EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Vertically assembled nanosheet networks for high-density thick battery electrodes.

As one of the prevailing energy storage systems, lithium-ion batteries (LIBs) have become an essential pillar in electric vehicles (EVs) during the past decade, contributing significantly to a carbon-neutral future. However, the complete transition to electric vehicles requires LIBs with yet higher energy and power densities. Here, we propose an effective methodology via controlled nanosheet self-assembly to prepare low-tortuosity yet high-density and high-toughness thick electrodes. By introducing a delicate densification in a three-dimensionally interconnected nanosheet network to maintain its vertical architecture, facile electron and ion transports are enabled despite their high packing density. This dense and thick electrode is capable of delivering a high volumetric capacity >1,600 mAh cm-3, with an areal capacity up to 32 mAh cm-2, which is among the best reported in the literature. The high-performance electrodes with superior mechanical and electrochemical properties demonstrated in this work provide a potentially universal methodology in designing advanced battery electrodes with versatile anisotropic properties.

Engineering High-Tortuosity 3D Gradient Structure and CFD-Assisted Multifield Analysis for Solar Interfacial Evaporation.

Solar interfacial evaporation is a promising method for solving the global shortage of fresh water. While 2D evaporators can efficiently localize solar-converted heat at the thin layer of the water-air interface, 3D solar evaporators can maximize energy reutilization while maintaining effective mass transport ability, few studies are conducted to explore the effect of gradient porosity on evaporation performance. In this study, a multifield assisted strategy based on a gradient 3D structure with high tortuosity is proposed, which creates a thermal field environment for efficient evaporation through high absorption of sunlight and excellent photothermal conversion and uses the gradient structure to optimize the internal pressure field to enhance water evaporation and transport. This hierarchically nanostructured solar absorber, with porosity inhomogeneity-induced pressure gradient and optimized temperature management, is a valuable design idea for manufacturing a more efficient 3D solar evaporator in the field of seawater desalination. Owing to the understanding of optimizing the dimension by various simulation parameters, the evaporation efficiencies of such structures are found to be 165.7%, suppressing the most evaporator. Moreover, it can provide new ideas and references for the fields of mass transfer and thermal management.

Enhancing Electrode Performance through Triple Distribution Modulation of Active Material, Conductive Agent, and Porosity.

The increasing demand for large-scale energy storage propels the development of lithium-ion batteries with high energy and high power density. Low tortuosity electrodes with aligned straight channels have proved to be effective in building such batteries. However, manufacturing such low tortuosity electrodes in large scale remains extremely challenging. In contrast, high-performance electrodes with customized gradients of materials and porosity are possible to be made by industrial roll-to-roll coating process. Yet, the desired design of gradients combining materials and porosity is unclear for high-performance gradient electrodes. Here, triple gradient LiFePO4 electrodes (TGE) are fabricated featuring distribution modulation of active material, conductive agent, and porosity by combining suction filtration with the phase inversion method. The effects and mechanism of active material, conductive agent, and porosity distribution on electrode performance are analyzed by experiments. It is found that the electrode with a gradual increase of active material content from current collector to separator coupled with the distribution of conductive agent and porosity in the opposite direction, demonstrates the best rate capability, the fastest electrochemical reaction kinetics, and the highest utilization of active material. This work provides valuable insights into the design of gradient electrodes with high performance and high potential in application.

Tortuosity Engineering of Water Channels to Customized Water Supply for Enhancing Hydrogel Solar Evaporation.

Hydrogel as a solar evaporator shows great potential in freshwater production. However, hydrogels often lead to an imbalance between solar energy input and water supply management due to their excessively high saturated water content. Thus, achieving a stable water-energy-balance in hydrogel evaporators remains challenging. Here, by tortuosity engineering designed water transport channels, a seamless high-tortuosity/low-tortuosity/high-tortuosity structured hydrogel (SHLH structure hydrogel) evaporator is developed, which enables the hydrogel with customized water transport rate, leading to the controlled water supply at the evaporator interface. An excellent equilibrium between the photothermal conversion and water supply is established, and the maximum utilization of solar energy is realized, thereby achieving an excellent evaporation rate of 3.64 kg m-2 h-1 under one solar illumination. This tortuosity engineering controlled SHLH structured evaporator provides a novel strategy to attain water-energy-balance and expands new approaches for constructing hydrogel-based evaporators with tailored water transportation capacity.

Iliac tortuosity increases reinterventions but not adverse outcomes following repair of juxtarenal aneurysms using physician-modified endografts.

