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The complex pathogenesis of lung ischemia-reperfusion injury (LIRI) was examined in a murine model, focusing on the role of pyroptosis and its exacerbation of lung injury. We specifically examined the levels and cellular localization of pyroptosis within the lung, which revealed alveolar macrophages as the primary site. The inhibition of pyroptosis by VX-765 reduced the severity of lung injury, underscoring its significant role in LIRI. Furthermore, the therapeutic potential of β-hydroxybutyrate (β-OHB) in ameliorating LIRI was examined. Modulation of β-OHB levels was evaluated by ketone ester supplementation and 3-hydroxybutyrate dehydrogenase 1 (BDH-1) gene knockout, along with the manipulation of the SIRT1-FOXO3 signaling pathway using EX-527 and pCMV-SIRT1 plasmid transfection. This revealed that β-OHB exerts lung-protective and anti-pyroptotic effects, which were mediated through the upregulation of SIRT1 and the enhancement of FOXO3 deacetylation, leading to decreased pyroptosis markers and lung injury. In addition, β-OHB treatment of MH-S cells in vitro showed a concentration-dependent improvement in pyroptosis, linking its therapeutic benefits to specific cell mechanisms. Overall, this study highlights the significance of alveolar macrophage pyroptosis in the exacerbation of LIRI and indicates the potential of β-OHB in mitigating injury by modulating the SIRT1-FOXO3 signaling pathway., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: We aimed to explore the treatment effect and therapeutic mechanisms of baicalin in Alzheimer's disease (AD)., Methods: The AD rat model was established by intracerebroventricular injection of Aβ1-40, with rats in the baicalin group receiving baicalin intraventricular injections. Morris Water Maze and Hematoxylin-eosin (H&E) Staining were employed to detect the successful model construction and baicalin treatment effect. The proteins extracted from the hippocampus were subjected to proteomics analysis. Bioinformatics technology was employed for differential protein screening, functional classification, and enrichment. Western Blot was employed to validate the expressions of differentially expressed proteins (DEPs) and the protein modification alternations., Results: Water maze test confirmed the successful AD model construction and baicalin can improve learning and memory abilities. A total of 26 DEPs associated with 28 Gene Ontology (GO) functions were identified in the model and 32 DEPs were obtained between the baicalin group and the model. Bioinformatics analysis demonstrated that AD occurrence resulted in neuronal dysfunction and was associated with immune responses. The baicalin therapeutic effect on AD may be associated with metabolic processes, vitamin response, angiogenesis regulation, and fatty acid response. Immunoglobulin heavy constant mu (Ighm) and Immunoglobulin G2a (IgG2a) exhibited significant increases in AD and baicalin attenuated their expressions, while Fatty acid desaturase 1 (Fads1) exhibited a significantly diminished expression and baicalin could reverse the trend. Succinylation detection exhibited the differentially expressed at 35 kD between the model and baicalin group., Conclusion: Baicalin intervention may ameliorate cognitive impairment in AD rats by modulating the expressions of proteins and the succinylation modifications.

Deoxynivalenol (DON) is widely found in food and feed, posing a threat to human and animal health. Lycopene (Lyc) is a natural plant extracts with significant antioxidant properties. This study was conducted to investigate the protective effects of Lyc on IPEC-J2 cells upon DON exposure. The detection of cell viability and trypan blue staining showed that Lyc alleviated cell damage and decreased cell apoptotic rate induced by DON. The analysis of reactive oxygen species (ROS) level and antioxidant parameter measurements showed that Lyc significantly down-regulated the content of ROS and restored antioxidant enzyme activity. Furthermore, mitochondrial membrane potential (ΔΨm) detection, mitochondrial DNA copy number (mtDNAcn) assay and adenosine triphosphate (ATP) concentration detection showed Lyc improved mitochondrial function after DON exposure. The results of transcriptome analysis, ROS detection and CCK8 assay suggested that Lyc may activated the oxidative phosphorylation (OXPHOS) to improve mitochondrial function. Conclusively, our results suggested that Lyc alleviated DON-induced oxidative stress by improving mitochondrial function through OXPHOS signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR + ) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC., Methods: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models., Results: Our PDX-derived metastasis (PDM) model collection comprises three AR + adenocarcinomas (ARPC) and one AR - neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR + PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification., Conclusion: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: To evaluate the risk factors for uterine clear-cell carcinoma (UCCC) and construct nomograms predicting 1-, 3-, and 5-year overall survival rates of patients with UCCC., Methods: The demographic and clinical information of 1674 patients diagnosed with UCCC between 2004 and 2015, including age, race, marital status, tumor size, American Joint Committee on Cancer (AJCC) stage, and details of surgery and radiotherapy/chemotherapy, was collected from the Surveillance, Epidemiology, and End Results (SEER) database. After excluding patients with unknown AJCC stage, race, marital status, or lymph node information, 1469 patients remained. Risk factors were determined using univariate and multivariate analyses, and nomograms were developed to predict 1-, 3-, and 5-year overall survival of UCCC. Various indicators were used to evaluate the performance of the nomogram, such as the C-index, net classification improvement (NRI) and decision curve analysis (DCA)., Results: Age, log odds of positive lymph nodes, AJCC stage, surgery status, and chemotherapy status were independent risk factors for UCCC. The C-indexes of the training group and AJCC stage groups were 0.771 and 0.697, respectively. The results for the area under the receiver operating characteristics curve, NRI, and calibration curves indicated that the nomogram had good predictive ability. DCA revealed that the nomogram had greater clinical applicability than AJCC stage alone. Internal validation using the validation cohort also demonstrated that this nomogram had good predictive performance., Conclusion: A new nomogram comprising a combination of demographic and clinical characteristics provided better survival predictions than the AJCC staging system alone, which will facilitate prognostic assessments and clinical decision-making., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: Epidemiological studies examining the association between circulating micronutrients and the risk of hypertensive disorders during pregnancy (HDP) have produced inconsistent results. Therefore, we conducted a Mendelian randomization (MR) analysis to evaluate the potential causal relationship between micronutrients and HDP., Methods: Nine micronutrients (beta-carotene, vitamin B6, vitamin B12, calcium, zinc, selenium, copper, folate, and phosphorus) were selected as the exposure factors. Summary data for gestational hypertension (14,727 cases and 196,143 controls) and preeclampsia/eclampsia (7212 cases and 174,266 controls) were extracted from the FinnGen consortium. The MR analysis employed the inverse variance weighted method and conducted a range of sensitivity analyses., Results: The inverse variance weighted method indicated no significant causal relationship between nine genetically predicted micronutrient concentrations and gestational hypertension, as well as preeclampsia/eclampsia. Sensitivity analyses suggested the absence of pleiotropy., Conclusion: There is no strong evidence to support the causation between circulating micronutrients and hypertensive disorder during pregnancy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Finding the optimal treatment strategy to accelerate wound healing is of utmost importance, but it presents a formidable challenge owing to the intrinsic nonlinear nature of the process. We propose an adaptive closed-loop control framework that incorporates deep learning, optimal control and reinforcement learning to accelerate wound healing. By adaptively learning a linear representation of nonlinear wound healing dynamics using deep learning and interactively training a deep reinforcement learning agent for tracking the optimal signal derived from this representation without the need for intricate mathematical modelling, our approach has not only successfully reduced the wound healing time by 45.56% compared to the one without any treatment, but also demonstrates the advantages of offering a safer and more economical treatment strategy. The proposed methodology showcases a significant potential for expediting wound healing by effectively integrating perception, predictive modelling and optimal adaptive control, eliminating the need for intricate mathematical models., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Z-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear., Methods: Cartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models., Results: We showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA., Conclusions: Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA., (© 2024. The Author(s).)

