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Abstract NLRP3 inflammasomes- pyroptosis axis is activated by microcirculation dysfunction and touched off severe acute pancreatitis (SAP). Activation of PGC-1α can improve microcirculation dysfunction by promoting mitochondrial biogenesis. Resveratrol (RSV), one typical SIRT1 agonist, possesses the ability of alleviating SAP and activing PGC-1α. Therefore, the study was designated to explore whether the protective effect of RSV in SAP was though suppressing NLRP3 inflammasomes- pyroptosis axis via advancing SIRT1/PGC-1α-dependent mitochondrial biogenesis. The models of SAP were induced by treating with sodium taurodeoxycholate in rats and AR42J cells. The pathological injury, water content (dry/wet ratio) and microcirculation function of pancreas, activity of lipase and amylase were used to evaluate pancreatic damage. The expression of inflammatory cytokine was measured by ELISA and RT-PCR. The damage of mitochondrial was evaluated by measuring the changes in Mitochondrial Membrane Potential (ΔΨm), mitochondrial ROS, ATP content and MDA as well as relocation of mtDNA and the activity of SOD and GSH. The expressions of NLRP3 inflammasomes- pyroptosis axis proteins were detected by Western blotting as well as SIRT1/PGC-1α/NRF1/TFAM pathway protein. Moreover, the modification of PGC-1α was measured by co-immunoprecipitation. The results displayed that RSV can significantly improve the damage of pancreas and mitochondrial, decrease the expression of pro-inflammatory factor and the activation of NLRP3 inflammasomes- pyroptosis axis, promote the expression of an-inflammatory factor and the deacetylation of PGC-1α together with facilitating SIRT1/PGC-1α-mediating mitochondrial biogenesis. Therefore, the protective effect of RSV in SAP is though inactivation of NLRP3 inflammasomes- pyroptosis axis via promoting mitochondrial biogenesis in a SIRT1/PGC-1α-dependent manner.

Abstract Alzheimer’s disease (AD) is a global healthcare challenge lacking a simple and affordable detection method. We propose a novel deep learning framework, Eye-AD, to detect Early-onset Alzheimer’s Disease (EOAD) and Mild Cognitive Impairment (MCI) using OCTA images of retinal microvasculature and choriocapillaris. Eye-AD employs a multilevel graph representation to analyze intra- and inter-instance relationships in retinal layers. Using 5751 OCTA images from 1671 participants in a multi-center study, our model demonstrated superior performance in EOAD (internal data: AUC = 0.9355, external data: AUC = 0.9007) and MCI detection (internal data: AUC = 0.8630, external data: AUC = 0.8037). Furthermore, we explored the associations between retinal structural biomarkers in OCTA images and EOAD/MCI, and the results align well with the conclusions drawn from our deep learning interpretability analysis. Our findings provide further evidence that retinal OCTA imaging, coupled with artificial intelligence, will serve as a rapid, noninvasive, and affordable dementia detection.

Using machine learning techniques to predict brain age from multimodal data has become a crucial biomarker for assessing brain development. Among various types of brain imaging data, structural magnetic resonance imaging (sMRI) and diffusion magnetic resonance imaging (dMRI) are the most commonly used modalities. sMRI focuses on depicting macrostructural features of the brain, while dMRI reveals the orientation of major white matter fibers and changes in tissue microstructure. However, their differential capabilities in reflecting newborn age and clinical implications have not been systematically studied. This study aims to explore the impact of sMRI and dMRI on brain age prediction. Comparing predictions based on T2-weighted(T2w) and fractional anisotropy (FA) images, we found their mean absolute errors (MAE) in predicting infant age to be similar. Exploratory analysis revealed for T2w images, areas such as the cerebral cortex and ventricles contribute most significantly to age prediction, whereas FA images highlight the cerebral cortex and regions of the main white matter tracts. Despite both modalities focusing on the cerebral cortex, they exhibit significant region-wise differences, reflecting developmental disparities in macro- and microstructural aspects of the cortex. Additionally, we examined the effects of prematurity, gender, and hemispherical asymmetry of the brain on age prediction for both modalities. Results showed significant differences (p

Abstract Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the axon and transported back to the soma. This transport is essential since the final degradation of the vesicular content occurs only close to or in the soma. Here, we established an in vivo live-imaging model in the rat optic nerve using viral vector mediated LC3-labeling and two-photon-microscopy to analyze axonal transport of AVs. Under basal conditions in vivo, 50% of the AVs are moving with a majority of 85% being transported in the retrograde direction. Transport velocity is higher in the retrograde than in the anterograde direction. A crush lesion of the optic nerve results in a rapid breakdown of retrograde axonal transport while the anterograde transport stays intact over several hours. Close to the lesion site, the formation of AVs is upregulated within the first 6 h after crush, but the clearance of AVs and the levels of lysosomal markers in the adjacent axon are reduced. Expression of p150Glued, an adaptor protein of dynein, is significantly reduced after crush lesion. In vitro, fusion and colocalization of the lysosomal marker cathepsin D with AVs are reduced after axotomy. Taken together, we present here the first in vivo analysis of axonal AV transport in the mammalian CNS using live-imaging. We find that axotomy leads to severe defects of retrograde motility and a decreased clearance of AVs via the lysosomal system.

Abstract Objective To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery. Methods We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months. Results All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100–145). Median estimated blood loss was 224 ml (IQR: 190–255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P

Background: Patients with fractures of the proximal humerus often local complications and failures attributed to osteoporosis. Currently, there is a lack of straight forward screening methods for assessing the extent of local osteoporosis in the proximal humerus. This study utilizes machine learning techniques to establish a diagnostic approach for evaluating local osteoporosis by analyzing the patient's demographic data, bone density, and X-ray ratio of the proximal humerus. Methods: A cohort comprising a total of 102 hospitalized patients admitted during the period spanning from 2021 to 2023 underwent random selection procedures. Resulting in exclusion of 5 patients while enrolling 97 patients for analysis encompassing patient demographics, shoulder joint anteroposterior radiographs, and bone density information. Using the modified Tingart index methodology involving multiple measurements denoted as M1 through M4 obtained from humeral shafts. Within this cohort comprised 76 females (78.4 %) and 21 males (21.6 %), with an average age of 73.0 years (range: 43–98 years). There were 25 cases with normal bone density, 35 with osteopenia, and 37 with osteoporosis. Machine learning techniques were used to randomly divide the 97 cases into training (n = 59) and validation (n = 38) sets with a ratio of 6:4 using stratified random sampling. A decision tree model was built in the training set, and significant diagnostic indicators were selected, with the performance of the decision tree evaluated using the validation set. Multinomial logistic regression methods were used to verify the strength of the relationship between the selected indicators and osteoporosis. Results: The decision tree identified significant diagnostic indicators as the humeral shaft medullary cavity ratio M2/M4, age, and gender. M2/M4 ≥ 1.13 can be used as an important screening criterion; M2/M4 < 1.13 was predicted as local osteoporosis; M2/M4 ≥ 1.13 and age ≥83 years were also predicted as osteoporosis. M2/M4 ≥ 1.13 and age

