Significant Modulation Research Articles

Identification of trait-associated microRNA modules in liver transcriptome of pig fed with PUFAs-enriched supplementary diet.

Dietary lipids provide energy, are cellular structural components, and are involved in physiological processes. Lipids are the dietary source in supplementary diet experiments in pigs. This study aims to investigate the dietary effects of PUFAs on the hepatic transcriptome and physiological pathways of two diets on two pig breeds. Polish Landrace (PL: n = 6) and six PLxDuroc (PLxD: n = 6) pigs were fed with a normal diet (n = 3) or PUFAs-enriched healthy diet (n = 3), and the hepatic miRNA profiles were studied for weighted gene co-expression network analysis biological interactions between gene networks and metabolic pathways of DE miRNA genes. The study identified trait-associated modules that were significantly associated with four phenotypic traits in the dietary groups of PL and PLxD: meat colour (a*), shoulder subcutaneous fat thickness, conductivity 24h post-mortem (PE24), and ashes. Trait-wise, a large set of co-expressed miRNAs of porcine liver were identified in these trait-associated significant modules (9, 7, 2, and 8) in PL and PLxD. Each module is represented by a module eigengene (ME). Forty-four miRNAs out of 94 miRNAs interacted with 6719 statistically significant target genes with a target score > 90. The GO/pathway analysis showed association with pathways including regulation of metallopeptidase activity, sebaceous gland development, collagen fibril organization, WNT signalling, epithelial tube morphogenesis, etc. The study showed the differences in miRNA expression between the dietary groups of PL and PLxD breeds. Hub genes of discovered miRNA clusters can be considered predicted miRNA genes associated with PE24, meat colour, shoulder subcutaneous fat thickness, and ashes. Discovered target genes for miRNA clusters play significant roles in biological functions such as (i) muscle and body growth development, (ii) different cellular processes and developments, (iii) system development, and (iv) metabolic processes.

QTL mapping and transcriptome analysis of seed germination under PEG-induced water stress in Lactuca spp.

The impact of limited water availability on lettuce growth has been well documented. However, the mechanisms by which lettuce controls seed germination under water stress remain unknown. Germination percentage was evaluated in the cv. Salinas (Lactuca sativa) (L. sativa) × US96UC23 (Lactuca serriola) (L. serriola) recombinant inbred line (RIL) population and USDA germplasm collection using 10% polyethylene glycol (PEG). About 50% of both populations displayed less than 90% germination. The average broad-sense heritability (H2) for germination percentage was 0.81 across both populations. Two quantitative trait loci (QTL) for germination percentage were identified on chromosomes 4 and 8 in the RIL population. The RNA-Seq and network analyses of wild lettuce, US96UC23, were performed using the control (distilled water, dH2O) and treatment (10% PEG) datasets. The number of differentially expressed genes (DEGs) was 4,095. The top 20 gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were assessed by enrichment analysis. The consensus network analysis captured 44 modules. Gene networks were constructed for the top 20 hub genes in 10 significant modules from each dataset. This study comprehensively explains QTL, GO terms, KEGG pathways, and gene networks associated with lettuce seed germination under osmotic stress.

Identification of Sequential Molecular Mechanisms and Key Biomarkers in Early Glaucoma by Integrated Bioinformatics Analysis.

