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Abstract. Objectives. This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors. Materials and methods. A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study. To assess the patients, several questionnaires were used. These included the General Situation Questionnaire, General Alienation Scale, Social Impact Scale, Modified Memorial Anxiety Scale for Prostate Cancer, and Perceived Social Support Scale. Pearson correlation analysis was conducted to examine the relationships between variables, whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy. Results. Patients who underwent radical prostatectomy had a mean total score of 44.13 ± 7.24 on the Social Alienation Scale. The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support (r = −0.627, p < 0.05) and positive associations with age, disease stigma, and anxiety (r = 0.325, 0.575, 0.421, all p’s < 0.01) among patients who underwent radical prostatectomy. The findings from multiple linear regression analysis demonstrated that educational level, age, urinary incontinence, disease stigma, anxiety, and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy (p < 0.05). Conclusions. Elderly patients who undergo radical prostatectomy often experience social alienation. This study found that social alienation was associated with factors such as educational level, age, urinary incontinence, social support, anxiety, and disease stigma. Consequently, healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.

AimThis study aims to explore the effectiveness and safety of Ginkgolide® in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) and moderate-to-severe stroke receiving intravenous alteplase thrombolysis (IVT).MethodsGinkgolide with Intravenous Alteplase Thrombolysis in Acute Ischemic Stroke Improving Neurological Function (GIANT) was an open-label, prospective, multicenter, cluster-randomized clinical trial and included AIS patients in 24 centers randomized to the intervention of intravenous Ginkgolide® or control group within the first 24 h after IVT. LVO was defined as any occlusion of the internal carotid artery, M1 or M2 of the middle cerebral artery, A1 or A2 of the anterior cerebral artery, P1 of the posterior cerebral artery, and V4 of the vertebral artery or the basilar artery. Stroke severity was assessed with the National Institutes of Health Stroke Scale (minor ≤5; moderate-to-severe >5). The primary outcome was a good outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days. Secondary outcomes were early neurological improvement (ENI), defined as ≥18% increase in the National Institutes of Health Stroke Scale (NIHSS) score at 7 days compared to baseline and distribution of mRS at 3 months.ResultsA total of 1,113 patients were included, with 268/913 (29.4%) presenting LVO and 508 (45.6%) presenting moderate-to-severe stroke. In patients with LVO, Ginkgolide® usage was independently associated with ENI (P = 0.001) but not with a good outcome (P = 0.154). In the moderate-to-severe stroke subgroup, Ginkgolide® was independently associated with both a good outcome (P = 0.009) and ENI (P = 0.028). Ginkgolide® did not increase the risk of hemorrhagic transformation (all P > 0.05).ConclusionUsing Ginkgolide® within 24-h after intravenous rt-PA is effective and safe in LVO and moderate-to-severe stroke patients.

Structural variations in the duck genome significantly impact the environmental adaptability and phenotypic diversity of duck populations. Characterizing these SVs in local domestic duck breeds from Shandong province offers valuable insights for breed selection and the development of new breeds. This study aimed to profile the genomic SVs in three local duck breeds (Matahu duck, Weishan partridge duck, and Wendeng black duck) and explore their differential distributions. A total of 21,673 SVs were detected using LUMPY (v0.2.13) and DELLY (v1.0.3) software, with 46% located in intergenic regions, 33% in intronic regions, and frameshift deletions being the most prevalent in exonic regions (3%). SVs distribution showed a decreasing trend with shorter chromosome lengths. Population structure analysis revealed distinct genetic profiles, with Matahu and Weishan partridge ducks showing closer affinities and the Wendeng black duck having a more homogeneous genetic background, likely due to geographic isolation. Functional annotation identified genes related to nervous system development, mitosis, spindle assembly, and energy metabolism. Notable genes included PLXNA4, NRP2, SEMA3A, PTEN, MYBL2, ADK, and COX4I1. Additionally, genes such as PRKG1, GABRA2, and FSHR were linked to energy metabolism and reproductive activity. The study provides a comprehensive analysis of SVs, revealing significant genetic differentiation and identifying genes associated with economically important traits, offering valuable resources for the genetic improvement and breeding of local duck breeds.

Abstract Ca2+ signaling is essential for oligodendrocyte (OL) development and myelin formation. Inositol 1,4,5‐trisphosphate receptor type 2 (ITPR2) is an endoplasmic reticulum calcium channel and shows stage‐dependent high levels in postmitotic oligodendrocyte precursor cells (OPCs). The role and potential mechanism of ITPR2 in OLs remain unclear. In this study, it is revealed that loss of Itpr2 in OLs disturbs Ca2+ homeostasis and inhibits myelination in adolescent mice. Animals with OL‐specific deletion of Itpr2 exhibit anxiety/depressive‐like behaviors and manifest with interrupted OPC proliferation, leading to fewer mature OLs in the brain. Detailed transcriptome profiling and signal pathway analysis suggest that MAPK/ERK‐CDK6/cyclin D1 axis underlies the interfered cell cycle progression in Itpr2 ablated OPCs. Besides, blocking MAPK/ERK pathway significantly improves the delayed OPC differentiation and myelination in Itpr2 mutant. Notably, the resting [Ca2+]i is increased in Itpr2 ablated OPCs, with the elevation of several plasma calcium channels. Antagonists against these plasma calcium channels can normalize the resting [Ca2+]i level and enhance lineage progression in Itpr2‐ablated OPCs. Together, the findings reveal novel insights for calcium homeostasis in manipulating developmental transition from OPCs to pre‐OLs; additionally, the involvement of OLs‐originated ITPR2 in depressive behaviors provides new therapeutic strategies to alleviate myelin‐associated psychiatric disorders.

Abstract Introduction This study aimed to investigate the association between atrial fibrillation (AF), particularly newly diagnosed AF, and remote intracerebral hemorrhage (rICH) in patients with ischemic stroke who were treated with intravenous thrombolysis (IVT). Methods This observational study was conducted on patients with ischemic stroke who received IVT with recombinant tissue-type plasminogen activator. The data were taken from a multicenter prospective registry of a Chinese population. rICH was defined as any extraischemic hemorrhage detected on computerized tomography (CT) 24 h after intravenous thrombolysis. We collected and compared the demographic data and clinical characteristics of all the patients with rICH to those of patients without any type of hemorrhagic transformation. The association between AF and rICH was analyzed using univariate analysis and binary logistic regression. Results A total of 20,697 patients were included in the study, with 1566 (7.6%) experiencing intracerebral hemorrhage (ICH), 586 (2.8%) experiencing rICH, and 19,131 (92.4%) not experiencing any form of hemorrhagic transformation. Univariate analysis revealed significant differences in age, pre-thrombolysis systolic blood pressure, baseline National Institute of Health Stroke Scale score, previously known AF, newly diagnosed AF, coronary heart disease, congestive heart failure, hyperhomocysteinemia, and history of thrombolysis between the rICH and control groups (P

Plumage color is a key trait for identifying waterfowl breeds with significant economic importance. A white-feathered group has recently emerged within the native Matahu duck population, presenting an opportunity for breeding new lines. However, the genetic basis for this plumage variation is still unknown, necessitating further research. This study aims to identify the genetic mechanisms underlying the emergence of white-feathered individuals in the Matahu duck population through combined genome and transcriptome analysis, providing insights for selective breeding and the development of new white-feathered lines. In this study, a total of 1344 selected genes and 1406 significantly differentially expressed genes were identified through selection signal analysis and transcriptomic analysis, respectively. The functional enrichment of these genes revealed several key signaling pathways, including those related to cGMP-PKG, cAMP, PI3K-Akt, and MAPK. Furthermore, important candidate genes involved in melanin biosynthesis, such as MITF, MC1R, TYR, TYRP1, and ABCB6, were identified. Notably, 107 genes were detected by both methods, and, among these, DGKI, GPRC5B, HMX1, STS, ADGRA1, PRKAR2B, and HOXB9 are suggested to play a role in melanin formation and potentially influence plumage traits. Through the integrative approach combining genomic selection signals and transcriptomic analyses, we identified several candidate genes directly associated with plumage color, including MITF, TYR, TYRP1, and MC1R, along with multiple signaling pathways linked to melanin formation. We hypothesize that the expression of DGKI, GPRC5B, HMX1, STS, ADGRA1, PRKAR2B, and HOXB9, detected by both methods, may be closely related to the regulation of plumage color traits. These findings provide a foundational basis for further research aimed at elucidating the genetic mechanisms governing plumage color variation in ducks.