The influence of starch granule surface proteins (SGSPs) and starch granule-associated proteins (SGAPs) on bread retrogradation was investigated in a reconstituted dough system. The removal of both SGSPs and SGAPs resulted in poor bread qualities, decreasing specific volume and crumb porosity, leading to more baking loss and compact crumb structure. Particularly, removing SGSPs was effective in promoting the bread retrogradation. After 7 days of storage, the hardness of bread without SGSPs showed an increase of 353.34 g than the bread without SGAPs. Proton population and relaxation times exhibited that the absence of SGSPs significantly decreased the content of bound water from 11.51 % to 7.03 %, indicating lower water-holding capacity due to the loosen gelling structure. Compared to the control group, bread without SGSPs accelerated the starch recrystallinity by a reduction in soluble starch content, thereby increasing the retrogradation enthalpy and relative crystallinity through promoting the molecular reassociation in starch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the myopia control efficacy of novel Lenslet-ARray-Integrated (LARI) spectacle lenses with positive power lenslets (PLARI) and negative power lenslets (NLARI) worn for 1 year in myopic children., Design: Randomized, double-masked, controlled clinical trial., Participants: A total of 240 children 6 to 12 years of age with spherical equivalent refraction (SER) between -4.00 and -1.00 diopters (D), astigmatism of ≤ 1.50 D, and anisometropia of ≤ 1.00 D., Methods: Participants were assigned randomly in a 1:1:1 ratio to PLARI, NLARI, and control (single-vision [SV]) groups. Cycloplegic autorefraction and axial length were measured at baseline and 6-month intervals after lens wear., Main Outcome Measures: Changes in SER, axial elongation (AE), and differences between groups., Results: After 1 year, SER changes and AE in the PLARI and NLARI groups were significantly less than those in the SV group (SER: -0.30 ± 0.48 D, -0.21 ± 0.35 D, and -0.66 ± 0.40 D, respectively; AE: 0.19 ± 0.20 mm, 0.17 ± 0.14 mm, 0.34 ± 0.18 mm, respectively; all P < 0.001). No significant differences were found in SER changes and AE between PLARI and NLARI groups (P = 0.54 and P = 1.00, respectively). Younger age was associated with more rapid SER increase and larger AE in the SV group (r = 0.40 [P < 0.001] and r = -0.59 [P < 0.001], respectively) and PLARI group (r = 0.46 [P < 0.001] and r = -0.52 [P < 0.001], respectively), but not in the NLARI group (r = -0.002 [P = 0.98] and r = -0.08 [P = 0.48], respectively)., Conclusions: Compared with the SV group, both PLARI and NARI groups showed significantly slower myopia progression in terms of SER and AE. Faster myopia progression, in terms of both SER and AE, was associated with younger age in the SV and PLARI groups but not the NLARI group., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: To compare the repeatability and reproducibility of corneal and corneal epithelial thickness mapping using anterior segment optical coherence tomography (AS-OCT) according to tear film break-up time (TBUT)., Methods: The included eyes were divided into three subgroups according to TBUT (group 1: TBUT ≤ 5 s, group 2: 5 s < TBUT ≤ 10 s, and group 3: TBUT > 10 s). All eyes were imaged separately thrice by two operators to obtain the thickness maps (TMs) of the cornea and corneal epithelium based on spatial zones encompassing a 9-mm-diameter area. Each TM consisted of 25 areas. Intraoperator (repeatability) and interoperator (reproducibility) standard deviations (Sws), coefficients of variation (CoVs), and intraclass correlation coefficients (ICCs) among the tests were calculated and compared in all the areas., Results: Altogether, 132 eyes of 67 subjects were included (50, 47, and 35 eyes in groups 1, 2, and 3; respectively). The ICCs of corneal epithelial thickness and corneal thickness were > 0.75 in most of the areas. Pairwise comparisons showed that AS-OCT exhibited lower repeatability in group 1 than in groups 2 and 3 (P < 0.05). However groups 2 and 3 showed similar results. Sws and CoVs of corneal epithelial thickness exhibited no significant interoperator differences. While no significant differences were observed in corneal thickness in most of the areas., Conclusions: TBUT significantly influences the repeatability of corneal and corneal epithelial thickness measurements. Poor tear film stability requires careful evaluation of corneal epithelial thickness., (© 2024. The Author(s).)

Background: Although the talar morphology has been well understood, studies on the corresponding tibial plafond are still lacking. Based on computed tomography (CT) data, this quantitative study divided the tibial plafond into anterior and posterior regions on five sagittal sections. The objectives of this study were (I) to determine whether the sagittal curvatures of the tibial plafond can be quantitatively and accurately described using the double-diameter method; (II) to compare the difference between the anterior and posterior diameters on five sagittal sections., Methods: In this study, CT data were collected from 100 adult ankles, and the three-dimensional (3D) ankle joint model was reconstructed using CT images. An anatomical coordinate system of the 3D ankle joint model was created to establish the standard coronal and sagittal planes. The measurement outcomes of sagittal curvatures included: the anterior and posterior diameters, the distal tibial arc length (TiAL) and the distal tibial mortise depth (TMD) on five sagittal sections (the most medial, medial 1/4, middle, lateral 1/4 and the most lateral section). Subgroup analysis was performed to compare the differences between males and females., Results: Analysis of the sagittal curvatures showed that the anterior diameter of tibial plafond was significantly smaller than the posterior diameter on five sagittal sections with a mean difference ranging from 3.9 to 6.8 mm (P<0.001). For the anterior diameters, the anteromedial curve had the smallest diameter (35.3±5.3 mm), and the anterolateral curve had the largest diameter (38.0±5.8 mm). For the posterior diameter, the posteromedial curve had the smallest diameter (39.2±6.4 mm), and the posterolateral 1/4 curve had the largest diameter (43.5±6.9 mm). One-way analysis of variance (ANOVA) revealed significant differences in the anterior and posterior diameters among five groups (P<0.012). Subgroup analysis showed that gender partly affected the results of sagittal curvature measurements., Conclusions: The sagittal curvatures of the tibial plafond can be described quantitatively and accurately using anterior and posterior diameters. Our study showed that there were significant differences between the anterior and posterior diameters, and gender was an important factor influencing the sagittal curvatures of the tibial plafond., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1807/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade., (© 2024 Wiley‐VCH GmbH.)

