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Comparative analysis of seven types of phosphate transporters in forty species from the phylogenetic and transcriptomic perspective
Acquisition of phosphorus (P), an essential macronutrient for plants, is a limiting factor in most soils. Phosphate transporter proteins (PTs) play an indispensable role in inorganic phosphate (Pi) transport across the membrane barriers in plants. To understand the mechanisms associated with the P use efficiency of plants, we performed a comprehensive analysis of seven types of phosphate transporters—Pi-H + co-transporters [PHT1, PHT2, PHT3, and PHT4], plastid phosphate transporters (pPTs), glycerol-3-phosphate permeases (G3Pps), and SPX domain-containing PTs—across 40 species, from bacteria to higher plants. Using the amino acid sequences of PTs obtained by BLASTp, phylogenetic and structural analysis was performed. Analysis of conserved motifs within and between types of PTs was performed using the MEME program, and a pairwise genetic distance matrix was calculated in MEGA. Moreover, transcriptomic expression patterns in five tissues (root, stem, leaf, flower, and fruit) or in P starvation were examined in eight vegetable species using public databases. In total, 564 PHT1s, 94 PHT2s, 134 PHT3s, 228 PHT4s, 116 G3Pps, 546 pPTs, and 480 SPX-domain PTs were identified. The presence or copy number of different PT types varied among taxa, indicating that PHT3s, pPTs, and SPX-domain PTs are of eukaryotic origin, whereas PHT1s, PHT2s, PHT4s, and G3Pps are of prokaryotic origin. The absence of common motifs between the various PT types suggests that they originated and diversified independently. PHT1, G3Pp, and SPX-domain PT genes showed tissue-specific and P starvation induced expression, and thus are likely candidates for genetic modification strategies to obtain P-efficient crops.
Analytical construction of needle-type solitons in a M-fractional paraxial wave framework with dynamical analysis
Double-cuff versus single-cuff bronchial blockers for video-assisted thoracoscopic lobectomy: A randomized controlled trial
Background Bronchial blockers (BBs) manage airways during thoracoscopic lobectomy and isolate lungs by occluding the bronchus at the surgical site. However, intraoperative malpositioning remains a concern. We compared the performance of a new double-cuff BB (DcBB) with an additional cuff near the end of a single-cuff BB (ScBB) with that of ScBBs during thoracoscopic lobectomy. Methods This single-center, randomized, parallel, controlled clinical study enrolled 80 patients undergoing thoracoscopic lobectomy for lung cancer at Nanpi People’s Hospital. The patients were randomized into two groups (n = 40 each); DcBB (DcBB used during one-lung ventilation) and ScBB (ScBB used during one-lung ventilation). The primary outcomes were the incidence and number of BB malpositioning. Secondary outcomes time for BB placement and positioning, surgical duration, hypoxemia, incidence of adverse cardiovascular events, grades of lung collapse, surgeon satisfaction, tracheal wall damage assessed during bronchoscopy, contamination rates of the non-surgical lung lobe on the surgical site determined by bronchoscopy, radiographic incidence of pulmonary infiltration on postoperative day 1, and intraoperative blood gas values. Results The incidence of malpositioning was significantly lower in the DcBB than the ScBB group (7.5% vs . 30%, P = 0.02). The incidence of malposition was significantly lower in the DcBB cohort (P = 0.002). However, positioning the DcBB required more time (32.28 ± 5.37 vs . 19.90 ± 4.16 sec, P < 0.001). Other secondary outcomes did not differ significantly. Conclusions In patients undergoing thoracoscopic lobectomy, the DcBB was associated with a lower incidence of malposition than the ScBB. The DcBB did not increase tracheal wall injury or cause significant adverse hemodynamic effects, and therefore may serve as a promising optional device for airway management during thoracoscopic lobectomy, particularly in clinical scenarios requiring high placement stability. Trial registration the Chinese Clinical Trial Registry ChiCTR2400086472
Effect of fluid resuscitation on the cognitive prognosis of patients with septic encephalopathy: a prospective cohort study
The inhibitors of miR-224-5p, miR-339-5p, and miR-1198-5p improve auditory function by promoting the expression of neuritin in hearing loss mice