Glaucoma is a neurodegenerative disease characterized by progressive optic nerve degeneration and retinal ganglion cell (RGC) loss. In early glaucoma, before obvious axon loss, highly organized pathological processes in RGCs occur sequentially, involving axons, dendrites and synaptic terminals. The optic nerve head (ONH) is the critical structure of early glaucomatous neurodegeneration. Taking advantage of high-throughput data from the ONH and the weighted gene coexpression network analysis (WGCNA) method, the current study aims to gain insight into the full scope of pathological events in early glaucoma and define their chronological sequence. The expression profiles of GSE26299, GSE110019, and GSE139605, which measure ONH gene expression in different glaucoma models, were downloaded from the Gene Expression Omnibus (GEO) database. In GSE26299, which uses 10.5-month-old DBA/2J mice, WGCNA was utilized to construct a gene coexpression network, and the most significant modules of early (NOE), moderate (MOD) and severe (SEV) glaucoma were identified. The differentially expressed genes (DEGs) of GSE110019 and GSE139605 significantly overlapped with the correlated module of the MOD group, so the 3 gene sets were analyzed together. Pathway enrichment analysis via the GO, KEGG, and Reactome pathways was subsequently performed, followed by protein‒protein interaction (PPI) analysis to screen key genes associated with each stage. Several hub gene expression patterns were identified in a glucocorticoid-induced glaucoma (GIG) model via quantitative PCR and immunostaining. The pink module was positively correlated with the NOE group (r = 0.48, p = 4e-04) and negatively correlated with the glaucoma stage (r = -0.88, p = 3e-17). The genes in the pink module were enriched in the synaptic transmission and axonal transport pathways. The tan module was negatively correlated with the NOE group (r = -0.43, p = 0.002) and positively correlated with the glaucoma stage (r = 0.77, p = 7e-11). The genes in the tan module were associated with pathways such as tight junctions, retinol metabolism, and linoleic acid metabolism. The purple module was positively correlated with the MOD group (r = 0.64, p = 5e-07). The common genes among the purple module and the DEGs of the two other datasets were enriched in pathways related to mitotic cell division, cytokine activity, and the extracellular matrix (ECM). The hub genes identified by PPI included Nrn1, Cplx1, Timp1, and Cdk1. Quantitative PCR and immunostaining confirmed that Limk1 expression was increased in the ONH of GIG mice. In early glaucomatous neuropathy, intrinsic changes in RGCs precede the activation of glial cells and ECM remodeling. These latter events are common pathological changes observed in the ONH in both cats and mice. Our study may provide new targets for the early detection and treatment of glaucoma.

Amorphous NiO nanopyramids with superior electrochromic energy storage properties

In this work, amorphous NiO nanopyramid film has been obtained by using the pulsed magnetron sputtering technique. The uniform amorphous NiO nanostructures exhibit significant electrochromic modulation efficiency in the visible and near-infrared ranges, achieving a high modulation efficiency of 60.73 % at 550 nm and 21.58 % at 1500 nm. It exhibits rapid response time (coloring takes 2.4 s, and bleaching takes 1.0 s) and significant coloring efficiency (43.23 cm2C-1). Moreover, amorphous NiO nanopyramid film displays promising properties of energy storage. The NiO nanopyramid film shows high areal capacitance (7.08 mF/cm2), along with satisfying rate capability. The alteration in the electrode color offers a convenient method for monitoring the quantity of energy stored. Furthermore, the microstructure characteristic, degree of crystallization and electrochemical performance of the NiO film are significantly influenced by both oxygen partial pressure and sputtering time. These findings highlight the potential of employing this bifunctional amorphous NiO nanopyramid film in diverse advanced nanodevices, encompassing electrochromic energy storage applications with superior performance.

Can Offset Analgesia Magnitude Provide Additional Information About Endogenous Pain Modulation in People With Knee Osteoarthritis? An Experimental Study.

