Association of myopia and astigmatism with postoperative ocular high order aberration after small incision lenticule extraction.

OBJECTIVE: To investigate the correlation between higher-order aberrations (HOA) after small incision lenticule extraction (SMILE) and the severity of myopia and astigmatism, along with the relevant factors. These findings will provide valuable insights for decreasing the occurrence of HOA after SMILE and enhancing visual quality. METHODS: A total of 75 patients (150 eyes) with myopia and astigmatism who underwent SMILE were categorized into four groups based on the severity of myopia and astigmatism: Myopia Group 1 (Group M1, spherical diopter ranged from -1.00 D to -4.00 D), Myopia Group 2 (Group M2, spherical diopter ranged from -4.10 D to -10.00 D), Astigmatism Group 1 (Group A1, cylindrical diopter ranged from 0 D to -1.00 D), and Astigmatism Group 2 (Group A2, cylindrical diopter ranged from -1.10 D to -3.00 D). A comprehensive assessment was performed to examine the association between HOA and various relevant factors, including a detailed analysis of the subgroups. RESULTS: Group M1 had significantly lower levels of total eye coma aberration (CA), corneal total HOA (tHOA), internal tHOA, and vertical CA ( Z 3 - 1 ) after SMILE than Group M2 (P < 0.05). Similarly, Group A1 had significantly lower levels of total eye tHOA, CA, trefoil aberration (TA), corneal tHOA, TA, and vertical TA ( Z 3 - 3 ) after SMILE than Group A2 (P < 0.05). Pearson correlation analysis indicated a statistically significant positive relationship between the severity of myopia/astigmatism and most HOA (P < 0.05). Subgroup evaluations demonstrated a notable increase in postoperative HOA associated with myopia and astigmatism in Groups M2 and A2 compared with the control group. Lenticule thickness, postoperative central corneal thickness (CCT), postoperative uncorrected distance visual acuity (UDVA), and postoperative corneal Km and Cyl were strongly correlated with most HOA. Age, eyes, and postoperative intraocular pressure (IOP) were only associated with specific HOA. CONCLUSION: HOA positively correlated with the severity of myopia and astigmatism after SMILE. However, this relationship was not linear. HOA after SMILE was influenced by various factors, and additional specialized investigations are required to establish its clinical importance.

Alkalinity control in sludge propels the conversion of concrete slurry waste into micro- and nano-sized biogenic CaCO3.

The utilization of Bacillus sp. for the production of bio-CaCO3 in concrete crack repair and strength enhancement has attracted considerable attention. However, microbial-induced calcium carbonate precipitation (MICP) has yet to be explored as a precedent with activated sludge. Here calcium sourced from concrete slurry waste (CSW) and carbon from sludge microbial ß-oxidation under alkaline were used to generate micro/nano CaCO3. The results indicate that the main crystalline form of the generated precipitated particles is calcite, with a particle size ranging from 0.7 to 10 µm. Minimal heavy metals were found in the supernatant following settling. And at the optimum pH of 8.5-9, carbon capture reached 743 mg L-1, and CaCO3 production reached 1,191 mg L-1, and dominant phylum were Proteobacteria and Bacteroidota, with Thauera being a prevalent genus adept in ß-oxidation. Mass balance analysis showed that alkali promotes microbial ß-oxidation of organisms to produce CO2 and facilitate storage. Thus, the alkaline regulation of metabolism between microbe and CSW provides a novel way of sludge to initiate MICP.

Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development.

The mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populations within tumors rather than tumor stem cells. Consequently, after a brief period of remission, tumors often relapse. Moreover, the exclusive targeting of tumor stemness cell disregards the potential for other tumor cells to regain stemness and acquire drug resistance. As a result, current drugs that solely target the HGF/c-MET axis and the Hh pathway demonstrate only moderate efficacy in specific types of cancer. Mounting evidence indicates that these two pathways not only play important roles in cancer but also exert significant influence on the development of resistance to single-target therapies through the secretion of their own ligands. In this comprehensive review, we analyze and compare the potential impact of the Hh pathway on the tumor microenvironment (TME) in HGF/c-MET-driven tumor models, as well as the interplay between different cell types. Additionally, we further substantiate the potential and necessity of dual-pathway combination therapy as a critical target in MET addicted cancer treatment. Video Abstract.

Effect of refractive status on retinal nerve fiber layer thickness in Chinese Population.