Abstract Objective This study aimed to analyze the distribution of different types of strabismus surgery in a tertiary hospital in Central China during the three-year period of the COVID-19 pandemic. Methods A retrospective analysis was conducted on the clinical data of strabismus patients who underwent surgery and were admitted to the Department of Strabismus and Pediatric Ophthalmology at the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2022. Results A total of 3939 strabismus surgery patients were collected, including 1357 in 2020, 1451 in 2021, and 1131 in 2022. The number of surgeries decreased significantly in February 2020, August 2021, and November and December 2022. Patients aged 0–6 years accounted for 37% of the total number of strabismus surgery patientsr. The majority (60%) of all strabismus surgery patients were diagnosed with exotropia, with intermittent exotropia accounting for the highest proportion (53%). There was no statistically significant difference in the proportion of intermittent exotropia and constant exotropia during the three-year period (χ 2 = 2.642, P = 0.267 and χ 2 = 3.012, P = 0.221, respectively). Among patients with intermittent exotropia, insufficient convergence type was the most common form of strabismus (accounting for over 70%). Non-accommodative esotropia accounted for more than 50% of all internal strabismus cases. Conclusion During the period from 2020 to 2022, the total number of strabismus surgeries in our hospital did not show significant fluctuations, but there was a noticeable decrease in the number of surgeries during months affected by the pandemic. Exotropia accounted for the highest proportion among strabismus surgery patients. Intermittent exotropia was the most common type among patients undergoing surgery for exotropia, and the most prevalent subtype was the insufficient convergence type. The age distribution of patients varied in different months, with a concentration of surgeries for strabismus patients in the 7–12 years old age group during the months of July and August each year.

Although single-atom M-N-C electrocatalysts have demonstrated their potential in metal-air batteries and fuel cells, their activity for oxygen reduction reaction (ORR) needs to be further improved. Regulating the electronic structure of M-Nx single sites to accelerate the activity and simultaneously directly identify the enhancement mechanisms is highly desirable but remains a challenge. Here we propose a stepwise thermal migration strategy to in situ introducing Cu nanoparticles (Cu-NPs) adjacent to single atoms Cu (Cu-SAs) confined into hierarchically porous carbon. The optimization of the electronic structure of the Cu-Nx site by adjacent Cu nanoparticles is confirmed by both enhanced ORR activity and theoretical calculations. The optimized CuSA-NP@NC exhibits a more positive half-wave potential (0.870 V) than CuSA@NC (0.842 V) and superior stability with an 86.6% ORR current retention after 24 hours of chronoamperometric test in alkaline electrolyte. When utilized as an air cathode in rechargeable Zn-air batteries, CuSA-NP@NC displays a high-power density of 224.1 mWcm−2 and a specific capacity of 802.0 mAh g−1. Theoretical calculations demonstrate that the introduction of Cu-NPs endows the Cu-N4 site with an enriched electron density, which optimizes the adsorption/desorption of ORR intermediates on the Cu-N4 sites. This work reports an effective way and provides insights into the ORR activity improvement of single-atom electrocatalysts.

Pin1 is a member of the peptidyl-prolyl cis/trans isomerase subfamily and is widely expressed in various cell types and tissues. Alterations in Pin1 expression levels play pivotal roles in both physiological processes and multiple pathological conditions, especially in the onset and progression of kidney diseases. Herein, we present an overview of the role of Pin1 in the regulation of fibrosis, oxidative stress, and autophagy. It plays a significant role in various kidney diseases including Renal I/R injury, chronic kidney disease with secondary hyperparathyroidism, diabetic nephropathy, renal fibrosis, and renal cell carcinoma. The representative therapeutic agent Juglone has emerged as a potential treatment for inhibiting Pin1 activity and mitigating kidney disease. Understanding the role of Pin1 in kidney diseases is expected to provide new insights into innovative therapeutic interventions and strategies. Consequently, this review delves into the molecular mechanisms of Pin1 and its relevance in kidney disease, paving the way for novel therapeutic approaches.

BackgroundAutomatic segmentation of corneal stromal cells can assist ophthalmologists to detect abnormal morphology in confocal microscopy images, thereby assessing the virus infection or conical mutation of corneas, and avoiding irreversible pathological damage. However, the corneal stromal cells often suffer from uneven illumination and disordered vascular occlusion, resulting in inaccurate segmentation.MethodsIn response to these challenges, this study proposes a novel approach: a nnUNet and nested Transformer-based network integrated with dual high-order channel attention, named U-NTCA. Unlike nnUNet, this architecture allows for the recursive transmission of crucial contextual features and direct interaction of features across layers to improve the accuracy of cell recognition in low-quality regions. The proposed methodology involves multiple steps. Firstly, three underlying features with the same channel number are sent into an attention channel named gnConv to facilitate higher-order interaction of local context. Secondly, we leverage different layers in U-Net to integrate Transformer nested with gnConv, and concatenate multiple Transformers to transmit multi-scale features in a bottom-up manner. We encode the downsampling features, corresponding upsampling features, and low-level feature information transmitted from lower layers to model potential correlations between features of varying sizes and resolutions. These multi-scale features play a pivotal role in refining the position information and morphological details of the current layer through recursive transmission.ResultsExperimental results on a clinical dataset including 136 images show that the proposed method achieves competitive performance with a Dice score of 82.72% and an AUC (Area Under Curve) of 90.92%, which are higher than the performance of nnUNet.ConclusionThe experimental results indicate that our model provides a cost-effective and high-precision segmentation solution for corneal stromal cells, particularly in challenging image scenarios.

ObjectiveThis study was conducted to explore the main indicators of ultrasonic shear wave elastography (SWE) for the diagnosis of osteoarthritis (OA) and its influencing factors.MethodsWe collected 910 patients between January 2018 and November 2023 from the department of ultrasound, Third Hospital of Hebei Medical University. Logistic regression was used to analyze the effects of age, gender, body mass index (BMI), smoking, alcohol, hypertension and diabetes on the diagnosis of OA by SWE.ResultsThe results showed that medial meniscal projection distance (MMPD) and OA had a positively correlated dose–response relationship (OR = 2.12, 95%CI (1.53, 3.95), trend p

Defect engineering of electrode materials is considered highly effective in regulating their performance, among which oxygen vacancies play a vital role. Thereupon, comprehensively understanding effects of oxygen vacancy in electrochemical processes of transition metal oxides stays hot and controversial, representatively for amorphous tungsten oxide films and their electrochromic (EC) behaviors. Upon long‐term cycling, amorphous tungsten oxide suffers from the universal trapping effect governed by the intrinsic host microstructure and transport kinetics of the inserted ions, implying that manipulating oxygen vacancies could be a potential solution to the ion‐trapping problem. Hence, systematic work is urgent for not only tackling the trapping effect but also understanding the effect of oxygen vacancies on EC behaviors. Herein, the concentration of oxygen vacancies in the amorphous tungsten oxide films is modulated over a wide range. In combination with comprehensive experiments and first‐principles calculations, the presence of oxygen vacancy is detrimental to the EC properties, but it greatly attenuates the trapping effect. Excellent cyclic stability is achieved with a 100% optical modulation rate and charge capacity retention after 5000 cyclic voltammetry cycles. This study elucidates understanding of oxygen vacancy engineering in transition metal oxides, particularly regarding trapping effect passivation.