Abstract Folate, a pteroylglutamic acid derivative, participates in fundamental cellular metabolism. Homocysteine, an amino acid, serves as an intermediate of the methionine cycle and can be converted back to methionine. Hyperhomocysteinemia is a recognized risk factor for atherosclerotic and cardiovascular diseases. In recent decades, elevated plasma homocysteine levels and low folate status have been observed in many patients with retinal vascular diseases, such as retinal vascular occlusions, diabetic retinopathy, and age-related degeneration. Homocysteine-induced toxicity toward vascular endothelial cells might participate in the formation of retinal vascular diseases. Folate is an important dietary determinant of homocysteine. Folate deficiency is the most common cause of hyperhomocysteinemia. Folate supplementation can eliminate excess homocysteine in plasma. In in vitro experiments, folic acid had a protective effect on vascular endothelial cells against high glucose. Many studies have explored the relationship between folate and various retinal vascular diseases. This review summarizes the most important findings that lead to the conclusion that folic acid supplementation might be a protective treatment in patients with retinal vascular diseases with high homocysteine or glucose status. More research is still needed to validate the effect of folate and its supplementation in retinal vascular diseases.

Background: The Nd:YAG laser is widely used in various aspects of work and life. Currently, it has become a popular cosmetic technique in beauty salons. The laser can be dangerous when it flashes into people's eyes. Case presentation: A 34-year-old female sustained a 1064-nm Q-switched Nd:YAG laser injury to her left eye. One month after the injury, she presented to our clinic with best-corrected visual acuity (BCVA) of 20/250 and a full-thickness macular hole on the optical coherence tomography (OCT). The patient received pars plana vitrectomy, internal limiting membrane peeling and sterile air injection 3 months after the injury. OCT showed closure of the hole 9 days postoperatively. After a 3-month follow-up, her BCVA improved to 20/100. Conclusions: This case report comprehensively introduces the whole progression of a cosmetic laser-induced macular hole from formation to recovery. Due to the potential threats of the laser and its irreversible damage to the retina and choroid, sufficient education should be given before performing any laser devices, especially those without professional knowledge.

Terson syndrome refers to intraocular haemorrhage that occurs due to subarachnoid bleeding associated with an acute increase in intracranial pressure. No previous study has reported a delayed macular hole (MH) secondary to Terson syndrome. A 17-year-old boy visited our department and presented with vitreous bleeding and a history of subarachnoid haemorrhage. Sub-internal limiting membrane (ILM) haemorrhage with ILM detachment and intraretinal haemorrhage were detected during pars plana vitrectomy. Additionally, a delayed MH was detected 1 week after the surgery. There was no sign of MH closure during a 2-month follow-up. Subsequently, an MH massage was performed to close the MH. Our findings suggest that a delayed MH can occur secondary to Terson syndrome. Elevated hydrodynamic pressure and hydrostatic pressure, which are caused by sub-ILM and intraretinal haemorrhages of the fovea, contribute to the formation of an MH. Additionally, ILM peeling may cause damage to the macula and facilitate the formation of MHs. Although the MH may close by itself, early surgical intervention is recommended when there is no sign that the MH will close spontaneously because a prolonged MH can lead to retinal damage.

BackgroundHeatstroke is a life-threatening disease clinically characterized by central nervous system dysfunction, multiorgan failure, and extreme hyperthermia. There are no reports about eye involvement in heat stroke. Here, we report a rare case of multilayered retinal hemorrhages in a patient with heatstroke.Case presentationA 55-year-old male with a one-month history of blurry vision in both eyes presented at our department after suffering from heatstroke. His visual acuity was 5/20 OD and 10/20 OS. Fundus examination revealed retinal hemorrhages in both eyes. Fundus autofluorescence images and near-infrared reflectance images revealed well-defined retinal lesions. Optical coherence tomography helped to accurately locate the different layers of the lesions, including the nerve fiber layer, sub-inner limiting membrane, outer plexiform layer, ellipsoid zone and Henle fiber layer hemorrhages. We followed up with the patient for 8 months. At the last follow-up, his visual acuity was 20/20 in both eyes, and fundus examination showed that retinal hemorrhages were almost completely absorbed.ConclusionTo our knowledge, this is the first report on multilayered retinal hemorrhages secondary to heat stroke. Intraretinal and preretinal hemorrhages can gradually resolve, and the patient’s vision will improve with the absorption of the retinal hemorrhages. Multimodal imaging may help to reveal additional details about retinal lesions and monitor the course of the disease.

Purpose. To evaluate the efficacy of spironolactone in the treatment of chronic central serous chorioretinopathy (CSC) and identify imaging characteristics that can predict the benefit of spironolactone treatment. Methods. Patients with chronic CSC were treated with spironolactone (20 mg/tid) and followed for 6 months. The primary outcome measure was complete resolution of the subretinal fluid (SRF), and the best-corrected visual acuity (BCVA), the SRF area, the central macular thickness (CMT), the subfoveal choroidal thickness (SFCT), and the density of the choriocapillaris vessel and adverse events were secondary outcome measures. Patients who presented complete resolution of SRF were included in the responder group and the other patients who had moderate or no resolution were included in the nonresponder group. Imaging characteristic comparisons between the responder and nonresponder groups were performed with regression analyses to identify factors that are predictive of a good response to treatment. Results. Forty-two eyes of 42 patients with a mean age of 46.06 ± 6.66 years were included. A total of 57.1% of the patients achieved a complete resolution of SRF. The mean SRF area, CMT, and SFCT decreased significantly (all P0.05). The vascular density of the choriocapillaris of the fellow eyes did not vary significantly during treatment. Logistic regression analysis revealed that SFCT (P=0.002) and the intact ellipsoid zone (P=0.001) were correlated with disease resolution. A relatively higher baseline SFCT was a predictive factor associated with a good response to treatment according to multivariate analysis. Conclusions. This study suggested that oral spironolactone could be an effective and safe therapy for chronic CSC patients. Eyes with a higher baseline SFCT and intact ellipsoid zone could have a good response. These parameters are an important prognostic marker.

