Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes.

Introduction: Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes. Methods: Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. Results: Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies. Discussion: Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.

Corneal Epithelial Remodeling Induced by Photorefractive Keratectomy Enhancement After Small-Incision Lenticule Extraction.

Purpose: To assess changes in corneal epithelial thickness (ET) within 9-mm diameter cornea after photorefractive keratectomy (PRK) retreatment after small-incision lenticule extraction (SMILE). Methods: A total of 28 eyes of 19 patients with mean spherical equivalent of -1.30 ± 0.60 D who underwent retreatment after SMILE were included in this retrospective study. ET mapped across a 9-mm diameter area was obtained using wide-field optical coherence tomography (OCT) before and at one, three, and six months after surgery. The ET changes were compared between the different time points and analyzed zones. Results: Before enhancement, the ET were 63.64 ± 6.01 µm and 61.25 ± 4.32 µm in central and paracentral zones, respectively. The ET of central and paracentral zones significantly decreased at one month and subsequently increased until six months. Six months after surgery, significant epithelial thickening occurred in 2- to 9-mm diameter cornea (all P < 0.05), whereas no significant change was observed in central 2-mm diameter cornea (P = 0.460). There was no significant difference in the ET between the central and paracentral zones (P = 1.00). The degree of myopic correction significantly correlated with the average ET in the central (P = 0.046) and paracentral (P = 0.033) zones at six months after PRK enhancement. No significant correlation was detected between the average ET of all zones and the postoperative spherical equivalent at six months after surgery (all P > 0.05). Conclusions: PRK enhancement did not alter the overall trend of corneal epithelial remodeling induced by SMILE. An asymmetric and flatter lenticule-like pattern of epithelial remodeling was observed six months after surgery, which did not affect the refractive outcomes. Translational Relevance: An asymmetric and centrally flattened lenticule-like pattern of epithelial remodeling was observed after PRK enhancement. Surgeons should consider expanding the intended optical zones for enhancement surgery after SMILE.

Ocular features in myopic eyes with longer horizontal ciliary sulcus diameters for intended implantable collamer lens surgery.

PURPOSE: To assess the ocular anterior segment characteristics in myopic eyes intended for ICL surgery with horizontal ciliary sulcus-to-sulcus (STS) diameters being greater than vertical STS diameters. METHODS: This retrospective, comparative case study included 1230 eyes of patients who underwent ICL implantation for the treatment of myopia or myopic astigmatism at the Zhongshan Ophthalmic Center from September 2020 to November 2021. The myopic eyes were divided into two groups according to the relatively long diameter of the ciliary sulcus. General parameters and anterior chamber parameters were compared between the two groups. RESULTS: 1230 eyes of 694 patients were included. The proportion of myopic eyes with longer horizontal STS diameters was 4.63%. Horizontal STS distances exceeding vertical meridians in these eyes were mainly attributed to the shortening of vertical STS distances (horizontal STS: P = 0.112; vertical STS: P < 0.001). Eyes with longer horizontal meridians of the ciliary sulcus displayed larger steep keratometry value (P = 0.001), larger corneal volume (P = 0.002), larger corneal astigmatism (P < 0.001), larger ocular residual astigmatism (P = 0.017), worse visual acuity (logMAR UDVA: P = 0.021; logMAR CDVA: P = 0.001), and more iridociliary cysts (P = 0.017) compared to eyes with vertically oval shapes. CONCLUSION: Myopic eyes with longer horizontal STS diameters are commonly accompanied by a change in corneal morphology and more iridociliary cysts. The anatomical features of the ciliary sulcus should be given sufficient consideration to ICL size and placement selection, contributing to more personalized and precise surgery.

Vault Height Is a Key Predictive Factor for Anterior Segment Measurement Error by IOLMaster 700 in Eyes With Phakic Intraocular Lens.

