Ambient Pressure Drying of Freeze-Cast Ceramics from Aqueous Suspension.

Freeze-casting has been wildly exploited to construct porous ceramics but usually requires costly and demanding freeze-drying (high vacuum, size limit, and supercooled chamber), which can be avoided by the ambient pressure drying (APD) technique. However, applying APD to freeze-cast ceramic based on an aqueous suspension is still challenging due to inert surface chemistry. Herein, a modified APD strategy is developed to improve the drying process of freeze-cast ceramics by exploiting the simultaneous ice etching, ionic cross-linking, and solvent exchange under mild conditions (-10-0 °C, ambient pressure). This versatile strategy is applicable to various ceramic species, metal ions, and freezing techniques. The incorporated metal ions not only enhance liquid-phase sintering, producing ceramics with higher density and mechanical properties than freeze-cast counterparts, but also render customizable coloration and antibacterial property. The cost-/time-efficient APD is promising for mass production and even successive production of large-size freeze-cast ceramics that exceed the size of commercial freeze-dryers.

Inhibition of interaction between ROCK1 and Rubicon restores autophagy in endothelial cells and attenuates brain injury after prolonged ischemia.

Acute ischemic stroke (AIS) induces cerebral endothelial cell death resulting in the breakdown of the blood-brain barrier (BBB). Endothelial cell autophagy acts as a protective mechanism against cell death. Autophagy is activated in the very early stages of ischemic stroke and declines after prolonged ischemia. Previous studies have shown that Rubicon can inhibit autophagy. The current study aimed to investigate whether continuous long-term ischemia can inhibit autophagy in endothelial cells after ischemic stroke by regulating the function of Rubicon and its underlying mechanism. Wild-type male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (tMCAO). ROCK1, ROCK2, and NOX2 inhibitors were injected into male mice 1 h before the onset of tMCAO. Disease severity and BBB permeability were evaluated. bEnd.3 cells were cultured in vitro and subjected to oxygen-glucose deprivation (OGD). bEnd.3 cells were pretreated with or without ROCK1, ROCK2, or NOX2 inhibitors overnight and then subjected to OGD. Cell viability and permeability were also evaluated. The expression of Rubicon, ROCK1, and autophagy-related proteins were analyzed. Increased BBB permeability was correlated with Rubicon expression in tMCAO mice and Rubicon was upregulated in endothelial cells subjected to OGD. Autophagy was inhibited in endothelial cells after long-term OGD treatment and knockdown of Rubicon expression restored autophagy and viability in endothelial cells subjected to 6-h OGD. ROCK1 inhibition decreased the interaction between Beclin1 and Rubicon and restored cell viability and autophagy suppressed by 6-h OGD treatment in endothelial cells. Additionally, ROCK1 inhibition suppressed Rubicon, attenuated BBB disruption, and brain injury induced by prolonged ischemia in 6-h tMCAO mice. Prolonged ischemia induced the death of brain endothelial cells and the breakdown of the BBB, thus aggravating brain injury by increasing the interaction of ROCK1 and Rubicon with Beclin1 while inhibiting canonical autophagy. Inhibition of ROCK1 signaling in endothelial cells could be a promising therapeutic strategy to prolong the therapeutic time window in AIS.

Biomedical evidence engineering for data-driven discovery.

MOTIVATION: With the rapid development of precision medicine, a large amount of health data (such as electronic health records, gene sequencing, medical images, etc.) has been produced. It encourages more and more interest in data-driven insight discovery from these data. A reasonable way to verify the derived insights is by checking evidence from biomedical literature. However, manual verification is inefficient and not scalable. Therefore, an intelligent technique is necessary to solve this problem. RESULTS: This article introduces a framework for biomedical evidence engineering, addressing this problem more effectively. The framework consists of a biomedical literature retrieval module and an evidence extraction module. The retrieval module ensembles several methods and achieves state-of-the-art performance in biomedical literature retrieval. A BERT-based evidence extraction model is proposed to extract evidence from literature in response to queries. Moreover, we create a dataset with 1 million examples of biomedical evidence, 10 000 of which are manually annotated. AVAILABILITY AND IMPLEMENTATION: Datasets are available at https://github.com/SendongZhao.

Stable Pyrene-Based Metal-Organic Framework for Cyclization of Propargylic Amines with CO2 and Detection of Antibiotics in Water.

