at pH 3.0 and pH 5.0. Although none exhibited antimicrobial properties, they inhibited Pseudomonas aeruginosa biofilm formation. Notably, HdVLPN demonstrated potential antioxidant activity (ORAC: 1.560 μmol TE/μmol of peptide; ABTS: 1.755 μmol TE/μmol of peptide) as well as HdLPN (ORAC: 0.195 μmol TE/μmol of peptide; ABTS: 0.128 μmol TE/μmol of peptide). Antioxidant activity decreased at pH 5.0 and pH 3.0. Interactions between the peptides and mucus synergistically enhanced antioxidant effects. HdVLPN and HdLPN were non-toxic to Caco-2 and HaCaT cells at 100 μg of peptide/mL. HdPPP showed potential antihypertensive and antidiabetic effects, with IC₅₀ values of 557 μg of peptide/mL for ACE inhibition and 1700 μg of peptide/mL for α-glucosidase inhibition. This study highlights the importance of validating peptide bioactivities in vitro, considering their native environment (mucus), and bioprospecting novel bioactive molecules while promoting species conservation. Full article

This review examines genetic markers associated with litter size in goats, a key reproductive trait impacting productivity in small ruminant farming. Goats play a vital socioeconomic role in both low- and high-income regions; however, their productivity remains limited due to low reproductive efficiency. Litter size, influenced by multiple genes and environmental factors, directly affects farm profitability and sustainability by increasing the output per breeding cycle. Recent advancements in genetic research have identified key genes and pathways associated with reproductive traits, including gonadotropin-releasing hormone (GnRH), inhibin (INHAA), Kit ligand (KITLG), protein phosphatase 3 catalytic subunit alpha (PPP3CA), prolactin receptor (PRLR), POU domain class 1 transcription factor 1 (POU1F1), anti-Müllerian hormone (AMH), bone morphogenetic proteins (BMP), growth differentiation factor 9 (GDF9), and KISS1 and suppressor of mothers against decapentaplegic (SMAD) family genes, among others. These genes regulate crucial physiological processes such as folliculogenesis, hormone synthesis, and ovulation. Genome-wide association studies (GWASs) and transcriptomic analyses have pinpointed specific genes linked to increased litter size, highlighting their potential in selective breeding programs. By incorporating genomic data, breeding strategies can achieve higher selection accuracy, accelerate genetic gains, and improve reproductive efficiency. This review emphasizes the importance of genetic markers in optimizing litter size and promoting sustainable productivity in goat farming. Full article

Policies aimed at reducing plant protection products (PPPs) are part of the UN’s 2030 Agenda for Sustainable Development. Sustainable management of PPPs is crucial for soil health, biodiversity, and ecosystem services, including food provision. While PPPs can control pests and enhance agricultural yields, they also pose environmental and health risks by contaminating water, soil, and non-target organisms through airborne drift. Investigating innovative and more sustainable distribution methods can support sustainability goals. This study aimed to evaluate the potential impact of the pesticide Spintor^® Fly on non-target soil organisms in olive orchards comparing two spraying methods: a traditional Casotti^® pump mounted on a tractor and an innovative Unmanned Aerial Vehicle (UAV) developed for the project. The study was conducted in 2021 in an organic olive orchard, which was divided into two plots: a Casotti-treated plot (CAS) and a drone-treated plot (DRO). A strip of uncultivated land at the edge of the orchard was used as a (non-treated) control plot (CAP). The impact on native soil microarthropod communities was assessed using the arthropod-based Soil Biological Quality Index (QBS-ar) and Bait Lamina Test (BLT). Soil samples were collected for earthworm avoidance tests and soil chemical–physical analysis. The results obtained with QBS-ar and BLT indicated no significant differences between DRO and CAS, in both sampling periods (pre- and post-treatment). However, DRO generally exhibited slightly better performance than CAS. The avoidance behaviour was confirmed for both CAS and DRO, although it was lower for the latter. Overall, drone aerial spray performed slightly better, suggesting a potentially lower impact on soil communities. Our results provide initial clues for the sustainable use of drones in agriculture with no increased risks for soil health compared to traditional methods. Further long-term studies should be conducted to validate these findings and possibly confirm the long-term benefits of drone applications compared to traditional methods. Full article