Introduction: Thromboembolism is a recognized complication of nephrotic syndrome (NS). Evidence supporting the use of rivaroxaban to prevent NS-related thrombosis is limited and controversial. This study aimed to explore the impact of NS on rivaroxaban pharmacokinetics and to collect observational data on the efficacy and safety of rivaroxaban as primary thromboprophylaxis in patients with NS. Methods: This prospective study analyzed 141 patients with NS who received rivaroxaban (10 mg/day) for thromboprophylaxis. High-performance liquid chromatography-tandem mass spectrometry was used to measure the trough and peak plasma concentrations (Ctrough and Cmax) of rivaroxaban. The influence of clinical and genetic factors on these concentrations was examined using multivariate logistic regression. Results: The median Cmax and Ctrough were 68.5 ng/mL (interquartile range [IQR], 31.7–105.5 ng/mL) and 4.4 ng/mL (IQR, 1.2–11.9 ng/mL), respectively. The incidence of thromboembolic events (TEs) was 12.8%, while that of bleeding events was 14.2%, although all were classified as minor. Albumin level was the most significant factor affecting Cmax (ρ = 0.55; p < 0.001) and was also significantly associated with TEs (0.81; 0.71–0.91 per 1.0 g/dL increase; p = 0.001) and bleeding risks (1.11; 1.03–1.19 per 1.0 g/dL increase; p = 0.008). Single nucleotide polymorphisms in the ABCB1 gene significantly influenced Ctrough but were not associated with clinical outcomes. Conclusion: Hypoalbuminemia significantly affects the pharmacokinetics of rivaroxaban in NS patients. A dose-adjustment strategy based on rivaroxaban concentrations, accounting for variable albumin levels, may improve the safety and efficacy of thromboprophylaxis in this population.

With the advancement of touch screen technology, the application of touch screens in civil aircraft cockpits has become increasingly popular. However, further analysis and research are required to fully promote its applications. The paper researched the usability of touch screens in aircraft cockpit considering the operation performance and subjective NASA-TLX workload evaluation, conducted experimental research on three touch gestures: click, drag, and zoom. Additionally, a comparative analysis was conducted on the touch performance under different layouts, positions, touch sizes, dragging direction angles, and zoom multiples. The touch performance indicators include operation time, error rate, operation speed, and workload. The experimental results show that the 21 mm size has the minimum operation time and workload, and 18 mm size has the lowest error rate in the clicking tasks. Additionally, the performance and workload of the captain's layout are better than those of the co-pilot's layout, and the performance of the center console position is best. The operation speed of the dragging tasks is faster when performed at position R3 compared to other positions. The dragging moving angles with better operation speed are 80°-190° and 250°-290°. The operation performance and workload of the zooming tasks vary depending on the zoom multiples. As the multiple increases, the operation time and workload also increase. There is no difference in operation performance or workload between zooming in and zooming out. The paper provides experimental support and suggestions based on human operation and subjective NASA-TLX workload evaluation for the application of touch screens in civil aircraft cockpits.

AbstractObjective This study aimed to explore the role of glomerular lesions in patients who suffered from acute kidney injury (AKI) during hemorrhagic fever with renal syndrome (HFRS).Methods The study comprised 66 patients with AKI during HFRS treated at the National Clinical Research Center of Kidney Diseases of China, Jinling Hospital, from January 2014 to December 2018. According to the kidney pathological findings, the 66 patients were divided into two groups: the tubulointerstitial injury group (HFRS-TI group, n = 43) and the tubulointerstitial injury with glomerular lesions group (HFRS-GL group, n = 23). The clinical and pathological characteristics of the 66 patients were analyzed.Results There were 9 cases of IgA nephropathy, 1 case of membranous nephropathy, 2 cases of diabetic nephropathy, and 11 cases of mesangial proliferative glomerulonephritis in the HFRS-GL group. There were more males in the HFRS-GL group than in the HFRS-TI group (92.3% vs. 69.8%, p

Early computer-aided early diagnosis (CAD) based on retinal imaging is critical to the timely management and treatment planning of retina-related diseases. However, the inherent characteristics of retinal images and the complexity of their pathological patterns, such as low image contrast and different lesion sizes, restrict the performance of CAD systems. Recently, ultra-wide-field (UWF) retinal images have become a useful tool for disease detection due to the capability of capturing much broader view of retina (i.e., up to 200°), in comparison with the most commonly used retinal fundus images (45°). In this paper, we propose an attention-based multi-branch network for the diseases classification of four different subject groups. The proposed method consists of a multi-scale feature fusion module and a dual attention module. Specifically, small-scale lesions are identified using the features extracted from the multi-scale feature fusion module. To better explore the obtained features, the dual attention module with a global attention graph is incorporated to enable the network to recognize the salient objects of interest. Comprehensive validations on both private and public datasets were carried out to verify the effectiveness of the proposed model.

Abstract Background It is well-established that biochemical recurrence is detrimental to prostate cancer (PCa). In the present study, we explored the mechanisms underlying PCa progression. Methods Five cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases were used to perform gene set variation analysis (GSVA) between nonrecurrent and recurrent PCa patients. We obtained the intersection of pathway enrichment results and extracted the corresponding gene list. LASSO Cox regression analysis was used to identify recurrence-free survival (RFS)-related significant genes and establish an RFS prediction gene signature and nomogram. MTT and colony formation assays were conducted to validate our findings. Results The E2F signaling pathway was activated in recurrent PCa patients compared to nonrecurrent patients. We established an E2F-related gene signature for RFS prediction based on the four identified E2F-related genes (CDKN2C, CDKN3, RACGAP1, and RRM2) using LASSO Cox regression in the Memorial Sloan Kettering Cancer Center (MSKCC) cohort. The risk score of each patient in MSKCC was calculated based on the expression levels of CDKN2C, CDKN3, RACGAP1, and RRM2. PCa patients with low-risk scores exhibited higher RFS than those with high-risk scores. Receiver operating characteristic (ROC) curve analysis validated the good performance and prognostic accuracy of the E2F-related gene signature, which was validated in the TCGA-prostate adenocarcinoma (TCGA-PRAD) cohort. Compared to patients with low Gleason scores and early T stages, PCa patients with high Gleason scores and advanced T stages had high-risk scores. Moreover, the E2F-related gene signature-based nomogram yielded good performance in RFS prediction. Functional experiments further confirmed these results. Conclusions The E2F signaling pathway is associated with biochemical recurrence in PCa. Our established E2F-related gene signature and nomogram yielded good accuracy in predicting the biochemical recurrence in PCa.

IntroductionNeuromyelitis optica spectrum disorders (NMOSD) are autoimmune central nervous system diseases characterized by the immune system's abnormal attack on glial cells and neurons. Optic neuritis (ON) is one of the indicators of NMOSD, often starting unilaterally and potentially affecting both eyes later in the disease progression, leading to visual impairment. Optical coherence tomography angiography (OCTA) has the potential to aid in the early diagnosis of NMOSD by examining ophthalmic imaging and may offer a window for disease prevention.MethodsIn this study, we collected OCTA images from 22 NMOSD patients (44 images) and 25 healthy individuals (50 images) to investigate retinal microvascular changes in NMOSD. We employed effective retinal microvascular segmentation and foveal avascular zone (FAZ) segmentation techniques to extract key OCTA structures for biomarker analysis. A total of 12 microvascular features were extracted using specifically designed methods based on the segmentation results. The OCTA images of NMOSD patients were classified into two groups: optic neuritis (ON) and non-optic neuritis (non-ON). Each group was compared separately with a healthy control (HC) group.ResultsStatistical analysis revealed that the non-ON group displayed shape changes in the deep layer of the retina, specifically in the FAZ. However, there were no significant microvascular differences between the non-ON group and the HC group. In contrast, the ON group exhibited microvascular degeneration in both superficial and deep retinal layers. Sub-regional analysis revealed that pathological variations predominantly occurred on the side affected by ON, particularly within the internal ring near the FAZ.DiscussionThe findings of this study highlight the potential of OCTA in evaluating retinal microvascular changes associated with NMOSD. The shape alterations observed in the FAZ of the non-ON group suggest localized vascular abnormalities. In the ON group, microvascular degeneration in both superficial and deep retinal layers indicates more extensive vascular damage. Sub-regional analysis further emphasizes the impact of optic neuritis on pathological variations, particularly near the FAZ's internal ring.ConclusionThis study provides insights into the retinal microvascular changes associated with NMOSD using OCTA imaging. The identified biomarkers and observed alterations may contribute to the early diagnosis and monitoring of NMOSD, potentially offering a time window for intervention and prevention of disease progression.