Background: It is well-known that body composition metrics can influence the prognosis of various diseases. This study investigated how body composition metrics predict acute respiratory distress syndrome (ARDS) prognosis, focusing on the ratio of visceral fat area (VFA) to subcutaneous fat area (SFA), SFA to standard body weight (SBW), VFA to SBW, and muscle area (MA) to SBW. These metrics were assessed at the level of the twelfth thoracic vertebra (T12 computed tomography [CT] level) to determine their correlation with the outcomes of ARDS. The goal was to utilize these findings to refine and personalize treatment strategies for ARDS., Methods: Patients with ARDS admitted to the intensive care units (ICUs) of three hospitals from January 2016 to July 2023 were enrolled in this study. Within 24 hours of ARDS onset, we obtained chest CT scans to measure subcutaneous fat, visceral fat, and muscle area at the T12 level. We then compared these ratios between survivors and non-survivors. Logistic regression was employed to identify prognostic risk factors. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cutoff for predictors of in-hospital mortality. Based on this cutoff, patients with ARDS were stratified. To reduce confounding factors, 1:1 propensity score matching (PSM) was applied. We conducted analyses of clinical feature and prognostic differences pre- and post-PSM between the stratified groups. Additionally, Kaplan-Meier survival curves were generated to compare the survival outcomes of these groups., Results: Of 258 patients with ARDS, 150 survived and 108 did not. Non-survivors had a higher VFA/SFA ratio ( P <0.001) and lower SFA/SBW and MA/SBW ratios (both P <0.001). Key risk factors were high VFA/SFA ratio (OR=2.081; P =0.008), age, acute physiology and chronic health evaluation (APACHE) II score, and lactate levels, while MA/SBW and albumin were protective. Patients with a VFA/SFA ratio ≥0.73 were associated with increased mortality, while those with an MA/SBW ratio >1.55 cm²/kg had lower mortality, both pre- and post-PSM ( P =0.001 and P <0.001, respectively). Among 170 patients with pulmonary-origin ARDS, 87 survived and 83 did not. The non-survivor group showed a higher VFA/SFA ratio ( P <0.001) and lower SFA/SBW and MA/SBW ( P =0.003, P <0.001, respectively). Similar risk and protective factors were observed in this cohort. For VFA/SFA, a value above the cutoff of 1.01 predicted higher mortality, while an MA/SBW value below the cutoff of 1.48 cm²/kg was associated with increased mortality (both P <0.001 pre-/post-PSM)., Conclusions: Among all patients with ARDS, the VFA to SFA ratio, MA to SBW ratio at the T12 level, age, APACHE II score, and lactate levels emerged as independent risk factors for mortality., Competing Interests: The authors declared that they had no competing interests., (© 2024 The Authors.)

Water-gas alternation technology (WAG) is considered to be one of the methods that can effectively improve the effect of the CO 2 flooding in heterogeneous reservoirs. The proportion of WAG and the timing of WAG adjustment are key factors affecting the oil displacement effect. This article analyzes the influence of adjusting the WAG ratio on the oil recovery effect of heterogeneous rock cores at different gas flooding stages based on gas flooding experiments. Second, the influence of WAG ratio changes on the recovery rate of displacement experiments under different saturation distributions was studied through numerical simulation. Finally, the oilfield model currently in production was used to optimize the WAG ratio adjustment of the reservoir recovery as a constraint condition. Moreover, the correlation between the fluid distribution of the reservoir and the timing of WAG adjustment was verified. The displacement experiment shows that adjusting the WAG ratio has a significant impact on the displacement effect of crude oil under the same heterogeneous conditions. After adjusting the WAG ratio from 1:2 to 2:1 at 0.5 HCPV and 1 HCPV, the final RF showed significant changes. There is an optimal timing for adjusting the WAG ratio under the same heterogeneity. If the WAG ratio is increased earlier, it will lead to a decrease in the CO 2 injection volume and reduce the effectiveness of CO 2 flooding. If the WAG ratio is increased later, it will lead to the formation of gas channeling channels and affect the effect of adjusting the WAG ratio on flooding., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: To quantify the presence of early structural alterations in the outer retinal layer and choroid among healthy subjects and diabetic patients with no or mild diabetic retinopathy, and to establish the correlation between the measured structural parameters and retinal sensitivity., Methods: In total, 31 eyes from subjects with type 2 diabetes and 29 eyes from healthy subjects were enrolled. Optical coherence tomography was used to measure outer retina layers and choroid, while microperimetry was used to characterize the changes of visual function in a 6-mm diameter area at macula. Quantitative analysis of structural and functional changes was performed between groups and the structure-function correlations were determined., Results: The thickness of myoid and ellipsoid zone, choroid and the mean retinal sensitivity were significantly smaller in diabetic group than that in controls (all P values < 0.05). Besides, thinner choroid and outer retina was associated with the decreased retinal sensitivity，especially in diabetic patients ( r  = 0.377, P  = 0.048; r  = 0.401, P  = 0.034; respectively). Final multiple regression models showed the outer retinal thickness (ORT) ( P  = 0.033), choroidal thickness ( P  = 0.003) and the interaction between ORT and choroidal thickness ( P  = 0.001) were significant predictors to retinal sensitivity., Conclusions: Thinning of choroid and outer retina were significantly correlated with reduced retinal sensitivity, which indicate outer retina and choroid might be potential imaging markers for evaluation of visual function related to neural impairment in type 2 diabetic patients without or in the early stage of diabetic retinopathy., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To explore the changes in microcirculation and microvasculature of the bulbar conjunctiva during the short-term wearing of the scleral lenses (ScCL). And investigate the factors affecting the microcirculation and microvasculature of the bulbar conjunctiva., Methods: In this prospective cross-sectional study, functional slit lamp biomicroscopy (FSLB) was used to image the ocular surface microcirculation and microvascular images at two different sites (under the area of ScCL and outside of the area of ScCL) before (baseline) and during the wearing of ScCL at 0 h, 1 h, 2 h and 3 h. Anterior segment optical coherence tomography (AS-OCT) (RTVue, Optovue Inc, USA) was also used to image central post-lens tear film (PoLTF) and the morphology changes of the conjunctiva under the landing zone at the same time period. The semi-automatic quantification of microcirculation and microvasculature including vessel density (D box ), vessel diameter (D), axial blood flow velocity (Va) and blood flow volume (Q). And the morphological changes of conjunctiva and PoLTF fogging grading were evaluated manually. The changes in the microcirculation and microvasculature of the ocular surface, PoLTF fogging grade and conjunctival morphology were compared before and during the ScCL wearing at different time periods, and the relationship between them was analyzed., Results: Nineteen eyes (11 right eyes, 8 left eyes) were analyzed in this study. Outside of the area of ScCL, the D box before wearing lenses was less than that at 0 h (P = 0.041). The Q at baseline was greater than that after 1 h ScCL wearing (P = 0.026). Under the area of the ScCL, the Q at 1 h was less than that at baseline and 3 h. During the ScCL wearing, statistically significant conjunctival morphology changes were found among different time stages (baseline (0 μm), 0 h (113.18 μm), 2 h (138.97 μm), 3 h (143.83 μm) (all P ＜0.05). Outside the area of the ScCL, the morphology changes of the conjunctiva were negatively correlated with the changes of Va (P＜0.001,r = -0.471) and Q (P = 0.003,r = -0.348),but positively correlated with the D box (P = 0.001,r = 0.386). Under the area of ScCL, the morphology changes of the conjunctiva were negatively correlated with the Q (P = 0.012, r = -0.291). The fogging grade was positively correlated with the Q under the area of the ScCL (P = 0.005, r = 0.331)., Conclusions: The microcirculation and microvasculature of the ocular surface and conjunctival morphology were changed after wearing ScCL in wearers, which indicated that the microvascular responses happened in the ScCL wearers and the severity of microvascular responses of the ocular surface related to the morphology changes of the conjunctiva. The quantification methods and findings in this study provide clues for the safety of ScCL wearing and may supervise the health of the wearer's ocular surface., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT)., Methods: This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included., Results: Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA ( P < 0.001) and NIBUTave ( P = 0.010). OSDI was negatively associated with upper RMGA ( r = -0.450, P < 0.001) and NIBUTave ( r = -0.414, P = 0.001), and positively associated with upper MG grade ( r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = -41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave., Conclusions: The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Quantifying the mechanical properties of the cornea can provide valuable insights into the occurrence and progression of keratoconus, as well as the effectiveness of corneal crosslinking surgery. This study presents a non-contact and non-invasive wave-based optical coherence elastography system that utilizes air-pulse stimulation to create a two-dimensional map of corneal elasticity. Homogeneous and dual concentration phantoms were measured with the sampling of 25 × 25 points over a 6.6 × 6.6 mm 2 area, to verify the measurement capability for elastic mapping and the spatial resolution (0.91 mm). The velocity of elastic waves distribution of porcine corneas before and after corneal crosslinking surgery were further mapped, showing a significant change in biomechanics in crosslinked region. This system features non-invasiveness and high resolution, holding great potential for application in ophthalmic clinics., (© 2024 Wiley‐VCH GmbH.)