Summary: Background: The aim of the present study was to estimate the incidence, years lived with disability (YLDs), and cause of eye injury at global, regional, and national levels by age and sex based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: This is a retrospective demographic analysis based on aggregated data. GBD 2019 included the burden of eye injury worldwide and its temporal and spatial characteristics in the past three decades. The Bayesian meta-regression tool and DisMod-MR 2.1 were used to analyse the estimates based on a linear regression mode of the age-standardised rates (ASR). Average annual percent change (AAPC) was calculated to represent the temporal trends of the ASR. Findings: Globally, there were 59,933.29 thousand (95% uncertainty interval [UI]: 45,772.34–77,084.03) incident cases and 438.4 thousand (95% UI: 132.44–898.38) YLDs of eye injury in 2019. Both the ASR of incidence and YLDs decreased from 1990 to 2019, with AAPC −0.46 (95% confidence interval [CI]: −0.52 to −0.39) and −0.45 (95% CI: −0.52 to −0.39), respectively. Males had higher rates of incidence and YLDs in all age groups. Young and middle-aged adults had higher disease burdens. Regionally, Australasia had the highest ASR of YLDs to be 9.51 (95% UI: 3.00–19.58) per 100,000. Nationally, New Zealand had the highest burden of eye injury to be 11.33 (95% UI: 3.57–23.10) per 100,000. Foreign bodies, exposure to mechanical forces, and falls were the main causes of global eye injury burden in 2019, and there was an increased worldwide burden due to road injuries and executions and police conflict compared with 1990. Interpretation: Our findings suggest that the incidence and burden of eye injury have decreased over the last 30 years, while the absolute number of eye injuries has substantially increased, representing a major public health concern. Males and young adults were affected to a greater degree than females and elder individuals. More attention should be paid to road injuries and executions and police conflict in order to prevent eye injury. Funding: Guangdong Provincial People's Hospital (GDPH) Supporting Fund for Talent Program (KY0120220263).

Abstract Aiming at solving the problem of the deterioration of the voltage quality of the distribution network caused by the fast charging load of large‐scale electric vehicles, a fast charging load guidance strategy based on adjustable tiered charging service fees is proposed to guide users to adopt the charging location decision with the least comprehensive charging cost, and then balance the charging load distribution of each charging station to improve the voltage quality of the distribution network. Firstly, considering the constraints of the regional road network and distribution network, a fast charging load forecasting model based on the trip chain theory and Monte Carlo method is established; secondly, a regional tiered charging service fee adjustment model is constructed with the optimization goal of minimizing the absolute sum of node voltage deviations of distribution network; then, the user charging location weighted decision model with the least comprehensive cost of charging service fee, trip time and road power consumption is constructed. Finally, from the calculation, it can be seen that the adjustable tiered charging service fees can more effectively guide users to change the charging location, thus improving voltage quality and reducing pressure on grid capacity.

BackgroundNumerous studies have demonstrated that retinal chronic inflammation plays a critical role in the pathogenesis of diabetic macular edema (DME). However, studies about the association between peripheral complete blood count, an inexpensive and easily measurable laboratory index, and DME are limited.Research design and methodsThe current study was a hospital-based, cross-sectional study. The participants were inpatients with type 2 diabetes who underwent vitrectomy for PDR, and the contralateral eyes in these PDR patients meeting the criteria were included in the study. Central macular thickness (CMT) was measured automatically and the DME was characterized as CMT ≥ 300 μm.ResultsA total of 239 PDR participants were enrolled. The average age was 55.46 ± 10.08 years old, and the average CMT was 284.23 ± 122.09 μm. In the fully adjusted model, for CMT, the results revealed a significantly negative association between CMT and both white blood cell (WBC) count and neutrophil count (β = −11.95, 95% CI: −22.08, −1.82; p = 0.0218; β = −14.96, 95% CI: −28.02, −1.90; p = 0.0259, respectively); for DME, the results showed an inverse association between DME and WBC count, monocyte count, and eosinophil count (OR = 0.75, 95% CI: 0.59, 0.95; p = 0.0153; OR = 0.07, 95% CI: 0.00, 0.92; p = 0.0431; OR = 0.03, 95% CI: 0.00, 0.88; p = 0.0420, respectively).ConclusionsIn conclusion, our results suggest that WBC and its subtypes in circulation may play an important role in the pathogenesis of DME in PDR patients.

Accurate diabetic retinopathy (DR) grading is crucial for making the proper treatment plan to reduce the damage caused by vision loss. This task is challenging due to the fact that the DR related lesions are often small and subtle in visual differences and intra-class variations. Moreover, relationships between the lesions and the DR levels are complicated. Although many deep learning (DL) DR grading systems have been developed with some success, there are still rooms for grading accuracy improvement. A common issue is that not much medical knowledge was used in these DL DR grading systems. As a result, the grading results are not properly interpreted by ophthalmologists, thus hinder the potential for practical applications. This paper proposes a novel fine-grained attention & knowledge-based collaborative network (FA+KC-Net) to address this concern. The fine-grained attention network dynamically divides the extracted feature maps into smaller patches and effectively captures small image features that are meaningful in the sense of its training from large amount of retinopathy fundus images. The knowledge-based collaborative network extracts a-priori medical knowledge features, i.e., lesions such as the microaneurysms (MAs), soft exudates (SEs), hard exudates (EXs), and hemorrhages (HEs). Finally, decision rules are developed to fuse the DR grading results from the fine-grained network and the knowledge-based collaborative network to make the final grading. Extensive experiments are carried out on four widely-used datasets, the DDR, Messidor, APTOS, and EyePACS to evaluate the efficacy of our method and compare with other state-of-the-art (SOTA) DL models. Simulation results show that proposed FA+KC-Net is accurate and stable, achieves the best performances on the DDR, Messidor, and APTOS datasets.

Age-related macular degeneration (AMD) is the predominant threat to human vision and ultimately results in blindness. With the increase in the aging population, it has become a more crucial issue to human health. AMD is a multifactorial disease with the unique feature of uncontrollable angiogenesis during initiation and progression. Although increasing evidence indicates that AMD is largely hereditary, the predominant efficient treatment is antiangiogenesis, which mainly involves VEGF and HIF-α as therapeutic targets. The repeated administration of this treatment over the long term, generally through intravitreal injection, has called for the introduction of long-term drug delivery systems, which are expected to be achieved by biomaterials. However, the clinical results of the port delivery system indicate that the optimization of medical devices toward prolonging the activities of therapeutic biologics in AMD therapy seems more promising. These results indicate that we should rethink the possibility and potential of biomaterials as drug delivery systems in achieving long-term, sustained inhibition of angiogenesis in AMD therapy. In this review, the etiology, categorization, risk factors, pathogenesis, and current clinical treatments of AMD are briefly introduced. Next, the development status of long-term drug delivery systems is discussed, and the drawbacks and shortages of these systems are emphasized. By comprehensively considering the pathological aspect and the recent application of drug delivery systems in AMD therapy, we hope to find a better solution for the further development of long-term therapeutic strategies for AMD.

Mangrove afforestation is considered an important measure in the “natural-based solution” for mitigating climate warming through sequestering massive carbon (C) into vegetation biomass, yet how the planted mangrove species facilitate soil C sequestration remains unclear. Here, we investigated the stock, source, and fraction of soil organic carbon (SOC) over 1 m depth after 20-year afforestation of five mangrove pure plantations (Acrostichum aureum, Acanthus ilicifolius, Aegiceras corniculatum, Kandelia obovate, and Excoecaria agallocha) on Qi’ao Island, South China. The results showed that SOC stocks did not significantly differ among the five plantations, with an average value of 16.7 kg C m−2. Based on the two-end-member mixing model with plant–soil C stable isotope signatures, the autochthonous (mangrove-derived) C source accounted for 20.2–34.1% of SOC but varied significantly among the plantations. The SOC stock in particulate fraction (1.2–2.0 g C kg−1) and mineral-associated fraction (14.3–16.0 g C kg−1) also significantly differed among the plantations. The similar SOC stock but different source contributions and C fractions among the plantations observed here may have important implications for mangrove afforestation to optimize stand structure and maximize C sequestration.