PURPOSE: To evaluate the relationship between retinal nerve fiber layer (RNFL) thickness and other related parameters measured by spectral-domain optical coherence tomography and the refractive error of eyes. METHODS: A total of 5394 subjects were enrolled in this population-based cohort study, who were divided into three groups by refractive state after they underwent a standardized ophthalmic examination: emmetropia (the absolute value should range from 0 to 0.5 D), low-moderate myopia (the absolute value of myopic error should range from 0.5 to 6 D), and high myopia (the absolute value of myopic error should be over than 6 D). R 3.6.1 software was adopted for statistical analysis. RESULTS: Two thousand five hundred fifty-two subjects (4548 eyes) were collected in this study, with an average age of 53.14 ± 10.64 years. There were significant differences among groups in average central corneal curvature, spherical equivalent, and axial length (P < 0.001). The measurements of average retinal nerve fiber layer (RNFL) were 113.95 ± 10.62 µm, 112.97 ± 11.59 µm, and 101.88 ± 15.67 µm, respectively, in the emmetropia, low-moderate, and high myopia groups (P < 0.001). Meanwhile, there was a decreasing trend of cup area, cup volume, disc area, and rim area in the high myopia group compared with the emmetropia group (P < 0.001). CONCLUSION: The measurements of RNFL thickness vary greatly with refractive error, and this study indicated that it is of great significance for the accurate diagnosis of glaucoma to establish an individualized RNFL thickness database.

Discovery of Clinical Manifestations in Spontaneous Glaucoma Suspect Nonhuman Primates.

INTRODUCTION: The primary aim of this study was to assess the longitudinal changes in retinal nerve fiber layer (RNFL) thickness and relative ONH parameters using spectral-domain optical coherence tomography (SD-OCT) in the living eyes of nonhuman primates with spontaneous glaucoma. METHODS: Totally 9 macaque subjects underwent a standard fundus photo and OCT examination, including 3 adult monkeys with stable elevated intraocular pressure (IOP) as the glaucoma suspect group and 6 normal IOP monkeys as the control group. Each eye of primates with IOP measurement was repeated three times. OCT measurements recorded RNFL, Bruch's membrane opening (BMO) minimum rim width (MRW). The follow-up scan of glaucomatous subjects was undergone in 10 months. RESULTS: The mean ages of glaucoma and healthy subjects are 19.33 ± 0.33 and 20.5 ± 1.46 years. Elevated IOP was achieved in three nonhuman primate eyes with an average increase of 10 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in all the regions and decreased RNFL phase retardation in the superior and inferior regions. When averaged over the entire retinal area, only the whole RNFL and temporal regions showed a significant decrease. The mean IPL thicknesses are 87.17 ± 2.15 µm in glaucomatous and 93.33 ± 1.51 µm in healthy eyes (p = 0.03). Lamina cribrosa parameters are measured from the OCT images and showed significant differences between glaucoma primates and normal primates. CONCLUSIONS: Of the measured parameters, decreased RNFL and MRW were correlated with glaucomatous damage. Natural glaucoma primate can be a natural glaucoma model which is closer to glaucoma in humans.

The Association between Myopia and Primary Open-Angle Glaucoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies identified myopia as a risk factor for primary open-angle glaucoma (POAG). However, recent studies have shown different results, and the definitive relationship between myopia and POAG remains controversial. OBJECTIVES: The aim of this study was to investigate the relationship between myopia and POAG. METHODS: Published articles were searched from PubMed, Embase, and Scopus databases between 1970 and 2020. A pooled analysis of the odds ratios (ORs) was performed using a random-effects model. RESULTS: Data on the association between myopia and POAG were obtained from 16 cross-sectional studies, and the pooled OR was 2.26 (95% confidence interval [CI], 1.77-2.89, p < 0.001) in random-effects model (I2 = 86%; p < 0.01). For the relationship of myopia and POAG progression, data from 7 longitudinal cohort studies were included, and the pooled OR was 0.85 (95% CI, 0.73-0.99, p = 0.042) in the random-effects model (I2 = 88%; p < 0.01). CONCLUSION: Our findings demonstrated that myopia may be a risk factor associated with POAG and a possible protective factor for POAG progression. It may be due to myopia with the presence of a lamina cribrosa defect, slowing down the visual field loss and also POAG progression. Further research for underlying mechanisms is still needed.