Background: Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia., Methods: This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups., Discussion: This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061800)., (© 2024. The Author(s).)

Introduction: Due to policy changes in the context of COVID-19 pandemic, online teaching has become the main form of class in many Chinese universities. Flipped classroom has been widely used in other disciplines, but there is a dearth of evidence available about the use in online teaching of emergency medicine. This study aimed to develop a flipped classroom for online emergency medicine teaching and evaluate its effectiveness by comparing it with traditional lecture-based online teaching., Methods: A total of 62 clinical medical undergraduates from Jinan University participated in this study from September to December in 2022. An online flipped classroom approach was developed (FC group, n  = 31). Traditional lecture-based online teaching was applied as a contrast (LBT group, n  = 31). The undergraduates completed examinations and questionnaires at the end of the course. A course experience questionnaire and course examination score were used to evaluate the effectiveness of the flipped classroom approach., Results: Regarding the five dimensions of the course experience questionnaire, the scores for good teaching (3.47 ± 0.50 vs. 2.34 ± 0.48, p  < .001), appropriate assessment (3.31 ± 0.68 vs. 2.95 ± 0.71, p  = .043) and generic skills (3.16 ± 0.60 vs. 2.72 ± 0.39, p  < .001) were higher for the FC group than for the LBT group. There was no significant difference between the two groups in clear goals and standards, and appropriate workload. The undergraduates in the FC group showed significantly higher overall satisfaction than those in the LBT group (3.52 ± 0.1.03 vs. 2.87 ± 0.92, p  = .012). The examination scores (77.936 ± 11.573 vs. 70.484 ± 7.434, p  < .001), especially the scores for questions related to case analysis (33.032 ± 5.363 vs. 26.968 ± 7.657, p  < .001), were significantly higher in the FC group than in the LBT group., Conclusions: The flipped classroom for online teaching was efficient in improving undergraduates' emergency medical academic performance and promoting the development of clinical case analysis ability. These findings provide an alternative flipped classroom approach for online teaching of emergency medicine.

α-Synuclein (α-Syn) is a key determinator of Parkinson disease (PD) pathology, but synapse and microcircuit pathologies in the retina underlying visual dysfunction are poorly understood. Herein, histochemical and ultrastructural analyses and ophthalmologic measurements in old transgenic M83 PD model (mice aged 16 to 18 months) indicated that abnormal α-Syn aggregation in the outer plexiform layer (OPL) was associated with degeneration in the C-terminal binding protein 2 (CtBP2) + ribbon synapses of photoreceptor terminals and protein kinase C alpha (PKCα) + rod bipolar cell terminals, whereas α-Syn aggregates in the inner retina correlated with the reduction and degeneration of tyrosine hydroxylase- and parvalbumin-positive amacrine cells. Phosphorylated Ser129 α-synuclein expression was strikingly restricted in the OPL, with the most severe degenerations in the entire retina, including mitochondrial degeneration and loss of ribbon synapses in 16- to 18-month-old mice. These synapse- and microcircuit-specific deficits of the rod pathway at the CtBP2 + rod terminals and PKCα + rod bipolar and amacrine cells were associated with attenuated a- and b-wave amplitudes and oscillatory potentials on the electroretinogram. They were also associated with the impairment of visual functions, including reduced contrast sensitivity and impairment of the middle range of spatial frequencies. Collectively, these findings demonstrate that α-Syn aggregates cause the synapse- and microcircuit-specific deficits of the rod pathway and the most severe damage to the OPL, providing the retinal synaptic and microcircuit basis for visual dysfunctions in PD., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Cellular behavior is regulated by mechanical signals within the cellular microenvironment. Additionally, changes of temperature, blood flow, and muscle contraction also affect cellular state and the development of diseases. In clinical practice, physical therapy techniques such as ultrasound, vibration, exercise, cold therapy, and hyperthermia are commonly employed to alleviate pain and treat diseases. However, the molecular mechanism about how these physiotherapy methods stimulate local tissues and control gene expression remains unknow. Fortunately, the discovery of YAP filled this gap, which has been reported has the ability to sense and convert a wide variety of mechanical signals into cell-specific programs for transcription, thereby offering a fresh perspective on the mechanisms by which physiotherapy treat different diseases. This review examines the involvement of Hippo/YAP signaling pathway in various diseases and its role in different physical therapy approaches on diseases. Furthermore, we explore the potential therapeutic implications of the Hippo/YAP signaling pathway and address the limitations and controversies surrounding its application in physiotherapy., (© 2024. The Author(s).)

Contact lenses (CLs) are prone to adhesion and invasion by pollutants and pathogenic bacteria, leading to infection and inflammatory diseases. However, the functionalization of CL (biological functions such as anti-fouling, antibacterial, and anti-inflammatory) and maintaining its transparency still face great challenges. In this work, as a member of the MXenes family, vanadium carbide (V 2 C) is modified onto CL via a water transfer printing method after the formation of a tightly arranged uniform film at the water surface under the action of the Marangoni effect. The coating interface is stable owing to the electrostatic forces. The V 2 C-modified CL (V 2 C@CL) maintains optical clarity while providing good biocompatibility, strong antioxidant properties, and anti-inflammatory activities. In vitro antibacterial experiments indicate that V 2 C@CL shows excellent performance in bacterial anti-adhesion, sterilization, and anti-biofilm formation. Last, V 2 C@CL displays notable advantages of bacteria elimination and inflammation removal in infectious keratitis treatment.

Aims: To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures., Methods: 34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values., Results: All patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density., Conclusions: Unilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The purpose of this study was to evaluate the effects of posterior vitreous detachment (PVD) on visual quality in patients with high myopia, as well as investigate the associated factors of photopic and mesopic contrast sensitivity function (CSF) in high myopia., Methods: Visual quality was comprehensively assessed in patients with high myopia. Visual acuity, contrast sensitivity (CS) at four spatial frequencies (3, 6, 12, and 18 cycles per degree [c.p.d.]) under photopic and mesopic conditions, as well as the modulation transfer function cutoff value (MTFcutoff), the objective scatter index (OSI), the Strehl ratio (SR), and internal aberrations, were measured in this cross-sectional study., Results: This study included 94 eyes from 47 subjects with bilateral high myopia, including 23 eyes with complete PVD (cPVD), 21 eyes with partial PVD (pPVD), and 50 eyes without PVD (nPVD). There was no significant difference in visual quality between the cPVD group and the nPVD group. Whereas in eyes with pPVD, there was a degradation of overall photopic CSF (versus nPVD, P = 0.048), photopic CS at 3 c.p.d. (versus cPVD, P = 0.009 and versus nPVD, P = 0.032), photopic CS at 18 c.p.d. (versus nPVD, P = 0.033), overall mesopic CSF (versus nPVD, P = 0.033), and secondary astigmatism (versus cPVD, P = 0.044). Under photopic conditions, the factors affecting CSF were pPVD and SR, whereas the factors affecting mesopic CSF were pPVD, OSI, and ganglion cell-inner plexiform layer thickness., Conclusions: The pPVD impaired visual quality in patients with high myopia compared to nPVD or cPVD, and pPVD could be a factor explaining CSF at both photopic and mesopic illumination., Translational Relevance: Clinicians need to closely monitor patients with high myopia with pPVD due to the potential decline in visual quality and the development of vitreoretinal disorders.