In recent years, there is a growing demand for materials that can both improve the mechanical properties of structures and carry out health monitoring and risk warning. In this case, in order to realize distributed deformation monitoring, a new method of making geogrid by 3D printing technology is proposed. The grille rib is made by embedding the conductive polymer (ground carbon fiber as conductive filler) into the insulating shell (PLA material) in the specified path, and then the rib is vertically crossed into each other to form a grille sample. In order to study the distributed deformation monitoring function of this grid, a manual push–pull testing machine was used to conduct a load–unload experiment to analyze the change rule of resistance on the grid plane. The following conclusions were obtained: the closer the ribs are to the load bearing point, the greater the change in resistance, and conversely, the farther the ribs are from the load bearing point, the smaller the change in resistance. Depending on the geogrid network characteristics, the electrical resistance distribution on the geogrid plane can be obtained by superimposing the resistance values of the horizontal and longitudinal ribs, then the location and the magnitude of deformation can be estimated. Additionally, this study carried out numerical simulation of the grid model based on ANSYS 15.0 software and compared with the loading experiment results to verify that the force deformation position can be retrieved through the change of resistance.

Background: Ultra-Wide-Field (UWF) fundus imaging is an essential diagnostic tool for identifying ophthalmologic diseases, as it captures detailed retinal structures within a wider field of view (FOV). However, the presence of eyelashes along the edge of the eyelids can cast shadows and obscure the view of fundus imaging, which hinders reliable interpretation and subsequent screening of fundus diseases. Despite its limitations, there are currently no effective methods or datasets available for removing eyelash artifacts from UWF fundus images. This research aims to develop an effective approach for eyelash artifact removal and thus improve the visual quality of UWF fundus images for accurate analysis and diagnosis.Methods: To address this issue, we first constructed two UWF fundus datasets: the paired synthetic eyelashes (PSE) dataset and the unpaired real eyelashes (uPRE) dataset. Then we proposed a deep learning architecture called Joint Conditional Generative Adversarial Networks (JcGAN) to remove eyelash artifacts from UWF fundus images. JcGAN employs a shared generator with two discriminators for joint learning of both real and synthetic eyelash artifacts. Furthermore, we designed a background refinement module that refines background information and is trained with the generator in an end-to-end manner.Results: Experimental results on both PSE and uPRE datasets demonstrate the superiority of the proposed JcGAN over several state-of-the-art deep learning approaches. Compared with the best existing method, JcGAN improves PSNR and SSIM by 4.82% and 0.23%, respectively. In addition, we also verified that eyelash artifact removal via JcGAN could significantly improve vessel segmentation performance in UWF fundus images. Assessment via vessel segmentation illustrates that the sensitivity, Dice coefficient and area under curve (AUC) of ResU-Net have respectively increased by 3.64%, 1.54%, and 1.43% after eyelash artifact removal using JcGAN.Conclusion: The proposed JcGAN effectively removes eyelash artifacts in UWF images, resulting in improved visibility of retinal vessels. Our method can facilitate better processing and analysis of retinal vessels and has the potential to improve diagnostic outcomes.

Microfluidic chips have shown their potential for applications in fields such as chemistry and biology, and 3D printing is increasingly utilized as the fabrication method for microfluidic chips. To address key issues such as the long printing time for conventional 3D printing of a single chip and the demand for rapid response in individualized microfluidic chip customization, we have optimized the use of DLP (digital light processing) technology, which offers faster printing speeds due to its surface exposure method. In this study, we specifically focused on developing a fast-manufacturing process for directly printing microfluidic chips, addressing the high cost of traditional microfabrication processes and the lengthy production times associated with other 3D printing methods for microfluidic chips. Based on the designed three-dimensional chip model, we utilized a DLP-based printer to directly print two-dimensional and three-dimensional microfluidic chips with photosensitive resin. To overcome the challenge of clogging in printing microchannels, we proposed a printing method that combined an open-channel design with transparent adhesive tape sealing. This method enables the rapid printing of microfluidic chips with complex and intricate microstructures. This research provides a crucial foundation for the development of microfluidic chips in biomedical research.

Abstract Background Anemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China. Methods This cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4 + T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann–Whitney U test, and chi-square statistics were applied in SPSS. Results The Hgb of HIV-HD and HD groups were 105.70 (95.93–112.08) g/L and 112.00 (93.00–126.00) g/L respectively (P = 0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55 ± 115.47 U/kg/week) compared to the HIV-negative HD group (161.86 ± 110.31 U/kg/week) (P = 0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P = 0.003). The ferritin levels were 316.50 (117.38–589.75) ng/ml and 272.70 (205.00–434.00) ng/ml in HIV-HD and HD groups respectively. Conclusions A higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.

Introduction: Resource environment load data are important for analyzing and improving the environmental performance, which are affected by the process condition of metal material machining processes. However, the environmental performance assessment in previous research focused on the results under the specific process conditions. The resource environment load data need to be re-collected when the process conditions are changed for a credible assessment, which is time- consuming and tedious.Methods: This paper proposed a process condition- oriented prediction method of resource environment load data with limited samples. The significance of process condition elements on the resource environment load data was analyzed, and then the resource environment load was predicted according to the similarity between the process condition to be predicted and the existing process conditions.Results and Dicussion: The results show that the average prediction accuracy of this method exceeds 90%, and further the accuracy for predicting the environmental performances using the predicted data is more than 93% which would help process designers to choose the better process condition for machining the metal materials.

MicroRNAs (miRNAs) are emerging as effective therapeutic agents. When testing whether miR-145-5p could alleviate kidney injury, we unexpectedly found that extracellular vesicles loaded with miR-145-5p induced proteinuria and podocyte foot process effacement in normal control mice. To explore the mechanism of miR-145-5p’s toxicity to podocytes, we hypothesized that miR-145-5p could enter podocytes and inhibit genes essential for podocytes. We demonstrated that systemically administered miRNA can enter podocytes. Next, we predicted 611 podocyte essential genes based on single-cell RNA sequencing (RNA-seq) and found that 32 of them are predicted to be targeted by miR-145-5p. Functional annotation of the 32 podocyte essential genes revealed small GTPase-mediated signal transduction as the top pathway. We experimentally validated that miR-145-5p targeted Arhgap24 and Srgap1, the essential regulators of the Rho family of small GTPases, increased the activity of Rac1 and Cdc42, and reduced RhoA activity, accompanied by cellular injury, in podocytes. These results explain how miR-145-5p has deleterious effect on podocytes. Most importantly, our study provides a novel approach to investigate how a miRNA affects a given cell type, allowing not only identification of the molecular mechanism underlying an observed side effect of a miRNA drug but also prediction of miRNA drug toxicity on various cell types.