OBJECTIVE: Increased angulation of the proximal aortic neck has been associated with complications following endovascular repair of infrarenal aortic aneurysms, including increased incidence of endoleaks, stent migration, secondary interventions, and conversions. However, knowledge on the impact of aortoiliac tortuosity on outcomes following fenestrated repair remains limited. This study aims to quantify the effect of aortoiliac tortuosity on outcomes following fenestrated repair. METHODS: A single-center, retrospective review of all patients who underwent a physician-modified endovascular repair for the treatment of juxtarenal aortic aneurysms under a single physician-sponsored investigation device exemption study from 2011 to 2021 was performed. Center luminal lines and geometric distances were obtained using TeraRecon software (San Mateo, CA). A tortuosity index was calculated (tortuosity index = centerline distance/geometric line distance) for each iliac vessel as well as for the infrarenal aorta according to Society for Vascular Surgery reporting standards. Aortic and iliac tortuosity were assessed independently and stratified as low and high. Demographics, comorbidities, anatomic and operative details, and outcomes were compared using univariable and multivariable analysis. RESULTS: A total of 135 patients were identified. Thirty-eight patients (28%) had high aortic tortuosity, and 55 patients (42%) had high iliac tortuosity. Patients with high tortuosity were older (aortic: 78 vs 76 years; P = .04; iliac: 78 vs 75 years; P = .01) and differed by sex. Twenty-two percent of men and 50% of women had high aortic tortuosity (P = .01). Forty-seven percent of men and 20% of women had high iliac tortuosity (P = .01). There were no differences in comorbidities based on aortic tortuosity, but coronary artery disease (high: 58% vs low: 36%; P = .01) and hypertension (high: 69% vs low: 86%; P = .02) differed based on iliac tortuosity. Aneurysm diameter was larger for patients with high iliac tortuosity (72 mm vs 64 mm; P < .01), and fluoroscopy time was longer for patients with high aortic tortuosity (41 vs 31 minutes; P = .02). When outcomes were assessed, high iliac tortuosity was associated with increased rate of reinterventions (hazard ratio, 2.6; 95% confidence interval, 1.2-6.0) and type 1 or 3 endoleak (hazard ratio, 5.2; 95% confidence interval, 1.7-16); however, all other outcomes were similar. CONCLUSIONS: Among patients treated with physician-modified endovascular repair for juxtarenal aneurysms, iliac tortuosity but not aortic tortuosity, is associated with increased reinterventions and type 1 or type 3 endoleaks. Long-term follow-up is critical for patients with high iliac tortuosity to ensure that high-risk endoleaks are identified and treated early to avoid the risk of rupture.

Role of mammalian target of rapamycin in the formation and progression of retinopathy of prematurity-like vascular abnormalities in neonatal rats.

Retinopathy of prematurity (ROP), a retinal disease that can occur in premature infants, can lead to severe visual impairment. In this study, we examined the preventive and therapeutic effects of mammalian target of rapamycin complex 1 (mTORC1) inhibition on abnormal retinal blood vessels in a rat model of ROP. To induce ROP-like vascular abnormalities, rats were subcutaneously treated with KRN633, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinase, on postnatal day 7 (P7) and P8. KRN633-treated (ROP) rats were treated subcutaneously with the mTORC1 inhibitor rapamycin according to preventive and therapeutic protocols, i.e., from P11 to P13 (P11-P13) and from P14 to P20 (P14-P20), respectively. To compare with the effects of VEGF inhibition, KRN633 was administered according to similar protocols. Changes in retinal vasculature, phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTORC1 activity, and the proliferative status of vascular cells were evaluated at P14 and P21 using immunohistochemistry. Rapamycin treatment from P11 to P13 prevented increases in arteriolar tortuosity, capillary density, and the number of proliferating vascular cells, and eliminated pS6 immunoreactivity in ROP rats. KRN633 treatment at P11 and P12 (P11/P12) also prevented the appearance of ROP-like retinal blood vessels. Rapamycin treatment from P14 to P20 failed to attenuate arteriolar tortuosity but prevented increases in capillary density and proliferating vascular cell number at the vascular front, but not at the central zone. KRN633 treatment from P14 to P20 significantly reduced abnormalities in the retinal vasculature; however, the effects were inferior to those of KRN633 treatment on P11/P12. These results suggest that activation of the mTORC1 pathway in proliferating endothelial cells contributes to the appearance and progression of ROP-like retinal blood vessels. Therefore, inhibition of mTORC1 may be a promising approach for selectively targeting abnormal retinal blood vessels in ROP.

Computer-assisted evaluation of retinal vessel tortuosity in children with sickle cell disease without retinopathy.