Abstract This study proposes a TOPSIS‐based method for assessing the ability of distribution networks to accept electric vehicles. This method establishes an assessment index system in terms of the rationality, safety, and economy of the distribution network operation, and assesses the capacity of the distribution network in all aspects. Firstly, a fuzzy theory‐based model of users' charging psychology under the influence of time‐of‐use electricity price was constructed, and the spatio‐temporal distribution of EV charging loads in the target area was predicted using travel chain theory and Monte Carlo methods. Secondly, considering the rationality, safety and economy of the distribution network operation, a comprehensive evaluation index system for acceptability has been constructed. Then, a comprehensive weighting method for evaluation indexes based on AHP and entropy weight method is proposed, and the improved TOPSIS is used to evaluate the acceptance capacity of the distribution network when EV charging loads are connected in different ways. Finally, a typical IEEE33 distribution network is used to simulate the time and space distribution of the charging load, and taking the charging load access schemes proposed in this paper to verify the effectiveness of the evaluation method.

Although gene mutations and aberrant chromosomes are associated with the pathogenesis and prognosis of uveal melanoma (UM), potential therapeutic targets still need to be explored. We aim to determine the predictive value and potential therapeutic target of EZH2 in uveal melanoma. Eighty-five uveal melanoma samples were recruited in our study, including 19 metastatic and 66 nonmetastatic samples. qRT-PCR, immunohistochemistry staining, and western blotting were applied to detect the expression of EZH2 and H3K27me3. We found that EZH2 (41/85, 48.24%) and H3K27me3 (49/85, 57.65%) were overexpressed in uveal melanoma. The expression of EZH2 was not significantly associated with metastasis. High H3K27me3 expression was correlated with poor patient prognosis. UNC 1999, an EZH2 inhibitor, can downregulate H3K27me3 expression and has the most potency to inhibit OMM1 cell growth by the cell cycle and ferroptosis pathway. These results indicate that H3K27me3 can be a biomarker predicting a poor prognosis of UM. EZH2 is the potential therapeutic target for UM.

The Pentose Phosphate Pathway (PPP), a metabolic offshoot of the glycolytic pathway, provides protective metabolites and molecules essential for cell redox balance and survival. Transketolase (TKT) is the critical enzyme that controls the extent of “traffic flow” through the PPP. Here, we explored the role of TKT in maintaining the health of the human retina. We found that Müller cells were the primary retinal cell type expressing TKT in the human retina. We further explored the role of TKT in human Müller cells by knocking down its expression in primary cultured Müller cells (huPMCs), isolated from the human retina (11 human donors in total), under light-induced oxidative stress. TKT knockdown and light stress reduced TKT enzymatic activities and the overall metabolic activities of huPMCs with no detectable cell death. TKT knockdown restrained the PPP traffic flow, reduced the expression of NAD(P)H Quinone Dehydrogenase 1 (NQO1), impaired the antioxidative response of NRF2 to light stress and aggravated the endoplasmic reticulum (ER) stress. TKT knockdown also inhibited overall glucose intake, reduced expression of Dihydrolipoamide dehydrogenase (DLD) and impaired the energy supply of the huPMCs. In summary, Müller cell-mediated TKT activity plays a critical protective role in the stressed retina. Knockdown of TKT disrupted the PPP and impaired overall glucose utilisation by huPMCs and rendered huPMCs more vulnerable to light stress by impairing energy supply and antioxidative NRF2 responses.

Abstract Objective Diabetic retinopathy, a common complication of diabetes mellitus and a major cause of blindness. circRNAs spongs target miRNA and thus influencing mRNA expression in DR. We investigated the mechanism of circ_001209 in regulating diabetic retinal vascular dysfunction. Methods QRT-PCR analysis was performed to detect the expression of miR-15b-5p, COL12A1 and circ_001209 in human retinal vascular endothelial cells (HRVECs) under high glucose conditions. Western blot assay, wound healing assay, transwell assay and tube formation were used to explore the roles of circ_001209/miR-15b-5p/COL12A1 in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, RNA-FISH, and overexpression assays were performed to reveal the mechanisms of the circ_001209/miR-15b-5p/COL12A1 interaction. TUNEL staining and H&E staining were used to evaluate the pathological changes in streptozotocin (STZ)-induced DR in rats. Results Downregulation of miR-15b-5p under HG conditions promoted proliferation, migration, and tube formation of HRVECs. QRT-PCR and western blot results revealed that miR-15b-5p affected the HRVECs function through targeting COL12A1. Under HG conditions, circ_001209, which acts as a sponge of miR-15b-5p, is upregulated. Besides, overexpression of circ_001209 can affect HRVEC function and aggravate retinal injury in diabetic rats. Conclusion Upregulation of circ_001209 contributes to vascular dysfunction in diabetic retinas through regulating miR-15b-5p and COL12A1, providing a potential treatment strategy for diabetic retinopathy.

BackgroundThis study qualitatively and quantitatively compared imaging characteristics between neovascular and atrophic pachychoroid spectrum disease (PSD) by optical coherence tomography (OCT), and OCT angiography (OCTA).MethodsThe subtypes of PSD were identified by multi-modality imaging approaches. Subfoveal choroidal thickness (SFCT), choroidal vascular index (CVI), and vascular density of choroidal neovascularization (CNV) were measured.ResultsThe CVI and SFCT of 174 PSD eyes were 67.6% ± 5.48% and 362.2 ± 131.88 μm, respectively. After adjustment for age, linear regression indicated that SFCT was positively associated with CVI (p < 0.001), and patched hyper-reflective lesions in choriocapillaris layers (p = 0.009). Compared with neovascular PSD eyes, atrophic PSD eyes had similar patient age (57.1 ± 16.72 years, p = 0.639), SFCT (332.0 ± 111.00 μm, p = 0.51), and CVI (67.6% ± 3.94%, p = 0.527). There were no differences between polypoidal choroidal vasculopathy (PCV) eyes with aneurysmal polypoidal lesions and PCV eyes with tangled polypoidal lesions in terms of age, CVI, SFCT, vascular density, or the occurrence of double layer signs (DLSs, all p > 0.05). Logistic regression indicated that age (p = 0.003), SFCT (p = 0.003), patched hyper-reflective lesions in choriocapillaris layers (p = 0.009), and DLSs (p < 0.001) were predictive factors for CNV progression in PSD eyes (all p < 0.05).ConclusionsOur study highlighted the similarities in SFCT and CVI between neovascular and atrophic PSD, both of which were late stage lesions. Besides, age, SFCT, patched hyper-reflective lesions in choriocapillaris layers, and DLSs were risk factors for CNV in PSD. Our results showed that atrophic PSD is an important change in the late stage of PSD disease, which is helpful for in-depth understanding of the pathological mechanism of PSD and corresponding intervention.

PurposeTo study the association between different hypoglycemic regimens and postoperative diabetic macular edema (DME).MethodsA secondary analysis based on a retrospective cohort study.ResultsIn this secondary analysis, 124 eyes from patients with proliferative diabetic retinopathy (PDR) who underwent pars plana vitrectomy (PPV) between January 2008 and September 2012 were included. We found that compared with oral hypoglycemic medication, oral hypoglycemic medication plus insulin treatment revealed an insignificant relationship with postoperative DME (odds ratio [OR]=0.8, 95% confidence interval [CI]: 0.12-5.21, P=0.8167), only insulin treatment revealed a significant association with postoperative DME (OR=0.10, 95% CI: 0.01-0.84, P=0.0337) after adjusted age, sex. After adjusted age, sex, diabetes mellitus (DM) duration, glycosylated hemoglobin (HbA1c), the results did not have obvious changes (OR=0.61, 95% CI: 0.09-4.26, P=0.6187; OR=0.07, 95% CI: 0.01-0.65, P=0.0197). Furthermore, after adjusted age, sex, DM duration, HbA1c, hypertension, intraoperative retinal photocoagulation, vitreous hemorrhage, macular detachment, fibrovascular membrane, intraocular lens implantation and microincision vitrectomy surgery, the results were consistent (OR=0.66, 95% CI: 0.05-9.49, P=0.7621; OR=0.06, 95% CI: 0.00-0.81, P=0.0342). The same trend was observed in these adjusted models as well (p for trend was 0.0254, 0.0141, and 0.0311, respectively).ConclusionIn conclusion, our results of the secondary analysis should be interpreted as a significant association between insulin treatment and reduced risks of postoperative DME in Japanese PDR patients with PPV surgery, compared with oral medications. Well glycemic control with longstanding insulin therapy may be beneficial to reduce the risks of postoperative DME in PDR patients. Our investigation calls for large-scale and long-term prospective clinical studies for a full evaluation of the exact role of insulin in the progression of postoperative DME.

