Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.

Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development.

Activity reconstitution of Kre33 and Tan1 reveals a molecular ruler mechanism in eukaryotic tRNA acetylation.

RNA acetylation is a universal post-transcriptional modification that occurs in various RNAs. Transfer RNA (tRNA) acetylation is found at position 34 (ac4C34) in bacterial tRNAMet and position 12 (ac4C12) in eukaryotic tRNASer and tRNALeu. The biochemical mechanism, structural basis and functional significance of ac4C34 are well understood; however, despite being discovered in the 1960s and identification of Kre33/NAT10 and Tan1/THUMPD1 as modifying apparatuses, ac4C12 modification activity has never been reconstituted for nearly six decades. Here, we successfully reconstituted the ac4C12 modification activity of yeast Kre33 and Tan1. Biogenesis of ac4C12 is primarily dependent on a minimal set of elements, including a canonical acceptor stem, the presence of the 11CCG13 motif and correct D-arm orientation, indicating a molecular ruler mechanism. A single A13G mutation conferred ac4C12 modification to multiple non-substrate tRNAs. Moreover, we were able to introduce ac4C modifications into small RNAs. ac4C12 modification contributed little to tRNA melting temperature and aminoacylation in vitro and in vivo. Collectively, our results realize in vitro activity reconstitution, delineate tRNA substrate selection mechanism for ac4C12 biogenesis and develop a valuable system for preparing acetylated tRNAs as well as non-tRNA RNA species, which will advance the functional interpretation of the acetylation in RNA structures and functions.

Neonatal GABAergic transmission primes vestibular gating of output for adult spatial navigation.

GABAergic interneurons are poised with the capacity to shape circuit output via inhibitory gating. How early in the development of medial vestibular nucleus (MVN) are GABAergic neurons recruited for feedforward shaping of outputs to higher centers for spatial navigation? The role of early GABAergic transmission in assembling vestibular circuits for spatial navigation was explored by neonatal perturbation. Immunohistochemistry and confocal imaging were utilized to reveal the expression of parvalbumin (PV)-expressing MVN neurons and their perineuronal nets. Whole-cell patch-clamp recording, coupled with optogenetics, was conducted in vitro to examine the synaptic function of MVN circuitry. Chemogenetic targeting strategy was also employed in vivo to manipulate neuronal activity during navigational tests. We found in rats a neonatal critical period before postnatal day (P) 8 in which competitive antagonization of GABAergic transmission in the MVN retarded maturation of inhibitory neurotransmission, as evidenced by deranged developmental trajectory for excitation/inhibition ratio and an extended period of critical period-like plasticity in GABAergic transmission. Despite increased number of PV-expressing GABAergic interneurons in the MVN, optogenetic-coupled patch-clamp recording indicated null-recruitment of these neurons in tuning outputs along the ascending vestibular pathway. Such perturbation not only offset output dynamics of ascending MVN output neurons, but was further accompanied by impaired vestibular-dependent navigation in adulthood. The same perturbations were however non-consequential when applied after P8. Results highlight neonatal GABAergic transmission as key to establishing feedforward output dynamics to higher brain centers for spatial cognition and navigation.

TGF-ß signaling pathway in spinal cord injury: Mechanisms and therapeutic potential.

Spinal cord injury (SCI) is a highly disabling central nervous system injury with a complex pathological process, resulting in severe sensory and motor dysfunction. The current treatment modalities only alleviate its symptoms and cannot effectively intervene or treat its pathological process. Many studies have reported that the transforming growth factor (TGF)-ß signaling pathway plays an important role in neuronal differentiation, growth, survival, and axonal regeneration after central nervous system injury. Furthermore, the TGF-ß signaling pathway has a vital regulatory role in SCI pathophysiology and neural regeneration. Following SCI, regulation of the TGF-ß signaling pathway can suppress inflammation, reduce apoptosis, prevent glial scar formation, and promote neural regeneration. Due to its role in SCI, the TGF-ß signaling pathway could be a potential therapeutic target. This article reported the pathophysiology of SCI, the characteristics of the TGF-ß signaling pathway, the role of the TGF-ß signaling pathway in SCI, and the latest evidence for targeting the TGF-ß signaling pathway for treating SCI. In addition, the limitations and difficulties in TGF-ß signaling pathway research in SCI are discussed, and solutions are provided to address these potential challenges. We hope this will provide a reference for the TGF-ß signaling pathway and SCI research, offering a theoretical basis for targeted therapy of SCI.

Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

Binary Nano-inhalant Formulation of Icariin Enhances Cognitive Function in Vascular Dementia via BDNF/TrkB Signaling and Anti-inflammatory Effects.