A pyrene-based metal-organic framework, Cd2(PTTB)(H2O)2 (WYU-11), was synthesized from the tetracarboxylic pyrene ligand H4PTTB (H4PTTB = 1,3,6,8-tetrakis(3-carboxyphenyl)pyrene) and Cd(NO3)2·4H2O. Powder X-ray diffraction analysis discloses that the framework is stable in acid, base, and various organic solvent environments. WYU-11 shows excellent catalytic performance on the cyclization reaction of propargylic amines with CO2 into 2-oxazolidinones under mild conditions (60 °C, atmospheric CO2). 1H NMR studies unveiled that WYU-11 and 1,1,3,3-tetramethylguanidine (TMG) can synergistically activate the propargylic amine substrate and promote the reaction. Importantly, WYU-11 represents a rare example of noble metal-free heterogeneous catalyst that can catalyze the cyclization of CO2 with propargylic amines. In addition, by virtue of the excellent water stability and luminescence properties, WYU-11 shows excellent detection performance for sulfathiazole (STZ) and ornidazole (ODZ) in water. Investigation reveals that the coexistence of photoinduced electron transfer and internal filtering effect could reasonably explain the luminescence quenching of WYU-11 by the antibiotics.

Deep learning based on susceptibility-weighted MR sequence for detecting cerebral microbleeds and classifying cerebral small vessel disease.

BACKGROUND: Cerebral microbleeds (CMBs) serve as neuroimaging biomarkers to assess risk of intracerebral hemorrhage and diagnose cerebral small vessel disease (CSVD). Therefore, detecting CMBs can evaluate the risk of intracerebral hemorrhage and use its presence to support CSVD classification, both are conducive to optimizing CSVD management. This study aimed to develop and test a deep learning (DL) model based on susceptibility-weighted MR sequence (SWS) to detect CMBs and classify CSVD to assist neurologists in optimizing CSVD management. Patients with arteriolosclerosis (aSVD), cerebral amyloid angiopathy (CAA), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) treated at three centers were enrolled between January 2017 and May 2022 in this retrospective study. The SWSs of patients from two centers were used as the development set, and the SWSs of patients from the remaining center were used as the external test set. The DL model contains a Mask R-CNN for detecting CMBs and a multi-instance learning (MIL) network for classifying CSVD. The metrics for model performance included intersection over union (IoU), Dice score, recall, confusion matrices, receiver operating characteristic curve (ROC) analysis, accuracy, precision, and F1-score. RESULTS: A total of 364 SWS were recruited, including 336 in the development set and 28 in the external test set. IoU for the model was 0.523 ± 0.319, Dice score 0.627 ± 0.296, and recall 0.706 ± 0.365 for CMBs detection in the external test set. For CSVD classification, the model achieved a weighted-average AUC of 0.908 (95% CI 0.895-0.921), accuracy of 0.819 (95% CI 0.768-0.870), weighted-average precision of 0.864 (95% CI 0.831-0.897), and weighted-average F1-score of 0.829 (95% CI 0.782-0.876) in the external set, outperforming the performance of the neurologist group. CONCLUSION: The DL model based on SWS can detect CMBs and classify CSVD, thereby assisting neurologists in optimizing CSVD management.

A Petrochemical-Free Route to Superelastic Hierarchical Cellulose Aerogel.

Cellulose aerogels are plagued by intermolecular hydrogen bond-induced structural plasticity, otherwise rely on chemicals modification to extend service life. Here, we demonstrate a petrochemical-free strategy to fabricate superelastic cellulose aerogels by designing hierarchical structures at multi scales. Oriented channels consolidate the whole architecture. Porous walls of dehydrated cellulose derived from thermal etching not only exhibit decreased rigidity and stickiness, but also guide the microscopic deformation and mitigate localized large strain, preventing structural collapse. The aerogels show exceptional stability, including temperature-invariant elasticity, fatigue resistance (∼5 % plastic deformation after 105  cycles), high angular recovery speed (1475.4° s-1 ), outperforming most cellulose-based aerogels. This benign strategy retains the biosafety of biomass and provides an alternative filter material for health-related applications, such as face masks and air purification.

Dual-binding nanoparticles improve the killing effect of T cells on solid tumor.

Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.

Accuracy of axial length, keratometry, and refractive measurement with Myopia Master in children with ametropia.