Diabetic retinopathy (DR) is one of the primary causes of visual impairment in the working-age population. Retinal cell death is recognized as a prominent feature in the pathological changes of DR. Several types of cell death occurrence have been confirmed in DR, which might be the underlying mechanisms of retinal cell loss. Regulated cell death (RCD) originates from too intense or prolonged perturbations of the intracellular or extracellular microenvironment for adaptative responses to cope with stress and restore cellular homeostasis. Pyroptosis, necroptosis, and ferroptosis represent the novel discovered RCD forms, which contribute to retinal cell death in the pathogenesis of DR. This evidence provides new therapeutic targets for DR. In this review, we summarize the mechanisms of three types of RCD and analyse recent advances on the association between novel RCD and DR, aiming to provide new insights into the underlying pathogenic mechanisms and propose a potential new strategy for DR therapy.

Background and PurposeCerebral venous systems play a key role in regulating stroke outcomes. We aimed to elucidate the effect of the transverse sinus (TS) filling patterns on edema expansion and neurological outcomes in patients with acute large artery occlusion (LAO).Materials and MethodsWe recruited consecutive patients with acute M1 middle cerebral artery and/or internal carotid artery occlusion who underwent pretreatment computed tomographic perfusion (CTP). On the reconstructed 4-dimensional computed tomographic angiography derived from CTP, the filling defect of the ipsilateral transverse sinus (FDITS) was defined as the length of contrast filling defect occupying at least half of the ipsilateral TS. An unfavorable outcome was defined as having a modified Rankin Scale (mRS) score of 3–6 at 3 months.ResultsA total of 318 patients were enrolled in the final analysis and 70 (22.0%) patients had baseline FDITS. The presence of FDITS was associated with the baseline NIHSS (odds ratio [OR] 1.119; 95% CI, 1.051–1.192; p < 0.001) and poor arterial collaterals (OR 3.665; 95% CI 1.730–7.766; p = 0.001). In addition, FDITS was associated with 24-h brain edema expansion (OR 7.188; 95% CI, 3.095–16.696; p < 0.001) and 3-month unfavorable outcome (OR 8.143; 95% CI 2.547–26.041; p < 0.001) independent of arterial collateral status. In the subgroup analysis of patients with FDITS who received reperfusion therapy, no significant difference was found in the rate of edema expansion and unfavorable outcome between non-reperfusion and reperfusion subgroups (both p > 0.05).ConclusionFilling defect of the ipsilateral transverse sinus was associated with edema expansion and an unfavorable outcome irrespective of the baseline arterial collateral status in patients with acute LAO, indicating that FDITS may be an important stroke-related prognostic imaging marker.

Retinal inflammation underlies multiple prevalent retinal diseases. While microglia are one of the most studied cell types regarding retinal inflammation, growing evidence shows that Müller glia play critical roles in the regulation of retinal inflammation. Müller glia express various receptors for cytokines and release cytokines to regulate inflammation. Müller glia are part of the blood-retinal barrier and interact with microglia in the inflammatory responses. The unique metabolic features of Müller glia in the retina makes them vital for retinal homeostasis maintenance, regulating retinal inflammation by lipid metabolism, purine metabolism, iron metabolism, trophic factors, and antioxidants. miRNAs in Müller glia regulate inflammatory responses via different mechanisms and potentially regulate retinal regeneration. Novel therapies are explored targeting Müller glia for inflammatory retinal diseases treatment. Here we review new findings regarding the roles of Müller glia in retinal inflammation and discuss the related novel therapies for retinal diseases.

Purpose: Choroidal neovascularization (CNV) is the main pathogenic process and a leading cause of severe vision loss in neovascular age-related macular degeneration (AMD). We investigated the antiangiogenic efficacy of dihydroartemisinin (DHA) in an experimental laser-induced CNV mouse model.Methods: After fluorescein angiography confirmed that CNV was induced by laser photocoagulation in C57BL/6J mice, DHA or vehicle was given by intragastric administration once a day. On day 6 and day 12, fluorescein angiography, optic coherence tomography, and flat-mounting analysis were performed to grade CNV leakage, measure CNV thickness and evaluate CNV areas, respectively. Immunofluorescence staining and Western blot analysis were performed to evaluate the expression of NF-κB, VEGF, and VEGFR2. To confirm the safety of intragastric DHA application, changes in retinal morphology and neural cell apoptosis were tested by histopathological examination and TUNEL assay, and retinal function was determined by electroretinogram (ERG).Results: Intragastric administration of DHA significantly suppressed CNV leakage and CNV formation in both thickness and area. Immunofluorescence showed that DHA suppressed VEGFR2 and NF-κB p65 expression in laser-induced lesions. Compared to the normal group, the protein expression of VEGF, VGFER2, NF-κB p65, and NF-κB1 p50 increased significantly in the vehicle group after laser photocoagulation, while it was profoundly inhibited by DHA treatment. In addition, histopathological examination, TUNEL analysis, and ERG test showed no obvious evidence of retinal toxicity caused by DHA.Conclusion: Systemic administration of DHA can effectively inhibit laser-induced CNV formation in mice, which might be due to the suppression of the classic NF-κB signaling pathway and downregulation of VEGFR2 and VEGF expression. The current results suggest that DHA could be a natural potential alternative therapeutic strategy for neovascular AMD.

Volatile organic compounds (VOCs) emitted from building and vehicle cabin materials seriously affect indoor and in-cabin air quality, as well as human health. Previous studies revealed that some VOCs from building materials could react with ozone to affect the concentration levels of the indoor environment, but seldom refers to vehicle cabin materials. In this study, we performed experimental investigation for two kinds of vehicle cabin materials (car carpet, sealing strip) and one furniture material (medium-density fiberboard) by conducting small-scale chamber tests under two different conditions, with ozone (about 110 μg/m3) and without ozone (about 10 μg/m3), to explore the effect of in-cabin chemistry on VOC emissions. We observed the VOC concentration changes in the two scenarios and found that ozone had a significant impact on the concentrations of aldehydes and ketones while having little impact on the concentrations of benzene series. We introduced a gain ratio to quantitatively reflect the concentration changes in the presence of ozone. The gain ratio for aldehydes and ketones is greater than one, while that for the benzene series is basically around one with a small fluctuation range. This study demonstrates that ozone can react with VOCs containing unsaturated carbon–carbon bonds or carbon–oxygen bonds emitted from varied materials to produce aldehydes and ketones, which will further reduce indoor and in-cabin air quality.