Vascular dementia (VaD) has a serious impact on the patients' quality of life. Icariin (Ica) possesses neuroprotective potential for treating VaD, yet its oral bioavailability and blood-brain barrier (BBB) permeability remain challenges. This research introduced a PEG-PLGA-loaded chitosan hydrogel-based binary formulation tailored for intranasal delivery, enhancing the intracerebral delivery efficacy of neuroprotective agents. The formulation underwent optimization to facilitate BBB crossing, with examinations conducted on its particle size, morphology, drug-loading capacity, in vitro release, and biodistribution. Using the bilateral common carotid artery occlusion (BCCAO) rat model, the therapeutic efficacy of this binary formulation was assessed against chitosan hydrogel and PEG-PLGA nanoparticles loaded with Ica. Post-intranasal administration, enhanced cognitive function was evident in chronic cerebral hypoperfusion (CCH) rats. Further mechanistic evaluations, utilizing immunohistochemistry (IHC), RT-PCR, and ELISA, revealed augmented transcription of synaptic plasticity-associated proteins like SYP and PSD-95, and a marked reduction in hippocampal inflammatory markers such as IL-1ß and TNF-α, highlighting the formulation's promise in alleviating cognitive impairment. The brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B (TrkB) pathway was activated significantly in the binary formulation compared with the other two. Our study demonstrates that the intranasal application of chitosan hydrogel loaded with Ica-encapsulated PEG-PLGA could effectively deliver Ica into the brain and enhance its neuroprotective effect.

Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling.

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 µg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.

Stripping away ion hydration shells in electrical double-layer formation: Water networks matter.

The double layer at the solid/electrolyte interface is a key concept in electrochemistry. Here, we present an experimental study combined with simulations, which provides a molecular picture of the double-layer formation under applied voltage. By THz spectroscopy we are able to follow the stripping away of the cation/anion hydration shells for an NaCl electrolyte at the Au surface when decreasing/increasing the bias potential. While Na+ is attracted toward the electrode at the smallest applied negative potentials, stripping of the Cl- hydration shell is observed only at higher potential values. These phenomena are directly measured by THz spectroscopy with ultrabright synchrotron light as a source and rationalized by accompanying molecular dynamics simulations and electronic-structure calculations.

Dilute Povidone-Iodine Solution Soaking Is Ineffective in Improving Outcomes of Necrotizing Fasciitis Caused by Diabetic Foot.

ABSTRACT: Wound soaking is a physical debridement method that helps reduce bacterial colonization and consequently promotes wound healing. Although soaking in povidone-iodine solution was ineffective in reducing bacterial colonization in acute trauma wounds, there is still a lack of evidence supporting the efficacy of this method in treating severe soft tissue infection. This study aimed to explore the effects of wound soaking in 1% dilute povidone-iodine solution on necrotizing fasciitis caused by diabetic foot ulcers. We retrospectively reviewed and finally included 153 patients who were admitted because of diabetic foot ulcers after undergoing fasciotomy for necrotizing infection from January 2018 to December 2021. Results showed no statistical difference in the outcomes between patients in the soaking and nonsoaking groups. End-stage renal disease (P = 0.029) and high serum C-reactive protein level (P = 0.007) were the only independent factors for below-knee amputation in the univariate and multivariate logistic regression analyses. Therefore, soaking diabetic wounds with severe infection in 1% dilute povidone-iodine solution may not reduce the hospital length of stay, risk of below-knee amputation, and readmission rate.

Bulked Segregant RNA-Seq Reveals Different Gene Expression Patterns and Mutant Genes Associated with the Zigzag Pattern of Tea Plants (Camellia sinensis).

The unique zigzag-patterned tea plant is a rare germplasm resource. However, the molecular mechanism behind the formation of zigzag stems remains unclear. To address this, a BC1 genetic population of tea plants with zigzag stems was studied using histological observation and bulked segregant RNA-seq. The analysis revealed 1494 differentially expressed genes (DEGs) between the upright and zigzag stem groups. These DEGs may regulate the transduction and biosynthesis of plant hormones, and the effects on the phenylpropane biosynthesis pathways may cause the accumulation of lignin. Tissue sections further supported this finding, showing differences in cell wall thickness between upright and curved stems, potentially due to lignin accumulation. Additionally, 262 single-nucleotide polymorphisms (SNPs) across 38 genes were identified as key SNPs, and 5 genes related to zigzag stems were identified through homologous gene function annotation. Mutations in these genes may impact auxin distribution and content, resulting in the asymmetric development of vascular bundles in curved stems. In summary, we identified the key genes associated with the tortuous phenotype by using BSR-seq on a BC1 population to minimize genetic background noise.