To investigate the relationship between offset analgesia magnitude and the responsiveness to conditioned pain modulation (CPM), temporal summation of (second) pain (TSP), and clinical pain severity in people with knee osteoarthritis (KOA). Electrical stimuli were applied to 88 participants with KOA to measure offset analgesia at the volar forearm of the dominant hand, and CPM and TSP at the most symptomatic knee and ipsilateral volar wrist. Clinical pain severity was assessed using the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOSPAIN). Linear mixed effects models evaluated pain modulatory effects across all tests, and Spearman's partial correlations assessed associations between offset analgesia, CPM, TSP, and KOOSPAIN while accounting for covariates of interest. Participants unable to validly finish all psychophysical tests were excluded from effect and correlation analyses but were evaluated for predictors of non-valid completion using bivariate Stochastic Search Variable Selection. Significant pain modulation was observed across all psychophysical tests (P < 0.05) and no meaningful predictors of non-valid test completion were found. Offset analgesia magnitude did not significantly correlate with CPM, TSP, or KOOSPAIN (p ≥ 0.05), with a maximum partial correlation coefficient of ρ = 0.21. Offset analgesia was not associated with CPM, TSP, or KOOSPAIN in people with KOA. Despite the lack of case-control studies comparing offset analgesia between people with KOA and healthy controls, these findings suggest that offset analgesia may provide information about endogenous pain modulation beyond CPM and TSP, though its clinical translation remains uncertain.

Haematology and histology studies on Moringa oleifera leaves and bark extracts in streptozotocin-induced diabetic albino rats

Alterations in haematological parameters are frequently observed in individuals with diabetes mellitus (DM). Oxidative stress has been identified as a contributing factor in the pathogenesis of organ damage and haematological dysfunction associated with DM. As a result, the potential positive impact of Moringa oleifera, a medicinal plant known for its antioxidant properties, on haematological parameters and kidney function in diabetic rats was investigated. A total of thirty-five rats were divided into seven groups, each consisting of five rats. Group I was administered only distilled water, while groups II to VII were induced with a single dose of 60mg/kg streptozotocin intraperitoneally. Subsequently, groups II to VI were treated with 150 mg/kg Moringa oleifera leaf methanol extract, 150 mg/kg Moringa oleifera bark methanol extract, 300 mg/kg Moringa oleifera leaf, 300 mg/kg Moringa oleifera bark, and metformin, respectively. The results showed positive modulation to most of the haematology parameters evaluated except neutrophils and lymphocytes by the treatments. The leaf extract showed a more significant modulation of platelets than other treatments. The histology of the kidney showed normal structure for all the treatments. Moringa oleifera especially the leaf extract is promising in the treatment of DM

X-ray and optical observations of the millisecond pulsar binary PSR J1431–4715

We present the first X-ray observation of the energetic millisecond pulsar binary PSR J1431−4715, performed with XMM-Newton and complemented with fast optical multi-band photometry acquired with the ULTRACAM instrument at ESO-NTT. It is found as a faint X-ray source without a significant orbital modulation. This contrasts with the majority of systems that instead display substantial X-ray orbital variability. The X-ray spectrum is dominated by non-thermal emission and, due to the lack of orbital modulation, does not favour an origin in an intrabinary shock between the pulsar and companion star wind. While thermal emission from the neutron star polar cap cannot be excluded in the soft X-rays, the dominance of synchrotron emission favours an origin in the pulsar magnetosphere that we describe at both X-ray and gamma-ray energies with a synchro-curvature model. The optical multi-colour light curve folded at the 10.8 h orbital period is double-humped and dominated by ellipsoidal effects, but also affected by irradiation. The ULTRACAM light curves are fit with several models encompassing direct heating and a cold spot, or heat redistribution after irradiation either through convection or convection plus diffusion. Despite the inability to constrain the best irradiation models, the fits provide consistent system parameters, giving an orbital inclination of 59 ± 6° and a distance of 3.1 ± 0.3 kpc. The companion is found to be an F-type star, underfilling its Roche lobe (fRL = 73 ± 4%) with a mass of 0.20 ± 0.04 M⊙, confirming the redback status, but hotter than the majority of redbacks. The stellar dayside and nightside temperatures of 7500 K and 7400 K, respectively, indicate a weak irradiation effect on the companion, likely due to its high intrinsic luminosity. Although the pulsar mass cannot be precisely derived, a heavy (1.8−2.2 M⊙) neutron star is favoured.