Background: Retinopathy of prematurity (ROP) is a major cause of childhood blindness. Antenatal corticosteroids (ACS) exposure is known to ameliorate the risk of and mortality of neonatal morbidities. However, the effect of ACS on ROP development is currently unknown. We conducted a meta-analysis with up-to-date evidence to assess the association between ACS exposure and the development of ROP in at-risk preterm infants.Methods: PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were systematically searched from inception to May 2021, supplemented with manual search from reference lists. Studies with a control group reporting ROP rate in ACS-exposed infants were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated utilizing a random-effects model. The Newcastle-Ottawa Scale was used for assessment of risk of bias in the included studies. Meta-regressions were performed to explore the predictive role of confounders for between-study variance.Results: A total of 63 studies, involving 196,264 infants, were included. Meta-analysis showed ACS exposure was not associated with ROP occurrence (uOR 0.92, 95% CI 0.80–1.07; aOR 0.87, 95% CI 0.7–1.08). Results from extremely immature subgroups revealed significant reduced risks of ROP occurrence in ACS-exposed infants. ACS exposure was associated with significantly lower odds of ROP progression in adjusted analysis (aOR 0.48, 95% CI 0.26–0.89) instead of unadjusted analysis (uOR 0.86, 95% CI 0.68–1.08). Meta-regression showed birth weight and patent ductus arteriosus of the cohort were associated with ROP occurrence, sample size and study design strongly associated with ROP progression in ACS-exposed infants.Conclusion: ACS treatment may decrease, but not prevent, the severity of ROP. Findings from severe ROP should be interpreted with caution owing to limited studies and the possibility of false-positive results. Considering the particular benefits in extremely immature infants, we recommend routine usage of ACS in mothers with threatened delivery to this particular birth cohort to prevent ROP occurrence. Future studies adjusting for major confounders are warranted to mitigate risk of bias in such observational evidence.

BackgroundTakayasu’s arteritis (TA) is a rare, chronic granulomatous large-vessel vasculitis that can lead to ocular ischemia. Ocular outcomes after therapeutic management in TA remain largely unknown. We herein conduct a case-based systematic review to address the current treatment options in this particular cohort.MethodsPubMed, Medline, and EMBASE databases were searched pertaining to ocular outcomes after systemic treatment in TA. Studies reporting ocular examinations before and after treatment in TA patients with ocular ischemia were included. Clinical characteristics, therapies, ocular outcomes, and complications were recorded.ResultsA 29-year-old woman with newly diagnosed TA showed dramatic regression of Takayasu’s retinopathy (TR) following balloon angioplasty. Optical coherence tomography angiography (OCTA) was used as a novel strategy for subsequent follow-up. A total of 117 eyes of 66 patients with a median age of 27 years were included for systematic review. TR was the most common ocular manifestation. Oral steroids were prescribed in nearly all patients (n = 65), followed by the use of methotrexate and antiplatelet therapy. Of the patients, 65.8% and 34.2% underwent open surgery and endovascular procedure, respectively. The median follow-up period was 12 weeks (interquartile range 8–33.5). Surgical therapy showed better ocular improvement (including visual and imaging responses) in both acute and chronic vision loss, along with fewer complications than medical therapy alone. In the surgical group, the visual prognosis was significantly better in patients with initial visual acuity better than 20/200 (p = 0.03) and those who underwent surgery before stage III TR (p = 0.01). Ocular outcomes were equivalent in the two surgical approaches.ConclusionClinicians should be familiar with ophthalmic manifestations of this potentially treatable complication in TA. Compared with medical therapy alone, surgical intervention might be a better choice for both acute and chronic vision loss. Surgery is best recommended before the onset of irreversible ischemia to the globe. A combined regimen (oral steroids, immunosuppressants, and antiplatelet drugs) might be effective for those with surgical contradictions or reluctance to an invasive procedure. Physicians should be aware of the importance of ocular examinations, including OCTA, during the diagnosis and follow-up in TA.

Introduction China has the largest number of adults with diabetes aged 20–79 years (116.4 million) in 2019. Due to the socioeconomic condition or a lack of awareness of diabetic complications, many adults with diabetes have proliferative diabetic retinopathy (PDR) or renal function impairment at their first visit to the clinic for a sudden loss of vision, and pars plana vitrectomy (PPV) is required for their treatment. Risk factors for the outcomes and complications of PPV surgery in PDR patients have been widely explored in many epidemiological studies and clinical trials. However, few prospective studies have analysed the association between renal function and surgical outcomes in PDR.Methods and analysis This is a single-centre, prospective cohort study of PDR patients with type 2 diabetes mellitus who have definite indications for PPV surgery with or without renal function impairment. We will consecutively enrol PDR patients who meet the inclusion and exclusion criteria from November 2020 to December 2023. Each participant will be followed up for at least 6 months after surgery. Clinical data from medical records and vitreous fluid will be collected.Demographic characteristics and study outcomes will be summarised using descriptive statistics. The variation will be described and evaluated using the χ² test or Kruskal-Wallis test. Generalise additive mixed models will be used to explore the association between the renal profile and surgical outcomes including BCVA, and retinal and choroidal microvasculature/microstructure. Multivariate ordinal regression analysis will be used to detect the independent association between renal profile and BCVA changes, and smooth curve fitting will be employed to briefly present the tendency.Ethics and dissemination The trial has received ethical approval from the West China Hospital of Sichuan University. Results of this trial will be disseminated through publication in peer-reviewed journals and presentations at local and international meetings.Trial registration number ChiCTR2000039698.

Background: We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD).Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost

Purpose: This network meta-analysis was conducted to obtain the relative effectiveness of different pharmacotherapy of macular edema secondary to retinal vein occlusion (RVO) by summarizing all available evidences.Methods: PubMed, Embase, and Cochrane Library databases were searched for all relevant randomized controlled trials. The outcomes were estimated through a network meta-analysis, including the mean change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness (CRT).Results: We identified 15 randomized controlled trials (RCTs) involving 3,431 patients with RVO in our study. Different therapeutic regimens were compared including three anti-vascular endothelial growth factor (VEGF) agents (ranibizumab, bevacizumab, and aflibercept), ranibizumab with laser, dexamethasone intravitreal implant, and laser. For branch RVO, ranibizumab 0.5 mg monthly [weighted mean difference (WMD) = 11, 95% confidence intervals (CrI) 3.6 to 19], ranibizumab 0.5 mg 3 + pro re nata (WMD = 9.4, 95% CrI 0.43–18) is most effective in terms of changes of BCVA and 15 letters or more of BCVA improvement. For central RVO, three anti-VEGF regimens can improve visual acuity and there is no significant difference of efficacy among ranibizumab, bevacizumab and aflibercept (p > 0.05). Ranibizumab 0.5 mg monthly could achieve additional efficacy in CRT reduction in eyes with branch RVO or central RVO (WMD = -130, 95% CrI -400 to 140 or WMD = -280, 95% CrI -590 to 16)). Dexamethasone intravitreal implant (WMD = 1.7, 95% CrI -4.2 to 7.1 or WMD = 0.38, 95% CrI -9.8 to 8.8)) did not show a significant improvement in visual acuity at the end of 6 months follow-up in eyes with branch RVO or central RVO.Conclusion: In summary, this network meta-analysis demonstrated several anti-VEGF agents had equivalent effects on mean visual acuity changes and anatomical recovery in 6 months in eyes with branch or central RVO. Only one injection of dexamethasone intravitreal implant in 6 months could not maintain the visual benefit. Patients and clinicians could choose pharmacotherapies with further consideration toward personal factors.

Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting of pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), and caspase-1 and cause autocatalytic activation of caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied by cytokine release. In recent years, the pathogenic roles of inflammasomes and pyroptosis in multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome activation and abnormal pyroptosis in eyes generally attenuates inflammation and benefits prognosis. Therefore, insight into the pathogenesis underlying pyroptosis and inflammasome development in various types of eye diseases may provide new therapeutic strategies for ocular disorders. Inhibitors of pyroptosis, such as NLRP3, caspase-1, and GSDMD inhibitors, have been proven to be effective in many eye diseases. The purpose of this article is to illuminate the mechanism underlying inflammasome activation and pyroptosis and emphasize its crucial role in various ocular disorders. In addition, we review the application of pyroptosis modulators in eye diseases.