In-vitro method and model to estimate methane emissions from liquid manure management on pig and dairy farms in four countries.

Methane (CH4) emissions from manure management on livestock farms are a key source of greenhouse gas emissions in some regions and for some production systems, and the opportunities for mitigation may be significant if emissions can be adequately documented. We investigated a method for estimating CH4 emissions from liquid manure (slurry) that is based on anaerobic incubation of slurry collected from commercial farms. Methane production rates were used to derive a parameter of the Arrhenius temperature response function, lnA', representing the CH4 production potential of the slurry at the time of sampling. Results were used for parameterization of an empirical model to estimate annual emissions with daily time steps, where CH4 emissions from individual sources (barns, outside storage tanks) can be calculated separately. A monitoring program was conducted in four countries, i.e., Denmark, Sweden, Germany and the Netherlands, during a 12-month period where slurry was sampled to represent barn and outside storage on finishing pig and dairy farms. Across the four countries, lnA' was higher in pig slurry compared to cattle slurry (p < 0.01), and higher in slurry from barns compared to outside storage (p < 0.01). In a separate evaluation of the incubation method, in-vitro CH4 production rates were comparable with in-situ emissions. The results indicate that lnA' in barns increases with slurry age, probably due to growth or adaptation of the methanogenic microbial community. Using lnA' values determined experimentally, empirical models with daily time steps were constructed for finishing pig and dairy farms and used for scenario analyses. Annual emissions from pig slurry were predicted to be 2.5 times higher than those from cattle slurry. Changing the frequency of slurry export from the barn on the model pig farm from 40 to 7 d intervals reduced total annual CH4 emissions by 46 %; this effect would be much less on cattle farms with natural ventilation. In a scenario with cattle slurry, the empirical model was compared with the current IPCC methodology. The seasonal dynamics were less pronounced, and annual CH4 emissions were lower than with the current methodology, which calls for further investigations. Country-specific models for individual animal categories and point sources could be a tool for assessing CH4 emissions and mitigation potentials at farm level.

The structural and functional properties of hemp protein isolate-epigallocatechin-3-gallate biopolymer covalent complex during heating.

BACKGROUND: It is well known that hemp proteins have the disadvantages of poor solubility and poor emulsification. To improve these shortcomings, an alkali covalent cross-linking method was used to prepare hemp protein isolate-epigallocatechin-3-gallate biopolymer (HPI-EGCG) and the effects of different heat treatment conditions on the structure and emulsifying properties of the HPI-EGCG covalent complex were studied. RESULTS: The secondary and tertiary structures, solubility, and emulsification ability of the HPI-EGCG complexes were evaluated using particle size, zeta potential, circular dichroism (CD), and fluorescence spectroscopy indices. The results showed that the absolute value of zeta potential of HPI-EGCG covalent complex was the largest, 18.6 mV, and the maximum binding amount of HPI to EGCG was 29.18 µmol g-1 . Under heat treatment at 25-35 °C, the α-helix content was reduced from 1.87% to 0%, and the ß-helix content was reduced from 82.79% to 0% after the covalent binding of HPI and EGCG. The solubility and emulsification properties of the HPI-EGCG covalent complexes were improved significantly, and the emulsification activity index (EAI) and emulsion stability index (ESI) were increased by 2.77-fold and 1.21-fold, respectively. CONCLUSION: A new HPI-EGCG covalent complex was developed in this study to provide a theoretical basis for the application of HPI-EGCG in food industry. © 2023 Society of Chemical Industry.

Characterization of structural and functional properties of soybean 11S globulin during renaturation after denaturation induced by changes in pH.

BACKGROUND: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin. RESULTS: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and ß-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the ß-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization. CONCLUSIONS: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry.

Creeping and erupting dynamics in a pure-quartic soliton fiber laser.

Pure-quartic solitons (PQSs) are gradually becoming a hotspot in recent years due to their potential advantage to achieve high energy. Meanwhile, the fundamental research of PQSs is still in the fancy stage, and exploring soliton dynamics can promote the development of PQSs. Herein, we comprehensively and numerically investigate the impact of saturation power, small-signal gain, and output coupler on PQS dynamics in passively mode-locked fiber lasers. The result indicates that altering the above parameters makes PQSs exhibit pulsating or creeping dynamics similar to traditional solitons. Moreover, introducing an intra-cavity filter combined with intra-cavity large fourth-order dispersion makes PQSs go through stationary, pulsating to erupting. That is, the intra-cavity filter changes PQS dynamics. These findings provide new insights into PQS dynamics in fiber lasers.

