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Enhancing education quality with hybrid clustering and evolutionary neural networks in a multi phase framework
Feasibility of long-read sequencing to identify molecular alterations in an Indonesian cohort of locally advanced to advanced nasopharyngeal cancer
LncRNA CTD-2555A7.2 promotes bone formation with LncRNA-specific cascade amplification strategy
Abstract Osteoporosis poses a significant threat to human health. Long non-coding RNAs (LncRNAs) have been deemed as crucial regulators in the pathogenesis of osteoporosis. However, the accuracy and efficiency of LncRNA-mediated regulation of bone formation require further improvement. Our previous study identified a repeat sequence in the human-derived LncRNA CTD-2555A7.2, suggesting its potential role in osteoporosis regulation. To investigate this hypothesis, we conducted systematic functional analyses of CTD-2555A7.2 in osteogenesis and explored its mechanisms and potential therapeutic applications. Through over-expression, siRNA silencing and repeat sequence over-expression in vitro and in vivo, our research demonstrate that CTD-2555A7.2 enhances bone formation by sequestering multiple miR-381-3p molecules through its repeat sequence. Through Western blot, siRNA silencing and luciferase reporter assay, we illuminated miR-381-3p suppresses osteogenic differentiation by concurrently targeting four essential genes of the Wnt signaling pathway: Apc , Lef1 , wnt5a , and Lrp6 . Notably, the mRNA of CTD-2555A7.2 repeat sequence exhibited pronounced therapeutic efficacy in ovariectomy osteoporosis models. Taken together, we identified a dual-amplification osteogenic axis (CTD-2555A7.2-miR-381-Wnt) that demonstrates significant regulatory effects on osteoporosis. This study has established an important theoretical framework for understanding osteogenic LncRNA mechanisms and provides novel insights for developing targeted therapeutics against osteoporosis.
Genetic association analysis between LDL-c lowering drugs and portal hypertension using Mendelian randomization analysis
Abstract Clinical guidelines recommend the use of statins to reduce portal pressure and alleviate portal hypertension (PH). However, there is a lack of population-level studies on the use of non-statin Low-Density Lipoprotein Cholesterol (LDL-c) reduction agents for the treatment of PH. This study utilized a novel method, Mendelian Randomization (MR) analysis, to investigate the impact of commonly used LDL-c-lowering medications on PH. Instrumental variables (IVs) for eight lipid-lowering drug-related genes were extracted from three large-scale LDL-c databases of Genome-Wide Association Studies (GWAS), followed by MR analysis. The MR results indicated that, compared to normal individuals, lower expression of CETP and NPC1L1 in whole blood (result of meta-analysis: CETP [OR: 0.322, 95%CI:0.130–0.795, P = 1.396e-02], NPC1L1 [OR: 0.057, 95%CI: 0.022–0.146, P = 2.670e-09]) is associated with reduced portal pressure. The IVs of target genes were subjected to MR analysis with coronary atherosclerosis (CAD) as a positive control, confirming that the IVs can effectively substitute for the biological function of the target gene, thereby further enhancing the reliability of the results. Subsequently, Summary-based Mendelian Randomization (SMR) analysis was conducted by using expression quantitative trait loci (eQTL) data to validate the results of the MR analysis. The SMR results suggested that only NPC1L1 is associated with PH (OR: 0.648, 95%CI: 0.472–0.891, P SMR = 7.502e-3, P HEIDI = 0.747) from genetic correlation. Additionally, mediation analysis indicates that the therapeutic effect of NPC1L1 inhibitors on PH is partially mediated by tissue factor (mediating effect accounted for 18.52%, and the P value was 0.01). Phenome-Wide MR indicated that NPC1L1 inhibitors may be associated with 23 diseases or symptoms. In addition, NPC1L1 had genetic correlation between and alkaline phosphatase as well as total bilirubin, but no genetic correlation with alanine aminotransferase, aspartate aminotransferase, direct bilirubin, or gamma glutamyltransferase. In conclusion, this study systematically analyzed the genetic correlation between lipid-lowering drug targets and PH. From a genetic correlation perspective, we revealed that the potential therapeutic effect of NPC1L1 on PH may not be mediated through the reduction of LDL-c but rather through the modulation of tissue factors. Additionally, the potential side effects associated with NPC1L1 inhibition also were explored.