Abstract Costimulatory molecules have been proven to enhance antitumor immune responses, but their roles in clear cell renal cell carcinoma (ccRCC) remain unexplored. In this study, we aimed to explore the gene expression profiles of costimulatory molecule genes in ccRCC and construct a prognostic signature to improve treatment decision-making and clinical outcomes. We performed the first comprehensive analysis of costimulatory molecules in patients with ccRCC and identified 13 costimulatory molecule genes with prognostic values and diagnostic values. Consensus clustering analysis based on these 13 costimulatory molecular genes showed different distribution patterns and prognostic differences for the two clusters identified. Then, a costimulatory molecule-related signature was constructed based on these 13 costimulatory molecular genes, and validated in an external dataset, showing good performance for predicting a patient’s prognosis. The signature was an independent risk factor for ccRCC patients and was significantly correlated with patients’ clinical factors, which could be used as a complement for clinical factors. In addition, the signature was associated with the tumor immune microenvironment and the response to immunotherapy. Patients identified as high-risk based on our signature exhibited a high mutation frequency, a high level of immune cell infiltration, and an immunosuppressive microenvironment. High-risk patients tended to have high cytolytic activity scores and immunophenoscore of CTLA4 and PD1/PD-L1/PD-L2 blocker than low-risk patients, suggesting these patients may be more suitable for immunotherapy. Therefore, our signature could provide clinicians with prognosis predictions and help guide treatment for ccRCC patients.

Morphological changes of the choroid have been proved to be associated with the occurrence and pathological mechanism of many ophthalmic diseases. Optical Coherence Tomography (OCT) is a non-invasive technique for imaging of ocular biological tissues, that can reveal the structure of the retinal and choroidal layers in micron-scale resolution. However, unlike the retinal layer, the interface between the choroidal layer and the sclera is ambiguous in OCT, which makes it difficult for ophthalmologists to identify with certainty. In this paper, we propose a novel boundary-enhanced encoder-decoder architecture for choroid segmentation in retinal OCT images, in which a Boundary Enhancement Module (BEM) forms the backbone of each encoder-decoder layer. The BEM consists of three parallel branches: 1) a Feature Extraction Branch (FEB) to obtain feature maps with different receptive fields; 2) a Channel Enhancement Branch (CEB) to extract the boundary information of different channels; and 3) a Boundary Activation Branch (BAB) to enhance the boundary information via a novel activation function. In addition, in order to incorporate expert knowledge into the segmentation network, soft key point maps are generated on the choroidal boundary, and are combined with the predicted images to facilitate precise choroidal boundary segmentation. In order to validate the effectiveness and superiority of the proposed method, both qualitative and quantitative evaluations are employed on three retinal OCT datasets for choroid segmentation. The experimental results demonstrate that the proposed method yields better choroid segmentation performance than other deep learning approaches. Moreover, both 2D and 3D features are extracted for statistical analysis from normal and highly myopic subjects based on the choroid segmentation results, which is helpful in revealing the pathology of high myopia. Code is available at https://github.com/iMED-Lab/Choroid-segmentation.

The development of efficient non-precious metal electrocatalysts for oxygen reduction reaction (ORR) to replace Pt-based methods is crucial for the applications of fuel cells and metal–air batteries. In this study, a bimetallic M-N-C catalyst with highly dispersed dual-atom Fe/Mn-Nx sites immobilized on N-doped bamboo-like carbon nanotubes is prepared by the ball-milling and calcination of dual-MOFs as precursors. The rich N-doping and abundant M–Nx species contribute to the excellent intrinsic ORR activity of the catalyst, and the unique bamboo-like nanotubes morphology is beneficial for facilitating electron transfer and mass transport while simultaneously enabling the exposure of active sites. As expected, the optimized Z-Fe1Mn1-NC catalyst exhibits efficient ORR activity with a half-wave potential (E1/2) of 0.80 V in acid and 0.82 V in alkaline, and a higher electrochemical stability with the current density maintained at 91% (in 0.1 M KOH) and 86% (0.1 M HClO4) of its initial current density after 15 h of a chronoamperometric test at a high potential of 0.7 V. When further applied to Zn–air batteries, the catalyst also delivers a high open-circuit voltage, large power density, and outstanding rate performance. This work provides a novel means of designing dual metal M–Nx site-based M-N-C catalysts for ORR sustainable energy applications.

Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3β (p-GSK3β[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease.

PurposeTo evaluate demographic and clinical characteristics of a Chinese population with giant cell arteritis using multimodal imaging focusing on ophthalmic examinations.DesignRetrospective observational case series.Materials and MethodsIn the neuro-ophthalmology division of the Eye, Ear, Nose, and Throat Hospital, Shanghai, we evaluated the demographic and clinical characteristics of patients diagnosed with giant cell arteritis between January 2016 and June 2021. Results of routine ophthalmic examinations including fundus examination, optical coherence tomography, color duplex ultrasonography of ocular and superficial temporal arteries, orbital magnetic resonance imaging, and superficial temporal artery biopsy were evaluated.ResultsA total of 15 patients (22 eyes; ten male and five female) were evaluated with a mean age of 77.0 ± 8.5 years. Among them, seven had bilateral involvement that occurred simultaneously or sequentially. Twelve patients presented with arteritic anterior ischemic optic neuropathy, two with arteritic anterior ischemic optic neuropathy combined with cilioretinal artery occlusion, and one with cotton-wool spots. In acute stages of optic neuropathy and retinopathy, optical coherence tomography revealed optic disc edema, thickening of the inner retinal nerve fiber layer and ganglion cell layer, and loss of layer structure. In late stages, optical coherence tomography revealed diffuse atrophy of the inner retina. The “halo” sign was observed in 12 patients in the superficial temporal artery ultrasound, and seven out of eight patients who underwent biopsy demonstrated classic giant cell arteritis pathological changes. Most patients having poor visual acuity but ability to perceive light; 10/22 eyes had permanent vision loss.ConclusionAlthough rare in Asians, giant cell arteritis may be underdiagnosed among elderly Chinese patients presenting with anterior ischemic optic neuropathy. Non-invasive superficial temporal artery ultrasound detecting inflammatory thickening of the intima as the “halo” sign combined with routine elevated erythrocyte sedimentation rate and C-reactive protein may be helpful in diagnosing patients with a high probability of having giant cell arteritis.

Delicate design and precise manipulation of electrode morphology has always been crucial in electrochemistry. Generally, porous morphology has been preferred due to the fast kinetic transport characteristics of cations. Nevertheless, more refined design details such as the granularity uniformity that usually goes along with the porosity regulation of film electrodes should be taken into consideration, especially in long-term cation insertion and extraction. Here, inorganic electrochromism as a special member of the electrochemical family and WO3 films as the most mature electrochromic electrode material were chosen as the research background. Two kinds of WO3 films were prepared by magnetron sputtering, one with a relatively loose morphology accompanied by nonuniform granularity and one with a compact morphology along with uniform particle size distribution, respectively. Electrochemical performances and cyclic stability of the two film electrodes were then traced and systematically compared. In the beginning, except for faster kinetic transport characters of the 50 W-deposited WO3 film, the two electrodes showed equivalent optical and electrochemical performances. However, after 5000 CV cycles, the 50 W-deposited WO3 film electrode cracked seriously. Strong stress distribution centered among boundaries of the nonuniform particle clusters together with the weak bonding among particles induced the mechanical damage. This discovery provides a more solid background for further delicate film electrode design.