Purpose: To identify risk factors of ocular anterior segment measurement error by the IOLMaster 700 in eyes implanted with an implantable Collamer lens (ICL). Methods: In total, 152 patients with clear lens (152 eyes, group 1) and another 32 cataract patients (57 eyes, group 2) who underwent ICL implantation were included, and the presence of measurement error by the IOLMaster 700 was determined based on B-scan images. The risk factors for measurement error were evaluated by logistic regression, and the optimal threshold was determined using receiver operating characteristic analysis. Results: The ICL was misidentified as the anterior surface of the crystalline lens in 51.97% of eyes (79/152) in group 1 and 80.70% of eyes (46/57) in group 2. For every 100-µm decrease in the vault height, a 3.57- and 5.78-fold increase in the risk of measurement error was observed in group 1 and group 2, respectively. We identified an optimal threshold of the vault height at 389.47 µm for predicting biometric measurement error in eyes implanted with ICL, which showed an area under the curve of 0.93 (95% confidence interval, 0.90-0.97), a sensitivity of 0.87, and a specificity of 0.86. Conclusions: Patients with ICL implantation, particularly those with a vault height less than 389.47 µm, are at a greater risk of anterior segment biometric measurement error by the IOLMaster 700. Translational Relevance: The threshold of vault height can help to identify high-risk patients and further optimize biometric measurement.

Predicting post-operative vault and optimal implantable collamer lens size using machine learning based on various ophthalmic device combinations.

BACKGROUND: Implantable Collamer Lens (ICL) surgery has been proven to be a safe, effective, and predictable method for correcting myopia and myopic astigmatism. However, predicting the vault and ideal ICL size remains technically challenging. Despite the growing use of artificial intelligence (AI) in ophthalmology, no AI studies have provided available choices of different instruments and combinations for further vault and size predictions. This study aimed to fill this gap and predict post-operative vault and appropriate ICL size utilizing the comparison of numerous AI algorithms, stacking ensemble learning, and data from various ophthalmic devices and combinations. RESULTS: This retrospective and cross-sectional study included 1941 eyes of 1941 patients from Zhongshan Ophthalmic Center. For both vault prediction and ICL size selection, the combination containing Pentacam, Sirius, and UBM demonstrated the best results in test sets [R2 = 0.499 (95% CI 0.470-0.528), mean absolute error = 130.655 (95% CI 128.949-132.111), accuracy = 0.895 (95% CI 0.883-0.907), AUC = 0.928 (95% CI 0.916-0.941)]. Sulcus-to-sulcus (STS), a parameter from UBM, ranked among the top five significant contributors to both post-operative vault and optimal ICL size prediction, consistently outperforming white-to-white (WTW). Moreover, dual-device combinations or single-device parameters could also effectively predict vault and ideal ICL size, and excellent ICL selection prediction was achievable using only UBM parameters. CONCLUSIONS: Strategies based on multiple machine learning algorithms for different ophthalmic devices and combinations are applicable for vault predicting and ICL sizing, potentially improving the safety of the ICL implantation. Moreover, our findings emphasize the crucial role of UBM in the perioperative period of ICL surgery, as it provides key STS measurements that outperformed WTW measurements in predicting post-operative vault and optimal ICL size, highlighting its potential to enhance ICL implantation safety and accuracy.

Modulation of IrO6 Chemical Environment for Highly Efficient Oxygen Evolution in Acid.

The sluggish kinetics of the oxygen evolution reaction (OER) limits the commercialization of oxygen electrochemistry, which plays a key role in renewable energy technologies such as fuel cells and electrolyzers. Herein, a facile and practical strategy is developed to successfully incorporate Ir single atoms into the lattice of transition metal oxides (TMOs). The chemical environment of Ir and its neighboring lattice oxygen is modulated, and the lattice oxygen provides lone-pair electrons and charge balance to stabilize Ir single atoms, resulting in the enhancement of both OER activity and durability. In particular, Ir0.08 Co2.92 O4 NWs exhibit an excellent mass activity of 1343.1 A g-1 and turnover frequency (TOF) of 0.04 s-1 at overpotentials of 300 mV. And this catalyst also displays significant stability in acid at 10 mA cm-2 over 100 h. Overall water splitting using Pt/C as the hydrogen evolution reaction catalyst and Ir0.08 Co2.92 O4 NWs as the OER catalyst takes only a cell voltage of 1.494 V to achieve 10 mA cm-2 with a perfect stability. This work demonstrates a simple approach to produce highly active and acid-stable transition metal oxides electrocatalysts with trace Ir.

A comparative and prospective study of corneal biomechanics after SMILE and FS-LASIK performed on the contralateral eyes of high myopia patients.