Background Sensorineural hearing loss (SNHL) is the main type of hearing impairment, and currently there is a lack of effective preventive or therapeutic drugs. Our previous research revealed that the expression of neurotrophic factor Neuritin decreased in hearing loss. After treatment with recombinant human Neuritin protein, the number of hair cells significantly increased. However, the molecular mechanism underlying the decreased expression of Neuritin in hearing loss remains unclear. Research indicates that Neuritin expression is regulated by microRNAs (miRNAs). This study aims to screen and validate the key miRNAs that regulate the expression of Neuritin and assess the feasibility of these miRNAs as therapeutic targets for SNHL. Methods This study utilized a mouse model of SNHL and employed high-throughput sequencing and bioinformatics analysis to screen for miRNAs that regulate the expression of neurofilament proteins in cochlear tissues. Subsequently, in vivo experiments were conducted to verify the regulatory effects of the candidate miRNAs on neurofilament proteins and to evaluate the improvement of SNHL by the corresponding miRNA inhibitors. Results After screening and identification, three miRNAs specifically inhibiting the expression of neurofilament protein were obtained, namely miR-224-5p, miR-339-5p and miR-1198-5p. The in vivo experimental results indicated that the inhibitors of the above three miRNAs had a significant improvement effect on the SNHL mouse model. Conclusion MiR-224-5p, miR-339-5p and miR-1198-5p can be involved in the pathogenesis of SNHL by regulating the expression of neurofilament proteins. Targeting these miRNAs or their inhibitors can provide new molecular targets and strategies for the prevention and treatment of SNHL.
Somatic evolution following cancer treatment in normal tissue
Abstract The extent to which exogenous sources, including cancer treatment, contribute to somatic evolution in normal tissue remains unclear. Here we used high-depth duplex sequencing 1 (more than 30,000× coverage) to analyse 168 cancer-free samples representing 16 organs from 22 patients with metastatic cancer enroled in the PEACE research autopsy study. In every sample, we identified somatic mutations (range 305–2,854 mutations) at low variant allele frequencies (median 0.0000323). We extracted 16 distinct single-base substitution mutational signatures, reflecting processes that have moulded the genomes of normal cells. We identified alcohol-induced mutation acquisition in liver, smoking-induced mutagenesis in lung and cardiac tissue, and multiple treatment-induced processes, which correlated with therapy type and duration. Exogenous sources, including treatment, underpinned, on average, more than 40% of mutations in liver but less than 10% of mutations in brain samples. Finally, we observed tissue-specific selection, with positive selection in tissues such as lung ( PTEN and PIK3CA ), liver ( NF2L2 ) and spleen ( BRAF and NOTCH2 ), and limited selection in others, such as brain and cardiac tissue. More than 25% of driver mutations in normal tissue exposed to systemic anti-cancer therapy, including in TP53 , could be attributed to treatment. Immunotherapy, although not associated with increased mutagenesis, was linked to driver mutations in PPM1D and TP53 , illustrating how non-mutagenic treatment can sculpt somatic evolution. Our study reveals the rich tapestry of mutational processes and driver mutations in normal tissue, and the profound effect of lifetime exposures, including cancer treatment, on somatic evolution.
Changes in myocardial elasticity derived from in-vivo cardiac MRI in a swine model of ischemic heart failure
ADVANTAGE: Advanced discovery of visceral analgesics by neuroimmune targets and the genetics of extreme human phenotype, a study protocol
Chronic visceral pain affects over 20% of adults globally but remains poorly understood, significantly impacting quality of life and healthcare costs. Limited understanding and diagnostic misconceptions hinder effective management, particularly during acute pain flares. This study aims to clarify underlying mechanisms and improve clinical management by combining detailed phenotyping, genetic analysis, immunological profiling, pain mapping, and wearable sensor data in three cohorts: Extreme Visceral Pain, Lack of Visceral Pain, and Healthy Controls. Participants with diverse visceral conditions, such as polycystic kidney disease, inflammatory bowel disease, chronic pancreatitis, endometriosis, painful bladder syndrome, vaginal mesh complications, and fibromyalgia, are recruited via clinical referrals from NHS Cambridge University Hospitals and NHS Lothian. Healthy control volunteers are recruited locally. Data collection involves daily pain ratings captured through a mobile app, wearable physiological monitoring, quantitative sensory testing, detailed medical and lifestyle questionnaires, and bio-sample analyses (genetic variants, autoantibodies). The primary confirmatory outcome evaluates the correlation between wearable sensor parameters and self-reported visceral pain intensity. Genetic analyses, including functional SNP allele discovery and Mendelian gene effect analysis, and immunological profiling will explore underlying biological mechanisms. Challenges anticipated include potential compliance and technical difficulties in remote data collection, potentially affecting data quality. Findings will be disseminated widely, aiming to refine diagnostic tools and inform treatment strategies, ultimately enhancing patient care and outcomes in chronic visceral pain management.