Recommendations for offline combustion-based nitrogen isotopic analysis of silicate minerals and rocks.

RATIONALE: Due to isotope fractionations during partial nitrogen release from minerals and rocks, the complete extraction of nitrogen for analysis is crucial to ensure high-quality nitrogen isotopic data. However, the appropriate nitrogen extraction conditions (e.g. temperature, duration) have not been established for most silicate minerals and rocks. METHODS: Nitrogen in a number of common minerals and rocks was extracted using the most robust sealed-tube offline combustion techniques, purified and quantified in a custom-made metal manifold, and carried by helium gas to an isotope ratio mass spectrometer for isotopic measurement at nanomolar nitrogen level. Each mineral or rock was combusted in a variety of temperature and duration conditions to compare the nitrogen yields and isotopic compositions. RESULTS: The nitrogen yields and isotopic compositions of minerals and rocks are strongly affected by combustion temperature and duration. The optimal combustion temperature is lowest for cyclosilicate minerals, followed by phyllosilicate, tectosilicate and inosilicate minerals. Preheating of samples can induce significant nitrogen loss and δ15 N shift. Heating of samples above their optimal temperatures may cause nitrogen re-assimilation by the residual mineral or rock. CONCLUSIONS: Each mineral or rock has a characteristic optimal temperature and duration for complete nitrogen release. Preheating, under-heating or over-heating can cause nitrogen loss and isotopic shift. Therefore, we recommend using the offline combustion techniques and the optimal combustion conditions obtained in this study for nitrogen quantification and isotopic analysis of silicate minerals and rocks.

The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases.

Transcription factors (TFs) constitute an essential component of epigenetic regulation. They contribute to the progression of vascular diseases by regulating epigenetic gene expression in several vascular diseases. Recently, numerous regulatory mechanisms related to vascular pathology, ranging from general TFs that are continuously activated to histiocyte-specific TFs that are activated under specific circumstances, have been studied. TFs participate in the progression of vascular-related diseases by epigenetically regulating vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). The Krüppel-like family (KLF) TF family is widely recognized as the foremost regulator of vascular diseases. KLF11 prevents aneurysm progression by inhibiting the apoptosis of VSMCs and enhancing their contractile function. The presence of KLF4, another crucial member, suppresses the progression of atherosclerosis (AS) and pulmonary hypertension by attenuating the formation of VSMCs-derived foam cells, ameliorating endothelial dysfunction, and inducing vasodilatory effects. However, the mechanism underlying the regulation of the progression of vascular-related diseases by TFs has remained elusive. The present study categorized the TFs involved in vascular diseases and their regulatory mechanisms to shed light on the potential pathogenesis of vascular diseases, and provide novel insights into their diagnosis and treatment.

Application and development of foam extraction technology in wastewater treatment: A review.

With the advancement of technology, wastewater treatment has become a significant challenge limiting the clean and sustainable development of chemical and metallurgical industries. Foam extraction, based on interfacial separation and mineral flotation, has garnered considerable attention as a wastewater treatment technology due to its unique physicochemical properties. Although considerable excellent accomplishments were reported, there still lacks a comprehensive summary of process features and contaminant removal mechanisms via foam extraction. According to the latest research progresses, the principles and characteristics of foam extraction technology, the classification and application of flotation reagents are systematically summarized in this work. Then comprehensively commented on the application fields and prospects of iterative flotation technology such as ion flotation, adsorption flotation and floating-extraction. The shortcomings and limitations of the current foam extraction technologies were discussed, and the feasible process intensification techniques were highlighted. This review aims to enchance the understanding of the foam extraction mechanism, and provides guidance for the selection appropriate reagents and foam extraction technologies in wastewater treatment.

Differences in ocular high order aberrations before and after small incision lenticule extraction for correction of myopia: a systematic review and meta-analysis.