Background: To compare the corneal biomechanical changes after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with the same programmed optical zone (POZ) and similar refractive correction in patients with high myopia. Methods: In this prospective comparative study of the contralateral eye, 50 patients with high myopia with the same POZ and similar refractive correction who underwent SMILE in one eye and FS-LASIK in the other eye. Corneal biomechanical parameters and central corneal thickness (CCT) were measured using a Corvis ST II. All the patients were evaluated during follow-up visits beyond one year. Additionally, the corneal volume (CV) of the 10-mm diameter region was measured using a Pentacam. Results: Ambrosio relational thickness to the horizontal profile (ARTh) and stiffness parameter A1 (SP-A1) decreased significantly after SMILE and FS-LASIK, whereas deformation amplitude ratio 2.0 mm (DA ratio 2.0 mm) and integrated radius (IR) increased significantly in both groups. The ARTh and SP-A1 were greater after SMILE than those after FS-LASIK at all the follow-up visits. In addition, there were greater amounts of CCT and CV after SMILE compared with that after FS-LASIK. Moreover, a positive correlation was found between ARTh and SP-A1 and postoperative CCT, while a negative correlation was found between IR and DA ratio 2.0 mm and postoperative CCT. A moderate correlation was observed between SP-A1 and CV after both SMILE and FS-LASIK, whereas there were no relationships between CV and ARTh, IR, or DA ratio 2.0 mm. Conclusions: SMILE had greater CCT, CV, ARTh, and SP-A1 than FS-LASIK in high myopia with the same POZ and similar refractive correction. Our results demonstrated that SMILE had lesser effect on corneal biomechanics than FS-LASIK in high myopia. Keywords: Corneal biomechanics; Corvis ST II; small incision lenticule extraction (SMILE); femtosecond laser-assisted in situ keratomileusis (FS-LASIK); high myopia.

Comparing Mycobacterium tuberculosis RNA Accuracy in Various Respiratory Specimens for the Rapid Diagnosis of Pulmonary Tuberculosis.

Objective: To evaluate the rapid diagnostic accuracy of Mycobacterium tuberculosis RNA (TB-RNA) for pulmonary tuberculosis (PTB) in a large patient sample and to evaluate the difference in TB-RNA diagnostic accuracy in various respiratory specimens. Methods: Patient medical records were retrospectively reviewed to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the acid-fast bacillus (AFB) smear and TB-RNA to evaluate their diagnostic accuracy against final clinical diagnosis. Results: Of the 2336 patients ultimately included, 1123 provided 1 sputum specimen each and 1213 provided 1 bronchoalveolar lavage fluid (BALF) specimen each. The overall sensitivity, specificity, PPV, NPV, and AUC of the AFB smear were 36.2%, 86.4%, 90.6%, 27.3%, and 0.61, respectively. The overall sensitivity, specificity, PPV, NPV, and AUC of TB-RNA for the rapid detection of PTB were 57.4%, 99.4%, 99.7%, 39.3%, and 0.78, respectively. When sputum and BALF specimens were used for AFB smear testing, the sensitivity, specificity, PPV, NPV, and AUC of the AFB smear were 44.5%, 81.5%, 87.5%, 33.5%, and 0.63; and 29.2%, 92.7%, 94.8%, 22.5%, and 0.61, respectively. The sensitivity, specificity, PPV, NPV, and AUC of TB-RNA for the rapid detection of PTB using sputum were 49.6%, 99.3%, 99.5%, 40.4%, and 0.74, respectively; whereas those of TB-RNA determined using BALF were 63.9%, 99.5%, 99.8%, 38.0%, and 0.82, respectively. Conclusion: The diagnostic accuracy of TB-RNA for PTB was moderate and considerably better than that of the AFB smear. The diagnostic accuracy of TB-RNA for various respiratory specimens differed; the diagnostic accuracy of TB-RNA for BALF specimens was substantially better than that for sputum samples, and BALF specimens were more suitable for TB-RNA.

Corneal Stiffness and Modulus of Normal-Tension Glaucoma in Chinese.