Background: Renal fibrosis is a key driver of progression in chronic kidney disease (CKD). Recent advances in diagnostic imaging techniques have shown promising results for the noninvasive assessment of renal fibrosis. However, the specificity and accuracy of these techniques are controversial because they indirectly assess renal fibrosis. This limits fibrosis assessment by imaging in CKD for clinical practice. To validate magnetic resonance imaging (MRI) assessment for fibrosis, we derived representative models by mapping histology-proven renal fibrosis and imaging in CKD. Methods: Ninety-seven adult Chinese CKD participants with histology were studied. The kidney cortex interstitial extracellular matrix volume was calculated by the Aperio ScanScope system using Masson’s trichrome slices. The kidney cortex microcirculation was quantitatively assessed by peritubular capillary density using CD34 staining. The imaging techniques included intravoxel incoherent motion diffusion-weighted imaging and magnetic resonance elastography (MRE) imaging. Relevant analyses were performed to evaluate the correlations between MRI parameters and histology variables. Multiple linear regression models were used to describe the relationships between a response variable and other variables. The best-fit lines, which minimize the sum of squared residuals of the multiple linear regression models, were generated. Results: MRE values were negatively associated with the interstitial extracellular matrix volume (Rho = −0.397, p < 0.001). The best mapping model of extracellular matrix volume with the MRE value and estimated glomerular filtration rate (eGFR) we obtained was as follows: Interstitial extracellular matrix volume = 218.504 – 14.651 × In(MRE) – 18.499 × In(eGFR). DWI-fraction values were positively associated with peritubular capillary density (Rho = 0.472, p < 0.001). The best mapping model of peritubular capillary density with DWI-fraction value and eGFR was as follows: Peritubular capillaries density = 17.914 + 9.403 × (DWI – fraction) + 0.112 × (eGFR). Conclusions: The study provides histological evidence to support that MRI can effectively evaluate fibrosis in the kidney. These findings picture the graphs of the mapping model from imaging and eGFR into fibrosis, which has significant value for clinical implementation.

Defined differently from apoptosis, necrosis, and autophagy, ferroptosis has been implicated in acute kidney injury (AKI) such as ischemia-reperfusion injury induced AKI, folic acid caused AKI and cisplatin induced AKI. However, whether ferroptosis is involved in LPS induced AKI could be remaining unclear and there is still a lack of therapies associated with ferroptosis in LPS induced AKI without side effects. This study aimed to elucidate the role of isoliquiritigenin (ISL) in ferroptosis of LPS-induced AKI. We used LPS to induce renal tubular injury, followed by treatment with ISL both in vitro and in vivo. Human renal tubular HK2 cells were pretreated with 50 μM or 100 μM ISL for 5 h before stimulation with 2 μg/mL LPS. Mice were administered a single dose of either 50 mg/kg ISL orally or 5 mg/kg ferroptosis inhibitor ferrostatin-1 intraperitoneally before 10 mg/kg LPS injection. We found that LPS could induce mitochondria injury of renal tubular presented as the shape of mitochondria appeared smaller than normal with increased membrane density and are faction or destruction of mitochondrial crista through scanning electron microscope. Ferrostatin-1 significantly protected mice against renal dysfunction and renal tubular damage in LPS-induced AKI. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. These results indicated the potential role of ISL against ferritinophagy-mediated ferroptosis in renal tubular following LPS stimulation.

Aiming at the current multimodal medical image fusion methods that cannot fully characterize the complex textures and edge information of the lesion in the fused image, a method based on Gabor representation of multi-CNN combination and fuzzy neural network is proposed. This method first filters the CT and MR image sets through a set of Gabor filter banks with different proportions and directions to obtain different Gabor representations pairs of CT and MR, each pair of different Gabor representations is used to train the corresponding CNN to generate a G- CNN and multiple G- CNN form a G- CNN group, namely G- CNNs; then when fusing CT and MR images, CT and MR are represented by Gabors to get Gabor representation pairs firstly, each Gabor representation pair is put into the corresponding trained G- CNN for preliminary fusion, then use the fuzzy neural network to fuse multiple outputs of the G- CNNs to obtain the final fused image. Compared with the nine recent state-of-the-art multimodal fusion methods, the average mutual information of the three groups of experiments has increased by 13%, 10.3%, and 10% respectively; the average spatial frequency has increased by 10.3%, 20%, and 10.7%; the average standard deviation has increased respectively 12.4%, 10.8%, 14.4%; the average edge retention information increased by 33.5%, 22%, and 43%. The experimental results show that the proposed fusion method is significantly better than the other comparative fusion methods in objective evaluation and visual quality. It has the best performance on the four indicators and can better integrate the rich texture features and the clear edge information of the source images into the final fused image, which improves the quality of multimodal medical image fusion, and effectively assists doctors in disease diagnosis.

The intrinsic heat-affected zone (HAZ) during the microsecond pulsed laser processing significantly affect the surface quality of the fused silica optics. This study employed both three-dimensional numerical simulations and experiments to analyze the heat accumulation effect, morphology evolution mechanism, and the HAZ distribution during CO2 laser processing of fused silica. Simulation results show that with the increases of process parameters such as the laser frequency, the overlap rate, and the pulse width, the residual temperature of the substrate rises gradually. The excessive laser repetition frequency mainly causes the heat accumulation and over-ablation. Analysis of the laser processed surface demonstrates that the superposition of the laser spot energy results in the periodic texture whose spatial internal is equal to the feeding distance of the laser spot. Increasing the track pitch will make the ridges and grooves of the ripple structure discrete, while reducing the laser moving speed within a certain range can improve the surface quality. Besides, the fictive temperature of the substrate tends to stabilize after the third laser pulse in each track. The thickness of the HAZ is close to the material removal depth, but it can be effectively suppressed with a pulse width less than 10 μs. Experiments are conducted to validate the simulation and the results match well with each. This study can provide a theoretical guidance for producing high-quality fused silica optics in high-power laser device applications.

Aim Novel coronavirus pneumonia (COVID-19) has become pandemic. It brings serious threat to hemodialysis (HD) patients. Therefore, we carried out a study on the clinical characteristics of HD patients with COVID-19. Methods We retrospectively analyzed the data of 31 HD patients with COVID-19. The clinical features of patients include epidemiology, clinical symptoms, laboratory and imaging test, treatment and prognosis. Results 61.3% were severe, and 38.7% were mild. 83.9% had a close contact history with COVID-19 patients. The average age was 62.3 years comprising of 58.1% men and 41.9% women. Ninety percent had chronic diseases except ESRD. Clinical symptoms include cough (85%), fever (43%), and shortness of breath (48.4%), etc. Complications included ARDS (25.8%), AHF (22.6%), and septic shock (16.1%), etc. 64.5% of patients had remission, and 35.5% of patients had no remission with 6.5% deaths. Compared with the baseline before infection, HD patients with COVID-19 had lower lymphocytes, albumin and glucose, and higher D-dimer, albumin, phosphorus, lactate dehydrogenase, and CRP. There was no significant correlation between the neutrophils/lymphocytes ratio and the severity of the disease. Conclusions Compared with the reported general population, the HD patients are susceptible to COVID-19 infection, especially older men and those with other underlying diseases. Moreover, HD patients have more severe infection and inflammation with less symptoms and worse outcome. COVID-19 infection can cause dialysis patients lower immunity, stronger inflammation, malnutrition, and internal environment disorder. Neutrophils/lymphocytes ratio does not reflect the severity of the HD patients with COVID-19.