Impact of the uniaxial strain on terahertz modulation characteristics in flexible epitaxial VO2 film across the phase transition.

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO2) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

Self-pulsing and dual-mode lasing in a square microcavity semiconductor laser.

Self-pulsing and dual-mode lasing in a square microcavity semiconductor laser are studied experimentally. Self-sustained pulses originating from undamped relaxation oscillation induced by a two-mode interaction are obtained, as the injection current is slightly above the laser threshold. A repetition frequency of 4.4 GHz and a pulse width of 30-40 ps are obtained at a current of 8 mA. The laser switches to continuous-wave operation when the injection current is higher than a certain value, and dual-mode lasing with 30.7 GHz at 16 mA and 10.7 GHz at 27 mA are observed in the lasing spectra. Furthermore, the relative intensity noise spectra are presented to reveal the relationship between the lasing states and the dynamics induced by relaxation oscillation and mode beating.

Evaluating prostate cancer bone metastasis using accelerated whole-body isotropic 3D T1-weighted Dixon MRI with compressed SENSE: a feasibility study.

OBJECTIVES: The study aimed to assess the efficiency of whole-body high-resolution compressed sensing-sensitivity encoding isotropic T1-Weighted Dixon (CSI-T1W-Dixon) scans in evaluating bone metastasis. METHODS: Forty-five high-risk prostate cancer patients with bone metastases were enrolled prospectively and underwent whole-body MRI sequences, which included the following: pre- and post-contrast CSI-T1W-Dixon and conventional multi-planar T1-Weighted Dixon (CMP-T1W-Dixon) (coronal, sagittal, and axial scans), short tau inversion recovery (STIR), and DWI. Comparison between the CMP-T1W-Dixon and CSI-T1W-Dixon images was done for the subjective image quality, the quantitative contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). Furthermore, the diagnostic performance based on per-lesion and per-patient basis utilizing non-contrast T1-weighted (T1)/T1+ contrasted T1-weighted (T1C)/T1 + T1C + STIR + DWI sequences was compared between the CSI-T1W-Dixon and CMP-T1W-Dixon methods using reference standards (combining biopsy data and 6-month imaging follow-up). RESULT: The CSI-T1W-Dixon images produced fewer image artifacts in the axial and coronal planes compared to the CMP-T1W-Dixon images. Also, the CSI-T1W-Dixon images provided better a CNR in fat-only images of all three planes and water-only images of the axial plane (p < 0.05). The CSI-T1W-Dixon showed a higher sensitivity than the CMP-T1W-Dixon techniques in analyzing T1-only images on a per-lesion basis (82.7% vs. 53.8% for sensitivity, p = 0.03). On a per-patient basis, no difference was found in the diagnostic capacity between the CSI-T1W-Dixon and CMP-T1W-Dixon sequences either alone or in combinations (p = 0.57-1). CONCLUSION: High-resolution CSI-T1W-Dixon with higher image quality and diagnostic capacity can replace the CMP-T1W-Dixon method in evaluating bone metastasis in clinical practice. KEY POINTS: • Compressed sensing isotropic acquisition for 3D T1-weighted Dixon images can improve the image quality with fewer artifacts compared to the anisotropic multiplanar acquisition. • Compressed sensing isotropic acquisition can save 67% of scanning time compared to anisotropic multiplanar acquisition. • Compressed sensing isotropic 3D T1-weighted Dixon images can offer better diagnostic performance with higher sensitivity compared to anisotropic multiplanar images.

Evaluating blood supply changes in the osteonecrosis of the femoral head using gadobutrol-based steady-state MR angiography.