Eco-friendly synthesis of silver oxide nanoparticles using Nepeta cataria L. (Lamiaceae) flowers extract: a multifaceted study of their antimicrobial and hemocompatible potential
Abstract This is the first report on the green synthesis of silver oxide nanoparticles (Ag 2 ONPs) using Nepeta cataria flower extract as a novel bioreducing and capping agent in an aqueous medium. This study aimed to describe these distinctive nanoparticles and explore their versatile biomedical applications through in silico molecular docking. UV-Vis, FTIR, XRD, SEM-EDX, Zeta Potential and DLS were used to characterize the synthesized Ag 2 ONPs. Their biological effects were measured based on antibacterial, antifungal, hemolytic, anticoagulant, and thrombolytic activities. Characterization confirmed the crystallization and formation of stable, crystalline, quasi-spherical Ag 2 ONPs, with an average crystallite size of 20.7 nm (XRD) and a particle size of 39 ± 2.4 nm (SEM). The zeta potential − 39 mV indicated excellent colloidal stability. The Ag 2 ONPs exhibited strong antibacterial activity (maximum inhibition zone of 30 mm against Bacillus subtilis ) and potent antifungal activity (up to 83 mm) against Trichophyton rubrum . These nanoparticles were highly hemocompatible and exhibited strong anticoagulant and thrombolytic properties. To provide deeper insight into their antimicrobial action, this study uniquely integrated in silico molecular docking to explore interactions between the nanoparticles and key microbial protein targets. In summary, N. cataria L. flowers represent a promising new source of biocompatible Ag 2 ONPs with potent antimicrobial and hemo-modulatory properties, making them potential candidates for future therapeutic applications.
Disparities in prostate cancer screening practices among general practitioners and urologists (PROSHADE study): A cross-sectional study
Introduction Recent European recommendations promote risk-based, patient-centred screening models that emphasise shared decision-making (SDM) in prostate cancer (PCa) screening with prostate-specific antigen (PSA) testing. Understanding how clinicians apply these practices is essential, particularly given the roles of general practitioners (GPs) and urologists in detection. The aim of this study was to compare the knowledge, attitudes, and practices of GPs and urologists in Spain regarding PSA testing, PCa screening, and SDM implementation. Methods Cross-sectional survey conducted via an online questionnaire. Members of the Spanish Association of Urology (AEU) and the Spanish Society of Family and Community Medicine (semFYC) were surveyed online. The survey, developed and validated using a modified Delphi process, contained 18 items assessing clinicians’ opinions, practices, and knowledge of guidelines. Data from 494 respondents (280 GPs and 214 urologists) were analysed using descriptive statistics and logistic regression to explore differences between specialty, demographics, and screening practices. Results Urologists were more likely than GPs to consider PSA testing important (97.2% vs. 83.2%) and useful (96% vs. 44.4%), and to recommend it to relatives (90.4% vs. 44%) (all p < 0.001). They reported to initiate testing earlier (50–59 years: 77.8% vs. 32%) and reported to perform it more frequently (annual testing: 60.7% vs. 45.6%, p < 0.001). GPs reported to more often engaged in SDM when ordering PSA tests (69.7% vs. 10%, p < 0.001). Knowledge of guidelines was higher among urologists (91% vs. 24.1%), yet 75.4% stated that they had not modified practice following updated recommendations. Conclusions Significant specialty-based differences exist in PSA testing practices, perceptions, and guideline adherence. Urologists show greater familiarity with recommendations, while GPs reported more patient-centred communication.
Specific combinations of human and viral genetic variants explain a cancer predisposition in southern China
Suppression of DNA coffee-ring by compacting agents via adsorption at water/substrate and water/air interfaces
Abstract The drying of sessile drops of DNA solutions commonly leads to inhomogeneous deposition caused by the so-called coffee-ring effect, which hampers uniform surface immobilization in biosensing and microarray applications. Here, we investigate how DNA-compacting agents influence DNA patterns formed on negatively and positively charged solid substrates upon drop drying. Using poly-L-lysine and spermine as model compacting agents, we demonstrate that the suppression of the coffee-ring effect can arise from two distinct phenomena depending on the compacting agent concentration regime. At low concentrations, compacting agents mainly induce electrostatic adsorption of DNA at the water/substrate interface. Conversely, at higher concentrations, DNA compacts and aggregates, leading to trapping of aggregates at the water/air interface during evaporation and preventing their transport to, and accumulation at, the drop contact line. These findings constitute a new way to suppress the coffee-ring effect through DNA neutralization and compaction, and establish adsorption at interfaces as a general strategy for achieving homogeneous DNA coatings.