PURPOSE: To evaluate the accuracy of axial length, keratometry, and refractive measurement with Myopia Master in ametropic children. METHODS: In this randomized prospective cross-sectional study, 125 children with ametropia (250 eyes) were recruited (55 boys and 70 girls; age range: 3-15 years). All examinations were performed under full cycloplegic conditions. Measurements of axial length (AL), keratometry, and autorefraction acquired with the Myopia Master were compared with those from the IOLMaster 500, IOLMaster 700, Nidek ARK-1, and manifest refraction. The differences between the different methods were analyzed, and their correlation was assessed by interclass correlation coefficients (ICCs), Bland-Altman plot, and correlation test. RESULTS: The ALs (mm) measured with Myopia Master, IOLMaster 500, and IOLMaster 700 were 23.67 ± 1.26, 23.68 ± 1.26, and 23.70 ± 1.25, respectively. The mean values and standard deviations for AL and keratometry readings from these devices were similar (P ≥ 0.059). The ICC analysis also revealed high consistency between the measurements (ICC ≥ 0.943). Additionally, the correlation coefficients were relatively high (r > 0.9, p < 0.001). Although the results of refraction obtained with the Myopia Master were slightly higher than those with manifest refraction (P ≤ 0.024), the agreement between these two measurements was excellent (ICC ≥ 0.858). The percentage of points outside the limits of agreements was < 5.22% in Bland-Altman plots for all analyses. CONCLUSIONS: Myopia Master could be a highly efficient tool for clinical use as a three-in-one system (AL, keratometry, and refractive measurements) for screening in children with ametropia.

Identification of differentially expressed long non-coding RNAs and mRNAs in orbital adipose/connective tissue of thyroid-associated ophthalmopathy.

Extracellular matrix remodeling and orbital adipose/connective tissue expansion are two key features of thyroid-associated ophthalmopathy (TAO). Recent studies have indicated the critical role of long non-coding RNAs (lncRNAs) in the pathogenesis of ocular disorders. However, little is known about the roles of lncRNAs in orbital adipose/connective tissue of TAO. In this study, the profiles of lncRNAs and mRNAs in the orbital adipose/connective tissue of TAO were identified by RNA sequencing. A total of 809 differential lncRNAs and 607 differential mRNAs were identified, among which 52 genes were found to be significantly related to the extracellular matrix. Co-expression network analysis suggested that lncRNAs might regulate extracellular matrix remodeling in orbital adipose/connective tissue of TAO. Additionally, the target genes of lncRNAs involved in the lipid metabolism and cytokine-cytokine receptor interaction were also identified. These results may provide potential regulatory mechanisms of lncRNAs in the orbital adipose/connective tissue of TAO.

Rare taxa maintain the stability of crop mycobiomes and ecosystem functions.

Plants harbour highly diverse mycobiomes which sustain essential functions for host health and productivity. However, ecological processes that govern the plant-mycobiome assembly, interactions and their impact on ecosystem functions remain poorly known. Here we characterized the ecological role and community assembly of both abundant and rare fungal taxa along the soil-plant continuums (rhizosphere, phyllosphere and endosphere) in the maize-wheat/barley rotation system under different fertilization practices at two contrasting sites. Our results indicate that mycobiome assembly is shaped predominantly by compartment niche and host species rather than by environmental factors. Moreover, crop-associated fungal communities are dominated by few abundant taxa mainly belonging to Sordariomycetes and Dothideomycetes, while the majority of diversity within mycobiomes are represented by rare taxa. For plant compartments, the abundant sub-community is mainly determined by stochastic processes. In contrast, the rare sub-community is more sensitive to host selection and mainly governed by deterministic processes. Furthermore, our results demonstrate that rare taxa play an important role in fungal co-occurrence network and ecosystem functioning like crop yield and soil enzyme activities. These results significantly advance our understanding of crop mycobiome assembly and highlight the key role of rare taxa in sustaining the stability of crop mycobiomes and ecosystem functions.

Protein A Immunoadsorption Relieves Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy after Unsuccessful Methylprednisolone Treatment.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is a recently defined autoimmune inflammatory disease of the central nervous system in which GFAP IgG is present in the cerebrospinal fluid (CSF). Its primary clinical manifestation is meningoencephalitis, and it usually responds well to corticosteroids. Herein, we report a case of a patient with GFAP-A with initial symptoms of psychological and cognitive impairment, which did not respond to high-dose methylprednisolone therapy but was successfully treated with protein A immunoadsorption (PAIA) therapy. METHODS: GFAP IgG was detected by indirect immunofluorescence assay. The patient's data were analyzed retrospectively. RESULTS: A 48-year-old man presented with anxiety, depression, cognitive decline, tremor, gait disturbance, and fecal and urine incontinence. Autoimmune GFAP-A was diagnosed based on the following: (1) T2-weighted and fluid-attenuated inversion recovery MRI findings of hypersensitive lesions in the subcortical and deep white matter of the brain, with multiple longitudinally extensive lesions in the cervical and chest regions of the spinal cord, and (2) high levels of GFAP IgG in the CSF. Clinical symptoms and abnormalities detected on neuroimaging worsened after administration of high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG) but improved significantly after PAIA therapy. CONCLUSION: Psychological impairment can be the first sign of autoimmune GFAP-A. PAIA might be an effective treatment for patients with GFAP-A who respond poorly to conventional IVMP and IVIG therapy.