Seed germination is crucial for plant survival, crop stand establishment, and achieving optimal grain yield. The main objective of this review is to explore the physiological and molecular mechanisms governing rice seed germination under aerobic (water stress) and anaerobic (hypoxic) conditions in direct-seeded rice (DSR) systems. Moreover, it discusses the recent genomic advancements and innovations to improve rice seed germination. Here, we discuss how coleoptile and mesocotyl elongation plays a vital role in anaerobic germination (AG) and the function of raised antioxidants, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in maintaining Reactive Oxygen Species (ROS), and malondialdehyde (MDA) homeostasis for stabilizing seed germination in water-scarce conditions. This study comprehensively highlights the functions and dynamics of phytohormones—GA (gibberellic acid) and ABA (abscisic acid)—key regulatory genes, transcription factors (TFs), key proteins, and regulatory metabolic pathways, including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA), in regulating seed germination under both conditions. Conventional agronomic and cultural practices, such as seed selection, seed priming, seed coating, and hardening, have proven to improve seed germination. Moreover, the utilization of molecular and novel approaches—such as clustered regularly interspaced short palindromic repeat (CRISPR-Cas9) mediated genome editing, marker-assisted selection (MAS), genome-wide associations studies (GWAS), single nucleotide polymorphisms (SNPs), multi-omics, RNA sequencing—combined with beneficial quantitative trait loci (QTLs) has expanded knowledge of crop genomics and inheritance. These advancements aid the development of specific traits for enhancing seed germination in DSR. Full article

Pseudorange bias refers to the receiver-dependent and satellite-dependent constant bias in the pseudorange resulting from the nonideal characteristics of a signal. The impact of pseudorange bias on high-precision satellite navigation services has long been ignored. This paper proposes a pseudorange bias calibration method for two collocated receivers. Then, we calibrate pseudorange biases for two types of collocated receivers at a monitoring station within China and evaluate their impact on two high-precision services: BeiDou Navigation Satellite System 3 (BDS-3) dual-frequency pseudorange augmentation and precise point precision (PPP). Theoretical analysis reveals that the calibrated pseudorange biases contribute 17.2% and 7.7% to the user equivalent ranging error (UERE) of BDS-3 and Global Positioning System (GPS) dual-frequency pseudorange augmentation, respectively, and that the convergence time of the GPS static and kinematic PPP increases from 6 min and 26 min to 19 min and 58 min, respectively. The experimental results indicate that the calibrated pseudorange biases are consistent as the receiver location and time vary. The spatial distribution consistency is generally better than 0.1 m, and the temporal consistency is better than 0.15 m. The pseudorange biases for BDS-3 B1C and B2a are approximately 0.7 m and 0.1 m, respectively, whereas those for GPS L1C/A and L2P are both approximately 0.25 m. Furthermore, The results show that after correction of the pseudorange biases, the average convergence time for BDS-3/GPS static PPP decreases from 48.83/24.03 min to 38.54/21.12 min, respectively, a decrease of approximately 21%/12%. For BDS-3/GPS/BDS-3 + GPS kinematic PPP, the average convergence time decreases from 109.53/45.10/39.15 min to 62.99/40.83/22.94 min, respectively, a decrease of approximately 42%/41%/9%. Similarly, the three-dimensional positioning accuracy for BDS-3/GPS/BDS-3 + GPS dual-frequency pseudorange augmentation improves from 3.25/3.94/2.49 m to 2.65/3.69/2.16 m, respectively, increasing by approximately 6.3%, 18.5%, and 13.3%, respectively. The above analysis and experiments demonstrate that pseudorange bias is an important error source affecting both dual-frequency pseudorange augmentation and PPP services. Full article

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy with an increased female incidence ratio. The specific traits of X chromosome inheritance may be implicated in gender differences of PTC predisposition. The aim of this study was to investigate the association of two X-linked genes, Forkhead Box P3 (FOXP3) and Protein Phosphatase 1 Regulatory Subunit 3F (PPP1R3F), with PTC predisposition and gender disparity. One hundred thirty-six patients with PTC and an equal number of matched healthy volunteers were enrolled in the study. Genotyping for rs3761548 (FOXP3) and rs5953283 (PPP1R3F) was performed using polymerase chain reaction–restriction fragment length polymorphism assay (PCR-RFLP). The methylation status of FOXP3 was assessed using the combined bisulfite restriction analysis (COBRA) method. The SPSS software was used for statistical analyses. Gender stratification analysis revealed that the CA and AA genotypes and the A allele of FOXP3 rs3761548 variant are associated with PTC predisposition only in females. Moreover, different methylation status was observed up to the promoter locus of FOXP3 between PTC female patients, carrying the CA and CC genotype, and controls. Both revealed associations may explain the higher PTC incidence in females through reducing FOXP3 expression as reported in immune related blood cells. Full article