OBJECTIVE: We assessed the predictive efficacy of automatically quantified retinal vascular tortuosity from the fundus pictures of patients with sickle cell disease (SCD) without evident retinopathy. METHODS: Retinal images were obtained from 31 healthy and 31 SCD participants using fundus imaging and analyzed using a novel computational automated metric assessment. The local and global vessel tortuosity and their relationship with systemic disease parameters were analyzed based on the images. RESULTS: SCD arteries had an increased local tortuosity index compared to the controls (0.0007 ±â€¯0.0019 vs. 0.0006 ±â€¯0.0014, p = 0.019). Furthermore, the SCD patients had wider vessel caliber mainly in the arteries (14.68 ±â€¯5.3 vs. 14.06 ±â€¯5.3, p < 0.001). The SCD global tortuosity did not differ significantly from that of the controls (p = 0.598). The female participants had significantly reduced retinal vessel tortuosity indices compared to the male participants (p = 0.018). CONCLUSION: Retinal arterial tortuosity and caliber were reliable and objective measures that could be used as a non-invasive prognostic and diagnostic indicator in sickle cell retinopathy. Further studies are required to correlate these local vascular parameters to systemic risk factors and monitor their progression and change over time.

Detection of Dolichoectasia and Atherosclerosis by Automated MRA Tortuosity Metrics in a Population-Based Study.

BACKGROUND: Intracranial vessel tortuosity is a key component of dolichoectasia and has been associated with atherosclerosis and adverse neurologic outcomes. However, the evaluation of tortuosity is mainly a descriptive assessment. PURPOSE: To compare the performance of three automated tortuosity metrics (angle metric [AM], distance metric [DM], and distance-to-axis metric [DTA]) for detection of dolichoectasia and presence of segment-specific plaques. STUDY TYPE: Observational, cross-sectional metric assessment. POPULATION: 1899 adults from the general population; mean age = 76 years, female = 59%, and black = 29%. FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional (3D) time-of-flight MRA and 3D vessel wall MRI. ASSESSMENT: Tortuosity metrics and mean luminal area were quantified for designated segments of the internal carotid artery, middle cerebral artery, anterior cerebral artery, posterior cerebral artery, vertebral artery, and entire length of basilar artery (BA). Qualitative interpretations of BA dolichoectasia were assessed based on Smoker's visual criteria. STATISTICAL TESTS: Descriptive statistics (2-sample t-tests, Pearson chi-square tests) for group comparisons. Receiver operating characteristics area under the curve (AUC) for detection of BA dolichoectasia or segment-specific plaque. Model inputs included 1) tortuosity metrics, 2) mean luminal area, and 3) demographics (age, race, and sex). RESULTS: Qualitative dolichoectasia was identified in 336 (18%) participants, and atherosclerotic plaques were detected in 192 (10%) participants. AM-, DM-, and DTA-calculated tortuosity were good individual discriminators of basilar dolichoectasia (AUCs: 0.76, 0.74, and 0.75, respectively), with model performance improving with the mean lumen area: (AUCs: 0.88, 0.87, and 0.87, respectively). Combined characteristics (tortuosity and mean luminal area) identified plaques with better performance in the anterior (AUCs ranging from 0.66 to 0.78) than posterior (AUCs ranging from 0.54 to 0.65) circulation, with all models improving by the addition of demographics (AUCs ranging from 0.62 to 0.84). DATA CONCLUSION: Quantitative vessel tortuosity metrics yield good diagnostic accuracy for the detection of dolichoectasia. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Vertebral artery dissection caused by atlantoaxial dislocation in a patient with Marfan syndrome.

A small number of case reports have documented a link between atlantoaxial dislocation (AAD) and vertebral artery dissection (VAD), but this association has never been described in patients with hereditary connective tissue disorders. We present a case of an 18-year-old female patient, diagnosed with Marfan syndrome since the age of one, who underwent brain MRA for intracranial aneurysm screening revealing tortuosity of the internal carotid and vertebral arteries as well as atlantoaxial dislocation. Since the patient was asymptomatic, a wait-and-see approach was chosen, but a follow-up MRA after 18 months showed the appearance of a dissecting pseudoaneurysm of the V3 segment of the left vertebral artery. Despite the patient being still asymptomatic, it was decided to proceed with C1-C2 stabilization to prevent further vascular complications. Follow-up imaging showed realignment of the atlantoaxial joint and reduction of the dissecting pseudoaneurysm of the left vertebral artery. In our patient, screening MRA has led to the discovery of asymptomatic arterial and skeletal abnormalities which, if left untreated, might have led to severe cerebrovascular complications. Therefore, AAD correction or close monitoring with MRA should be provided to MFS patients with this craniovertebral junction anomaly, even if asymptomatic.