Simvastatin inhibits the immunosuppressive effects of endometrial cancer-associated mesenchymal stem cells through TGF-β2/SMAD2/3 signaling and reduces tumor growth
The effect of compositional fluctuations in a liquid Fe–O alloy on the nucleation of Earth’s inner core
Abstract The Earth’s solid inner core plays a fundamental role in determining the past and present properties and dynamics of the Earth’s deep interior. Inner core growth powers the geodynamo, producing the protective global magnetic field, and provides a record of core evolution spanning geological timescales. However, the origins of the inner core remain enigmatic. Traditional core evolution models assume that the inner core formed when the core first cooled to its melting temperature, but this neglects the physical requirement that liquids must be supercooled to below their melting point before freezing. Prior estimates from mineral physics calculations of the supercooling $$\delta T$$ required to homogeneously nucleate the inner core from candidate binary alloys exceed constraints of $$\delta T \lesssim 400$$ K inferred from geophysical observations, while a plausible scenario for heterogeneous nucleation has yet to be identified. Here we consider a different possibility, that atomic-scale compositional fluctuations can increase the local melting temperature, and hence supercooling, available for homogeneous nucleation. Using molecular dynamic simulations of Fe-O alloys we find that compositional fluctuations producing O-depleted regions are too rare to aid nucleation, while O-enriched regions can reduce the undercooling by $$\sim$$ 50 K ( $$\delta T \sim 700$$ K) for a bulk concentration of 20 mol.% O or $$\sim$$ 400 K ( $$\delta T \sim 300$$ K) for a bulk concentration of 30 mol.% O. While these results do not explain the nucleation of Earth’s inner core, they do show that compositional fluctuations can aid the process of homogeneous nucleation.
High-energy argon implantation in carbon nanowalls as a way to produce electrodes for supercapacitor applications
Fluid dynamics model of the cerebral ventricular system
Hydrocephalus, a neurological condition characterized by an excessive buildup of cerebrospinal fluid (CSF) in the brain, affects millions worldwide and leads to severe consequences. Current treatments, such as ventriculoperitoneal shunts, divert excess CSF from the brain but often face complications, mainly due to shunt obstructions caused by biological matter accumulation. While previous shunt designs aimed to improve fluid flow and reduce occlusion, they often lacked the precision needed for real-world applications due to simplified simulation models that did not fully capture the dynamics of the cerebral ventricular system. Here, we introduce BrainFlow, a computational model that integrates detailed anatomical and physiological features to simulate CSF dynamics in the presence of shunt implants. BrainFlow incorporates patient-specific medical imaging data, pulsatile flow to mimic cardiac cycles, adjustable parameters for various hydrocephalus conditions, and a biomolecule tracking feature to evaluate the long-term risk of shunt occlusion due to flow-mediated biomolecular transport. This model provides a more nuanced understanding of the factors contributing to shunt obstruction, offering insights into optimal shunt placement, design, and materials choice. Through validation against four-dimensional MRI flow data, BrainFlow demonstrates robust accuracy across multiple flow metrics. Our work lays the groundwork for the development of next-generation shunts tailored to individual patient anatomy and pathology, ultimately aiming to improve hydrocephalus treatment through informed, patient-specific design strategies.
Efforts to link HIV-positive and high-risk blood donors to HIV testing, and treatment services, Mozambique, 2019–2020
Abstract Mozambique’s National Blood Transfusion Services (NBTS) is tasked with providing safe and available blood but also conducting systematic screening of at-risk potential donors, notifying seropositive blood donors, and linking them to HIV care and treatment services. Potential blood donors who were deferred from donating following a behavioral risk screening and all blood donors who screened seropositive for HIV were notified and offered linkage to HIV testing, care, and treatment services by community-based organizations. A prospective study among HIV-positive blood donors and deferred donors was conducted from May 2019 to July 2020 at Maputo Central Hospital Blood Bank and the National Reference Blood Center. The associations between testing, initiating care and treatment services among HIV-positive blood donors and prospective deferred donors were estimated using fully Bayesian multivariable logistic models and odds ratios. Among 885 prospective blood donors enrolled, 173 (20%) were deferred due to self-reported high-risk behaviors identified through a screening questionnaire, and 712 (80%) passed the behavioral-risk screening tool, donated, and the blood donation tested positive for HIV. There were more than 2.5 times as many male donors as female donors with a positive HIV test, and among the deferred donors, more than 84% were males. 36% (256/712) of seropositive donors and 35% (61/173) of deferred donors were referred to HIV testing services. 62% (158/256) of seropositive donors and 4.9% (3/61) of deferred donors who were successfully referred were linked to care and treatment services, and 96% (152/158) of these seropositive donors and 100% (3/3) of deferred as high-risk donors initiated antiretroviral therapy (ART). Of the three service organizations used, one outperformed the other two in linking seropositive donors to ART treatment. The NBTS can serve as a critical entry point for identifying HIV-positive persons. Improved implementation of risk behavior screening tools is needed and could contribute to early identification and initiation of ART for potential donors. Innovative strategies and solutions by community-based organizations can be used to improve blood donor notification and linkage to HIV testing and treatment services.