High-fidelity simulations of microramp-controlled shock wave/boundary layer interaction

Microvortex generators (MVGs) are a promising solution to control shock wave/turbulent boundary layer interactions (SBLIs), especially in supersonic inlets. In this study, we examine the effects of a microramp vortex generator on an SBLI generated by an oblique shock wave and a turbulent boundary layer using direct numerical simulations (DNSs). Two cases, with and without the presence of a microramp, are compared in terms of their mean and unsteady flow features at free-stream Mach number equal to 2 and friction Reynolds number at the inviscid shock impingement equal to 600. The long integration period allows us to assess how microramps affect the typical low-frequency unsteadiness observed in SBLIs, and the data generated may serve as a reference for simulations of lower fidelity or reduced order models. The analysis shows that the three-dimensional microramp wake alters the interaction region dramatically, inducing a significant spanwise modulation and topology change of the separation. For example, tornado-like structures redistribute the flow in both the spanwise and wall-normal directions inside the recirculation region. The increase in momentum close to the wall by the ramp vortices effectively delays the onset of the separation and, thus, the separation length, but at the same time leads to a significant increase in the intensity of the wall-pressure fluctuations. We then characterise the mutual interaction between the arch-like vortices around the ramp wake and the SBLI. The specific spanwise vorticity shows that these vortices follow the edge of the separation and their intensity, apart from mean compressibility effects, is not affected by the shocks. The shocks, instead, are deformed in shape by the periodic impingement of the vortices, although the spectral analysis did not reveal any significant trace of their shedding frequency in the separation region. These Kelvin–Helmholtz vortices, however, may be relevant in the closure of the separation bubble. Fourier analysis also shows a constant increase, in both value and magnitude, in the low-frequency peak all along the span, suggesting that the motion of the separation shock remains coherent while being disturbed by the arch-like vortices and oscillating at a higher frequency in absolute terms.

Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches

BackgroundIn addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors.MethodsIn a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague–Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration.ResultsBoth doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP.ConclusionsThe findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.

π-Conjugation-Induced In Situ Nanoscale Ordering of Spiro-OMeTAD Boosts the Efficiency and Stability of Perovskite Solar Cells.

Spiro-OMeTAD hole transport materials typically exhibit an amorphous state in perovskite solar cells. However, the lack of structural ordering leads to weak intermolecular interaction, inferior carrier transfer, and poor stability in devices. Herein, we developed a π-conjugation-induced short-range ordering strategy to modulate the stacking order of spiro-OMeTAD during film formation. A clear molecular ordering at the nanoscale is observed, which enhances intermolecular π-π stacking in spiro-OMeTAD and enables effective carrier extraction and favorable energy level alignment. The nanoscale-ordered spiro-OMeTAD allows the achievement of perovskite solar cells with a champion efficiency of 25.37%, surpassing devices utilizing amorphous spiro-OMeTAD (23.52%). The unencapsulated device demonstrates enhanced operational stability by retaining 98% of its initial efficiency under continuous 1 sun equivalent illumination at 60 °C for 840 h. This work establishes a significant and valid modulation concept for the stacking order of organic transport materials, paving the way for the development of efficient and stable perovskite solar cells.

Impairment of Neuronal Activity in the Dorsolateral Prefrontal Cortex Occurs Early in Parkinsonism.

Parkinson's disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition. Investigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task. Using a within-subject design, single and multi-unit neuronal activity was recorded in the DLPFC of a nonhuman primate before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions. These results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.

Comparison of Micro-CT and Morphometric Outcomes in a Modified Experimental Rat Model of Periodontitis.