Development of a protocol for intravenous infusion management in patients with aggressive behavior due to mental disorders: A Donabedian framework approach
To establish a scientifically grounded and feasible intravenous infusion management protocol for patients with Aggressive behavior due to mental disorders. Methods: Guided by Donabedian’s theory, an initial draft of the management protocol was developed through a comprehensive literature review and semi-structured interviews with clinical experts. From June to July 2024, two rounds of expert consultation were conducted, and revisions were made until the final protocol was established. Results: The response rate for both rounds of expert questionnaires was 100%, with authority coefficients of 0.915 and 0.92. After the second round, the coefficients of variation for item importance ranged from 0 to 0.115 and from 0 to 0.107, while Kendall’s W coefficients were 0.506 and 0.628, respectively, indicating statistically significant expert consensus (P < 0.05). Ultimately, the final protocol comprised 3 first-level items, 17 second-level items, and 41 third-level items. Conclusion: The intravenous infusion management protocol developed on the basis of Donabedian’s theory is both rigorous and targeted, providing a foundation for the comprehensive management of intravenous infusion in patients with aggressive behavior.
Explainable zero-day attack detection in IoMT using transformer-based time-series modeling
Identifying and validating ITGB2 and HNRNPAB as diagnostic biomarkers in chronic obstructive pulmonary disease using bioinformatics and Integrated Machine Learning Methods
Background and Aim COPD is a common respiratory disease characterized by progressive airflow restriction that severely affects patients’ quality of life and leads to significant mortality rates worldwide. This study aims to strengthen the early diagnosis of COPD and develop personalized treatment strategies. Methods The methodology involved a comprehensive approach, including differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and machine learning techniques. Data from the combined datasets GSE37768 and GSE38974 were utilized to identify differentially expressed genes (DEGs). The machine learning integrated model was employed to screen for diagnostic molecular biomarkers related to COPD. Additionally, pathway analysis, transcription factor gene regulatory network analysis, immune cell composition analysis using CIBERSORT, and mendelian randomization analysis were conducted to elucidate the molecular mechanisms and potential biomarkers for COPD. Finally, we validated the model using Polymerase Chain Reaction (PCR), immunohistochemistry (IHC) and Immunofluorescence (IF). Results This study employed bioinformatics and Integrated Machine Learning Methods to identify ITGB2 and HNRNPAB as potential related targets for COPD. Subsequent verification through PCR, IHC, and IF experiments confirmed that ITGB2 and HNRNPAB were key biomarkers for COPD. Pathway analysis revealed that ITGB2 and HNRNPAB were mainly involved in immune responses and metabolic pathways. Conclusion This comprehensive study presents an in-depth investigation of the molecular mechanisms of COPD and identifies candidate exploratory biomarkers for further research toward early diagnosis and potential personalized treatment strategies. In future studies, the identified exploratory biomarkers should be validated in larger cohorts and their therapeutic significance explored.