PURPOSE: To assess and compare the corneal biomechanics of normal-tension glaucoma (NTG), high-tension glaucoma (HTG), and normal controls based on stiffness and modulus. The correlations among central corneal thickness (CCT), visual field, retinal nerve fiber layer (RNFL) thickness, and corneal biomechanics in glaucoma eyes were also evaluated. DESIGN: A prospective, cross-sectional, comparative study. METHODS: This study included 334 eyes of 108 NTG patients, 113 HTG patients, and 113 control subjects at Zhongshan Ophthalmic Center, Sun Yat-Sen University. Corneal biomechanics were evaluated using a corneal indentation device (CID) and corneal visualization Scheimpflug technology (Corvis ST). Visual field and RNFL thickness were obtained using standard automated perimetry and spectral-domain optical coherence tomography. One-way analyses of variance with Bonferroni post hoc tests and a multivariable linear regression analysis with adjustment were conducted. Correlations among corneal biomechanical parameters, CCT, visual field, and RNFL thickness were analyzed. RESULTS: The corneal stiffness of the NTG patients (71.0 ± 10.9 N/m) was significantly lower than that of the HTG patients (77.3 ± 15.6 N/m; P = .001) and the CCT- and IOP-matched normal controls (75.6 ± 11.0 N/m; P = .023). The patients in the NTG group had lower corneal stiffness than those in the control group (ß = -4.88, 95% CI -9.002, -0.758; P = .020) after adjusting for confounders. Stiffness was positively correlated with CCT in the NTG group (P = .028) but not in the HTG group (P = .509). There was no significant correlation (P > .05) between corneal biomechanics, visual field, or RNFL thickness. CONCLUSIONS: The corneas of NTG patients were softer than those of HTG patients and controls, as assessed by CID, which were associated with thinner CCT. These might suggest different ocular biomechanical properties in NTG and HTG.

Evaluation of Wide Corneal Epithelial Remodeling after Small Incision Lenticule Extraction (SMILE) with Wide-Field Optical Coherence Tomography.

Purpose: This study aims to assess the corneal epithelial remodeling within a 9 mm diameter zone induced by small incision lenticule extraction (SMILE) and evaluate its relationship with the refractive outcomes. Methods: A total of 64 eyes of 64 patients were included. Wide-field optical coherence tomography (OCT) was used to measure the epithelial thickness (ET) across a 9 mm diameter area, preoperatively, and after one day, one week, one month, three months, and six months postoperatively. The ET changes were compared among the different time points and analyzed zones. Results: The ET increases from one week to three months and stabilized from three months to six months. Compared to the preoperative values, the mean ET changes at six months in central (2 mm), paracentral (2-5 mm), mid-peripheral (5-7 mm), and peripheral (7-9 mm) zones were 4.37, 4.36, 1.61, and -1.59 µm, respectively. The correlation between the epithelial thickening and the amount of myopia correction was positive in central (P = 0.001) and paracentral zones (P < 0.001) and negative in peripheral zone (P = 0.006). The intended diameter of the optical zone was negatively related to epithelial hyperplasia in the central (P = 0.020) and paracentral zone (P = 0.006), and the correlation was positive in the mid-peripheral zone (P = 0.001). The epithelial thickening of central zone (P = 0.012) and the difference of mean ET between central and paracentral zone (P = 0.020) were negatively related to the spherical equivalent at six months. Conclusion: An asymmetric lenticule-like pattern of epithelial remodeling occurred in 9 mm diameter cornea at six months after myopic SMILE. The epithelial remodeling may affect the refractive outcomes of SMILE.

Prospective, Randomized, Contralateral Eye Comparison of Functional Optical Zone, and Visual Quality After SMILE and FS-LASIK for High Myopia.