To assess the correlation between micro-computed tomography (micro-CT) and linear morphometric measurements in terms of mandibular bone levels in a modified experimental periodontitis model in rodents to study the mechanisms of association between periodontal destruction and neuroinflammation. The proposed invivo experimental periodontitis model involves the administration of oral rinses with Porphyromonas gingivalis and Fusobacterium nucleatum, four times per week during 4, 8 or 12 weeks, in 24 male Wistar Hannover rats (180 g, 5 weeks old). After euthanasia, hemi-mandibles were collected. One hemi-mandible was analysed using morphometry, while the other was assessed with micro-CT. Linear measurements were taken at the buccal aspect and furcation level for both techniques, and volumetric measurements were also obtained with micro-CT. Passing-Bablok regression analysis was used to compare the results of both techniques, with morphometric measurements serving as the reference. Moreover, Lin's Concordance correlation coefficient was calculated to assess the level of agreement. Periodontal clinical variables with neuroinflammatory parameters from the frontal cortex were used to evaluate the association between the resulting condition and neuroinflammation. Twenty-one out of the initial 24 rats were analysed. The micro-CT linear measurements demonstrated high concordance values with the linear morphometric measurements at the buccal surfaces of the roots in molars (r = 0.714) but not at the furcation area (r = 0.052). At 12 weeks, there was a significant impact on neuroinflammation with significant decreases in iNOS levels and p-mTOR levels at 4 and 8 weeks. The proposed invivo experimental periodontitis model demonstrated a high degree of correlation between morphometric and micro-CT measurements in buccal areas but not at the furcation level. Concomitantly, there was a significant temporary modulation of the neuroinflammatory response.

A Wide Color Gamut and Noniridescent Zinc-Anode Asymmetric Electrochromic Device for Self-Sustaining Color-Adaptive Bio-Camouflage System.

Inspired by camouflage-colored organisms, the development of bio-camouflage systems using electrochromic (EC) technology has gained significant interest. However, existing EC systems struggle with achieving a wide color gamut, noniridescent colors, and self-sustainability. Herein, a self-sustainable color-adaptive bio-camouflage system integrating EC and nanogenerator (NG) technologies, enabling environmental color adaptation, and thermal regulation without an external power source is proposed. The system is based on a zinc-anode EC device (ZECD) with an asymmetric structure, incorporating flexible tungsten oxide and vanadium oxide electrodes. During the EC process, tungsten oxide shifts between blue and transparent, allowing near-infrared thermal modulation, while the vanadium oxide transitions from yellow to transparent. This design enables reversible near-infrared modulation and noniridescent color conversion among black, blue, green, yellow, and transparent. For the self-sustainability of the system, an electromagnetic and triboelectric hybrid NG that collects biomechanical energy is developed. In a typical driven cycle, the integrated system transitions colors and achieves significant near-infrared spectral modulation, demonstrating environmental adaptability and thermal regulation. Experiments on human skin and simulated chameleon color changes further confirm the system's effectiveness. This work highlights the potential of integrating EC and NG technologies to advance color-adaptive camouflage systems, opening new an avenue for bio-camouflage design.

Anti-fatigue effect of an enzymatically derived deer velvet extract through muscle damage recovery and improvement of antioxidant levels