OBJECTIVES: Assess the feasibility of using gadobutrol-based steady-state (SS) MR angiography (MRA) to evaluate the blood supply changes of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Participants were recruited in this prospective study from December 2021 to May 2022 in a single center. The number of superior retinacular arteries (SRAs), inferior retinacular arteries (IRAs), anterior retinacular arteries (ARAs), and overall retinacular arteries (ORAs), as well as the affected rates of SRA and IRA, were determined and compared between healthy and ONFH hips and between hips across the Association Research Circulation Osseous (ARCO) staging I-IV. RESULTS: Twenty healthy and 64 ONFH hips were evaluated in 54 participants. There were significant differences between ARCO I-IV for the number of ORAs (mean of 3.5, 2.3, 1.7, and 0.8 for ARCO I-IV, respectively; p < .001), SRAs (median of 2.5, 1, 0.5, and 0 for ARCO I-IV, respectively; p < .001), and the affected rate of SRAs (20.00%, 65.22%, 77.78%, 92.31% for ARCO I-IV, respectively, p = 0.002). There were significant differences between ONFH and healthy hips for the number of ORAs (median of 5 vs. 2; p < .001), SRAs (median of 3 vs. 1; p < .001), IRAs (median of 1 vs. 1; p < .001), ARAs (median of 0 vs. 0; p = 0.04), and also the affected rate of SRAs (5.00% vs. 67.20%, p < .001) and IRAs (30% vs. 84.4%, p < .001). CONCLUSION: Gadobutrol-enhanced SS MRA is a feasible method for evaluation of hemodynamics in ONFH. CLINICAL RELEVANCE STATEMENT: Gadobutrol-enhanced magnetic resonance angiography can evaluate blood supply changes of ONFH and therefore helps to aid in the diagnosis and guide treatment of ONFH. KEY POINTS: • Gadobutrol-enhanced magnetic resonance angiography showed changes in the retinacular artery related to the severity of femoral osteonecrosis. • Gadobutrol-enhanced magnetic resonance angiography revealed a reduced blood supply to the ischemic necrotic femoral head compared to the healthy counterparts.

Evaluation of retinal microvasculature in exotropia with abnormal binocular vision by optical coherence tomography angiography.

BACKGROUND: To explore the retinal microvasculature in large-angle concomitant exotropia patients with abnormal binocular vision using optical coherence tomography angiography (OCTA) analysis. METHODS: OCTA images of 52 healthy and 100 strabismic eyes were analyzed to quantify the retinal thickness (RT), superficial capillary plexus (SCP), deep capillary plexus (DCP), and foveal avascular zone (FAZ). Paired t-tests were performed to compare differences between the two groups, the dominant eye and the deviated eye in the exotropia group, respectively. A p-value < 0.01 was considered significant. RESULTS: The mean angle of deviation was 79.38 [± 25.64] (prism diopters, PD). There were significant differences in the DCP in deviated eyes between the exotropia group and the control group (fovea: p = 0.007; temporal: p = 0.014; nasal: p = 0.028; inferior: p = 0.013). The temporal SCP in the exotropia group was significantly higher than in the control group in deviated eyes (p = 0.020). No significant difference was found between dominant eyes and strabismic eyes (p > 0.01). CONCLUSIONS: The study showed that OCTA revealed subnormal DCP in patients with large-angle exotropia and abnormal binocularity which may be related to retinal suppression. Changes in the macular microvasculature may provide valuable insights into the development of strabismus. Further studies are needed to determine the clinical relevance of this finding. TRIAL REGISTRATION: This trial is registered as ChiCTR2100052577 at www.Chictr.org.cn .

Diagnostic and prognostic value of echocardiography in pulmonary hypertension: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: The role of echocardiography in the diagnostic and prognostic assessment of pulmonary hypertension (PH) has been widely studied recently. However, these findings have not undergone normative evaluation and may provide confusing evidence for clinicians. To evaluate and summarize existing evidence, we performed an umbrella review. METHODS: Systematic reviews and meta-analyses were searched in PubMed, Embase, Web of Science, and Cochrane Library from inception to September 4, 2022. The methodological quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the quality of evidence. RESULTS: Thirteen meta-analyses (nine diagnostic and four prognostic studies) were included after searching four databases. The methodological quality of the included studies was rated as high (62%) or moderate (38%) by AMSTAR. The thirteen included meta-analyses involved a total of 28 outcome measures. The quality of evidence for these outcomes were high (7%), moderate (29%), low (39%), and very low (25%) using GRADE methodology. In the detection of PH, the sensitivity of systolic pulmonary arterial pressure is 0.85-0.88, and the sensitivity and specificity of right ventricular outflow tract acceleration time are 0.84. Pericardial effusion, right atrial area, and tricuspid annulus systolic displacement provide prognostic value in patients with pulmonary arterial hypertension with hazard ratios between 1.45 and 1.70. Meanwhile, right ventricular longitudinal strain has independent prognostic value in patients with PH, with a hazard ratio of 2.96-3.67. CONCLUSION: The umbrella review recommends echocardiography for PH detection and prognosis. Systolic pulmonary arterial pressure and right ventricular outflow tract acceleration time can be utilized for detection, while several factors including pericardial effusion, right atrial area, tricuspid annular systolic displacement, and right ventricular longitudinal strain have demonstrated prognostic significance. TRIAL REGISTRATION: PROSPERO (CRD42022356091), https://www.crd.york.ac.uk/prospero/ .