The low-strain integrity testing of large-diameter piles has attracted more and more attention because of its wide application in offshore engineering, such as for wind turbines, etc. Body and Rayleigh waves generate on the top surface of large-diameter piles after the excitation load. The multi-reflections of these waves from the pile side result in the obvious three-dimensional effect at the pile top. Therefore, one-dimensional wave theory is no longer suitable for interpreting the wave propagation in the pile body under vertical excitation. In this paper, based on the “pile in pile” conception, both the pile and soil were simulated using a three-dimensional continuum model, considering the vertical displacement, to investigate the influence of the three-dimensional effect of the pile-soil system on the vertical dynamic response of large-diameter piles in low-strain integrity testing. The axisymmetric solution to the three-dimensional pile-soil system was obtained, and the rationality of the proposed solution was verified by comparing it with the results of the finite element method and the results of other existing solutions. Arithmetic examples were used to describe the influence of the three-dimensional effect of the pile-soil system on the vertical dynamic response of large-diameter piles.

To improve the stability of the bridge structure, we detect bolts in the bridge which cause the symmetry failure of the bridge center. For data acquisition, bolts are small-scale objects under complex background in images, and their feature expression ability is limited. Due to those questions, we propose a new bolt positioning detection based on improved YOLOv5 for bridge structural health monitoring. This paper makes three major contributions. Firstly, according to the calibration anchor boxes of bolts, the size and proportion parameters of the initial anchor boxes are optimized by K-means++ clustering algorithm to solve the initial clustering problem of anchor boxes in object detection. Second, the hypercolumn (HC) technique fuses the low-level global features of the trunk and the high-level local features of three different scales to solve the problem of the inefficient distribution of anchors and insufficient extraction of classification features. In this way, we improve the detection accuracy and speed of bolt detection. Finally, we establish a dataset of bridge bolts through network collection and public datasets, including 1494 images. We compare and verify the new method in the collected bolt dataset. The experimental results show that the precision (P) of the improved YOLOv5x is up to 87.3%, and the average precision (AP) is up to 86.3%, which are 6.5% and 5.9% higher than the original YOLOv5x, respectively.

Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However, intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore, in this study, taking fluorescent labeled PLGA (poly (lactic-co-glycolic acid)) nanoparticles as a tool, the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method (MPT). Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate (SDS) increased the complex viscosity and viscoelastic properties of mucus, but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants, the penetration of nanoparticles in intestinal villus was obviously increased. In summary, the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile. Keywords: Mucus barrier, Mucus modulating agents, Rheology, PLGA nanoparticles, Surfactants

Due to its particularity and importance, long-distance oil and gas pipelines need to be well protected from damage by backfill materials. In this study, construction waste and expanded polystyrene (EPS) were used to replace conventional fine aggregate, and ethylene vinyl acetate-resin (EVA) was used to modify the surface of EPS to prepare lightweight controlled low strength materials (CLSM). Lightweight CLSM was tested in mechanics and physics and its microstructure was studied using microscopic analysis methods. The results revealed that the surface modification of EPS by EVA could greatly improve the compatibility of EPS with inorganic cementitious materials and prepare CLSM with a fluidity greater than 200 mm. EPS and cement content in cementitious materials play an important role in the development of material strength. When the volume ratio of EPS to construction waste was 2, and the content of cement in the cementitious materials was 35%, CLSM’s unconfined compressive strength at 28 days was only 0.48 MPa. In order to obtain the lightweight CLSM that meets the mechanical properties, the EPS content should not be too large. It can be concluded from the microscopic analysis that the increase of EPS content will lead to poor pore uniformity of the specimen, forming a loose mesh structure of defects, which is not conducive to the development of strength. In this study, EPS and construction waste are used to provide a green idea for preparing lightweight controlled low strength materials, which provides a reference for the backfill protection of the material in oil and gas pipelines in the future.

The human retina, which is part of the central nervous system, has exceptionally high energy demands that requires an efficient metabolism of glucose, lipids, and amino acids. Dysregulation of retinal metabolism disrupts local energy supply and redox balance, contributing to the pathogenesis of diverse retinal diseases, including age-related macular degeneration, diabetic retinopathy, inherited retinal degenerations, and Macular Telangiectasia. A better understanding of the contribution of dysregulated metabolism to retinal diseases may provide better therapeutic targets than we currently have.

Plant leaf nutrient concentrations and resorption are sensitive to fertilization, yet their co-responses under different nutrient-limited conditions have not been well studied. We conducted a meta-analysis from a global dataset of 43 reports, including 130 observations of studies with plant leaf nitrogen (N) or phosphorus (P) concentrations and nitrogen resorption efficiency (NRE) or phosphorus resorption efficiency (PRE), in response to fertilization under different nutrient-limited conditions divided by the thresholds of leaf N:P ratio values of 10 and 20. The results showed that N fertilization generally increased leaf N concentration and decreased NRE, with greater magnitudes under N-limited conditions. P fertilization also generally increased leaf P concentration and decreased PRE, with greater magnitudes under P-limited conditions. N fertilization decreased leaf P concentration and increased PRE only under the N-limited condition. Under the P-limited or N and P co-limited conditions, however, N fertilization increased leaf P concentration and did not change PRE. Moreover, P fertilization did not change leaf N concentration under all nutrient-limited conditions but significantly increased NRE under the N-limited or N and P co-limited conditions. These findings suggest that plants cope with fertilization-induced N limitation vs. P limitation at the leaf level with different nutrient-use strategies.

Background The purpose of this study was to determine whether the presence of antegrade blood flow was related to stroke subtype in patients with acute intracranial large artery occlusion. Methods and Results The prospectively collected data for consecutive patients who had occlusion of the unilateral M1 segment of the middle cerebral artery with or without internal carotid artery and received reperfusion therapy were retrospectively reviewed. Stroke causes were determined according to the Trial of ORG 10172 in Acute Stroke Treatment standard. We defined antegrade flow as early opacification at the distal interface of the clot with subsequent distal extension on 4‐dimensional computed tomography angiography. A total of 387 large artery occlusion patients were analyzed (229 men and 158 women; mean age, 71±14 years), including 77 (19.9%) with large artery atherosclerosis (LAA), 206 (53.2%) with cardioembolism, and 104 (26.9%) with undetermined causes. Antegrade flow was found in 206 (53.2%) patients, and 181 (46.8%) presented with retrograde flow. The rate of antegrade flow was much higher in patients with LAA than in those with cardioembolism (85.7% versus 42.2%, P

Volatile organic compounds (VOCs) emitted from vehicle parts and interior materials can seriously affect in-cabin air quality. Prior studies mainly focused on indoor material emissions, while studies of emissions in-cabins were relatively scarce. The emission behaviors of VOCs from vehicle cabin materials can be characterized by three key emission parameters: the initial emittable concentration (C0), diffusion coefficient (Dm), and partition coefficient (K). Based on a C-history method, we have performed a series of tests with a 30 L small-scale chamber to determine these three key emission parameters for six VOCs, benzene, toluene, ethylbenzene, xylene, formaldehyde, and acetaldehyde, from typical vehicle cabin materials, car roof upholstery, carpet, and seat. We found that acetaldehyde had the highest level in the gas-phase concentration and C0, which differs from residential indoor environments where formaldehyde is usually the most prevalent pollutant. The influence of temperature on the key emission parameters was also investigated. When the temperature rose from 25 °C to 65 °C, C0 increased by 40–640%, Dm increased by 40–170%, but K decreased by 38–71% for different material-VOC combinations. We then performed an independent validation to demonstrate the accuracy of the measured key emission parameters. Furthermore, considering that in reality, several materials coexist in vehicle cabins, we made a first attempt at applying a multi-source model to predict VOC emission behaviors in a simulated 3 m3 vehicle cabin, using the key emission parameters obtained from the small-scale chamber tests. The good agreement between the predictions and experiments (R2 = 0.82–0.99) demonstrated that the three key emission parameters measured via chamber tests can be scaled to estimate emission scenarios in realistic vehicle cabin environments. A pollution contribution analysis for the tested materials indicated that the car seat could significantly contribute to the total emissions.