The ‘Feizixiao’ litchi cultivar, predominantly grown in Hainan Province, faces the issue of “sugar receding” during fruit ripening. The application of mixed foliar nutrients containing calcium and magnesium (Ca+Mg) during the fruit pericarp’s full coloring stage was investigated to overcome this issue. Experimental trials unveiled significant alterations in litchi pulp physiochemical properties, including the main nutrient and flavor quality, the total respiration rates of the main respiratory pathways, and the activities of some important enzymes associated with Embden–Meyerhof–Parnas (EMP), the tricarboxylic acid cycle (TCA) and the pentose phosphate pathway (PPP). The Ca+Mg treatment showed higher sugar levels than the control (CK) during ripening. Notably, the application of Ca+Mg in litchi pulp inhibited respiration rates through the EMP, TCA, and PPP pathways, resulting in a strong effect. RNA sequencing analysis revealed the impact of Ca+Mg treatment on respiratory pathways, revealing differentially expressed genes (DEGs) such as pyruvate PK1, PK2 (pyruvate kinase), and PDC (pyruvate dehydrogenase complex), validated through qRT-PCR with a significant correlation to RNA-seq results. In general, Ca+Mg treatment during litchi fruit ripening overcame “sugar receding” by inhibiting the expression of respiration key metabolic pathway genes. These findings provide insights for enhancing cultivation management strategies. Full article

Background and objective: The symptoms of most neurodegenerative diseases, including Parkinson’s disease (PD), usually do not occur until substantial neuronal loss occurs. This makes the process of early diagnosis very challenging. Hence, this research used variant call format (VCF) analysis to detect variants and novel genes that could be used as prognostic indicators in the early diagnosis of prodromal PD. Materials and Methods: Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI), and we analyzed prodromal patients with gVCF data collected in the 2021 cohort. A total of 304 participants were included, including 100 healthy controls, 146 prodromal genetic individuals, 21 prodromal hyposmia individuals, and 37 prodromal individuals with RBD. A pipeline was developed to process the samples from gVCF to reach variant annotation and pathway and disease association analysis. Results: Novel variant percentages were detected in the analyzed prodromal subgroups. The prodromal subgroup analysis revealed novel variations of 1.0%, 1.2%, 0.6%, 0.3%, 0.5%, and 0.4% for the genetic male, genetic female, hyposmia male, hyposmia female, RBD male, and RBD female groups, respectively. Interestingly, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300, and PPP6R2) that were recently detected in PD patients were detected in the prodromal stage of PD. Conclusions: Genetic biomarkers are crucial for the early detection of Parkinson’s disease and its prodromal stage. The novel PD genes detected in prodromal patients could aid in the use of gene biomarkers for early diagnosis of the prodromal stage without relying only on phenotypic traits. Full article

Compared to the traditional ionospheric-free (IF) precise point positioning (PPP) model, the undifferenced and uncombined (UU) PPP has the advantages of lower observation noise and the ability to obtain ionospheric information. Thanks to the IGS (International GNSS Service), real-time service (RTS) can provide RT vertical total electron content (VTEC) products, and an enhanced RT UU-PPP based on the RT-VTEC constraints can be achieved. The global performance of the BeiDou Navigation Satellite System-2 (BDS-2) and BDS-3 joint RT UU-PPP using different RTS products was investigated. There is not much difference in the RTS orbit accuracy of medium earth orbit (MEO) satellites among all analysis centers (ACs), and the optimal orbit accuracy is better than 5, 9, and 7 cm in the radial, along-track, and cross-track directions, respectively. The orbit accuracy of inclined geosynchronous orbit (IGSO) satellites is worse than that of MEO satellites. Except for CAS of 0.46 ns, the RTS clock accuracy of MEO satellites for other ACs achieves 0.2–0.27 ns, and the corresponding accuracy is about 0.4 ns for IGSO satellites. In static positioning, due to the limited accuracy of RT-VTEC, the convergence time of the enhanced RT UU-PPP is longer than that of RT IF-PPP for most ACs and can be better than 25 and 20 min in the horizontal and vertical components, respectively. After convergence, the 3D positioning accuracy of the static RT UU-PPP is improved by no more than 8.7%, and the optimal horizontal and vertical positioning accuracy reaches 3.5 and 7.0 cm, respectively. As for the kinematic mode with poor convergence performance, with the introduction of RT-VTEC constraints, the convergence time of RT UU-PPP can be slightly shorter and reaches about 55 and 60 min in the horizontal and vertical components, respectively. Both the horizontal and vertical positioning accuracies of the kinematic RT UU-PPP can be improved and achieve around 7.5 and 10 cm, respectively. Full article

This study was to explore potential SNP loci for reproductive traits in Chinese Holstein cattle and identify candidate genes. Genome-wide Association Study based on mixed linear model was performed on 643 Holstein cattle using GeneSeek Bovine 50 K SNP chip. Our results detected forty significant SNP loci after Bonferroni correction. We identified five genes (VWC2L, STAT1, PPP3CA, LDB3, and CTNNA3) as being associated with pregnancy ratio of young cows, five genes (PAEP, ACOXL, EPAS1, GLRB, and MARVELD1) as being associated with pregnancy ratio of adult cows, and nine genes (PDE1B, SLCO1A2, ARHGAP26, ADAM10, APBB1, MON1B, COQ9, CDC42BPB, MARVELD1, and HPSE2) as being associated with daughter pregnancy rate. Our study may provide valuable insights into identifying genes related to reproductive traits and help promote the application of molecular breeding in dairy cows. Full article