Oxidative potential of PM1, PM2.5, and PM10 collected in car and tram tunnels to analyse their impact on public health
Identification of spastic ataxia-related proteins via comparative proteomic analysis of the cerebellum of conditional Ankfy1 knockout mice
Abstract Ankyrin repeat and FYVE domain containing 1 (ANKFY1) is an indispensable protein in the development of cerebellar Purkinje cells. Our preliminary study revealed that its absence caused progressive spastic ataxia, accompanied by the loss of Purkinje cells in mice. Here, we generated Ankfy1-floxed (Ankfy1 f/f) mice, in which conditional inactivation of the Ankfy1 gene was achieved specifically in cerebellar Purkinje cells via crossing with a transgenic mouse strain expressing Cre recombinase under the regulatory control of the Purkinje cell protein 2 (PCP2) promoter. We employed data-independent acquisition (DIA) mass spectrometry to compare the protein expression profiles in cerebellar samples. The samples were obtained from two groups of male mice. The first group consisted of three Pcp2-Cre; Ankfy1 f/f male mice, where the Ankfy1 gene was conditionally knocked out in Purkinje cells, and these mice were designated as the conditional knockout (CKO) group. The second group included three Cre-negative; Ankfy1 f/f littermate male mice served as the wild-type (WT) control group. The results identified 69 (45 upregulated and 24 downregulated) differentially expressed proteins (DEPs) in CKO vs. WT male mice with a 1.5-fold change. Enrichment analyses of these DEPs based on the Gene Ontology (GO), Orthologous Groups of Proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases revealed functional clusters associated with neuronal cell morphogenesis, extracellular structures, regulation of Rho-GTPase, calcium signaling pathway, etc. Itgb2, which was upregulated in CKO mice, was the top hub gene according to protein–protein interaction (PPI) analysis. We selected seven interesting differentially expressed genes (Arhgdib, Impa2, Pcp2, Pcp4, Ppp1r17, Rhobtb2, and Cdc123) for further validation. Arhgdib and Imp2a expression was increased in the cerebellum of CKO male and female mice, and Pcp2 and Pcp4 expression was decreased. Western blotting and immunofluorescence verified the upregulation of ARHGDIB and the downregulation of PCP2 in the cerebellum. Our proteomic analysis of conditional Ankfy1 knockout mice may guide future research to help develop treatments for progressive spastic ataxia.
MRI-derived articular cartilage strains predict patient-reported outcomes six months post anterior cruciate ligament reconstruction
Analysis of closed and open numerical systems of geochemical data in spatial statistics environment in order to separate anomalous areas
The proteome of circulating extracellular vesicles and their functional effect on platelets vary with the isolation method
Risk factors associated with health literacy among community residents in China based on multiple correspondence analysis and ordinal logistic regression
Dynamic assessment and zoning strategies for ecosystem health in Poyang lake urban agglomeration
Abstract Assessing and appropriately managing the ecosystem health of urban agglomerations are significant for safeguarding regional ecological security and sustainable development. From a spatiotemporal dynamic perspective, with the Poyang Lake urban agglomeration as a case, this study established a ‘Vigour–Organisation–Resilience–Service’ framework to assess ecosystem health, analysed spatiotemporal characteristics, identified key driving factors and their interactions contributing to spatial differentiation and ultimately adopted a ‘level–type’ zoning control strategy. The results show that: (1) From 2005 to 2022, the natural ecosystem health index declined in 14.70% of the region, with a central concentration of low values in the Poyang Lake area. The ecosystem service index decreased in 11.10% of the region but remained high in the Poyang Lake area. Varying degrees of positive spatial spillover effects were observed for both indices. (2) The average regional comprehensive ecosystem health index was 0.2914, with an overall downward trend. In the urban agglomeration, the comprehensive ecosystem health index remained stable in 78.18% of the total area, indicating a notable ‘polarisation’ in health levels among different areas. (3) Socioeconomic factors significantly influence ecosystem health in the urban agglomeration. (4) The urban agglomeration displayed distinct spatial patterns in terms of the types of changes in ecosystem health. Considering both current status and trends, zoning control and differentiated management strategies were implemented for the urban agglomeration. The approaches of differentiated management and zoning control can promote the coordinated development of the Poyang Lake urban agglomeration, facilitating a dynamic balance between urbanisation and ecological protection.
Make forensic case reports required legal and scientific documents
Implied object direction from eye location enhances animacy ratings but not detection of chasing behavior
Abstract Understanding how humans perceive animacy in dynamic visual stimuli is fundamental to elucidating the mechanisms underlying visual social cognition. While both object geometry and eye-like features are known to independently influence animacy impressions, their interactive effects remain insufficiently explored. This study investigates how the combination of object geometry and the location of eye-like patterns modulates the perception of animacy in non-living moving objects. In Experiment 1, we manipulated the pointing direction of triangular objects and the location of eye-like features (near the vertex, near the edge, or absent), and found that animacy impressions were enhanced when the direction of motion aligned with the gaze-implied object direction, irrespective of the object’s geometrical shape. Experiment 2 examined whether this effect generalizes to an objective task, in which participants identify a target triangle chasing a green disk among distractors. Although the gaze-implied object direction did not significantly influence detection sensitivity, the spatial location of the eye pattern within the triangular shape continued to weakly modulate participants’ performance. These findings suggest that cues related to eye location contribute to subjective animacy at multiple stages of cognitive processing, with their impact varying depending on task demands and perceptual context.