Purpose: To evaluate the effect of low-concentration (0.01% and 0.05%) atropine eyedrops on ocular surface characteristics in young adults., Methods: Twenty-six myopic students aged 18 to 30 years were randomly assigned to receive either 0.01% or 0.05% atropine once nightly for 14 days, followed by cessation, with a ≥14-day interval between each administration. Assessments were conducted one, two, seven, and 14 days after using atropine with corresponding timepoints after atropine cessation. Tear meniscus height and first and average noninvasive keratograph tear film breakup time (NIKBUT-first, NIKBUT-average) were measured using Keratograph 5M, whereas the objective scatter index (OSI) was measured by OQAS II devices; the ocular surface disease index (OSDI) score was also obtained., Results: The mean OSI peaked after two days of administration of 0.05% atropine (β = 0.51, P = 0.001), accompanied by significant decreases in NIKBUT-first (β = -7.73, P < 0.001) and NIKBUT-average (β = -8.10, P < 0.001); the OSDI peaked after 14 days (β = 15.41, P < 0.001). The above parameters returned to baseline one week after atropine discontinuation (all P > 0.05). NIKBUT-first and NIKBUT-average reached their lowest points after 14 days of 0.01% atropine administration (NIKBUT-first: β = -4.46, P = 0.005; NIKBUT-average: β = -4.42, P = 0.001), but those significant changes were diminished once atropine treatment stopped., Conclusions: Young adult myopes experienced a significant but temporary impact on the ocular surface with 0.05% atropine administration, whereas 0.01% atropine had a minimal effect., Translational Relevance: The investigation of the ocular surface effects of different concentrations of atropine may inform evidence-based clinical decisions regarding myopia control in young adults.

Purpose: This study aimed to investigate the impact of eyelid pressure (ELP) and eye contour factors on rigid corneal contact lens fitting., Methods: This prospective cross-sectional study involved 20 participants (one eye per person). Rigid corneal contact lenses with three different base curves were selected for each participant. The base curves were calculated according to the average keratometry value. The original value and its variations (+0.1 mm and - 0.1 mm) were considered. Eye contour factors, lens decentration under natural eye position (LD I) and full eyelid exposure (LD II), and lens vertical movement were taken by a Canon camera mounted on a digital slit lamp biomicroscope. Upper and lower ELPs were measured by a novel blepharo-tensiometer., Results: The mean values of LD I, LD II, and lens vertical movement significantly increased as the base curve increased (P＜0.001, ＜0.001, and = 0.005). Upper ELP was positively correlated with lens vertical movement of the three base curves (P = 0.047, 0.001, and 0.004). Furthermore, upper ELP (odds ratio [OR]: 1.039; 95 % confidence [CI]: 1.009-1.069; P = 0.009) and flat keratometry values (OR: 0.873; 95 % CI: 0.786-0.969; P = 0.011) independently influenced lens vertical movement., Conclusions: ELP and base curve independently influenced rigid corneal contact lens fitting. Thus, ELP should be considered during rigid corneal contact lens fitting in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To explore changes in corneal epithelial thickness (CET) after femtosecond laser-assisted laser in situ keratomileusis in patients with high astigmatism., Methods: CET was measured at every intersection of the concentric circles and specific axes using AngioVue optical coherence tomography (Angio-OCT) preoperatively and 1 month postoperatively. The average thickness of corneal central, paracentral, and peripheral regions was the mean of the points within the central 2, 2 to 5, and 5 to 7 mm areas, respectively. Correlation analysis was performed to investigate the association between CET along different axes and other preoperative and postoperative parameters., Results: Forty-two eyes of 28 patients were included. CET along the astigmatic (K1) and perpendicular (K2) axes in the central and paracentral areas increased ( P < .001), whereas that along the K2 axis decreased in the peripheral area 1 month postoperatively ( P = .001). The amount of CET change in the peripheral area between the K1 and K2 axes was significantly different ( P < .001). In the central area, the change in CET along the K2 axis was positively correlated with ablation depth ( r = 0.315, P = .042) and negatively with refractive power after surgery ( r = -0.347, P = .024). In the peripheral area, the changes in CET along both K1 and K2 axes were negatively correlated with ablation depth ( r = -0.431, P = .004; r = -0.387, P = .011, respectively)., Conclusions: Epithelial modeling differed between the different astigmatism axes after refractive surgery. The compensatory response of the corneal epithelium is more pronounced along the steeper axis. [ J Refract Surg . 2024;40(4):e239-e244.] .