Large-energy mode-locked fiber lasers are extensively studied due to their indispensable use in various fields and applications. Recently, ferromagnetic insulators have attracted tremendous research interest in ultra-fast photonics because of their unique ferromagnetic properties and typical layered structure. In our work, Cr2Si2Te6 nanosheets are prepared and utilized as a saturable absorber (SA) in a large-energy mode-locked erbium-doped fiber (EDF) laser. With a total cavity length of 240 m, a stable mode-locked operation characterized by maximum pulse energy as high as 244.76 nJ with a repetition rate of 847.64 kHz is achieved. When the cavity length is extended to 390 m, the output maximum pulse energy is successfully scaled up to 325.50 nJ. To our knowledge, this is the largest pulse energy and highest output power level to be achieved in mode-locked fiber lasers by two-dimensional (2D) material saturable absorbers (SAs) so far. This work not only makes a forward step to the investigation of the generation of large-energy pulses in mode-locked fiber lasers but also fully proves that the ferromagnetic insulator-Cr2Si2Te6 possesses an excellent nonlinear absorption property, antioxidant capacity in ambient conditions, as well as outstanding thermal stability, which enriches our insight into 2D materials.

Biochar addition is a promising solution to improve soil nitrogen (N) availability and enhance crop productivity. However, a comprehensive understanding of the impact of soil N dynamics on crop productivity under biochar addition remains elusive. Here, we conducted a meta-analysis from 93 peer-reviewed field experiments to synthesize the linkage of crop productivity to soil N dynamics under biochar addition. The results show that biochar addition significantly enhanced crop productivity by 12.8% and plant N uptake (PNU) by 22.6%, and there was a strongly positive relationship between crop productivity and PNU. Biochar addition also significantly increased the contents of soil total N (TN), inorganic N (IN), microbial biomass N (MBN), and biological N2 fixation (BNF) by 3.34–18.7%, but reduced nitrous oxide (N2O) emission by 15.9%. Further analysis with the aggregated boosted tree model indicated that the TN and BNF played the most important roles in biochar-induced change in crop productivity. However, while crop productivity was positively correlated with TN under biochar addition, it showed a negative correlation with BNF. These findings suggest that biochar addition could enhance crop growth and productivity through increasing the soil N resource and N uptake, but this was not true for some N2-fixing crops, probably because they were usually constrained by nutrients other than N.

Abstract Background The Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu) scale, a leukemia-specific instrument for determining the health-related quality of life (HRQOL) in patients with leukemia, had been developed and validated, but there have been no reports on the development of a simplified Chinese version of this scale. This is a new exploration to analyze the reliability of the HRQOL measurement using multivariate generalizability theory (MGT). This study aimed to develop a Chinese version of the FACT-Leu scale and evaluate its reliability using MGT to provide evidence to support the revision and improvement of this scale. Methods The Chinese version of the FACT-Leu scale was developed by four steps: forward translation, backward translation, cultural adaptation and pilot-testing. The HRQOL was measured for eligible inpatients with leukemia using this scale to provide data. A single-facet multivariate Generalizability Study (G-study) design was demonstrated to estimate the variance–covariance components and then several Decision Studies (D-studies) with varying numbers of items were analyzed to obtain reliability coefficients and to understand how much the measurement reliability could be vary as the number of items in MGT changes. Results One-hundred and one eligible inpatients diagnosed with leukemia were recruited and completed the HRQOL measurement at the time of admission to the hospital. In the G-study, the variation component of the patient-item interaction was largest while the variation component of the item was the smallest for the four of five domains, except for the leukemia-specific (LEUS) domain. In the D-study, at the level of domain, the generalizability coefficients (G) and the indexes of dependability (Ф) for four of the five domains were approximately equal to or greater than 0.80 except for the Emotional Well-being (EWB) domain (>0.70 but

Background and Purpose: Patients with large vessel occlusion stroke (LVOS) need to be rapidly identified and transferred to comprehensive stroke centers (CSC). However, previous pre-hospital strategy remains challenging. We aimed to develop a modified scale to better predict LVOS.Methods: We retrospectively reviewed our prospectively collected database for acute ischemic stroke (AIS) patients who underwent CT angiography (CTA) or time of flight MR angiography (TOF-MRA) and had a detailed National Institutes of Health Stroke Scale (NIHSS) score at admission. Large vessel occlusion (LVO) was defined as the complete occlusion of large vessels, including the intracranial internal carotid artery (ICA), M1, and M2 segments of the middle cerebral artery (MCA), and basilar artery (BA). The Conveniently-Grasped Field Assessment Stroke Triage (CG-FAST) scale consisted of Level of Consciousness (LOC) questions, Gaze deviation, Facial palsy, Arm weakness, and Speech changes. Receiver Operating Characteristic (ROC) analysis was used to obtain the Area Under the Curve (AUC) of CG-FAST and previously established pre-hospital prediction scales.Results: Finally, 1,355 patients were included in the analysis. LVOS was detected in 664 (49.0%) patients. The sensitivity, specificity, positive predictive value, and negative predictive value of CG-FAST were 0.617, 0.810, 0.785, and 0.692 respectively, at the optimal cutoff (≥4). The AUC, Youden index and accuracy of the CG-FAST scale (0.758, 0.428, and 0.728) were all higher than other pre-hospital prediction scales.Conclusions: CG-FAST scale could be an effective and simple scale for accurate identification of LVOS among AIS patients.

Retinal vein occlusion (RVO) is a differential diagnosis for Coats’ disease due to retinal arterial Leber’s aneurysms. Occasionally, RVO shows a Coats-like appearance. The differential diagnosis between Coats’ disease and RVO is essential for clinical therapy, especially for those obsolete RVOs with collateral vessels and without retinal hemorrhage. In this case report, we describe and discuss the imaging characteristics of bilateral RVO-simulated Coats’ disease with tortuous retinal arterioles and its prognosis after anti-vascular endothelial growth factor therapy, which will be beneficial for its definite diagnosis and aid further investigation.

Background: Large core is associated with poor outcome in acute ischemic stroke (AIS) patients. It is unclear whether endovascular treatment (EVT) could bring benefits to patients with core volume ≥70 ml before treatment. We aimed to compare the impact of EVT with intravenous thrombolysis (IVT) on the outcome in patients with core volume ≥70 ml.Methods: We included consecutive anterior circulation AIS patients who underwent MR or CT perfusion within 6 h post stroke onset, which revealed a core ≥70 ml before reperfusion therapy. Good outcome was defined by modified Rankin Scale of 0 to 2 at 90-day. Reperfusion was defined as a reduction in hypoperfusion volume of ≥70% between baseline and 24 h.Results: One hundred four patients were included. Among them, 76 received IVT only, and 28 received EVT. After adjusting for age, NIHSS score, baseline core volume and onset to imaging time, patients in EVT group were more likely to achieve good outcome compared to IVT patients (OR, 3.875; 95% Cl 1.068–14.055, p = 0.039). More patients in EVT group achieved recanalization (84.0 vs. 58.5%, p = 0.027) and reperfusion (66.7 vs. 33.3%, p = 0.010) than in IVT group. Reperfusion also independently predicted good outcome (OR, 7.718; 95% Cl 1.713-34.772, p = 0.008). All patients with good outcome achieved recanalization at 24 h.Conclusions: Our data indicated that patients with core volume ≥70 ml might still benefit from EVT, which was related to its high reperfusion rate.