Objective: To examine the causes and factors that lead to high order aberration (HOA) during the treatment of myopia using small incision lenticule extraction (SMILE), as well as the differences between SMILE and other corneal refractive surgeries through a systematic review and meta-analysis. Methods: A systematic search was conducted from January 2015 to February 2023 in Pubmed, Embase, Web of Science, and Google Scholar databases to gather relevant studies on SMILE and HOA. Studies meeting specific criteria were chosen, and clinical data was retrieved for analysis. Results: This meta-analysis resulted in the inclusion of 19 studies involving 1,503 eyes. Pooled results showed significant induction of total HOA (tHOA, d = -0.21, p < 0.001), spherical aberration (SA, d = -0.11, p < 0.001) and coma aberration (CA, d = -0.18, p < 0.001) after SMILE compared to pre-SMILE, while no significant change in trefoil aberration (TA) was observed (d = -0.00, p = 0.91). There was a significantly lower induction of tHOA after SMILE compared to femtosecond laser-assisted in situ keratomileusis (FS-LASIK, d = 0.04, p < 0.001), and no significant difference was observed compared to wavefront aberration-guided (WFG) refractive surgery (d = 0.00, p = 0.75). There was also a significant association between different levels of myopia and astigmatism, duration of follow-up, lenticule thickness, and preoperative central corneal thickness (CCT) on the induction of tHOA after SMILE (p < 0.05), while the higher preoperative myopia group (sphere > -5D), lower preoperative astigmatism group (cylinder ≤ -1D), larger lenticule thickness group (lenticule thickness > 100 µm), shorter follow-up group (follow-up 1 month postoperatively) and the thicker CCT group (CCT > 550 µm) brought a significant induction of tHOA compared to the opposite comparison group (p < 0.001). Conclusion: While SMILE can induce HOA significantly, it induces less HOA than FS-LASIK. Postoperative HOA following SMILE can be affected by factors such as myopia, astigmatism, lenticule thickness, CCT, and duration of follow-up. Future research should continue to explore techniques to decrease the induction of HOA by using this methodology. Systematic review registration: https://www.crd.york.ac.uk/prospero/.

Quantitative Phosphoproteomics Analysis Reveals the Protective Mechanism of Chlorogenic Acid on Immunologically Stressed Broiler Meat Quality.

Modern poultry production is stressful for the birds, and this stress is recognized as a major cause of inferior meat quality. Chlorogenic acid (CGA), a plant phenolic acid, has excellent antioxidant and anti-inflammatory properties. The antioxidant capacity and phosphoproteomics of immunologically stressed broiler breast muscle were assessed to elucidate the mechanism of the beneficial effects of CGA on meat quality. Dietary CGA decreased drip and cooking loss, postmortem pH and antioxidant capacity of breast muscle from stressed broilers, and increased MyHC-I mRNA levels. Quantitative phosphoproteomics revealed that CGA supplementation downregulated the phosphorylation of myofibrillar proteins, glycolytic enzymes, and endoplasmic reticulum proteins involved in homeostasis, which contributed to improving the meat quality of broilers. Moreover, 14 phosphorylation sites (e.g., P13538-Ser1236 and F1NN63-Ser117) in 13 phosphoproteins were identified as key regulators of processes related to broiler meat quality. Together, these findings provide novel regulatory targets and nutritional strategies for improving the stressed broiler meat quality.

Integrating Clinical Data and Radiomics and Deep Learning Features for End-to-End Delayed Cerebral Ischemia Prediction on Noncontrast CT.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia is hard to diagnose early due to gradual, symptomless development. This study aimed to develop an automated model for predicting delayed cerebral ischemia following aneurysmal SAH on NCCT. MATERIALS AND METHODS: This retrospective study included 400 patients with aneurysmal SAH (156 with delayed cerebral ischemia) who underwent NCCT. The study used ATT-Deeplabv3+ for automatically segmenting hemorrhagic regions using semisupervised learning. Principal component analysis was used for reducing the dimensionality of deep learning features extracted from the average pooling layer of ATT-DeepLabv3+. The classification model integrated clinical data, radiomics, and deep learning features to predict delayed cerebral ischemia. Feature selection involved Pearson correlation coefficients, least absolute shrinkage, and selection operator regression. We developed models based on clinical features, clinical-radiomics, and a combination of clinical, radiomics, and deep learning. The study selected logistic regression, Naive Bayes, Adaptive Boosting (AdaBoost), and multilayer perceptron as classifiers. The performance of segmentation and classification models was evaluated on their testing sets using the Dice similarity coefficient for segmentation, and the area under the receiver operating characteristic curve (AUC) and calibration curves for classification. RESULTS: The segmentation process achieved a Dice similarity coefficient of 0.91 and the average time of 0.037 s/image. Seventeen features were selected to calculate the radiomics score. The clinical-radiomics-deep learning model with multilayer perceptron achieved the highest AUC of 0.84 (95% CI, 0.72-0.97), which outperformed the clinical-radiomics model (P = .002) and the clinical features model (P = .001) with multilayer perceptron. The performance of clinical-radiomics-deep learning model using AdaBoost was significantly superior to its clinical-radiomics model (P = .027). The performance of the clinical-radiomics-deep learning model and the clinical-radiomics model with logistic regression notably exceeded that of the model based solely on clinical features (P = .028; P = .046). The AUC of the clinical-radiomics-deep learning model with multilayer perceptron (P < .001) and the clinical-radiomics model with logistic regression (P = .046) were significantly higher than the clinical model with logistic regression. Of all models, the clinical-radiomics-deep learning model with multilayer perceptron showed best calibration. CONCLUSIONS: The proposed 2-stage end-to-end model not only achieves rapid and accurate segmentation but also demonstrates superior diagnostic performance with high AUC values and good calibration in the clinical-radiomics-deep learning model, suggesting its potential to enhance delayed cerebral ischemia detection and treatment strategies.