PURPOSE: To compare the functional optical zone (FOZ) and visual quality after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in correcting high myopia. METHODS: Ninety-two eyes of 46 high myopic patients with the same programmed optical zone (POZ) received SMILE in one eye and FS-LASIK in the contralateral eye. FOZ was calculated using a refractive power method. The decentration, visual outcomes, wavefront aberrations, contrast sensitivity, and quality of vision (QoV) questionnaire were analyzed at 6 months postoperatively. RESULTS: The postoperative visual and refractive outcomes were comparable between SMILE and FS-LASIK. The FOZ for SMILE (5.62 ± 0.31 mm) was larger than for FS-LASIK (5.35 ± 0.28 mm; P < 0.001). Moreover, the total decentration for SMILE (0.29 ± 0.14 mm) was greater than in FS-LASIK (0.22 ± 0.11 mm; P < 0.001). The induced change in spherical aberration was less for SMILE than for FS-LASIK (P < 0.001). There was better contrast sensitivity under the mesopic condition with glare for SMILE than for FS-LASIK (P = 0.024). However, no significant difference was found in QoV scores between the two groups. CONCLUSIONS: SMILE created a larger FOZ and greater decentration than FS-LASIK when the same POZ was designed in high myopia. Objective and subjective visual symptoms were comparable between SMILE and FS-LASIK. TRANSLATIONAL RELEVANCE: The differences in FOZ and decentration between SMILE and FS-LASIK have little effect on vision outcomes. Surgeons should consider the FOZ and decentration in surgical options in high myopia.

Wide Corneal Epithelial Thickness Mapping in Eyes With Topical Antiglaucoma Therapy Using Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the corneal epithelial thickness (CET) of the 9-mm diameter zone in patients treated using topical antiglaucoma medications and to evaluate the factors associated with CET changes. Methods: Seventy-five patients treated using topical antiglaucoma medications and 65 healthy subjects were included in this cross-sectional study. Each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent examinations including the Schirmer I test, tear breakup time (TBUT), and fluorescein staining. CET mapping of the 9-mm diameter zone was performed using RTVue XR. The CET of the different analyzed zones was compared between groups. The relationship between CET and confounding factors was investigated. Results: The patient group had a significantly shorter TBUT, shorter Schirmer I test, and greater fluorescein staining than those of the control group (all P < 0.05). The mean CET of patients with glaucoma was significantly lower than that of controls in the central, paracentral, mid-peripheral, and peripheral zones (all P < 0.001). Age affected the CET in the paracentral, mid-peripheral, and peripheral zones (all P < 0.01). The number of medications affected the CET in the central, paracentral, and mid-peripheral zones (all P < 0.05). The duration of treatment affected the CET in the central and peripheral zones (all P < 0.05). Conclusions: Use of topical IOP-lowering medications leads to epithelial thinning in the 9-mm diameter zone in glaucomatous eyes. Epithelial protection should be considered in older patients and patients treated with multiple medications from the early stages of long-term topical antiglaucoma therapy. Translational Relevance: The 9-mm diameter CET mapping by using widefield optical coherence tomography (OCT) can be a valuable and convenient method to assess the ocular surface damage in patients with topical antiglaucoma therapy.

A Novel Indentation Assessment to Measure Corneal Biomechanical Properties in Glaucoma and Ocular Hypertension.

Purpose: To evaluate the ability of the new in vivo corneal indentation device (CID) to measure corneal biomechanical properties. Methods and Results: In total, 186 eyes from 46 healthy subjects, 107 patients with primary open-angle glaucoma, and 33 patients with ocular hypertension were enrolled in a cross-sectional study. Measurements were performed using corneal visualization Scheimpflug technology (Corvis ST) and the CID. The deformation amplitude (DA), inward applanation time, inward applanation velocity (A1V), outward applanation time (A2T), outward applanation velocity (A2V), highest concavity time, DA ratio, max inverse radius (MIR), integrated radius, and stiffness parameter A1 were included as Corvis ST parameters, and stiffness and modulus were included as CID parameters. Associations between the Corvis ST and CID parameters and correlations between central corneal thickness and corneal biomechanical parameters were analyzed. The stiffness was significantly correlated with all the Corvis ST parameters (P < 0.05). The modulus was significantly correlated with the DA, A1V, A2T, A2V, highest concavity time, and MIR (P < 0.05). The DA, inward applanation time, A1V, A2T, A2V, DA ratio, MIR, integrated radius, and stiffness parameter A1 values and both CID-derived values were significantly correlated with central corneal thickness (P < 0.05). Conclusions: Parameters derived from the CID and Corvis ST demonstrated agreement in the measurement of corneal biomechanical properties. The stiffness and modulus can characterize in vivo corneal biomechanical properties. Translational Relevance: Agreeing with the Corvis ST regarding the assessment of corneal biomechanical properties, the CID can be a novel clinical tool for biomechanical evaluation of the cornea.