Ethnopharmacological relevanceDeer velvet (DV) has been extensively used in traditional Oriental medicine to treat various diseases. Its pharmacological spectrum encompasses tonicity, longitudinal bone growth of adolescence, blood retention, hemopoiesis facilitation, enhancement of organ function, physical function improvement, and augmentation of physical vitality. Among its myriad effects, DV notably exhibits anti-fatigue properties; however, its specific mode of action is yet to be fully elucidated. Aim of the studyThis study was undertaken to investigate the anti-fatigue and exercise performance-enhancing effects of YC-1101(HENKIV®), an enzymatically derived DV extract, in C2C12 cell lines and forced swimming mouse models. Materials and methodsThe effect of YC-1101 on increasing cell growth and lowering lactate dehydrogenase (LDH) activity was assessed in C2C12. The antioxidative effects of YC-1101 and its mechanistic underpinnings were also evaluated in C2C12 cells. Moreover, mice were subjected to an exhaustive swimming test subsequent to 3 weeks of YC-1101 extract administration. Fatigue-associated biochemical parameters, such as LDH activity and lactate, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels, were measured in serum and muscle tissues. ResultsYC-1101 significantly promoted myoblast growth and reduced LDH activity, indicative of a cell-proliferative effect. Notably, free radical scavenging assays and analysis of reactive oxygen species production and antioxidant-related mRNA expression corroborated the significant involvement of YC-1101 in antioxidation, an important mechanism in anti-fatigue processes. Furthermore, animal experiments demonstrated prolonged swimming endurance and inhibition of muscle LDH accumulation in forced swimming mouse models. Serum biochemical analysis further revealed significant modulation of the expression of anti-fatigue-related biomarkers. Various bioactive low-molecular-weight DV peptides were enriched in YC-1101 compared to YHC-BE-2038 (a DV extract without enzymatic digestion). The anti-fatigue effect of YC-1101 was significantly stronger than that of YHC-BE-2038. ConclusionsThese findings suggest the potential of YC-1101 as a nutraceutical adjunct in ameliorating fatigue, concurrently facilitating muscle damage recovery, and exerting antioxidant effects via the nuclear factor E2-related factor 2-Kelch-like ECH-associated protein-1 pathway. It can be assumed that the complex action of low-molecular-weight DV peptides produced during the enzymatic degradation process was effective, and the further research is needed.

Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis

Changes in chondrocyte gene expression can contribute to the development of osteoarthritis (OA), and so recognition of the regulative processes during chondrogenesis can lead to a better understanding of OA. microRNAs (miRNAs) are key regulators of gene expression in chondrocytes/OA, and we have used a combined experimental, bioinformatic, and systems biology approach to explore the multiple miRNA–mRNA interactions that regulate chondrogenesis. A longitudinal chondrogenesis bioinformatic analysis identified paralogues miR-199a-5p and miR-199b-5p as pro-chondrogenic regulators. Experimental work in human cells demonstrated alteration of miR-199a-5p or miR-199b-5p expression led to significant inverse modulation of key chondrogenic genes and extracellular matrix production. miR-199a/b-5p targets FZD6, ITGA3 and CAV1 were identified by inhibition experiments and verified as direct targets by luciferase assay. The experimental work was used to generate and parameterise a multi-miRNA 14-day chondrogenesis kinetic model to be used as a repository for the experimental work and as a resource for further investigation of this system. This is the first multi-miRNA model of a chondrogenesis-based system, and highlights the complex relationships between regulatory miRNAs, and their target mRNAs.

Sr-Doping-Modulated Metal-Insulator Transition in NdNiO3 Epitaxial Films

Abstract Perovskite-structured nickelates, ReNiO3 (Re = rare earth), have long garnered significant research interest due to their sharp and highly tunable metal-insulator transitions (MITs). Doping the parent compound ReNiO3 with alkaline earth metal can substantially suppress this MIT. Recently, intriguing superconductivity has been discovered in doped infinite-layer nickelates (ReNiO2), while the mechanism behind A-site doping-suppressed MIT in the parent compound ReNiO3 remains unclear. To address this problem, we grew a series of Nd1−x Sr x NiO3 (NSNO, x = 0–0.2) thin films and conducted systematic electrical transport measurements. Our resistivity and Hall measurements suggest that Sr-induced excessive holes are not the primary reason for MIT suppression. Instead, first-principles calculations indicate that Sr cations, with larger ionic radius, suppress breathing mode distortions and promote charge transfer between oxygen and Ni cations. This process weakens Ni–O bond disproportionation and Ni2+/Ni4+ charge disproportionation. Such significant modulations in lattice and electronic structures convert the ground state from a charge-disproportionated antiferromagnetic insulator to a paramagnetic metal, thereby suppressing the MIT. This scenario is further supported by the weakened MIT observed in the tensile-strained NSNO/SrTiO3(001) films. Our work reveals the A-side doping-modulated electrical transport of perovskite nickelate films, providing deeper insights into novel electric phases in these strongly correlated nickelate systems.