Pristine Antarctic ice records the Solar System’s travels
DEF-CRYPT-Q: a quantum-enhanced hybrid encryption framework for privacy-preserving distributed defense communications
Abstract The rapid transformation of defense communication ecosystems into distributed, AI-enabled, and multi-domain operational environments has exposed significant vulnerabilities in existing cryptographic infrastructures. These vulnerabilities are particularly critical in light of the imminent advancement of quantum computing, which threatens conventional public-key encryption schemes, and the operational limitations imposed by lightweight encryption mechanisms deployed on resource-constrained battlefield devices. The traditional public-key algorithm like RSA and ECC, could be exploited by quantum attacks, and the resource-efficient ciphers are not always effective to protect against advanced cyber-warfare, interception, and integrity-compromise in high-mobility tactical networks. This paper suggests DEF-CRYPT-Q (Defense Cryptographic Quantum-Enhanced Privacy-Preserving Hybrid Framework) to secure distributed defense communication data because it is motivated by the requirement of having a single, quantum-resilient, and privacy-preserving security architecture that is suitable in the context of heterogeneous defense settings. The suggested architecture will have four synergistic elements, namely (i) a Context-Aware Lightweight Defense Encryption (CALDE) module that is optimized to support constrained soldier wearables, UAV nodes, and edge sensors; (ii) a Quantum-Resistant Cryptographic Layer (QRCL) that uses lattice-based post-quantum primitives, such as CRYSTALS-Kyber to support the encapsulation of secure keys and CRYSTALS-Dilithium to support the generation of digital signatures, providing long-term quantum safety The experimental assessment of a heterogeneous model of a defense communication demonstrates the shortening of the encryption latency, the limited computational costs of the models of constrained platforms, the high level of integrity, and the resistance to classical and quantum adversarial models, which in turn makes it possible to claim that DEF-CRYPT-Q is a scalable and prospective cryptographic paradigm that is consistent with the strategic goals of modernizing its defense. Simulation results demonstrate that Adaptive DDP-QKA reduces encryption latency to 14.83 ms (vs. 18.21 ms classical and 21.48 ms naïve PQC) and bandwidth overhead to 13.9% (vs. 124.6% PQC), while maintaining moderate energy use (1.14 units). It achieves high quantum resistance (0.92 score), mission adaptability (0.95), and low residual risk (< 0.1 for major threats), verifying appropriateness for latency-sensitive defense communications.
‘Just Play’ (JP) - creative arts therapies-based dyadic intervention for children with intellectual disability and their mothers: Study protocol for a mixed-methods randomized controlled trial
Background Play is a fundamental aspect of children’s development, fostering their cognitive, social, and emotional growth. However, children with intellectual disability (ID) experience limitations in their ability to engage in play, which can impact their relationships with caregivers. Parents of children with ID face heightened stress and reduced playfulness in their interactions with their children. Existing early interventions have primarily focused on behavioral parent training programs to manage challenging child behaviors, lacking a direct and positive approach to enhancing parent-child play interactions and relationships. Objective This study aims to develop, implement, and evaluate ‘Just Play’(JP), a creative arts therapies-based dyadic early intervention to enhance the quality of mother-child interactions through positive playful engagement. Methods A mixed-methods randomized controlled trial will be conducted with 60 mother-child dyads (children aged 3–7 with a prior ID diagnosis). Participants will be randomly assigned to either the JP dyadic intervention or to psycho-educational parent counseling control group. Quantitative data will include measures of emotional availability, mother and child playfulness, and the level of interpersonal synchrony between mothers and their children at baseline and post-intervention. Additionally, qualitative interviews with a subset of mothers in the JP group will be conducted at post-intervention and two-month follow-up to explore their experiences and identify the best practices of the intervention. Results & Implications This study will provide empirical evidence on the effectiveness of JP dyadic intervention in strengthening positive mother-child relationships in families of children with ID. Findings will inform future early intervention strategies, contributing to evidence-based guidelines for practitioners working with children with ID while emphasizing the unique contribution of creative arts therapies to this population. Trial registration ClinicalTrials.gov, registered August 6, 2024 ( NCT06541782 || https://clinicaltrials.gov/study/NCT06541782 ).
Stress-strength reliability inference in multicomponent systems under the unit-gamma Gompertz–Weibull distribution based on progressive Type-II censoring
Precision improvement for indoor positioning based on fuzzy inference system with ultra-wideband wireless communications
This paper investigates the enhancement of positioning accuracy in indoor non-line-of-sight (NLOS) environments using ultra-wideband (UWB) and angle of arrival (AoA) technologies. It examines the application of moving average filters and the adaptive offset cancellation (AOC) method in known target’s location area scenario. Furthermore, this study evaluates the performance of positioning accuracy using various input membership functions in fuzzy inference systems for aera recognition in unknown target’s location area situation, in conjunction with the AOC method. Experimental results show that the AOC method effectively reduces positioning errors by an average of 29.38 cm across twelve test points when the area where the target is located are known, achieving an error reduction to within 20 cm. In cases where target’s location area is unknown, the fuzzy inference system using fuzzy triple std as input membership function achieves an average regional recognition accuracy of 95.68%, outperforming other methods. The proposed fuzzy inference combined with AOC (FAOC) method improves the average positioning error by 40.9% compared to the original positioning method, reducing from 69.03 cm to 44.48 cm.