Regulating immune memory and reversing tumor thermotolerance through a step-by-step starving-photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) is a highly effective treatment for solid tumors and can induce long-term immune memory worked like an in situ vaccine. Nevertheless, PTT inevitably encounters photothermal resistance of tumor cells, which hinders therapeutic effect or even leads to tumor recurrence. Naïve CD8+ T cells are mainly metabolized by oxidative phosphorylation (OXPHOS), followed by aerobic glycolysis after activation. And the differentiate of effector CD8+ T cell (CD8+ Teff) into central memory CD8+ T cell (CD8+ TCM) depends on fatty acid oxidation (FAO) to meet their metabolic requirements, which is regulated by adenosine monophosphate activated protein kinase (AMPK). In addition, the tumor microenvironment (TME) is severely immunosuppressive, conferring additional protection against the host immune response mediated by PTT. METHODS: Metformin (Met) down-regulates NADH/NADPH, promotes the FAO of CD8+ T cells by activating AMPK, increases the number of CD8+ TCM, which boosts the long-term immune memory of tumor-bearing mice treated with PTT. Here, a kind of PLGA microspheres co-encapsulated hollow gold nanoshells and Met (HAuNS-Met@MS) was constructed to inhibit the tumor progress. 2-Deoxyglucose (2DG), a glycolysis inhibitor for cancer starving therapy, can cause energy loss of tumor cells, reduce the heat stress response of tumor cell, and reverse its photothermal resistance. Moreover, 2DG prevents N-glycosylation of proteins that cause endoplasmic reticulum stress (ERS), further synergistically enhance PTT-induced tumor immunogenic cell death (ICD), and improve the effect of immunotherapy. So 2DG was also introduced and optimized here to solve the metabolic competition among tumor cells and immune cells in the TME. RESULTS: We utilized mild PTT effect of HAuNS to propose an in situ vaccine strategy based on the tumor itself. By targeting the metabolism of TME with different administration strategy of 2DG and perdurable action of Met, the thermotolerance of tumor cells was reversed, more CD8+ TCMs were produced and more effective anti-tumor was presented in this study. CONCLUSION: The Step-by-Step starving-photothermal therapy could not only reverse the tumor thermotolerance, but also enhance the ICD and produce more CD8+ TCM during the treatment.

Oxygen nanocarrier broke the hypoxia trap of solid tumors and rescued transfection efficiency for gene therapy.

BACKGROUND: Gene therapy shows great promise for a broad array of diseases. However, we found that hypoxic tumor microenvironment (TME) exerted significant inhibitory effects on transfection efficiency of a variety of gene vectors (such as Lipo 2000 and PEI) in an oxygen-dependent manner. Solid tumors inevitably resulted in acute hypoxic areas due to the rapid proliferation of tumor cells and the aberrant structure of blood vessels. Thus, the hypoxic TME severely limited the efficiency and application of gene therapy. METHODS: In our previous study, we constructed endoplasmic reticulum-targeted cationic liposomes, PAR-Lipo, which could effectively deliver genes and ensure high transfection efficiency under normoxia. Unsatisfactorily, the transfection efficiency of PAR-Lipo was rather poor under hypoxia. We believed that reoxygenation was the most direct and effective means to rescue the low transfection under hypoxia. Hence, we fabricated liposomes modified with perfluorooctyl bromide (PFOB@Lipo) to load oxygen and deliver it to tumor sites, which effectively alleviated the hypoxic nature of tumor. Then PAR-Lipo were applied to mediate high-efficiency delivery of tumor suppressor gene pTP53 to inhibit tumor progression. RESULTS: The results showed that such staged strategy augmented the expression of P53 protein in tumors and extremely suppressed tumor growth. CONCLUSION: This work was the first attempt to utilize an oxygen nanocarrier to assist the therapeutic effect of gene therapy under hypoxia, providing a new reference for gene therapy in malignant tumors. GRAPHICAL ABSTARCT.