Corneal Epithelial Thickness Changes Following SMILE for Myopia With High Astigmatism.

PURPOSE: To evaluate the corneal epithelial thickness (CET) profile changes after small incision lenticule extraction (SMILE) surgery for myopic astigmatism correction of greater than 2.00 diopters (D). METHODS: This prospective observational study included 40 eyes (23 patients) treated with SMILE for myopia with cylinders of -2.25 to -4.50 D. Along with standard ophthalmic examinations, CET maps with a diameter of 9 mm were measured by high-resolution spectral-domain optical coherence tomography preoperatively and postoperatively. Correlations between the degree of residual astigmatism and the difference in CET values between preoperative flat and steep meridians were analyzed. RESULTS: The CET showed significant changes in the central (2 mm), paracentral (2 to 5 mm), midperipheral (5 to 7 mm), and peripheral (7 to 9 mm) zones 6 months after SMILE (P < .001). Among the regions, the CET in the paracentral zones displayed the largest increase (9.75%) with the highest average thickness (57.29 µm). Moreover, symmetrical regional epithelial thickening at the preoperative astigmatism axis was observed in the midperipheral zones. The difference in CET between preoperative flat and steep meridians in the mid-peripheral zones continuously increased from postoperative 1 day to 6 months. This difference was positively correlated with the residual cylinder errors at 6 months postoperatively (r = -0.334, P = .035). CONCLUSIONS: The 9-mm diameter CET in eyes with high astigmatism significantly increased 6 months after SMILE. Additionally, the difference in CET between preoperative flat and steep meridians in midperipheral zones may be related to astigmatic undercorrection in SMILE. [J Refract Surg. 2021;37(4):224-230.].

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG.

Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an in vivo study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.

Construction of electric vehicle driving cycle for studying electric vehicle energy consumption and equivalent emissions.

This paper proposes an effective and scientific method for the construction of a representative driving cycle for electric vehicles (EV) and takes it as a foundation for studying the energy consumption and equivalent emissions for EV. First, a test route is developed through the analysis of the topology of the Xi'an road structure and traffic flow. Second, the vehicle driving pattern data is gathered through an integrated method of chase car method and on-board method. The velocity-acceleration (V-A) grid method is used to divide speed and acceleration data into micro-states. Third, the proposed driving cycle construction method incorporates the Markov chain and Monte Carlo (MCMC) simulation method. Then, a filter process is designed to screen out the most representative driving cycle. Finally, the comparison of the simulation result and test results shows the constructed EV driving cycle is in line with reality, and estimating the EV's energy consumption per kilometer, driving range, and equivalent emissions under official driving cycles results in large relative errors. Therefore, the construction of a real-world driving cycle for specific cities or areas is necessary to evaluate energy consumption, driving range, and equivalent emissions of EV.

AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodelling in ET-1-induced POAG.

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of ß-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.

Comparison of Biomechanically Corrected Intraocular Pressure Obtained by Corvis ST and Goldmann Applanation Tonometry in Patients With Open-angle Glaucoma and Ocular Hypertension.

PRECIS: Biomechanically corrected intraocular pressure (bIOP) measurements provided by the new Corvis ST (CST) were higher than measurements obtained with Goldman applanation tonometry (GAT) in eyes with ocular hypertension (OHT) or open-angle glaucoma (OAG). PURPOSE: To compare bIOP obtained with a new version of CST with GAT measurements in patients with OAG and OHT, and to identify factors affecting IOP measurement differences between these methods. METHODS: A total of 122 eyes with OAG or OHT were enrolled. Sixty eyes were treated with prostaglandin analogs (PGA) and 62 eyes with selective laser trabeculoplasty (SLT). IOP was measured with CST, followed by GAT. Central corneal thickness (CCT) was measured with ultrasound pachymetry. Measurements obtained with these 2 approaches were compared. RESULTS: The overall mean IOP was 15.2±3.0 mm Hg and 14.1±3.2 mm Hg with the CST and GAT, respectively (r=0.74; P<0.0001). There was a 1.17 mm Hg bias between tonometers, with 95% limits of agreement of -2.66 to 5.01 mm Hg. According to multivariate regression analysis, differences between bIOP and GAT-IOP were associated with CCT (P=0.001) and age (P=0.007) in the PGA group, but only with CCT in the SLT group (P=0.002). bIOP and GAT-IOP values were influenced by age (PGA: P=0.014; SLT: P=0.006) and CCT (PGA: P=0.007; SLT: P=0.032), respectively. CONCLUSIONS: BIOP values were higher and less affected by CCT than GAT-IOP values in eyes with OAG and OHT. However, these measurements may not be interchangeable in the clinic.