Comparative Analyses of Dynamic Transcriptome Profile of Heart Highlight the Key Response Genes for Heat Stress in Zhikong Scallop Chlamys farreri.

Heat stress resulting from global climate change has been demonstrated to adversely affect growth, development, and reproduction of marine organisms. The Zhikong scallop (Chlamys farreri), an important economical mollusk in China, faces increasing risks of summer mortality due to the prolonged heat waves. The heart, responsible for transporting gas and nutrients, is vital in maintaining homeostasis and physiological status in response to environmental changes. In this study, the effect of heat stress on the cardiac function of C. farreri was investigated during the continuous 30-day heat stress at 27 °C. The results showed the heart rate of scallops increased due to stress in the initial phase of high temperature exposure, peaking at 12 h, and then gradually recovered, indicating an acclimatization at the end of the experiment. In addition, the levels of catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) exhibited an initial increase followed by recovery in response to heat stress. Furthermore, transcriptome analysis of the heart identified 3541 differentially expressed genes (DEGs) in response to heat stress. Subsequent GO and KEGG enrichment analysis showed that these genes were primarily related to signal transduction and oxidative stress, such as the phosphatidylinositol signaling system, regulation of actin cytoskeleton, MAPK signaling pathway, FoxO signaling pathway, etc. In addition, two modules were identified as significant responsive modules according to the weighted gene co-expression network analysis (WGCNA). The upregulation of key enzymes within the base excision repair and gap junction pathways indicated that the heart of C. farreri under heat stress enhanced DNA repair and maintained cellular integrity. In addition, the variable expression of essential signaling molecules and cytoskeletal regulators suggested that the heart of C. farreri modulated cardiomyocyte contraction, intracellular signaling, and heart rate through complex regulation of phosphorylation and calcium dynamics in response to heat stress. Collectively, this study enhances our understanding of cardiac function and provides novel evidence for unraveling the mechanism underlying the thermal response in mollusks.

Identification of molecular targets of Hypericumperforatum in blood for major depressive disorder: a machine-learning pharmacological study

BackgroundMajor depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Hypericumperforatum (HP) is a traditional herb that has been shown to have antidepressant effects, but its mechanism is unclear. This study aims to identify the molecular targets of HP for the treatment of MDD.MethodsWe performed differential analysis and weighted gene co-expression network analysis (WGCNA) with blood mRNA expression cohort of MDD and healthy control to identify DEGs and significant module genes (gene list 1). Three databases, CTD, DisGeNET, and GeneCards, were used to retrieve MDD-related gene intersections to obtain MDD-predicted targets (gene list 2). The validated targets were retrieved from the TCMSP database (gene list 3). Based on these three gene lists, 13 key pathways were identified. The PPI network was constructed by extracting the intersection of genes and HP-validated targets on all key pathways. Key therapeutic targets were obtained using MCODE and machine learning (LASSO, SVM-RFE). Clinical diagnostic assessments (Nomogram, Correlation, Intergroup expression), and gene set enrichment analysis (GSEA) were performed for the key targets. In addition, immune cell analysis was performed on the blood mRNA expression cohort of MDD to explore the association between the key targets and immune cells. Finally, molecular docking prediction was performed for the targets of HP active ingredients on MDD.ResultsDifferential expression analysis and WGCNA module analysis yielded 933 potential targets for MDD. Three disease databases were intersected with 982 MDD-predicted targets. The TCMSP retrieved 275 valid targets for HP. Separate enrichment analysis intersected 13 key pathways. Five key targets (AKT1, MAPK1, MYC, EGF, HSP90AA1) were finally screened based on all enriched genes and HP valid targets. Combined with the signaling pathway and immune cell analysis suggested the effect of peripheral immunity on MDD and the important role of neutrophils in immune inflammation. Finally, the binding of HP active ingredients (quercetin, kaempferol, and luteolin) and all 5 key targets were predicted based on molecular docking.ConclusionsThe active constituents of Hypericumperforatum can act on MDD and key targets and pathways of this action were identified.