Glucocorticoids are commonly used to treat anti-GBM crescentic glomerulonephritis, however, the mechanism underlying its therapeutic effectiveness is not completely understood. Since podocyte EGFR/STAT3 signaling is known to mediate the development of anti-GBM glomerulonephritis, we investigated the effect of glucocorticoids on EGFR/STAT3 signaling in podocytes. We found that the levels of phosphorylated (activated) EGFR and STAT3 in podocytes were markedly elevated in anti-GBM patients without glucocorticoids treatment, but were normalized in patients with glucocorticoids treatment. In a rat model of anti-GBM glomerulonephritis, glucocorticoids treatment significantly attenuated the proteinuria, crescent formation, parietal epithelial cell (PEC) activation and proliferation, accompanied by elimination of podocyte EGFR/STAT3 signaling activation. In cultured podocytes, glucocorticoids were found to inhibit HB-EGF-induced EGFR and STAT3 activation. The conditioned medium from podocytes treated with HB-EGF in the absence but not presence of glucocorticoids was capable of activating Notch signaling (which is known to be involved in PEC proliferation and crescent formation) and enhancing proliferative activity in primary PECs, suggesting that glucocorticoids prevent podocytes from producing secreted factors that cause PEC proliferation and crescent formation. Furthermore, we found that glucocorticoids can downregulate the expression of EGFR ligands, EGF and HB-EGF, while upregulate the expression of EGFR inhibitor, Gene 33, explaining how glucocorticoids suppress EGFR signaling. Taken together, glucocorticoids exert therapeutic effect on anti-GBM crescentic glomerulonephritis through inhibiting podocyte EGFR/STAT3 signaling and the downstream pathway that leads to PEC proliferation and crescent formation.

Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

Background: Cytological detection of early esophageal squamous cell carcinoma (ESCC) remains challenging. Therefore, we introduced a rapid cytological screening method and evaluated its efficacy as a pre-endoscopy screening for early ESCC and precursor lesions. Methods: This method consisted of a sponge sample retrieval, automatic liquid-based cytological treatment and slides preparation, computer-assisted screening and manual diagnosis. Efficacy for detection of early ESCC and precursor lesions was evaluated. Also, diagnostic efficiency was compared with manual diagnosis. Results: Eighty-three patients with early ESCC and precursor lesions and 2,090 asymptomatic participants with high risks of ESCC were enrolled. Whole procedure was accomplished within two working days. Abnormal cells were detected in all 83 patients, and in 272 (13.01%) subjects among 2,090 asymptomatic participants. Early ESCC, high-grade intraepithelial neoplasia, low-grade intraepithelial neoplasia and reflux esophagitis and normal endoscopic findings were detected in 8, 13, 11, 187 and 53 participants with abnormal cells, respectively. The calculated sensitivity, specificity, positive predictive value and negative predictive value for detection of early ESCC and precursor lesions were 100%, 88.34%, 11.76%, and 100%, respectively. Compared with manual diagnosis, this method was accomplished in a shorter time duration (5.4 ± 0.45 min vs 320.2 ± 132.4 min, p

Trigeminal neuralgia caused by paroxysmal and severe pain in the distribution of the trigeminal nerve is a rare chronic pain disorder. It is generally accepted that compression of the trigeminal root entry zone by vascular structures is the major cause of primary trigeminal neuralgia, and vascular decompression is the prior choice in neurosurgical treatment. Therefore, accurate preoperative modeling/segmentation/visualization of trigeminal nerve and its surrounding cerebrovascular is important to surgical planning. In this paper, we propose an automated method to segment trigeminal nerve and its surrounding cerebrovascular in the root entry zone, and to further reconstruct and visual these anatomical structures in three-dimensional (3D) Magnetic Resonance Angiography (MRA). The proposed method contains a two-stage neural network. Firstly, a preliminary confidence map of different anatomical structures is produced by a coarse segmentation stage. Secondly, a refinement segmentation stage is proposed to refine and optimize the coarse segmentation map. To model the spatial and morphological relationship between trigeminal nerve and cerebrovascular structures, the proposed network detects the trigeminal nerve, cerebrovasculature, and brainstem simultaneously. The method has been evaluated on a dataset including 50 MRA volumes, and the experimental results show the state-of-the-art performance of the proposed method with an average Dice similarity coefficient, Hausdorff distance, and average surface distance error of 0.8645, 0.2414, and 0.4296 on multi-tissue segmentation, respectively.

Purpose: To investigate the thickness changes of outer retinal layers in subjects with white matter hyperintensities (WMH) and Parkinson's Disease (PD).Methods: 56 eyes from 31 patients with WMH, 11 eyes from 6 PD patients, and 58 eyes from 32 healthy controls (HC) were enrolled in this study. A macular-centered scan was conducted on each participant using a spectral-domain optical coherence tomography (SD-OCT) device. After speckle noise reduction, a state-of-the-art deep learning method (i.e., a context encoder network) was employed to segment the outer retinal layers from OCT B-scans. Thickness quantification of the outer retinal layers was conducted on the basis of the segmentation results.Results: WMH patients had significantly thinner Henle fiber layers, outer nuclear layers (HFL+ONL) and photoreceptor outer segments (OS) than HC (p = 0.031, and p = 0.005), while PD patients showed a significant increase of mean thickness in the interdigitation zone and the retinal pigment epithelium/Bruch complex (IZ+RPE) (19.619 ± 4.626) compared to HC (17.434 ± 1.664). There were no significant differences in the thickness of the outer plexiform layer (OPL), the myoid and ellipsoid zone (MEZ), and the IZ+RPE layer between WMH and HC subjects. Similarly, there were also no obvious differences in the thickness of the OPL, HFL+ONL, MEZ and the OS layer between PD and HC subjects.Conclusion: Thickness changes in HFL+ONL, OS, and IZ+RPE layers may correlate with brain-related diseases such as WMH and PD. Further longitudinal study is needed to confirm HFL+ONL/OS/IZ+RPE layer thickness as potential biomarkers for detecting certain brain-related diseases.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is an inflammatory immune disease characterized by intraprostatic leukocyte infiltration and pelvic or perineal pain. Macrophages play vital roles in the pathogenesis of CP/CPPS. However, the mechanisms controlling the activation and chemotaxis of macrophages in CP/CPPS remain unclear. This study aimed to investigate the roles of the CXCL10/CXCR3 pathway in the activation and chemotaxis of macrophages in CP/CPPS patients. The serums of CP/CPPS patients and healthy volunteers were collected and measured. Results showed that CXCL10 expression was significantly elevated and correlated with the severity of CP/CPPS patients. The experimental autoimmune prostatitis (EAP) model was generated, and adeno-associated virus and CXCR3 inhibitors were used to treat EAP mice. Immunofluorescence, flow cytometry, and Western blotting were used to analyze the functional phenotype and regulation mechanism of macrophages. Results showed that CXCL10 deficiency ameliorates EAP severity by inhibiting infiltration of macrophages to prostate. Moreover, CXCL10 could induce macrophage migrations and secretions of proinflammatory mediators via CXCR3, which consequently activated the downstream Erk1/2 and p38 MAPK signaling pathways. We also showed that prostatic stromal cell is a potential source of CXCL10. Our results indicated CXCL10 as an important mediator involved in inflammatory infiltration and pain symptoms of prostatitis by promoting the migration of macrophages and secretion of inflammatory mediators via CXCR3-mediated ERK and p38 MAPK activation.

Modern manufacturing industries thrive on greenness, which means ensuring acceptable environmental impacts and required surface quality of the products during the manufacturing process. However, there is a conflict between surface quality and environmental performances in the milling process. The current research only considers energy consumption rather than total environmental impacts. In this respect, this research focuses on the multiobjective optimization of machining parameters for balancing the surface quality (i.e., surface roughness, Ra) and total environmental impact (TEI), which includes raw materials usage, energy consumption, and output pollutant emission during the milling of AL6061 alloy. First, life cycle assessment (LCA) of the milling process is used for evaluating the TEI. Then, multiobjective optimization is conducted using Grey Relational Analysis. The results indicated that the improvement of Ra and TEI can be achieved with higher cutting speed, higher depth, and wet conditions in milling. The optimization work showed that cutting speed of 165 m/min, feed rate of 0.28 mm/rev, depth of cut of 2 mm, and width of cut of 3 mm are the optimal combination among existing experiments. Compared to single objective optimization results, multiple responses (Ra and TEI) can be improved simultaneously.