Purpose: To investigate the effects of eyelash extensions on the ocular surface., Methods: This prospective study included 32 participants with eyelash extensions in both eyes. Symptoms and clinical parameters such as conjunctival vascular density, tear meniscus height (TMH), noninvasive tear break-up time, bulbar redness, meibography, lipid layer thickness, and corneal staining were assessed in the right eyes. These measurements were taken at baseline and 1 h, 1 day, 1 week, and 1 month after eyelash extensions were applied., Results: At 1 h after eyelash extensions, ocular symptoms were reported by 27 participants (84.44 %), the most common being foreign body sensation (59.38 %). However, the Ocular Surface Disease Index scores were not statistically different between baseline, 1 week, and 1 month after eyelash extension (P > 0.05). TMH increased significantly at 1 h after eyelash extensions, from 0.27 ± 0.08 mm (baseline) to 0.29 ± 0.07 mm (P = 0.02). Subsequently, TMH decreased and was the lowest at 1 week at 0.24 ± 0.08 mm. First tear break-up time and average tear break-up time decreased to the lowest at 1 week after eyelash extension, with 8.36 ± 4.6 s and 10.71 ± 4.99 s, respectively, both of which were statistically different from baseline (P < 0.05). Corneal staining score was highest at 1 h after eyelash extensions at 0.78 ± 1.34. However, there were no significant differences in the conjunctival vascular density, bulbar redness, meiboscore, or lipid layer thickness., Conclusion: This study demonstrates that eyelash extensions can lead to an imbalance in ocular surface homeostasis, resulting in corneal epithelial defects and short-term decreased tear film stability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: RigidCare is an electrolysis-based device that recently obtained approval from the US's FDA to sterilise microorganisms and remove proteins for orthokeratology (O-K) lenses. The study was conducted to investigate the device's performance in varied clinical circumstances., Methods: Trial lenses and private lenses were employed by O-K lens wearers from five hospitals for an evaluation of disinfection and sterilisation and an assessment of protein removal, respectively. Menicon multipurpose solution and protein remover were selected for use with the control group. Following the instructions, pre-cleaning lens samples, post-cleaning lens samples and residual solution samples of trial lenses of the experimental and control groups were collected for microorganism examinations by an experienced third-party testing organisation. The levels of protein deposition for these two approaches were rated by senior O-K experts. Categorical variables were analysed using statistical tests, such as the chi-squared test and Fisher's exact test., Results: The microbial positive rate detected from the pre-cleaning and post-cleaning lens samples and the residual solution of the trial lenses for the experimental and control group was 4/76 vs 1/74 (P = 0.37), 1/76 vs 0/74 (P = 1.00) and 0/76 vs 8/74 (P = 0.006), respectively. Following protein removal, the experimental group exhibited a significantly higher overall proportion of lenses rated as 'clean' or with a 'mild deposit' (96.4 %, 79/82) compared to the control group (85.7 %, 66/77), with a significant difference (P < 0.05)., Conclusion: This multi-center study demonstrated that RigidCare exhibited superior efficacy in disinfection, sterilisation and protein removal as compared to Menicon multipurpose solution and protein remover., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Perceptual learning (PL) can significantly improve human performance in perceptual tasks primarily through template reweighting. Previous studies have documented how PL changes perceptual template in stimulus feature space. We investigated how PL reweights visual information in time. With a dynamic external noise paradigm and the elaborated perceptual template model (ePTM) analysis, we found that training with an orientation identification task in the zero external noise condition reduced contrast thresholds in both zero and high external noise conditions, whereas training in the high external noise condition only reduced contrast thresholds in high external noise conditions. The ePTM analysis showed that training in both zero and high external noise changed the overall amplitude, but not the shape of the temporal window of the perceptual template to exclude external noise across time, and training in zero external noise additionally reduced additive internal noise. Our results provided additional constraints for models of PL. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Excess iron contributes to Hemophilic Arthropathy (HA) development. Divalent metal transporter 1 (DMT1) delivers iron into the cytoplasm, thus regulating iron homeostasis., Objectives: We aimed to investigate whether DMT1-mediated iron homeostasis is involved in bleeding-induced cartilage degeneration and the molecular mechanisms underlying iron overload-induced chondrocyte damage., Methods: This study established an in vivo HA model by puncturing knee joints of coagulation factor VIII gene knockout mice with a needle, and mimicked iron overload conditions in vitro by treatment of Ferric ammonium citrate (FAC)., Results: We demonstrated that blood exposure caused iron overload and cartilage degeneration, as well as elevated expression of DMT1. Furthermore, DMT1 silencing alleviated blood-induced iron overload and cartilage degeneration. In hemophilic mice, articular cartilage degeneration was also suppressed by intro-articularly injection of DMT1 adeno-associated virus 9 (AAV9). Mechanistically, RNA-sequencing analysis indicated the association between iron overload and cGAS-STING pathway. Further, iron overload triggered mtDNA-cGAS-STING pathway activation, which could be effectively mitigated by DMT1 silencing. Additionally, we discovered that RU.521, a potent Cyclic GMP-AMP Synthase (cGAS) inhibitor, successfully suppressed the downward cascades of cGAS-STING, thereby protecting against chondrocyte damage., Conclusion: Taken together, DMT1-mediated iron overload promotes chondrocyte damage and murine HA development, and targeted DMT1 may provide therapeutic and preventive approaches in HA., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Age-related blepharoptosis, or ptosis, affects vision and appearance. Associations with age, gender, BMI, and diabetes have been explored, but the link to blood lipids remains unclear. The impact on refraction also lacks consensus. This study addresses gaps by investigating ptosis prevalence and factors in a representative Chinese population, aiming for a comprehensive understanding., Methods: A cross-sectional study was conducted among individuals aged 50 and above who were willing to participate in comprehensive systemic check-ups, behavioral questionnaires, and ophthalmic examinations at Yaoxi Community Health Center in Wenzhou City, Zhejiang Province., Results: The prevalence of blepharoptosis among the elderly participants at this health center was 27.16%. Individuals with blepharoptosis tended to be older, male, exhibited slightly higher body mass index, wider waist circumference, engaged in lower exercise frequency, and had a higher prevalence of hypertension, diabetes, and with-the-rule astigmatism compared to their counterparts without these conditions. Adjusting for all other confounding variables, older age, being male, higher fasting plasma glucose (FPG), and lower exercise frequency displayed statistically significant relationships with blepharoptosis. After examining the distribution of blepharoptosis degrees within relevant factor subgroups, we noted a higher prevalence of severe ptosis in subgroups associated with older age, male gender, higher FPG, and against-the-rule astigmatism., Conclusion: The notable associations with age, gender, FPG, and exercise level suggest a multifactorial etiology for blepharoptosis. The observed link between with-the-rule astigmatism and blepharoptosis implies a potential contributory role in the refractive aspect of blepharoptosis., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA., Methods: In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP-RIPK1-NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1β and in the post-traumatic OA model., Results: In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA., Conclusions: These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis., (© 2024. The Author(s).)

Clinical Relevance: It is particularly important to perform reasonable and effective optical correction to enable visual development after primary lens removal surgery for congenital cataracts. Aphakic infants need a suitable addition power of prescription (ADD) to help them focus on close visual objects., Background: It is challenging to obtain appropriate ADD power for infants due to poor cooperation and lack of subjective feedback. We aimed to determine the appropriate ADD for aphakic infants using a recently developed smart wearable device called Clouclip., Methods: The study was a cross-sectional, observational pilot study. Twenty-three aphakic infants (aged from 6 months to 3.5 years) were invited to wear a smart wearable device for 7 days consecutively to monitor the near viewing distance in real life. Viewing habits and its associations with the possible influencing factors were investigated based on the data obtained from the device., Results: The average proportion of near viewing time was 77.9% (95% confidence interval (CI) 72.1-83.7%). The average of the median near viewing distance was 23.8 cm (95% CI 20.6 cm-27.0 cm), which corresponded to an ADD of +4.25 D (95% CI + 3.75 D - +4.75 D) spectacle prescription. The height of the child was found to be positively correlated with the median of near viewing distance ( r  = 0.646, p  = 0.001). Age, current ADD, age of cataract extraction surgery and bilaterality or monocularity of the aphakic eyes showed no significant correlation with the aforementioned viewing habits (all p  > 0.05)., Conclusion: By using the novel wearable device, we found the suitable ADD of spectacle prescription for aphakic infants is about +4.25 D. The height of the child was an influencing factor for ADD.

Translocator protein (18 kDa) (TSPO) plays an important role in retinal neuroinflammation in the early stage of diabetic retinopathy (DR). Studies have found that a FGF1 variant (FGF1 ΔHBS ) with reduced proliferative potency exerts excellent anti-inflammatory effects and potential therapeutic value for diabetic complications. In this study, intravitreal injection of FGF1 ΔHBS was administrated every week for one month in db/db mice, which are genetically predisposed to develop type 2 diabetes mellitus and early retinopathy. Changes in retinal function and structure in the animal models were detected by electrophysiology (ERG) and optical tomography coherence (OCT). TSPO expression and retinal inflammation were analyzed by immunofluorescence, Western blot and real-time qPCR. In the retina of T2D (db/db) mice, FGF1 was significantly down-regulated while FGFR1 was up-regulated (both p < 0.05). TSPO and retinal inflammatory factors were all up-regulated. TSPO and FGFR1 were mainly co-stained in the inner retina. After FGF1 ΔHBS treatment, ERG showed that the total amplitude of dark-adapted b-wave and oscillating potentials (Ops) was significantly improved, and OCT showed that the thickness of the retina around the optical nerve head was significantly preserved in T2D mice (all p < 0.05). The TSPO signal was significantly suppressed by FGF1 ΔHBS . The activation of NF-κB p65 and the expression of inflammatory factors such as TNF-α, IL-1β, IL-6, COX-2, MIP-1α, and iNOS were all significantly down-regulated (all p < 0.05). Collectively, our current data demonstrated that intravitreal FGF1 ΔHBS treatment can effectively inhibit retinal inflammation via suppressing TSPO signal and to preserve retinal function and structure in a T2D mouse model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Conventional inorganic coagulants (Al, Fe) and Al/Fe-based covalently bonded flocculants (CAFMs) had different hydrolysis species at different pHs, which subsequently led to differences in their binding sites and complexation ability with humic acid (HA). Studying the binding sites and interactions between CAFMs, AlCl 3 (Al), and FeCl 3 (Fe) hydrolysates and HA molecules is critical to understanding the coagulation mechanism. The results found that CAFM 0.6 , Al, and AlCl 3 combined FeCl 3 (Al/Fe) removed more than 90% of HA at pH 6, and CAFMs showed higher HA removal rate than that of Al, Fe, and Al/Fe under the same reaction conditions. The flocs of CAFMs contained abundant -NH 2 /OH as well as the large particle size, compact structure, and excellent settling performance. The hydrolyzed species of Al and Fe were predominantly Al b and Fe b at pH 6, but the hydrolyzed species of CAFMs were primarily (Al + Fe) c . Moreover, the hydrolyzed species of Al and Al/Fe were found to complex with HA functional groups such as -COOH, C = O, C-H/C-C, C = C, and C-OH to form ligand bonds, while the hydrolyzed species (Al + Fe) c of CAFMs could deeply interact with HA functional groups including C-O, -COOH, C = O, C-H/C-C, C = C, and C-OH by the adsorption and sweeping., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