Comparison of Small Incision Lenticule Extraction Surgery With and Without Cyclotorsion Error Correction for Patients With Astigmatism.

PURPOSE: To evaluate the add-on effect of manual cyclotorsion error correction by the cornea-marking method over standard small incision lenticule extraction (SMILE) surgery in astigmatic eyes. METHODS: Consecutive patients (84) who had preoperative myopic astigmatism of -0.75 diopters (D) or more and were seeking surgical refractive correction by SMILE surgery during July 2017 to August 2017 were included in this study and randomized to treatment with standard SMILE surgery (S group: 30 eyes) or cyclotorsion compensated SMILE surgery (CC group: 54 eyes). The visual acuity and refractive outcomes were analyzed preoperatively and postoperatively. Refractive astigmatic changes were analyzed by the Alpins method. RESULTS: The S and CC groups were comparable preoperatively regarding age, manifest spherical equivalent, and manifest refractive cylinder. The mean position-related cyclotorsion degree in the enrolled astigmatic eyes for the S and CC groups was 1.7 ± 2.2 degrees (ranging from 0 to 10 degrees) and 2.19 ± 1.74 degrees (ranging from 0 to 10 degrees), respectively. The mean cylinder was -1.67 ± 0.54 D versus -1.72 ± 0.71 D preoperatively. Six months after treatment, the surgical outcomes in the CC group were significantly better than those of the S group, with a postoperative corrected distance visual acuity of -0.07 ± 0.07 versus 0.016 ± 0.13. A vector analysis of astigmatism also yielded better outcomes in the CC group. However, these 2 groups were statistically similar in spherical equivalent. CONCLUSIONS: SMILE surgery combined with cyclotorsion error compensation yielded a significant improvement in surgical outcomes regarding safety, efficiency, and predictability for patients with astigmatism.

Correction of Astigmatism With SMILE With Axis Alignment: 6-Month Results From 622 Eyes.

PURPOSE: To evaluate postoperative clinical outcomes in myopic eyes with astigmatism that underwent femtosecond laser small incision lenticule extraction (SMILE) surgery with axis alignment. METHODS: Overall, 622 eyes from 353 patients with myopia and astigmatism greater than -0.75 diopters (D) who had SMILE were included in this prospective study. Standard examinations were performed and visual acuity and vector astigmatism values were analyzed preoperatively and postoperatively. RESULTS: Preoperative manifest spherical equivalent (SE) was -6.11 ± 1.68 D (range: -0.50 to -11.25 D) and manifest refractive cylinder was -1.60 ± 0.65 D (range: -0.75 to -6.25 D). In 622 enrolled eyes with astigmatism, 29.9% did not require rotation modification during surgery, and the average rotation degree (absolute) was 2.82° ± 1.44° (range: 0° to 10°). By 6 months after SMILE, all eyes showed improved uncorrected distance visual acuity (UDVA); approximately 96.8% of eyes with astigmatism achieved the same or better UDVA postoperatively compared to the preoperative corrected distance visual acuity (CDVA). Moreover, the cylinder of all eyes was within ±1.00 D, and 97% of eyes were within ±0.50 D. Only 47 eyes exhibited a low degree of astigmatism (range: -0.75 to 0.50 D). In patients with high astigmatism (>-3.00 D), the preoperative CDVA was -0.02 ± 0.11 logMAR and the 6-month postoperative UDVA was -0.01 ± 0.16 logMAR (n = 24, P > .05), further implying the effectiveness of modified SMILE for refractive correction in patients with astigmatism. CONCLUSIONS: SMILE with axis alignment provides efficient, predictable, and safe refractive correction in patients with myopic astigmatism. [J Refract Surg. 2019;35(3):138-145.].