Piezo1-driven mechanotransduction as a key regulator of cartilage degradation in early osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative disease characterized by pain and cartilage damage in its later stages, while early OA is marked by the loss of cartilage's mechanical function. Recent studies suggest that Piezo1, a mechanotransducer, may contribute to cartilage degradation under abnormal physical stress. This study investigates the mechanism by which Piezo1 mediates the loss of cartilage's mechanical properties. Using rat chondrocytes cultured in a 3D in vitro model, we found that fluid flow-induced physical stress activates constitutively expressed Piezo1, leading to increased catabolic activity and apoptosis, which, in turn, disrupts the matrix structure. Ex vivo cartilage experiments further demonstrated that the mechanical stress-induced loss of cartilage's physical properties (approximately 10% reduction in relaxation modulus) is mediated by Piezo1 and depends on cell viability. Notably, Piezo1 agonists alone did not alter the mechanical behavior of cartilage tissue. In vivo, using an OA rat model induced by anterior cruciate ligament transection, we observed cartilage integrity degradation and loss of mechanical properties, which were partially mitigated by Piezo1 inhibition. RNA sequencing revealed significant modulation of the PI3K signaling and matrix regulation pathways. Collectively, this study demonstrates that Piezo1-mediated catabolic activity in chondrocytes is a key driver of the loss of cartilage's mechanical function during the relaxation phase.

12366 The Association Between Obstructive Sleep Apnea And Bone Health: A Systematic Review And Meta-analysis

Abstract Disclosure: C. Teo: None. Y. Chan: None. J. Tay: None. C. Cheong: None. Importance: Obstructive sleep apnea (OSA) is a globally prevalent yet underdiagnosed sleep disorder with well-known metabolic consequences. However, the relationship between OSA and bone health, especially osteoporosis, remains poorly understood. Given that both OSA and osteoporosis are highly prevalent chronic conditions with significant public health indications, elucidating the relationship between these conditions is important. Objective: To investigate the association of OSA with bone health, specifically if individuals with OSA had a higher risk of developing osteoporosis, and discuss its clinical implications. Data Sources: A systematic search of MEDLINE (via PubMed), Embase and Cochrane Library from inception to 22 November 2023. Keywords related to obstructive sleep apnea, osteoporosis and bone density were included. Study Selection: Studies that reported on the association between OSA and osteoporosis in adults aged 18 years and above were included. Outcomes of interest included any markers of osteoporosis or bone mineral density. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and data extracted independently by two observers. Meta-analysis across studies was pooled using a random-effects model. Main Outcome(s) and Measure(s): Correlation of OSA with bone mineral density, as well as the mean difference in bone density scores and the risk of developing osteoporosis among between individuals with OSA and without OSA. Results: We identified 15 studies comprising 158,273 individuals. All studies had low or moderate risk of bias. The presence of OSA was negatively correlated with bone mineral density on meta-analysis (pooled correlation = -0.30; 95% CI -0.42 – -0.17; N = 8). Individuals with OSA also had poorer bone mineral density scores (mean difference = -0.58, 95% CI, -1.15 – 0.01; N = 8), and had significantly higher risk of developing osteoporosis (adjusted odds ratio = 2.18; 95% CI, 1.14–4.136; N = 4). Notably, both body mass index (BMI) and age were not significant effect modulators in the correlation of OSA and bone density. Conclusions and Relevance: OSA is associated with diminished bone health and a significant risk in developing osteoporosis. Further studies are required to determine if treatment of OSA may have the potential to mitigate these risks. Presentation: 6/3/2024