Faba bean (Vicia faba L.) is one of the most widely grown cool season legume crops in the world. Winter faba bean normally has a vernalization requirement, which promotes an earlier flowering and pod setting than unvernalized plants. However, the molecular mechanisms of vernalization in faba bean are largely unknown. Discovering vernalization-related candidate genes is of great importance for faba bean breeding. In this study, the whole transcriptome of faba bean buds was profiled by using next-generation sequencing (NGS) and single-molecule, real-time (SMRT) full-length transcriptome sequencing technology. A total of 29,203 high-quality non-redundant transcripts, 21,098 complete coding sequences (CDS), 1,045 long non-coding RNAs (lncRNAs), and 12,939 simple sequence repeats (SSRs) were identified. Furthermore, 4,044 differentially expressed genes (DEGs) were identified through pairwise comparisons. By Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, these differentially expressed transcripts were found to be enriched in binding and transcription factor activity, electron carrier activity, rhythmic process, and receptor activity. Finally, 50 putative vernalization-related genes that played important roles in the vernalization of faba bean were identified; we also found that the levels of vernalization-responsive transcripts showed significantly higher expression levels in cold-treated buds. The expression of VfSOC1, one of the candidate genes, was sensitive to vernalization. Ectopic expression of VfSOC1 in Arabidopsis brought earlier flowering. In conclusion, the abundant vernalization-related transcripts identified in this study will provide a basis for future researches on the vernalization and faba bean breeding and established a reference full-length transcriptome for future studies on faba bean.

Objective: To delineate the relationship between clinical symptoms and tauopathy of the hippocampal subfields under different amyloid statuses.Methods: One hundred and forty-three subjects were obtained from the ADNI project, including 87 individuals with normal cognition, 46 with mild cognitive impairment, and 10 with Alzheimer’s disease (AD). All subjects underwent the tau PET, amyloid PET, T1W, and high-resolution T2W scans. Clinical symptoms were assessed by the Neuropsychiatric Inventory (NPI) total score and Alzheimer’s Disease Assessment Scale cognition 13 (ADAS-cog-13) total score, comprising memory and executive function scores. The hippocampal subfields including Cornu Ammonis (CA1–3), subiculum (Sub), and dentate gyrus (DG), as well as the adjacent para-hippocampus (PHC) and entorhinal cortex (ERC), were segmented automatically using the Automatic Segmentation of Hippocampal Subfields (ASHS) software. The relationship between tauopathy/volume of the hippocampal subfields and assessment scores was calculated using partial correlation analysis under different amyloid status, by controlling age, gender, education, apolipoprotein E (APOE) allele ɛ4 carrier status, and, time interval between the acquisition time of tau PET and amyloid PET scans.Results: Compared with amyloid negative (A−) group, individuals from amyloid positive (A+) group are more impaired based on the Mini-mental State Examination (MMSE; p = 3.82e-05), memory (p = 6.30e-04), executive function (p = 0.0016), and ADAS-cog-13 scores (p = 5.11e-04). Significant decrease of volume (CA1, DG, and Sub) and increase of tau deposition (CA1, Sub, ERC, and PHC) of the hippocampal subfields of both hemispheres were observed for the A+ group compared to the A- group. Tauopathy of ERC is significantly associated with memory score for the A- group, and the associated regions spread into Sub and PHC for the A+ group. The relationship between the impairment of behavior or executive function and tauopathy of the hippocampal subfield was discovered within the A+ group. Leftward asymmetry was observed with the association between assessment scores and tauopathy of the hippocampal subfield, which is more prominent for the NPI score for the A+ group.Conclusion: The associations of tauopathy/volume of the hippocampal subfields with clinical symptoms provide additional insight into the understanding of local changes of the human HF during the AD continuum and can be used as a reference for future studies.

C3 glomerulopathy (C3GP) is a disease entity caused by abnormality of the complement alternative pathway (AP) and characterized by C3 deposition in glomeruli. Many variations or mutations of complement factors are believed to underlie the susceptibility to C3GP, but there is a lack of experimental evidence. We have recently reported a patient with C3 glomerulonephritis (C3GN) and compound heterozygosity of two novel variations in the complement factor (CFI). Here, we generated a mouse model to mimic the CFI variations for studying pathogenicity of CFI variations in C3GN development. We used the CRISPR/Cas9 system to make mutant mouse lines that carried D288G and P467S mutations in CFI, respectively, and crossed them to generate mice with compound heterozygosity of CFI D288G and P467S. The mice were all normal in either SPF (specific pathogen free) or regular environment. When treated with lipopolysaccharides (LPS), a bacterial endotoxin that mimics infection and sepsis, the mice developed albuminuria, kidney function impairment, and C3 glomerular deposition at levels comparable with the wild-type mice. The mice with other genotypes concerning CFI D288G and P467S were also tested in parallel. Unexpectedly, we found that the D288G homozygotes all developed severe mesangial deposition of C3 in the LPS model, indicating that CFI D288G variation was involved in the C3 deposition, a key feature of C3GN. The mouse lines generated in the present study can be used to further study the role of CFI variations in C3GN development; in addition, they may be used to screen and test infections and environmental factors capable of triggering C3GN.

Background: Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Although various studies have demonstrated the efficacy of tacrolimus combined with corticosteroids for treating IMN, both tacrolimus and corticosteroids have been shown to be diabetogenic, particularly following organ transplantation. Furthermore, the frequency and risk factors for new-onset diabetes mellitus (NODM) in IMN patients treated with tacrolimus plus low-dose corticosteroids remain unclear. Objectives: To evaluate the incidence of NODM in IMN patients undergoing tacrolimus plus low-dose corticosteroid therapy and to confirm the risk factors for NODM development. Methods: This retrospective study recruited 72 eligible patients with biopsy-proven IMN from our center, between September 2013 and June 2018. All subjects were treated with tacrolimus plus low-dose corticosteroids for a minimum of 3 months. The primary outcome was NODM development during the follow-up period. The secondary outcome was complete or partial remission. Patients were divided into 2 groups: patients with NODM (NODM group) and those without NODM (No-NODM group). Demographic and clinical data at baseline and follow-up were assessed. Results: During follow-up, 31 of the 72 patients developed NODM (43.0%). The median time to occurrence was 3 months after treatment initiation. NODM patients were significantly older (median age 59 vs. 40 years) than No-NODM patients. Baseline fasting blood glucose levels were slightly higher in the NODM group; however, the difference was not significant (p = 0.07). Older age was an independent risk factor for NODM (OR 1.73 and 95% CI 1.20–2.47, p = 0.003). Overall kidney remission rates were 80.6%. There was no significant difference in remission rate between groups. There was a significant difference in development of pulmonary infection, which occurred in 7 NODM patients and only in 1 No-NODM patient (p = 0.018). IMN reoccurred in 5 NODM patients but only 1 No-NODM patient. Conclusions: Tacrolimus plus low-dose corticosteroid therapy was an efficient treatment for IMN; however, it was accompanied by increased NODM morbidity, which should be considered serious, due to the increased risk of life-threatening complications. Increasing age was a major risk factor for NODM in IMN patients treated with tacrolimus plus low-dose corticosteroid therapy.