Liproxstatin-1 Alleviated Ischemia/Reperfusion-Induced Acute Kidney Injury via Inhibiting Ferroptosis.

Ferroptosis, as a novel regulable cell death, is characterized by iron overload, glutathione depletion, and an accumulation of lipid peroxides. Recently, it has been discovered that ferroptosis is involved in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and plays a crucial role in renal tubular cell death. In this study, we tried to investigate the effect and mechanism of liproxstatin-1 (Lip-1) in I/R-induced AKI and seek the key regulator of ferroptosis in I/R-induced AKI. Mice were administrated with clamping bilateral renal pedicles for 30 min. We found that early growth response 1 (EGR1) might be a key regulator of ferroptosis, and Lip-1 could suppress ferroptosis via EGR1. Meanwhile, Lip-1 could reduce macrophage recruitment and the release of inflammatory cytokines. These findings indicated that Lip-1 alleviated I/R-induced AKI via regulating EGR1, and it might pave the theoretical basis of a new therapeutic strategy for I/R-induced AKI.

Prevention and treatment strategies for kidney transplant recipients in the context of long-term existence of COVID-19.

The sudden outbreak of coronavirus disease 2019 (COVID-19) in early 2020 posed a massive threat to human life and caused an economic upheaval worldwide. Kidney transplant recipients (KTRs) became susceptible to infection during the COVID-19 pandemic owing to their use of immunosuppressants, resulting in increased hospitalization and mortality rates. Although the current epidemic situation is alleviated, the long-term existence of COVID-19 still seriously threatens the life and health of KTRs with low immunity. The Omicron variant, a highly infectious but less-pathogenic strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns among transplant physicians regarding managing KTRs diagnosed with this variant. However, currently, there are no clear and unified guidelines for caring for KTRs infected with this variant. Therefore, we aimed to summarize the ongoing research on drugs that can treat Omicron variant infections in KTRs and explore the potential of adjusting immunotherapy strategies to enhance their responsiveness to vaccines. Herein, we discuss the situation of KTRs since the emergence of COVID-19 and focus on various prevention and treatment strategies for KTRs since the Omicron variant outbreak. We hope to assist physicians in managing KTRs in the presence of long-term COVID-19 variants.

Single-cell RNA sequencing identifies IFNICs as a cellular target for mitigating the progression of abdominal aortic aneurysm and rupture risk.

AIMS: Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signaling pathways involved in the development and progression of AAAs is essential for the development of medical therapy. METHODS AND RESULTS: We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE-/- mice, conducted scRNA-seq, identified a unique population of interferon-inducible monocytes/macrophages (IFNICs), which were amply found in the abdominal aortic aneurysms (AAAs). Gene set variation analysis (GSVA) revealed that activation of the cytosolic DNA sensing cGAS-STING and JAK-STAT pathways promoted the secretion of type I interferons in monocytes/macrophages and differentiated them into IFNICs. We generated myeloid cell-specific deletion of Sting1 (Lyz2-Cre+/-; Sting1flox/flox) mice and performed bone marrow transplantation and found that myeloid cell-specific deletion of Sting1 or Ifnar1 significantly reduced the incidence of AAA, aortic rupture rate and diameter of the abdominal aorta. Mechanistically, the activated pyroptosis- and inflammation-related signaling pathways, regulated by IRF7 in IFNICs, play critical roles in the developing AAAs. CONCLUSION: IFNICs is a unique monocyte/macrophage subset implicated in the development of AAAs and aortic rupture.