PDL1 blockade therapy holds great promise in cancer immunotherapy. Ultrasound imaging of PDL1 expression in the tumor is of great importance in predicting the therapeutic efficacy. As a proof-of-concept study, a novel ultrasound contrast agent has been innovated here to image and block PDL1 in the tumor tissue. Briefly, extracellular vesicles (EVs) are engineered to display truncated PD1 (tPD1) on the surface to bind PDL1 with high affinity by fusion to EV-abundant transmembrane protein PTGFRN. The engineered EVs are then encapsulated with Ca(HCO 3 ) 2 via electroporation and designated as Gp-EV tPD1 , which would recognize PDL1 highly expressed cells and produce gas in the endosomes and lysosomes. On the one hand, the echogenic signal intensity correlates well with the PDL1 expression and immune response inhibition in the tumor. On the other hand, during the trajectory of Gp-EV tPD1 in the recipient cells, tPD1 on the EV binds PDL1 and triggers the PDL1 endocytosis and degradation in endosomes/lysosomes in a sequential manner, and thus boosts the anti-tumor immunity of cytotoxic T cells. In summary, Gp-EV tPD1 serves as a novel ultrasound contrast agent and blocker of PDL1, which might be of great advantage in imaging PDL1 expression and conquering immune checkpoint blocker resistance., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Using traditional Chinese medicine residues as raw materials, different biochars (BC) were prepared through oxygen-limited pyrolysis at 300 °C, 500 °C, and 700 °C, and BC was ball-milled to produce ball-milled biochar (BMC). Using these adsorbents to adsorb the allelopathic autotoxic substance quercetin. The physical and chemical properties of various biochars derived from traditional Chinese medicine residues were characterized using the Brunauer-Emmett-Teller-N2 surface areas (BET), scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), X-ray diffraction (XRD), and Raman spectroscopy (Raman). The study investigated the effects of the initial pH value, different humic acid concentrations, and multiple adsorption-desorption experiments on the removal of quercetin from the solution. The article discusses the adsorption mechanism of quercetin in solution by biochar from a traditional Chinese medicine residue, based on the results of adsorption kinetics and adsorption isotherm fitting. The findings indicate that increasing the pyrolysis temperature reduces the oxygen-containing functional groups of BC, enhances the aromaticity, and stabilizes the carbon structure. The pore structure of BMC becomes more complex after ball milling, which increases the number of oxygen-containing functional groups on the surface. Among the samples tested, BMC700 exhibits the best adsorption performance, with an adsorption capacity of 293.3 mg·g -1 at 318 K. The adsorption process of quercetin by BMC700 follows the pseudo-second-order kinetic model and the Freundlich adsorption isotherm model. The process is primarily a form of multimolecular layer adsorption. Its mechanism involves the pore-filling effect, hydrogen-bonding interaction, electrostatic interaction, and π-π coexistence, as well as the yoke effect. Additionally, they are highly recyclable and show promise in addressing continuous cropping issues., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status., (© 2024. The Author(s).)

Objective: This study aims to assess the efficacy of laparoscopic modified uterine incision pressure repair in treating type II-III cesarean scar pregnancy (CSP)., Methods: A total of 20 patients diagnosed with type II-III CSP and admitted to the Affiliated Hospital of Guizhou Medical University between April 2021 and May 2023 were enrolled. The patients were divided into two groups: the study group (Group A), consisting of newly treated surgical patients, and the control group (Group B), including patients with type II-III CSP treated by doctors of similar grade and surgical experience (non-novel). Various parameters, including age, menopause duration, pregnancy and delivery history, cesarean section frequency, preoperative human chorionic gonadotropin (HCG) levels, pregnancy sac size, HCG turnover time, operation duration, intraoperative blood loss, blood transfusion requirements, and hospitalization costs, were compared., Results: When comparing mean age, menopause duration, preoperative HCG levels, pregnancy and cesarean section frequencies, pregnancy sac size, and HCG turnover time, no statistically significant differences were observed (P > .05). The number of transfusions and hospitalization costs in Group A were lower than in Group B, although the differences were not statistically significant (P > .05). However, operative time, intraoperative bleeding, and hospitalization costs were significantly lower in Group A compared to Group B (P < .05)., Conclusions: The laparoscopic modified uterine incision pressure repair method demonstrated clinical value with its advantages of short operation time, reduced bleeding, lower costs, and rapid recovery for type II-III CSP.

Fundus tessellation (FT) is a prevalent clinical feature associated with myopia and has implications in the development of myopic maculopathy, which causes irreversible visual impairment. Accurate classification of FT in color fundus photo can help predict the disease progression and prognosis. However, the lack of precise detection and classification tools has created an unmet medical need, underscoring the importance of exploring the clinical utility of FT. Thus, to address this gap, we introduce an automatic FT grading system (called DeepGraFT) using classification-and-segmentation co-decision models by deep learning. ConvNeXt, utilizing transfer learning from pretrained ImageNet weights, was employed for the classification algorithm, aligning with a region of interest based on the ETDRS grading system to boost performance. A segmentation model was developed to detect FT exits, complementing the classification for improved grading accuracy. The training set of DeepGraFT was from our in-house cohort (MAGIC), and the validation sets consisted of the rest part of in-house cohort and an independent public cohort (UK Biobank). DeepGraFT demonstrated a high performance in the training stage and achieved an impressive accuracy in validation phase (in-house cohort: 86.85 %; public cohort: 81.50 %). Furthermore, our findings demonstrated that DeepGraFT surpasses machine learning-based classification models in FT classification, achieving a 5.57 % increase in accuracy. Ablation analysis revealed that the introduced modules significantly enhanced classification effectiveness and elevated accuracy from 79.85 % to 86.85 %. Further analysis using the results provided by DeepGraFT unveiled a significant negative association between FT and spherical equivalent (SE) in the UK Biobank cohort. In conclusion, DeepGraFT accentuates potential benefits of the deep learning model in automating the grading of FT and allows for potential utility as a clinical-decision support tool for predicting progression of pathological myopia., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Splanchnic nerve neurolysis (SNN) is commonly used as an alternative pain control technique to celiac plexus neurolysis (CPN) in patients with distortion of anatomy, but the analgesic effect and relative risks of the 2 procedures remain controversial in general condition., Objectives: The aim of this study was to evaluate the pain condition, safety, and symptom burden of SNN compared with CPN., Study Design: A systematic review and meta-analysis of neurolysis therapy for intractable cancer-related abdominal pain., Methods: A systematic search was performed for randomized controlled trials comparing SNN and CPN using the PubMed, Medline, Cochrane Library, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases. Meta-analysis was performed using Stata Version 15.0. Outcomes included pain condition, opioid consumption, adverse effects, quality of life (QOL), and survival rate. Standardized mean difference (SMD) was calculated for continuous outcomes with its corresponding 95% CI., Limitations: Study limitations include challenges to make subgroup analysis by intervention measures and addressing inevitable heterogeneity. Larger studies are needed for survival rates and further insights., Results: Seven studies involving 359 patients were included. No significant difference was found in pain condition at 2 weeks [SMD = 0.75, 95% CI (-0.25, 1.74), P > 0.05], 2 months [SMD = 1.10, 95% CI (-0.21, 2.40), P > 0.05] and 6 months [SMD = 0.53, 95% CI (-0.02, 1.08), P > 0.05] between SNN and CPN. Opioid consumption was comparable at 2 weeks [SMD = 0.57, 95% CI (-1.21, 2.34), P > 0.05] and one month [SMD = 0.37, 95% CI (-1.33, 2.07), P > 0.05]. However, SNN was associated with a statistically significant reduction in the opioid consumption at 2 months postoperatively [SMD = 0.99, 95% CI (0.68, 1.30), P < 0.05]. A systematic review was performed for adverse effects and QOL., Conclusions: Our evidence supports that the analgesic effect of SNN is equivalent to that of CPN, independent of changes in the anatomical structure of the abdominal nerve plexus. SNN requires less use of opioids at 2 months and does not show greater improvement in pain burden compared to CPN.