Differentially expressed circular RNAs in orbital adipose/connective tissue from patients with thyroid-associated ophthalmopathy.

Our study aimed to investigate the differentially expressed circRNAs and their potential roles in orbital adipose/connective tissue from patients with thyroid-associated ophthalmopathy (TAO). The orbital adipose/connective tissue samples from three TAO patients and three control individuals were collected for RNA sequencing after depletion of ribosomal RNA. Differentially expressed mRNAs and up-regulated circRNAs were used for co-expression analysis. Functional and pathway enrichment analysis were conducted for the up- and down-regulated mRNAs in the circRNA-mRNA co-expression network. Meanwhile, circRNA-miRNA interaction network was established by miRanda software. The expression levels of mRNAs and circRNAs in control and TAO samples were determined by qRT-PCR. Among all the 16,329 circRNAs predicted from RNA sequencing data, 163 circRNAs (95 down-regulated and 68 up-regulated) were differentially expressed in TAO samples. Besides, 607 differentially expressed mRNAs were identified. The co-expression analysis showed circRNA_14940 was correlated with CCND1 and TNXB, while circRNA_10135 was correlated with PTGFR, and circRNA_14936 was correlated with TNFRSF19. The up-regulated CCND1 participated in Wnt signaling pathway. The down-regulated TNXB was involved in the ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. PTGFR participated in neuroactive ligand-receptor interaction and calcium signaling pathway. TNFRSF19 was involved in cytokine-cytokine receptor interaction. In the interaction network, circRNA_14936 could interact with hsa-miR-10392-3p, and circRNA_12367 could interact with hsa-miR-1228-3p. Moreover, the expression changes of MMP2, TNXB, PTGFR, CCND1, and TNFRSF19, as well as circRNA_14936, circRNA_14940, and circRNA_12367 were validated by qRT-PCR. In conclusion, the differentially expressed circRNAs might participate in pathogenesis of TAO, and we speculated that circRNA_14940-CCND1-Wnt signaling pathway might be an important regulatory axis.

Integrative transcriptomics and proteomic analysis of extraocular muscles from patients with thyroid-associated ophthalmopathy.

Our study aimed to reveal the underlying pathologic mechanisms of thyroid-associated ophthalmopathy (TAO) by integrative transcriptomics and proteomic analysis of extraocular muscles (EOM). The study involved 11 TAO patients (clinical activity score ≤ 2) and 11 control donors. Total RNA was extracted from EOM samples of 5 TAO patients and 5 control individuals for gene microarray analysis to reveal differentially expressed genes. Concurrently, EOM samples from 3 TAO patients and 3 control individuals were lysed for quantitative proteomic analysis. Differentially expressed genes and proteins were identified, followed by functional and pathway enrichment analysis and protein-protein interaction network construction. Concordance between proteins and transcripts was examined, and functional annotations were conducted. Expressions of versican (VCAN) and lipocalin 1 (LCN1) in EOM samples from another 3 TAO patients and 3 control individuals were measured by western blotting. In total, 952 genes and 137 proteins were identified as differentially expressed, as well as 96 differentially expressed proteins without significantly changed mRNA abundance. Proteins mainly related to the composition (such as MYH1, MYH2, and MYH13) and contraction force (MYH3, MYH8, ACTN3, and TNNT1) of the muscle fibers were significantly up-regulated in EOM samples of TAO, as well as those (such as VCAN, MPZ, and PTPRC) associated with cell adhesion. In addition, differentially expressed proteins related to the components and metabolism of extracellular matrix (ECM) (such as COL1A1, COL1A2, COL2A1, VCAN, OGN, and DCN) were identified. Similarly, expressions of genes involved in cell adhesion and ECM metabolism were significantly different between EOM samples of TAO patients and controls. Western blotting verified that VCAN involved in ECM proteoglycans and diseases associated with glycosaminoglycan metabolism was markedly higher in EOM samples of TAO, whereas LCN1 was obviously decreased. In conclusion, this study demonstrated the significantly altered cellular components of EOM, muscle contraction, cell adhesion and ECM metabolism, which might be involved in the pathologic mechanisms and/or consequences of TAO.

Inhibiting Hypoxia and Chemotherapy-Induced Cancer Cell Metastasis under a Valid Therapeutic Effect by an Assistance of Biomimetic Oxygen Delivery.