A filter pad design-based multiplexed lateral flow immunoassay for rapid simultaneous detection of PDCoV, TGEV, and PEDV in swine feces.

Swine Enteric Coronaviruses (SECoVs), with high lethality and infectiousness, are the main pathogens causing fatal and watery diarrhea in piglets and spreading globally. Moreover, these SECoVs can cause similar clinical manifestations and are often co-infected, requiring an accurate assay suitable for rapid, in situ, and differential detection. Here, we developed a multiplexed fluorescent-based lateral flow immunoassay (mFB-LFIA) for the detection of three SECoVs, including porcine delta coronaviruses (PDCoV), transmissible gastroenteritis virus (TGEV), and porcine epidemic diarrhea virus (PEDV), in swine fecal samples. Thanks to the filter pad design and reasonable optimization, the mFB-LFIA was achieved within 15 min for three SECoVs detection simultaneously and improved the tolerance of the strips for feces samples. The limit of detection (LoD) of detecting PDCoV, TGEV, and PEDV were 2.1 × 104 TCID50 mL-1, 3.4 × 102 TCID50 mL-1, and 3.6 × 102 TCID50 mL-1, respectively. Additionally, the proposed assay was successfully applied to the detection of PDCoV, TGEV, and PEDV in swine feces with high accuracy. Compared with the gold standard nucleic acid testing, the total coincidence rate of the proposed assay was more than 90 %. Moreover, the mFB-LFIA performed excellent stability and repeatability. The proposed mFB-LFIA allows for rapid, in situ, more cost-effective and simultaneous detection of PDCoV, TGEV, and PEDV compared with nucleic acid testing. To the best of our knowledge, this is the first report to describe a multiplexed point-of-care assay capable of detecting PDCoV, TGEV, and PEDV in swine fecal samples. We believe our approach has a great potential for application to pig farm.

Discovery of a small-molecule NDR1 agonist for prostate cancer therapy.

Prostatic cancer (PCa) is a common malignant neoplasm in men worldwide. Most patients develop castration-resistant prostate cancer (CRPC) after treatment with androgen deprivation therapy (ADT), usually resulting in death. Therefore, investigating new therapeutic targets and drugs for PCa patients is urgently needed. Nuclear Dbf2-related kinase 1 (NDR1), also known as STK38, is a serine/threonine kinase in the NDR/LATS kinase family that plays a critical role in cellular processes, including immunity, inflammation, metastasis, and tumorigenesis. It was reported that NDR1 inhibited the metastasis of prostate cancer cells by suppressing epithelial-mesenchymal transition (EMT), and decreased NDR1 expression might lead to a poorer prognosis, suggesting the enormous potential of NDR1 in antitumorigenesis. In this study, we characterized a small-molecule agonist named aNDR1, which specifically bound to NDR1 and potently promoted NDR1 expression, enzymatic activity and phosphorylation. aNDR1 exhibited drug-like properties, such as favorable stability, plasma protein binding capacity, cell membrane permeability, and PCa cell-specific inhibition, while having no obvious effect on normal prostate cells. Meanwhile, aNDR1 exhibited good antitumor activity both in vitro and in vivo. aNDR1 inhibited proliferation and migration of PCa cells and promoted apoptosis of PCa cells in vitro. We further found that aNDR1 inhibited subcutaneous tumors and lung metastatic nodules in vivo, with no obvious toxicity to the body. In summary, our study presents a potential small-molecule lead compound that targets NDR1 for clinical therapy of PCa patients.

Retinal nerve fibre layer thickness measured with SD-OCT in a population-based study: the Handan Eye Study.