Introduction: The role of ophthalmologists is defined by tasks requiring visual effort, emphasizing the importance of examining their condition within the realm of occupational visual health. Our goal was to explore the occurrence of asthenopia among Chinese ophthalmologists and identify contributing factors through the use of a reliable and validated survey instrument., Methods: A national cross-sectional online survey was carried out in June 2017, involving 6,220 practicing ophthalmologists in China. Utilizing an 11-item Asthenopia Survey Questionnaire with established reliability and validity. Prevalence rates of asthenopia among subgroups categorized by age, gender, hospital classification, physician level, daily near vision activity duration, sleep duration, sleep quality, presbyopia status, and history of eye surgery were determined using the independent t -test, chi-square test and bonferroni test. Multiple logistic regression analysis was employed to pinpoint independent factors linked to asthenopia., Results: Out of the 5,009 ophthalmologists who completed the survey, a 40.7% prevalence of asthenopia was identified. Multivariate analysis revealed that good sleep quality (OR: 0.24, 95%CI: 0.20-0.30), moderate sleep quality (OR: 0.47, 95%CI: 0.38-0.59), engaging in daily near vision activities for less than 7 h (OR: 0.76, 95%CI: 0.68-0.86), having daily sleep duration exceeding 7 h (OR: 0.87, 95%CI: 0.77-0.98), and working in tertiary hospitals (OR: 0.88, 95%CI: 0.78-0.99) were protective factors against asthenopia. Conversely, presbyopia was identified as a risk factor (OR: 1.33, 95%CI: 1.04-1.70). All calculated p values were below 0.05. Age, gender, physician level, and eye surgery history were not related factors., Conclusion: Asthenopia is prevalent among Chinese ophthalmologists, with employment in tertiary hospitals providing a protective effect and presbyopia is a risk factor. Preventive strategies include improving sleep quality, restricting daily near vision activity to under 7 h, and extending daily sleep duration to over 7 h. Further investigation is needed to explore the protective implications of working in tertiary hospitals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Zhu, Wu, Yang, Lu and Deng.)

Ochratoxin A (OTA) is one of the mycotoxins that poses a serious threat to human and animal health. Curcumin (CUR) is a major bioactive component of turmeric that provides multiple health benefits. CUR can reduce the toxicities induced by mycotoxins, but the underlying molecular mechanisms remain largely unknown. To explore the effects of CUR on OTA toxicity and identify the key regulators and metabolites involved in the biological processes, we performed metabolomic and transcriptomic analyses of livers from OTA-exposed mice. We found that CUR can alleviate the toxic effects of OTA on body growth and liver functions. In addition, CUR supplementation significantly affects the expressions of 1584 genes and 97 metabolites. Integrated analyses of transcriptomic and metabolomic data showed that the pathways including Arachidonic acid metabolism, Purine metabolism, and Cholesterol metabolism were significantly enriched. Pantothenic acid (PA) was identified as a key metabolite, the exogenous supplementation of which was observed to significantly alleviate the OTA-induced accumulation of reactive oxygen species and cell apoptosis. Further mechanistical analyses revealed that PA can downregulate the expression level of proapoptotic protein BAX, enhance the expression level of apoptosis inhibitory protein BCL2, and decrease the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). This study demonstrated that CUR can alleviate the adverse effects of OTA by influencing the transcriptomic and metabolomic profiles of livers, which may contribute to the application of CUR in food and feed products for the prevention of OTA toxicity.

Abstract: Pulmonary fibrosis is an important factor affecting the prognosis of severe septic patients with acute lung injury. The objective of this study was to explore the effect of norepinephrine (NE) and α 2 -adrenoreceptor (AR) on sepsis-associated pulmonary fibrosis and the mechanism underlying these effects. We found pulmonary fibrotic changes, and increased NE production and α 2A -AR expression in the pulmonary tissue of mice subjected to cecal ligation and puncture surgery. Reserpine and yohimbine alleviated pulmonary fibrosis in mice with sepsis by exhausting NE derived from the lung's adrenergic nerve and blocking α 2 -AR, respectively. There was no significant difference in the expression of the three α 1 -AR subtypes. The effect of NE on promoting pulmonary fibroblast differentiation in vitro was suppressed by yohimbine. Both the protein and mRNA expression levels of α 2A -AR were increased in pulmonary fibroblasts treated with LPS. Clonidine, a selective α 2 -AR agonist, enhanced LPS-induced differentiation in pulmonary fibroblasts, as indicated by the increase in α-smooth muscle actin and collagen I/III, which was mitigated by inhibiting PKC and p38. Further in vivo results indicated that yohimbine alleviated pulmonary fibrosis and inhibited the phosphorylation of PKC, p38, and Smad2/3 in lung tissue of mice exposed to LPS for 4 weeks. Clonidine showed the opposite effect to yohimbine, which aggravated LPS-induced pulmonary fibrosis. These findings demonstrated that the sepsis-induced increase in NE promoted fibroblast differentiation via activating α 2 -AR. Blockage of α 2 -AR effectively ameliorated sepsis-associated pulmonary fibrosis by abolishing NE-induced lung fibroblast differentiation and inhibiting the PKC-p38-Smad2/3 pathway., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Objective: To investigate relationship of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with mild cognitive impairment (MCI) and dementia in a community-based study1., Methods: This cross-sectional study incorporated the participants of the Jidong Eye Cohort Study. Optical coherence tomography angiography was performed to obtain RCP vessel density and GCC thickness with detailed segments. The Mini-mental State Examination and Montreal Cognitive Assessment were used to assess cognitive status by professional neuropsychologists. Participants were thus divided into three groups: normal, mild cognitive impairment, and dementia. Multivariable analysis was used to measure relationship of ocular parameters with cognitive impairment., Results: Of the 2678 participants, the mean age was 44.1 ± 11.7 years. MCI and dementia occurred in 197 (7.4%) and 80 (3%) participants, respectively. Compared to the normal group, the adjusted odds ratio (OR) with the 95% confidence interval was 0.76 (0.65-0.90) for the correlation of lower deep RCP with MCI. We found the following items significantly associated with dementia compared with the normal group: a superficial (OR, 0.68 [0.54-0.86]) and deep (OR, 0.75 [0.57-0.99]) RCP, as well as the GCC (OR, 0.68 [0.54-0.85]). Compared to the MCI group, those with dementia had decreased GCC (OR, 0.75 [0.58-0.97])., Conclusions: Decreased deep RCP density was associated with MCI. Decreased superficial and deep RCP and the thin GCC were correlated with dementia. These implied that the retinal microvasculature may develop into a promising non-invasive imaging marker to predict severity of cognitive impairment., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)