Tumor metastasis is the most dangerous stage in tumorigenesis and its evolution, which causes about 80% clinical death. However, common therapies including chemotherapy may increase the risk of tumor metastasis while killing cancer cells. Tumor metastasis is closely related to many factors in the tumor microenvironment, especially hypoxia. As one of the characteristics of a malignant tumor microenvironment, hypoxia plays an important role in the growth, metabolism, and metastasis of tumors. Upregulation of the hypoxia-inducible factor (HIF) would stimulate the metastasis and migration of cancer cells. In this study, we developed an artificial oxygen carrier system, a hemoglobin-loaded liposome (Hb@lipo), which was capable of effectively delivering oxygen to tumor. The way of providing oxygen not only alleviated tumor hypoxia but also downregulated the expression of HIF, which is conducive to reducing tumor malignancy. Alleviating the tumor hypoxic microenvironment alone is not enough to inhibit tumor metastasis; thus, we prepared the liposome containing a chemotherapeutic agent cabazitaxel (CBZ@lipo). Our data indicated that the combination therapy of Hb@lipo and CBZ@lipo can efficiently kill cancer cells and inhibit tumor growth. At the same time, it can effectively entrap cancer cells in tumor sites by relieving the hypoxic microenvironment of tumors and reduce the metastasis of cancer cells during and after the chemotherapy. Our research may provide a clinical cancer chemotherapy reference that reduces the risk of cancer cell metastasis while inhibiting tumor growth.

The comparison of visual outcomes, aberrations, and Bowman's layer micro-distortions after femtosecond laser small-incision lenticule extraction (SMILE) for the correction of high and moderate myopia and myopic astigmatism.

BACKGROUND: This study compares the clinical outcomes of femtosecond laser small-incision lenticule extraction (SMILE) for the correction of myopia and myopic astigmatism greater than - 10 D, and - 10 D or less respectively. METHODS: 60 eyes/patients were equally selected into group 1 (myopia and myopic astigmatism of - 10 D or less) and group 2 (myopia and myopic astigmatism of over - 10 D), both of which were treated with SMILE. Visual and refractive outcomes, corneal higher-order aberrations, and Bowman's layer micro-distortions were evaluated preoperatively, 3 months, and 6 months postoperatively. RESULTS: LogMAR corrected distance visual acuity (CDVA) of group 1 and group 2 was - 0.069 ± 0.047 and - 0.053 ± 0.073 6 months postoperatively (P = 0.48). 100% eyes in group 1 and 97% in group 2 were within 1 D of targeted correction (P = 0.45). Meanwhile, 100% eyes in group 1 and 97% in group 2 had an uncorrected distance visual acuity of 20/25 or better (P = 0.20). Changes in corneal higher-order aberrations root mean square, coma, and trefoil were similar between the two groups but spherical aberration was higher in group 2 (P < 0.01). Micro-distortions were observed in 53% in group 1 and 77% in group 2. More micro-distortions were observed in group 2 (3.40 ± 2.66) than in group 1 (2.07 ± 2.29) (P = 0.041). The total number of micro-distortions was not correlated with postoperative CDVA (P = 0.77). CONCLUSIONS: Visual outcomes showed similar results of SMILE for myopic correction of > - 10 D and ≤ - 10 D. Refractive outcomes showed slightly under-correction in higher myopic eyes. Higher myopic treatment tends to induce more spherical aberrations. Micro-distortions had no impact in visual and refractive outcomes.

MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor.

BACKGROUND/AIMS: Atherosclerosis, a multifactorial chronic disease, is the main cause of death and impairment in the world. Endothelial cells (ECs) apoptosis plays a crucial role in the onset and development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a well-defined tumor suppressor in several types of cancer, while the role of miR-142-3p in ECs apoptosis and the development of atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-142-3p in ECs apoptosis during atherosclerosis and the underlying mechanism. METHODS: Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT-PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay. Prediction of the binding between miR-142-3p and 3'-UTR of Rictor mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis were further analyzed in an in vivo model using ApoE-/- mice fed with high-fat diet (HFD). RESULTS: MiR-142-3p expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti-apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway was found to mediate the beneficial effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded the progression of atherosclerosis in the aorta of ApoE-/- mice. CONCLUSIONS: Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic development by up-regulating the expression of Rictor and activating the Akt/eNOS signaling pathway. This indicates that miR-142-3p may be a potential target for the prevention and treatment of atherosclerosis.