PURPOSE: To examine the normative profile of retinal nerve fibre layer (RNFL) thickness and ocular parameters based on spectral-domain optical coherence tomography (SD-OCT) and its associations with related parameters among the Chinese population. METHODS: This population-based cohort Handan Eye Study (HES) recruited participants aged≥30 years. All subjects underwent a standardised ophthalmic examination. Peripapillary RNFL thickness was obtained using SD-OCT. Mixed linear models were adopted to evaluate the correlation of RNFL thickness with ocular parameters as well as systemic factors. R V.3.6.1 software was used for statistical analysis. RESULTS: 3509 subjects (7024 eyes) with the average age of 55.54±10.37 were collected in this analysis. Overall mean RNFL thickness measured was 113.46±10.90 µm, and the thickest quadrant of parapapillary RNFL was the inferior quadrant, followed by the superior quadrant, the nasal quadrant and the temporal quadrant. In the multivariate linear regression model, thinner RNFL thickness was remarkable association with male (p<0.001), older age (p<0.001), increased body mass index (>30, p=0.018), absence of diabetes (p=0.009), history of cataract surgery (p=0.001), higher intraocular pressure (p=0.007), lower spherical equivalent (p<0.001) and increased axial length (p=0.048). CONCLUSIONS: In non-glaucoma individuals, this difference of RNFL thickness in Chinese population should be noted in making disease diagnoses. Meanwhile, multiple ocular and systemic factors are closely related to the thickness of RNFL. Our findings further emphasise the need to demonstrate ethnic differences in RNFL thickness and the specificity of associated ocular and systemic factors, as well as to develop better normative databases worldwide. TRIAL REGISTRATION NUMBER: HES was registered in Chinese Clinical Trial Registry website, and the registry number was ChiCTR-EOC-17013214.

HyperTDP-Net: A Hyper-densely Connected Compression-and-Decomposition Network Based on Trident Dilated Perception for PET and MRI Image Fusion.

Objective. Since medical images generated by medical devices have low spatial resolution and quality, fusion approaches on medical images can generate a fused image containing a more comprehensive range of different modal features to help physicians accurately diagnose diseases. Conventional methods based on deep learning for medical image fusion usually extract only local features without considering their global features, which often leads to the problem of unclear detail information in the final fused image. Therefore, medical image fusion is a challenging task of great relevance.Approach.This paper proposes a novel end-to-end medical image fusion model for PET and MRI images to achieve information interaction between different pathways, termed as hyper-densely connected compression-and-decomposition network based on trident dilated perception for PET and MRI image fusion (HyperTDP-Net). In particular, in the compression network, a dual residual hyper densely module is constructed to take full advantage of middle layer information. Moreover, we establish the trident dilated perception module to precisely determine the location information of features, and improve the feature representation capability of the network. In addition, we abandon the ordinary mean square error as the content loss function and propose a new content-aware loss consisting of structural similarity loss and gradient loss, so that the fused image not only contains rich texture details but also maintains sufficient structural similarity with the source images.Main results. The experimental dataset used in this paper is derived from multimodal medical images published by Harvard Medical School. Extensive experiments illustrate that our model contains more edge information and texture detail information in the fusion result than the 12 state-of-the-art fusion models and ablation study results demonstrate the effectiveness of three technical innovations.Significance. As medical images continue to be used in clinical diagnosis, our method is expected to be a tool that can effectively improve the accuracy of physician diagnosis and automatic machine detection.

Macular thickness and its associated factors in a Chinese rural adult population: the Handan Eye Study.

PURPOSE: To describe the normal macular thickness and assess its associations. METHODS: The Handan Eye Follow-up Study was conducted between 2012 and 2013. Macular thickness was scanned by spectral-domain optical coherence tomography (OCT). The built-in software generated a retinal thickness (RT) map, which was divided into three regions (central, internal and external regions) and nine quadrants (one in central and four in internal and external regions each). RESULTS: For 5394 subjects in the Handan Eye Follow-up Study, 4793 received OCT examination, 2946 of whom (accounting for 61.46% of the total subjects, mean age 58.91±10.95, 55.6% were women) were included for analysis. The mean RT in central macula, inner and outer rings were (237.38 µm±23.05 µm), (309.77 µm±18.36 µm) and (278.29 µm±14.38 µm), respectively (overall difference, p＜0.001). In inner ring, the RT in temporal was thinnest, followed by nasal, superior and inferior. In outer ring, the RT in superior was thinnest, with the next subfields being temporal, inferior and nasal, respectively. The RT in central macula, inner and outer rings were significantly thicker in men than in women. Multivariate linear regression analysis showed that in central macula, RT increased in subjects younger than 60 years and thinned above the age of 60. In inner and outer rings, RT thinned along with age (p＜0.001). CONCLUSIONS: This study finds that RT in central macula is the thinnest, followed by the outer ring, the RT in the inner ring is the thickest. Age and gender are related to RT. These associated factors need to be considered when explaining RT.